New Delhi metallo-β-lactamase (NDM) had been reported to be the predominant carbapenemase among Escherichia coli in Taiwan. However, studies focusing on the clonal background and epidemiology of ...plasmids carrying NDM genes were limited. Between 2016 and 2018, all clinical E. coli and Klebsiella pneumoniae isolates that were non-susceptible to ertapenem, meropenem, and imipenem were tested for carbapenemase-encoding genes (CEGs) and antimicrobial susceptibilities. Molecular typing was performed on all carbapenemase-producing isolates. Whole genome sequencing (WGS) was performed on all NDM-positive E. coli isolates. Twenty-three (29.5%) of 78 carbapenem non-susceptible E. coli and 108 (35.3%) of 306 carbapenem non-susceptible K. pneumoniae isolates carried CEGs. The most prevalent CEGs in carbapenemase-producing E. coli (CPEc) were bla
(39.1%) and bla
(30.4%), while that in carbapenemase-producing K. pneumoniae was Klebsiella pneumoniae carbapenemase (KPC) (72.2%). Fifteen sequence types were identified among 23 CPEc, and 55.6% of NDM-positive E. coli isolates belonged to ST410. WGS showed ST410 isolates were highly clonal and similar to those from other countries. All NDM-5-positive E. coli isolates carried identical IncX3 plasmid harboring bla
but no other antimicrobial resistance (AMR) genes. In each of the four NDM-1-positive E. coli isolates, the bla
was present in a ∼ 300 kb IncHI2/IncHI2A plasmid which carried an array of AMR genes. NDMs are the most prevalent carbapenemase among CPEc in Taiwan. Awareness should be raised as the prevalence of NDM-positive E. coli might increase rapidly with IncX3 plasmid and globally distributed strain ST410 being the potential vectors for wide dissemination.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
The measurement of hypertensive patients’ stroke knowledge is an important stroke prevention indicator of health care service quality. The aim of this study was to develop a Chinese version ...of the Stroke Knowledge Test and examine its psychometric properties, reliability, and validity for hypertensive patients. A sample of 200 hypertensive patients completed the Chinese version of the Stroke Knowledge Test, and 30 of the participants were retested after 2 weeks. The final Chinese version of the Stroke Knowledge Test included 20 items with acceptable content validity (I-CVI = 0.88 ~ 1.00, S-CVI/Ave = 0.97). These items showed satisfactory internal reliability consistency (Kuder Richardson-20 = 0.62) and test–retest reliability was 0.77. The 40% of the difficulty index was in the acceptable range, and 25% was in the difficult range, as well as the 90% items overall values for discrimination were ranged from 0.2 to > 0.4. Known-group validity testing was performed based on the education level, and the result exhibited significant difference (F = 21.21, p < 0.001). The Chinese version of the Stroke Knowledge Test demonstrated acceptable psychometric properties, thus providing a new tool for the future care of hypertensive patients in Taiwan. It also could be as a reference for healthcare providers to educate hypertensive patients on stroke prevention.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Real-time radar rainfall forecasting models based on RF and SVM are proposed.•Radar rainfalls for 1- to 3-h ahead are forecasted by the proposed models.•Single-mode and multiple-mode models based on ...RF and SVM are compared.•Single-mode model gives better forecasts than multiple-mode model.•SVM-based single-mode model performs better than RF-based single-mode model.
This study aims to compare two machine learning techniques, random forests (RF) and support vector machine (SVM), for real-time radar-derived rainfall forecasting. The real-time radar-derived rainfall forecasting models use the present grid-based radar-derived rainfall as the output variable and use antecedent grid-based radar-derived rainfall, grid position (longitude and latitude) and elevation as the input variables to forecast 1- to 3-h ahead rainfalls for all grids in a catchment. Grid-based radar-derived rainfalls of six typhoon events during 2012–2015 in three reservoir catchments of Taiwan are collected for model training and verifying. Two kinds of forecasting models are constructed and compared, which are single-mode forecasting model (SMFM) and multiple-mode forecasting model (MMFM) based on RF and SVM. The SMFM uses the same model for 1- to 3-h ahead rainfall forecasting; the MMFM uses three different models for 1- to 3-h ahead forecasting. According to forecasting performances, it reveals that the SMFMs give better performances than MMFMs and both SVM-based and RF-based SMFMs show satisfactory performances for 1-h ahead forecasting. However, for 2- and 3-h ahead forecasting, it is found that the RF-based SMFM underestimates the observed radar-derived rainfalls in most cases and the SVM-based SMFM can give better performances than RF-based SMFM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The combination of EGF, CHIR99021, A83-01, SB431542, VPA, and Y27632 (EGF/CASVY) facilitates the derivation of trophoblast stem (TS) cells from human blastocysts and first-trimester, but not term, ...cytotrophoblasts. The mechanism underlying this chemical induction of TS cells remains elusive. Here we demonstrate that the induction efficiency of cytotrophoblast is determined by functional antagonism of the placental transcription factor GCM1 and the stemness regulator ΔNp63α. ΔNp63α reduces GCM1 transcriptional activity, whereas GCM1 inhibits ΔNp63α oligomerization and autoregulation. EGF/CASVY cocktail activates ΔNp63α, thereby partially inhibiting GCM1 activity and reverting term cytotrophoblasts into stem cells. By applying hypoxia condition, we can further reduce GCM1 activity and successfully induce term cytotrophoblasts into TS cells. Consequently, we identify mitochondrial creatine kinase 1 (CKMT1) as a key GCM1 target crucial for syncytiotrophoblast differentiation and reveal decreased CKMT1 expression in preeclampsia. Our study delineates the molecular underpinnings of trophoblast stemness and differentiation and an efficient method to establish TS cells from term placentas.
Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score ...(PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Downscaling local daily precipitation from large-scale weather variables is often necessary when studying how climate change impacts hydrology. This study proposes a two-step statistical downscaling ...method for projection of daily precipitation. The first step is classification to determine whether the day is dry or wet, and the second is regression to estimate the amount of precipitation conditional on the occurrence of a wet day. Predictors of classification and regression models are selected from large-scale weather variables in NECP reanalysis data based on statistical tests. The proposed statistical downscaling method is developed according to two methodologies. One methodology is support vector machine (SVM), including support vector classification (SVC) and support vector regression (SVR), and the other is multivariate analysis, including discriminant analysis (for classification) and multiple regression. The popular statistical downscaling model (SDSM) is analyzed for comparison. A comparison of downscaling results in the Shih-Men Reservoir basin in Taiwan reveals that overall, the SVM reproduces most reasonable daily precipitation properties, although the SDMS performs better than other models in small daily precipitation (less than about 10
mm). Finally, projection of local daily precipitation is performed, and future work to advance the downscaling method is proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Osteoarthritis is more prevalent than any other form of arthritis and is characterized by the progressive mechanical deterioration of joints. Glucosamine, an amino monosaccharide, has been used for ...over fifty years as a dietary supplement to alleviate osteoarthritis-related discomfort. Silibinin, extracted from milk thistle, modifies the degree of glycosylation of target proteins, making it an essential component in the treatment of various diseases. In this study, we aimed to investigate the functional roles of glucosamine and silibinin in cartilage homeostasis using the TC28a2 cell line. Western blots showed that glucosamine suppressed the N-glycosylation of the gp130, EGFR, and N-cadherin proteins. Furthermore, both glucosamine and silibinin differentially decreased and increased target proteins such as gp130, Snail, and KLF4 in TC28a2 cells. We observed that both compounds dose-dependently induced the proliferation of TC28a2 cells. Our MitoSOX and DCFH-DA dye data showed that 1 µM glucosamine suppressed mitochondrial reactive oxygen species (ROS) generation and induced cytosol ROS generation, whereas silibinin induced both mitochondrial and cytosol ROS generation in TC28a2 cells. Our JC-1 data showed that glucosamine increased red aggregates, resulting in an increase in the red/green fluorescence intensity ratio, while all the tested silibinin concentrations increased the green monomers, resulting in decreases in the red/green ratio. We observed increasing subG1 and S populations and decreasing G1 and G2/M populations with increasing amounts of glucosamine, while increasing amounts of silibinin led to increases in subG1, S, and G2/M populations and decreases in G1 populations in TC28a2 cells. MTT data showed that both glucosamine and silibinin induced cytotoxicity in TC28a2 cells in a dose-dependent manner. Regarding endoplasmic reticulum stress, both compounds induced the expression of CHOP and increased the level of p-eIF2α/eIF2α. With respect to O-GlcNAcylation status, glucosamine and silibinin both reduced the levels of O-GlcNAc transferase and hypoxia-inducible factor 1 alpha. Furthermore, we examined proteins and mRNAs related to these processes. In summary, our findings demonstrated that these compounds differentially modulated cellular proliferation, mitochondrial and cytosol ROS generation, the mitochondrial membrane potential, the cell cycle profile, and autophagy. Therefore, we conclude that glucosamine and silibinin not only mediate glycosylation modifications but also regulate cellular processes in human chondrocytes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Candida tropicalis is the leading cause of non-C. albicans candidemia in tropical Asia and Latin America. We evaluated isolates from 344 patients with an initial episode of C. tropicalis candidemia. ...We found that 58 (16.9%) patients were infected by fluconazole-nonsusceptible (FNS) C. tropicalis with cross resistance to itraconazole, voriconazole, and posaconazole; 55.2% (32/58) of patients were azole-naive. Multilocus sequence typing analysis revealed FNS isolates were genetically closely related, but we did not see time- or place-clustering. Among the diploid sequence types (DSTs), we noted DST225, which has been reported from fruit in Taiwan and hospitals in Beijing, China, as well as DST376 and DST505-7, which also were reported from hospitals in Shanghai, China. Our findings suggest cross-boundary expansion of FNS C. tropicalis and highlight the importance of active surveillance of clinical isolates to detect dissemination of this pathogen and explore potential sources in the community.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less ...characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound.
We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units).
A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 17.2% vs. 1 3.7%, P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0–8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 109/L) was associated with viral rebound among overall population (adjusted odds ratio aOR, 5.34; 95% confidence interval CI, 1.33–21.71), and remained significant (aOR, 4.50; 95% CI, 1.05–19.25) even when patients receiving NMV/r were considered.
Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, ...the optimal timing to start dexamethasone remains uncertain.
We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians’ decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days.
A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio aOR, 1.03; 95% confidence interval CI, 0.97–1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94–1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12–1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02–1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01–1.98).
An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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