An analysis of the key drivers of the Japanese digital therapeutics patents: A cross-sectional study.

Background: Digital therapeutics (DTx) are software or other tools that support or implement medical practices such as disease prevention, diagnosis, and treatment using digital technology. DTx has been approved in Japan, and it is anticipated that the number of approvals will increase in the future. DTx differs from conventional medical devices in that its primary purpose is treatment. Aim: This study aims to identify the key drivers of DTx in Japan by analyzing patents in the field of medical information, including DTx. Methodology: This study visualizes the results of patent analyses for DTx and examines patent applications that feature applied technology and indications in the medical information field as the key drivers. The study will also employ patent citation analysis. It can be argued that the more citations a patent receives, the more similar research and development activities are being conducted, and the greater the competition. The number of citations per patent application will also be calculated to help identify areas where the value per patent application is high and competition intensifies. A patent citation matrix analysis will be conducted for notable Japanese companies in the DTx field. The citation matrix analysis consists of the number of citations and the company's selfcitation ratio to visualize the patent value. This study investigates the key drivers of DTx by analyzing patent technologies, focusing on patent applications with a high number of citations or a high selfcitation ratio. Results: Key drivers of digital therapeutics were examined by analyzing patents in the fields of healthcare informatics and diagnostics. In terms of the number of patent applications and citations in Japan, numerous patents were related to "applications," "sensors," "medical imaging," "central nervous system/psychiatry," and "heart." As a result, Japanese companies are expected to conduct R&D with an eye toward overseas expansion.

Relationships between cognitive appraisal and roles/personality traits in basic life support.

Objective: To examine the relationship between the cognitive assessment of stress (cognitive appraisal) caused in a scenario requiring basic life support (BLS) and the roles during BLS/personality traits in nursing students. Methods: We conducted an anonymous self-administered questionnaire survey for 264 freshman and senior nursing students. The study period was one month from June 2019. The questionnaire included characteristics, roles (active involvement group/passive involvement group/no involvement group), Cognitive Appraisal Rating Scale (CARS), and Maudsley Personality Inventory (MPI). We only included data for female students (107 people) in the analysis because very little data is available for male students. The Mann-Whitney test was used for the comparison between two groups and the Kruskal-Wallis test was used for the comparison between three groups. The significance level was set at p<0.05. Results: The total number of responses was 133 (50.4%), and the number of valid responses was 107 (40.5%). As a result of analyzing the relationship between the role and the CARS subscale, the controllability of the active and passive involvement groups was significantly lower than that of the no involvement group (p=0.046). Also, the analysis of the relationship between the grade and the CARS subscale showed that the controllability was significantly lower in freshmen than seniors (p=0.020). Conclusion: This study showed the relationship between controllability and cognitive appraisal of stress in the simulation scenario of BLS. Therefore, it was suggested that support for improving controllability is necessary as a preventive measure to reduce the stress associated with BLS.

Effect of Prolyl-hydroxyproline (Pro-Hyp), a food-derived collagen peptide in human blood, on growth of fibroblasts from mouse skin.

We examined the effect of prolyl-hydroxyproline (Pro-Hyp), which occurs in human peripheral blood after ingestion of collagen peptide, on the migration and growth of mouse skin fibroblasts. Mouse skin discs were cultured on a 24-well plastic plate in a fetal bovine serum (FBS)-free medium. Addition of Pro-Hyp (200 nmol/mL) significantly increased the number of fibroblasts migrating from the skin to the plate after incubation for 72 h. This effect of Pro-Hyp was abolished by the addition of mitomycin C. The fibroblasts that had migrated from the mouse skin were collected and cultured on collagen gel. The growth of fibroblasts on the collagen gel was suppressed even in the presence of FBS, while rapid fibroblast growth was observed on the plastic plate. Addition of Pro-Hyp (0-1000 nmol/mL) to the medium containing 10% FBS enhanced the growth of fibroblasts on the collagen gel in a dose-dependent manner. These results suggest that Pro-Hyp might stimulate the growth of fibroblasts in the skin and consequently increase the number of fibroblasts migrating from the skin.

Thiazolidinediones exhibit different effects on preadipocytes isolated from rat mesenteric fat tissue and cell line 3T3-L1 cells derived from mice.

The effects of PPAR-gamma agonists, thiazolidinediones (TZDs), on preadipocytes isolated from rat mesenteric adipose tissue and murine cell line 3T3-L1 were compared using an in vitro cell culture system. After each cell formed a confluent monolayer under appropriate medial conditions, pioglitazone or troglitazone was applied at 10 microM to each medium for cell maturation. We observed morphological changes in each cell, especially the accumulation of lipid droplets in the cytoplasm, during the culture periods. At the end of culture, DNA content, triglyceride (TG) content and glycerol-3-phosphate dehydrogenase (GPDH) activity were determined. Adiponectin concentrations in each culture medium were also measured during appropriate experimental periods. Application of TZDs increased the DNA content, TG accumulation and GPDH activity in the 3T3-L1 cells but not in the mesenteric adipocytes. Although TG accumulation was unchanged, the number of lipid particles was decreased and the size of lipid particles in the mesenteric adipocytes was increased by TZD application. Although the TZDs increased adiponectin release from the 3T3-L1 cells, adiponectin release from mesenteric adipocytes was suppressed (P<0.05). Thus, the effects of TZDs differed between the primary culture of mesenteric adipose cells and the line cell culture of 3T3-L1 cells. The source of adipocytes is an important factor in determining the action of TZDs in vitro, and particular attention should be paid when evaluating the effect of PPAR-gamma agonists on adipose tissues.