Negative DNA supercoiling enhances DARS2 binding of DNA-bending protein IHF in the activation of Fis-dependent ATP-DnaA production.

Oscillation of the active form of the initiator protein DnaA (ATP-DnaA) allows for the timely regulation for chromosome replication. After initiation, DnaA-bound ATP is hydrolyzed, producing inactive ADP-DnaA. For the next round of initiation, ADP-DnaA interacts with the chromosomal locus DARS2 bearing binding sites for DnaA, a DNA-bending protein IHF, and a transcription activator Fis.

Planning and Implementing Master Protocol Trials in Japan: Key Considerations of the Japanese Guideline.

The importance of master protocol trials, which encompass basket, umbrella, and platform trials, has been increasingly recognized worldwide for their efficiency in evaluating multiple drugs or diseases within a single trial. While the US Food and Drug Administration and European regulatory bodies have issued guidelines to facilitate such trials, Japan only recently introduced its own set of guidelines to address the unique challenges and opportunities within its regulatory and healthcare landscape. Our study elaborates on these newly issued Japanese guidelines, which were developed through a collaborative effort involving biostatisticians, physicians, clinical trialists, regulatory authorities, and industry representatives.

Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis.

Background: The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab as first-line (1L) maintenance therapy + best supportive care (BSC) vs BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with 1L platinum-containing chemotherapy. Efficacy and safety were assessed in patients enrolled in Japan.

Methods: Patients with locally advanced or metastatic UC that had not progressed with 4-6 cycles of 1L platinum-containing chemotherapy were randomized to avelumab (10 mg/kg intravenously every 2 weeks) + BSC or BSC alone.

A phase 2b, randomized, double-blind, multicenter, vehicle-controlled study to assess the efficacy and safety of two crisaborole regimens in Japanese patients aged 2 years and older with mild-to-moderate atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, xerosis, and eczematous lesions. In Japan, treatment options, such as topical corticosteroids and tacrolimus, are associated with efficacy and safety concerns. Crisaborole ointment, 2%, is a topical non-steroidal anti-inflammatory agent approved in several countries for the treatment of mild-to-moderate AD.

Changes in oral and cognitive functions among older Japanese dental outpatients: A 2-year follow-up study.

Background: The relationship between oral and cognitive functions among older people is highly debated.

Objective: To examine whether oral functions are related to changes in the levels of mild cognitive impairment (MCI) biomarkers in older Japanese outpatients.

Methods: This observational study included 52 outpatients aged ≥65 years who underwent dental examinations at the Fukuoka Dental College Hospital.

Expression of aquaporins in response to distinct dehydration stresses that confer stress tolerance in the Antarctic midge Belgica antarctica.

Larvae of the Antarctic midge Belgica antarctica Jacobs (Diptera: Chironomidae) are highly tolerant of diverse environmental stresses, including freezing, severe desiccation, and osmotic extremes. Furthermore, dehydration confers subsequent desiccation and freeze tolerance. While a role for aquaporins-channels for water and other solutes-has been proposed in these dehydration processes, the types of aquaporins involved in dehydration-driven stress tolerance remain unknown.

Relationship between cerebral atrophy and number of present teeth in elderly individuals with cognitive decline.

Background And Aim: Recent shifts in the distribution of Japan's population towards older ages, have meant that the chance of encountering patients with dementia in dental clinics is increasing. Many studies have shown that the brain volume decreases along with the progression of dementia. Although previous studies have reported a relationship between tooth loss or periodontitis and the onset of dementia, the pathological mechanisms underlying this association have not been elucidated.

Safety and efficacy of first-line dacomitinib in Japanese patients with advanced non-small cell lung cancer.

In a subgroup of Japanese patients in the ARCHER 1050 randomized phase 3 trial, we evaluated the efficacy and safety and determined the effects of dose modifications on adverse events (AE) and therapy management of first-line oral dacomitinib 45 mg compared with oral gefitinib 250 mg, each once daily in 28-d cycles, in patients with EGFR-activating mutation-positive (EGFR-positive; exon 19 deletion or exon 21 L858R substitution mutations) advanced non-small cell lung cancer (NSCLC). The primary endpoint was progression-free survival (PFS; RECIST, version 1.1, by blinded independent review).

Expression Profiles of NOS Isoforms in Dental Pulp and Odontoblasts in nNOS Knockout Mice.

Active oxygen and free radicals are involved in metabolism in cells and tissues. Immunohistological studies of related enzymes are few, and the morphological dynamics of these enzymes in dental pulp and odontoblasts remain to be elucidated. Nitric oxide synthase (NOS) has 3 isoforms: nNOS, iNOS, and eNOS.

Phase 1 study of crisaborole in Japanese healthy volunteers and patients with atopic dermatitis.

Crisaborole ointment, 2%, is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD). This parallel-cohort, phase 1 study was conducted to investigate skin irritation potential and safety of crisaborole in healthy Japanese adults (cohort 1) and the safety and pharmacokinetic profile of crisaborole and metabolites AN7602 and AN8323 in Japanese adults with mild to moderate AD (cohort 2). In cohort 1, 20 healthy volunteers received single applications of crisaborole and vehicle simultaneously on separate locations under 48-h occlusion.

The effect of midazolam administration for the prevention of emergence agitation in pediatric patients with extreme fear and non-cooperation undergoing dental treatment under sevoflurane anesthesia, a double-blind, randomized study.

Sevoflurane is generally the preferred anesthetic agent for general anesthesia in pediatric patients, due to its rapid induction and recovery characteristics. However, it has been recognized that a major complication is emergence agitation when awakening from general anesthesia. The aim of this study was to evaluate the occurrence rate of emergence agitation in the operating room and postoperative recovery area following intraoperative administration of midazolam to pediatric patients under general anesthesia.

A Retrospective, Cross-Sectional Study on the Prevalence of Hyperuricemia Using a Japanese Healthcare Database.

Objectives: This study aims to evaluate the prevalence of hyperuricemia (HU) considering both serum uric acid (SUA) levels and medication status of urate-lowering drugs (ULDs), and the association between HU and its comorbidities using a Japanese healthcare database.

Materials And Methods: The study population consisted of 60,828 subjects who had at least one serum uric acid measurement between the fiscal years (FYs) 2010 and 2014 in a Japanese employment-based health insurance database (MinaCare Co., Ltd.

Parental Satisfaction with Ambulatory Anesthesia during Dental Treatment for Disabled Individuals and Their Preference for Same in Future.

The purpose of this study was to survey parental satisfaction with ambulatory anesthesia during dental treatment in disabled patients. Factors associated with parental preference for general anesthesia during future dental treatment in such patients were also investigated. A questionnaire was mailed to the parents of 181 disabled individuals who underwent dental treatment under ambulatory anesthesia at Tokyo Dental College Suidobashi Hospital between 2012 and 2016.

Interim analysis based on the weighted log-rank test for delayed treatment effects under staggered patient entry.

Fleming and Harrington's G(ρ,γ) class of weighted log-rank tests is appropriate for detecting delayed treatment effects such as those seen in cancer vaccines. A conditional power (CP) and an alpha spending function (ASF) approach are useful for interim analyses that are conducted with the aim of early termination due to futility and efficacy, respectively. However, calculation of the CP and the total Type I error probability are often not considered for delayed effects under the staggered patient entry.

Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine compared to the 23-valent pneumococcal polysaccharide vaccine in elderly Japanese adults.

Streptococcus pneumoniae is a major cause of severe disease worldwide, particularly in the elderly population. Due to increasing life expectancy in Japan and elsewhere, an effective vaccine which offers the possibility of prolonged protection is required. Protein conjugated pneumococcal vaccines, which have the ability to boost immunity (immunologic memory) on natural exposure or revaccination, may meet these requirements.

Estimation of treatment effect adjusting for dependent censoring using the IPCW method: an application to a large primary prevention study for coronary events (MEGA study).

Background: The MEGA study is a randomized controlled trial conducted in Japan to evaluate the primary preventive effect of pravastatin against coronary heart disease (CHD), in which 8214 subjects are randomized to diet or diet plus pravastatin. Pravastatin reduces the incidence of CHD (hazard ratio=0.67; 95%CI: 0.

Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA.

The A1555G mutation in the mitochondrial 12S ribosomal RNA gene is often found in patients with hearing loss after aminoglycoside exposure. A second pathogenic mutation in this gene, deletion of thymidine at position 961 with varying numbers of cytosines inserted (delT961Cn), has recently been found to predispose patients to aminoglycoside-induced deafness. We report on a Japanese patient bearing the delT961Cn who had streptomycin-induced deafness.