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Katsuaki Ogushi,1,* Makoto Chuma,1,* Haruki Uojima,2 Hisashi Hidaka,2 Kazushi Numata,1 Satoshi Kobayashi,3 Shunji Hirose,4 Nobuhiro Hattori,5 Tomoaki Fujikawa,6 Takahide Nakazawa,2 Naohisa Wada,2 Shuitirou Iwasaki,2 Taito Fukushima,3 Yusuke Sano,3 Makoto Ueno,3 Kuniyuki Kawano,3 Kota Tsuruya,4 Masako Shomura,4 Tsunamasa Watanabe,5 Kotaro Matsunaga,5 Yosuke Kunishi,7 Yusuke Saigusa,8 Kuniyasu Irie,9 Shogo Iwabuchi,6 Makoto Kako,10 Manabu Morimoto,3 Tatehiro Kagawa,4 Katsuaki Tanaka,11 Shin Maeda9 1Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan; 2Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan; 3Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan; 4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan; 6Department of Gastroenterology, Shonan Fujisawa General Hospital, Fujisawa, Japan; 7Department of Gastroenterology, Kanagawa Prefectural Ashigarakami Hospital, Kanagawa, Japan; 8Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 9Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Japan; 10Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Japan; 11Gastroenterology Division, Hadano Red Cross Hospital, Hadano, Japan*These authors contributed equally to this workCorrespondence: Makoto Chuma Gastroenterological CenterYokohama City University Medical Center, 4-57 Urafune-Cho, Minami-Ku, Yokohama, Kanagawa 2320024, JapanTel +81 45 261 5656Fax +81 45 253 9955Email chuma@yokohama-cu.ac.jpPurpose: To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC).Methods: Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines.Results: Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P < 0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥ 0.7 vs < 0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5– 7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment.Conclusion: Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.Keywords: lenvatinib, tyrosine kinase inhibitor, hepatocellular carcinoma, Child-Pugh, adverse events, overall survival

In order to accelerate the spherical/spheroidal harmonic synthesis of any function, we developed a new recursive method to compute the sine/cosine series coefficient of the 4π fully- and Schmidt quasi-normalized associated Legendre functions. The key of the method is a set of increasing-degree/order mixed-wavenumber two to four-term recurrence formulas to compute the diagonal terms. They are used in preparing the seed values of the decreasing-order fixed-degree, and fixed-wavenumber two- and three-term recurrence formulas, which are obtained by modifying the classic relations. The new method is accurate and capable to deal with an arbitrary high degree/ order/wavenumber. Also, it runs significantly faster than the previous method of ours utilizing the Wigner d function, say around 20 times more when the maximum degree exceeds 1,000.

Tomoya Harada, Akira Yamasaki, Takehito Fukushima, Kiyoshi Hashimoto, Miki Takata, Masahiro Kodani, Ryota Okazaki, Kenichi Takeda, Masanari Watanabe, Jun Kurai, Eiji Shimizu Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Tottori University, Yonago, Japan Background: The administration of inhaled corticosteroids and worldwide usage of several asthma guidelines have improved asthma mortality. Elderly patients with asthma show high mortality rates, and may have several comorbidities, including overlap with chronic obstructive pulmonary disease (COPD). Among patients showing asthma overlapped with COPD (asthma–COPD overlap syndrome; ACOS), mortality is worse than for asthma alone. Therefore, we investigated comorbidities, malignancies, and causes of death in patients with asthma and ACOS. Methods: This was a retrospective study. From January 2000 to March 2012, 650 patients were followed up at Tottori University Hospital. Medical records were reviewed to collect data regarding patient characteristics and comorbidities, and causes of death were recorded for patients who died during the study period.Results: Eighty-seven patients died during the study period. The most frequent cause of death was malignancy. The proportion of malignant disease was 21.7% in all patients, 19.4% in patients with asthma alone, and 32.4% in patients with ACOS. One patient died from an asthma attack during this period.Conclusion: The most frequent cause of death in patients with asthma and ACOS was malignant disease. It is necessary to control not only asthma but also comorbidities in patients with asthma, especially in those with ACOS. Keywords: asthma, chronic obstructive pulmonary disease, asthma-COPD overlap syndrome, mortality

Akira Yamasaki,1 Yuji Kawasaki,2 Kenichi Takeda,1 Tomoya Harada,1 Takehito Fukushima,1 Miki Takata,1 Kiyoshi Hashimoto,1 Masanari Watanabe,1 Jun Kurai,1 Koichi Nishimura,3 Eiji Shimizu1 1Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Tottori University, Yonago, Japan; 2Division of Pulmonary Medicine, Tsuyama Daiichi Hospital, Tsuyama, Japan; 3Department of Pulmonary Medicine, National Center for Geriatrics and Gerontology, Obu, Japan Background: Sleep disturbance is commonly observed in patients with asthma, especially in those with poorly controlled asthma. Evaluating sleep quality to achieve good control of asthma is important since nocturnal asthmatic symptoms such as cough, wheezing, and chest tightness may disturb sleep. Actigraphy is an objective, ambulatory monitoring method for tracking a patient's sleep and wake activities and for assessing sleep quality, as reflected by total sleep time, sleep efficiency, duration of awakening after sleep onset (WASO), and sleep onset latency. Patients and methods: Fifty patients with asthma were enrolled in this study. Sleep quality was assessed employing wristwatch-type actigraphy (Actiwatch 2). The level of asthma control was assessed by the Asthma Control Questionnaire (ACQ), and asthma-related quality of life was assessed by the Asthma Quality of Life Questionnaire (AQLQ). The parameters for sleep quality were compared using ACQ scores, AQLQ scores, and pulmonary function test results. Results: The total sleep time was 387.2 minutes, WASO was 55.8 minutes, sleep efficiency was 87.01%, sleep onset latency was 8.17 minutes, and the average ACQ was 0.36. Neither sleep efficiency nor WASO correlated with respiratory functions, ACQ scores, or AQLQ scores. Conclusion: Sleep-related parameters assessed by actigraphy in well-controlled asthma do not correlate with pulmonary functions, the asthma control level, or daytime quality of life. Sleep quality should be evaluated independently when asthma is well-controlled. Keywords: asthma control, respiratory function, sleep efficiency, actigraphy

We investigate the phase stability and magnetism of V 2 based antiferromagnetic semiconductors by first-principles calculations. We first analyze the phase stability of the designed alloys by calculating the convex hull and find that keeping Al atoms in the Z sites is crucial to guarantee the stability against the segregation. The V 2 Y Al (Y = V , Nb, and Ta) systems have relatively small hull distances and Néel temperatures higher than 1000 K are evaluated. The strong antiferromagnetic coupling between V atoms is rapidly decreasing with increasing the number of electrons due to the appearance of ferromagnetic double-exchange interaction. By applying a uniaxial strain to induce tetragonal distortion, a relatively large magneto-crystalline anisotropy energy is obtained for V 2 TaAl. It is claimed that V 2 Y Al are thought to be good candidates for antiferromagnetic spintronics including gate-tunable magnetic properties. [ABSTRACT FROM AUTHOR]

Minoru Kawaguchi,1,2 Jun Yamazaki,2,3 Jun Ohno,2,4 Tadao Fukushima2,51Department of Dental Engineering, Biomaterials Section, Fukuoka Dental College, Sawara-ku, Fukuoka; 2Japan Science and Technology Agency, Core Research of Evolutional Science and Technology, Chiyoda-ku, Tokyo; 3Department of Physiological Science and Molecular Biology, Section of Cellular and Molecular Regulation, 4Department of Morphological Biology, Pathology Section, 5Center for Regenerative Medicine, Fukuoka Dental College, Sawara-ku, Fukuoka, JapanAbstract: Carbon nanotubes have been explored as heat-delivery vehicles for thermal ablation of tumors. To use single-walled carbon nanotubes (SWNT) as a “molecular heater” for hyperthermia therapy in cancer, stable dispersibility and smart-delivery potential will be needed, as well as lack of toxicity. This paper reports the preparation of a model complex comprising DNA-treated SWNT and anti-human IgG antibody and the specific binding ability of this model complex with the targeted protein, ie, human IgG. Treatment with double-stranded DNA enabled stable dispersibility of a complex composed of SWNT and the antibody under physiological conditions. Quartz crystal microbalance results suggest that there was one immobilized IgG molecule to every 21,700 carbon atoms in the complex containing DNA-treated SWNT and the antibody. The DNA-SWNT antibody complex showed good selectivity for binding to the targeted protein. Binding analysis revealed that treatment with DNA did not interfere with binding affinity or capacity between the immobilized antibody and the targeted protein. The results of this study demonstrate that the DNA-SWNT antibody complex is a useful tool for use as a smart “molecular heater” platform applicable to various types of antibodies targeting a specific antigen.Keywords: carbon nanotubes, DNA functionalization, complex, antibody, binding ability