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The study challenges the conventional understanding of awn loss as a domestication syndrome, showing instead that many awned varieties continued to be widely grown in Japan until the early twentieth century and that selection for awn reduction was active at that time, demonstrating that awn loss is not a domestication syndrome but "a trait that emerged during crop improvement". Although selection for awnless mutants was carried out independently using different types of awned cultivars in the early twentieth century in Japan, awn loss was caused by the mutation in OsEPFL1. This suggests that a single mutant haplotype of OsEPFL1 was conserved in the genomes of different cultivars and subsequently selected within each line to meet the demand for awnless varieties. The study also conducts phylogenetic analyses of EPFL1 in 48 grass plants, revealing its unique involvement in awn formation in rice while potentially playing a different role in the domestication of other grass plants. Finally, an attempt is made to isolate an awn-forming gene that has not been identified from the awned rice cultivar "Omachi", which is still cultivated in Japan. The results presented in this paper provide a new perspective on domestication against the conventional understanding of awn development, shedding light on its potential as a useful organ for breeding to mitigate environmental stress. [ABSTRACT FROM AUTHOR]

In the early 1900s, mutation breeding to select varieties with desirable traits using spontaneous mutation was actively conducted around the world, including Japan. In rice, the number of fixed mutations per generation was estimated to be 1.38-2.25. Although this low mutation rate was a major problem for breeding in those days, in the modern era with the development of next-generation sequencing (NGS) technology, it was conversely considered to be an advantage for efficient gene identification. In this paper, we proposed an in silico approach using NGS to compare the whole genome sequence of a spontaneous mutant with that of a closely related strain with a nearly identical genome, to find polymorphisms that differ between them, and to identify the causal gene by predicting the functional variation of the gene caused by the polymorphism. Using this approach, we found four causal genes for the dwarf mutation, the round shape grain mutation and the awnless mutation. Three of these genes were the same as those previously reported, but one was a novel gene involved in awn formation. The novel gene was isolated from Bozu-Aikoku, a mutant of Aikoku with the awnless trait, in which nine polymorphisms were predicted to alter gene function by their whole-genome comparison. Based on the information on gene function and tissue-specific expression patterns of these candidate genes, Os03g0115700/LOC_Os03g02460, annotated as a shortchain dehydrogenase/reductase SDR family protein, is most likely to be involved in the awnless mutation. Indeed, complementation tests by transformation showed that it is involved in awn formation. Thus, this method is an effective way to accelerate genome breeding of various crop species by enabling the identification of useful genes that can be used for crop breeding with minimal effort for NGS analysis. [ABSTRACT FROM AUTHOR]

Background: Risk-based monitoring (RBM) is a slow uptake in some trial sponsors. There are three main reasons for this. First, there is the fear of making large investments into advanced RBM technology solutions. Second, it is considered that RBM is most suitable for large, complex trials. Third, there is the fear of errors in both critical and non-critical data, appearing as reduced on-site monitoring is being conducted. Methods: Our RBM team identified, evaluated, and mitigated trial risks, as well as devised a monitoring strategy. The clinical research associate (CRA) assessed the site risks, and the RBM team conducted central monitoring. We compared all data errors and on-site monitoring time between the partial switching sites [sites that had switched to partial source data verification (SDV) and source data review (SDR)] and the 100% SDV and SDR sites (sites that had implemented 100% SDV and SDR). Results: Partial switching sites did not require any critical data correction and had a smaller number of data corrections through on-site monitoring than the 100% SDV and SDR sites. The RBM strategy reduced the on-site monitoring time by 30%. Conclusions: The results suggest that RBM can be successfully implemented through the use of site risk assessment and central monitoring with practically no additional investment in technology and still produced similar results in terms of subject safety and data quality, as well as the cost savings that have been reported in global complex studies. [ABSTRACT FROM AUTHOR]

Background: Two issues in clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, the relationship between rare events and endpoints, and the differences in multiplicity adjustment between regions, and (2) the current practice on multiplicity adjustment and sample size calculation. This article summarizes the results of the survey on the second issue. Methods: Eligible trials for this survey fulfilled the following conditions: (1) confirmatory phase 3 trial; (2) use of multiple primary endpoints, co-primary endpoints, key secondary endpoint(s) or composite endpoint(s); (3) inclusion of Japanese participants; and (4) protocols created in 2010 or later. The survey was conducted at member companies of the Japan Pharmaceutical Manufacturers Association from October 2017 to November 2017. Results: Useable responses were obtained from 78 trials in 13 companies based in Japan and 9 companies based in other countries. The Bonferroni procedure was mostly used in clinical trials with multiple primary endpoints, while multiple testing procedures that consider a hierarchy of endpoints or a structure of hypotheses were used in clinical trials with key secondary endpoint(s). In sample size calculation, we can consider the probability of study success, such as the probability of statistical significance in at least one comparison of primary endpoints; however, other probabilities were also considered. This survey reveals that multiplicity adjustment and the correlation of endpoints were not always considered in sample size calculation. Conclusions: In clinical trials with multiple endpoints, clinical importance was considered when determining multiple testing procedures. Challenges remain with the definition of power, the consideration of multiple testing procedures and the correlation between endpoints in sample size calculation. [ABSTRACT FROM AUTHOR]

Background: Two issues on clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, relationship between rare events and endpoints, and differences in multiplicity adjustment between regions; and (2) the current practice on multiplicity adjustment and sample size calculation. This article provides a summary of the results of a survey on the first issue. Methods: The survey was conducted among 63 members of the Japan Pharmaceutical Manufacturers Association from October to November 2017. Results: Thirty-five companies based in Japan and 12 companies based in other countries, 47 companies in total, responded to the survey. The terms c o-primary endpoints, secondary endpoint, and composite endpoint were used in a variety of ways. An endpoint for a clinically most important event that is expected to occur rarely differed between regions. Although the Pharmaceuticals and Medical Devices Agency did not demand multiplicity adjustment, it was considered in clinical trials with multiple endpoints for approval in Japan. Conclusions: The use of terminology differed from the definition in the Food and Drug Administration guidance and the European Medicines Agency guideline. There remain challenges on a clinically most important event that is expected to occur rarely and multiplicity adjustment in clinical trials with multiple endpoints. [ABSTRACT FROM AUTHOR]

Two huge earthquakes struck Kumamoto, Japan, in April 2016, forcing residents to evacuate. Few studies have reported early-phase disease and injury trends among evacuees following major inland earthquakes. We evaluated the trends among evacuees who visited a medical clinic in a shelter located at the epicenter of the 2016 Kumamoto earthquakes. The clinic opened on April 15, the day after the foreshock, and closed 3 weeks later. We reviewed medical charts related to 929 outpatient visits and conducted descriptive analyses. The evacuees experienced mild injuries and common diseases. The types of diseases changed weekly. Elderly people needed medical support for longer than other age groups. Future earthquakes may be inevitable, but establishing arrangements for medical needs or making precautions for infectious diseases in shelters could reduce the effects of earthquake-related health problems. [ABSTRACT FROM AUTHOR]

Background: This study provides the results of a survey on the current practice of multiplicity adjustment and sample size calculation in multi-arm clinical trials. Methods: The survey was aimed at members of the Japan Pharmaceutical Manufacturers Association (JPMA) and was conducted in 2015. Results: Of the 66 JPMA member companies, effective responses were obtained on 151 trials from 33 companies based in Japan and 11 companies based in other countries. The results from this survey indicate that multiplicity adjustment in confirmatory multi-arm trials is adequate in terms of controlling the familywise error rate. Multiplicity was adjusted in 38.3% of exploratory multi-arm trials. Various multiple comparison procedures (MCPs) were applied, with the fixed sequence procedure being the one applied most frequently. This survey also reveals that there are issues that need to be addressed within sample size calculation. Conclusions: To adequately design a multi-arm clinical trial, it is important within sample size calculation to consider whether to perform multiplicity adjustment, select MCPs, and define their power. [ABSTRACT FROM AUTHOR]

Background The increase in implant patients is expected to give rise to a new problem: the changing general health status of those who have had implants placed. Purpose The aim of this present study was to find out the needs of and proper measures for elderly implant patients in long-term care facilities. Materials and Methods A questionnaire was sent by mail to 1,591 long-term care health facilities, daycare services for people with dementia, and private nursing homes for the elderly in the Osaka area, which is in the middle area of Japan, in order to extract patients with cerebrovascular disease or dementia who were possibly at risk of inadequate oral self-care, as well as patients with implants. Results Approximately half of all facilities responded that they cannot recognize implants, and many facilities did not know anything about oral care for implant patients. Residents with implants were reported at 19% of all facilities. Also, the facilities pointed out problems with implants relating to the difference in oral care between implants and natural teeth. Conclusions There are people with implants in some 20% of caregiving facilities, and there is a low level of understanding regarding implants and their care among nurses and care providers who are providing daily oral care. [ABSTRACT FROM AUTHOR]

The article discusses a study that surveyed the Japanese practice in handling and prevention of clinical trial missing data of Japanese and international pharmaceutical companies in 2013 as to regulatory guidelines. Topics covered include the last observation carried forward (LOCF), LOCF imputation, the baseline observation carried forward (BOCF) method and mixed-effect models for repeated measures (MMRM). Results showed the popular use of LOCF imputation in confirmatory trials.

In Japan, Trichophyton tonsurans infection has become an increasing problem among combat sports participants. We investigated the prevalence of T. tonsurans infection in athletes affiliated to judo clubs in the 21 First Division universities that were registered with the University Judo Federation of Tokyo in 2008. Study procedures performed by the subjects included (i) completion of a questionnaire concerning lifestyle, risk factors for tinea corporis and medical history; (ii) scrubbing the scalp with a circular hairbrush to obtain samples for fungal culture; (iii) anti-fungal treatment as recommended by a dermatologist, based on the number of fungal colonies isolated from the hairbrush; and (iv) repeat testing using the hairbrush method 3 months after treatment recommendations were received. Of 902 study subjects, 102 (11.3%) yielded positive hairbrush culture results. Of these, 14 individuals (13.7%) had tinea corporis; the remainder were asymptomatic. Conversion to negative fungal culture was observed in 85 of 96 culture-positive individuals who performed the second hairbrush culture test following treatment. Control of T. tonsurans infection among judo athletes could be achieved by educating athletes, trainers and coaches in judo clubs concerning detection, prevention, and treatment of T. tonsurans infection. [ABSTRACT FROM AUTHOR]

It has been seven years sine an outbreak of trichophyton tonsurans infection occurred in Japan. We have examined the state of T. tonsurans infection by a hairbrush test of athletes and a questionnaire survey of doctors' experience in its treatment, but have not completely grasped the actual state of infection at the sites of judo matches and its treatment or application of preventive measures. Subjects and Methods: The questionnaire was distributed to the leaders of all judo clubs analyzed. These leaders were asked about (1) members of the club, (2) recognition of the infection, (3) experience of the breakout of infection at present and in the past, (4) present state of preventive measures, and (5) their opinions and requests. Results: A higher percentage of the leaders of junior high school physical education judo clubs and primary school judo clubs responded they "did not know" about the infection , as compared with leaders of the other age groups. The answer regarding the "experience of the outbreak of infection" was "yes" in responses from 371 clubs (30.9%), with a significantly higher percentage of leaders of senior high school judo clubs replying in the affirmative. Concerning preventive measures such as providing shower rooms, 540 clubs (45.1%) answered "no measures taken", which was more frequent in junior high school and primary school judo clubs. Since T. tonsurans infection is expected to spread to younger age groups in the future a nationwide campaign by the All Japan Federation for the education of risk of infection is urgently needed. [ABSTRACT FROM AUTHOR]

Many reports have indicated a correlation between climate and crime. Here, we examine the correlation between climatic factors and forensic autopsies, and show that higher rates of murder, manslaughter, and bodily injury resulting in death occur on sunny days than on non-sunny days. The largest number of autopsies was associated with days on which the weather was unstable. In addition to increased activity of people on sunny days, unstable and uncomfortable weather may result in crime through induction of psychiatric stress. More hit-and-run cases occurred on rainy days than on non-rainy days, and unstable weather may also be associated with traffic crimes. We conclude that weather factors, in addition to social factors, are important in murder and in fatalities due to hit-and-run traffic crimes. [ABSTRACT FROM AUTHOR]

The spread of Trichophyton tonsurans infection among high school students and university undergraduates who practice Judo is an emerging problem in Japan and other countries. However, the extent of infection among Judo practitioners in junior high school in Japan is unknown. We conducted an epidemiological study of T. tonsurans infection among students who participated in the national junior high school Judo tournament in 2005. Of the 1,039 tournament participants invited to undergo screening, 496 (218 boys and 278 girls) consented, and 45 participants (9.1%) were found to be positive by hairbrush culture. We found the following to be relative risk factors for T. tonsurans infection: 1) male gender, 2) frequent judo practice in groups at either a high school or a dojo, 3) presence of tinea corporis in practice partners, 4) history of tinea corporis, 5) classification in lower-weight categories. 45 culture positive subjects were offered treatment and re-examined by hairbrush culture 3 months later. All twelve of them had negative cultures after miconazole shampoo treatment. A half of 12 subjects who had systemic antifungal therapy with itraconazole had positive culture. These observations suggest that T. tonsurans infection is rapidly spreading among junior high school Judo players in Japan. We speculate that the outbreak is caused, at least in part, by ignorance of the disease among Judo students, coaches and officials due to the high incidence of carriers and the mild or asymptomatic form of disease seen in infected individuals. Appropriate measures should be taken immediately to prevent more severe outbreak of this disease. [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia has emerged as an independent risk factor for cardiovascular events, despite low-density lipoprotein-cholesterol (LDL-C) well-controlled with statins. We pooled data from the first 12 weeks of six randomized double-blind placebo-controlled studies of pemafibrate in Japan and investigated its efficacy and safety with and without statins, particularly focusing on patients with renal dysfunction. Subjects were 1253 patients (677 in the "with-statin" group and 576 in the "without-statin" group). At Week 12 (last observation carried forward), triglyceride (TG) was significantly reduced at all pemafibrate doses (0.1, 0.2, and 0.4 mg/day), both with and without statin, compared to placebo (p < 0.001 vs. placebo for all groups). In the "with-statin" group, the estimated percent change from baseline was −2.0% for placebo and −45.1%, −48.5%, and −50.0%, respectively, for the pemafibrate groups. Findings for both groups showed significant decreases in TG-rich lipoproteins and atherogenic lipid parameters compared to placebo. The incidence of adverse events was similar between the pemafibrate and placebo groups and was also similar for patients with and without renal dysfunction in the "with-statin" group. Pemafibrate lowered TG and improved atherogenic dyslipidemia without a significant increase in adverse events in comparison to the placebo, even among "with-statin" patients who had renal dysfunction. [ABSTRACT FROM AUTHOR]

Ivermectin is an antiparasitic drug administered to hundreds of millions of people worldwide. Fundamental research suggests that ivermectin is effective against coronavirus disease 2019 (COVID-19); therefore, we investigated the efficacy and safety of ivermectin as a COVID-19 treatment option. This multi-regional (Japan and Thailand), multicenter, placebo-controlled, randomized, double-blind, parallel-group, Phase III study evaluated the efficacy and safety of ivermectin in patients with mild COVID-19 (IVERMILCO Study). The participants took a specified number of the investigational product (ivermectin or placebo) tablets of, adjusted to a dose of 0.3–0.4 mg/kg, orally on an empty stomach once daily for three days. The primary efficacy endpoint was the time at which clinical symptoms first showed an improving trend by 168 h after investigational product administration. A total of 1030 eligible participants were assigned to receive the investigational product; 502 participants received ivermectin and 527 participants received a placebo. The primary efficacy endpoint was approximately 96 h (approximately four days) for both ivermectin and placebo groups, which did not show statistically significant difference (stratified log-rank test, p = 0.61). The incidence of adverse events and adverse drug reactions did not show statistically significant differences between the ivermectin and placebo groups (chi-square test, p = 0.97, p = 0.59). The results show that ivermectin (0.3–0.4 mg/kg), as a treatment for patients with mild COVID-19, is ineffective; however, its safety has been confirmed for participants, including minor participants of 12 years or older (IVERMILCO Study ClinicalTrials.gov number, NCT05056883.). [ABSTRACT FROM AUTHOR]

Background: T. tonsurans infection is spreading among combat sport athletes in Japan, and preventive measures are necessary. Methods: A questionnaire survey and hairbrush-culture tests were conducted over a 4-year period on university judo athletes from about 50 university teams affiliated with the University Judo Federation of Tokyo. Culture-positive individuals were given specific treatment recommendations based on culture results and were advised to seek treatment at a medical clinic. Culture-positive individuals were re-tested at 3 months post-treatment. Results: Approximately 65 % of participants reported a history of T. tonsurans infection. The incidence of hairbrush culture-positive individuals overall gradually decreased from 11.3% (academic year 2008) to 5.4% (2011). Each year the incoming freshmen had the highest infection rate of the four academic classes. Beginning in 2009 the infection rates decreased sharply among those who had participated in the survey the previous year, and the decreases continued the following year (s) until graduation. Among culture-positive individuals, the incidence of asymptomatic carriers increased each year, from 86% in 2008 to 98% in 2011. The culture-negative conversion rate was 86% overall for those undergoing treatment Conclusion: Preventive measures against T. tonsurans infection in the University Judo Federation of Tokyo were successful in increasing awareness of the disease, lowering the incidence of infection, and detecting asymptomatic carriers who require treatment. [ABSTRACT FROM AUTHOR]