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Background: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. Methods: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. Results: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432–5p and miRNA-382–3p were upregulated in patients with abnormal SSS. Conclusion: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.

Climatic factors are closely associated with the occurrence of vector-borne diseases, and they also influence the distribution of vectors. The occurrence of plague is closely related to the population dynamics of fleas and their host animals, as well as climatic conditions. This study focused on Xilingol League, utilizing climatic and flea index data from 2012 to 2021. Spearman correlation and ''Boruta'' importance analysis were conducted to screen for climatic variables. A generalized additive model (GAM) was employed to investigate the influence of climatic factors and rodent density on the flea index. GAM analysis revealed distinct trends in flea index among different rodent hosts. For Meriones unguiculatus, the flea index declined with increased density and with higher humidity, yet rose with greater lagged sunshine duration. For Spermophilus dauricus, an initial increase in flea index with density was observed, followed by a decrease, and a rise in the index was noted when ground temperatures were low. This study reveals the nonlinear interactions and lag effects among climatic factors, density, and flea index. Climatic factors and density variably influence the flea index of two Yersinia pestis hosts. This research advances the prediction and early warning efforts for plague control, providing a theoretical basis for rodent and flea eradication strategies.

Background: This study aimed to understand the longitudinal relationship between psychosocial stress with tic exacerbation in children with Tourette syndrome (TS) and chronic tic disorder. Methods: Consecutive ratings of tic severity as well as child and parental reports of psychosocial stress were obtained for 373 children (296 males, 77 females; mean age 9y 5mo; SD 3y 3mo) with TS and chronic tic disorder between January 2018 and December 2020. The Yale Global Tic Severity Scale (YGTSS) global severity score, total tic score, and impairment rating were calculated. The stressful events and YGTSS measurements were used and treated as time-varying variables in the analyses. Models that controlled for non-independence among the repeated observations using a random intercept and random slope model were employed. Each participant was treated as a random factor in the modelling. Results: Family-related stress, personal relationship stress and school-related stress were independently associated with increasing YGTSS global severity, total tic score, and impairment rating over time. An increased number of stressful events were associated with increased severity of tics. Conclusion: Family, personal relationships, and school-related stress were consistently associated with the exacerbation of tics. Managing these stressful events is important in the treatment of TS and chronic tic disorder.

Abstract Pulex simulans and Polygenis gwyni are vectors of many flea‐borne diseases. They were widely recorded in the United States and Mexico between 1970 and 2000. Maximum entropy models were used to explore the habitats of both fleas under different climate scenarios to provide the scientific basis for the surveillance and control of flea‐borne diseases. We screened climate variables by principal component analysis and Pearson's correlation test and evaluated model performance by ROC curve. ArcMap was used to visualize expressions. Under current climatic conditions, the medium and highly suitable areas for P. simulans are estimated to be 9.16 × 106 km2 and 4.97 × 106 km2, respectively. These regions are predominantly located in South America, along the Mediterranean coast of Europe, the southern part of the African continent, the Middle East, North China, and Australia. For P. gwyni, the medium and highly suitable areas under current climatic conditions are approximately 4.01 × 106 and 2.04 × 106 km2, respectively, with the primary distribution in North China extending to the Himalayas, near the Equator in Africa, and in a few areas of Europe. Under future climate scenarios, in the SSP3‐7.0 scenario for the years 2081–2100, the area of high suitability for P. simulans is projected to reach its maximum. Similarly, in the SSP2‐4.5 scenario for 2061–2080, the area of high suitability for P. gwyni is expected to reach its maximum. Under global climate change, there is a large range in the potential distribution for both fleas, with an overall upward trend in the area of habitat under future climate scenarios. Governments should develop scientific prevention and control measures to prevent the invasive alien species flea.

Abstract Background Marginally low birth weight (MLBW) is defined as a birth weight of 2000 ~ 2499 g. Inconsistent findings have been reported on whether children with low birth weight had higher rates of neurological, attention, or cognitive symptoms. No studies have explored the occurrence of clinically diagnosed psychiatric disorders in term- born MLBW infants. We aimed to investigate the risk of subsequent psychiatric disorders in term-born children with MLBW. Methods This is a nationwide retrospective cohort study, by analysing the data from Taiwan’s National Health Insurance Research Database from 2008 to 2018. The study population includes propensity-score-matched term-born infants with MLBW and those without MLBW (birth weight ≥ 2500 g). Cox proportional hazard analysis was used after adjustment for potential demographic and perinatal comorbidity confounders. Incidence rates and hazard ratios (HR) of 11 psychiatric clinical diagnoses were evaluated. Results A total of 53,276 term-born MLBW infants and 1,323,930 term-born infants without MLBW were included in the study. After propensity score matching for demographic variables and perinatal comorbidities, we determined that the term-born MLBW infants (n = 50,060) were more likely to have attention deficit and hyperactivity disorder (HR = 1.26, 95% confidence interval (CI) [1.20, 1.33]), autism spectrum disorder (HR = 1.26, 95% CI [1.14, 1.40]), conduct disorder (HR = 1.25, 95% CI [1.03, 1.51]), emotional disturbance (HR: = 1.13, 95% CI [1.02, 1.26]), or specific developmental delays (HR = 1.38, 95% CI [1.33, 1.43]) than term-born infants without MLBW (n = 50,060). Conclusion MLBW was significantly associated with the risk of subsequent psychiatric disorder development among term-born infants. The study findings demonstrate that further attention to mental health and neurodevelopment issues may be necessary in term-born children with MLBW. However, possibilities of misclassification in exposures or outcomes, and risks of residual and unmeasured confounding should be concerned when interpreting our data.

Objective: In patients with atrial fibrillation (AF) and end-stage renal disease (ESRD), oral anticoagulants are contraindicated, and left atrial appendage occlusion (LAAO) is an alternative treatment. However, the efficacy of thromboembolic prevention using LAAO in these patients has rarely been reported in Asian populations. To our knowledge, this is the first long-term LAAO study in patients with AF undergoing dialysis in Asia. Methods: In this study, 310 patients (179 men) with a mean age of 71.3 ± 9.6 years and mean CHA2DS2-VASc 4.2 ± 1.8 were consecutively enrolled at multiple centers in Taiwan. The outcomes of 29 patients with AF and ESRD undergoing dialysis who underwent LAAO were compared to those without ESRD. The primary composite outcomes were stroke, systemic embolization, or death. Results: No difference in mean CHADS-VASc score was noted between patients with versus without ESRD (4.1 ± 1.8 vs. 4.6 ± 1.9, p = 0.453). After a mean follow-up of 38 ± 16 months, the composite endpoint was significantly higher in patients with ESRD (hazard ratio, 5.12 [1.4–18.6]; p = 0.013) than in those without ESRD after LAAO therapy. Mortality was also higher in patients with ESRD (hazard ratio, 6.6 [1.1–39.7]; p = 0.038). The stroke rate was numerically higher in patients with versus without ESRD, but the difference was not statistically significant (hazard ratio, 3.2 [0.6–17.7]; p = 0.183). Additionally, ESRD was associated with device-related thrombosis (odds ratio, 6.15; p = 0.047). Conclusion: Long-term outcomes of LAAO therapy may be less favorable in patients with AF undergoing dialysis, possibly because of the poor condition of patients with ESRD.

Background and purpose: Pneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. Methods: This retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. Results: The cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p

BackgroundA jaundice-predominant presentation of Kawasaki disease (KD) is atypical.MethodsA total of 12 children with KD with a predominant manifestation of jaundice at MacKay Children's Hospital were reviewed, along with 42 cases reported in the literature since 1990.ResultsThe median age of the 12 patients was 1.85 years (range: 3 months–4 years), and 66.6% were male. All of the patients had elevated liver function at presentation, 50% had hydrops of the gallbladder, and almost 60% had gastrointestinal symptoms and signs. Complete KD was evident in 11 of the 12 patients (91.7%), and two patients (16.7%) had recurrent episodes. All of the patients received intravenous immunoglobulin (IVIG); however, one-third were refractory to treatment. Corticosteroids were used in five (41.7%) of the patients. Three (25%) of the patients had shock, and seven (58.3%) had coronary artery abnormalities, of whom one (8.3%) had persistent coronary artery aneurysm and the others recovered. A review of the 42 cases in the literature showed that the children with a jaundice-predominant presentation of KD had high rates of IVIG-refractory disease (25%), coronary artery abnormalities (25%), shock (13.2%), and corticosteroid treatment (24.2%).ConclusionsChildren with KD presenting with a jaundice-predominant manifestation are at a higher risk of IVIG-refractory disease, coronary artery abnormalities, and more recurrent episodes. Physicians should be aware of the risk of shock in this population.

Background Implantation of the left atrial appendage occluder (LAAO) has been proven to prevent stroke effectively in patients with atrial fibrillation who cannot tolerate anticoagulants. Incomplete endothelization of LAAO may cause device‐related thrombus, and currently no good image modality exists to clearly see LAAO endothelialization. We aimed to use coronary optic coherence tomography (OCT) to visualize LAAO endothelialization. Methods and Results We enrolled 14 patients (72.8±9.4 years old) undergoing pulmonary vein isolation with a preexisting LAAO implanted more than 1 year ago (5 Watchman and 9 Amulet). After pulmonary vein isolation, we did OCT via steerable sheath and coronary guiding catheter to adjust OCT probe location and injected contrast medium to visualize the LAAO surface. In vitro testing was also performed to see the bare occluder. In vitro OCT showed the surface of the bare device as an interrupted granule pattern, which included the Watchman surface polytetrafluoroethylene membrane string, Amulet disc metal strut, and inner polytetrafluoroethylene membrane string. In the implanted Watchman, OCT showed endothelialization as a smooth surface layer with noninterrupted coarser granules. In the implanted Amulet, OCT showed endothelialization as thin (early) or thick (late) endothelialization layer covering struts with OCT shadows. Among patients with Watchman, 2 showed no, 2 early, and 1 complete endothelialization. Among patients with Amulet, 2 showed no, 3 early, and 4 late endothelialization. Conclusions We demonstrated the feasibility of OCT to visualize LAAO endothelization with high resolution. Further studies are needed to determine antithrombotic regimens if incomplete endothelization is detected. A new OCT catheter may be designed specifically for LAAO.

Abstract Background It is common to support cardiovascular function in critically ill patients with extracorporeal membrane oxygenation (ECMO). The purpose of this study was to identify patients receiving ECMO with a considerable risk of dying in hospital using machine learning algorithms. Methods A total of 1342 adult patients on ECMO support were randomly assigned to the training and test groups. The discriminatory power (DP) for predicting in-hospital mortality was tested using both random forest (RF) and logistic regression (LR) algorithms. Results Urine output on the first day of ECMO implantation was found to be one of the most predictive features that were related to in-hospital death in both RF and LR models. For those with oliguria, the hazard ratio for 1 year mortality was 1.445 (p

Distributed state estimation is one of the critical technologies in the field of target tracking, where the process noise and measurement noise may have a heavy-tailed distribution. Traditionally, heavy-tailed distributions like the student-t distribution are employed, but our observation reveals that Gaussian noise predominates in many instances, with occasional outliers. This sporadic reliance on heavy-tailed distributions can degrade performances or necessitate frequent parameter adjustments. To overcome this, we introduce a novel distributed consensus multi-distribution state estimation method that combines Gaussian and student-t filters. Our approach establishes a system model using both Gaussian and student-t distributions. We derive a multi-distribution filter for a single sensor, assigning probabilities to Gaussian and student-t noise models. Parallel estimation under both distributions, utilizing Gaussian and student-t filters, allows us to calculate the likelihood of each distribution. The fusion of these results yields a mixed-state estimation and corresponding error matrix. Recognizing the increasing degrees of freedom in the student-t distribution over time, we provide an effective approximation. An information consensus strategy for multi-distribution filters is introduced, achieving global estimation through consensus on fused local filter results via interaction with neighboring nodes. This methodology is extended to the distributed case, and the recursive process of the distributed multi-distribution consensus state estimation method is presented. Simulation results demonstrate that the estimation accuracy of the proposed algorithm improved by at least 20% compared to that of the traditional algorithm in scenarios involving both Gaussian and heavy-tailed distributions.

The potential adverse effects of coronavirus disease 2019 (COVID-19) vaccinations raise public concerns. Data from Taiwan’s Vaccine Injury Compensation Program (VICP) can provide valuable insights. This study analyzed the preliminary application data for COVID-19 vaccine compensation in Taiwan’s VICP, focusing on applicants receiving vaccines between March 2021 and June 2022. Among the 2941 adverse events, 113 cases (3.8%) were deemed causally associated with vaccination, 313 (10.6%) were indeterminate, and 2515 (85.5%) had no causal association. Nearly half (47.6%) of the applicants were over 60 years old, and 76.6% had a history of pre-existing chronic diseases. Among the 426 vaccine-associated or indeterminate cases, the most common causes were hematological diseases and thrombosis. There were 920 mortality cases reported, and 97.4% were unassociated with vaccination. Only five deaths were judged to be associated with the COVID-19 vaccination, all involving the adenovirus vector vaccine and thrombosis with thrombocytopenia syndrome. In conclusion, most compensation applications were not causally linked to vaccination. Compared to other countries, the number of applications in Taiwan’s VICP is relatively high. These findings may indicate a need to adjust the application requirements for compensation in Taiwan’s program.

This study developed a DC-free technique that used dark-mode scanning capacitance microscopy (DM-SCM) with a small-area contact electrode to evaluate and image equivalent oxide thicknesses (EOTs). In contrast to the conventional capacitance–voltage (C–V) method, which requires a large-area contact electrode and DC voltage sweeping to provide reliable C–V curves from which the EOT can be determined, the proposed method enabled the evaluation of the EOT to a few nanometers for thermal and high-k oxides. The signal intensity equation defining the voltage modulation efficiency in scanning capacitance microscopy (SCM) indicates that thermal oxide films on silicon can serve as calibration references for the establishment of a linear relationship between the SCM signal ratio and the EOT ratio; the EOT is then determined from this relationship. Experimental results for thermal oxide films demonstrated that the EOT obtained using the DM-SCM approach closely matched the value obtained using the typical C–V method for frequencies ranging from 90 kHz to 1 MHz. The percentage differences in EOT values between the C–V and SCM measurements were smaller than 0.5%. For high-k oxide films, DM-SCM with a DC-free operation may mitigate the effect of DC voltages on evaluations of EOTs. In addition, image operations were performed to obtain EOT images showing the EOT variation induced by DC-stress-induced charge trapping. Compared with the typical C–V method, the proposed DM-SCM approach not only provides a DC-free approach for EOT evaluation, but also offers a valuable opportunity to visualize the EOT distribution before and after the application of DC stress.

In this paper, Cu-BTC derived mesoporous CuS nanomaterial (m-CuS) was synthesized via a two-step process involving carbonization and sulfidation of Cu-BTC for colorimetric glutathione detection. The Cu-BTC was constructed by 1,3,5-benzenetri-carboxylic acid (H3BTC) and Cu2+ ions. The obtained m-CuS showed a large specific surface area (55.751 m2/g), pore volume (0.153 cm3/g), and pore diameter (15.380 nm). In addition, the synthesized m-CuS exhibited high peroxidase-like activity and could catalyze oxidation of the colorless substrate 3,3′,5,5′-tetramethylbenzidine to a blue product. Peroxidase-like activity mechanism studies using terephthalic acid as a fluorescent probe proved that m-CuS assists H2O2 decomposition to reactive oxygen species, which are responsible for TMB oxidation. However, the catalytic activity of m-CuS for the oxidation of TMB by H2O2 could be potently inhibited in the presence of glutathione. Based on this phenomenon, the colorimetric detection of glutathione was demonstrated with good selectivity and high sensitivity. The linear range was 1–20 μM and 20–300 μM with a detection limit of 0.1 μM. The m-CuS showing good stability and robust peroxidase catalytic activity was applied for the detection of glutathione in human urine samples.

Background: Since 2015, 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program in Taiwan. Subsequently, the serotypes of the main circulating Streptococcus pneumoniae strains have changed. PCV administration is also associated with changes in the antimicrobial susceptibility of S. pneumoniae strains. Therefore, in this study, we analyzed the serotype distribution and antimicrobial susceptibility of S. pneumoniae in pediatric infections. Methods: Children with S. pneumoniae infections, including invasive pneumococcal disease (IPD) and non-IPD, were enrolled from January 2010 to December 2020. The samples were collected from Mackay Memorial Hospital, MacKay Children's Hospital, and Hsinchu Mackay Hospital in Taiwan. We analyzed the epidemiology of sample collection site, infection diagnosis, and the serotype and antimicrobial susceptibility of S. pneumoniae strains. The study period was divided into time points before and after PCV13 administration. Results: In total, 322 isolates were collected during the study period. The incidence of IPD declined annually, from 29.7% before 2015 to 7.3% after 2015 (p

Background and purpose: Urinary tract infections (UTIs) are the most common bacterial infection in young children. This study aimed to formulate nomogram plots for clinicians to predict UTIs in children aged

Field-effect transistor (FET)-based biosensors are powerful analytical tools for detecting trace-specific biomolecules in diverse sample matrices, especially in the realms of pandemics and infectious diseases. The primary concern in applying these biosensors is their stability, a factor directly impacting the accuracy and reliability of sensing over extended durations. The risk of biosensor degradation is substantial, potentially jeopardizing the sensitivity and selectivity and leading to inaccurate readings, including the possibility of false positives or negatives. This paper delves into the documented degradation of silicon nanobelt FET (NBFET) biosensors induced by buffer solutions. The results highlight a positive correlation between immersion time and the threshold voltage of NBFET devices. Secondary ion mass spectrometry analysis demonstrates a gradual increase in sodium and potassium ion concentrations within the silicon as immersion days progress. This outcome is ascribed to the nanobelt’s exposure to the buffer solution during the biosensing period, enabling ion penetration from the buffer into the silicon. This study emphasizes the critical need to address buffer-solution-induced degradation to ensure the long-term stability and performance of FET-based biosensors in practical applications.

We present an extension of our study of the energy shift of the atomic emissions subject to charged-neutral outside dense plasma following the good agreement between the experimental measurements and our recent theoretical estimates for the α and β emission lines of a number of H-like and He-like ions. In particular, we are able to further demonstrate that the plasma-induced transition energy shift could indeed be interpolated by the simple quasi-hydrogenic picture based on the application of the Debye–Hückel (DH) approximation for the n=3 to n=2 transitions of the He-like ions. Our theoretically estimated redshifts of those emissions may offer the impetus for additional experimental measurement to facilitate the diagnostic efforts in the determination of the temperature and density of the dense plasma.

BackgroundCoronavirus disease 2019 (COVID-19) had caused huge impacts worldwide. Polymerase chain reaction (PCR) is the mainstay diagnostic modality. In most hospitals in Taiwan, samples for PCR are collected at emergency department (ER) or outdoor clinics to avoid virus spread inside hospitals. Home rapid antigen test (RAT) is a feasible, low-cost, and convenient tool with moderate sensitivity and high specificity, which can be performed at home to reduce hospital visits. Due to comparably low severity of omicron variant and high vaccine coverage (~80% residents fully vaccinated with AstraZeneca, Moderna, or Pfizer BioNTech COVID-19 vaccines as of March 2022), the policy was shifted from containment to co-existing with COVID-19 in Taiwan. Virus spread rapidly in the community after the ease of social restrictive measurements. To acquire a confirmed diagnosis, PCR testing was requested for people with suspected COVID-19 infection. As a consequence, people with respiratory symptoms or contact history surged into hospitals for PCR testing, thus, the medical capacity was challenged. The diagnostic policy was altered from PCR to RAT, but the impact of diagnostic policy change remains unclear.ObjectivesWe conducted this study to investigate the number of COVID-19 cases, PCR testing, hospitalizations, mortalities, and hospital visits during the epidemic and evaluate the impact of diagnostic policy change on hospital visits.MethodsThe diagnostic policy change was implemented in late May 2022. We used nationwide and hospital-based data of COVID-19 cases, PCR testing, hospitalizations, mortalities, and hospital visits before and after policy change as of 31 Jul 2022.ResultsDuring the omicron epidemic, significant and synchronous increase of COVID-19 patients, PCR testing, hospital visits were observed. COVID-19 cases increased exponentially since April 2022 and the COVID-19 patients peaked in June (1,943, 55,571, and 61,511 average daily new cases in April, May, and June, respectively). The PCR testing peaked in May (85,788 daily tests) with high positive rate (81%). The policy of RAT as confirmatory diagnosis was implemented on 26 May 2022 and a substantial decline of PCR testing numbers occurred (85,788 and 83,113 daily tests in May and June). People hospitalized for COVID-19 peaked in June (821.8 patients per day) and decreased in July (549.5 patients). The mortality cases also peaked in June (147 cases/day). This trend was also validated by the hospital-based data with a significant decrease of emergency department visits (11,397 visits in May while 8,126 visits in June) and PCR testing (21,314 in May and 6,158 in June). The proportion of people purely for PCR testing also decreased (10–26 vs. 5–14%, before and after policy change, respectively).ConclusionsThe impact of diagnostic policy change was a complicated issue and our study demonstrated the huge impact of diagnostic policy on health seeking behavior. The PCR testing numbers and emergency department visits had substantial decrease after diagnostic policy change, and the plateau of epidemic peak eased gradually in ~1 month later. Widespread RAT application may contribute to the decreased hospital visits and preserve medical capacity. Our study provides some evidences for policy maker's reference.

Purpose: This study examined the efficacy of prescribing antibiotics, specifically a single dose of vancomycin, in reducing the incidence of culture-positive and culture-negative sepsis prior to the removal of peripherally inserted central catheters (PICCs). Materials and methods: We retrospectively reviewed charts of infants who had PICCs in a tertiary level hospital during the period from 2010 to 2019. The incidence of post-catheter removal clinical sepsis between the groups with or without antibiotics was compared. The antibiotic group was defined by receiving a single dose of vancomycin or any other antibiotic prior to line removal. Results: We enrolled 585 PICC removal episodes in 546 infants for analysis. Antibiotics were given prior to removal in 257 cases (43.9%) and not given prior to removal in 328 cases (56.1%). There were 13 episodes of post-catheter removal clinical sepsis detected within 72 h (2.2%), 2 of which were culture-positive (0.3%). A 9.3-fold decrease in the odds for clinical sepsis was observed in the antibiotic group (p = 0.01). The incidence of post-catheter removal sepsis was decreased by a single prophylactic dose of vancomycin (p = 0.02), whereas the use of other antibiotics showed no effect (p = 0.35). Logistic regression analysis demonstrated that comorbidities with gastrointestinal diseases (p = 0.01), PICC insertion sites in the scalp and neck (p = 0.04), and no vancomycin administration prior to line removal (p = 0.02) were independent risk factors for subsequent clinical sepsis. Conclusion: A single prophylactic dose of vancomycin prior to PICC line removal might reduce clinical sepsis events in infants.

Background/purpose: Central nervous system infections can cause severe complications and even death in children. Early diagnosis of the causative pathogen can guide appropriate treatment and improve outcomes. The BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) is a multiplex polymerase chain reaction (PCR) assay targeting 14 pathogens. We aimed to examine FA-ME performance compared with conventional assays and its effect on antimicrobial usage. Methods: We prospectively enrolled 55 pediatric patients with suspected meningitis or encephalitis and simultaneously performed FA-ME and conventional assays. Sixty-three hospitalized patients with CNS infection before implementing FA-ME were considered controls. We compared the FA-ME results with conventional assays and the empiric antimicrobial usage and hospital stay between the two study groups. Results: Nine patients (16.4%) tested positive by FA-ME, four were bacterial, and five were viral. Three additional pathogens were detected by conventional assays: Enterococcus faecalis, Leptospira, and herpes simplex virus type 2. In the control group, two bacterial pathogens were detected by CSF culture and four viral pathogens by single PCRs. Compared with the control group, the FA-ME group had a shorter time for pathogen detection, but there were no significant differences in pathogen detection rate, duration of empiric antimicrobial therapy, and length of hospital stay. Conclusion: Although no significant difference was found in empiric antimicrobial duration and length of stay between patients tested with FA-ME and conventional assays, FA-ME had the advantage of a shorter detection time and early exclusion of potential causative pathogens. The FA-ME results should be interpreted carefully based on the clinical presentation.

Abstract Adolescents and children play an important role in SARS-CoV-2 transmission and epidemiology. MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on stabilized spike protein adjuvanted with CpG 1018 and aluminum hydroxide that has received emergency use approval (EUA) for adults in Taiwan. In this study, we have investigated the safety and immunogenicity of two doses of MVC-COV1901 in adolescents. Healthy adolescents from the age of 12–17 years were randomly assigned to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups, with the most commonly reported adverse events being pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. The results here advocate the use of MVC-COV1901 in adolescents in the ongoing efforts to control the pandemic. ClinicalTrials.gov registration: NCT04951388.

Abstract Background Ventricular premature complex (VPC) is a common arrhythmia in clinical practice. VPC could trigger ventricular tachycardia/fibrillation or VPC-induced cardiomyopathy in susceptible patients. Existing screening methods require prolonged monitoring and are limited by cost and low yield when the frequency of VPC is low. Twelve-lead electrocardiogram (ECG) is low cost and widely used. We aimed to identify patients with VPC during normal sinus rhythm (NSR) using artificial intelligence (AI) and machine learning-based ECG reading. Methods We developed AI-enabled ECG algorithm using a convolutional neural network (CNN) to detect the ECG signature of VPC presented during NSR using standard 12-lead ECGs. A total of 2515 ECG records from 398 patients with VPC were collected. Among them, only ECG records of NSR without VPC (1617 ECG records) were parsed. Results A total of 753 normal ECG records from 387 patients under NSR were used for comparison. Both image and time-series datasets were parsed for the training process by the CNN models. The computer architectures were optimized to select the best model for the training process. Both the single-input image model (InceptionV3, accuracy: 0.895, 95% confidence interval [CI] 0.683–0.937) and multi-input time-series model (ResNet50V2, accuracy: 0.880, 95% CI 0.646–0.943) yielded satisfactory results for VPC prediction, both of which were better than the single-input time-series model (ResNet50V2, accuracy: 0.840, 95% CI 0.629–0.952). Conclusions AI-enabled ECG acquired during NSR permits rapid identification at point of care of individuals with VPC and has the potential to predict VPC episodes automatically rather than traditional long-time monitoring.

Purpose: This study aimed to evaluate whether vitamin D supplementation can reduce the incidence of influenza and enterovirus infection in Taiwanese children. Methods: This randomized, double-blind, controlled trial included children aged two to five years between April 2018 and October 2019 from daycare centers. All the participants were randomly assigned to a vitamin D supplementation group (2000 IU/day) or placebo group for one month. The primary outcome was the incidence of influenza and enterovirus infection in the following six months, and the secondary outcome was the incidence of influenza and enterovirus infection in the children's household members. Results: Two hundred and forty-eight children participated. The vitamin D group showed a relative risk reduction of 84% against influenza compared to the placebo group but did not reach statistical significance. Kaplan–Meier curves revealed that the placebo group had a higher probability of influenza infection than the vitamin D group (log-rank test, p = 0.055), but the incidence of enterovirus infection was similar between the two groups (p = 0.946) among children. Among children's household members, the incidence of influenza (p = 0.586) and enterovirus infection (p = 0.528) were both similar between the two groups. All children who were tested for serum 25(OH)D levels after vitamin D intervention had 25(OH)D levels above 30 ng/ml Conclusion: Vitamin D supplementation may have a small preventative effect against influenza infection but does not affect enterovirus infection among preschool children. A high-dose short-term vitamin D intervention might be a way to elevate children's serum vitamin D levels in the first month of starting kindergarten.

Purpose: This study aimed to describe the etiology, clinical features, hospital course, and outcomes of hospitalized children with skin and soft tissue infections (SSTIs) and to test if clinical and laboratory variables at admission could differentiate between community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-sensitive S. aureus (CA-MSSA). Methods: We reviewed the clinical, laboratory, treatment, and outcome data for children hospitalized with SSTIs, aged 0–18 years at MacKay Children's Hospital between 2010 and 2019. Multivariable logistic regression was used to identify independent predictors of CA-MRSA and CA-MSSA SSTIs. Results: A total of 1631 patients were enrolled. Erysipelas/cellulitis (73.8%) was the most common pediatric SSTI type, followed by acute lymphadenitis (13.6%) and abscess/furuncle/carbuncle (8.6%). Among the 639 culture-positive isolates (purulent SSTIs), 142 (22.2%) were CA-MSSA and 363 (56.8%) were CA-MRSA. The age group 0–1 month (OR, 6.52; 95% CI 1.09–38.92; P = 0.04) and local lymph node reaction (OR, 2.47; 95% CI 1.004–6.08; P = 0.049) were independent factors for differentiating children with CA-MSSA from those with CA-MRSA SSTIs. MRSA isolates in our cohort were highly susceptible to glycopeptides (100%), linezolid (100%), daptomycin (100%), and sulfamethoxazole/trimethoprim (98.6%) but were significantly less susceptible to clindamycin compared with MSSA (34.2% vs. 78.2%, P

Electrocatalytic CO2 reduction (ECR) to high value-added chemicals by using renewable electricity presents a promising strategy to realize “carbon neutrality”. However, the ECR system is still limited by its low current density and poor CO2 utilization efficiency. Herein, by using the confinement effect of covalent organic frameworks (COFs) to confine the in-situ growth of metal nanoclusters (NCs), we develop a series of Cu NCs encapsulated on COF catalysts (Cu-NC@COF) for ECR. Among them, Cu-NC@CuPc-COF as a gas diffusion electrode (GDE) achieves a maximum CO2-to-CH4 Faradaic efficiency of 74 ​± ​3% (at −1.0 ​V vs. Reversible Hydrogen Electrode (RHE)) with a current density of 538 ​± ​31 ​mA ​cm−2 (at −1.2 ​V vs. RHE) in a flow cell, making it one of the best among reported materials. More importantly, the current density is much higher than the relevant industrial current density (200 ​mA ​cm−2), indicating the potential for industrial application. This work opens up new possibilities for the design of ECR catalysts that utilize synergistic strategy.

Background Atrial fibrillation (AF) is associated with increasing risk of thromboembolic or ischemic stroke. The CHA2DS2‐VASc score is a well‐established predictor of AF stroke. Patients with AF have an increased risk of stroke if they have diabetes. Use of sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) has been shown to be associated with favorable cardiovascular outcomes in patients with diabetes. It was unknown whether use of SGLT2i decreased stroke risk in patients with AF who have diabetes. Methods and Results A total of 9116 patients with AF and diabetes from the National Taiwan University historical cohort were longitudinally followed up for 5 years (January 2016–December 2020). The risk of stroke related to SGLT2i use was evaluated by Cox model, adjusting CHA2DS2‐VASc score in the propensity score–matched population with 474 SGLT2i users and 3235 nonusers. Adverse thromboembolic end points during follow‐up were defined as ischemic stroke. The mean age was 73.2±10.5 years, and 61% of patients were men. There were no significant differences of baseline characteristics between users and nonusers of SGLT2i, including CHA2DS2‐VASc score in the propensity score–matched population. The stroke rate was 3.4% (95% CI, 2.8–4.2) patient‐years in SGLT2i users and 4.3% (95% CI, 4.0–4.6) in nonusers (P=0.021). SGLT2i users had a 20% reduction of stroke (hazard ratio, 0.80 [95% CI, 0.64–0.99]; P=0.043) after adjustment for the CHA2DS2‐VASc score. Conclusions Use of SGLT2i was associated with a lower stroke risk in patients with diabetes and AF, and it may be considered to escalate SGLT2i to the first‐line treatment in patients with diabetes and AF.

Background Coronavirus disease 2019 (COVID-19) has caused an enormous loss of life worldwide. The spike protein of the severe acute respiratory syndrome coronavirus 2 is the cause of its virulence. Bamlanivimab, a recombinant monoclonal antibody, has been used alone or in combination with etesevimab to provide passive immunity and improve clinical outcomes. A systematic review and meta-analysis was conducted to investigate the therapeutic effects of bamlanivimab with or without etesevimab (BAM/ETE) treatment. Methods Our study was registered in PROSPERO (registry number CRD42021270206). We searched the following electronic databases, without language restrictions, until January 2023: PubMed, Embase, medRxiv, and the Cochrane database. A systematic review and meta-analysis was conducted based on the search results. Results Eighteen publications with a total of 28,577 patients were identified. Non-hospitalized patients given bamlanivimab with or without etesevimab had a significantly lower risk of subsequent hospitalization (18 trials, odds ratio (OR): 0.37, 95% confidence interval (CI): [0.29–0.49], I2: 69%; p < 0.01) and mortality (15 trials, OR: 0.27, 95% CI [0.17–0.43], I2: 0%; p = 0.85). Bamlanivimab monotherapy also reduced the subsequent risk of hospitalization (16 trials, OR: 0.43, 95% CI [0.34–0.54], I2: 57%; p = 0.01) and mortality (14 trials, OR: 0.28, 95% CI [0.17–0.46], I2: 0%; p = 0.9). Adverse events from these medications were uncommon and tolerable. Conclusions In this meta-analysis, we found the use of bamlanivimab with or without etesevimab contributed to a significantly-reduced risk of subsequent hospitalization and mortality in non-hospitalized COVID-19 patients. However, resistance to monoclonal antibodies was observed in COVID-19 variants, resulting in the halting of the clinical use of BAM/ETE. Clinicians’ experiences with BAM/ETE indicate the importance of genomic surveillance. BAM/ETE may be repurposed as a potential component of a cocktail regimen in treating future COVID variants.

Vaccination has been a game-changer in the long battle against COVID-19. However, waning vaccine-induced immunity and the immune evasion of emerging variants create challenges. The rapid-fire development of bivalent vaccines (BVs), comprising ancestral strains and a new variant, was authorized to prevent COVID-19, but the effectiveness of the updated vaccines remains largely unclear. Electronic databases were searched to investigate the immunogenicity and reactogenicity of BVs in humans. As of March 2023, 20 trials were identified. Compared with monovalent vaccination, the induced immunogenicity against ancestral strains was similar. The BVs demonstrated approximately 33–50% higher immunogenicity values against additional variant strains. An observational cohort study showed the additional clinical effectiveness of the BVs. The adverse events were similar. In conclusion, our systematic review found that the BVs had equal immunogenicity against ancestral strains without safety concerns. Approximately 33–50% increased additional antibody titers and clinical effectiveness against additional variant strains were observed in subjects with a BV vaccine with moderate heterogeneity, especially for BA.1-containing BVs.