Population-Based Evaluation of Vaccine Effectiveness against SARS-CoV-2 Infection, Severe Illness, and Death, Taiwan.

Taiwan provided several COVID-19 vaccine platforms: mRNA (BNT162b2, mRNA-1273), adenoviral vector-based (AZD1222), and protein subunit (MVC-COV1901). After Taiwan shifted from its zero-COVID strategy in April 2022, population-based evaluation of vaccine effectiveness (VE) became possible. We conducted an observational cohort study of 21,416,151 persons to examine VE against SARS-CoV-2 infection, moderate and severe illness, and death during March 22, 2021-September 30, 2022. After adjusting for age and sex, we found that persons who completed 3 vaccine doses (2 primary, 1 booster) or received MVC-COV1901 as the primary series had the lowest hospitalization incidence (0.04-0.20 cases/100,000 person-days). We also found 95.8% VE against hospitalization for 3 doses of BNT162b2, 91.0% for MVC-COV1901, 81.8% for mRNA-1273, and 65.7% for AZD1222, which had the lowest overall VE. Our findings indicated that protein subunit vaccines provide similar protection against SARS-CoV-2---associated hospitalization as mRNA vaccines and can inform mix-and-match vaccine selection in other countries.

Risk factors and mortality of SARS-CoV-2 reinfection during the Omicron era in Taiwan: A nationwide population-based cohort study.

BACKGROUND: Prior to 2022, Taiwan had effectively contained the domestic COVID-19 epidemic. However, during 2022, the country encountered multiple large outbreaks of COVID-19, with patients experiencing their first or second infection (reinfection) were both predominantly caused by the Omicron variant. Data are lacking on the risk factors and mortality of COVID-19 reinfection in Omicron era. METHODS: In this retrospective population-based cohort study, we recruited COVID-19 patients with their first episode confirmed between April 1, 2022 and June 11, 2022. A reinfection patient was defined as an individual who infected again by SARS-CoV-2 with an interval of more than 90 days. Demographic characteristics, severity of underlying diseases, and vaccination status were adjusted to identify risk factors for reinfection and to further evaluate the hazard of all-cause mortality within 30 days between reinfection and non-reinfection patients. RESULTS: There were 28,588 reinfection patients matched with 142,940 non-reinfection patients included in this study. We found that being female, younger in age, having more severe underlying diseases, and not being fully vaccinated against COVID-19 were risk factors for reinfection. After adjusting for confounding factors, reinfection patients were at a significantly higher risk of all-cause mortality within 30 days (aHR = 4.29, 95% CI: 3.00-6.12, p < 0.001) comparing with non-reinfection patients. CONCLUSION: During the SARS-CoV-2 Omicron era, reinfection patients were observed to have an increased risk of all-cause mortality. To reduce the disease burden and minimize the risk of reinfection, it is crucial for vulnerable patients to receive full vaccination and adhere to recommended precautions.

Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein-mediated viral translation.

Diabetes mellitus (DM) is highly comorbid with severe dengue diseases; however, the underlying mechanisms are unclear. Patients with DM have a 1.61-fold increased risk of developing dengue hemorrhagic fever. In search of host factors involved in dengue virus (DENV) infection, we used high-glucose (HG) treatment and showed that HG increased viral protein expression and virion release but had no effects on the early stages of viral infection. After HG stimulation, DENV-firefly luciferase-transfected assay and cellular replicon-based assay indicated increased viral translation, whereas using the glucose uptake inhibitor phloretin blocked this effect. HG treatment increased the translational factor poly(A)-binding protein (PABP) in a glucose transporter-associated, PI3K/AKT-regulated manner. Silencing PABP significantly decreased HG-prompted virion production. HG enhanced the formation of the PABP-eukaryotic translation initiation factor 4G complex, which is regulated by protein-disulfide isomerase. Hyperglycemia increased PABP expression, mortality rate, viral protein expression, and viral loads in streptozotocin-induced DM mice. Overall, hyperglycemic stress facilitates DENV infection by strengthening PABP-mediated viral translation.

Nanoscale plasmonic wires with maximal figure of merits as a superior flexible transparent conducting electrode for RGB colors.

Based on incredibly increasing applications in modern optoelectronic devices, the demand for securing a superior conductive transparent electrode (TCE) candidate becomes significant and urgent. However, boosting both transmittance and conductance simultaneously is an intrinsic limitation. In this work, we present silver nanoscale plasmonic wires (Ag NPWs) to function as TCEs in the visible light region by lowering their corresponding plasma frequencies. By carefully designing geometric dimensions of the Ag NPWs, we also optimize the performance for red, green, and blue colors, respectively. The demonstrated figure of merits for RGB colors appeared respectively 443.29, 459.46, and 133.78 in simulation and 302.75, 344.11, and 348.02 in experiments. Evidently, our Ag NPWs offer much greater FoMs beyond conventional TCEs that are most frequently comprised of indium tin oxide and show further advantages of flexibility and less Moire effect for the applications of flexible and high-resolution optoelectronic devices.

Lower risk of primary Sjogren's syndrome in patients with dengue virus infection: a nationwide cohort study in Taiwan.

The data concerning the association between dengue viruses (DV) infection and autoimmune diseases (ADs) remain unclear and are scarce. This nationwide population-based cohort study assessed the risk of ADs among patients with DV infection. We analyzed Taiwanese medical data from the Registry of the National Notifiable Disease Reporting System of Taiwan's Centers for Disease Control between 1998 and 2015 and identified patients with DV infection. From the entire general population data in the National Health Insurance Research Database, we randomly selected a comparison cohort that was individual matching by age, sex, residence, and index date. We analyzed the risk of ADs using a Cox proportional hazards regression model stratified by sex, age, and residence. We enrolled 29,365 patients with DV infection (50.68% men; mean age, 44.13 years) and 117,460 age-, sex-, and residence-matched controls in the present study. The incidence rates of organ-specific ADs were nonsignificantly higher in the DV cohort than in the non-DV control cohort. An approximately 70% lower risk of primary Sjogren syndrome (pSS) was evident in the DV cohort than in the non-DV control cohort with an adjusted hazard ratio of 0.30 (95% confidence interval 0.13-0.67) after adjusting for comorbidities in matched design. By contrast, the other systemic ADs were nonsignificantly lower in the DV cohort than in the non-DV control cohort. This nationwide long-term cohort study demonstrated that patients with DV infection had a lower risk of primary Sjogren syndrome than those without DV infection. Key Points • This retrospective, longitudinal cohort observational study shows that patients with DV infection had a lower risk of pSS than those without DV infection. • The DV cohort had an approximately 70% lower risk of pSS than the control group, with a multivariate-adjusted HR of 0.30. • On the basis of this result, we contended that DV infection has a protective effect that reduces the risk of pSS.

Real-Time Surveillance of Infectious Diseases: Taiwan's Experience.

Integration of multiple surveillance systems advances early warning and supports better decision making during infectious disease events. Taiwan has a comprehensive network of laboratory, epidemiologic, and early warning surveillance systems with nationwide representation. Hospitals and clinical laboratories have deployed automatic reporting mechanisms since 2014 and have effectively improved timeliness of infectious disease and laboratory data reporting. In June 2016, the capacity of real-time surveillance in Taiwan was externally assessed and was found to have a demonstrated and sustainable capability. We describe Taiwan's disease surveillance system and use surveillance efforts for influenza and Zika virus as examples of surveillance capability. Timely and integrated influenza information showed a higher level and extended pattern of influenza activity during the 2015-16 season, which ensured prompt information dissemination and the coordination of response operations. Taiwan also has well-developed disease detection systems and was the first country to report imported cases of Zika virus from Miami Beach and Singapore. This illustrates a high level of awareness and willingness among health workers to report emerging infectious diseases, and highlights the robust and sensitive nature of Taiwan's surveillance system. These 2 examples demonstrate the flexibility of the surveillance systems in Taiwan to adapt to emerging infectious diseases and major communicable diseases. Through participation in the GHSA, Taiwan can more actively collaborate with national counterparts and use its expertise to strengthen global and regional surveillance capacity in the Asia Pacific and in Southeast Asia, in order to advance a world safe and secure from infectious disease.

Using financial incentives to improve the care of tuberculosis patients.

OBJECTIVES: Tuberculosis (TB) is a serious public health concern, and Taiwan has implemented a pay-for-performance (P4P) program to incentivize healthcare professionals to provide comprehensive care to TB patients. This study aims to examine the effects of the TB P4P program on treatment outcomes and related expenses. STUDY DESIGN: A population-based natural experimental design with intervention and comparison groups. METHODS: Propensity score matching was conducted to increase the comparability between the P4P and non-P4P group. A total of 12,018 subjects were included in the analysis, with 6009 cases in each group. Generalized linear models and multinomial logistic regression were employed to examine the effects of the P4P program. RESULTS: The regression models indicated that patients enrolled in the P4P program had 14% more ambulatory visits than non-P4P patients (P < .001), but there were no differences in hospitalization rates. On average, P4P enrollees spent $215 (4.6%) less on TB-related expenses than their counterparts. In addition, P4P enrollees had a higher likelihood of being successfully treated (odds ratio, 1.56; P < .001) and were less likely to die compared with nonenrollees. CONCLUSIONS: Patients in the P4P program were less likely to die, were more likely to be treated successfully, and incurred lower costs. Providing financial incentives to healthcare institutions could be a feasible model for better TB control.

Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2.

We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

A gene delivery system for insect cells mediated by arginine-rich cell-penetrating peptides.

Most bioactive macromolecules, such as protein, DNA and RNA, basically cannot permeate into cells freely from outside the plasma membrane. Cell-penetrating peptides (CPPs) are a group of short peptides that possess the ability to traverse the cell membrane and have been considered as candidates for mediating gene and drug delivery into living cells. In this study, we demonstrate that three arginine-rich CPPs (SR9, HR9 and PR9) are able to form stable complexes with plasmid DNA and deliver DNA into insect Sf9 cells in a noncovalent manner. The transferred plasmid DNA containing enhanced green fluorescent protein (EGFP) and red fluorescent protein (RFP) coding regions could be expressed in cells functionally assayed at both the protein and RNA levels. Furthermore, treatment of cells with CPPs and CPP/DNA complexes resulted in a viability of 84-93% indicating these CPPs are not cytotoxic. These results suggest that arginine-rich CPPs appear to be a promising tool for insect transgenesis.

Trends in tuberculosis in Taiwan, 2002-2008.

BACKGROUND/PURPOSE: Tuberculosis (TB) remains an important infectious disease in Taiwan. To control TB effectively, the Taiwan Centers for Disease Control implemented the National Tuberculosis Program (NTP) in 2006, modeled on the World Health Organization global TB control program. The goal of the program was to reduce the number of TB cases by half within a decade. This study was designed to describe the epidemiology of TB in Taiwan, and to evaluate the preliminary effectiveness of the NTP. METHODS: We conducted a retrospective study of data from the National Tuberculosis Registry System collected between 2002 and 2008. Demographics, geographic distribution of disease, and change in rates of TB incidence and mortality were analyzed. RESULTS: From 2002 to 2008, new TB cases declined from 16,758 to 14,265, and incidence decreased from 75 per 100,000 population to 62 per 100,000 population. More than 50% of new cases occurred among elderly adults. Over the study period, TB mortality decreased from 5.7 per 100,000 population to 3.3 per 100,000 population, with over half of TB deaths occurring among patients aged ≥ 65 years. Since the NTP was implemented, from 2005 to 2008, TB incidence and mortality declined by 14% and 23%, respectively. CONCLUSION: TB-associated incidence and mortality decreased over the course of the study. Nevertheless, there continue to be high-incidence areas that show the opposite trend; these areas should strive to improve case management and consultation. In the most populous districts, rigorous surveillance is necessary to track incidence and mortality rate fluctuations.

A gene delivery system for human cells mediated by both a cell-penetrating peptide and a piggyBac transposase.

The piggyBac (PB) transposable element has recently accumulated enormous attention as a tool for the transgenesis in various eukaryotic organisms. Arginine-rich cell-penetrating peptides (CPPs) are protein transduction domains containing a large amount of basic amino acids that were found to be capable of delivering biologically active macromolecules into living cells. In this study, we demonstrate a strategy, which we called "transposoduction", which is a one-plasmid gene delivery system mediated by the nontoxic CPP-piggyBac transposase (CPP-PBase) fusion protein to accomplish both protein transduction and transposition. CPPs were proven to be able to synchronously deliver covalently linked PBase and noncovalently linked a cis plasmid into human cells. The expression of promoterless reporter genes coding for red (dTomato) and yellow (mOrange) fluorescent proteins (RFP and YFP) with PB elements could be detected in cells treated with the PBase-expressing plasmid after 3 days indicating transposition of coding regions to downstream of endogenous promoter sequences. An enhanced green fluorescent protein (EGFP) plasmid-based excision assay further confirmed the efficiency of the bifunctional CPP-PBase fusion protein. In conclusion, this strategy representing a combinational concept of both protein transduction and mobile transposition may provide tremendous potential for safe and efficient cell line transformation, gene therapy and functional genomics.

Multiple morbidity combinations impact on medical expenditures among older adults.

This study aims to explore the medical needs of patients who have different combinations of multiple chronic diseases in order to improve care strategy for chronic patients. This study was based on a national probability proportional to size (PPS) sampling to older adults over 50 years old. We collaborated the files of the 2000-2001 health insurance claims and selected 8 types of common chronic diseases among seniors, for the discussion of multiple combinations of chronic diseases, including hypertension, diabetes, heart disease, stroke, dementia, cancer, arthritis and chronic obstructive pulmonary disease. Among the NHI users, there are 50.6% of the cases suffering from at least one chronic disease, 27.3% suffering from two types of chronic diseases and above. From possible combinations of eight common chronic diseases, it is found hypertension has the highest prevalence rate (7.5%); arthritis ranks the next (6.2%); the combination of hypertension and heart disease ranks the third (3.4%). In the 22 types of major chronic disease clusters, the average total medical expense for people who have five or more chronic diseases ranks the highest, USD 4465; the combination of hypertension, diabetes, heart disease, and arthritis ranks the next, USD 2703; the combination of hypertension, diabetes, and heart disease ranks the third, USD 2550; cancer only ranks the fourth, USD 2487. Our study may provide statistical data concerning co-morbidity among older adults and their medical needs. Through our analysis, the major population that exhausts the medical resources may be discovered.

The prevalence of chronic conditions and medical expenditures of the elderly by chronic condition indicator (CCI).

The aim of this study was to understand the prevalence of chronic conditions and medical expenditures of the elderly for health care planning development of chronic conditions. This research is based on the representative sample (N=114,873) of seniors over 65 years nationwide. The CCI by the U.S. Agency for Healthcare Research and Quality (AHRQ), and clinical classifications software (CCS) were adopted to determine chronic condition diagnosis codes and classify the diseases. The results are presented by descriptive and multiple regression analysis. The chronic condition prevalence for seniors is 70.4% and the medical expenditures for seniors with chronic conditions accounts for 92.7% of the total medical expenditures for seniors, while 25% of the medical expenditure is spent on 8.2% of seniors who have five chronic conditions and above. Chronic conditions suffered by the elderly, in the order of its prevalence, are hypertension (36.1%), COPD (23.7%), and cataracts (16.7%). From the viewpoint of annual average medical expenditures, cardiovascular diseases rank the most costly diseases, with average medical expenditures as high as $4291. Urinary disease and diabetes ranks the second and the third most costly with an average expenditure of $3644 and $3594. This research showed that the average medical expenditure for seniors with chronic conditions is 5.4 times higher compared with seniors without chronic conditions. It is recommended to further study the characteristics of the target population that spends the most in medical expenditures to outline a more beneficial disease management model, reduce avoidable medical costs and achieve the goal of saving medical resources.

Arginine-rich intracellular delivery peptides synchronously deliver covalently and noncovalently linked proteins into plant cells.

Protein transduction domains (PTDs) are small peptides with a high content of basic amino acids, and they are responsible for cellular uptake. Many PTDs, including arginine-rich intracellular delivery (AID) peptides, have been shown to transport macromolecules across membranes and into cells. In this study, we demonstrated for the first time that AID peptides could rapidly and efficiently deliver proteins into plant cells in both covalent and noncovalent protein transductions (CNPT) simultaneously. The optimal molecular ratio between an AID peptide carrier and cargo in CNPT was about 3:1. Fluorescence resonance energy transfer (FRET) analysis revealed protein-protein interactions between AID peptide carriers and cargos after CNPT in cells. The possible mechanisms of AID peptides-mediated cellular entry might involve a combination of multiple internalization pathways. Therefore, applications by AID peptide-mediated CNPT may provide a simple and direct transport strategy for delivering two proteins in agricultural systems.