Predicting Workers' Stress: Application of a High-Performance Algorithm Using Working-Style Characteristics.

BACKGROUND: Work characteristics, such as teleworking rate, have been studied in relation to stress. However, the use of work-related data to improve a high-performance stress prediction model that suits an individual's lifestyle has not been evaluated. OBJECTIVE: This study aims to develop a novel, high-performance algorithm to predict an employee's stress among a group of employees with similar working characteristics. METHODS: This prospective observational study evaluated participants' responses to web­based questionnaires, including attendance records and data collected using a wearable device. Data spanning 12 weeks (between January 17, 2022, and April 10, 2022) were collected from 194 Shionogi Group employees. Participants wore the Fitbit Charge 4 wearable device, which collected data on daily sleep, activity, and heart rate. Daily work shift data included details of working hours. Weekly questionnaire responses included the K6 questionnaire for depression/anxiety, a behavioral questionnaire, and the number of days lunch was missed. The proposed prediction model used a neighborhood cluster (N=20) with working-style characteristics similar to those of the prediction target person. Data from the previous week predicted stress levels the following week. Three models were compared by selecting appropriate training data: (1) single model, (2) proposed method 1, and (3) proposed method 2. Shapley Additive Explanations (SHAP) were calculated for the top 10 extracted features from the Extreme Gradient Boosting (XGBoost) model to evaluate the amount and contribution direction categorized by teleworking rates (mean): low: <0.2 (more than 4 days/week in office), middle: 0.2 to <0.6 (2 to 4 days/week in office), and high: ≥0.6 (less than 2 days/week in office). RESULTS: Data from 190 participants were used, with a teleworking rate ranging from 0% to 79%. The area under the curve (AUC) of the proposed method 2 was 0.84 (true positive vs false positive: 0.77 vs 0.26). Among participants with low teleworking rates, most features extracted were related to sleep, followed by activity and work. Among participants with high teleworking rates, most features were related to activity, followed by sleep and work. SHAP analysis showed that for participants with high teleworking rates, skipping lunch, working more/less than scheduled, higher fluctuations in heart rate, and lower mean sleep duration contributed to stress. In participants with low teleworking rates, coming too early or late to work (before/after 9 AM), a higher/lower than mean heart rate, lower fluctuations in heart rate, and burning more/fewer calories than normal contributed to stress. CONCLUSIONS: Forming a neighborhood cluster with similar working styles based on teleworking rates and using it as training data improved the prediction performance. The validity of the neighborhood cluster approach is indicated by differences in the contributing features and their contribution directions among teleworking levels. TRIAL REGISTRATION: UMIN UMIN000046394; https://www.umin.ac.jp/ctr/index.htm.

Determination of optimal prevention strategy for COVID-19 based on multi-agent simulation.

This study proposes a direction for the utilization of multi-agent simulation (MAS) to consider an optimal prevention strategy for the spread of the coronavirus disease of 2019 (COVID-19) through a pandemic modeling example in Japan. MAS can flexibly express macroscopic phenomena formed through the interaction of micro-agents modeled to act autonomously. The use of MAS can provide a variety of recommendations for bringing a pandemic under control, even in the case of the COVID-19 pandemic, which has become more intense as of 2021. However, models that do not consider individual heterogeneity, such as analytical Susceptible-Exposed-Infectious-Recovered (SEIR) models, are often used as predictive models for infectious diseases and the main reference for decision-making. In this study, we show that by constructing a MAS that simulates a metropolitan city in Japan in a simple manner while considering the heterogeneity of age and other background information, we can capture the effects of various measures such as vaccinations on the spread of infections in a more realistic setting. Moreover, it is possible to offer various recommendations for optimal strategies to suppress a pandemic by combining reinforcement learning with MAS. This study explicates the potential of MAS in the development of strategies to prevent the spread of infection.

Efficacy and safety of guanfacine extended-release in Japanese adults with attention-deficit/hyperactivity disorder: Exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study.

AIM: Previously, we reported on the efficacy and safety of guanfacine extended-release (GXR) in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) from a phase 3, double-blind, placebo-controlled, randomized trial. In this exploratory post hoc analysis, we assessed the efficacy and/or safety of GXR in the following subgroups: ADHD-combined (ADHD-C) and ADHD-predominantly inattentive (ADHD-I) subtypes, age (≥31, <31 years), sex (male, female), and body weight (≥50, <50 kg). METHODS: The primary efficacy endpoint was change from baseline in the Japanese version of the investigator-rated ADHD-Rating Scale-IV (ADHD-RS-IV) with adult prompts (total scores) at week 10. RESULTS: The efficacy analysis population included 200 patients (GXR, 100; placebo, 100). ADHD-RS-IV total score effect sizes (GXR vs placebo) were similar across all subgroups (total population: 0.52, ADHD-C: 0.51, ADHD-I: 0.52, ≥31 years: 0.61, <31 years: 0.47, male: 0.50, female: 0.57). There were no major differences in the incidence/types of treatment-emergent adverse events (TEAEs) across the subgroups. The incidence of significant TEAEs (34.3%, 10.6%) and TEAEs leading to discontinuation (34.3%, 12.1%) were approximately three times higher in females than males, respectively. The incidence of TEAEs in patients weighing <50 kg and ≥50 kg was 100% and 73.6% during dose optimization and 40% and 24.4% during the maintenance period, respectively. CONCLUSION: Findings from this post hoc analysis in adults with ADHD support the efficacy and safety of GXR regardless of ADHD subtype, age, or sex and suggest that careful monitoring for TEAEs and GXR dose optimization is considered for all patients, as needed.

Design, synthesis, and biological evaluation of artemisinin-indoloquinoline hybrids as potent antiproliferative agents.

A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a-7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested. Nearly all of the tested compounds (7-9, except for compounds 7d and 7e against HCT-116) showed an increased antitumor activity against HCT-116 and A549 cell lines when compared to the dihydroartemisinin control. Especially for the artemisinin-indoloquinoline hybrid 8, with an 11-aminopropylamino-10H-indolo[3,2-b]quinoline substituent, the antiproliferative activity against the A549 cell line had improved more than ten times. The IC50 value of hybrid 8 against A549 cell lines was decreased to 1.328 ± 0.586 µM, while dihydroartemisin showed IC50 value of >20 µM in the same cell line. Thus, these results have proven that the strategy of introducing a planar basic fused aromatic moiety, such as the indoloquinoline skeleton, could improve the antiproliferative activity and selectivity towards cancer cell lines.

Synthesis, ß-haematin inhibition, and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11.

A series of indolo[3,2-c]quinolines were synthesized by modifying the side chains of the ω-aminoalkylamines at the C6 position and introducing substituents at the C2 position, such as F, Cl, Br, Me, MeO and NO2, and a methyl group at the N11 position for an SAR study. The in vitro antiplasmodial activities of the derivative agents against two different strains (CQS: NF54 and CQR: K1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that compounds 6k and 6l containing the branched methyl groups of 3-aminopropylamino at C6 with a Cl atom at C2 exhibited a very low cytotoxicity with IC50 values above 4000 nM, high antimalarial activities with IC50 values of about 11 nM for CQS (NF54), IC50 values of about 17 nM for CQR (K1), and RI resistance indices of 1.6. Furthermore, the compounds were tested for ß-haematic inhibition, and QSAR revealed an interesting linear correlation between the biological activity of CQS (NF54) and three contributing factors, namely solubility, hydrophilic surface area, and ß-haematin inhibition for this series. In vivo testing of 6l showed a reduction in parasitaemia on day 4 with an activity of 38%.