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Abstract Aim The anti‐tumor effects of natural killer (NK) cells vary among individuals. Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) expressed on liver NK cells is a marker of anti‐tumor cytotoxicity against hepatocellular carcinoma (HCC) in immune cell therapy. This study aimed to develop a liver immune status index (LISI) that predicts low TRAIL expression and validates its ability to predict recurrence after initial hepatectomy for primary HCC. Methods A functional analysis of liver NK cells co‐cultured with interleukin‐2 for 3 days was performed of 40 liver transplant donors. The LISI, which predicted low TRAIL expression (25% quartile:

Overhead contact lines (OCLs) are subjected to longitudinal displacement due to factors such as temperature changes and external force. Excessive longitudinal displacement may prevent the tension balancers from performing their proper tension adjustment function. It is therefore important to develop a method for calculating the longitudinal displacement of OCLs and to make it possible to predict the longitudinal displacement in response to changes in temperature and external forces. This paper presents a model to represent the longitudinal displacement of OCLs on a curved track installing tensioning devices and hinged cantilevers at each support point and proposes calculation methods to find the equilibrium points of the longitudinal displacement of the OCL. Furthermore, the validation of the proposed calculation methods was confirmed by scale model tests.

Abstract Background Liver‐resident natural killer (lr‐NK) cells are distinct from conventional NK cells and exhibit higher cytotoxicity against hepatoma via tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL). However, the mechanism by which partial hepatectomy (PH) significantly suppresses TRAIL expression in lr‐NK cells remains unclear. Methods This study aimed to investigate the PH influence on the function and characteristics of liver‐resident NK (lr‐NK) cells using a PH mouse model. Results Here, we report that PH alters the differentiation pattern of NK cells in the liver, and an aryl hydrocarbon receptor (AhR) molecule is involved in these changes. Treatment with the AhR agonist 6‐formylindolo[3,2‐b]carbazole (FICZ) inhibited the maturation of NK cells. FICZ increased the immature subtype proportion of NK cells with high TRAIL activity and decreased the mature subtype of NK cells with low TRAIL activity. Consequently, FICZ increased the expression of TRAIL and cytotoxic activity of NK cells in the liver, and this effect was confirmed even after hepatectomy. The participation of AhR promoted FoxO1 expression in the mTOR signaling pathway involved in the maturation of NK cells, resulting in TRAIL expression. Conclusion Our findings provide direct in‐vivo evidence that partial hepatectomy affects lrNK cell activity through NK cell differentiation in the liver. Perioperative therapies using an AhR agonist to improve NK cell function may reduce the recurrence of hepatocellular carcinoma after hepatectomy.

The on-board components mounted on the structural panel of spacecraft are exposed to a severe random vibration environment, mainly induced by the acoustic excitation of the panel structure due to the large acoustic noise from the launch vehicle. To verify the components' resistance against the vibrational environment, random vibration tests of the components are generally performed at the excitation level based on vibroacoustic prediction. In order to consider the prediction uncertainty, there actually needs to add a margin, which often poses an excess of design and testing. JAXA has been involved with predicting wide frequency band vibro-acoustic behavior of the structural panel using SEA (Statistical Energy Analysis), in which we have to add margin to take into account spatial and frequency bandwidth uncertainties. These kinds of uncertainty margin may result in over conservative margin and causes costly over conservative design. To reduce the over conservative margin in SEA method, in this paper, a wavenumber expression of joint acceptance method calculated by fast Fourier transform approach on finite element model parameter of panel, i.e., mode frequency and mode shape is proposed. The proposed method is applied to two structural panels of actual spacecraft and compared with acoustic test results. It is shown by comparison with the test result of an actual panel that the proposed method achieved less conservative prediction in each individual component mounting location rather than enveloping every mounting location that SEA calculates.

Abstract The effects of acute portal hypertension (PHT), which is reported as poor prognostic factors in patients with hepatocellular carcinoma, are not well known on the liver immune system, including natural killer (NK) cells. The aim of this study, therefore, was to investigate how acute PHT influences the functions and characteristics of liver‐resident NK (lr‐NK) cells using an acute PHT mouse model. Acute PHT decreased the number of tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL+) lr‐NK cells by about 20% and attenuated cytotoxic activity against the Hepa1‐6 cell line by about 40%. Among various cytokine, only interleukin‐33 (IL‐33), which inhibits NK activity, significantly increased after portal vein ligation (PVL). Because lr‐NK cells highly expressed ST2/IL‐33R, IL‐33 co‐culture significantly suppressed TRAIL expression on lr‐NK cells by about 50%, and IL‐33 administration markedly decreased TRAIL expression and cytotoxic activity of lr‐NK cells. Furthermore, the TRAIL+ NK cells population was maintained by anti‐IL33 antibody or following portosystemic shunt procedure even after PVL. Finally, we demonstrated that IL‐33 decreased TRAIL expression in lr‐NK cells via AKT–forkhead box O (FoxO) and mitogen‐activated protein kinase (MAPK) signaling. Conclusion: This work demonstrates that PHT suppresses the TRAIL+ lr‐NK cell population and antitumor activities in the liver. Additionally, Akt‐FoxO and MAPK signaling pathways attenuate the TRAIL expression in lt‐NK cells via IL‐33 receptor in mice.

Abstract Background Bloodstream infections (BSIs) are among the most lethal complications of liver transplantation (LT). Natural killer (NK) cells are an important component of innate immunity and play an essential role in infection and cancer. Adoptive transfer of activated NK cells has the potential to decrease post-LT infections, including BSIs. Methods In this prospective, single-center, interventional, single-arm, historical control, phase I/II study, 37 LT recipients will enroll. The patient will receive a single infusion of donor liver-derived NK cells 3−5 days after LT. Discussion The primary endpoint is the incidence of BSIs during the first month after LT. Secondary endpoints include overall survival, adverse events, immunological responses, hepatocellular or de novo malignancy, and incidence of infectious disease. Trial registration This study was prospectively registered with UMIN000019183 ( https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000022074 ) on November 1, 2015 and jRCTa060190036 on February 27, 2020.

Spacecraft are exposed to acoustic loads during flights to space by launch vehicles. The endurance of spacecraft structure is verified by a ground acoustic test specified in test standard documents of the aerospace community. These standard documents require the execution of ground acoustic tests in a reverberant chamber on the assumption that it can generate a diffuse sound field which is normally defined as “completely isotropic and equal probability of energy flow in all directions”. However, in the space development industry and related studies, the directions of incident sounds which cause non-diffuseness has not been identified by the experimental comparison with the theoretical values of an ideal diffuse sound field (e.g. reverberation times, homogeneity of sound pressures and spatial correlation functions). Therefore, the conventional standard documents do not clearly specify the quantitative requirements regarding the directional properties of sound fields inside reverberant chambers. To specify the quantitative requirement on the directional properties of sounds, this paper focused on calculating the degree of isotropy of a sound field by the direct measurement of directional properties of sound waves as angular spectra. In this paper, the method to obtain the angular spectrum based on the theory of the expansion of the plane wave into spherical harmonics by using a spherical microphone array was firstly combined with the existing formula of the isotropy indicator, which allowed us to determine the frequency range when we apply the combined method to sound fields. The method to determine the applicable frequency range was demonstrated and the process of obtaining the angular spectrum and isotropy indicator was verified by numerical simulation. Finally, the combined method was applied to the sound field in the reverberant chamber of JAXA 1600m3 acoustic test facility.

Abstract Aim The clinical impact of abdominal aortic calcification (AAC) in patients who undergo hepatectomy for hepatocellular carcinoma (HCC) is unknown. Methods To evaluate the impact of AAC on clinical outcomes, we analyzed 203 patients who underwent hepatectomy for HCC between 2010 and 2013. Results Kaplan–Meier survival curve analysis showed significantly worse overall survival (OS) in the high AAC group than in the low AAC group. The recurrence‐free survival (RFS) was also significantly worse in the high AAC group. In the multivariate analysis, high AAC (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.24–5.09; P = .01) was an independent risk factor for poor OS after hepatectomy for HCC. High AAC was also an independent risk factor for poor RFS (HR, 1.69; 95% CI, 1.04–2.76; P = .04). Conclusions Abdominal aortic calcification had a strong relationship with poor OS and RFS after hepatectomy for HCC. We suggest that AAC had a relationship with smoking and diabetes; therefore, AAC could reflect a surrogate for older age, worse health status, and inflammatory score.

Introduction Hepatocellular carcinoma (HCC) remains a major clinical problem as more than half of these cases recur after radical resection. Natural killer (NK) cells are at the forefront of the innate immune system and attack microcarcinomas and circulating tumour cells. The objective of this study was to evaluate the feasibility and toxicity of peripheral blood CD34+ stem cell-derived NK cell infusion after radical hepatectomy for HCC.Methods and analysis This is an open-label, single-arm, single-centre phase I study. Patients who have undergone initial hepatectomy for HCC with three or more risk factors for recurrence (≥10 ng/mL of Alpha fetoprotein (AFP), ≥360 mAU/mL of PIVKA-II, multiple tumours and ≥3 peripheral blood circulating tumour cells) will be enrolled and be treated with three peripheral blood CD34+ stem cell-derived NK cell infusions every 3 months. The primary endpoint will be safety assessment including the type and severity of adverse events, frequency of occurrence and duration of occurrence. The secondary endpoints will include survival, effect of immune response and clinical laboratory test results.Ethics and dissemination Ethical approval of the trial was obtained from the Certified Committee for Regenerative Medicine Hiroshima University in Japan. The trial results will be shared with the scientific community at international conferences and by publication in a peer-reviewed journal.Trial registration number jRCTb060200020.

Neurostimulation is an essential technique to trigger and modulate the spatiotemporal activity of local neuronal circuits. Current stimulation methods have a trade-off relationship among aiming precision, temporal resolution, and noninvasiveness, making it difficult to stimulate and monitor a single target neuron for a long term. Here, we show that a method using two needle electrodes in combination of micropatterning techniques provides new possibilities for targeting and stimulating a single neuron selectively. Results of physiological experiments as well as analog circuit simulation reveal that two needle electrodes can stimulate a target neuron selectively by placing the two needle electrodes in proximity to and to straddle the target neuron, and that the steepness of voltage applied to two needle electrodes is important for the target neuron to fire at a low voltage. The proposed method enables a noninvasive stimulation suitable for measuring long-term activity of local neuronal circuits.

Background and aims: Lenvatinib (LEN) is a newly developed tyrosine kinase inhibitor, and is approved as a first-line treatment for advanced hepatocellular carcinoma (HCC) in Japan. This retrospective multi-center study investigated the effect of the relative dose intensity (RDI) of LEN on response rate, progression-free survival (PFS), and overall survival (OS). Methods: This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December 2019. These patients were divided into two groups: RDI ≥70% (RDI 70 group, N = 70) or RDI

Background: Although radiofrequency ablation (RFA) is a minimally invasive treatment for early-stage hepatocellular carcinoma (HCC), it remains unclear whether RFA achieves favorable outcomes in patients aged ≥80 years. This study aimed to determine the efficacy and safety of RFA for HCC in patients aged ≥80 years. Methods: A total of 512 naïve patients with HCC who had undergone RFA from January 2001 to December 2016 were enrolled. They were categorized into the ≥80-year-old group and the control group (aged

Abstract Background and Objective Experience of the use of lenvatinib (LEN) in the clinical setting remains limited. We conducted this study to elucidate the factors associated with progression-free survival (PFS) in patients with advanced HCC treated with LEN. Methods In this multicenter retrospective study, we analyzed data on patient characteristics, treatment outcomes, and adverse events (AEs) for 77 patients with advanced hepatocellular carcinoma (HCC). We also analyzed PFS and factors that influence PFS. Results The response rate to LEN was 29.9% and the disease control rate was 77.9%. Patients who achieved relative dose intensities of more than 70% had better outcomes (response rate 45.2% vs. 11.4%, P

Image-guided percutaneous ablation is considered best in the treatment of early-stage hepatocellular carcinoma (HCC). Ablation is potentially curative, minimally invasive, and easily repeatable for recurrence. Ethanol injection used to be the standard in ablation. However, radiofrequency ablation has recently been the most prevailing ablation method for HCC. Many investigators have reported that radiofrequency ablation is superior to ethanol injection, from the viewpoints of treatment response, local tumor curativity, and overall survival. New-generation microwave ablation can create a larger ablation volume in a shorter time period. Further comparison studies are, however, mandatory between radiofrequency ablation and microwave ablation, especially in terms of complications and long-term survival. Irreversible electroporation, which is a non-thermal ablation method that delivers short electric pulses to induce cell death due to apoptosis, requires further studies, especially in terms of long-term outcomes. It is considerably difficult to compare outcomes in ablation with those in surgical resection. However, radiofrequency ablation seems to be a satisfactory alternative to resection for HCC 3 cm or smaller in Child-Pugh class A or B cirrhosis. Furthermore, radiofrequency ablation may be a first-line treatment in HCC 2 cm or smaller in Child-Pugh class A or B cirrhosis. Various innovations would further improve outcomes in ablation. Training programs may be effective in providing an excellent opportunity to understand basic concepts and learn cardinal skills for successful ablation. Sophisticated ablation would be more than an adequate alternative of surgery for small- and possibly middle-sized HCC.

Silica-supported Cu (Cu/SiO2) catalyst prepared by using organic additive-assisted impregnation was employed for the chemoselective hydrogenation of a C=O bond in 6-methyl-5-hepten-2-one (1) to produce 6-methyl-5-hepten-2-ol (2) in a vapor phase at a temperature between 140 and 200 °C and an ambient pressure of H2 flow. The Cu was responsible for the selectivity to 2, and the organic additive increased the Cu surface area (SACu), which consecutively enhanced the performance of the Cu/SiO2 catalyst. The proportional correlation between the SACu and the formation rate of 2 further confirmed the benefits of the utilization of organic additives during the impregnation protocol. [ABSTRACT FROM AUTHOR]