Application of Word Embedding to Drug Repositioning

As a key technology of rapid and low-cost drug development, drug repositioning is getting popular. In this study, a text mining approach to the discovery of unknown drug-disease relation was tested. Using a word embedding algorithm, senses of over 1.7 million words were well represented in sufficiently short feature vectors. Through various analysis including clustering and classification, feasibility of our approach was tested. Finally, our trained classification model achieved 87.6% accuracy in the prediction of drug-disease relation in cancer treatment and succeeded in discovering novel drug-disease relations that were actually reported in recent studies.

A rare case of hyaline-type Castleman disease in the liver

Castleman disease often develops in the neck, mediastinum and pulmonary hilum. Its onset in the peritoneal cavity is very rare. The patient, a woman in her 70s, was referred to our department for a detailed examination of an abdominal mass. On abdominal ultrasonography, computed tomography scan, magnetic resonance imaging and positron emission tomography, a mass approximately 15 mm in diameter was noted in the hepatic S6. We attempted radical treatment and conducted a laparoscope-assisted right lobectomy. On the basis of histopathological findings, the patient was diagnosed as having hyaline type Castleman disease in the liver, a very rare condition.

Treatment strategies for advanced hepatocellular carcinoma:Sorafenib vs hepatic arterial infusion chemotherapy

Sorafenib is used worldwide as a first-line standardsystemic agent for advanced hepatocellular carcinoma(HCC) on the basis of the results of two large-scale Phase Ⅲ trials. Conversely,hepatic arterial infusion chemotherapy(HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC,several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib,whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization,good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally,sorafenib is generally used to treat patients with Child-Pugh A,while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings,we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A,while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.

Partial stent-in-stent placement of biliary metallic stents using a short double-balloon enteroscopy

Endoscopic intervention is less invasive than percutaneous or surgical approaches and should be considered the primary drainage procedure in most cases with obstructive jaundice.Recently,therapeutic endoscopic retrograde cholangiopancreatography(ERCP) using double-balloon enteroscopy(DBE) has been shown to be feasible and effective,even in patients with surgically altered anatomies.On the other hand,endoscopic partial stent-in-stent(PSIS) placement of selfexpandable metallic stents(SEMSs) for malignant hilar biliary obstruction in conventional ERCP has also been shown to be feasible,safe and effective.We performed PSIS placement of SEMSs for malignant hilar biliary obstruction due to liver metastasis using a short DBE in a patient with Roux-en-Y anastomosis and achieved technical and clinical success.This procedure can result in quick relief from obstructive jaundice in a single session and with short-term hospitalization,even in patients with surgically altered anatomies.

Effects of an oral iron chelator, deferasirox, on advanced hepatocellular carcinoma

AIM To evaluate the inhibitory effects of deferasirox(DFX) against hepatocellular carcinoma(HCC) through basic and clinical studies.METHODS In the basic study, the effect of DFX was investigated in three hepatoma cell lines(Hep G2, Hep3 B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day. The duration of a single course of DFX therapy was 28 consecutive days. In the event of dose-limiting toxicity(according to the Common Terminology Criteria for Adverse Events v.4.0), DFX dose was reduced.RESULTS Administration of DFX inhibited the proliferation of hepatoma cell lines and induced the activation of caspase-3 in a dose-dependent manner in vitro. In the murine model, DFX treatment significantly suppressed the development of liver tumors(P < 0.01), and significantly upregulated the mR NA expression levels of hepcidin(P < 0.05), transferrin receptor 1(P < 0.05), and hypoxia inducible factor-1α(P < 0.05) in both tumor and non-tumor tissues, compared with control mice. In the clinical study, anorexia and elevated serum creatinine were observed in four and all six patients, respectively. However, reduction in DFX dose led to decrease in serum creatinine levels in all patients. After the first course of DFX, one patient discontinued the therapy. We assessed the tumor response in the remaining five patients; one patient exhibited stable disease, while four patients exhibited progressive disease. The one-year survival rate of the six patients was 17%.CONCLUSION We demonstrated that DFX inhibited HCC in the basic study, but not in the clinical study due to dose-limiting toxicities.

Successful biliary drainage using a metal stent through the gastric stoma

We report a case of biliary drainage for malignant stricture using a metal stent with an ultrathin endoscope through the gastric stoma. A 78-year-old female was referred to our hospital for jaundice and fever. She had undergone percutaneous endoscopic gastrostomy(PEG) for esophageal obstruction after radiation therapy for cancer of the pharynx. Abdominal contrast-enhanced computed tomography showed a 3-cm enhanced mass in the middle bile duct and dilatation of the intrahepatic bile duct. We initially performed endoscopic retrograde cholangiopancreatography(ERCP) with a trans-oral approach. However, neither the side-viewing endoscope nor the ultrathin endoscope passed through the esophageal orifice. Thus, we eventually performed ERCP via the PEG stoma using an ultrathin endoscope. We performed biliary drainage with a 6F introducer selfexpanding metal stent. The cytology findings obtained by brush cytology showed malignancy. Her laboratory results were restored to normal levels after drainage and no complication occurred.

Dilation of a severe bilioenteric or pancreatoenteric anastomotic stricture using a Soehendra Stent Retriever

Bilioenteric or pancreatoenteric anastomotic stric-tures often occur after surgery for a pancreaticobiliary disorder. Therapeutic endoscopic retrograde cholan-giopancreatography using balloon enteroscopy has been shown to be feasible and effective in patients with such strictures. However, when a benign anas-tomotic stricture is severe, a dilation catheter cannot pass through the stricture despite successful insertion of the guidewire. We report on the usefulness of the Soehendra Stent Retriever over a guidewire for dilating a severe bilioenteric or pancreatoenteric anastomotic stricture under short double-balloon enteroscopy, in two patients with surgically altered anatomies.

Concomitant Increases of the Developing Seed Phosph<i>oenol</i>pyruvate Carboxylase Ac-tivity and the Seed Protein Content of Field-Grown Wheat with Nitrogen Supply

Wheat seed storage protein is of great importance for human food. To increase the contents of storage proteins effectively, nitrogen fertilizer at flowering stages is commonly applied. In our previous study, rice phosphoenolpyruvate carboxylase (PEPCase) activity in developing seeds was observed in response to nitrogen application at a flowering stage and was positively correlated to the response of the protein content in seeds of six cultivars. This observation might indicate that the seeds have a biological system for accepting nitrogen in seeds by using PEPCase. To test whether this physiological event occurs in wheat, we examined the PEPCase activity and protein content in field-grown wheat seeds under different nitrogen supply conditions. With only basal dressing, seeds showed lower PEPCase activity and protein content (both 0.90-fold) compared to seeds without basal fertilizer. With ammonium sulfate application at 8.3 and 25 g/m2 at a flowering stage, seeds showed higher PEPCase activity (1.08- and 1.17-fold, respectively) and protein content (1.15- and 1.42-fold, respectively), depending on the nitrogen level. We investigated the relationship between PEPCase activity and protein content in the seeds among four conditions. The effect of the nitrogen supply on PEPCase activity during grain-filling stages was validated by the results of a hydroponic culture experiment. Together the results demonstrate that our hypothesis seems to apply to field-grown wheat.

Applications of quantum computing for investigations of electronic transitions in phenylsulfonyl-carbazole TADF emitters

A quantum chemistry study of the first singlet(S_(1))and triplet(T_(1))excited states of phenylsulfonyl-carbazole compounds,proposed as useful thermally activated delayed fluorescence(TADF)emitters for organic light emitting diode(OLED)applications,was performed with the quantum Equation-Of-Motion Variational Quantum Eigensolver(qEOM-VQE)and Variational Quantum Deflation(VQD)algorithms on quantum simulators and devices.These quantum simulations were performed with double zeta quality basis sets on an active space comprising the highest occupied and lowest unoccupied molecular orbitals(HOMO,LUMO)of the TADF molecules.The differences in energy separations between S_(1) and T_(1)(ΔEST)predicted by calculations on quantum simulators were found to be in excellent agreement with experimental data.Differences of 17 and 88 mHa with respect to exact energies were found for excited states by using the qEOM-VQE and VQD algorithms,respectively,to perform simulations on quantum devices without error mitigation.By utilizing state tomography to purify the quantum states and correct energy values,the large errors found for unmitigated results could be improved to differences of,at most,4 mHa with respect to exact values.Consequently,excellent agreement could be found between values ofΔEST predicted by quantum simulations and those found in experiments.

Coupling of plasmonic nanopore pairs: facing dipoles attract each other

Control of the optical properties of nano-plasmonic structures is essential for next-generation optical circuits and high-throughput biosensing platforms.Realization of such nano-optical devices requires optical couplings of various nanostructured elements and field confinement at the nanoscale.In particular,symmetric coupling modes,also referred to as dark modes,have recently received considerable attention because these modes can confine light energy to small spaces.Although the coupling behavior of plasmonic nanoparticles has been relatively well studied,couplings of inverse structures,that is,holes and pores,remain partially unexplored.Even for the most fundamental coupling system of two dipolar holes,comparison of the symmetric and antisymmetric coupling modes has not been performed.Here we present,for the first time,a systematic study of the symmetric and anti-symmetric coupling of nanopore pairs using cathodoluminescence by scanning transmission electron microscopy and electromagnetic simulation.The symmetric coupling mode,approximated as a pair of facing dipoles,is observed at a lower energy than that of the anti-symmetric coupling mode,indicating that the facing dipoles attract each other.The anti-symmetric coupling mode splits into the inner-and outer-edge localized modes as the coupling distance decreases.These coupling behaviors cannot be fully explained as inverses of coupled disks.Symmetric and anti-symmetric coupling modes are also observed in a short-range ordered pore array,where one pore supports multiple local resonance modes,depending on the distance to the neighboring pore.Accessibility to the observed symmetric modes by far field is also discussed,which is important for nanophotonic device applications.

Activity of superior interferon α against HIV-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes

Background Interferon （IFN） can inhibit human immunodeficiency virus type 1 （HIV-1） replication in vitro and in clinic.However, IFN therapy for HIV infection was limited by its moderate antiviral efficacy and its frequent adverse effects. In the present study we evaluated the anti-HIV efficacy of a novel synthesized superior interferon α （slFNα）.Methods We performed in vitro experiments with HIV-1 IIB infected MT4 cells, and evaluated in vivo anti-HIV efficacy of slFNα in severe combined immunodeficient （SClD） mice reconstituted with human peripheral blood leukocytes （hu-PBL-SClD mice）.Results We found that the 50% effective concentrations （EC5o） of slFNα against the replication of HIV-1 in MT4 cells was 0.06 ng/ml, representing stronger antiviral activity than interferon-α in vitro. In the hu-PBL-SCID mice, a dose-dependent protection pattern was observed： with 0.45 μg and 1.35 μg slFNα daily treatments, parts of SCID mice were protected from HIV infection, whereas 2.25 μg sIFNα daily treatments resulted in a terminally complete protection.Conclusions slFNα shows good anti-HIV activity both in vitro and in SCID mice, may be a promising anti-HIV agent deserving clinical investigation, especially considering the potential of IFN-α to inhibit HIV replication in patients infected with drug-resistant variants or co-infected with hepatitis C virus （HCV）.

In vitro evaluation of the anti-diabetic potential of soymilk yogurt and identification of inhibitory compounds on the formation of advanced glycation end-products

In this study, we aimed to identify starter strains of lactic acid bacteria (LAB) to produce soymilk yogurt that can decrease the risk of diabetes mellitus (DM) and its complications. The inhibition assays of the dipeptidyl peptidase IV (DPP- IV) and advanced glycation end products (AGEs) formation were conducted using 70% ethanol (EtOH) extraction of freeze-dried soymilk yogurt. Soymilk yogurt produced using Weissella confusa TOKAI 2 showed the highest inhibition rate in the α-amylase inhibition assay, while soymilk yogurt produced using Lactiplantibacillus plantarum TOKAI 17 showed the highest inhibition rates in the α-glucosidase and DPP-Ⅳ inhibition assays, respectively. Soymilk yogurt produced using Streptococcus macedonicus TOKAI 4 showed the highest inhibitory activities in Nω-(carboxymethyl) arginine (CMA) and Nε-(carboxymethyl) lysine (CML) formation, respectively. Furthermore, soymilk yogurt prepared using Lb. plantarum TOKAI 17 and Lactiplantibacillus pentosus TOKAI 35 exhibited higher proportions of aglycone isoflavones than soymilk and showed a higher fluorescent AGEs inhibitory activity than that of soymilk (p < 0.05). Interestingly, the inhibition assay assessing fluorescent AGEs formation using isoflavones indicated that aglycone-type isoflavones, such as genistein and daidzein, had higher inhibitory activities than that of glycosides (p < 0.05). These results indicate that soymilk yogurt produced using Lb. plantarum TOKAI 17 and Lb. pentosus TOKAI 35 had inhibitory effects on α-glucosidase, DPP-Ⅳ, and AGEs formation in vitro, and that aglycone isoflavones might inhibit the formation of fluorescent AGEs.