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Dae Hun Kim,1,* Jae Yeol Kim,1,* Rae Man Kim,1 Pooja Maharjan,1 Yu-Geun Ji,2 Dong-Jin Jang,3 Kyoung Ah Min,1 Tae-Sung Koo,2 Kwan Hyung Cho1 1Department of Pharmacy, Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae, Republic of Korea; 2Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea; 3Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea *These authors contributed equally to this work Background: The present study aimed to develop orlistat-loaded solid self-nanoemulsifying drug delivery system preconcentrate (SSP) with the minimum use of lipid excipients for the enhanced solubility, in vitro dissolution, lipase inhibition, and in vivo performance. Materials and methods: In the screening of solubilizing vehicles, Solutol HS15 and Lauroglycol 90 were selected as the surfactant and oil phase, respectively. A pseudo-ternary phase diagram composed of Solutol HS15, Lauroglycol 90, and orlistat as an anti-obesity agent and lipid component was constructed, and the SSP regions were confirmed in terms of the particle size distribution in water, melting point by differential scanning calorimetry, and crystallinity by X-ray diffraction. Results: Physicochemical interaction between Solutol HS15 and orlistat resulted in SSP with various melting points in the range of 26°C~33°C. The representative maximum orlistat-loaded SSP (orlistat/Solutol HS15/Lauroglycol 90=55/40/5, weight ratio) showed the melting point of 32.23°C and constructed uniform nanoemulsion with the particle size of 141.7±1.1 nm dispersed in water. In the dissolution test at pH 1.2 without any detergent, the SSP reached 98.12%±0.83% until 45 minutes, whereas raw orlistat showed no significant dissolution rate. The dissolution samples containing SSP showed a lipase inhibition of 90.42%±1.58% within 45 minutes. In terms of the reduction level of fat absorption in rats, the intake group of SSP gave a significantly higher fat excretion into stool than the one observed in the raw orlistat group (P

Purpose: To construct humanistic nursing practice guidelines suitable for stroke patients., Design: This study was a development and validation study of guidelines using multiple methods, including literature review, qualitative research, questionnaire survey, thematic discussion, and Delphi expert consultation., Methods: Twenty-five experts from seven provinces and municipalities in China were interviewed over two rounds from December 2020 to February 2021. The first-level index was scored for importance and rationality, while the second-level index was scored for importance and feasibility using a five-point Likert scale. Delphi data was collected via a paper version of the questionnaire. The coefficients of variation and coordination were used to represent the degree of dispersion of expert opinions., Findings: In the two rounds of letter consultation, the questionnaire's recovery and effective rates were both 100%, while the opinion submission rates of the two rounds were 84 and 52%, respectively. Moreover, the expert authority coefficient was 0.91, and the coordination coefficients of expert opinions in the first round were as follows: importance of 0.03 and rationality of 0.07 for the first-level index; importance of 0.09 and feasibility of 0.11 for the secondary index. In round two, the coordination coefficients of expert opinions were as follows: importance of 0.04 and rationality of 0.05 for the first-level indicators; importance of 0.12 and feasibility of 0.10 for the secondary index. The results for the secondary index were P < 0.001 for the two rounds. The humanistic nursing practice guidelines for stroke patients that were ultimately formed included five first-level indicators (physiological care, safety care, emotional care, dignity care, and rehabilitation needs) and 46 s-level indicators., Conclusion: Our results show that the "Practice Guidelines for Humanistic Nursing for Stroke" established by experts adopts Maslow's hierarchy of needs as its structural framework. It meets people's basic needs and can provide a reference for the construction of a humanistic nursing specialty practice for stroke patients., Clinical Relevance: Humanistic nursing guidelines for stroke could provide a reference for the construction of humanistic nursing practice in the stroke specialty., Clinical Resources: Copeptin and long-term risk of recurrent vascular events after transient ischemic attack and ischemic stroke: population-based study https://pubmed.ncbi.nlm.nih.gov/26451023/. Effectiveness and usage of a decision support system to improve stroke prevention in general practice: a cluster randomized controlled trial https://pubmed.ncbi.nlm.nih.gov/28245247/. Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association https://pubmed.ncbi.nlm.nih.gov/27145936/., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Ji, Yang and Xie.)

Purpose: This study aims to design that using formative assessment as an instructional strategy in real-time online classes, and to explore the application of Bloom's taxonomy in the development of formative assessment items., Methods: We designed the instruction using formative assessment in real-time online classes, developed the items of formative assessment, analyzed the items statistically, and investigated students' perceptions of formative assessment through a survey., Results: It is designed to consist of 2-3 learning outcomes per hour of class and to conduct the formative assessment with 1-2 items after the lecture for each learning outcome. Formative assessment was 31 times in the physiology classes (total 48 hours) of three basic medicine integrated. There were nine "knowledge" items, 40 "comprehension" items, and 55 "application" items. There were 33 items (31.7%) with a correct rate of 80% or higher, which the instructor thought was appropriate. As a result of the survey on students' perceptions of formative assessment, they answered that it was able to concentrate on the class and that it was helpful in achieving learning outcomes., Conclusion: The students focused during class because they had to take formative assessment immediately after the learning outcome lecture. "Integration of lesson and assessments" was maximized by solving the assessment items as well as through the instructor's immediate explanation of answers. Through formative assessment, the students were able to utilize metacognition by learning what content they understood or did not understand. Items that consider Bloom's taxonomy allow students to remember, understand, and apply to clinical contexts.

This study aims to investigate the effects of non-driving-related tasks (NDRTs) on the transition of control in highly automated driving (HAD) by investigating the effects of NDRT physical, visual, and cognitive attributes during transition of control. A conceptual model of the takeover process is proposed by dividing this process into motor and mental reactions. A laboratory experiment was conducted to evaluate the effects of each NDRT attribute on the corresponding stage of the process of taking over control. A prediction model was developed using the results of multiple linear regression analysis. Additionally, a validation experiment with nine NDRTs and a baseline condition was conducted to determine the extent to which the developed model explains the takeover time for each NDRT condition. The results showed that the timing aspects of the transition of control in HAD largely consist of participant motor reactions that are affected by the physical attributes of NDRTs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We aimed to investigate the effects of the visual complexity of in-vehicle information display and driver's age in a driving context. A driving simulator study was conducted where participants performed visual search tasks at different visual complexity levels while driving. Two groups were included, 20 younger drivers (mean age = 28.75 years) and 14 older drivers (mean age = 54.87 years). Older drivers were found to be more vulnerable to the effects of increased visual complexity when performing a visual search task. The task completion time of the younger group increased by about 20% (from 7.69 s to 9.30 s), while the older group increased by about 47% (from 8.92 s to 13.14 s). Further, the driving performance of the older group deteriorated, unlike the younger group. The subjective workload score supported the results of the objective performance measures. These differences can be explained by glance behavior. The total off-road glance duration of older drivers was longer than that of younger drivers, but the average off-road glance duration of younger drivers was longer. In other words, older drivers have a more conservative strategy when dealing with increased visual complexity in a driving context so as not to affect their driving. The findings of this study show that the visual complexity level has a significant effect on driving behaviors, especially in older drivers, which provides insights for designing in-vehicle information displays., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lung cancer is the second most common cancer in the United States and the leading cause of mortality in cancer patients. Biomarkers predicting survival of patients with lung cancer have a profound effect on patient prognosis and treatment. However, predictive biomarkers for survival and their relevance for lung cancer are not been well known yet. The objective of this study was to perform machine learning with data from The Cancer Genome Atlas of patients with lung adenocarcinoma (LUAD) to find survival-specific gene mutations that could be used as survival-predicting biomarkers. To identify survival-specific mutations according to various clinical factors, four feature selection methods (information gain, chi-squared test, minimum redundancy maximum relevance, and correlation) were used. Extracted survival-specific mutations of LUAD were applied individually or as a group for Kaplan-Meier survival analysis. Mutations in MMRN2 and GMPPA were significantly associated with patient mortality while those in ZNF560 and SETX were associated with patient survival. Mutations in DNAJC2 and MMRN2 showed significant negative association with overall survival while mutations in ZNF560 showed significant positive association with overall survival. Mutations in MMRN2 showed significant negative association with disease-free survival while mutations in DRD3 and ZNF560 showed positive associated with disease-free survival. Mutations in DRD3, SETX, and ZNF560 showed significant positive association with survival in patients with LUAD while the opposite was true for mutations in DNAJC2, GMPPA, and MMRN2. These gene mutations were also found in other cohorts of LUAD, lung squamous cell carcinoma, and small cell lung cancer. In LUAD of Pan-Lung Cancer cohort, mutations in GMPPA, DNAJC2, and MMRN2 showed significant negative associations with survival of patients while mutations in DRD3 and SETX showed significant positive association with survival. In this study, machine learning was conducted to obtain information necessary to discover specific gene mutations associated with the survival of patients with LUAD. Mutations in the above six genes could predict survival rate and disease-free survival rate in patients with LUAD. Thus, they are important biomarker candidates for prognosis., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Antioxidants provide a promising therapeutic effect for the cardiovascular disease. Luteolin, a polyphenolic bioflavonoid, is known to confer cardioprotection, although the underlying mechanisms, especially the role of luteolin on the antioxidant enzymes, such as the peroxiredoxin family, remain unknown., Experimental Approach: We measured the effects of luteolin on myocardial ischaemia/reperfusion (MI/R) injury in vivo (Sprague-Dawley rats) and in vitro, together with the underlying mechanisms, with a focus on signalling by peroxiredoxins. H9c2 cells were used to assess the changes in peroxiredoxins and the other antioxidant enzymes. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also assayed., Key Results: Luteolin exerted significant cardioprotective effects in vivo and in vitro via improving cardiac function, increasing the expression of anti-apoptotic protein Bcl-2 and decreasing the pro-apoptotic protein Bax and active caspases 3 and 9, associated with MI/R. Mechanistically, luteolin markedly enhanced expression of peroxiredoxin II, without significant effects on other forms of peroxiredoxin, catalase or SOD1. Molecular docking showed that luteolin could indeed bind to the enzymic active pocket of peroxiredoxin II. Furthermore, down-regulation of peroxiredoxin II by peroxiredoxin II-antisense, administered by adenovirus infection of H9c2 cardiomyocytes, and inhibition of peroxiredoxin II in vivo significantly reversed the cardioprotective effects of luteolin., Conclusions and Implications: Our findings, for the first time, demonstrate that luteolin protects against MI/R injury through promoting signalling through the endogenous antioxidant enzyme, peroxiredoxin II, indicating the important beneficial role of this antioxidant system in the heart., (© 2018 The British Pharmacological Society.)

Purpose: To investigate the effect of combined inhibition of protein kinase B (AKT) and SRC on the growth and metastatic potential of human pancreatic cancer cells., Materials and Methods: AKT and SRC were inhibited using 10-DEBC and PP2, respectively. The expression of their messenger RNAs were down-regulated by specific small interfering RNA (siRNA). Changes in pancreatic cancer cell growth and metastatic potential were determined using a cell viability assay and a xenotransplant model of pancreatic cancer, as well as cell migration and invasion assays. Signal proteins were analyzed by Western blot., Results: The inhibitors 10-DEBC and PP2 suppressed cell proliferation in a dose-dependent fashion in pancreatic cancer cell lines MIA PaCa-2 and PANC-1. The simultaneous inhibition of AKT and SRC at low concentrations resulted in a significant suppression of cell proliferation. Knockdown of AKT2 and SRC using siRNAs also significantly decreased cell proliferation. In a pancreatic cancer model, combined treatment with 10-DEBC and PP2 also significantly suppressed the growth of pancreatic cancer. Application of 10-DEBC with PP2 significantly reduced the metastatic potential of pancreatic cancer cells by inhibiting migration and invasion. The combined inhibition suppressed the phosphorylation of mTOR and ERK in pancreatic cancer cells., Conclusion: Combined targeting of AKT and SRC resulted in a synergistic efficacy against human pancreatic cancer growth and metastasis., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

In automated driving, a driver can completely concentrate on non-driving-related tasks (NDRTs). This study investigated the flow experience of a driver who concentrated on NDRTs and tasks that induce mental workload under conditional automation. Participants performed NDRTs under different demand levels: a balanced demand-skill level (fit condition) to induce flow, low-demand level to induce boredom, and high-demand level to induce anxiety. In addition, they performed the additional N-Back task, which artificially induces mental workload. The results showed participants had the longest reaction time when they indicated the highest flow score, and had the longest gaze-on time, road-fixation time, hands-on time, and take-over time under the fit condition. Significant differences were not observed in the driver reaction times in the fit condition and the additional N-Back task, indicating that performing NDRTs that induce a high flow experience could influence driver reaction time similar to performing tasks with a high mental workload., (Copyright © 2017. Published by Elsevier Ltd.)

This study aimed at investigating the effect of two smartphone form factors (width and bottom bezel) on touch behaviors with one-handed interaction. User experiments on tapping tasks were conducted for four widths (67, 70, 72, and 74 mm) and five bottom bezel levels (2.5, 5, 7.5, 10, and 12.5 mm). Task performance, electromyography, and subjective workload data were collected to examine the touch behavior. The success rate and task completion time were collected as task performance measures. The NASA-TLX method was used to observe the subjective workload. The electromyogram signals of two thumb muscles, namely the first dorsal interosseous and abductor pollicis brevis, were observed. The task performances deteriorated with increasing width level. The subjective workload and electromyography data showed similar patterns with the task performances. The task performances of the bottom bezel devices were analyzed by using three different evaluation criteria. The results from these criteria indicated that tasks became increasingly difficult as the bottom bezel level decreased. The results of this study provide insights into the optimal range of smartphone form factors for one-handed interaction, which could contribute to the design of new smartphones., (Copyright © 2017. Published by Elsevier Ltd.)

Haptic technology is used in various fields to transmit information to the user with or without visual and auditory cues. This study aimed to provide preliminary data for use in developing a haptic interface for an antigravity (anti-G) suit. With the structural characteristics of the anti-G suit in mind, we determined five areas on the body (lower back, outer thighs, inner thighs, outer calves, and inner calves) on which to install ten bar-type eccentric rotating mass (ERM) motors as vibration actuators. To determine the design factors of the haptic anti-G suit, we conducted three experiments to find the absolute threshold, moderate intensity, and subjective assessments of vibrotactile stimuli. Twenty-six fighter pilots participated in the experiments, which were conducted in a fixed-based flight simulator. From the results of our study, we recommend 1) absolute thresholds of ∼11.98-15.84 Hz and 102.01-104.06 dB, 2) moderate intensities of 74.36 Hz and 126.98 dB for the lower back and 58.65 Hz and 122.37 dB for either side of the thighs and calves, and 3) subjective assessments of vibrotactile stimuli (displeasure, easy to perceive, and level of comfort). The results of this study will be useful for the design of a haptic anti-G suit., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This research proposes an assessment model for quantifying the perceived visual complexity (PVC) of an in-vehicle instrument cluster. An initial study was conducted to investigate the possibility of evaluating the PVC of an in-vehicle instrument cluster by estimating and analyzing the complexity of its individual components. However, this approach was only partially successful, because it did not take into account the combination of the different components with random levels of complexity to form one visual display. Therefore, a second study was conducted focusing on the effect of combining the different components. The results from the overall research enabled us to suggest a basis for quantifying the PVC of an in-vehicle instrument cluster based both on the PVCs of its components and on the integration effect., (Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Background: 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1). We hypothesized that polymorphisms in the genes encoding these proteins would be associated with CRC patient survival., Patients and Methods: We genotyped the following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS 1494del6, MTHFR 677C>T and 1298A>C, and RFC1 -43T>C, 80G>A, and 696C>T. Using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between these polymorphisms and overall survival (OS)., Results: The combined TS 1494 0bp6bp+6bp6bp genotype was associated with reduced OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the RFC1 -43CC and 80AA genotypes were associated with favorable OS., Conclusions: Our data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in Korean patients. Further studies are needed to verify these findings., (© 2013 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to evaluate whether measuring the ratio of descending aortic enhancement (DAE) to main pulmonary artery enhancement (MPAE) on pulmonary computed tomography angiography (PCTA) can predict poor outcome in patients with acute massive or submassive pulmonary embolism (PE)., Methods: We retrospectively, reviewed computed tomgraphy findings and charts of 37 patients with acute PE and right ventricular dysfunction. We divided the enrolled patients into 3 groups; group Ia (n=8), comprised of patients with major adverse event (MAE); group Ib (n=5), consisted of those with PE-related MAE; and group II (n=29), those without MAE. We analyzed the right ventricular diameter (RVD)/left ventricular diameter (LVD) and DAE/MPAE on PCTA., Results: For observer 1, RVD/LVD in group Ia (1.9±0.36 vs. 1.44±0.38, p=0.009) and group Ib (1.87±0.37 vs. 1.44±0.38, p=0.044) were significantly higher than that of group II. For observer 2, RVD/LVD in group Ia (1.71±0.18 vs. 1.41±0.47, p=0.027) was significantly greater than that of group II, but RVD/LVD of group Ib was not (1.68±0.2 vs. 1.41±0.47, p=0.093). For both observers, there was a significant difference of DAE/MPAE between group Ib and group II (0.32±0.15 vs. 0.64±0.24, p=0.005; 0.34±0.16 vs. 0.64±0.22, p=0.004), but no significant difference of DAE/MPAE between group Ia and group II (0.51±0.3 vs. 0.64±0.24, p=0.268; 0.53±0.29 vs. 0.64±0.22, p=0.302). Intra-class correlation coefficient (ICC) for the measurement of DAE/MPAE (ICC=0.97) was higher than that of RVD/LVD (ICC=0.74)., Conclusion: DAE/MPAE measured on PCTA may predict PE-related poor outcomes in patients with massive or submassive PE with an excellent inter-observer agreement.