Artificial intelligence (AI) is expected to support clinical judgement in medicine. We constructed a new predictive model for diabetic kidney diseases (DKD) using AI, processing natural language and longitudinal data with big data machine learning, based on the electronic medical records (EMR) of 64,059 diabetes patients. AI extracted raw features from the previous 6 months as the reference period and selected 24 factors to find time series patterns relating to 6-month DKD aggravation, using a convolutional autoencoder. AI constructed the predictive model with 3,073 features, including time series data using logistic regression analysis. AI could predict DKD aggravation with 71% accuracy. Furthermore, the group with DKD aggravation had a significantly higher incidence of hemodialysis than the non-aggravation group, over 10 years (N = 2,900). The new predictive model by AI could detect progression of DKD and may contribute to more effective and accurate intervention to reduce hemodialysis.

Graphene oxide (GO) exhibits relatively high proton conduction even at low relative humidity (RH) and temperatures. Thus, multilayered GO film (GO paper) is a promising electrolyte in various cells and batteries. We report the in-plane and through-plane proton conductivities of GO paper at low RH and room temperature. The conductivities were 10 −5 -10 −4 S/cm at RH of 10-20%. We examined the performance of a graphene oxide fuel cell (GOFC) with GO paper as the electrolyte at low RH (<20%) and room temperature. We demonstrated that a simple membrane electrode assembly (MEA) based on Pt/GO/Pt system functioned as a H 2 /O 2 fuel cell. The GOFC with Pt/C electrodes afforded better fuel cell performance than a MEA composed of Pt/C electrodes and Nafion electrolyte. GO paper composed of nano-sized GO (nanoGO) flakes enhanced the performance of the GOFC, particularly the current density. Furthermore, a composite of Fe phthalocyanine (PcFe) /reduced GO (rGO)/TiO 2 could act as the Pt-free oxygen electrode in GOFC, although the fuel cell performance should be improved for practical applications. Our study suggests that a low cost GOFC without a Nafion electrolyte and noble metal electrodes could be fabricated in the near future. GO is a promising material because of its many excellent chemical and physical properties, which arise from various oxygenated functional groups.1-6 Multi-layered GO nanosheets (GO paper) exhibit high proton conduction. [7][8][9] The main oxygenated functional group in GO is epoxide. It acts as the site for proton transfer after water molecules bind to it, even at low RH and room temperature. 10 The relatively high proton conductivity under these conditions suggests that GO paper could act as a proton electrolyte in various cells and batteries. [11][12][13][14][15][16] The proton conductivity of the GO paper is lower than that of the conventional Nafion electrolyte, which is usually used at high RH (∼100%), 17,18 while the overall conduction of the GO paper will be similar to that of Nafion if the GO paper is less than a tenth of the thickness of the Nafion.It has been reported that various gases do not pass through the GO paper, even when the GO is very thin (0.1 μm).19 This means thin GO paper is well suited as an electrolyte for the H 2 /O 2 fuel cell, because of the high proton conduction and the H 2 and O 2 gas shielding. Nafion electrolytes must be thick in order to achieve gas shielding (>10 2 μm). Moreover, GO paper is much cheaper than Nafion. A mixture of GO paper and Nafion has been used as the electrolyte for a fuel cell, and it acted as an electrolyte even at relatively low RH (25%).8 Sulfonic acid functionalized GO (SGO) has been used as an electrolyte without Nafion, and tested in a H 2 /O 2 fuel cell at 25% RH and 40• C, with Pt/C electrodes. 12Here we report the performance of a simple H 2 /O 2 fuel cells with a 100% GO paper (< 1 atom% S) electrolyte (GOFC) as well as the proton conductivities at low RH and 23-25• C. ExperimentalSynthesis of GO and nanoGO.-The GO was prepared f...

Epirubicin is widely used to treat various human tumors. However, it is difficult to achieve a sufficient antitumor effect because of dosage limitation to prevent cardiotoxicity. We hypothesized that epirubicin-incorporating micelle would reduce cardiotoxicity and improve the antitumor effect. NC-6300 comprises epirubicin covalently bound to PEG polyaspartate block copolymer through an acid-labile hydrazone bond. The conjugate forms a micellar structure of 40-80 nm in diameter in an aqueous milieu. NC-6300 (10, 15 mg ⁄ kg) and epirubicin (10 mg ⁄ kg) were given i.v. three times to mice bearing s.c. or liver xenograft of human hepatocellular carcinoma Hep3B cells. Cardiotoxicity was evaluated by echocardiography in C57BL ⁄ 6 mice that were given NC-6300 (10 mg ⁄ kg) or epirubicin (10 mg ⁄ kg) in nine doses over 12 weeks. NC-6300 showed a significantly potent antitumor effect against Hep3B s.c. tumors compared with epirubicin. Moreover, NC-6300 also produced a significantly longer survival rate than epirubicin against the liver orthotopic tumor of Hep3B. With respect to cardiotoxicity, epirubicin-treated mice showed significant deteriorations in fractional shortening and ejection fraction. In contrast, cardiac functions of NC-6300 treated mice were no less well maintained than in control mice. This study warrants a clinical evaluation of NC-6300 in patients with hepatocellular carcinoma or other cancers. (Cancer Sci 2013; 104: 920-925) H epatocellular carcinoma (HCC) is the fifth most common cancer and the third largest cause of cancer mortality worldwide.(1,2) The range of available oncological treatment for HCC is sometimes limited due to poor liver function caused by concomitant chronic liver disease, especially liver cirrhosis, which is mainly the result of hepatitis virus infection. Surgical resection is widely considered the mainstay for curative treatment and yields a certain survival rate. However, <20% of patients with HCC can undergo surgical resection. (3,4) With the exception of patients at an early stage and with adequate liver function, recurrence rates after surgical resection are unfortunately high. High recurrence rates are also seen in patients treated by other local treatment options, such as ablation, percutaneous ethanol injection, and trans-arterial chemoembolization.(5) For advanced HCC, the only available option is sorafenib, a tyrosine kinase inhibitor, which was recently approved; however, the survival rate associated with its use is far from satisfactory.

Despite the pathological importance of fibrin clot formation, little is known about the structure of these clots because X-ray and nuclear magnetic resonance (NMR) analyses are not applicable to insoluble proteins. In contrast to previously reported anti-fibrin monoclonal antibodies (mAbs), our anti-fibrin clot mAb (clone 102–10) recognises an uncovered region that is exposed only when a fibrin clot forms. The epitope of the 102–10 mAb was mapped to a hydrophobic region on the Bβ chain that interacted closely with a counterpart region on the γ chain in a soluble state. New anti-Bβ and anti-γ mAbs specific to peptides lining the discovered region appeared to bind exclusively to fibrin clots. Furthermore, the radiolabelled 102–10 mAb selectively accumulated in mouse spontaneous tumours, and immunohistochemistry using this mAb revealed greater fibrin deposition in World Health Organization (WHO) grade 4 glioma than in lower-grade gliomas. Because erosive tumours are apt to cause micro-haemorrhages, even early asymptomatic tumours detected with a radiolabelled 102-10 mAb may be aggressively malignant.

NK105 is a micellar nanoparticle formulation designed to enhance the delivery of paclitaxel (PTX) to solid tumours. It has been reported to exert antitumour activity in vivo and to have reduced neurotoxicity as compared to that of free PTX. The purpose of this study was to investigate the radiosensitising effect of NK105 in comparison with that of PTX. Lewis lung carcinoma (LLC)-bearing mice were administered a single intravenous (i.v.) injection of PTX or NK105; 24 h after the drug administration, a proportion of the mice received radiation to the tumour site or lung fields. Then, the antitumour activity and lung toxicity were evaluated. In one subset of mice, the tumours were excised and specimens were prepared for analysis of the cell cycle distribution by flow cytometry. Combined NK105 treatment with radiation yielded significant superior antitumour activity as compared to combined PTX treatment with radiation (P ¼ 0.0277). On the other hand, a histopathological study of lung sections revealed no significant difference in histopathological changes between mice treated with PTX and radiation and those treated with NK105 and radiation. Flowcytometric analysis showed that NK105-treated LLC tumour cells showed more severe arrest at the G2/M phase as compared to PTX-treated tumour cells. The superior radiosensitising activity of NK105 was thus considered to be attributable to the more severe cell cycle arrest at the G2/M phase induced by NK105 as compared to that induced by free PTX. The present study results suggest that further clinical trials are warranted to determine the efficacy and feasibility of combined NK105 therapy with radiation.