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Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or superselective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, superselective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and 3 patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug-free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread. [ABSTRACT FROM AUTHOR]

Background: During restoration of poorly fitting complete dentures (CDs) in edentulous patients, liners are used to reconstruct the concave surfaces of CDs with a new base material. These relining materials are classified into resilient liners (RLs) and non-resilient liners (NRLs), but the clinical effects of these liners and their selection criteria remain unclear. The purpose of this study is to evaluate the clinical efficacy of relining mandibular CDs using RL and NRL and to conduct a follow-up study.Methods: The study is currently being conducted at eight centers, and a parallel-group randomized controlled trial (RCT) is underway. One hundred thirty-two edentulous patients with poorly fitting mandibular CDs will be assigned to two groups based on whether they will receive RL or NRL. Participants will have an RL or NRL applied for relining their CDs using an indirect method of dynamic impressions. Data will be recorded at 1 week and 3, 6, and 12 months after denture delivery. The primary outcome will be assessment of the patients' general satisfaction by using a 100-mm visual analog scale (VAS). Secondary outcomes will be measured as patient-reported outcomes, including food intake status and oral hygiene-related quality of life. Masticatory performance and the number of sore spots on the oral mucosa will also be recorded. Comparisons between the two groups and within-subject comparisons of pre- and post-intervention measurements will be conducted.Discussion: For dentists and prosthetic researchers in Japan, this RCT will provide information on the clinical efficacy of RL materials in comparison to RNL in CD wearers. The new evidence regarding the use of RL materials in an aging population will also be useful to dentists in other countries in their routine clinical practice.Trial Registration: This clinical trial has been registered at the University Hospital Medical Information Network (UMIN) Center (UMIN000041950). [ABSTRACT FROM AUTHOR]

We examined the evolution of the magma feeding system at Zao volcano (NE Japan) during seven episodes of Komakusadaira pyroclastic activity (ca. 33–12.9 ka). The rocks, which are calc-alkaline and medium-K basaltic andesite to andesite (54.9–59.5% SiO2), are herein suggested to have been derived from two main magmatic end-members: silicic andesite magma (59~60% SiO2, 940~970°C, cpx-opx-plg as phenocrysts) and basaltic magma (52% SiO2, ~ 1085°C, Fo78~80 olv-plg as phenocrysts). These two end-members retained their compositional integrities throughout all seven eruptive episodes. The presence of Mg-rich (Fo> 80) olivine phenocrysts suggests the basaltic end-member was derived from fairly primitive magma (> 1100°C), which differentiated during ascent. By examining temporal variations in the chemical compositions of the phenocrystic minerals, three evolutionary pathways that produced the erupted products are defined; these are reflected in seven sequential episodes: (1) Crystal-rich silicic andesite magma was repeatedly withdrawn from the reservoir by the forced injection of basaltic magma (episode 1). (2) Crystal-poorer intermediate magma was formed by effective mixing of injected basaltic magma. Subsequent eruption of the intermediate magma was triggered by a new injection of mafic magma. The percentage of intermediate magma involved in the eruptions decreased over time (episodes 2–4). (3) By repeated fairly primitive to basaltic magma injections, the percentage of the mobilized part of the silicic andesite magma involved in the erupted magma gradually increased over time (episodes 5–7). [ABSTRACT FROM AUTHOR]

Transmission clusters of HIV-1 subtype B uniquely associated with the epidemic among men who have sex with men (MSM) in East Asia have recently been identified. Using the Los Alamos HIV sequence database and the UK HIV drug resistance database, we explored possible links between HIV MSM epidemics in East Asia and the rest of the world by using phylogenetic and molecular clock analyses. We found that JP.MSM.B-1, a subtype B MSM variant that accounts for approximately one-third of the infections among Japanese MSM, was detected worldwide, in the United Kingdom (n=13), mainland China (n=3), the United States, Germany, Canada, and Taiwan (n=1 each). Interestingly, 10 United Kingdom samples plus two from Germany and the United States formed a distinct monophyletic subgroup within JP.MSM.B-1. The estimated divergence times of JP.MSM.B-1 and the latter subgroup were ~1989 and ~1999, respectively. These dates suggest that JP.MSM.B-1 was circulating for many years in Japan among MSM before disseminating to other countries, most likely through global MSM networks. A significant number of other Asian MSM HIV lineages were also detected in the UK HIV drug resistance database. Our study provides insight into the regional and global dispersal of Asian MSM HIV lineages. Further study of these strains is warranted to elucidate viral migration and the interrelationship of HIV epidemics on a global scale. [ABSTRACT FROM AUTHOR]

Abstract: We reviewed research on the broodstock management and larviculture of the Pacific northern bluefin tuna (PBT) Thunnus orientalis in Japan. Japan has been at the forefront of PBT research since 1970 due to the participation by federal and prefectural governments and universities in a national project aimed to optimize productivity of the sea around Japan. In 1979, scientists at Kinki University succeeded in the first spontaneous spawning in captivity by the broodstock of 5year-old PBT. Successful spawning was also performed in 1980 and 1982, but no spawning then occurred until 1993, when Maruha Nichiro Holdings, Inc. (MNH) and Nippon Formula Feed Manufacturing Company, Ltd. (NFFMC) became involved in tuna farming and succeeded in the spawning of four-year-old broodstock. Since then, successful spawning of PBT in captivity has been reported from several sites as well as spawning in Kinki Univ. since 1994. With the successful spawning of PBT, the Fisheries Research Agency (FRA; formerly, Japan Sea Farming Association) of Kinki University, in conjunction with MNH, NFFMC, and Takuyo Ltd., has actively carried out research on and development of tuna larviculture technology. Thus, knowledge about broodstock management and larviculture has accumulated in Japan, but technical problems with larviculture still remain to be solved. There are 9 sites of successful spawning in net pens in Japan so far. At 4 of these sites in regions around Amami Island, yearly spawning has stably occurred. We have been accumulating data about the period of maturation, environmental key factors triggering the spawning, the age of onset of spawning, and the pattern of spawning through measurement of the ambient environment, gonad morphometry, endocrinology, mitochondrial DNA analysis, and daily careful observation of broodstock. Research on PBT larviculture at Kinki University, FRA, MNH, NFFMC, and Takuyo have succeeded in producing tens of thousands of hatchery-raised juveniles. As a result, Kinki University succeeded in establishing the full life cycle of PBT in captivity, and also achieved its aquaculture life cycle. However, solutions are needed for the remaining technological issues of PBT larviculture, including sinking syndrome, where larvae die on the bottom of the tank during the early phase of larviculture, the search for appropriate food (species, size, and nutrition) around the transition stage from larva to juvenile, cannibalism and collision against walls in the juvenile, and malformation and viral diseases in the young stage. [Copyright &y& Elsevier]

Periprosthetic bone loss is a well documented phenomenon after cementless total hip arthroplasty. We compared the bone mineral density (BMD) in 33 patients using the three dimension taper shape stem and 13 patients with a straight component with a distal taper. Postoperative follow-up was evaluated by dual-energy X-ray absorptiometry. BMD was recorded in seven Gruen zones. BMD was correlated with clinical examination, Harris Hip Score (HHS), Body Mass Index (BMI) and age. Clinical assessment took place at 12 months post operation. Periprosthetic BMD loss using the three dimensional straight tapered stem was consistently much less in comparison with the straight type component with a distal tapered design stem. BMD in Gruen zone 1 was maintained. There was no correlation between periprosthetic bone mineral density and clinical factors. [ABSTRACT FROM AUTHOR]

Physical conditions such as oceanic turbulence related to food availability are considered to be important factors affecting fish larval survival. Rearing experiments were conducted to elucidate the effects of turbulence on the survival and feeding rates during the initial feeding period of Pacific bluefin tuna Thunnus orientalis. Six levels of turbulence intensity were provided by changing flow rates from pipes set on the bottom of rearing tanks. The result showed a dome-shaped relationship between turbulence level and survival rate, in which the feeding rate appeared higher at a logged turbulence energy dissipation rate of −6.32, and decreased at both higher and lower turbulence levels. Compared with the turbulence intensity in the ocean, the optimal turbulence level for Pacific bluefin tuna larvae corresponded to the turbulence caused by sea surface winds with speeds of 4–12.5 m/s. The estimated optimal turbulence intensity for Pacific bluefin tuna larvae is comparable to that for yellowfin tuna Thunnus albacares. [ABSTRACT FROM AUTHOR]

Abstract: Measurements of fog and rain water chemistry at the summit of Mt. Fuji, the highest peak in Japan, as well as at Tarobo, the ESE slope of Mt. Fuji in September 2002. The pH of fog and rain water sampled at Mt. Fuji varied over a range of 4.0–6.8. Acidic fogs (pH<5.0) were observed at the summit when the air mass came from the industrial regions on the Asian continent. The ratio of [SO4 2−]/[NO3 −] in the fog water was lower at Tarobo than at the summit. High concentrations of Na+ and Cl− were determined in the rain water sampled at the summit, possibly because of the long-range transport of sea-salt particles raised by a typhoon through the middle troposphere. The vertical transport of sea-salt particles would influence the cloud microphysical properties in the middle troposphere. Significant loss of Mg2+ was seen in the rain water at the summit. The concentrations of peroxides in the fog and rain water were relatively large (10–105 μM). The potential capacity for SO2 oxidation seems to be strong from summer to early autumn at Mt. Fuji. The fog water peroxide concentrations displayed diurnal variability. The peroxide concentrations in the nighttime were significantly higher than those in the daytime. [Copyright &y& Elsevier]

The article presents a case study of a 39-year-old man admitted at Iwate Medical University Hospital in Japan for complex dysfunction of occlusion and mastication. The patient was diagnosed with malunited maxillary fracture after an occlusal examination. It mentions the treatment with dental prosthesis to restore mandibular function and facial asymmetry.

The geologic and petrologic study of the Kattadake pyroclastics (around 10 ka) from the Zao volcano (NE Japan) revealed the structure of the magma plumbing system and the mixing behavior of the shallow chamber. The Kattadake pyroclastic succession is divided into lower and upper parts by a remarkable discontinuity. All rocks belong to medium-K, calc-alkaline rock series and correspond to ol-cpx-opx basaltic-andesite to andesite with 20–28 vol% phenocrystic modal percentage. All rocks were formed by mixing between andesitic magma and near aphyric basalt. The petrologic features of andesites of lower and upper parts are similar, 59–61 wt% SiO2, having low-An plagioclase and low-Mg pyroxenes, with pre-eruptive conditions corresponding to 960–980 °C, 1.9–3.5 kb, and 1.9–3.4 wt% H2O. However, the basalts were ca. 49.4 wt% SiO2 with Fo~84 olivine in the lower part and 51.8 wt% SiO2 with Fo~81 olivine and high-An plagioclase the in upper one. The percentage of basaltic magma in the mixing process was lower, but the temperature of the basalt was higher in the lower part than the upper one. This means that the shallow magma chamber was reactivated more efficiently by the hotter basalts and that the mixed magma with a 70–80% of melt fraction was formed by a smaller percentage of the basaltic magma. [ABSTRACT FROM AUTHOR]

Malignant melanomas were found in 15.8% of xeroderma pigmentosum (XP) patients with skin cancer in Japan. When multiple cancers were scored separately depending on the histopathologic types, 12.1% of the skin cancers in XP patients was malignant melanoma. The relative incidence of malignant melanoma in skin cancer in XP patients is similar to that in skin cancer in general (12.6%), reported previously. Most of the malignant melanoma in XP patients developed in skin exposed to sunlight, in contrast to the high incidence of malignant melanoma in general in the unexposed skin of Japanese people. A DNA repair defect of UV damage is strongly suggested to be responsible for the high incidence of skin cancer in XP patients. The onset of malignant melanoma in XP patients was about ten years old, and was as early as those of basal cell carcinoma and squamous cell carcinoma in the patients with very low DNA repair capacities. Among nine genetic complementation groups and a variant type, group A XP cells were found to be extremely hypermutable by ultraviolet light, while group C XP cells were also hypermutable, but at the same level as normal cells when adjusted for survival. Mutagenesis as a possible mechanism of carcinogenesis in XP is supported by these results, but evidence in other cancer-prone hereditary diseases is yet to be obtained. [ABSTRACT FROM AUTHOR]

Abstract Zao volcano is one of the representative active stratovolcanoes in northeast Japan, having many historical eruption records, as the last one occurred in 1940. Since 2013 to present, precursory phenomena, such as volcanic tremors and deformation of the summit area, have been detected in this volcano; thus, it is urgently necessary to thoroughly characterize the magma feeding system beneath the volcano. Our aim is to understand the magma chamber structure and dynamics associated with the recent activity (ca. ~2 ka) of Zao volcano in NE Japan. We conducted petrological and geochemical studies in the representative pyroclastic products and youngest lavas of its recent activity. The products are divided into the GSN (Goshikidake-nanbu) pyroclastics, GST (Goshikidake-tobu) pyroclastics and GS lavas (Furikodaki lava and Goshikidake-nanpo lava and associated pyroclastic deposits). The rock samples are calc-alkaline olivine-bearing pyroxene andesites originated as the result of mixing between felsic (containing Mg-poor pyroxenes + anorthite (An)-poor plagioclases) and mafic (containing forsterite (Fo)-rich olivines + An-rich plagioclases magmas). Thermodynamic modelling indicates that the temperature (T)–pressure (P)–water activity (H 2 O) conditions of the felsic (ca. 60–61 wt% SiO 2 , 968–1000 °C, 1.6–2.0 kbar and 1.8–2.2 wt% H 2 O) and the mafic (ca. 48.0–50.5 wt% SiO 2 , 1113–1170 °C, <2.4 kbar and 1.0–2.2 wt% H 2 O) end–members are similar between the GSN, GST pyroclastics and GS lavas. Compositional zoning of orthopyroxene phenocrysts suggests the formation of two mixed magmas, namely the main mixed and the Mg-rich mixed ones. The mafic magma from a deeper source entered repeatedly into a shallower felsic magma chamber. As a result, the main mixed magma developed within the chamber. The Mg-rich-mixed magma tentatively developed by the injection and simultaneous mixing of both the main mixed magma and the injected mafic one, merging later on into the main mixed magma. The Fe-Mg diffusion modelling on orthopyroxenes reveal that the injections occurred from <60 days to 1.7 years for thin-darker-zone types, and multiple injections of mafic magma occurred from 2.5 years to 150 years for broad-darker-zone types until the eruptions. The thin-darker-zone type orthopyroxene phenocrysts are abundant in the GSN and GST pyroclastics but rare in the GS lavas. Instead, the broad-darker-zone type orthopyroxenes are rare in the GSN and GST pyroclastics and abundant in the GS lavas. Thus, the main mixed layer was more evolved for the GS lavas than for the GSN and GST pyroclastics. The injected mafic magmas for the GS lavas were merged more extensively than the GSN and GST pyroclastics, resulting in a larger release of volatile components that triggered the effusive episodes. Given that local precursory phenomena have been currently detected in Zao volcano, we are confident that any research to thoroughly characterize the magma feeding system under this active volcano is essential for society to better react to any potential volcanic hazard in the near future. Highlights • Revealing magma chamber structure and dynamics beneath the Goshikidake-Zao volcano • Pyroclastic and lava products evidence two main different magma chambers structure • Calc–alkaline andesites by mixing of felsic and mafic magmas • Residence timescales from 60 days to 150 years through opx diffusion modelling • Shorter timescale for pyroclastics than for lavas ejection [ABSTRACT FROM AUTHOR]

Background Organ donor scarcity remains a restricting factor for pancreatic islet transplantation. To date, limited information is available on the impact of long-distance transportation on transplantable pancreatic islets. The objective of this study was to assess the effects of transportation on the viability and function of murine pancreatic islet cells. Methods The isolated murine pancreatic islets were transported from Japan to Korea with the use of commercial modes of transportation: subway and commercial airplane. After transportation, the islets were assessed by performing a viability assay and by evaluating the islets' insulin secretion in response to glucose stimulation. A comparative study was performed for evaluating the insulin secretory responses of transported and control islets (not transported). Results There was no evidence of contamination in the transported pancreatic islets. No significant differences were observed in the viability and functionality of the transported and control islet cells. Conclusions These findings show the feasibility of pancreatic islet transportation from Japan to Korea. Our data could be used not only for the inter-Asian but also for global advancement of animal and human islet transportation methods and transplantation research. [ABSTRACT FROM AUTHOR]

A survey of HIV-1 strains circulating in the Tokyo-Kanagawa metropolitan area of Japan during 2004 to 2011 (n = 477) identified six Japanese males (patients 1 to 6), who harbored viruses with genome segments derived from a distinct CRF01_AE variant uniquely found among men who have sex with men (MSM) in China (designated CN.MSM.01-1). These six HIV infections were diagnosed in 2010 and 2011 among MSM (3 of 75) and men with unknown risk factors (3 of 63) and differed from the vast majority of HIV infections among MSM in Japan, which are overwhelmingly characterized by sub-type B (239 of 246 [97.2%]). Approximately one-third (91 of 239 [38.1%]) of subtype B strains from MSM in Japan belong to a large monophyletic cluster (designated JP.MSM.B-1). In addition, we identified a smaller subtype B cluster (n = 8) (designated JP.MSM.B-2) that also contains strains from two Chinese MSM living in Japan. Interestingly, patients 5 and 6 were found to be coinfected with CRF01_AE (CN.MSM.01-1) and subtype B (JP.MSM.B-2 or JP.MSM.B-1) variants that are unique to the HIV-1 epidemics among MSM in China and Japan, respectively. Our study demonstrates for the first time the effect of the expanding HIV epidemic among MSM in China on transmission in neighboring countries and shows the on-going mixing of CRF01_AE and subtype B lineages unique to HIV-1 that cocirculate in MSM populations in East Asia. This finding highlights the importance of strengthening epidemiological surveillance in the region and the need for effective measures to limit transmission among MSM in East Asia. [ABSTRACT FROM AUTHOR]

Background Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. Materials In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. Results In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. Conclusions To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval. [ABSTRACT FROM PUBLISHER]

Background/purpose: To determine the short- and long-term results of surgical treatments for chronic pancreatitis (CP) at a high-volume center in Japan., Methods: The records of 151 consecutive patients undergoing surgery for CP were retrospectively reviewed. Selection of surgical procedures used had been according to the Japanese Clinical Practice Guidelines for CP 2015. Long-term (≥1 year) follow-up was performed in 100 patients (median of 37 months)., Results: Surgical drainage procedures were performed in 107 patients (Frey operation in 81, longitudinal pancreaticojejunostomy in 26), pancreatic resection in 37 (subtotal stomach-preserving pancreaticoduodenectomy in 11, distal pancreatectomy in 26), and other procedures in six. The rates of postoperative mortality and morbidity were 1% and 26%, respectively. The rates of complete and partial pain relief were 62% and 37%. The frequency of occurrence of severe morbidity was significantly higher after pancreatic resection than in patients receiving drainage procedures (13% vs 2%, P = .019). The rate of new-onset diabetes was also significantly higher after resection than drainage (60% vs 25%, P = .017)., Conclusions: Surgical treatment for painful chronic pancreatitis can be safe and effective. An optimal procedure should guarantee pain relief and preserve a maximum of pancreatic function., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)