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Background Trauma is a heterogeneous condition, and specific clinical phenotypes may identify target populations that could benefit from certain treatment strategies. In this retrospective study, we determined clinical phenotypes and identified new target populations of trauma patients and their treatment strategies. Methods We retrospectively analyzed datasets from the Japan Trauma Data Bank and determined trauma death clinical phenotypes using statistical machine learning techniques and evaluation of biological profiles. Results The analysis included 71,038 blunt trauma patients [median age, 63 (interquartile range [IQR], 40–78) years; 45,479 (64.0%) males; median Injury Severity Score, 13 (IQR, 9–20)], and the derivation and validation cohorts included 42,780 (60.2%) and 28,258 (39.8%) patients, respectively. Of eight derived phenotypes (D-1–D-8), D-8 ( n  = 2178) had the highest mortality (48.6%) with characteristic severely disturbed consciousness and was further divided into four phenotypes: D-8α, multiple trauma in the young ( n  = 464); D-8β, head trauma with lower body temperature ( n  = 178); D-8γ, severe head injury in the elderly ( n  = 957); and D-8δ, multiple trauma, with higher predicted mortality than actual mortality ( n  = 579). Phenotype distributions were comparable in the validation cohort. Biological profile analysis of 90 trauma patients revealed that D-8 exhibited excessive inflammation, including enhanced acute inflammatory response, dysregulated complement activation pathways, and impaired coagulation, including downregulated coagulation and platelet degranulation pathways, compared with other phenotypes. Conclusions We identified clinical phenotypes with high mortality, and the evaluation of the molecular pathogenesis underlying these clinical phenotypes suggests that lethal trauma may involve excessive inflammation and coagulation disorders.

The Pacific Rim Application and Grid Middleware Assembly (PRAGMA) is an international community of researchers that actively collaborate to address problems and challenges of common interest in eScience. The PRAGMA Experimental Network Testbed (PRAGMA-ENT) was established with the goal of constructing an international software-defined network (SDN) testbed to offer the necessary networking support to the PRAGMA cyberinfrastructure. PRAGMA-ENT is isolated, and PRAGMA researchers have complete freedom to access network resources to develop, experiment, and evaluate new ideas without the concerns of interfering with production networks. In the first phase, PRAGMA-ENT focused on establishing an international L2 backbone. With support from the Florida Lambda Rail (FLR), Internet2, PacificWave, JGN-X, and TWAREN, PRAGMA-ENT backbone connects Open\\-Flow-enabled switches at University of Florida (UF), University of California San Diego (UCSD), Nara Institute of Science and Technology (NAIST, Japan), Osaka University (Japan), National Institute of Advanced Industrial Science and Technology (AIST, Japan), and National Center for High-Performance Computing (Taiwan). The second phase of PRAGMA-ENT consisted of evaluation of technologies for the control plane that enables multiple experiments (i.e., OpenFlow controllers) to co-exist. Preliminary experiments with FlowVisor revealed some limitations leading to the development of a new approach, called AutoVFlow. This paper will share our experience in the establishment of PRAGMA-ENT backbone (with international L2 links), its current status, and control plane plans. Discussion on preliminary application ideas, including optimization of routing control; multipath routing control; and remote visualization will also be discussed.

Background Biomolecules in body fluids such as gingival crevicular fluid and saliva are used for the diagnosis of periodontitis. Saliva is easy to collect and salivary biomarkers are useful in screening periodontitis. The suitable salivary biomarkers and their measuring system are important for screening periodontitis in mass dental examination. Therefore, this study examined the potential of few salivary biomarkers for screening and diagnosis of periodontitis and aimed to evaluate more effective biomarkers and their measuring methods in dental examination. Methods Ninety-three individuals with and without periodontitis participated in this clinical examination and were classified into the non-periodontal diseases or stage I periodontitis (control, n  = 26) and stage II-IV periodontitis groups (periodontitis, n  = 67) after periodontal examinations. Unstimulated saliva samples were collected from participants. The levels of salivary biomarkers including calprotectin, hemoglobin (Hb), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), alanine aminotransferase and aspartate aminotransferase (AST) were automatically measured using the latex agglutination turbidimetric immunoassay (LATIA) and enzyme assay systems. Differences in clinical indicator and biomarker levels in the control and periodontitis groups and their correlations were statistically analyzed. A receiver operating characteristic (ROC) analysis of the ability of salivary biomarkers to predict periodontitis was also performed. Results Salivary calprotectin, Hb, LDH, ALP and AST levels were significantly higher in the periodontitis group than that in the control group. At the initial stage of periodontitis, a significant difference was only observed in calprotectin levels. Calprotectin and LDH levels strongly correlated with clinical indicators including probing pocket depth, clinical attachment level, bleeding on probing, gingival index and periodontal inflamed surface area with high correlation coefficient (calprotectin: 0.582–0.660, LDH: 0.534–0.614). Calprotectin showed a higher area under the ROC curve value (0.894), with 91% sensitivity and 73% specificity, than the other salivary biomarkers. Conclusions Salivary calprotectin showed a high effectiveness for the diagnosis of periodontitis, and the measurement of salivary calprotectin using the LATIA system that is a high throughput method is suitable for population-based screening of periodontal diseases.

The aim of this study was to investigate the impact of oral hygiene, periodontal diseases, and dental caries on all-cause mortality in hemodialysis. This prospective cohort study included 266 patients with end-stage renal disease who were undergoing hemodialysis. Medical interviews, blood biochemical tests, and comprehensive dental examinations including periodontal pocket examination on all teeth and dental plaque accumulation by debris index-simplified (DI-S), were performed. Survival rates were assessed at a 3-year follow-up. Overall, 207 patients were included in the longitudinal analysis, and 38 subjects died during the follow-up period. Cox proportional hazards analysis of the multivariate model demonstrated that the highest tertile of DI-S had a significantly higher risk of all-cause mortality than the lowest two tertiles after adjustment for age, sex, smoking habit, body mass index, diabetes, prior cardiovascular disease, hemodialysis vintage, high sensitivity C-reactive protein, albumin, and number of remaining teeth (hazard ratio, 3.04; 95% confidence interval, 1.50–6.17; p  = 0.002). Moreover, the number of decayed teeth significantly increased the hazard ratio to 1.21 (95% confidence interval, 1.06.1.37; p  = 0.003). This study suggests that accumulated dental plaque and untreated decay, but not periodontal disease, may be independently associated with all-cause mortality in patients undergoing hemodialysis.

PurposeThis study aimed to assess whether short repetition time (TR) diffusion-weighted imaging (DWI) could improve diffusion contrast in patients with prostate cancer (PCa) compared with long TR (conventional) reference standard DWI.Materials and methodsOur Institutional Review Board approved this retrospective study and waived the need for informed consent. Twenty-five patients with suspected PCa underwent multiparametric magnetic resonance imaging (mp-MRI) using a 3.0-T system. DWI was performed with TR of 1850 ms (short) and 6000 ms (long) with b-values of 0, 1000, and 2000s/mm2. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), visual score, apparent diffusion coefficient (ADC), and diagnostic performance were compared between short and long TR DWI for both b-values. The statistical tests included paired t-test for SNR and CNR; Wilcoxon signed-rank test for VA; Pearson's correlation and Bland–Altman plot analysis for ADC; and McNemar test and receiver operating characteristic analysis and Delong test for diagnostic performance.ResultsRegarding b1000, CNR and visual score were significantly higher in short TR compared with long TR (P = .003 and P = .002, respectively), without significant difference in SNR (P = .21). Considering b2000, there was no significant difference in visual score between short and long TR (P = .07). However, SNR and CNR in long TR were higher (P = .01 and P = .04, respectively). ADC showed significant correlations, without apparent bias for ADC between short and long TR for both b-values. For diagnostic performance of DWI between short and long TR for both b-values, one out of five readers noted a significant difference, with the short TR for both b-values demonstrating superior performance.ConclusionsOur data showed that the short TR DWI1000 may provide better image quality than did the long TR DWI1000 and may improve visualization and diagnostic performance of PCa for readers.

Recent developments in the field of π-conjugated polymers have led to considerable improvements in the performance of solution-processed organic light-emitting devices (OLEDs). However, further improving efficiency is still required to compete with other traditional light sources. Here we demonstrate efficient solution-processed multilayer OLEDs using small molecules. On the basis of estimates from a solvent resistance test of small host molecules, we demonstrate that covalent dimerization or trimerization instead of polymerization can afford conventional small host molecules sufficient resistance to alcohols used for processing upper layers. This allows us to construct multilayer OLEDs through subsequent solution-processing steps, achieving record-high power efficiencies of 36, 52 and 34 lm W −1 at 100 cd m −2 for solution-processed blue, green and white OLEDs, respectively, with stable electroluminescence spectra under varying current density. We also show that the composition at the resulting interface of solution-processed layers is a critical factor in determining device performance. High-efficiency organic light-emitting devices usually require the growth of many layers of different materials by vapour deposition in vacuum. Naoya Aizawa et al . demonstrate the fabrication of high-efficiency multilayer organic LEDs from solution.

Aims/Introduction Glutamine is the most abundant amino acid in the circulation. In this study, we investigated cell signaling in the amplification of insulin secretion by glutamine. Materials and Methods Clonal pancreatic β‐cells MIN6‐K8, wild‐type B6 mouse islets, glutamate dehydrogenase (GDH) knockout clonal β‐cells (Glud1KOβCL), and glutamate‐oxaloacetate transaminase 1 (GOT1) knockout clonal β‐cells (Got1KOβCL) were studied. Insulin secretion from these cells and islets was examined under various conditions, and intracellular glutamine metabolism was assessed by metabolic flux analysis. Intracellular Ca2+ concentration ([Ca2+]i) was also measured. Results Glutamine dose‐dependently amplified insulin secretion in the presence of high glucose in both MIN6‐K8 cells and Glud1KOβCL. Inhibition of glutaminases, the enzymes that convert glutamine to glutamate, dramatically reduced the glutamine‐amplifying effect on insulin secretion. A substantial amount of glutamate was produced from glutamine through direct conversion by glutaminases. Glutamine also increased [Ca2+]i at high glucose, which was abolished by inhibition of glutaminases. Glutamic acid dimethylester (dm‐Glu), a membrane permeable glutamate precursor that is converted to glutamate in cells, increased [Ca2+]i as well as induced insulin secretion at high glucose. These effects of glutamine and dm‐Glu were dependent on calcium influx. Glutamine also induced insulin secretion in clonal β‐cells MIN6‐m14, which otherwise exhibit no insulin secretory response to glucose. Conclusions Glutamate converted from glutamine is an essential mediator that enhances calcium signaling in the glutamine‐amplifying effect on insulin secretion. Our data also suggest that glutamine exerts a permissive effect on glucose‐induced insulin secretion. Glutamine amplifies glucose‐induced insulin secretion through its conversion to glutamate. Glutamate converted from glutamine functions as an essential mediator that enhances calcium signaling in glutamine‐amplified insulin secretion.

Aims/Introduction This study assessed the association between periodontal disease and the development of diabetes mellitus, as well as the effects of sex differences and obesity on this association. Materials and Methods The study included 4051 employees (2497 men and 1554 women) aged 35–55 years at a metal product manufacturing company in Japan. Periodontal disease was assessed using the Community Periodontal Index. Diabetes mellitus was determined based on annual health checkups. Results The prevalence of periodontal disease was 36.9% (41.9% in men and 29.5% in women). During the 12-year follow-up, 229 participants developed diabetes. The cumulative incidence rates (per 1000 person-years) were 10.1 for all participants, 7.8 for those without periodontal disease, and 14.5 for those with periodontal disease. The multivariate-adjusted hazard ratio (HR) for diabetes incidence in the periodontal disease group was 1.36 (95% confidence interval: 1.04–1.78); this was significantly higher than in the non-periodontal disease group. In men, the multivariate-adjusted HR for diabetes incidence was significantly higher in the periodontal disease group, at 1.37 (1.02–1.83), than in the non-periodontal disease group. No significant association was detected in women. When stratified according to sex and obesity status, the non-obese male group showed a significantly higher HR for diabetes incidence in the periodontal disease group (1.75 [1.15–2.66]) compared with the non-periodontal disease group. Conclusions This 12-year prospective cohort study demonstrated that periodontal disease significantly increased the risk of diabetes; the association was more pronounced in men, particularly non-obese men.

The present study aimed to investigate the periodontal regenerative effect of enamel matrix derivative (EMD) in diabetes. Thirty-six rats were assigned to streptozotocin-induced diabetes or control (non-diabetic) groups. Three-wall intrabony defects were surgically generated in the bilateral maxilla molar, followed by application of EMD or saline. Primary wound closure and defect fill were evaluated via histomorphological analysis and micro-computed tomography. mRNA expression levels of inflammatory and angiogenic factors in the defects were quantified via real-time polymerase chain reaction. Gingival fibroblasts were isolated from control animals and cultured in high-glucose (HG) or control medium. The effects of EMD on insulin resistance and PI3K/Akt/VEGF signaling were evaluated. The achievement rate of primary closure and the parameters of defect fill were significantly higher at EMD-treated site than at EMD-untreated sites in both diabetic and non-diabetic rats, although defect fill in the diabetic groups was significantly lower in the control groups on two-way repeated-measures analysis of variance (for both, p<0.05). Newly formed bone and cementum were significantly increased at EMD-treated sites in diabetic rats than at EMD-untreated sites in control rats (for both, p<0.05). Vegf was significantly upregulated at EMD-treated sites in both diabetic and non-diabetic rats (for both, p<0.05). In vitro, insulin or EMD-induced Akt phosphorylation was significantly lower in cells cultured in HG medium (p<0.05). EMD-mediated Vegf upregulation was suppressed by the Akt inhibitor wortmannin, although the effect was significantly lower in HG medium (p<0.01). In conclusion, EMD might promote periodontal tissue regeneration via Akt/VEGF signaling, even in a diabetic condition.