Objective: Environmental deprivation, a type of childhood maltreatment, has been reported to constrain the cognitive developmental processes such as associative learning and implicit learning, which may lead to functional and morphological changes in the ventral pallidum (VP) and pessimism, a well-known cognitive feature of major depression. We examined whether neonatal isolation (NI) could influence the incidence of learned helplessness (LH) in a rat model mimicking the pessimism, and the number of vesicular glutamate transporter 2 (VGLUT2)-expressing VP cells and Penk-expressing VP cells. Methods: The number of escape failures from foot-shocks in the LH test was measured to examine stress-induced depression-like behavior in rats. The number of VGLUT2-expressing VP cells and Penk-expressing VP cells was measured by immunohistochemistry. Results: In NI rats compared with Sham rats, the incidence of LH in adulthood was increased and VGLUT2-expressing VP cells but not Penk-expressing VP cells in adulthood were decreased. VGLUT2-expressing VP cells were decreased only in the LH group of NI rats and significantly correlated with the escape latency in the LH test. Conclusion These findings suggest that the aberrant VP neuronal activity due to environmental deprivation early in life leads to pessimistic associative and implicit learning. Modulating VP neuronal activity could be a novel therapeutic and preventive strategy for the patients with this specific pathophysiology.

The purpose of this study was to examine the relationship of the Rohrer index and physical activity on motor function. The subjects were 143 elementary school children in the 5th and 6th grades. Motor function was measured based on musculoskeletal examination. The Rohrer index was calculated from height and weight, and ≥140 was defined as a tendency to be overweight. Physical activity was investigated using a self-reported questionnaire, the WHO Health Behaviour in School-aged Children in Japanese version (HBSC-J). A total of 130 students and their parents agreed to participate in this study, and the data of 127 students were analyzed. The main results were as follows: 26 students had a Rohrer index ≥140, and 60 students (47.2%) had abnormalities in one or more items of motor function. In particular, there were many who reported “Impossible to fully squat” and “Limitation of standing forward flexion”. When compared by sex, “Impossible to fully squat”, “Limitation of standing forward flexion”, and “Pain in shoulder” were particularly frequent in boys. The Rohrer index was particularly high in those who reported that it was “Impossible to fully squat”, but it was not associated with HBSC-J. “Impossible to fully squat” was particularly low in HBSC-J (days of Moderate to vigorous Physical Activity and frequency of Vigorous Physical Activity). The results suggested that children of impossible to fully squat is a lot of low activity and obesity. In conclusion, children who are unable to squat should be followed up to promote physical activity and improve obesity.

Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center (https://brc.riken.jp) and the Experimental Animal Division (https://mus.brc.riken.jp/) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG+ (https://molossinus.brc.riken.jp/mogplus/), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.

Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center (https://brc.riken.jp) and the Experimental Animal Division (https://mus.brc.riken.jp/) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG+ (https://molossinus.brc.riken.jp/mogplus/), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
Antigens, CD274 ; Biopsy ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Flow Cytometry ; Heavy Ion Radiotherapy ; Humans ; Radiotherapy ; Treatment Outcome ; Uterine Cervical Neoplasms

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT). METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes. RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS. CONCLUSION CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.

Drug dispensing is a statutory and designated duty of a pharmacist. We aimed to examine the changes in the nature of drug dispensing using a text mining method. Our corpus consisted of text documents from “Chozai Shishin”, the most standard manual for dispensing drugs in Japan, Editions 1 to 13 (Japan Pharmaceutical Association), and we used the KH Coder software for text mining. We constructed networks showing the association between frequent word co-occurrence and edition number, and co-occurrence relations for frequent words in each edition. We found that “patient” superseded “dispensing” as a frequent term over time. “Dispensing” was another frequent term with a highly centralized node in each edition. Accordingly, we targeted the term “dispensing” for network analysis to depict its co-occurrence relations. We found that the range of related words for “dispensing” broadened from “preparation” and “compounding” to include “patient adherence instructions”, “assessment”, “medical treatment”, and “information provision”. Accordingly, we concluded that the content of “dispensing”, which is a pharmacist’s duty, has expanded from the duties of “dispensing drugs” to include “responding to patients” within the definition of “dispensing”, and we were able to present this finding as objective data by using the mechanical method known as text mining.

Drug dispensing is a statutory and designated duty of a pharmacist. We aimed to examine the changes in the nature of drug dispensing using a text mining method. Our corpus consisted of text documents from “Chozai Shishin”, the most standard manual for dispensing drugs in Japan, Editions 1 to 13 (Japan Pharmaceutical Association), and we used the KH Coder software for text mining. We constructed networks showing the association between frequent word co-occurrence and edition number, and co-occurrence relations for frequent words in each edition. We found that “patient” superseded “dispensing” as a frequent term over time. “Dispensing” was another frequent term with a highly centralized node in each edition. Accordingly, we targeted the term “dispensing” for network analysis to depict its co-occurrence relations. We found that the range of related words for “dispensing” broadened from “preparation” and “compounding” to include “patient adherence instructions”, “assessment”, “medical treatment”, and “information provision”. Accordingly, we concluded that the content of “dispensing”, which is a pharmacist’s duty, has expanded from the duties of “dispensing drugs” to include “responding to patients” within the definition of “dispensing”, and we were able to present this finding as objective data by using the mechanical method known as text mining.

Objective: In this study, we evaluated distinctive types of physical predisposition in patients with common side effects.
Method: We selected 500 and 1,200 individuals with and without a previous diagnosis of side effects, respectively, through web-based research.  Then, we conducted a decision tree analysis for investigating the status of 100 types of physical predisposition in these individuals.
Results and Conclusion: The individuals who had suffered from hepatic disorder and answered “relevant” for “predisposition to swelling” (likelihood ratio of a positive result [LR+] 2.17; p=0.004) and “very relevant” for “predisposition to skin dryness” (LR+ 3.52; p<0.001) enhanced the probability of extracting individuals who developed side effects.  The individuals who had suffered from skin disorder and answered “relevant” for “predisposition to eczema and inflammation” and “not relevant” for “predisposition to higher temperature” had an LR+ of 2.22 (p<0.001).  The individuals with “predisposition to worsening of physical condition on a rainy or high-humidity day” are more likely to develop side effects with the use of antibiotics and NSAIDs, compared to those without this predisposition (antibiotics: LR+ 2.33; NSAIDs: LR+ 2.51).  The results of this study indicate that we can identify patients with a high risk of side effects through an interview on predisposition.