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Summary The pandemic coronavirus SARS‐CoV‐2 in the world has caused a large infected population suffering from COVID‐19. To curb the spreading of the virus, WHO urgently demanded an extension of screening and testing; thus, a rapid and simple diagnostic method is needed. We applied a reverse transcription‐loop‐mediated isothermal amplification (RT‐LAMP) to achieve the detection of SARS‐CoV‐2 in 30 min. We designed four sets of LAMP primers (6 primers in each set), targeting the viral RNA of SARS‐CoV‐2 in the regions of orf1ab, S gene and N gene. A colorimetric change was used to report the results, which enables the outcome of viral RNA amplification to be read by the naked eye without the need of expensive or dedicated instrument. The sensitivity can be 80 copies of viral RNA per ml in a sample. We validated the RT‐LAMP method in a hospital in China, employing 16 clinic samples with 8 positives and 8 negatives. The testing results are consistent with the conventional RT‐qPCR. In addition, we also show that one‐step process without RNA extraction is feasible to achieve RNA amplification directly from a sample. This rapid, simple and sensitive RT‐LAMP method paves a way for a large screening at public domain and hospitals, particularly regional hospitals and medical centres in rural areas. A rapid method for the detection of SARS‐CoV‐2 RNA virus.

Stem cells with the capability to self-renew and differentiate into multiple cell derivatives provide platforms for drug screening and promising treatment options for a wide variety of neural diseases. Nevertheless, clinical applications of stem cells have been hindered partly owing to a lack of standardized techniques to characterize cell molecular profiles noninvasively and comprehensively. Here, we demonstrate that a label-free and noninvasive single-cell Raman microspectroscopy (SCRM) platform was able to identify neural cell lineages derived from clinically relevant human induced pluripotent stem cells (hiPSCs). By analyzing the intrinsic biochemical profiles of single cells at a large scale (8,774 Raman spectra in total), iPSCs and iPSC-derived neural cells can be distinguished by their intrinsic phenotypic Raman spectra. We identified a Raman biomarker from glycogen to distinguish iPSCs from their neural derivatives, and the result was verified by the conventional glycogen detection assays. Further analysis with a machine learning classification model, utilizing t-distributed stochastic neighbor embedding (t-SNE)-enhanced ensemble stacking, clearly categorized hiPSCs in different developmental stages with 97.5% accuracy. The present study demonstrates the capability of the SCRM-based platform to monitor cell development using high content screening with a noninvasive and label-free approach. This platform as well as our identified biomarker could be extensible to other cell types and can potentially have a high impact on neural stem cell therapy.

Background Use of combinations of long-acting β 2 agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant. Aim The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies. Methods We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017–2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS). Results Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78–1.01) for the composite events, 0.80 (95% CI, 0.61–1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68–3.25) for unstable angina, 1.00 (95% CI, 0.80–1.24) for congestive heart failure, 0.62 (95% CI, 0.37–1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66–1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses. Conclusion Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.

This study developed a real-time rainfall forecasting system that can predict rainfall in a particular area a few hours before a typhoon’s arrival. The reflectivity of nine elevation angles obtained from the volume coverage pattern 21 Doppler radar scanning strategy and ground-weather data of a specific area were used for accurate rainfall prediction. During rainfall prediction and analysis, rainfall retrievals were first performed to select the optimal radar scanning elevation angle for rainfall prediction at the current time. Subsequently, forecasting models were established using a single reflectivity and all elevation angles (10 prediction submodels in total) to jointly predict real-time rainfall and determine the optimal predicted values. This study was conducted in southeastern Taiwan and included three onshore weather stations (Chenggong, Taitung, and Dawu) and one offshore weather station (Lanyu). Radar reflectivities were collected from Hualien weather surveillance radar. The data for a total of 14 typhoons that affected the study area in 2008–2017 were collected. The gated recurrent unit (GRU) neural network was used to establish the forecasting model, and extreme gradient boosting and multiple linear regression were used as the benchmarks. Typhoons Nepartak, Meranti, and Megi were selected for simulation. The results revealed that the input data set merged with weather-station data, and radar reflectivity at the optimal elevation angle yielded optimal results for short-term rainfall forecasting. Moreover, the GRU neural network can obtain accurate predictions 1, 3, and 6 h before typhoon occurrence.

The biocharacteristics of xenogeneic grafts make them a possible substitute for autogenous bone grafts in dental bone graft procedures. This study aimed to develop a novel porcine graft with collagen capable of generating new bone in bone defects via osteoconduction over 8 weeks of healing and to compare it with a porcine graft. The porcine collagen graft was made to undergo a cell viability test (MTT) and alkaline phosphatase assay (ALP). The surgical procedure was performed in 20 male adult New Zealand white rabbits. Four calvarial critical-size defects of 6 mm in diameter were prepared in each rabbit. The upper left defect was filled with a porcine graft of 500–1000 μm, the upper right with a porcine collagen graft, the lower left with hydroxyapatite/beta-tricalcium phosphate and the lower right served as the control without any filling material. The rabbits were divided and sacrificed at 2, 4, 6 and 8 weeks after surgery. Histological and micro-CT scan results showed that the performance of the porcine collagen graft is superior for regenerating new bone. Porcine collagen graft showed cell viability and osteoblast-like cell differentiation in vitro . The results indicate that porcine collagen graft is a potential bone substitute for clinical application.

We have optimised a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of SARS-CoV-2 from extracted RNA for clinical application. We improved the stability and reliability of the RT-LAMP assay by the addition of a temperature-dependent switch oligonucleotide to reduce self- or off-target amplification. We then developed freeze-dried master mix for single step RT-LAMP reaction, simplifying the operation for end users and improving long-term storage and transportation. The assay can detect as low as 13 copies of SARS-CoV2 RNA per reaction (25-μL). Cross reactivity with other human coronaviruses was not observed. We have applied the new RT-LAMP assay for testing clinical extracted RNA samples extracted from swabs of 72 patients in the UK and 126 samples from Greece and demonstrated the overall sensitivity of 90.2% (95% CI 83.8–94.7%) and specificity of 92.4% (95% CI 83.2–97.5%). Among 115 positive samples which Ct values were less than 34, the RT-LAMP assay was able to detect 110 of them with 95.6% sensitivity. The specificity was 100% when RNA elution used RNase-free water. The outcome of RT-LAMP can be reported by both colorimetric detection and quantifiable fluorescent reading. Objective measures with a digitized reading data flow would allow for the sharing of results for local or national surveillance.

The purpose of this study was to develop an optimal estimation model for rainfall rate retrievals using radar reflectivity, thereby gaining an effective grasp of rainfall information for disaster prevention uses. A process was designed for evaluating the optimal retrieval models using various dataset combinations with radar reflectivity and ground meteorological attributes. Various ground meteorological attributes (such as relative humidity, wind speed, precipitation, etc.) were obtained using the land-based weather stations affiliated with Taiwan’s Central Weather Bureau (CWB). This study used nine radar reflectivity provided by the Hualien weather surveillance radar station’s Volume Cover Pattern 21 system. The developed models are built using multiple machine learning algorithms, including linear regression (REG), support vector regression (SVR), and extreme gradient boosting (XGBoost), in addition to the Marshall–Palmer formula (MP). The study examined 14 typhoons that occurred from 2008 to 2017 at Chenggong station in southeast Taiwan, and Lanyu station in the outlying islands, and the top four major rainfall events were designated as test typhoons—Nanmadol (2011), Tembin (2012), Matmo (2014), and Nepartak (2016). The results indicated that for rainfall retrievals, radar reflectivity at a scanning (elevation) angle of 6.0° combined with ground meteorological attributes were the optimal input variables for the Chenggong station, whereas radar reflectivity at an elevation angle of 4.3° combined with ground meteorological attributes were optimal for the Lanyu station. In terms of model performance, XGBoost models had the lowest error index at Chenggong and Lanyu stations compared with MP, REG, and SVR models. XGBoost models at Lanyu station had the highest efficiency coefficient (0.903), and those at Chenggong station had the second highest (0.885). As a result, pairing the combination of optimal radar reflectivity and ground meteorological attributes, as verified by the evaluation process, with a high-efficiency algorithm (XGBoost) can effectively increase the accuracy of rainfall retrieval during typhoons.

Drug-related problems (DRPs) in a pharmacist-managed anticoagulation clinic (AC) have not been extensively studied. We aimed to characterize the DRPs in a pharmacist-managed AC, identify the factors associated with the solved status of DRPs, and analyze the secondary outcomes, including the safety and efficacy of AC service. The patients receiving services at a pharmacist-managed AC in a medical center for the first time from March 2019 to August 2020 were reviewed retrospectively. The DRPs were retrieved from a self-developed Intelligent AC Service System and classified according to the Pharmaceutical Care Network Europe Foundation v9.0 classification system. Logistic regression models were performed to identify the potential factors associated with the solved status of DRPs. A total of 78 direct oral anticoagulant (DOAC) and 34 warfarin users were included. The major types of DRPs identified at the initial service were adverse drug events (ADEs) (68.4%) and untreated symptoms or indications (14.8%) in the DOAC group, and ADEs (51.6%) and suboptimal effect of drug treatment (38.7%) in the warfarin group. The rates of totally solved DRPs were 56.8% and 51.6% in the DOAC and warfarin groups, respectively. According to the multivariable analysis, receiving AC services 3 times or more in 180 days (OR 3.11, 95% CI 1.30–7.44) was associated with the totally solved status of DRPs in the DOAC group, but no relevant factor was identified in the warfarin group. The secondary outcomes showed that DOAC users demonstrated fewer thromboembolism events, major bleeding, and bleeding-related hospitalizations after AC services, whereas the warfarin users increased percentage time in therapeutic range (TTR% 55.0% vs. 74.6%, P = 0.006) after AC services. These findings may be utilized to develop DOAC and warfarin AC services.

The incidence rates and consequences of inappropriate dosing of glucose-lowering drugs remain limited in patients with chronic kidney disease (CKD). A retrospective cohort study was conducted to estimate the frequency of inappropriate dosing of glucose-lowering drugs and to evaluate the subsequent risk of hypoglycemia in outpatients with an estimated glomerular filtration rate (eGFR) of < 50 mL/min/1.73 m 2 . Outpatient visits were divided according to whether the prescription of glucose-lowering drugs included dose adjustment according to eGFR or not. A total of 89,628 outpatient visits were included, 29.3% of which received inappropriate dosing. The incidence rates of the composite of all hypoglycemia were 76.71 and 48.51 events per 10,000 person-months in the inappropriate dosing group and in appropriate dosing group, respectively. After multivariate adjustment, inappropriate dosing was found to lead to an increased risk of composite of all hypoglycemia (hazard ratio 1.52, 95% confidence interval 1.34, 1.73). In the subgroup analysis, there were no significant changes in the risk of hypoglycemia regardless of renal function (eGFR < 30 vs. 30–50 mL/min/1.73 m 2 ). In conclusion, inappropriate dosing of glucose-lowering drugs in patients with CKD is common and associated with a higher risk of hypoglycemia.

The present work examines a severe, long-lived bow echo in South China during 12–13 April 2016 and investigates the favorable factors for its strength and longevity using a series of 20 cloud-resolving ensemble experiments. Analysis of observational data indicated that this system developed near a surface front under unstable and favorable conditions with dynamic uplifting by approaching troughs at 500–700 hPa. After formation, it propagated rapidly toward the east–southeast across South China and made landfall in Southern Taiwan. The ensemble used four different datasets as initial and boundary conditions and started at five different initial times, whereby comparing the better-performing members with worse ones, four key factors promoting its strength and longevity were identified: (1) A stronger and moister low-level southwesterly flow to the south of the front to enhance convergence and moisture flux at the leading edge—where a stronger inflow with higher equivalent potential temperature (θe) values could feed into the bow echo—leading to a stronger and taller updraft and overall more abundant hydrometeors and rainfall; (2) stronger northwesterly to westerly winds near 700 hPa and thus stronger low-level vertical wind shear, resulting in a stronger rear inflow jet (RIJ), bookend vortices behind the bow apex, and, eventually, a faster propagation speed; (3) a deeper low to the northeast of the bow echo near 850 hPa, where its circulation also helped to bring in low-θe air from farther away and enhance the RIJ and cold pool; and (4) a convective initiation location farther to the east in a more favorable environment, with higher θe and a faster speed to remain in such a better environment. Helped by the above factors, the bow echo in the present case could reach the observed severity and long duration (~15 h) through interactions and reinforcement among its structural components, including the tilted updraft/downdraft, the low-level inflow and stratiform region, the RIJ and bookend vortices, and the cold pool and gust front.