Incubation Period and Serial Interval of Mpox in 2022 Global Outbreak Compared with Historical Estimates.

Understanding changes in the transmission dynamics of mpox requires comparing recent estimates of key epidemiologic parameters with historical data. We derived historical estimates for the incubation period and serial interval for mpox and contrasted them with pooled estimates from the 2022 outbreak. Our findings show the pooled mean infection-to-onset incubation period was 8.1 days for the 2022 outbreak and 8.2 days historically, indicating the incubation periods remained relatively consistent over time, despite a shift in the major mode of transmission. However, we estimated the onset-to-onset serial interval at 8.7 days using 2022 data, compared with 14.2 days using historical data. Although the reason for this shortening of the serial interval is unclear, it may be because of increased public health interventions or a shift in the mode of transmission. Recognizing such temporal shifts is essential for informed response strategies, and public health measures remain crucial for controlling mpox and similar future outbreaks.

Transmission Dynamics and Effectiveness of Control Measures during COVID-19 Surge, Taiwan, April-August 2021.

An unprecedented surge of COVID-19 cases in Taiwan in May 2021 led the government to implement strict nationwide control measures beginning May 15. During the surge, the government was able to bring the epidemic under control without a complete lockdown despite the cumulative case count reaching >14,400 and >780 deaths. We investigated the effectiveness of the public health and social measures instituted by the Taiwan government by quantifying the change in the effective reproduction number, which is a summary measure of the ability of the pathogen to spread through the population. The control measures that were instituted reduced the effective reproduction number from 2.0-3.3 to 0.6-0.7. This decrease was correlated with changes in mobility patterns in Taiwan, demonstrating that public compliance, active case finding, and contact tracing were effective measures in preventing further spread of the disease.

Early Prompt Response to COVID-19 in Taiwan: Comprehensive surveillance, decisive border control, and information technology support.

Since the COVID-19 outbreak was detected in Wuhan in December 2019 by the event-based surveillance of Taiwan Centers for Disease Control, Taiwan has been aligning risk management to policy planning with the assistance of comprehensive surveillance and regular rapid risk assessments. Taiwan Central Epidemic Command Center (CECC) promptly initiated stepwise border control for major cities and provinces in China, European and American countries, and eventually expanded it to the whole world in March 2020. With stringent quarantine measures, the early response not only successfully blocked the first wave of imported cases, but also slowed down subsequent large local outbreaks. Digital technologies including digital fencing and government database linkage were adopted to facilitate the application of public health interventions and data collection. The experience of Taiwan's prompt and comprehensive response at the early stage may contribute to the preparedness for the next disease X outbreak.

Ocean Wind Observation Based on the Mean Square Slope Using a Self-Developed Miniature Wave Buoy.

Real-time, continuous, and long-term marine monitoring data benefits ocean research. This study developed a low-cost, multi-parameter, miniature wave buoy. High spatial and temporal resolution of sea surface parameters, including wind, waves, and current, can be obtained at low cost through the deployment of numerous buoys, thus forming an observation array. Tested in the laboratory water tank, the relative error of water surface slope measurement of the buoy was approximately 5.6% when the slope angle was less than 15°. For frequencies between 0.1 and 1.0 Hz, the measurement of slope spectrum was almost identical to that of the wave gauge. The buoy underestimated the slope spectrum between 1.0−1.56 Hz. A good relationship (r2 = 0.75) was obtained between wind speed at 10 m above sea surface (U10) and the low-pass-filtered mean square slope (LPMSS). After incorporating the wave age into the U10 inversion process, the root mean square error (RMSE) and BIAS were reduced to 1.15 m/s and 0.02 m/s, respectively. The 2D distribution of buoy-measured slope components was used to detect the wind direction, with an RMSE of 23.7°. The spectral tail slope steepened with increasing wind speed at low wind speeds (<7 m/s). A technical flow chart of the miniature wave buoy is proposed to observe the sea surface parameters. This miniature buoy will play an essential complementary role in the growing demand for sea state monitoring, especially in nearshore oceans.

Proactive and blended approach for COVID-19 control in Taiwan.

Coronavirus disease 2019 (COVID-19) has become the greatest threat to human society in a century. To better devise control strategies, policymakers should adjust policies based on scientific evidence in hand. Several countries have limited the epidemics of COVID-19 by prioritizing containment strategies to mitigate the impacts on public health and healthcare systems. However, asymptomatic/pre-symptomatic transmission of COVID-19 complicated traditional symptom-based approaches for disease control. In addition, drastic population-based interventions usually have significant societal and economic impacts. Therefore, in Taiwan, the containment strategies consisted of the more extended case-based interventions (e.g., case detection with enhanced surveillance and contact tracing with active monitoring and quarantine of close contacts) and more targeted population-based interventions (e.g., face mask use in recommended settings and risk-oriented border control with corresponding quarantine requirement). The success of the blended approach emphasizes not only the importance of evidence-supported policymaking but also the coordinated efforts between the government and the people.

Taiwan's COVID-19 response: Timely case detection and quarantine, January to June 2020.

The coronavirus disease 2019 (COVID-19) pandemic has become severe threats to economic, societal, and healthcare systems. To analyze the epidemiological characteristics of the COVID-19 outbreak in Taiwan and evaluate the key interventions, we conducted a retrospective cohort study during January 17-June 30, 2020. As of June 30, the COVID-19 outbreak, including 447 laboratory-confirmed cases, was eliminated by mixed approaches: border control, enhanced surveillance, case detection with contact tracing, quarantine, and population-based interventions like face mask use. The improvement of median time from disease onset to notification (5 days [range -3 to 27] before March 1 to 1 day [range -8 to 22] after March 1) suggested the timeliness and comprehensiveness of surveillance and contact tracing. Travel restrictions with quarantine, resulting in fewer clusters, were also complementary to minimize disease spread. Under combined interventions, Taiwan successfully contained the COVID-19 spread within the country and minimized its impact on the society.

Applying Machine Learning Models with An Ensemble Approach for Accurate Real-Time Influenza Forecasting in Taiwan: Development and Validation Study.

BACKGROUND: Changeful seasonal influenza activity in subtropical areas such as Taiwan causes problems in epidemic preparedness. The Taiwan Centers for Disease Control has maintained real-time national influenza surveillance systems since 2004. Except for timely monitoring, epidemic forecasting using the national influenza surveillance data can provide pivotal information for public health response. OBJECTIVE: We aimed to develop predictive models using machine learning to provide real-time influenza-like illness forecasts. METHODS: Using surveillance data of influenza-like illness visits from emergency departments (from the Real-Time Outbreak and Disease Surveillance System), outpatient departments (from the National Health Insurance database), and the records of patients with severe influenza with complications (from the National Notifiable Disease Surveillance System), we developed 4 machine learning models (autoregressive integrated moving average, random forest, support vector regression, and extreme gradient boosting) to produce weekly influenza-like illness predictions for a given week and 3 subsequent weeks. We established a framework of the machine learning models and used an ensemble approach called stacking to integrate these predictions. We trained the models using historical data from 2008-2014. We evaluated their predictive ability during 2015-2017 for each of the 4-week time periods using Pearson correlation, mean absolute percentage error (MAPE), and hit rate of trend prediction. A dashboard website was built to visualize the forecasts, and the results of real-world implementation of this forecasting framework in 2018 were evaluated using the same metrics. RESULTS: All models could accurately predict the timing and magnitudes of the seasonal peaks in the then-current week (nowcast) (ρ=0.802-0.965; MAPE: 5.2%-9.2%; hit rate: 0.577-0.756), 1-week (ρ=0.803-0.918; MAPE: 8.3%-11.8%; hit rate: 0.643-0.747), 2-week (ρ=0.783-0.867; MAPE: 10.1%-15.3%; hit rate: 0.669-0.734), and 3-week forecasts (ρ=0.676-0.801; MAPE: 12.0%-18.9%; hit rate: 0.643-0.786), especially the ensemble model. In real-world implementation in 2018, the forecasting performance was still accurate in nowcasts (ρ=0.875-0.969; MAPE: 5.3%-8.0%; hit rate: 0.582-0.782) and remained satisfactory in 3-week forecasts (ρ=0.721-0.908; MAPE: 7.6%-13.5%; hit rate: 0.596-0.904). CONCLUSIONS: This machine learning and ensemble approach can make accurate, real-time influenza-like illness forecasts for a 4-week period, and thus, facilitate decision making.

Ice-associated norovirus outbreak predominantly caused by GII.17 in Taiwan, 2015.

BACKGROUND: On 5 March 2015, Taiwan Centers for Disease Control was notified of more than 200 students with gastroenteritis at a senior high school during excursion to Kenting. We conducted an outbreak investigation to identify the causative agent and possible vehicle of the pathogen. METHODS: We conducted a retrospective cohort study by using a structured questionnaire to interview all students for consumed food items during their stay at the resort. Students were defined as a gastroenteritis case while having vomiting or diarrhea after the breakfast on 4 March. We inspected the environment to identify possible contamination route. We collected stool or vomitus samples from ill students, food handlers and environmental specimens for bacterial culture for common enteropathogens, reverse transcription polymerase chain reaction (RT-PCR) for norovirus and enzyme-linked immunosorbent assay (ELISA) for rotavirus. Norovirus PCR-positive products were then sequenced and genotyped. RESULTS: Of 267 students enrolled, 144 (54%) met our case definition. Regression analysis revealed elevated risk associated with iced tea, which was made from tea powder mixed with hot water and self-made ice (risk ratio 1.54, 95% confidence interval 1.22-1.98). Ice used for beverages, water before and after water filter of the ice machine and 16 stool and vomitus samples from ill students were tested positive for norovirus; Multiple genotypes were identified including GI.2, GI.4 and GII.17. GII.17 was the predominant genotype and phylogenetic analyses showed that noroviruses identified in ice, water and human samples were clustered into the same genotypes. Environmental investigation revealed the ice was made by inadequate-filtered and un-boiled water. CONCLUSIONS: We identified the ice made by norovirus-contaminated un-boiled water caused the outbreak and the predominant genotype was GII.17. Adequately filtered or boiled water should be strongly recommended for making ice to avoid possible contamination.

Using Novel Method to Detect Different Cancer-Cell Stages of Model Human Lung Carcinoma.

BACKGROUND: Synchrotron radiation infrared (SR-IR) microspectroscopy and SR-IR spectroscopic imaging are extremely valuable techniques for determining the molecular composition of biological and biomedical samples. In this work, SR-IR is applied in the study of the lung cancer cells in different cell cycles. METHODS: We use a novel synchrotron based radiation infrared system combined synchronized model human lung carcinoma to reveal its unique character pattern. RESULTS: After using SR-IR microspectroscopy, we discovered that the ratio of protein to lipid in G1 and G2 states is around 4.0 and 6.1, respectively. Moreover, for the DNA at the wavenumber position of 1225 cm(-1) , the intensity ratio of G2 state to G1 state is approximately 1.6. These data indicate that the cell in G1 state has more lipid composition to prepare for the DNA synthesis, but the cell in G2 state has more protein composition to prepare for the mitosis. The cell has larger DNA concentration in G2 state, which can be explained for the DNA synthesis. CONCLUSION: Through our research, we demonstrate that different growth state of cancer cell presenting unique functional groups concentration profiles and distribution via using SR-IR microspectrometry. These applications will provide another ways to improve modern cancer screening in the future.

The correlation between the presence of viremia and clinical severity in patients with enterovirus 71 infection: a multi-center cohort study.

BACKGROUND: Enterovirus 71 (EV71) is a great disease burden across the whole world, particularly in Southeast Asia. However, in recent decades, the pathogenesis of severe EV71 infection was not well understood. This study was aimed to investigate the correlation between the presence of viremia and the clinical severity of EV71 infection. METHODS: We organized a prospective cohort study and enrolled laboratory-confirmed EV71 cases in six tertiary care hospitals in Taiwan during the EV71 epidemic from 2011 to 2012. Blood samples were collected once in the acute stage, on the first day of admission. We used real-time RT-PCR to detect EV71 viremia. Demographical and clinical data were collected and the clinical severity was categorized into four grades. Data analysis was performed to identify the risk factors of viremia and the correlation between viremia and clinical severity of EV71 infection. RESULTS: Of the total 224 enrolled patients, 59 (26%) patients were confirmed to have viremia. Two-thirds (68%) of viremic cases were detected within the first three days of infection. Viremia occurred more frequently in children under the age of one year old (odds ratios [OR] 4.82, p < 0.001) but the association between the presence of viremia and complicated EV71 infection was not found (OR 1.02, p = 0.96). In the viremia group, patients had significantly more severe complications if viremia was detected after the third day of disease onset (26% vs. 5%, p = 0.03). CONCLUSIONS: Viremia occurred more frequently in children under the age of one year and viremia detected beyond three days after the onset of disease correlated with more severe disease in EV71 patients.

Thermoelectric active cooling for transient hot spots in microprocessors.

Modern microprocessor performance is limited by local hot spots induced at high frequency by busy integrated circuit elements such as the clock generator. Locally embedded thermoelectric devices (TEDs) are proposed to perform active cooling whereby thermoelectric effects enhance passive cooling by the Fourier law in removing heat from the hot spot to colder regions. To mitigate transient heating events and improve temperature stability, we propose a novel analytical solution that describes the temperature response of a periodically heated hot spot that is actively cooled by a TED driven electrically at the same frequency. The analytical solution that we present is validated by experimental data from frequency domain thermal reflectance (FDTR) measurements made directly on an actively cooled Si thermoelectric device where the pump laser replicates the transient hot spot. We herein demonstrate a practical method to actively cancel the transient temperature variations on circuit elements with TEDs. This result opens a new path to optimize the design of cooling systems for transient localized hot spots in integrated circuits.

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.

Antioxidant, Analgesic, Anti-Inflammatory, and Hepatoprotective Effects of the Ethanol Extract of Mahonia oiwakensis Stem.

The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOS(EtOH)). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOS(EtOH) was analyzed by high-performance liquid chromatography (HPLC). The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOS(EtOH) exhibited antioxidative activity using the DPPH assay (IC(50), 0.743 mg/mL). The DPPH radical scavenging activity of MOS(EtOH) was five times higher that that of vitamin C. MOS(EtOH) was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOS(EtOH) (100 and 500 mg/kg) or silymarin (200 mg/kg) decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the CCl(4)-treated group. Histological evaluation showed that MOS(EtOH) reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOS(EtOH) were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA) level and nitric oxide (NO) contents. Our findings suggest that MOS(EtOH) has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOS(EtOH) for relieving pain and inflammation in folk medicine.

Antidepressive mechanisms of rhynchophylline in mice with chronic unpredictable stress-induced depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla ([Mi] Jack) (gouteng) exerts antidepressive effects. Rhynchophylline (RH), a major component of U. rhynchophylla, exerts similar pharmacological effects to those of gouteng. Thus, RH may have antidepressive effects. AIM OF THE STUDY: To investigate the anti-depressive effects of RH in chronic unpredictable mild stress (CUMS)-induced depressive mice. The anti-depressive mechanism of RH determined by measuring the 5-HT levels, the expressions of cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in cortex and hippocampus. MATERIALS AND METHODS: The behaviors of CUMS-induced depressive mice were measured using an open field test (OFT), forced swimming test (FST), and tail suspension test (TST). 5-HT levels were measured using an ELISA kits. The expressions of BDNF and CREB were determined using western blot test. RESULTS: RH increased the frequency of rearing and grooming in the OFT and decreased the immobility time in the FST and TST. RH effectively increased the 5-HT level and BDNF and CREB expressions in the cortex and hippocampus. CONCLUSION: Our findings indicate that the antidepressive mechanism of RH is related to increased levels of 5-HT from regulating CREB and BDNF expressions in cortex and hippocampus.

An evaluation of the safety and immunogenicity of MVC-COV1901: Results of an interim analysis of a phase III, parallel group, randomized, double-blind, active-controlled immunobridging study in Paraguay.

BACKGROUND: Data from previous studies of the MVC-COV1901 vaccine, a subunit vaccine against SARS-CoV-2 based on the stable prefusion spike protein (S-2P) adjuvanted with CpG 1018 adjuvant and aluminum hydroxide, suggest that the vaccine is generally safe and elicits a good immune response in healthy adults and adolescents. By comparing with AZD1222, this study adds to the findings from previous trials and further evaluates the breadth of protection offered by MVC-COV1901. METHODS: In this phase 3, parallel group, randomized, double-blind, active-controlled trial conducted in 2 sites in Paraguay, we assigned adults aged 18-91 years in a 1:1 ratio to receive intramuscular doses of MVC-COV1901 or AZD1222 administered as scheduled in the clinical trial. Serum samples were collected on the day of vaccination and 14 days after the second dose. Primary and secondary safety and immunogenicity endpoints were assessed. In addition, other outcomes investigated were cross-reactive immunity against the Omicron strain and the induction of IgG subclasses. RESULTS: A total of 1,030 participants underwent randomization. Safety data was derived from this set while primary immunogenicity data involved a per-protocol immunogenicity (PPI) subset including 225 participants. Among the participants, 58% are seropositive at baseline. When compared against AZD1222, MVC-COV1901 exhibited superiority in terms of neutralizing antibody titers and non-inferiority in terms of seroconversion rates. Reactogenicity was generally mild and no serious adverse event was attributable to MVC-COV1901. Both vaccines have a Th1-biased response predominated by the production of IgG1 and IgG3 subclasses. Omicron-neutralizing titers were 44.5 times lower compared to wildtype-neutralizing titers among seronegative individuals at baseline. This fold-reduction was 3.0 times among the seropositive. CONCLUSION: Safety and immunogenicity data of MVC-COV1901 from the study in Paraguay confirm previous results. The previous infection coupled with vaccination of this vaccine may offer protection against the Omicron strain though its durability is still unknown.

Safety and immunogenicity of homologous versus heterologous booster dose with AZD1222, mRNA-1273, or MVC-COV1901 SARS-CoV-2 vaccines in adults: An observer-blinded, multi-center, phase 2 randomized trial.

OBJECTIVES: To report the safety and immunogenicity profile of a protein subunit vaccine (MVC-COV1901) compared to AZD1222 and mRNA-1273 when given as a third (booster) dose to individuals who have completed different primary vaccine regimens. METHODS: Individuals were classified according to their primary vaccine regimens, including two-dose MVC-COV1901, AZD1222, or mRNA-1273. A third dose of either half-dose MVC-COV1901, full-dose MVC-COV1901, standard-dose AZD1222, half-dose mRNA-1273 was administered in a 1:1:1:1 treatment ratio to individuals with an interval range of 84-365 days after the second dose. Endpoints included safety, humoral immunogenicity, and cell-mediated immune response on trial days 15 and 29. Exploratory endpoint included testing against variants of concern (Omicron). RESULTS: Overall, 803 participants were randomized and boosted - 201 received half-dose MVC-COV1901, 196 received full-dose MVC-COV1901, 203 received AZD1222, and 203 received half-dose mRNA-1273. Reactogenicity was mild to moderate, and less in the MVC-COV1901 booster group. Heterologous boosting provided the best immunogenic response. Boosting with mRNA-1273 in MVC-COV1901 primed individuals induced the highest antibody titers, even against Omicron, and cell-mediated immune response. CONCLUSIONS: Overall, MVC-COV1901 as a booster showed the best safety profiles. MVC-COV1901 as a primary series, with either homologous or heterologous booster, elicited the highest immunogenic response. CLINICALTRIALS: gov registration NCT05197153.

Efficient production of an engineered apoptin from chicken anemia virus in a recombinant E. coli for tumor therapeutic applications.

BACKGROUND: Apoptin, a nonstructural protein encoded by the VP3 gene of chicken anemia virus (CAV), has been shown to not only induce apoptosis when introduced into the precursors of chicken thymocytes, but has been found to specifically kill human cancer cells, tumor cell and transformed cells without affecting the proliferation of normal cells. This tumor-specific apoptotic characteristic of the protein potentially may allow the development of a protein drug that has applications in tumor therapy. However, several major problems, which include poor expression and poor protein solubility, have hampered the production of apoptin in bacteria. RESULTS: Significantly increased expression of recombinant full-length apoptin that originated from chicken anemia virus was demonstrated using an E. coli expression system. The CAV VP3 gene was fused with a synthetic sequence containing a trans-acting activator of transcription (TAT) protein transduction domain (PTD). The resulting construct was cloned into various different expression vectors and these were then expressed in various E. coli strains. The expression of the TAT-Apoptin in E. coli was significantly increased when TAT-Apoptin was fused with GST-tag rather than a His-tag. When the various rare amino acid codons of apoptin were optimized, the expression level of the GST-TAT-Apoptin(opt) in E. coli BL21(DE3) was significantly further increased. The highest protein expression level obtained was 8.33 g/L per liter of bacterial culture after induction with 0.1 mM IPTG for 4 h at 25 °C. Moreover, approximately 90% of the expressed GST-TAT-Apoptin(opt) under these conditions was soluble. After purification by GST affinity chromatography, the purified recombinant TAT-Apoptin(opt) protein was used to evaluate the recombinant protein's apoptotic activity on tumor cells. The results demonstrated that the E. coli-expressed GST-TAT-apoptin(opt) showed apoptotic activity and was able to induce human premyelocytic leukemia HL-60 cells to enter apoptosis. CONCLUSIONS: On expression in E. coli, purified recombinant TAT-Apoptin(opt) that has been fused to a GST tag and had its codons optimized, was found to have great potential. This protein may in the future allow the development of a therapeutic protein that is able to specifically kill tumor cells.