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.
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.
The BioBank Japan (BBJ) Project was launched in 2003 with the aim of providing evidence for the implementation of personalized medicine by constructing a large, patient-based biobank (BBJ). This ...report describes the study design and profile of BBJ participants who were registered during the first 5-year period of the project.
The BBJ is a registry of patients diagnosed with any of 47 target common diseases. Patients were enrolled at 12 cooperative medical institutes all over Japan from June 2003 to March 2008. Clinical information was collected annually via interviews and medical record reviews until 2013. We collected DNA from all participants at baseline and collected annual serum samples until 2013. In addition, we followed patients who reported a history of 32 of the 47 target diseases to collect survival data, including cause of death.
During the 5-year period, 200,000 participants were registered in the study. The total number of cases was 291,274 at baseline. Baseline data for 199,982 participants (53.1% male) were available for analysis. The average age at entry was 62.7 years for men and 61.5 years for women. Follow-up surveys were performed for participants with any of 32 diseases, and survival time data for 141,612 participants were available for analysis.
The BBJ Project has constructed the infrastructure for genomic research for various common diseases. This clinical information, coupled with genomic data, will provide important clues for the implementation of personalized medicine.
•The BioBank Japan Project (BBJ) enrolled 200,000 patients with 47 target diseases.•The BBJ is one of the largest patient-based biobanks in the world.•The BBJ may allow for personalized medicine in the future.
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.
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;Nr5a1
and Sox9-Cre;Nr5a1
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;Nr5a1
but not Sox9-Cre;Nr5a1
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.
Polygenic risk scores suffer reduced accuracy in non-European populations, exacerbating health disparities. We propose PolyPred, a method that improves cross-population polygenic risk scores by ...combining two predictors: a new predictor that leverages functionally informed fine-mapping to estimate causal effects (instead of tagging effects), addressing linkage disequilibrium differences, and BOLT-LMM, a published predictor. When a large training sample is available in the non-European target population, we propose PolyPred
, which further incorporates the non-European training data. We applied PolyPred to 49 diseases/traits in four UK Biobank populations using UK Biobank British training data, and observed relative improvements versus BOLT-LMM ranging from +7% in south Asians to +32% in Africans, consistent with simulations. We applied PolyPred
to 23 diseases/traits in UK Biobank east Asians using both UK Biobank British and Biobank Japan training data, and observed improvements of +24% versus BOLT-LMM and +12% versus PolyPred. Summary statistics-based analogs of PolyPred and PolyPred
attained similar improvements.
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.
Abstract This study presents a parametric analysis of the steady-state temperature elevation in rat skin models due to millimeter wave exposure at frequencies from 6–100 GHz. The statistical data of ...the thickness of skin layers, namely epidermis, dermis, dermal white adipose tissue, and panniculus carnosus, were measured for the first time using the excised tissues of real male Sprague–Dawley rats. Based on the precise structure obtained from the histological analysis of rat skin, we solve the bioheat transfer equation to investigate the effects of changes in parameters, such as body parts and thermal constants, on the absorbed power density and temperature elevation of biological tissues. Owing to the notably thin dermal white adipose tissue layer, the surface temperature elevation in the rat head and dorsal skin at 6–100 GHz is 52.6–32.3% and 83.3–58.8% of the average values of different human skin models, respectively. Our results also reveal that the surface temperature elevation of rat skin may correlate with the tissue thickness and deep blood perfusion rates.
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 1.0×10−7Scm−1 at 573K. 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.
•Hydroxyapatite conductivity is studied via complex permittivity measurements.•The hydroxyapatite consists of conductive grains and insulative grain boundaries.•Interfacial polarization is confirmed via depolarization current measurements.•The interfacial polarization makes the hydroxyapatite an electret.
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.
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.
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.
We described lifestyle characteristics of colorectal cancer patients in BBJ and examined the impacts on subsequent all-cause mortality.
•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.
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