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Recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC) has a poor prognosis. Although nivolumab is approved in Japan for treating R/MHNSCC, the response rate is low. Therefore, identifying pretreatment prognostic factors is necessary. This study assessed the utility of the neutrophil-to-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) as biomarkers of response to nivolumab. We retrospectively collected the data of 56 R/MHNSCC patients treated with nivolumab between May 2017 and December 2019. The Kaplan-Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), and multivariate Cox hazard regression analysis was used to identify independent predictors of survival. Patients with a low pretreatment NLR had prolonged OS, and patients with a low pretreatment GPS had increased OS and PFS. A performance score (PS) of 0-1, development of immune-related adverse events, and GPS of 0-1 were significantly associated with OS in multivariate analysis. In summary, baseline pretreatment NLR and GPS are independently associated with OS in R/MHNSCC patients treated with nivolumab. Administration of nivolumab while maintaining the PS reflects a immune status of the host and leads to a good OS.

This paper reports the results of vibration and meteorological observations of a buildng built on Hashima, Nagasaki, southern part of Japan, which was registered as a World Heritage Site in 2015 [1], and analyzes its dynamic characteristics. Hashima is called "Battleship Island" because its appearance resembles a battleship due to the many buildings standing upon it. The structure contributing most to the battleship appearance is No. 3 Building. An accelerometer and a weather sensor have been installed in No. 3 Building for long-term measurements. Multi-modal analysis of vibration and meteorological data was performed for 5 months, and the dynamic characteristics of No. 3 Building were examined.

We measured magnetizations of doped spin-Peierls Cu_Zn_xGeO_3 with x=0, 0.005, 0.010 and 0.020 in order to study effects of impurities on a magnetic phase. A rapid change of the magnetization associated with a phase transition from dimerized to other phases is seen. The magnetization above 16 T shows weak x and temperature dependence. A critical field associated with the phase transition decreases with increasing x. Effects of impurities on the magnetic phase are weaker than on the dimerized phase. The soliton model is applicable to the magnetic phase.

Tissue factor pathway inhibitor (TFPI) inhibits factor VIIa-tissue factor and factor Xa through its first and second Kunitz-type domains, respectively. Previous studies have shown that heparin binds to TFPI at two sites and enhances the inhibitory activity of TFPI towards factor Xa. We have studied the effect of heparin of the TFPI-mediated inhibition of factor VIIa-relipidated tissue factor amiodolytic activity and factor VIIa-tissue factor proteolytic activity towards factor IX and factor X on a human bladder carcinoma cell line, J82. The inhibitory activity of full-length TFPI on factor VIIa-tissue factor amidolytic and proteolytic activities was greatly enhanced by heparin, whereas the inhibitory activity of a truncated form of TFPI lacking the third Kunitz-type domain and carboxy-terminal tail (TFPI1-161) was not affected by heparin. Optimal inhibition of factor VIIa-tissue factor by TFPI was observed at 0.1 U/ml heparin. Heparin enhanced the inhibitory activity of TFPI towards factor Xa even in the presence of factor VIIa-tissue factor complexes in solution phase. In addition, heparin augmented the ability of TFPI to inhibit factor VIIa-tissue factor amidolytic activity in the presence of active-site mutated factor X (S376A factor X). Our collective results suggest that heparin may play a significant role in augmenting the physiological regulation of factor VIIa-tissue factor activity by TFPI.

The effect of two arginine-specific cysteine proteinases (gingipains R) from Porphyromonas gingivalis, an aetiological factor of adult periodontitis, on the activation of human factor IX was investigated in the presence of ethylene glycol, an activity enhancer of activated factor IX (factor IXa), with the use of a fluorogenic oligopeptide substrate. Each gingipain R rapidly activated factor IX but the 95 kDa proteinase complex (HRgpA) that contains both haemagglutinin/adhesion and catalytic domains was 2.4-fold more efficient than the single-chain 50 kDa gingipain R (RgpB), which has only a catalytic domain. SDS/PAGE and N-terminal sequence analysis of factor IX digestion fragments indicated that, like all endogenous activators, gingipains R also produce factor IXabeta via an IXa intermediate. Significantly, phospholipids augmented the activation of factor IX by HRgpA but not by RgpB in a Ca(2+)-dependent manner. In the presence of both cofactors the kinetic efficiency of HRgpA to activate factor IX (k(cat)/K(m)=1.9x10(6) M(-1).s(-1)) was 8.5-fold higher than that of RgpB (k(cat)/K(m)=2.3x10(5) M(-1).s(-1)) and double that of the factor VIIa-tissue factor complex, but 8-fold lower than that for factor XIa. A comparison of the relative activation rates of factor IX, factor X and prothrombin directly in plasma by HRgpA suggests a significant contribution for factor IX conversion in blood coagulation induced by gingipains R. Taken together, gingipains R are the first-reported activators of factor IX of bacterial origin. By this effect they could be involved in the production of thrombin as well as the subsequent generation of prostaglandins and interleukin 1, all of which have been found to be associated with the development and progression of periodontitis.