Search

Virtual contexts play a crucial role in assisting students' learning. Researchers have taken advantage of the potential of immersive virtual reality (VR) for situating students in inaccessible places, and for engaging them in learning activities. Meanwhile, several previous studies have reported that, in VR-based learning contexts, students' perception of immersion and learning motivation could be low owing to the lack of clear objectives and problem-solving scenarios. On the other hand, digital game-based learning is capable of enhancing students' engagement in a task. In this study, we designed a learning approach (namely RPG-VR) by means of integrating a role-playing game with VR technology to enhance students' science learning. Furthermore, a quasi-experiment was conducted to evaluate the students' learning effectiveness via, respectively, providing the RPG-VR learning approach and the conventional VR (called C-VR) learning approach for the experimental and control groups. The experimental results indicated that this approach significantly enhanced the students' perceptions of immersion, self-efficacy and extrinsic learning motivation, in comparison with the C-VR learning approach. Specifically, students who learned with the RPG-VR learning approach perceived more immersion in the engagement and the total immersion stages. This study contributes to existing knowledge of VR technology by providing that a digital role-playing game could reinforce the main characteristics of VR-based learning environments and enhance students' concentration on a learning task. However, no significant difference was found between the two groups in terms of promoting students' learning achievements, implying that more instructional assistance is needed to improve students' knowledge gains in VR-based learning environments.

Developing students' scientific literacy is the most important educational goal and challenge of the 21st century. Many studies have confirmed that flipped learning has significantly impacted learning science. Researchers indicate that the lack of an appropriate learning guidance strategy in the pre-class stage for flipped learning will influence students' understanding of learning content and affect in-class learning activities. In order to tackle this problem, the present study proposed a flipped learning approach based on identification, summarization, self-reflective questioning, and application (ISSA), further exploring the influences on students' scientific literacy, communication tendency, problem-solving tendency, learning motivation, and cognitive load. In addition, the study used a true experimental design to assess the effectiveness of the proposed learning method, and 58 university students were recruited to participate in a natural science course. The experimental group (N = 29) adopted the proposed learning approach, while the control group adopted the conventional flipped learning approach. The results showed that the experimental group had higher scientific literacy, communication tendency, problem-solving tendency, and extrinsic motivation than the control group. The interviews showed that the ISSA flipped learning method could improve students' understanding of the learning content. In particular, the process of peer interaction promoted their self-reflection and scientific literacy skills.

Computational thinking (CT) has gained considerable attention and in-depth discussion over the last two decades. Although the significance of CT has been highlighted, it could be challenging for educators to teach CT. Fortunately, adopting robots in education has been evidenced to be of benefit to promoting students' learning motivation, CT, and higher-order thinking skills. However, several significant factors affecting students' programming performances in robot-assisted learning activities have been identified, such as cognitive needs and organization. In this study, a CMR-BBP (concept map robot block-based programming) approach was designed by integrating concept maps into robot block-based programming to enhance students' programming learning. Moreover, a three-group experiment was carried out in an elementary school to evaluate their learning outcomes. The experimental results revealed that the CMR-BBP approach benefited the students' perceptions of their computational thinking and problem solving in comparison with the R-BBP (robot block-based programming) and C-BBP (conventional block-based programming) approaches. Furthermore, regarding cognitive load, both the CMR-BBP and R-BBP approaches enhanced the students' germane cognitive load, while the CMR-BBP approach effectively reduced their extrinsic cognitive load. This study could be a notable reference for designing other courses in conjunction with programming learning activities.

The objective of this study was to retrospectively assess the impact of manual reduction (MR) on patients with subacute osteoporotic thoracolumbar burst fractures and severe compression fractures (OTLBFSCFs). From January 2016 to May 2020, 101 cases of OTLBFSCFs were reviewed, comprising 73 women and 28 men, with an average age of 77.4 ± 8.5 years. Preoperative radiographs, CT or MRI scans, intraoperative C-arm fluoroscopic images, and postoperative X-ray films were utilized to evaluate spinal radiographic parameters. Initially, all patients underwent 3 min of prone positioning as posture reduction (PR), followed by 1–3 sessions of six-member MR to approximate anatomical reduction of the fracture. The average preoperative anterior body height ratio (ABH%) and lateral Cobb angle (LCA) were 38.8% ± 6.2% and 22.6° ± 4.2°, respectively. Post-PR, the average ABH% and LCA were 50.5% ± 8.0% and 14.7° ± 2.7°, respectively. Following MR, the average ABH% and LCA were 99.6% ± 2.4% and 0.4° ± 2.4°, respectively. PR achieved an ABH% correction of 11.7%, while MR achieved 49.1%. LCA restoration was 7.9° with PR and 14.3° with MR. It was deduced that MR proved to be safe and efficacious for subacute OTLBFSCFs and could potentially alter the approach to subsequent surgeries.

Abstract Background The activation of G protein-coupled receptors (GPCR) signaling by external stimuli has been implicated in inducing cardiac stress and stress responses. GPR22 is an orphan GPCR expressed in brains and hearts, while its expression level is associated with cardiovascular damage in diabetes. Previous studies have suggested a protective role of GPR22 in mechanical cardiac stress, as loss of its expression increases susceptibility to heart failure post-ventricular pressure overload. However, the involvement and underlying signaling of GPR22 in cardiac stress response to ischemic stress remains unexplored. Methods In this study, we used cultured cells and a transgenic mouse model with cardiomyocyte-specific GPR22 overexpression to investigate the impact of ischemic stress on GPR22 expression and to elucidate its role in myocardial ischemic injury. Acute myocardial infarction (AMI) was induced by left coronary artery ligation in eight-week-old male GPR22 transgenic mice, followed by histopathological and biochemical examination four weeks post-AMI induction. Results GPR22 expression in H9C2 and RL-14 cells, two cardiomyocyte cell lines, was decreased by cobalt chloride (CoCl2) treatment. Similarly, reduced expression of myocardial GPR22 was observed in mice with AMI. Histopathological examinations revealed a protective effect of GPR22 overexpression in attenuating myocardial infarction in mice with AMI. Furthermore, myocardial levels of Bcl-2 and activation of PI3K-Akt signaling were downregulated by ischemic stress and upregulated by GPR22 overexpression. Conversely, the expression levels of caspase-3 and phosphorylated ERK1/2 in the infarcted myocardium were downregulated with GPR22 overexpression. Conclusion Myocardial ischemic stress downregulates cardiac expression of GPR22, whereas overexpression of GPR22 in cardiomyocytes upregulates Akt signaling, downregulates ERK activation, and mitigates ischemia-induced myocardial injury.

Background: Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and empagliflozin (EMPA) in DKD rats. Methods: Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 [DKD + ADMSCs (6.0 × 105/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 106/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration)] and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction. Results: The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p

Background and purposeMotor deficits of the ipsilateral lower limb could occur after stroke and may be associated with walking performance. This study aimed to determine whether the accuracy and movement path of targeted movement in the ipsilateral lower limb would be impaired in the chronic stage of stroke and whether this impairment would contribution to gait.MethodsTwenty adults with chronic stroke and 20 age-matched controls went through Mini Mental Status Examination (MMSE), and a series of sensorimotor tests. The targeted movement tasks were to place the big toe ipsilateral to the lesion at an external visual target (EXT) or a proprioceptive target (PRO, contralateral big toe) with eyes open (EO) or closed (EC) in a seated position. A motion analysis system was used to obtain the data for the calculation of error distance, deviation from a straight path, and peak toe-height during the targeted movement tasks and gait velocity, step length, step width and step length symmetry of the lower limb ipsilateral to the brain lesion during walking.ResultsThe stroke group had significantly lower MMSE and poorer visual acuity on the ipsilateral side, but did not differ in age or other sensorimotor functions when compared to the controls. For the targeted movement performance, only the deviation in PRO-EC showed significant between-group differences (p = 0.02). Toe-height in both EXT-EO and in PRO-EO was a significant predictor of step length (R2 = 0.294, p = 0.026) and step length symmetry (R2 = 0.359, p = 0.014), respectively.Discussion and conclusionsThe performance of ipsilateral lower limb targeted movement could be impaired after stroke and was associated with step length and its symmetry. The training of ipsilateral targeted movement with unseen proprioceptive target may be considered in stroke rehabilitation.

Background An increased risk of recurrent stroke is noted in patients with atrial fibrillation despite direct oral anticoagulant (DOAC) use. We investigated the efficacy and safety of treatment with each of 4 different DOACs or warfarin after DOAC failure. Methods and Results We retrospectively analyzed patients with atrial fibrillation with ischemic stroke despite DOAC treatment between January 2002 and December 2016. The different outcomes of patients with DOAC failure were compared, including recurrent ischemic stroke, major cardiovascular events, intracranial hemorrhage and subarachnoid hemorrhage, mortality, and net composite outcomes according to switching to different DOACs or vitamin K antagonist after index ischemic stroke. We identified 3759 patients with DOAC failure. A total of 84 patients experienced recurrent ischemic stroke after switching to different oral anticoagulants, with a total follow‐up time of 14 years. Using the vitamin K antagonist group as a reference, switching to any of the 4 DOACs was associated with a 69% to 77% reduced risk of major cardiovascular events (adjusted hazard ratio [aHR], 0.25 [95% CI, 0.16–0.39] for apixaban, 0.23 [95% CI, 0.14–0.37] for dabigatran, 0.23 [95% CI, 0.09–0.60] for edoxaban, and 0.31 [95% CI, 0.21–0.45] for rivaroxaban), and a 69% to 83% reduced risk of net composite outcomes (aHR, 0.25 [95% CI, 0.18–0.35] for apixaban, 0.17 [95% CI, 0.11–0.25] for dabigatran, 0.31 [95% CI, 0.17–0.56] for edoxaban, and 0.31 [95% CI, 0.23–0.41] for rivaroxaban). Conclusions In Asian patients with DOAC failure, continuing DOACs after index stroke was associated with fewer undesirable outcomes than switching to a vitamin K antagonist. Alternative pharmacologic and nonpharmacologic strategies warrant investigation.

This paper addresses the design of ultra-wideband (UWB) impedance matching networks operating in the unlicensed 3.1–10.6 GHz frequency band for low-power applications. It improves the simplified real frequency technique (SRFT) by adding a realizability check and employing an iterative approach with different initial guesses in optimization to achieve realizable solutions under the requirements of UWB, low-power consumption, and a minimum number of circuit components. The comparison of solutions obtained using the SRFT with published solutions based on the Chebyshev filter theory is presented. It is shown that the optimal SRFT solution requires fewer components in the impedance matching network, maximizes the RF power delivery over the UWB spectrum with a reflection coefficient below −10 dB, and allows for circuit optimization to reduce power consumption. Using the improved SRFT, it demonstrates a systematic approach to find the strategies and limitations of designing the input matching networks for low-power UWB applications using GlobalFoundries 90 nm BiCMOS technology.

Background: The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia species, and to explore changes in antimicrobial susceptibilities in this era of multidrug resistance. Methods: Nocardia isolates were identified to the species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA, hsp65, and secA1 gene sequencing, and minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were assessed with the broth microdilution method. Results: Eighty-nine isolates from 68 patients were identified to species level. The most common species were Nocardia brasiliensis (n = 28, 31.5%), followed by N. farcinica (n = 24, 27%) and N. cyriacigeorgica (n = 16, 18%). Skin and soft tissue were the most common sites of nocardiosis. In multivariate analysis, cutaneous infection (OR, 0.052; p = 0.009), immunosuppressant use (OR, 16.006; p = 0.013) and Charlson combidity index (OR, 1.522; p = 0.029) were significant predictors for death. In total, 98.9% isolates were susceptible to trimethoprim-sulfamethoxazole and linezolid. Further, the MIC range and resistance rate of all Nocardia species to ceftriaxone, imipenem, and amoxicillin-clavulanic acid were found to generally increase over time. Conclusion: Considering that trimethoprim-sulfamethoxazole is effective against most Nocardia species, it is the antibiotic of choice in Taiwan. Besides, amikacin, tigecycline, and linezolid showed high activity against Nocardia species and are thus good alternatives or additional therapies to treat nocardiosis, depending on patient's underlying conditions and site of infection.

Background and purposeIt is common to walk under different conditions, such as looking straight head, looking down at the feet or in dimly lit environment. The purpose of this study was to determine the impact of these different conditions on walking performance in persons with and without stroke.MethodsThis was a case-control study. Persons with chronic unilateral stroke and age-matched control (n = 29 each) underwent visual acuity test, Mini Mental Status Examination (MMSE) and joint position sense test of the knee and ankle. The participants walked at their preferred speed under three walking conditions, looking ahead (AHD), looking down (DWN), and in dimly lit environment (DIM). A motion analysis system was used for the recording of the limb matching test and walking tasks.ResultsStroke participants differed from the control group in MMSE, but not in age, visual acuity or joint position sense. For the control group, the differences between the three walking conditions were nonsignificant. For the stroke group, DWN had significantly slower walking speed, greater step width and shorter single leg support phase, but not different symmetry index or COM location, compared to AHD. The differences between AHD and DIM were nonsignificant.ConclusionHealthy adults did not change their gait patterns under the different walking conditions. Persons with chronic stroke walked more cautiously but not more symmetrically when looking down at the feet, but not in dimly lit environment. Ambulatory persons with stroke may need to be advised that looking down at the feet while walking could be more challenging.

Abstract Background This study tested whether two doses of human umbilical-derived mesenchymal stem cells (hUC-MSCs) were superior to one dose for protecting the brain against intracranial hemorrhage (ICH) induced by intracranial injection collagenase and the capacity of ironic-magnetic-nanoparticles (Ir-MNa) coated hUC-MSCs tracked by MRI. Methods and results Adult male SD rats (n = 40) were equally categorized into group 1 (sham-operated-control), group 2 (ICH), group 3 [ICH + Ir-MNa-coated hUC-MSCs/1.2 × 106 cells with an extracorporeal magnet over rat head (eCMag)/administered by left internal carotid artery (LICA) at post-3 h ICH], and group 4 (ICH + Ir-MNa-coated hUC-MSCs/1.2 × 106 cells with an eCMag/administered post-3 h ICH by LICA and 24 h by IV) and euthanized by day 28. The result showed that by day 28 after ICH induction the neurological function was severely impaired in group 2 than in group 1 that was significantly improved in group 3 and further significantly improved in group 4, whereas ICH volume exhibited an opposite pattern of neurological impairment among the groups (all p

We present the design and the performance evaluation of a new interconnect for large-scale densely packed electronically scanned antenna arrays that utilize a high-speed digital board-to-board vertical connector. The application targets microwave tissue, imaging in the frequency range from 3 GHz to 8 GHz. The tissue-imaging arrays consist of hundreds of active antenna elements, which require low-reflection, low-loss, and low-crosstalk connections to their respective receiving and transmitting circuits. The small antenna size and the high array density preclude the use of coaxial connectors, which are also expensive and mechanically unreliable. Modern board-to-board high-speed connectors promise bandwidths as high as 12 GHz, along with high pin density, mechanical robustness, and low cost. However, their compatibility with the various transmission lines leading to/from the miniature printed antenna elements and microwave circuitry is not well studied. Here, we focus on the design of the transitions from coplanar waveguide transmission lines to/from a high-speed vertical connector. The performance of the interconnect is examined through electromagnetic simulations and measurements. Comparison is carried out with the expensive sub-miniature push-on sub-micro coaxial connectors commonly used in miniature radio-frequency electronics. The results demonstrate that high-speed vertical connectors can provide comparable performance in the UWB frequency range.

Background: Gastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals. Additionally, the study aimed to analyze the sequencing changes following proton pump inhibitor (PPI) treatment and identify predictive factors associated with refractory GERD. Methods: A prospective cohort of 105 individuals with reflux esophagitis and a control group of 50 participants without acid reflux symptoms were enrolled. Psychosomatic evaluations, including GERDQ, GERDQLQ, RSI, BAI, BDI, and SSS-8, were assessed at baseline and during treatment. HRV parameters were also evaluated. Multivariate analysis was used to identify predictive factors for refractory GERD. PPIs were administered regularly for the initial 2 months and then used on-demand. Refractory GERD was defined as less than 50% improvement in symptom relief or GERDQLQ score ≥ 20 after 8 weeks of PPI treatment. Results: The GERD group had higher scores in all psychosomatic evaluations compared to the control group (all p-values < 0.001). There were no significant changes in any parameters of HRV before and after treatment in the GERD group. Strong and consistent correlations were observed between GERD symptoms and psychological scores (BAI, BDI, and SSS-8) across all time points (W0, W4, and W8). Sequential reductions in GERD symptom scores and psychosomatic evaluations were observed during the initial eight weeks of treatment. Higher GERDQ (≥10) and SSS-8 (≥12) scores were predictive of refractory GERD (p = 0.004 and p = 0.009, respectively). Conclusions: This study emphasizes the importance of considering physiological and psychological factors in the management of GERD. Psychosomatic evaluations provide valuable insights for assessing and treating GERD patients. Integrating stress management and comprehensive assessments into personalized treatment strategies is crucial.

Artificial intelligence (AI) technology has been progressively utilized in educational environments in recent years, due to the advances in computing and information processing techniques. The automatic speech recognition technique (ASR) provides students with instantaneous feedback and interactive oral practice for supporting a context with self-paced learning. Corrective feedback (CF) should be combined with ASR-based systems to enhance students’ speaking performance, and to reduce their cognitive load. However, learners’ perceptions of CF are mixed, and CF might give rise to learning anxiety. In this study, a dynamic assessment-based speech recognition (called DA-SR) learning system was designed to facilitate students’ English speaking. Moreover, a quasi-experiment was implemented to evaluate the effects of the proposed approach on students’ speaking learning effectiveness, via respectively providing the DA-SR and the corrective feedback-based speech recognition (called CF-SR) approaches for the experimental and control groups. The experimental results revealed that both the DA-SR group and the CF-SR group can effectively improve the students’ English speaking skills, and decrease their English speaking learning anxiety. Moreover, this study further demonstrated that the DA-SR approach successfully reduced students’ English class performance anxiety, and extraneous cognitive load in comparison with the CF-SR approach. It could be a valuable reference for designing English speaking learning activities in EFL learning environments.

While previous studies have investigated the factors influencing Internet adoption, the findings may not be transferable to explain blockchain technology (BCT) adoption, despite its similarities to the Internet. This study addresses this gap by developing an extended technology acceptance model (TAM) to investigate the factors influencing BCT adoption. The model consists of four key factors, including strategic management and social influence at the firm level, and individual innovation and self-efficacy at the individual level. Data were collected from 384 employees at Taiwan Stock Exchange companies, and structural equation modeling was utilized to test the hypotheses. Results reveal that strategic management and social influence at the firm level have a direct impact on BCT adoption, which is indirectly influenced by perceived usefulness. Subsequently, training and support provided by the firm can enhance individual innovation and self-efficacy, which has direct effects on BCT adoption at the individual level and is partially mediated by perceived ease of use.

Abstract Background This study tested whether human induced-pluripotent stem-cell-derived mesenchymal-stem-cells (iPS-MSCs) would offer an additional benefit to the rodent with acute kidney injury (AKI) (ischemia for 1 h followed by reperfusion for 120 h) associated sepsis syndrome (SS) (by cecal-ligation-puncture immediately after AKI-induction) undergoing ciprofloxacin therapy. Results Male-adult SD rats (n = 80) were categorized into group 1 (sham-operated-control, n = 10), group 2 (AKI + SS, n = 24), group 3 (AKI + SS + ciprofloxacin/3 mg/kg, orally for 120 h, n = 12), group 4 (AKI + SS + iPS-MSCs/1.2 × 106/intravenously administered by 3 h after AKI, n = 12), group 5 (AKI + SS + iPS-MSCs/1.2 × 106/intravenously administered by 18 h after AKI, n = 12), group 6 (AKI + SS + iPS-MSCs/1.2 × 106/intravenously administered by 3 h after AKI induction + ciprofloxacin, n = 10] and euthanized by 120 h. The result showed that the mortality was significantly higher in group 2 than in other groups (all p

This study utilized the Kano model to practically identify the key attributes of online service quality of e-learning education companies. Along with a review of theoretical sources related to service quality, this paper placed similar attributes into the same cluster and finalized four constructs, i.e., reliability, responsiveness, competence, and engagement. In addition, consumer perception plays a mediating role in the relationship between online service quality and online purchase intention, while online customer referral is taken as a moderator indirectly influencing customer perceptions because people like to share their purchasing and usage experiences online. Subsequently, a structured questionnaire was designed and survey data were collected from 418 respondents through various social media. Hypotheses were tested using the structural equation modeling (SEM) and SPSS Process Model 4 and 7. The outcomes show (1) consumer perception significantly mediates the relationship between online service quality and online purchase intention, and (2) online customer referral has a profound effect on consumer perception, indicating that it indirectly affects purchase intention. Online customer referral, therefore, may help e-learning education companies to improve service quality with key features that better positions them to target online learners.

Background: Although bevacizumab in combination with afatinib or erlotinib is an effective and safe first-line therapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), there are very few clinical data comparing afatinib and erlotinib combined with bevacizumab. We performed a retrospective multicenter analysis for the comparison of two combination therapies. Methods: Between May 2015 and October 2020, data of 135 stage IIIB/IV EGFR-mutated NSCLC patients receiving first-line afatinib or erlotinib combined with bevacizumab combination therapy in Linkou, Keelung, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals were retrieved and retrospectively analyzed. Results: In all, 67 patients received afatinib plus bevacizumab, and 68 patients received erlotinib plus bevacizumab. Afatinib combined with bevacizumab had an objective response rate (ORR) of 82.1% and a disease control rate (DCR) of 97.0%, and the ORR and DCR were 83.8 and 95.6%, respectively, in the erlotinib combined with bevacizumab group ( p = 0.798 and p = 1.000). The median progression-free survival was 20.7 and 20.3 months for the afatinib plus bevacizumab group and the erlotinib plus bevacizumab group, respectively [hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.891–1.953; p = 0.167). The overall survival was 41.9 and 51.0 months for the afatinib plus bevacizumab group and erlotinib plus bevacizumab group, respectively (HR = 1.42; 95% CI, 0.829–2.436; p = 0.201). The secondary EGFR-T790M mutation rates after disease progression were 44% in the afatinib plus bevacizumab group and 58.8% in the erlotinib plus bevacizumab group ( p = 0.165). Skin toxicity was the most frequent treatment-related adverse event (AE) in both treatment groups. Diarrhea, an AE, occurred significantly more frequently in the afatinib plus bevacizumab group than in the erlotinib plus bevacizumab group ( p

(1) Background: The study investigated whether the ankle–brachial index (ABI) and pulse wave velocity (baPWV) could reflect the severity of small vessel disease (SVD) and large artery atherosclerosis (LAA). (2) Methods: A total of 956 consecutive patients diagnosed with ischemic stroke were prospectively enrolled from July 2016 to December 2017. SVD severity and LAA stenosis grades were evaluated via magnetic resonance imaging and carotid duplex ultrasonography. Correlation coefficients were calculated between the ABI/baPWV and measurement values. Multinomial logistic regression analysis was performed to determine predictive potential. (3) Results: Among the 820 patients included in the final analysis, the stenosis grade of extracranial and intracranial vessels was inversely correlated with the ABI (p < 0.001, respectively) and positively correlated with the baPWV (p < 0.001 and p = 0.004, respectively). Abnormal ABI, not baPWV, independently predicted the presence of moderate (adjusted odds ratio, aOR: 2.18, 95% CI: 1.31–3.63) to severe (aOR: 5.59, 95% CI: 2.21–14.13) extracranial vessel stenosis and intracranial vessel stenosis (aOR: 1.89, 95% CI: 1.15–3.11). Neither the ABI nor baPWV was independently associated with SVD severity. (4) Conclusions: ABI is better than baPWV in screening for and identifying the existence of cerebral large vessel disease, but neither test is a good predictor of cerebral SVD severity.

Background: Cardiorenal syndrome (CRS) remains the leading cause of death in hospitalized patients for all disease entities. Sacubitril/Valsartan (Sac/Val) therapy has been proved to improve prognostic outcome in patients with heart failure or chronic kidney disease. This study tested the hypothesis that combined levosimendan and Sac/Val was superior to just one therapy on protecting the heart and kidney against simultaneous heart and kidney ischemia (I) (for 50-min)-reperfusion (R) (for 7-days) (i.e., double IR) injury (defined as CRS). Methods and results: Adult-male Spraque-Dawley rats (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (double IR), group 3 [double IR+levosimendan (10 mg/kg by intra-peritoneum administration at 30 min/followed by days 1–5 once daily after IR procedure)], group 4 [double IR+Sac/Val (10 mg/kg, orally at 30 min/followed by days 1–5 twice daily after IR procedure)], and group 5 (double IR+Sac/Val+levosimendan). By day 7 after double-IR, the left-ventricular-ejection fraction (LVEF)/left-ventricular-fraction-shortening (LVFS) were highest in group 1, lowest in group 2 and significantly higher in group 5 than in groups 3/4, but they showed no difference between groups 3/4, whereas the circulatory heart-failure (brain-natriuretic peptide)/proinflammatory (suppression of tumorigenicity-2) biomarkers, blood-urea-nitrogen/creatinine and ratio of urine protein to creatinine (all p

BackgroundAmong poststroke morbidities, poststroke epilepsy (PSE) has been identified as a significant clinical issue. Although middle cerebral artery (MCA) infarct is the most common type of stroke among all vascular territories, very few studies specifically focused on the risk factors leading to PSE in patients with MCA infarct.MethodsA population study in Taiwan has been conducted, linking the National Health Insurance Research Database and Hospital Stroke Registry, from 2001 to 2015 and 2006 to 2010, respectively. Patients were divided into MCA and non-MCA groups, and the diagnosis of incident epilepsy between the groups has been compared. The multivariable Cox proportional hazard model was used to identify the risk factors for developing PSE. The distribution of time to PSE was estimated using the Kaplan–Meier method.ResultsIn total, 1,838 patients were recruited, with 774 and 1,064 in the MCA and non-MCA groups, respectively. PSE incidence in the MCA group was 15.5% vs. 6.2% in the non-MCA group, with a hazard ratio of (95% CI) 2.06 (1.33–3.19). Factors significantly associated with PSE included atrial fibrillation, depression, National Institutes of Health Stroke Scale (NIHSS) scores of ≥ 16, and alert on arrival. For patients with MCA infarct, higher NIHSS and Glasgow coma scale scores, the presence of visual field defects and weakness, urination control impairment, and complications during hospitalization were associated with a higher risk for PSE development.ConclusionsThis study established the conditions leading to a higher risk of PSE and identified the important clinical risk factors in patients experiencing MCA infarct. Efforts to manage these risk factors may be important in preventing PSE in patients with MCA infarct.

Background Insufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses. Methods and Results This multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk‐scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non‐AF group, the AF group exhibited a 2‐ to 3‐fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk [RR], 2.10 [95% CI, 1.35–3.26]). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke‐Monitoring Study standards did not significantly differ between the AF and non‐AF groups. In addition, the low‐dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 [95% CI, 1.63–4.96]). A validation study confirmed these findings after adjustment for scores determined using different stroke risk‐scoring tools. Conclusions Different alteplase dosages did not affect functional status at 90 days in the AF and non‐AF groups. Thus, the adoption of low‐dose alteplase simply because of AF is not recommended.

BackgroundThe efficacy and safety of intravenous alteplase administered 3–4.5 h after acute ischemic stroke have been demonstrated. However, whether responses differ between low-dose and standard-dose alteplase during this time window and whether certain subgroups benefit more remain unknown.Patients and MethodsThe current analysis was based on a multicenter matched-cohort study conducted in Taiwan. The treatment group comprised 378 patients receiving intravenous alteplase 3–4.5 h after stroke onset, and the control group comprised 378 age- and sex-matched patients who did not receive alteplase treatment during the same period. Standard- and low-dose alteplase was administered to patients at the physician's discretion.ResultsOverall, patients receiving alteplase exhibited more favorable outcomes than did controls [34.0 vs. 22.7%; odds ratio (OR): 1.75, 95% confidence interval (CI): 1.27–1.42], and the effectiveness was consistent in all subgroups. Although patients in the standard-dose group (n = 182) were younger than those in the low-dose (n = 192) group, the proportions of patients with favorable outcomes (36.3 vs. 31.8%; OR: 1.22, 95% CI: 0.80–1.88) and symptomatic hemorrhage (2.8 vs 4.2%; OR: 0.65, 95% CI: 0.21–2.02) were consistently comparable in a covariate-adjusted model and an age-matched cohort. In the subgroup analysis, patients with cardioembolism, atrial fibrillation, and hypercholesterolemia were more likely to achieve favorable outcomes after receiving standard-dose than low-dose alteplase.ConclusionIn the 3–4.5 h time window, the effectiveness and safety of standard-dose and low-dose alteplase may be comparable. A standard dose may be selected for patients with cardioembolism, atrial fibrillation, or hypercholesterolemia.

BackgroundThe triglyceride-glucose (TyG) index has recently been proposed as a reliable marker of insulin resistance. There is insufficient evidence to verify that the TyG index is correlated with functional outcomes and hemorrhagic transformation and in patients with stroke treated with intravenous thrombolysis (IVT).MethodsWe designed a multicenter cohort study, which enrolled patients with acute ischemic stroke treated with IVT between December 2004 and December 2016. The TyG index was divided into tertiles and calculated on a continuous scale. Unfavorable functional outcomes were defined by the modified Rankin Scale of 3–6 at 90 days and the incident rates of symptomatic intracranial hemorrhage (SICH) within 36 h of IVT onset were surveyed. Stroke severity was defined as mild (4–8), moderate (9–15), or high (≥16) based on the National Institutes of Health Stroke Scale (NIHSS) scores.ResultsAmong 914 enrolled patients, the tertiles of the TyG index were 8.48 for T1, 8.48–9.04 for T2, and 9.04 for T3. T3 showed an increased risk of unfavorable functional outcomes at 90 days [odds ratio (OR): 1.76; P = 0.0132]. The TyG index was significantly associated with unfavorable functional outcomes at 90 days (OR: 1.32; P = 0.0431 per unit increase). No association was found between the TyG index and SICH. These findings were applicable for T3 with stroke of moderate (OR, 2.35; P = 0.0465) and high severity (OR: 2.57, P = 0.0440) patients with stroke.ConclusionThis study supports the strong association between the increased TyG index and increased unfavorable functional outcomes at 90 days in patients with acute ischemic stroke treated with IVT. These findings were found to be robust in patients with moderate and high stroke severity.

Abstract Background Flipped classroom is known to improve learning efficiency and to develop one’s ability to apply high-level knowledge. To investigate the effect of flipped classroom approach on teaching evidence-based medicine to medical technology students, we conducted a tailor-made six flipped classroom based EBM courses for medical technology students. Methods This study adopted a qusai-experimental design with 62 medical technology interns as the research object. Students in the experimental group attended the flipped classroom course, while students in the control group attended the traditional course. The learning outcomes were evaluated by Fresno test in both groups. Furthermore, to understand student’s perceptions on the flipped classroom approach, students in the experimental group were required to fill in a satisfaction survey and answer some open-ended questions. Results The Fresno test scores of the experimental group were significantly higher than that of the control group. From the results of the satisfaction survey, we know that students were satisfied with this course format. Students claimed that the flipped classroom approach could improve their learning efficiency and the interactions with teacher could help them to think more deeply. Conclusions To conclude, most students showed positive attitudes and views on flipped classroom strategy. Moreover, students’ questions were solved more effectively during class resulting in an improvement of effectiveness of evidence-based medicine trainings.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

Since the Young’s modulus of the separator is weaker than that of the other materials inside a lithium-ion battery, local deformation may cause blockage or rupture of the separator, resulting in internal short-circuit or other disasters. This study collects the stress–strain relationship of various materials within the battery, and combines the mechanical model with the electrochemical model through the coupled relationship between the volumetric strain and the volume fractions of solid and liquid phases. From a two-dimensional electrochemical simulation of a spherical indentation on a layer-structured battery, it is found that there is local negative value of the side reaction overpotential on the negative electrode adjacent to the separator after the battery is deformed. A higher strain will cause a decrease in the negative overpotential, leading to a more serious deposition of lithium during the charge process. The deformation-dependent overpotential is evaluated and the lithium deposition is then quantified. Moreover, the issue of the separator thickness is explored. We find that under an indentation, the thickness does not affect the charging voltage, while a thinner layer will reduce the separator porosity and thus lower the overpotential and increase the chance of lithium deposition.

3β-Hydroxysteroid dehydrogenase/isomerase is essential for the synthesis of active steroid hormones. Interleukin 4 (IL4) induces the expression of HSD3B1 in various human cancer cell lines. Here, we demonstrated that administration of IL4 to an HT-29 colon cancer cell line induced high expression of HSD3B1 at the mRNA and protein levels. In the HT-29 cells, IL4 stimulated the activity of signal transducer and activator of transcription 6 (STAT6) and promoted its binding to the STAT6-binding site in the HSD3B1 promoter. The STAT6 inhibitor significantly suppressed HSD3B1 induction by IL4 in a dose-dependent manner. Moreover, inhibition of the PI3-kinase/AKT pathway strongly suppressed the IL4-induced HSD3B1 expression. Glycogen synthase kinase 3 (GSK3), a downstream target of AKT, had a stimulatory effect on the IL4-induced HSD3B1 expression. However, IL4 stimulated the phosphorylation of AKT, which inhibited the GSK3 activity at the early stage. Hence, GSK3 potentiated the HSD3B1 levels at the late stage of the IL4 stimulation. Additionally, inhibitors of mitogen-activated protein kinases (MAPKs), ERK1/2 and p38, but not of JNK, partly reduced the HSD3B1 expression following the IL4 stimulation. We further demonstrated that IL4 potently promoted steroid synthesis. Our results indicate that IL4 induces HSD3B1 expression via multiple signaling pathways in HT-29 cells and may play a role in the regulation of steroid synthesis.

In this work, an Al coating prepared using the arc spray process was carried out with a corrosion–wear analysis by a block-on-ring system. The interaction of corrosion and wear of coatings in seawater was also investigated. The effect of different corrosion potentials on the corrosion and wear of the coating was discussed, and the structure and corrosion products of the coating were observed by SEM. The results of dynamic potential polarization curves and friction coefficient measurements were used to clarify the corrosion and wear behavior of aluminum coatings in seawater. After quantitative analysis of a corrosion and wear test, it was found that with the increase in polarization potential, the total weight loss of corrosion and wear (Wtotal) of the aluminum coating increased significantly. This means that the corrosion–wear interaction accounts for most of the weight loss of the coating.

Background Concurrent chemoradiotherapy (CCRT) is an optimal recommended treatment for stage III non‐small cell lung cancer (NSCLC). Herein, we aimed to investigate the efficacy and safety of oral vinorelbine plus cisplatin with concomitant radiotherapy for stage III NSCLC. Methods This prospective, open‐label, single‐arm, observational cohort study was performed between January 2010 and September 2016. Patients were treated with two cycles of chemotherapy with 60 mg/m2 intravenous cisplatin on day 1 and 50 mg/m2 oral vinorelbine on days 1, 8, and 15; radiotherapy was administered concurrently from day 1 when chemotherapy was initiated. A total dose of 66–70 Gy radiotherapy was delivered in daily fractions of 2 Gy for 6.5–7 consecutive weeks. The tumor response was assessed after completing concomitant treatment. Results A total of 58 patients were enrolled and analyzed; 31 patients had stage IIIA NSCLC and 27 had stage IIIB NSCLC. After induction CCRT, 31 patients achieved an objective response (complete response in one and partial response in 30; the response rate was 53.4%). The median progression‐free survival was 6.73 months (95% confidence interval [CI], 5.42–7.91), duration of response was 12.30 months (95% CI, 5.59–19.01), and overall survival was 24.83 months (95% CI, 19.26–30.21). No treatment‐related mortality was observed, and neutropenia was the most common grade 3 and 4 treatment‐related toxicity (11 patients; 18.9%). Conclusions CCRT with the weekly regimen of oral vinorelbine plus triweekly cisplatin was effective and safe for stage III NSCLC.

Background: Platelets play an important role in the pathogenesis of acute coronary syndrome (ACS). Patients with ACS have an increased mean platelet volume (MPV) and immature platelet fraction (IPF) resulting in elevation of thrombotic ability. In this study, we evaluated the diagnostic performance of MPV and IPF in identifying suspected ACS patients at emergency department. Moreover, we investigated the correlation between MPV or IPF with initial troponin I (TnI), one of the current ACS biomarkers. Methods: This was a single-center study recruiting suspected ACS patients who had acute chest pain at the emergency department. Whole blood samples were obtained from all participants and MPV and IPF were measured by Sysmex XE-5000 hematology analyzer within 20 min of blood sampling. The diagnostic values of MPV and IPF in identifying ACS were analyzed retrospectively. Result: In this study, 63 in 104 suspected ACS patients were diagnosed as ACS (65.3%). MPV and IPF were higher in ACS patients compared to non-ACS patients (MPV: 10.7 ± 0.80 fL vs 10.0 ± 0.64 fL, p

Background: The macrofollicular variant of papillary thyroid cancer (MFVPTC) is a rare histological variant of papillary thyroid cancer (PTC), with only 71 cases reported through 2014. This study analyzed the clinical, preoperative thyroid ultrasonography (US), and fine needle aspiration cytology (FNAC) features; and therapeutic outcomes of 11 patients with MFVPTC. Methods: The records of 393 patients with histologically diagnosed follicular variant of papillary thyroid carcinoma (FVPTC), including 11 with MFVPTC, were retrospectively reviewed. Preoperative thyroid US findings, clinical presentation, treatment outcomes, and survival rates were analyzed. Result: Mean tumor size was significantly greater in patients with MFVPTC than that in those with FVPTC (4.2 ± 2.1 cm vs. 2.9 ± 1.7 cm; p = 0.016). No patient with MFVPTC had lymph node involvement, but one had a micrometastasis to the lung, which responded well to therapeutic radioiodine. All MFVPTC lesions were isoechoic on US. Eight nodules had calcifications and eight had irregular margins. FNAC showed that these tumors had low cellularity, absence or focal presence of enlarged clear nuclei, and subtle or focal nuclear features of PTC. Cells were, arranged in microfollicular pattern, with abundant colloid background. Multifocal PTCs were detected in the opposite lobe of two patients. All 11 patients with MFVPTC had excellent outcomes. No patient experienced recurrence, and survival rates were high. Conclusions: Malignant US criteria combined with FNAC features have a low preoperative diagnostic rate for MFVPTC. Surgery is recommended for patients with thyroid nodules larger than 4 cm and those with subtle and focal atypical nuclei in FNAC. Keywords: Total thyroidectomy, Thyroglobulin, Radioactive iodide, Cancer-specific mortality

Renal dysfunction is common after stroke. We aimed to investigate the clinical predictability of the ankle–brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) on poststroke renal deterioration. A total of 956 consecutive participants with acute ischemic stroke between 1 July 2016, and 31 December 2017 were enrolled and a final of 637 patients were recruited for final analysis. By using the group-based trajectory model (GBTM), the patients’ renal function trajectories were grouped into the low, intermediate, and high categories (LC, IC, and HC). Significant deterioration in the slope was noted in the IC (p < 0.001) and LC (p = 0.002) groups but was nonsignificant in the HC (p = 0.998) group. Abnormal ABI (ABI ≤ 0.9) was independently related to LC (adjusted odds ratio: 2.40; 95% CI, 1.16–4.95; p = 0.019) and was also independently associated with increased risks of a ≥30% decline in eGFR (adjusted hazard ratio [aHR], 2.28; 95% CI, 1.29–4.05; p = 0.005), a doubling of serum creatinine (aHR, 3.60; 95% CI, 1.93–8.34; p < 0.001) and ESRD (HR, 3.28; 95% CI, 1.23–8.74; p = 0.018). However, baPWV did not have a significant relationship with any of the renal outcomes. Patients with a lower ABI during acute stroke should receive regular renal function tests and should be closely monitored to improve poststroke renal care.