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Despite being one of the bilaterians, the body plan of echinoderms shifts from bilateral symmetry to five-fold radial, or pentaradial symmetry during embryogenesis or their metamorphosis. While the clarification of the developmental mechanism behind this transition will be a basis for understanding their unique body plan evolution, it is still poorly understood. With this regard, the hydrocoel, a mesodermal coelom formed on the left side of bilateral larva, would be a clue for understanding the mechanism as it is the first pentaradial structure that appears before metamorphosis and develops into the water vascular system of adults. By analyzing the development of a sea cucumber, Apostichopus japonicus, we found that the hydrocoel expresses genes related in muscle and neural formation such as myosin heavy chain, tropomyosin, soxC, and elav, implying that cells of the hydrocoel contributes to muscle and neural structures in the adult. Furthermore, ablation of one of the hydrocoel lobes led to incomplete development of adult pentameral structures. The ablation of primary hydrocoel lobes resulted in the reduction in tentacles and the ablation of secondary hydrocoel lobes resulted in the reduction in water vascular canals and nerve cords. Our findings suggest that the hydrocoel lobes may serve as a potential organizing center for establishing the pentaradial body plan in echinoderms.

Glenohumeral internal rotation deficit is generally recognized as a risk factor for throwing disability in baseball players. However, the pathology, timing of onset, role in the onset of humeral retrotorsion angle (HTA) and soft tissue extensibility (STE), and the relationship with age remain unclear. Therefore, the purpose of this cross-sectional study was to investigate age-related glenohumeral internal rotation deficit, HTA, and STE in Japanese baseball players and determine whether these factors correlate with throwing disability.Participants were 172 male baseball players divided into a symptomatic group (n = 68) and an asymptomatic group (n = 104). The mean age at examination was 15.4 ± 3.2 (range, 8-22) years. Measurement items were range of motion of bilateral internal and external rotation at 90° abduction (2ndIR and 2ndER, respectively), bilateral HTA, and posterior shoulder muscle elasticity. Correlations of age, symptom, and dominance with these measurements were investigated, and significant bilateral differences in HTA and STE by age and symptom were analyzed.HTA and 2ndER of the dominant side were significantly greater than those of the nondominant side in those over the age of 13 years in both the asymptomatic and symptomatic groups. In contrast, 2ndIR of the dominant side was significantly smaller than that of the nondominant side in those over the age of 13 years in both the asymptomatic and symptomatic groups. The difference in HTA between the dominant and nondominant sides increased and then plateaued at 12° after the age of 16 years. STE was observed only in the symptomatic group, and the value of STE was significantly greater in players aged16 years compared with that in players aged12 years (P = .001). Muscle elasticity did not differ significantly between sides and showed no correlation with STE.The difference in HTA between the dominant and nondominant sides increased with age until 16 years old regardless of symptoms. STE in the dominant side was observed only in symptomatic baseball players after the age of 13 years and increased with age, plateauing around the age of 16 years. Posterior shoulder muscle elasticity was not indicated as a cause of STE.

Background: Previous studies showed that hydroxyapatite electret (HAE) accelerates the regeneration of vascular endothelial cells and angiogenesis. This study investigated the effects of HAE in myocardial infarction (MI) model mice. Methods and Results: MI was induced in mice by ligating the left anterior descending artery. Immediately after ligation, HAE, non-polarized hydroxyapatite (HAN), or water (control) was injected into the infarct border myocardium. Functional and histological analyses were performed 2 weeks later. Echocardiography revealed that HAE injection preserved left ventricular systolic function and the wall thickness of the scar, whereas HAN-injected mice had impaired cardiac function and thinning of the wall, similar to control mice. Histological assessment showed that HAE injection significantly attenuated the length of the scar lesion. There was significant accumulation of CD31-positive cells and increased expression of vascular endothelial growth factor (Vegf), intercellular adhesion molecule-1 (Icam1), vascular cell adhesion molecule-1 (Vcam1), hypoxia-inducible factor-1α (Hif1a), and C-X-C motif chemokine ligand 12 (Cxcl12) genes in the infarct border zone of HAE-injected mice. These effects were not induced by HAN injection. Anti-VEGFR2 antibody canceled the beneficial effect of HAE. In vitro experiments in a human cardiovascular endothelial cell line showed that HAE dose-dependently increased VEGFA expression. Conclusions: Local injection of HAE attenuated infarct size and improved cardiac function after MI, probably due to angiogenesis. The electric charge of HAE may stimulate angiogenesis via HIF1α-CXCL12/VEGF signaling.

Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer; GU) or duodenum (duodenal ulcer; DU). We conducted a large-scale cross-ancestry meta-analysis of PUD combining genome-wide association studies with four Japanese and two European studies (52,032 cases and 905,344 controls), and discovered 25 novel loci highly concordant across ancestries. Based on these loci, an examination of similarities and differences in genetic architecture between GU and DU demonstrated that GU shared the same risk loci as DU, although with smaller genetic effect sizes and higher polygenicity than DU, indicating higher heterogeneity of GU.H. pylori(HP)-stratified analysis found an HP-related host genetic locus, marking its role in HP-mediated PUD etiology. Integrative analyses using bulk and single-cell transcriptome profiles highlighted the genetic factors of PUD to be enriched in the highly expressed genes in stomach tissues, especially in somatostatin-producing D cells. Our results provide genetic evidence that gastrointestinal cell differentiations and hormone regulations are critical in PUD etiology.

Whole-genome sequencing (WGS) is being used in research and clinical settings in cancer genomics. Studies show that cancer patients generally have positive attitudes toward tumor profiling tests; however, few works revealed their attitudes toward WGS. This study clarifies the expectations, concerns, and result preferences of cancer patients (CPs), family members (FMs) and general adults (GAs) regarding WGS study in Japan. We conducted an anonymous survey with 1204 CPs, 5958 FMs, and 2915 GAs in 2021. Despite low awareness of the WGS studies, CPs had the highest expectations for it. FMs had a higher level of concern than CPs and GAs; feeling anxious by knowing the results, being treated unfavorably if germline findings were detected. Both the FMs and CPs were highly concerned about the protection of genetic information. CPs preferred results with actionability, however, only half preferred to know germline findings. Given the possibility of detecting variants across multidisciplinary diseases and the long-term continuity of WGS research, a system is needed in which study participants can consult and receive decision-making support at any time according to their needs.

Gene therapy has been explored as a future alternative for treating heart disease. Among several gene delivery systems aimed at penetrating specific target cells, we focused on safe and non-viral gene delivery materials with a high transfection efficiency. Although various techniques have been developed, the mechanisms underlying the cellular uptake of gene delivery materials have not yet been sufficiently studied in cardiomyocytes. The aim of this study was to determine how hydroxyapatite (HAp) nanoparticles contribute to the delivery of plasmid DNA (pDNA) into cardiomyocytes. We fabricated HAp nanoparticles using the water-in-oil (W/O) emulsion method and used these nanoparticles as the delivery vector for transfecting cardiomyocyte-derived HL-1 cells. HAp exhibited particles on the nanoscale and with a low cytotoxicity in HL-1 cells. The transfection assay performed with several endocytosis inhibitors suggested that the HAp/pDNA complexes were internalized by HL-1 cells through macropinocytosis. Furthermore, this HL-1 cell uptake was generated in response to HAp stimulation. Thus, HAp is a positive regulator of macropinocytosis in HL-1 cells and a good system for gene delivery in cardiomyocytes.

This study investigated the efficacy of copper (Cu) as an antibacterial element incorporated on titanium (Ti) surface by electrochemical treatment. Cu was incorporated onto Ti surface by micro-arc oxidation (MAO). A small amount of Cu was incorporated into the oxide layer and was found to be in oxidized states. Cu-incorporated samples exhibited no-harmful effect on the proliferation of osteoblastlike cells. Moreover, the difference in antibacterial property between fresh and incubated samples was evaluated using gram-positive and gram-negative facultative anaerobic bacteria. The specific antibacterial property of Cu incorporated into the Ti surface were confirmed. The antibacterial property prolonged upon immersion in physiological saline for 28 days. In other words, MAO-treated Ti containing Cu in this study is expected to achieve long-term antibacterial property in practical usage.

Osteochondral defects of articular cartilage cannot regenerate spontaneously. For its surgical treatment, advancements in cartilage tissue engineering have particularly focused on subchondral bone lesions that tend to delay healing. Therefore, it is important to understand interactions between subchondral bone and chondrocytes. This study aimed to investigate the behavior of chondrogenic ATDC5 cells on oriented hydroxyapatite (HAp) films that mimic bone surfaces. HAp nanoparticles prepared herein were needle like and plate like. HAp films were formed through self-organization of the nanoparticles and had 2D structures regularly arrayed with the particles. Both films prominently comprised a-plane orientation surfaces but differed in the degree of hydrophilicity because of the patterns of particle self-assembly. ATDC5 cells cultured on the HAp film with plate-like particles could adhered in a shorter period but could not spread. The adhesive force of cells was weaker with the hydrophilic surface than with other surfaces, as determined using a trypsin-based cell detachment assay. In addition, ATDC5 cells displayed enhanced proliferation and chondrogenic differentiation. Our results suggest that the oriented HAp film formed using plate-like particles provided chondrogenic cells with a desired scaffold as that of subchondral bone to increase cell proliferation and differentiation.

Background The scaffold for head and neck reconstruction needs mechanical strength to maintain specific forms. Hydroxyapatite (HA) enhances the mechanical strength of hydrogel and is routinely used for cartilage regeneration. However, there is a demand for hydroxyapatite that controls chondrogenic cell behavior. Objective Our aim was to regulate HA morphology through a hydrothermal process using organic acid and enhance chondrocyte proliferation and differentiation using shaped-regulated HA. Methods HA was synthesized from dodecanedioic acid (DD:HA) and oleic acid (OA:HA) by a hydrothermal method and then coated onto glass plates. Surface properties of the samples were compared by various techniques. Surface roughness and contact angles were calculated. Proliferation and differentiation of chondrogenic cells were measured by MTT assays and Alcian Blue staining, respectively, after various incubation periods. Results The morphological structures of DD:HA and OA:HA were different; however, the crystallinity and chemical structures were similar. Surface roughness and hydrophilic behavior were higher on DD:HA. DD:HA enhanced chondrogenic cell proliferation over time. The differentiation of ATDC5 cells was also increased on the DD:HA surface compared with those in other groups. Conclusions DD:HA enhanced cell viability to a greater extent than OA:HA did, indicating its excellent potential as an inorganic material compatible with chondrocyte regeneration.

Various hypotheses have been used to examine gender inequality in careers, while at the same time comparative and historical sociology has developed around certain areas of interest. This introduction clarifies that there is a need for a comparative and historical sociology specifically related to women’s careers. It presents the rationale for this special issue, which gathers articles opening gateways to further research in this vein.

Genomic tumor profiling tests (GTPTs) to find molecular targeted drugs for patients with advanced cancer are being introduced into clinical settings, which may result in secondary germline findings. Although small-scale qualitative studies have revealed patients’ attitudes toward GTPTs and preferences on receiving germline findings, no large-scale quantitative research exists that includes family members. We conducted anonymous surveys with 757 cancer patients (CPs), 763 family members (FMs), and 3697 general adults (GAs) in Japan. Awareness of GTPTs was low in all groups, however, both CPs and FMs showed a higher degree of recognition in the benefits of GTPTs. FMs wanted information on germline findings to be shared more than the CPs. Since advanced CPs may have psychological burdens that make it difficult to express their opinions on their therapeutic options and sharing germline findings, GTPTs should be offered with advanced care planning for patients.

We demonstrated the crystallization of calcium carbonate in the presence of polyaspartic acid (PAsp) and polylysine (PLys) under double-diffusion conditions in agar hydrogels. The crystallization of precipitated CaCO3 was discussed based on the equivalency rule, and it was suggested that the nucleation of CaCO3 in the presence of PLys and PAsp occurred heterogeneously on the polypeptide assemblies that act as templates for nucleation. With PLys alone, the precipitates had calcite as the major component and vaterite as the minor component, where calcite and vaterite adopted dendritic and spherulitic morphologies, respectively. In the presence of PAsp alone and a mixture of PLys and PAsp, the precipitates comprised calcite spherulites only. The spherulites had a hierarchal structure with an inner part (the core) having a loose structure and an outer part composed of calcite crystals that grew radically from the core. The cores completely dissolved during crystallization, resulting in the formation of spheru...

Steroidogenic factor 1 (NR5A1) is essential for gonadal development. To study the importance of NR5A1 during early gonadal sex differentiation, we generated Sox9-Cre-Nr5a1 conditional knockout (cKO) mice: Sox9-Cre;Nr5a1flox/flox and Sox9-Cre;Nr5a1flox/− mice. Double-immunostaining for NR5A1 and AMH revealed silenced NR5A1 in Sertoli cells and reduced AMH+ cells in the gonads of XY Sox9-Cre-Nr5a1 cKO mice between embryonic days 12.5 (E12.5) and E14.5. Double-immunostaining for SOX9 and FOXL2 further indicated an early block in Sertoli cells and ectopic granulosa cell differentiation. The number of cells expressing the Leydig cell marker 3βHSD obviously reduced in the gonads of XY Sox9-Cre;Nr5a1flox/− but not Sox9-Cre;Nr5a1flox/flox mice at E15.5. The presence of STRA8+ cells indicated that germ cells entered meiosis in the gonads of XY Sox9-Cre-Nr5a1 cKO mice. The results of qRT-PCR revealed remarkably reduced and elevated levels of testis and ovary markers, respectively, in the gonads of XY Sox9-Cre-Nr5a1 cKO mice at E12.5‒E13.5. These data suggested that the loss of Nr5a1 abrogates the testicular pathway and induces the ectopic ovarian pathway, resulting in postnatal partial/complete male-to-female gonadal sex reversal. Our findings provide evidence for the critical role of NR5A1 in murine gonadal sex determination in vivo.

Recently, the problem of infection on implanted devices caused by the formation of biofilms has been recognized. Surface treatment to prevent the initial stages of bacterial adhesion and subsequent bacterial growth is the only possible solution against such infection. In this study, simple electrochemical treatment was used for introducing silver, an antibiotic agent, on the titanium surface. A porous oxide layer containing small amounts of silver was formed on the metal of the substrate. This was done by microarc oxidation using the electrolyte with silver nitrate. The porous oxide layer was almost amorphous with a small fraction of anatase phase. The samples prepared using the electrolyte containing 0.04 mM or a higher concentration of silver nitrate showed an excellent antibacterial effect against both

Recently, silver (Ag) and copper (Cu) have been incorporated into a titanium (Ti) surface to realize their antibacterial property. This study investigated both the durability of the antibacterial effect and the surface change of the Ag- and Cu-incorporated porous titanium dioxide (TiO2) layer. Ag- and Cu-incorporated TiO2 layers were formed by micro-arc oxidation (MAO) treatment using the electrolyte with Ag and Cu ions. Ag- and Cu-incorporated specimens were incubated in saline during a period of 0&ndash, 28 days. The changes in both the concentrations and chemical states of the Ag and Cu were characterized using X-ray photoelectron spectroscopy (XPS). The durability of the antibacterial effects against Escherichia coli (E. coli) were evaluated by the international organization for standardization (ISO) method. As a result, the Ag- and Cu-incorporated porous TiO2 layers were formed on a Ti surface by MAO. The chemical state of Ag changed from Ag2O to metallic Ag, whilst that of Cu did not change by incubation in saline for up to 28 days. Cu existed as a stable Cu2O compound in the TiO2 layer during the 28 days of incubation in saline. The concentrations of Ag and Cu were dramatically decreased by incubation for up to 7 days, and remained a slight amount until 28 days. The antibacterial effect of Ag-incorporated specimens diminished, and that of Cu was maintained even after incubation in saline. Our study suggests the importance of the time-transient effects of Ag and Cu on develop their antibacterial effects.

Hyperostosis frontalis interna (HFI) is a condition characterized by abnormal bone outgrowth on the inner surface of the frontal bone. Most HFI cases occur in post-menopausal elderly women. The pathology of HFI development is uncertain. The estimated incidence of HFI ranges from 5 to 12% in Western countries, but few cases have been reported in the Japanese population. Here, we report a case of HFI in an 86-year-old Japanese female cadaver. Macroscopically, the internal surface of the frontal bone exhibited bilateral nodular protrusion with sparing of the midline, while the external surface was normal. According to the morphological classification of HFI proposed by Hershkovitz et al. this case belongs to type D, the most severe type. Using computed tomography (CT), we defined five layers, designated as I–V from the inner to the outer layer, in the nodular region of HFI; however, the normal frontal bone is composed of three layers. Histological results demonstrated that layers I, III, and V consisted of the cortical bone, and layers II and IV consisted of the trabecular bone. We also observed increases in the numbers of lamellar bone and blood vessels on the dural side of layer I, indicating increased vascularization and active osteogenesis. These results indicate that layer II represents a new diploe within the inner table, which split into layers I and III, suggesting that diploization within the inner table by activated remodeling may be involved in the development of hyperostosis in this case.

Surface modification techniques have been employed for the use of biocompatible and bioresorbable hydroxyapatite (HAp) nanoparticles in cell biology and medicine for the delivery of bioactive molecules. We demonstrated the effects of glucose modification of HAp (GlcHAp) on the transfection efficiency in endothelial cells. After preparing homogeneous HAp nanoparticles with a microemulsion technique, the particles with or without glucose modification and plasmid DNA (pDNA) complexes were transfected into endothelial cells. The transfection efficiency of GlcHAp/pDNA was higher than that of HAp/pDNA. To elucidate the mechanism underlying the improvement in the transfection efficiency following glucose modification, the uptake route into the cells and the inhibition of DNA degradation were investigated. GlcHAp/pDNA enhanced the transfection efficiency after interacting with the glucose transporter 1, as observed by the selective inhibitor assay. In addition, GlcHAp/pDNA was more stable than HAp/pDNA in the DNA degradation assay. Our results suggest that the glucose modification could promote the uptake of HAp nanoparticles by cells and protect the internalized DNA; properties essential for non-viral transfection carriers. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 61-66, 2019.

Hydroxyapatite (HAp) plates were successfully synthesized using dodecanedioic acid (DDDA). Following the preparation of an ethanolic solution of DDDA, solutions of calcium and phosphate were added in succession to produce a white slurry upon mixing. Subsequent processing of this slurry under hydrothermal conditions provided HAp plates of various sizes. Indeed, the plate size could be changed by varying the quantity of DDDA employed in the synthesis, with larger particles being obtained in the presence of larger quantities of DDDA. It was confirmed that a calcium–DDDA complex (Ca-DDD, calcium dodecanedioate) was formed upon mixing of the DDDA and calcium solutions. The observed morphological control could potentially be accounted for by the formation of Ca-DDD. More specifically, during crystal growth, Ca-DDD plays the role of a nucleation substrate (template), a pH buffer, and a calcium reservoir. Finally, we demonstrated that the obtained HAp plates could be employed to prepare a HAp film with high cryst...

Genome editing of human embryos could become a fundamental treatment approach for genetic diseases; however, a few technical and ethical issues need to be resolved before its application in clinical settings. Presently, the Japanese government has issued a statement prohibiting human germline editing and emphasizing the need for discussions that include a wide range of perspectives. However, current discussions tend to exclude the general public. Therefore, we conducted a survey of 10,881 general adults and 1044 patients in Japan who indicated that their disease conditions are related to their genetic makeup, and clarified their attitude toward this technology. The results clearly indicated that the Japanese people generally accepted the use of genome editing for disease-related genes, but many were concerned about the risks. In addition, many Japanese people did not understand the technology well. To improve awareness and understanding about genome editing, it is important that scientists and science communicators create opportunities for the public to participate in relevant discussions without harming vulnerable participants. It is also important to continuously track changes in the acceptance of genome editing by the public.

Hydroxyapatite (HAp), a type of calcium phosphate found in bones and teeth, exhibits proton conductivity. In this study, its conductivity is investigated by measuring the complex permittivity of polycrystalline hydroxyapatite samples obtained via a sintering process. The dielectric dispersions measured from samples with different grain sizes are successfully explained using the Maxwell-Wagner interfacial polarization model. The results show that polycrystalline hydroxyapatite consists of both a high impedance grain boundary and a proton-conductive grain that has a conductivity of about 1.0 × 10− 7 S cm− 1 at 573 K. The interfacial polarization is confirmed using thermally stimulated depolarization current measurements. Additionally, electrets are prepared with the polycrystalline HAp via a poling process, and it is demonstrated that the electret formation is caused by the interfacial polarization.

We demonstrated the crystallization of calcite on nonpolarized and polarized (10.4)-oriented calcite single crystal substrates in the presence of poly-lysine (PLys) as a poly amino acid. The PLys and the electric field due to polarized calcite substrates showed a significant effect on the morphologies of calcite precipitates. At a small amount of PLys, rhombohedral calcite crystals, with notches in the edges of the rhombohedra, formed through homoepitaxy and constructed aggregates with an island structure. At a large amount of PLys, the calcite precipitates had overgrown calcite crystals, which were formed by epitaxial growth on each of the rhombohedral surfaces of already formed calcite rhombohedra, and the calcite aggregates became elongated in the direction perpendicular to the substrate. As the amount of PLys increased, the overgrown calcite crystals tapered toward their ends, and some of the overgrown calcite crystals exhibited a cone-shaped appearance. These cone-shaped crystals consisted of aggrega...

Micro-/nanostructured implant surfaces mimicking natural bone architecture are expected to have positive effects on osteoblast proliferation. In this study, to clarify the optimal microstructure scale on micro-/nano-titanium surfaces, highly controlled microstructure surfaces were fabricated with a titania nanotube oxide layer by sandblast treatment and electrochemical anodization. Average surface roughness (Ra ) and mean width of the profile elements (RSm ) increased in proportion to the size of the blasting media. The crystalline structure and wettability were similar for all samples after anodizing and annealing. MG63 osteoblast-like osteosarcoma cells showed reduced spreading area on smaller microstructure surfaces after incubation for 24 h. Cell proliferation assays, including cell counting and cell cycle analyses, showed that micro-/nanosurfaces with smaller microstructures (Ra = 0.6 µm, RSm = 11.1 µm) had the most positive effect. This result indicated that smaller microstructures of hierarchical surfaces enhanced cell proliferation, despite similar chemical compositions and wettabilities. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2589-2596, 2017.

Background Prostate cancer is the sixth leading cause of cancer-related deaths in Japan. We aimed to elucidate the clinical and histopathological characteristics of patients with prostate cancer in the BioBank Japan (BBJ) project. Methods Four thousand, seven hundred and ninety-three patients diagnosed with prostate cancer in the BBJ project were included. Clinical and histopathological data, including causes of death, were analyzed. Relative survival (RS) rates of prostate cancer were calculated. Results Four thousand, one hundred and seventy-one prostate cancer patients with available histological data had adenocarcinoma. The mean age of the patients was 72.5 years. The proportion of patients who were non-smokers, non-drinkers, had a normal body mass index, did not exercise, had a normal prostate-specific antigen level, and had a family history of prostate cancer were 30.7%, 28.0%, 66.6%, 58.1%, 67.6%, and 6.5%, respectively. The proportion of patients with Stage II, III, and IV disease were 24.4%, 7.3%, and 4.4%, respectively. After limiting to patients with a time from the initial diagnosis of prostate cancer to entry into the study cohort of ≤90 days (n = 869), the 5- and 10-year RS rates were 96.3% and 100.5%, respectively, although we were unable to consider management strategies due to a plenty of data missing. Conclusions We provide an overview of patients with prostate cancer in the BBJ project. Our findings, coupled with those from various high throughput “omics” technologies, will contribute to the implementation of prevention interventions and medical management of prostate cancer patients., Highlights • Prostate cancer represents the second leading cause of cancer incidence worldwide. • We aimed to provide an overview of patients with prostate cancer. • Based on prostate cancer histology, 99.3% had adenocarcinoma. • The 5- and 10-year relative survival rates were 96.3% and 100.5%. • Future studies will help develop preventive programs for prostate cancer.

Background Liver cancer is the fifth cause of cancer-related deaths in Japan. The BioBank Japan (BBJ) project included 200,000 patients with 47 diseases and samples; their clinical information can be used for further studies. Methods Patients diagnosed with liver cancer (n = 1733; 1316 men, 417 women) were included. Histology, patient characteristics, clinical characteristics, and causes of death were collected. Cumulative and relative survival rates for liver cancer were calculated. Results Of the 1354 patients with available liver cancer histology, 91.9% had hepatocellular carcinoma (HCC). Compared with the National Health and Nutrition Examination Survey, greater proportions of the male patients in this cohort were daily alcohol consumers (26%), and a greater proportion of the men was overweight/obesity (22%). Although Japan is the only Asian country with a predominance of hepatitis C virus (HCV)-related HCC, the prevalence of HCV infection (44%) was lower than that in a previous study. The 3-, 5-, and 10-year cumulative survival rates were 57%, 47%, and 25% in men, respectively, and 49%, 41%, and 27% in women, respectively. Conclusions The present results provide an overview of the patients with liver cancer in the BBJ project. We are planning further analyses combined with various high-throughput ‘omics’ technologies., Highlights • Liver cancer is the second leading cause of death worldwide. • We aimed to provide an overview of patients with liver cancer. • Based on liver cancer histology, 91.9% had hepatocellular carcinoma. • The 10-year relative survival rates were 34% in men and 38% in women. • Future studies will help develop preventive programs for liver cancer.

Background Breast cancer is currently the most common type of cancer in Japanese females. Unlike most other types of cancer, breast cancer develops more frequently in middle-aged females than in elderly females. Methods Of all Japanese female breast cancer patients aged ≥20 years whom the BioBank Japan Project originally enrolled between 2003 and 2008, 2034 were registered within 90 days after their diagnosis. We described the lifestyle and clinical characteristics of these patients at study entry. Furthermore, we examined the effect of these characteristics on all-cause mortality. Results In the female patients registered within 90 days after diagnosis, the frequency of stage 0 or unclassified, stage I, II, III and IV were 11.4%, 47.9%, 37.0%, 2.9% and 0.8%, respectively. The proportion of histological types was 12.9% for non-invasive carcinoma (ductal carcinoma and lobular carcinoma), 81.0% for invasive carcinoma (papillotubular carcinoma, solid tubular carcinoma, scirrhous carcinoma and special types), 0.2% for Paget's diseases and 5.8% for others. Those positive for the estrogen and progesterone receptors accounted for 75.8% and 62.1% of all patients, respectively. Among 1860 female participants registered within 90 days, 218 participants died during 144,54 person-years of follow-up. More advanced stage, elevation of serum carcinoembryonic antigen and carbohydrate antigen 15-3 levels and absence of the estrogen receptor at study entry were crudely associated with an increased risk of all-cause mortality after adjustment for age. Conclusions This study showed the association of several clinical characteristics with all-cause mortality in female breast cancer patients., Highlights • About 1% of Japanese female breast cancer patients were diagnosed as stage IV. • Invasive carcinoma was much more common than non-invasive carcinoma. • Papillotubular carcinoma was the most common type of invasive carcinoma. • About 75% were positive for estrogen receptor and 60% for progesterone receptor. • Some characteristics would affect all-cause mortality in breast cancer patients.

Background Colorectal cancer is the third most common cancer worldwide, and in Japan, it is estimated that about 10% of men and 8% of women will be diagnosed with colorectal cancer during their lifetime. Methods We focused on 5864 participants (3699 men and 2165 women) who had colorectal cancer and were registered with BioBank Japan (BBJ) between April 2003 and March 2008. Characteristics of colon and rectal cancer patients were calculated separately. Among the enrolled patients registered in BBJ within 90 days after diagnosis, we also calculated the 5-year cumulative and relative survival rates, and estimated the effect of lifestyle factors on all-cause mortality. Results Our participants included younger men than those in the Patient Survey and the Cancer Registry Japan. In more than 95% of cases the histological type was adenocarcinoma both in colon and rectal cancer. Rectal cancer patients tended to eat more meat and less green leafy vegetables compared with colon cancer patients. The 5-year cumulative survival rate was 73.0% (95% CI; 70.1%–75.7%) and the 5-year relative survival rate was 80.6% (77.4%–83.6%), respectively, for colon cancer. For rectal cancer, the rates were 73.3% (69.1%–77.0%) and 80.9% (76.3%–85.0%), in the same order. Lifestyle factors such as consuming less green leafy vegetables, being underweight, smoking, not consuming alcoholic beverages and being physically inactive were found to be related to poor survival. Conclusions We described lifestyle characteristics of colorectal cancer patients in BBJ and examined the impacts on subsequent all-cause mortality., Highlights • More than 95% were adenocarcinoma both in colon and rectal cancer. • Rectal cancer patients ate more meat and less green vegetables than colon cancer. • Eating green vegetables and drinking alcohol moderately decreased the mortality risk.

Synthetic hydroxyapatite (HAp) is used clinically as a material for bone prostheses owing to its good bone-bonding ability; however, it does not contribute to bone remodeling. Carbonate-substituted hydroxyapatite (CAp) has greater bioresorption capacity than HAp while having similar bone-bonding potential, and is therefore considered as a next promising material for bone prostheses. However, the effects of the CAp instability on inflammatory and immune responses are unknown in detail. Here, we show that the surface layer of CAp is more hydrated than that of HAp and induces changes in the shape and function of macrophage-like cells. HAp and CAp were synthesized by wet method and molded into disks. The carbonate content of CAp disks was 6.2% as determined by Fourier transform (FT) infrared spectral analysis. Diffuse reflectance infrared FT analysis confirmed that physisorbed water and surface hydroxyl groups (OH- ) were increased whereas structural OH- was decreased on the CAp as compared to the HAp surface. The degree of hydroxylation in CAp was comparable to that in bone-apatite structures, and the CAp surface exhibited greater hydrophilicity and solubility than HAp. We investigated immune responses to these materials by culturing RAW264 cells (macrophage precursors) on their surfaces. Cell spreading on the CAp disk was suppressed and the secretion level of inflammatory cytokines was reduced as compared to cells grown on HAp. These results indicate that the greater surface hydration of CAp surface can attenuate adverse inflammatory responses to implanted bone prostheses composed of this material. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1063-1070, 2017.