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In the central nervous system, astrocytes enable appropriate synapse function through glutamate clearance from the synaptic cleft; however, it remains unclear how astrocytic glutamate transporters function at peri-synaptic contact. Here, we report that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synapse formation and function in the developing cerebellum. Dscam -mutant mice show defects in CF synapse translocation as is observed in loss of function mutations in the astrocytic glutamate transporter GLAST expressed in Bergmann glia. These mice show impaired glutamate clearance and the delocalization of GLAST away from the cleft of parallel fibre (PF) synapse. GLAST complexes with the extracellular domain of DSCAM. Riluzole, as an activator of GLAST-mediated uptake, rescues the proximal impairment in CF synapse formation in Purkinje cell-selective Dscam -deficient mice. DSCAM is required for motor learning, but not gross motor coordination. In conclusion, the intercellular association of synaptic and astrocyte proteins is important for synapse formation and function in neural transmission. The glutamate transporter GLAST in astrocyte regulates synapse function by glutamate clearance. Here, the authors show that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synaptogenesis through the intercellular association with GLAST in the developing cerebellum.

Recent studies have emphasized the association between tubulin gene mutations and developmental abnormalities of the cortex. In this study, the authors identified a mutation in the tubulin-encoding class III β-tubulin (TUBB3) gene in a 4-year-old boy presenting with brain abnormalities and unilateral hypohidrosis. The patient showed a left internal strabismus, moderate developmental delay, and congenital hypohidrosis of the right side of the body. Magnetic resonance imaging disclosed gyral disorganization mainly in the left perisylvian region, dysmorphic and hypertrophic basal ganglia with fusion between the putamen and caudate nucleus without affecting the anterior limb of the internal capsule, and moderate hypoplasia of the right brain stem and cerebellum. Diffusion tensor imaging studies revealed disorganization of the pyramidal fibers. The amplitude of the sympathetic skin response was low in the right arm, which led to a diagnosis of focal autonomic neuropathy. Sequencing the TUBB3 gene revealed a de novo missense mutation, c.862G>A (p.E288K).

The ocean plays important roles not only in the global climate system but also in the global material cycling through biogeochemical processes, and has close relationships with the daily lives of people through fisheries, marine energy and resources, ocean transportation, marine sports, ocean relaxation activities, and others. The Ocean Literacy movement began in the U.S. in the early 2000s, and has recently become international as shown by the Ocean Literacy Portal website operated by IOC/UNESCO. In Japan, the present national standard course of study at elementary school has not given any room for ocean education while the Oceanographic Society of Japan (JOS) and 34 other academic societies/committees gave a proposal entitled, “On the Setting up of a class named, ‘the role of Ocean’ in the national standard course of study for the 4th grade students in the elementary science education” to the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in April 2016. In the U.S., aiming to serve as a community-based measurement tool that allows the comparison of levels of ocean knowledge across time and location, the International Ocean Literacy Survey (IOLS) project has been started since 2015. Fauville et al. (2018, https://doi.org/10.1080/13504622.2018.1440381) published the results from IOLS Version 2, and the English version IOLS Version 4 was finalized after reviewing the English IOLS Version 3 by IOLS Advisory Board consisting of international marine researchers, communicators, teachers, and psychometricians. The English version of the IOLS Version 4 was translated into 14 languages (Catalan, Chilean, Dutch, Greek, Italian, Japanese, Korean, Polish, Portuguese, Simplified Chinese, Spanish, Tagalog, Thai, and Traditional Chinese) and its field testing was conducted during February and March 2019 with nominal 6945 participants worldwide including nominal 567 participants from Japan. In collaboration with IOLS Version 4 field testing, JOS and the Marine Learning Center took part in correcting the original Japanese draft of IOLS Version 4, sponsored IOLS Version 4 field testing, and made a wide campaign to high-school teachers through sending recommendation letters to academic societies and other ocean-related organizations.

Hiroyuki Mano and colleagues report fusions involving DUX4 in 16.4% of Ph-negative adolescent and young adult acute lymphoblastic leukemia (AYA-ALL) cases. Transplantation assays in mice support an oncogenic role for the DUX4-IGH fusion gene, which expresses DUX4 protein with an aberrant C terminus at high levels in patients with AYA-ALL. The oncogenic mechanisms underlying acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA; 15–39 years old) remain largely elusive 1 , 2 , 3 . Here we have searched for new oncogenes in AYA-ALL by performing RNA-seq analysis of Philadelphia chromosome (Ph)-negative AYA-ALL specimens ( n = 73) with the use of a next-generation sequencer. Interestingly, insertion of D4Z4 repeats containing the DUX4 gene into the IGH locus was frequently identified in B cell AYA-ALL, leading to a high level of expression of DUX4 protein with an aberrant C terminus. A transplantation assay in mice demonstrated that expression of DUX4 - IGH in pro-B cells was capable of generating B cell leukemia in vivo . DUX4 fusions were preferentially detected in the AYA generation. Our data thus show that DUX4 can become an oncogenic driver as a result of somatic chromosomal rearrangements and that AYA-ALL may be a clinical entity distinct from ALL at other ages.

PurposeThis study sought to explore whether the experience level of the first assistant surgeon influences perioperative organ injuries (ureteral, bladder, and intestinal injuries) in patients undergoing total laparoscopic hysterectomy (TLH) for benign diseases. We defined an experienced surgeon as a surgeon certified by the Skill Qualification Committee of the Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy or a surgeon with equivalent surgical skills.MethodsWe reviewed our surgical registry database of TLH for benign indications between 2014 and 2020 and only selected cases performed by an experienced primary surgeon. Patients were divided into two groups based on the experience level of the first assistant. Inverse probability of treatment weighting by propensity score, which was adjusted for patient and procedure characteristics, was used to examine differences in perioperative organ injuries according to the experience level of the first assistant.ResultsAmong 1682 patients who underwent TLH, 18 organ injuries were found (0.83%). In the propensity score inverse probability of treatment weighting models, less experience of the first assistant had no significant impact on the occurrence of perioperative organ injuries (p = 0.348).ConclusionIn TLH for benign indications at our hospital, given an experienced primary surgeon, the inclusion of a less experienced first assistant does not negatively affect the occurrence of perioperative organ injuries.

Outpatient medical facilities tend to have high antimicrobial prescription rates and are therefore major targets for antimicrobial stewardship programs (ASPs). Pediatric primary emergency medical centers in Japan have difficulties in implementing conventional ASPs due to the low continuity of stewardship. Accordingly, there is a need to develop effective ASP models for these facilities. We conducted a single-center, quasi-experimental study to evaluate the effects of a nudge-based ASP in reducing unnecessary third-generation cephalosporin (3GC) prescriptions in a pediatric primary emergency care center (PEC). The implemented ASP utilizes monthly newsletters that report current antimicrobial use patterns and prescribing targets. We compared the monthly 3GC prescription numbers and proportions of unnecessary prescriptions before and after the ASP was implemented. The trends in 3GC prescriptions were examined using an interrupted time-series analysis. The numbers of patients before and after ASP implementation were 129,156 and 28,834, respectively. The number of unnecessary 3GC prescriptions decreased by 67.2% in the year after ASP implementation. The interrupted time-series analysis showed that the ASP was significantly associated with a reduction in 3GC prescriptions (regression coefficient − 0.58, P < 0.001).Conclusion: The nudge-based ASP was effective in reducing 3GC use in a Japanese PEC. This simple and inexpensive approach may have applications in other outpatient facilities.What is Known:• Outpatient medical facilities tend to have high antimicrobial prescription rates. Despite the development of several strategies for outpatient antimicrobial stewardship programs, these approaches have not sufficiently reduced antimicrobial use.What is New• Our nudge-based antimicrobial stewardship program using newsletters was shown to be a simple, inexpensive, and feasible method for reducing unnecessary antimicrobial use in a pediatric primary emergency care center. This may represent an effective antimicrobial stewardship strategy in Japanese outpatient facilities.

The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in the pathogenesis of Epstein-Barr virus-positive diffuse large B cell lymphoma, not otherwise specified (EBV+ DLBCL, NOS). Here, we describe PD-L1 expression by EBV+ DLBCL, NOS in order to evaluate its possible contribution to the pathogenesis of this tumor. The study included 57 cases of EBV+ DLBCL, NOS. The median patient age was 69 years and 95% (n = 54) were aged > 45. Extranodal lesions were present in 39 (69%) at initial diagnosis. PD-L1 expression (mAb SP142-positive staining) was present in more than 5% of tumor cells in only six cases (11%), in clear contrast to the 77% reported in cases aged under 45 years. Among the PD-L1+ cases, three were nodal lesions. All six PD-L1+ cases progressed in the 3 years after diagnosis and four of the six patients died of the disease within 2 years. PD-L1+ cases had significantly shorter PFS (P = 0.002) and relatively short OS (P = 0.26), compared with PD-L1− cases. EBV+ DLBCL, NOS in the elderly infrequently expressed PD-L1 and had poor prognosis. PD-L1 expression in EBV+ DLBCL, NOS of the elderly sheds light on the pathogenetic role of immune senescence.

To examine the annual trends in the occurrence of eosinophilic gastrointestinal disease (EGID) in Japan. This study examined data from patients with EGID who underwent endoscopy at 716 facilities between January 2015 and March 2023. Data extracted from the Japanese Endoscopy Database (JED) included endoscopic procedure counts, patient demographics, infection status, comorbidities, and balloon dilatation. Analyses incorporated both confirmed and suspected EGID cases. In total, 9,940,870 endoscopic procedures were performed, identifying 9669 cases of EGID. From 2015 to 2023, the Cochran-Armitage trend test showed a significant increase in cases of eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), and eosinophilic duodenitis (EoD) ( < 0.001). However, no significant trend was observed for eosinophilic enteritis (EoN) or eosinophilic colitis (EoC) ( = 0.136). The number of EoE cases increased, with reporting rates changing from 36 (0.0464%) in 2015 to 3631 (0.176%) in 2022 ( < 0.001). EoG + EoD cases increased from one (0.0013%) to 410 (0.0199%) ( < 0.001), while EoN + EoC cases remained stable ( = 0.136). The JED project data showed increasing detection of EoE, EoG, and EoD in Japan, while EoN and/or EoC cases remained stable. These findings are based on reporting rates from individuals undergoing endoscopy, rather than estimates from population-based endoscopist reporting rates.