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Housing tenure is an important aspect to determine health. However, even though renters tend to have more socioeconomic disadvantages than homeowners, mortality risk between private and public renters compared with homeowners remains unclear. Japanese public rented housing, such as the Urban Renaissance Agency, has been developed for supplying an adequate living environment since 1950s. This study aimed to examine the mortality risk among older Japanese residents living in private and public rented houses compared with those living in owner-occupied houses using 9-year follow-up data. This study drew upon a 9-year follow-up of participants in the Japan Gerontological Evaluation Study, a population-based cohort study of Japanese independent adults aged ≥ 65 years. Mortality from 2010 to 2019 was analyzed for 44,007 respondents. Housing tenure was defined by a questionnaire. Cox regression models were used for calculating the hazard ratio for mortality. Bonferroni correction was used to account for multiple testing between rental houses. Overall, 10,638 deaths occurred during the follow-up period. Compared with housing owners, all rental housing groups had a significantly higher risk of mortality. Among renters, participants who lived in public rental housing had the lowest risk of mortality even after adjusting for sociodemographic characteristics, health status, social status, and environmental status. Multiple testing among renters with Bonferroni correction showed that public renters had 0.80 times (95% CI 0.72-0.89) lower mortality risk than private renters. Although Japanese older adults living in public rental housing had a higher mortality risk than homeowners, this risk was lower than that among private renters. A positive neighborhood environment based on well-planned urban development may have contributed to this result. The results suggest that planned urban development lowers the risk of mortality in older renters in Japan., (© 2024. The Author(s).)

We previously reported that dendritic cells (DCs) transduced with the full-length tumor-associated antigen (TAA) gene induced TAA-specific cytotoxic T lymphocytes (CTLs) to elicit antitumor responses. To overcome the issue of quantity and quality of DCs required for DC vaccine therapy, we focused on induced pluripotent stem cells (iPSCs) as a new tool for obtaining DCs and reported efficacy of iPSCs-derived DCs (iPSDCs). However, in clinical application of iPSDC vaccine therapy, further enhancement of the antitumor effect is necessary. In this study, we targeted mesothelin (MSLN) as a potentially useful TAA, and focused on the ubiquitin-proteasome system to enhance antigen-presenting ability of iPSDCs. The CTLs induced by iPSDCs transduced with MSLN gene (iPSDCs-MSLN) from healthy donors showed cytotoxic activity against autologous lymphoblastoid cells (LCLs) expressing MSLN (LCLs-MSLN). The CTLs induced by iPSDCs transduced ubiquitin-MSLN fusion gene exhibited higher cytotoxic activity against LCLs-MSLN than the CTLs induced by iPSDCs-MSLN. The current study was designed that peripheral T-cell tolerance to MSLN could be overcome by the immunization of genetically modified iPSDCs simultaneously expressing ubiquitin and MSLN, leading to a strong cytotoxicity against tumors endogenously expressing MSLN. Therefore, this strategy may be promising for clinical application as an effective cancer vaccine therapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

We aimed to assess the reliability and validity of OpenPose, a posture estimation algorithm, for measuring hip-knee-ankle (HKA) angle in patients with knee osteoarthritis, by comparing it with radiography. In this prospective study, we analysed 60 knees (30 patients) with knee osteoarthritis. We measured HKA angle using OpenPose and radiography before or after total knee arthroplasty and assessed the test-retest reliability of each method with intraclass correlation coefficient (1, 1). We evaluated the ability to estimate the radiographic measurement values from the OpenPose values using linear regression analysis and used intraclass correlation coefficients (2, 1) and Bland-Altman analyses to evaluate the agreement and error between OpenPose and radiographic measurements. OpenPose had excellent test-retest reliability (intraclass correlation coefficient (1, 1) = 1.000) and excellent agreement with radiography (intraclass correlation coefficient (2, 1) = 0.915), with regression analysis indicating a large correlation (R 2  = 0.865). OpenPose also had a 1.1° fixed error and no systematic error when compared with radiography. This is the first study to validate the use of OpenPose for the estimation of HKA angle in patients with knee osteoarthritis. OpenPose is a reliable and valid tool for measuring HKA angle in patients with knee osteoarthritis. OpenPose, which enables non-invasive and simple measurements, may be a useful tool to assess changes in HKA angle and monitor the progression and post-operative course of knee osteoarthritis. Furthermore, this validated tool can be used not only in clinics and hospitals, but also at home and in training gyms; thus, its use could potentially be expanded to include self-assessment/monitoring., (© 2023. The Author(s).)

Significant efficacy of induced pluripotent stem cells (iPSCs) in generating DCs for cancer vaccine therapy was suggested in our previous studies. In clinical application of DC vaccine therapy, however, few DC vaccine systems have shown strong clinical response. To enhance immunogenicity in the DC vaccine, we transfected patient-derived iPSDCs with in vitro transcriptional RNA (ivtRNA), which was obtained from tumors of three patients with colorectal cancer. We investigated iPSDCs-ivtRNA which were induced by transfecting ivtRNA obtained from tumors of three colorectal cancer patients, and examined its antitumor effect. Moreover, we analyzed neoantigens expressed in colorectal cancer cells and examined whether iPSDCs-ivtRNA induced cytotoxic T lymphocytes (CTLs) against the predicted neoantigens. CTLs activated by iPSDCs-ivtRNA exhibited cytotoxic activity against the tumor spheroids in all three patients with colorectal cancer. Whole-exome sequencing revealed 1251 nonsynonymous mutations and 2155 neoantigens (IC 50  < 500 nM) were predicted. For IFN-γ ELISPOT assay, these candidate neoantigens were further prioritised and 12 candidates were synthesized. IFN-γ ELISPOT assay revealed that the CTLs induced by iPSDCs-ivtRNA responded to one of the candidate neoantigens. In vitro CTLs obtained by transfecting tumor-derived RNA into iPSDCs derived from three patients with colorectal cancer showed potent tumor-specific killing effect., (© 2022. The Author(s).)

When compared with the second/third generation da Vinci S/Si, the fourth generation Xi surgical system may allow for greater efficiency and result in shorter operation times during robotic gastrectomy (RG) for gastric cancer (GC). We directly compare surgical outcomes between the conventional S/Si and the newer Xi robotic platform for the treatment of GC. This is a single-center retrospective study of 148 consecutive patients with GC who underwent RG. Of these patients, 20 patients were treated with the S, 30 patients with the Si, and 98 patients with the Xi. The overall operation time was significantly longer in the S group (386.5 min) than in the other groups (Si group: 292 min; Xi group: 297 min) (S vs. Si: P = 0.010; S vs. Xi: P = 0.001). We observed no difference, however, between the newer Xi and Si systems in operation time. Intraoperative blood loss was similar across the three groups. The overall postoperative complication rate in the Xi group (8.2%) was lower than that of the S group (10%) and the Si group (13.3%), but the difference was not significant. The newer Xi system did not provide significant intraoperative or early postoperative advantages over the Si system.

CEACAM1 is associated with malignant potential of various cancers. The current study aims to clarify the association between carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression and malignant potential of gastric cancer and to address whether CEACAM1 cytoplasmic domain isoform balance modulates the properties of gastric cancer cells. Immunohistochemical analyses for CEACAM1 were performed in 235 patients with gastric cancer who underwent surgery. Risk factors for overall survival and peritoneal metastasis were calculated based on CEACAM1 expression in the gastric cancer tissue. Patients with CEACAM1 long (CEACAM1-L) or short (CEACAM1-S) cytoplasmic isoform dominance were compared with patients with null CEACAM1 expression in terms of overall survival. CEACAM1 transfected or knockdown gastric cancer cell line, NUGC3 and MKN7 cells, were examined by invasion assay and three dimensional (3D) culture, in order to clarify whether CEACAM1 modulate invasion, lumen formation and tumor growth of gastric cancer cells. Multivariate analysis demonstrated that gastric cancer without CEACAM1 is an independent prognostic factor and a risk factor for peritoneal dissemination. Patients with CEACAM1-S dominance had better prognosis than those with CEACAM1-L. CEACAM1-4L overexpression induced less invasion, more lumen formation, and less tumor growth of NUGC3 cells. CEACAM1-4S overexpression had less invasion and more lumen formations, but not less tumor growth. Knockdown of CEACAM1 expression had less invasion, but not less lumen formations of MKN7 cells. Loss of CEACAM1 is associated with poor prognosis and peritoneal dissemination of patients with gastric cancer. Expression of CEACAM1 in gastric cancer cells modulates invasiveness, lumen formation, and tumor growth.

Despite the progress in massive gene analysis of brown algal species, no alginate-degrading enzyme from brown alga has been identified, impeding the understanding of alginate metabolism in brown alga. In the current study, we identified and characterized alginate lyase from Saccharina japonica using a protein-based approach. First, cDNA library was prepared from the S. japonica sporophyte. Expression screening was then performed; the encoding gene was identified and cloned; and the recombinant enzyme was purified and characterized. Alginate lyase production in algal tissues was evaluated by western blotting. The identified alginate lyase, SjAly (359 amino acids, with a predicted N-terminal secretion signal of 27 residues), is encoded by an open reading frame comprising seven exons. Recombinant SjAly exhibited endolytic alginate lyase activity, specifically toward stretches of consecutive β-D-mannuronic acid units. The optimum temperature, pH, and NaCl concentration were 30 °C, pH 8.0, and 100 mM, respectively. SjAly exhibited pronounced activity below 20 °C, the S. japonica growth temperature. SjAly was highly expressed in the blade but not the stipe and rhizoid. The data indicate that S. japonica possesses at least one active alginate lyase. This is the first report of a functional alginate lyase from brown alga, the major natural alginate producer.

Clinical application of dendritic cell (DC) vaccine therapy is hindered by the need for a large quantity of DCs generated from peripheral blood monocytes of the patient. We investigated whether genetically modified human induced pluripotent stem cell (iPSC)-derived dendritic cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce CEA-specific cytotoxic T cells in a human model and whether genetically modified mouse iPSDCs (miPSDCs) expressing CEA showed an actual antitumor effect using a CEA transgenic mouse model. We differentiated hiPSDCs from iPSCs of three healthy donors and transduced CEA cDNA into the hiPSDCs. The surface marker expression, cytokine secretion and migratory capacity of the hiPSDCs were equivalent to those of human monocyte-derived DCs (hMoDCs). Cytotoxic T cells activated by hiPSDCs-CEA exhibited CEA-specific cytotoxic activity against the target cells expressing CEA. Furthermore, in the CEA transgenic mouse model, cytotoxic T cells activated in mice immunized with miPSDCs-CEA displayed CEA-specific cytotoxic activity against MC38-CEA. In the subcutaneous tumour model, vaccination with miPSDCs-CEA achieved a significant growth inhibitory effect on MC38-CEA. No adverse events caused by the administration of miPSDCs were observed. Genetic modification of iPSDCs, inducing the expression of CEA, is a promising tool for clinical applications of vaccine therapy for treating gastrointestinal cancer patients.

We report a rapid and cost-effective monoclonal antibody screening method from single animal B cells using reverse transcription (RT)-PCR and Escherichia coli cell-free protein synthesis (CFPS), which allows evaluation of antibodies within 2 working days. This process is named "Ecobody technology". The method includes strategies to isolate B cells that specifically bind an antigen from the peripheral blood of immunised animals, and single-cell RT-PCR to generate DNA fragments of the V H and V L genes, followed by CFPS for production of fragments of antigen binding (Fab). In the CFPS step, we employed our techniques: 1) 'Zipbody' as a method for producing Fab, in which the association of heavy and light chains is facilitated by adhesive leucine zipper peptides fused at the C-termini of the Fab; and 2) an N-terminal SKIK peptide tag that can increase protein expression levels. Using Ecobody technology, we obtained highly-specific monoclonal antibodies for the antigens Vibrio parahaemolyticus and E. coli O26. The anti-V. parahaemolyticus Zipbody mAb was further produced in E. coli strain SHuffle T7 Express in inclusion bodies and refolded by a conventional method, resulting in significant antigen-binding activity (K D  = 469 pM) and productivity of 8.5 mg purified antibody/L-culture.

Laminarinase from Flavobacterium sp. strain UMI-01, a new member of the glycosyl hydrolase 16 family of a marine bacterium associated with seaweeds, mainly degrades β-1,3-glucosyl linkages of β-glucan (such as laminarin) through the hydrolysis of glycosidic bonds. We determined the crystal structure of ULam111 at 1.60-Å resolution to understand the structural basis for its thermostability and substrate specificity. A calcium-binding motif located on the opposite side of the β-sheet from catalytic cleft increased its degrading activity and thermostability. The disulfide bridge Cys31-Cys34, located on the β2-β3 loop near the substrate-binding site, is responsible for the thermostability of ULam111. The substrates of β-1,3-linked laminarin and β-1,3-1,4-linked glucan bound to the catalytic cleft in a completely different mode at subsite -3. Asn33 and Trp113, together with Phe212, formed hydrogen bonds with preferred substrates to degrade β-1,3-linked laminarin based on the structural comparisons. Our structural information provides new insights concerning thermostability and substrate recognition that will enable the design of industrial biocatalysts.

Glycosphingolipids (GSLs) are glycoconjugates that function as mediators of cell adhesion and modulators of signal transduction. Some well-defined markers of undifferentiated human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are glycoconjugates, such as SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. However, Comprehensive GSL profiles of hiPSCs have not yet been elucidated. The global images of GSLs from the parental cells, hiPSCs, and differentiated cells revealed that there are parental cell-independent specific glycolipids, including Globo H (fucosyl-Gb5Cer) and H type1 antigen (fucosyl-Lc4Cer) that are novel markers for undifferentiated hiPSCs. Interestingly, undifferentiated hiPSCs expressed H type 1 antigen, specific for blood type O, regardless of the cells' genotypes. Thus, in this study, we defined the dynamics of GSL remodeling during reprogramming from parental cell sets to iPSC sets and thence to iPSC-neural cells.

It has been reported that masked hypertension, a state in which patients show normal clinic blood pressure (BP) but elevated out-of-clinic BP by self-measured home BP, is a predictor of cardiovascular morbidity much like sustained hypertension. In addition, nocturnal BP is closely associated with cardiovascular disease. This might mean that ambulatory and self-measured home BP monitoring each provide independent information. We performed ambulatory BP monitoring, self-measured home BP monitoring, echocardiography and carotid ultrasonography in 165 community-dwelling subjects. We subclassified the patients according to the ambulatory and self-measured home BP levels as follows: in the masked nocturnal hypertension group, the self-measured home BP level was <135/85 mmHg and the ambulatory nocturnal BP level was >or=120/75 mmHg; in the normotensive group, the self-measured home BP level was <135/85 mmHg and the ambulatory nocturnal BP level was <120/75 mmHg. The intima-media thickness (IMT) and relative wall thickness (RWT) were greater in the masked nocturnal hypertension group than in the normotensive group (IMT: 0.76+/-0.20 vs. 0.64+/-0.14 mm, p<0.05; RWT: 0.50+/-0.14 vs. 0.41+/-0.10, p<0.05). Even in hypertensives with well-controlled self-measured home BP, elevated ambulatory nocturnal BP might promote target organ damage. We must rule out masked hypertension using self-measured home BP monitoring, and we might also need to rule out nocturnal masked hypertension using ambulatory BP monitoring.

To establish a practical monitoring system of human herpesviruses reactivation in patients undergoing stem cell transplantation, we developed a new, very rapid, highly sensitive, and quantitative PCR assay for accurate measurement of human cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) DNA using LightCycler. The LightCycler system revealed that there was a linear correlation in the wide range of viral template DNA at the indicated number of PCR cycles. Peripheral blood cells were collected from 16 patients undergoing stem cell transplantation. The cut-off level of CMV and HHV-6 was assessed as 10(2) copies/microg and that of EBV as 10(3). High numbers of CMV genomes were detected in 3/13 patients after transplant, and reactivation of HHV-6 was frequently seen, whereas none of the patient showed an elevation of EBV genome copies until the end of the observation period. In the present study, the reactivation of beta herpesviruses is associated with the occurrence of thrombotic microangiopathy (TMA) in two patients undergoing allogeneic BMT. Therefore, it may contribute in clarifying the pathological potential of human herpesviruses using a large number of clinical samples. Our results suggest that this system may be useful for monitoring viral reactivation.