Physical Activity Pattern of Adults With Metabolic Syndrome Risk Factors: Time-Series Cluster Analysis.

Background: Physical activity plays a crucial role in maintaining a healthy lifestyle, and wrist-worn wearables, such as smartwatches and smart bands, have become popular tools for measuring activity levels in daily life. However, studies on physical activity using wearable devices have limitations; for example, these studies often rely on a single device model or use improper clustering methods to analyze the wearable data that are extracted from wearable devices. Objective: This study aimed to identify methods suitable for analyzing wearable data and determining daily physical activity patterns. This study also explored the association between these physical activity patterns and health risk factors. Methods: People aged >30 years who had metabolic syndrome risk factors and were using their own wrist-worn devices were included in this study. We collected personal health data through a web-based survey and measured physical activity levels using wrist-worn wearables over the course of 1 week. The Time-Series Anytime Density Peak (TADPole) clustering method, which is a novel time-series method proposed recently, was used to identify the physical activity patterns of study participants. Additionally, we defined physical activity pattern groups based on the similarity of physical activity patterns between weekdays and weekends. We used the χ2 or Fisher exact test for categorical variables and the 2-tailed t test for numerical variables to find significant differences between physical activity pattern groups. Logistic regression models were used to analyze the relationship between activity patterns and health risk factors. Results: A total of 47 participants were included in the analysis, generating a total of 329 person-days of data. We identified 2 different types of physical activity patterns (early bird pattern and night owl pattern) for weekdays and weekends. The physical activity levels of early birds were less than that of night owls on both weekdays and weekends. Additionally, participants were categorized into stable and shifting groups based on the similarity of physical activity patterns between weekdays and weekends. The physical activity pattern groups showed significant differences depending on age (P=.004) and daily energy expenditure (P<.001 for weekdays; P=.003 for weekends). Logistic regression analysis revealed a significant association between older age (≥40 y) and shifting physical activity patterns (odds ratio 8.68, 95% CI 1.95-48.85; P=.007). Conclusions: This study overcomes the limitations of previous studies by using various models of wrist-worn wearables and a novel time-series clustering method. Our findings suggested that age significantly influenced physical activity patterns. It also suggests a potential role of the TADPole clustering method in the analysis of large and multidimensional data, such as wearable data.

Use of geographically weighted regression models to inform retail endgame strategies in South Korea: application to cigarette and ENDS prevalence.

BACKGROUND: Reducing tobacco retailer availability is a key tobacco endgame policy. The development and evaluation of retail-based policies require spatial methodologies. We modelled the prevalence of adult cigarette and electronic nicotine delivery system (ENDS) use according to tobacco retailer density, considering geographical variations. METHODS: Registration data for tobacco retail businesses, a population-representative survey of South Koreans aged ≥19 years, and population and land area data were used. We merged the datasets according to geographical units. Ordinary least squares (OLS) and geographically weighted regression (GWR) analyses were conducted to model cigarette and ENDS use prevalence, respectively. FINDINGS: Tobacco retailer density was associated with increased cigarette use prevalence in the OLS model (ß=2.19, p=0.02). A 1.9-fold difference by region was identified for the coefficient, indicating an association with tobacco retailer density (minimum 1.39, maximum 2.65), in the GWR analysis. No significant association was present between tobacco retailer density and ENDS prevalence in either the OLS (ß=0.24, p=0.37) or the GWR model (minimum 0.20, maximum 0.28). CONCLUSION: Our results suggest the importance of using spatial methods to develop and evaluate retail-based endgame policies. The establishment of tobacco retailer databases by the introduction of licensing is necessary to develop and evaluate the effectiveness of tobacco retailer regulations.

Predicting Habitual Use of Wearable Health Devices Among Middle-aged Individuals With Metabolic Syndrome Risk Factors in South Korea: Cross-sectional Study.

BACKGROUND: Prevention of the risk factors for metabolic syndrome (MetS) in middle-aged individuals is an important public health issue. Technology-mediated interventions, such as wearable health devices, can aid in lifestyle modification, but they require habitual use to sustain healthy behavior. However, the underlying mechanisms and predictors of habitual use of wearable health devices among middle-aged individuals remain unclear. OBJECTIVE: We investigated the predictors of habitual use of wearable health devices among middle-aged individuals with risk factors for MetS. METHODS: We proposed a combined theoretical model based on the health belief model, the Unified Technology of Acceptance and Use of Technology 2, and perceived risk. We conducted a web-based survey of 300 middle-aged individuals with MetS between September 3 and 7, 2021. We validated the model using structural equation modeling. RESULTS: The model explained 86.6% of the variance in the habitual use of wearable health devices. The goodness-of-fit indices revealed that the proposed model has a desirable fit with the data. Performance expectancy was the core variable explaining the habitual use of wearable devices. The direct effect of the performance expectancy on habitual use of wearable devices was greater (ß=.537, P<.001) than that of intention to continue use (ß=.439, P<.001), and the total effect estimate of the performance expectancy was 0.909 (P<.001), including the indirect effect (ß=.372, P=.03) on habitual use of wearable devices via intention to continue use. Furthermore, performance expectancy was influenced by health motivation (ß=.497, P<.001), effort expectancy (ß=.558, P<.001), and risk perception (ß=.137, P=.02). Perceived vulnerability (ß=.562, P<.001) and perceived severity (ß=.243, P=.008) contributed to health motivation. CONCLUSIONS: The results suggest the importance of the users' performance expectations for wearable health devices for the intention of continued use for self-health management and habituation. Based on our results, developers and health care practitioners should find better ways to meet the performance expectations of middle-aged individuals with MetS risk factors. They also should generate device use easier and find a way to encourage users' health motivation, thereby reducing users' effort expectancy and resulting in a reasonable performance expectancy of the wearable health device, to induce users' habitual use behaviors.

SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination.

Lipid droplets (LDs) are involved in various biological events in cells along with their primary role as a storage center for neutral lipids. Excessive accumulation of LDs is highly correlated with various diseases, including metabolic diseases. Therefore, a basic understanding of the molecular mechanism of LD degradation would be beneficial in both academic and industrial research. Lipophagy, a selective autophagy mechanism/LD degradation process, has gained increased attention in the research community. Herein, we sought to elucidate a novel lipophagy mechanism by utilizing the LD-degrading small molecule, SB2301, which activates ubiquitin-mediated lipophagy. Using a label-free target identification method, we revealed that ethanolamine-phosphate cytidylyltransferase 2 (PCYT2) is a potential target protein of SB2301. We also demonstrated that although SB2301 does not modulate PCYT2 function, it induces the cellular translocation of PCYT2 to the LD surface and spatially increases the phosphatidylethanolamine (PE)/phosphatidylcholine (PC) ratio of the LD membrane, causing LD coalescence, leading to the activation of lipophagy process to maintain energy homeostasis.

Health-Related Indicators Measured Using Earable Devices: Systematic Review.

BACKGROUND: Earable devices are novel, wearable Internet of Things devices that are user-friendly and have potential applications in mobile health care. The position of the ear is advantageous for assessing vital status and detecting diseases through reliable and comfortable sensing devices. OBJECTIVE: Our study aimed to review the utility of health-related indicators derived from earable devices and propose an improved definition of disease prevention. We also proposed future directions for research on the health care applications of earable devices. METHODS: A systematic review was conducted of the PubMed, Embase, and Web of Science databases. Keywords were used to identify studies on earable devices published between 2015 and 2020. The earable devices were described in terms of target health outcomes, biomarkers, sensor types and positions, and their utility for disease prevention. RESULTS: A total of 51 articles met the inclusion criteria and were reviewed, and the frequency of 5 health-related characteristics of earable devices was described. The most frequent target health outcomes were diet-related outcomes (9/51, 18%), brain status (7/51, 14%), and cardiovascular disease (CVD) and central nervous system disease (5/51, 10% each). The most frequent biomarkers were electroencephalography (11/51, 22%), body movements (6/51, 12%), and body temperature (5/51, 10%). As for sensor types and sensor positions, electrical sensors (19/51, 37%) and the ear canal (26/51, 51%) were the most common, respectively. Moreover, the most frequent prevention stages were secondary prevention (35/51, 69%), primary prevention (12/51, 24%), and tertiary prevention (4/51, 8%). Combinations of ≥2 target health outcomes were the most frequent in secondary prevention (8/35, 23%) followed by brain status and CVD (5/35, 14% each) and by central nervous system disease and head injury (4/35, 11% each). CONCLUSIONS: Earable devices can provide biomarkers for various health outcomes. Brain status, healthy diet status, and CVDs were the most frequently targeted outcomes among the studies. Earable devices were mostly used for secondary prevention via monitoring of health or disease status. The potential utility of earable devices for primary and tertiary prevention needs to be investigated further. Earable devices connected to smartphones or tablets through cloud servers will guarantee user access to personal health information and facilitate comfortable wearing.

Fluorophore Labeling of Proteins: a Versatile Trigger-Release-Conjugation Platform Based on the Quinone Methide Chemistry.

In situ conjugation of fluorescent molecules to biomolecules such as proteins under spatiotemporal control offers a powerful means for studying biological systems. For that purpose, the o-quinone methide chemistry involving a sequence of the trigger-release-conjugation (TRC) process provides a versatile conjugation method. We have developed a new TRC platform bearing a quaternary ammonium salt for the release process, which can be structurally modified and readily synthesized from commonly used aryl alcohol-type organic fluorophores under environmentally benign conditions. We show that different aryl alcohol fluorophores containing the o-(morpholinium)methyl group for the release process allow efficient fluorophore labeling of proteins under both light- and chemical-triggering conditions. The bioconjugation in cells as well as in tissues was further demonstrated with an o-(morpholinium)methyl analogue containing a triggering group sensitive to reactive oxygen species. The new TRC system thus provides a versatile and unique platform for in situ fluorophore labeling of proteins in biological systems under spatiotemporal control.

The Unequal Effects of Social Distancing Policy on Subway Ridership during the COVID-19 Pandemic in Seoul, South Korea.

In the Republic of Korea, social distancing policies relied on voluntary participation by citizens and exhibited short-term changes. In this situation, the effects of such policies varied depending on each community's capacity to comply. Here, we collected subway ridership data for 294 stations on nine Seoul Metro lines and aggregated the data for each station to the 184 smallest administrative areas. We found that the mean percent change in subway ridership was fitted by an additive model of the log-transformed percent ratio of the restaurant industry (estimated degrees of freedom (EDF) = 3.24, P < 0.001), the Deprivation Index (DI) (EDF = 3.66, P = 0.015), and the proportion of essential workers (ß = - 0.10 (95% confidence interval - 0.15 to - 0.05, P < 0.001). We found a distinct decrease in subway ridership only in the least deprived areas, suggesting that social distancing is costly.

Candidates' and policymakers' perspectives on the needs for a master's program in nursing.

BACKGROUND: Quality and safe care requires nurses with advanced knowledge and skills. Cambodia does not have a graduate-level nursing program; therefore, nurses are required to pursue advanced degrees in other countries. However, a master's degree nursing program is being established in this country. OBJECTIVES: To explore the needs of stakeholders in the master's nursing program in Cambodia to establish the curriculum. DESIGN: Students and graduates of Bachelor of Sciences in Nursing were surveyed, and policymakers were interviewed face-to-face. PARTICIPANTS: As candidates for the master's nursing program, 94 undergraduates and 37 graduates participated in the survey, and four policymakers working at the Ministry of Health and Cambodian Council of Nurses were interviewed. METHODS: Descriptive statistics and frequency analyses were utilized for quantitative data and qualitative data were thematically analyzed. RESULTS: All 131 undergraduates and graduates were willing to apply to the master's program in nursing mainly to improve their knowledge and skills. They cited financial burden as a challenge for their study. Their educational demands were closely related to Cambodia's social situation and reflected their aspiration for advanced degrees and to become nursing leaders. The policymakers unanimously agreed on the need for the program and suggested policies and strategies to operate the course and recognize the role of graduates with this qualification. They reinforced that the curriculum should be based on the law, regulation, and policy and reflect Cambodia's current situation by identifying the needs of students and hospital officials and investigating available resources. Their perspectives revealed their expectations for graduates to plan healthcare policies and support them as their coworkers. CONCLUSIONS: The establishment of nursing master's course should be accompanied by a policy to support nursing students. Nursing educators and experienced senior nurses should be included in this policymaking and they must participate in the development of the curriculum. It is suggested to develop an eclectic master's program in nursing that aggregates all opinions of stakeholders.

Work hours and overtime of nurses working in Cambodian hospitals.

AIM: To examine the nature and prevalence of Cambodian nurses' work hours and overtime and related factors BACKGROUND: The chronic shortage of nursing workforce is a major cause of overtime among nurses. INTRODUCTION: Nursing shortage and working overtime among nurses negatively affect nurse and patient outcomes, but nurses' work hours and overtime in Cambodia have not been comprehensively examined. METHODS: A multicenter cross-sectional study was conducted in four Cambodian hospitals. Data were collected from 253 nurses providing direct nursing care using a questionnaire. The STROBE checklist was used for reporting this study. RESULTS: More than a fifth of staff nurses worked more than 48 h, which is the legal work hour limit in Cambodia. Two major reasons for working mandatory or voluntary overtime, on-call or 24-h on-call were (a) not wanting to let down colleagues and (b) able to get all work done. The number of patients cared for was related to whether or not nurses worked 48 h or more. CONCLUSION: Overtime work and adverse nurse scheduling are common in Cambodia. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse managers and healthcare institutes in Cambodia need to monitor Cambodian nurses' work hours, which are often beyond the legal work hour limit. Moreover, it is important to understand why nurses work overtime and develop health policies, strategies, and programs that can help promote patient and nurse safety and retain qualified nursing staff. The 24-h on-call practice needs to be regulated according to the labor policy in healthcare institutes to prevent adverse nurse and patient outcomes.

Generic Logic Model for Coronavirus Disease-2019 Responses Based on the South Korean Experience.

BACKGROUND: As the global coronavirus disease-2019 (COVID-19) pandemic continues, many countries have implemented public health policies, such as lockdowns and physical distancing measures, to prevent its spread. South Korea's response to COVID-19, which prevented an increase in confirmed cases and increased resilience, has been considered very effective. PURPOSE: To analyze Korea's response to COVID-19 in 2020 and develop a logic model to evaluate performance effectiveness in follow-up studies. METHODS: By content analysis of Korea Disease Control and Prevention Agency (KDCA) press releases, we defined the problems and identified the causes of the health and social effects of the COVID-19 outbreak. Next, we created a problem tree and developed a logic model that comprised inputs, activities, outputs, outcomes, and impacts. Finally, we held expert consultations to obtain expert opinions regarding the logic model and to ensure the model's validity. RESULTS: South Korea's COVID-19 response policy mitigated the social and health impacts. The 2020 COVID-19 responses had four outcomes (identifying cases on time, preventing transmission of coronavirus infection, effective treatment of COVID-19 cases, protecting public resilience and well-being) and 12 outputs; South Korea conducted 32 activities. CONCLUSION: The results can be a practical reference for managing problems faced in other countries. Korean policy may be of interest in the future for international decision-makers in charge of policy enforcement and those who may be called on to respond to new infectious diseases.

Callyspongiolide kills cells by inducing mitochondrial dysfunction via cellular iron depletion.

The highly cytotoxic marine natural product callyspongiolide holds great promise as a warhead of antibody-drug conjugate in cancer therapeutics; however, the mechanism underlying its cytotoxicity remains unclear. To elucidate how callyspongiolide kills cells, we employed label-free target identification with thermal stability-shift-based fluorescence difference in two-dimensional (2-D) gel electrophoresis (TS-FITGE), which allowed observation of a unique phenomenon of protein-spot separation on 2-D gels upon treatment with callyspongiolide at increasing temperatures. During our exploration of what proteins were associated with this phenomenon as well as why it happens, we found that callyspongiolide induces mitochondrial/lysosomal dysfunction and autophagy inhibition. Moreover, molecular biology studies revealed that callyspongiolide causes lysosomal dysfunction, which induces cellular iron depletion and leads to mitochondrial dysfunction and subsequent cytotoxicity. Notably, these effects were rescued through iron supplementation. Although our approach was unable to reveal the direct protein targets of callyspongiolide, unique phenomena observed only by TS-FITGE provided critical insight into the mechanism of action of callyspongiolide and specifically its cytotoxic activity via induction of mitochondrial dysfunction through cellular iron depletion caused by lysosomal deacidification, which occurred independent of known programmed cell death pathways.

Phenotypic Discovery of SB1501, an Anti-obesity Agent, through Modulating Mitochondrial Activity.

Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α-UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities.

Phenotypic Discovery of Neuroprotective Agents by Regulation of Tau Proteostasis via Stress-Responsive Activation of PERK Signaling.

Tau protein aggregates are a recognized neuropathological feature in Alzheimer's disease as well as many other neurodegenerative disorders, known as tauopathies. The development of tau-targeting therapies is therefore extremely important but efficient strategies or protein targets are still unclear. Here, we performed a cell-based phenotypic screening under endoplasmic reticulum (ER) stress conditions and identified a small molecule, SB1617, capable of suppressing abnormal tau protein aggregation. By applying label-free target identification technology, we revealed that the transient enhancement of protein kinase-like endoplasmic reticulum kinase (PERK) signaling pathway through the inhibition of stress-responsive SB1617 targets, PDIA3 and DNAJC3, is an effective strategy for regulating proteostasis in tauopathies. The molecular mechanism and the promising efficacy of SB1617 were demonstrated in neuronal cells and a mouse model with traumatic brain injury, a tauopathy known to involve ER stress.

The challenges and achievements of graduates of the nurse bridging program in Cambodia: A qualitative study.

BACKGROUND: As the shortage of qualified nurses is one of the primary healthcare issues in Cambodia, a two-year Nurse Bridging Program which grants bachelor's degrees to nurses with associate degrees was introduced. OBJECTIVES: This study explores the challenges and achievements that the graduates experienced during and after the Nurse Bridging Program. DESIGN: A qualitative approach was used in this study. SETTING: The Nurse Bridging Program was conducted in a university in Cambodia from 2015 to 2016. This study was conducted 1 year after the Nurse Bridging Program. PARTICIPANTS: A group of 38 graduates participated in the online survey and 3 graduates participated in a focus group interview. METHODS: Sequential data collection for explanatory follow-up design was used in this study. The data obtained were analyzed using content and thematic analyses. RESULTS: Participants reported challenges such as unfamiliarity with research, difficulty with a foreign language, and shortage of time. They tried to overcome these challenges, and this experience improved their nursing and research competencies, which improved their job prospects and aspirations of further studies. CONCLUSIONS: The Nurse Bridging Program helped the nurses improve the quality of their work and develop their potential as nursing leaders.

Recent advances in identifying protein targets in drug discovery.

Phenotype-based screening has emerged as an alternative route for discovering new chemical entities toward first-in-class therapeutics. However, clarifying their mode of action has been a significant bottleneck for drug discovery. For target protein identification, conventionally bioactive small molecules are conjugated onto solid supports and then applied to isolate target proteins from whole proteome. This approach requires a high binding affinity between bioactive small molecules and their target proteins. Besides, the binding affinity can be significantly hampered after structural modifications of bioactive molecules with linkers. To overcome these limitations, two major strategies have recently been pursued: (1) the covalent conjugation between small molecules and target proteins using photoactivatable moieties or electrophiles, and (2) label-free target identification through monitoring target engagement by tracking the thermal, proteolytic, or chemical stability of target proteins. This review focuses on recent advancements in target identification from covalent capturing to label-free strategies.

Label-free target identification in drug discovery via phenotypic screening.

Phenotypic screening has demonstrated its advantage in the discovery of first-in-class therapeutics, whereas target-based screening has showed strength for follower drugs. Owing to the unbiased nature of phenotypic screening, novel druggable proteins can be uncovered by target identification. Chemical label-free target identification methods can eliminate the functionalization step of an original bioactive compound. Herein, we summarize recent advances in the development of label-free target identification methods, which are based on changes in protein stability against proteolysis, and chemical and thermal denaturation. Owing to the increasing application of shift in thermal stability for protein analysis in live cells and tissues, we mainly focus on the cellular stability shift assay and its proteome-wide application for target identification.

Label-free target identification using in-gel fluorescence difference via thermal stability shift.

Target engagement is a prerequisite for the therapeutic effects of bioactive small molecules, and unbiased identification of their target proteins can facilitate drug discovery and chemical biology research. Structural modifications of bioactive natural products for target identification exhibit potential limitations such as synthetic difficulties, limited supplies from natural sources, and loss of original efficacy. Herein, we developed a label-free method for proteome-wide target identification using in-gel fluorescence difference caused by thermal stability shift, namely TS-FITGE. Quantitative intra-gel image analysis of each protein spot revealed target proteins with shifted thermal stability upon drug engagement, and plotting of melting curves by inter-gel analysis confirmed the positive targets. We demonstrated the robustness and applicability of the TS-FITGE method by identifying target proteins, including membrane-anchored proteins, of complex bioactive compounds. Furthermore, we identified and functionally validated nucleophosmin as a novel target protein of hordenine, a natural product upregulator of in vitro translation.

A pyrazolo[1,5-a]pyridine-fused pyrimidine based novel fluorophore and its bioapplication to probing lipid droplets.

A new fluorescent core skeleton containing pyrazolo[1,5-a]pyridine-fused pyrimidine, called fluoremidine (FD), was discovered. FD analogues were prepared via a one-pot silver-catalyzed cascade cyclization. An N,N-dimethylamino group at the R(1)- and R(2)-positions plays important roles in controlling fluorescence brightness and emission wavelength. An N-acetyl group at the R(3) position contributes to red shifting of the emission wavelength. FD shows excellent solvatochromism with turn-on fluorescence in the lipophilic environment, which was utilized to design a fluorescent probe, FD13, for visualizing lipid droplets in living cells.