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A 69-year-old woman with chronic hepatitis C virus (HCV) infection was referred to our hospital due to liver enzyme abnormalities. Four years after anti-HCV therapy, the patient with sustained virologic response and no clinical symptoms developed an oval hepatic mass with mixed high and low internal echoes near the portal vein on ultrasound. Magnetic resonance imaging (MRI) of the liver lesion showed a slightly hypo intense pattern on T1-weighted images, a hyper intense pattern both on T2- and diffusion-weighted images, a slight rim enhancement pattern with no intra-lesional enhancement up to the late phase, and a very low intense pattern on hepatobiliary phase images. Positron emission tomography/computed tomography (PET / CT) showed no areas of avid radiotracer uptake in the liver. No tumor markers showed abnormally high values. All these images and laboratory findings led us to the assessment of the liver lesion as a non-neoplastic disorder. However, due to the patient's strong preference to get both definitive diagnosis and cure of the lesion, the patient underwent laparoscopic partial hepatectomy. Pathological study showed 2 necrotic areas surrounded by multiple lymph follicles, epithelioid cells, lymphocytes, collagen fibers, and plasma cells, leading to the diagnosis of focal coagulative necrosis of the liver (FCNL). Physicians should note that FCNL can occur without any symptoms and can be diagnosed at least as a non-neoplastic disorder with combined MRI and PET/CT analysis.

A 71-year-old man with slight fever and dull abdominal pain was referred to our hospital. He had been receiving methotrexate (MTX) to treat his rheumatoid arthritis for more than 6 years but stopped taking MTX after admission due to the rapid aggravation of his liver function. Computed tomography (CT) showed multiple liver lesions with late enhancement, highly suggesting them to be cholangiocarcinomas. Tumor marker levels were normal except for a slightly elevated PIVKA-II level, i.e., 45 mAU/mL (range 0–40 mAU/mL). We did a biopsy to the largest lesion and endoscopic biliary drainage to make a definitive diagnosis of the hepatic lesions and treat jaundice, respectively. Pathological study showed round, polygonal, and spindle-shaped epithelial atypical cells growing in a sarcomatoid fashion. Atypical cells were positive for CD31, CD34, vimentin, and TFE3, and some of them had intracellular vacuoles, leading to the diagnosis of epithelioid hemangioendothelioma (EHE) of the liver. The patient got well 4 weeks after the endoscopic biliary drainage. CTs showed marked regression of the EHE lesions 3 months after biliary drainage and complete regression in 12 months. The patient further developed Hodgkin lymphoma in the para-aortic lymph nodes 23 months after the biliary drainage and is now under chemotherapy for the malignant lymphoma. We, however, have not detected any EHE lesions in the liver or distant organs for at least 16 months after the confirmation of complete regression of the EHE lesions. Oncologists should note the spontaneous regression of the EHE and investigate the correlation between MTX cessation and EHE regression.

Neoantigens/ are tumor-specific antigens that evade central immune tolerance mechanisms in the thymus. Long-term tumor-specific cytotoxic T lymphocyte activity maintenance requires class II antigen-reactive CD4+ T cells. We had previously shown that intranodal vaccination with class I neoantigen peptide-pulsed dendritic cells (DCs) induced a robust immune response in a subset of patients with metastatic cancer. The present study aimed to perform a detailed ex vivo analysis of immune responses in four patients receiving an intranodal hybrid human leukocyte antigen class II neoantigen peptide encompassing a class I neoantigen epitope (hybrid neoantigen)-pulsed DC vaccine. After vaccination, strong T-cell reactions against the hybrid class II peptide and the class I-binding neoantigen peptide were observed in all four patients. We found that hybrid class II neoantigen peptide-pulsed DCs stimulated CD4+ T cells via direct antigen presentation and CD8+ T cells via cross-presentation. Further, we demonstrated that hybrid class II peptides encompassing multiple class I neoantigen epitope-pulsed DCs could present multiple class I peptides to CD8+ T cells via cross-presentation. Our findings provide insight into the mechanisms underlying hybrid neoantigen-pulsed DC vaccine therapy and suggest future neoantigen vaccine design.

Abstract A 78-year-old male presented with a positive fecal occult blood test. Rectal cancer was detected during lower gastrointestinal endoscopy, and further investigations led to a diagnosis of cT1N0M0 cStage I (UICC classification, 8th edition). Preoperative contrast-enhanced computed tomography (CT) showed that the patient also had Leriche syndrome, which is associated with reduced blood flow to the rectum that may result in ischemic anastomosis during rectal cancer surgery with anastomotic reconstruction. The inferior epigastric arteries often function as collateral pathways to the lower limbs in patients with Leriche syndrome; therefore, care is needed to avoid vascular damage during trocar insertion when performing laparoscopic surgeries. We herein described a case of safe laparoscopic low anterior resection in a rectal cancer patient with Leriche syndrome using vascular architecture images obtained by preoperative CT angiography.

Abstract Chemical sensing is vital to the survival of all organisms. Bacterial chemotaxis is conducted by multiple receptors that sense chemicals to regulate a single signalling system controlling the transition between the direction (clockwise vs. counterclockwise) of flagellar rotation. Such an integrated system seems better suited to judge chemicals as either favourable or unfavourable, but not for identification purposes though differences in their affinities to the receptors may cause difference in response strength. Here, an experimental setup was developed to monitor behaviours of multiple cells stimulated simultaneously as well as a statistical framework based on Bayesian inferences. Although responses of individual cells varied substantially, ensemble averaging of the time courses seemed characteristic to attractant species, indicating we can extract information of input chemical species from responses of the bacterium. Furthermore, two similar, but distinct, beverages elicited attractant responses of cells with profiles distinguishable with the Bayesian procedure. These results provide a basis for novel bio-inspired sensors that could be used with other cell types to sense wider ranges of chemicals.

Abstract Background Troubleshooting intraoperative complications requires careful management, and the safest technique should be chosen. We recently experienced a unique intraoperative bronchial complication during pulmonary lobectomy in robot-assisted thoracic surgery (RATS). There is no consensus on whether to continue RATS or convert to a more familiar technique, such as video-assisted thoracic surgery (VATS) or thoracotomy, for intraoperative complications that occur during RATS, and the decision should be determined individually. Case presentation A 74-year-old woman with primary lung adenocarcinoma (clinical stage IA2) underwent robot-assisted right lower lobectomy under one-lung ventilation and CO2 insufflation. Intraoperatively, the anesthesiologist placed the endobronchial suction tube in the right bronchus with intention of maintaining the right lung collapse, which was simultaneously stapled with the right lower bronchus during the right lower lobe bronchial closure using a robotic stapler. During robot-assisted manipulation, we removed the staples involved with the suction tube, one by one, using robotic-arm forceps and sutured the partially opened stump. Subsequently, the bronchial stump was covered with a pedicled pericardial fat pad. The postoperative course was uneventful, and the patient developed no complications when followed up 8 months after discharge. Hence, we could rectify this intraoperative bronchial complication using a robot-assisted technique and avoid conversion to VATS or thoracotomy. Conclusion The precise manipulation techniques in RATS contributed to facilitate the successful execution of surgical procedures, such as staple removal and re-suturing of the bronchial stump and may be a useful as a method for such troubleshooting such intraoperative complications.

Thermal analysis of spacecraft is one of the most important processes to ensure the safety of spacecraft systems. However, the thermal mathematical model has uncertainty such as thermal contact conductance or thermal optical properties. These uncertain parameters in the model are non-negligible for long-term missions because these parameters can change during operation on orbit. Despite the uncertainties, the spacecraft system has only a few onboard temperature sensors compared to large and complex systems. In this study, an advanced thermal analysis method based on data assimilation is proposed to estimate the thermal state of a complex system with limited temperature data. Firstly, this paper describes a new state estimation algorithm called Assisted Ensemble Kalman Filter, which is an advanced state estimation algorithm based on Ensemble Kalman Filter (EnKF). Here, an external estimation algorithm by calculating the heat balance equation was applied to the conventional method to improve the estimation performance of the EnKF. Secondly, we propose a new parameter that indicates observability based on heat flux and temperature sensitivity, and the influence of temperature sensor location on estimation performance was discussed. These proposed approaches were applied to a simple thermal mathematical model, and numerical experiments have confirmed their availability.

Dolphins are well known as excellent swimmers for being capable of efficient cruising and sharp acceleration. While studies of the thrust production and power consumption of dolphin swimming have been the main subject for decades, time-varying acceleration process during successive fluke beats still remains poorly understood. In this study, we quantified the time-varying kinematics of a dolphin (Lagenorhynchus obliquidens) by directly recording its burst-accelerating swimming before vertical jump in an aquarium with two synchronized high-speed video cameras. We tracked the three-dimensional trajectories of its beak, body sides, and fluke. We found that dolphin could quickly accelerate from 5.0 m s-1 to 8.7 m s-1 merely by 5 strokes (i.e. 2.5 fluke beats) in 0.7 seconds. During the strokes, it was further found that the dolphin demonstrated a great acceleration in downstroke but less acceleration or even a slight deceleration in upstroke. Hydrodynamic forces and thrust power for each stroke were further estimated based on the equation of body motion and a static hydrodynamic model. The drag coefficient of the dolphin was estimated through computational fluid dynamics (CFD) modeling of the steady flows around a realistic geometric model based on 3-D scan data. The thrust and thrust power were then calculated by combining the body kinematics and the drag coefficient, resulting in a maximum stroke-averaged thrust and power-to-mass ratio of 1.3 × 103 N and 90 W kg-1 at downstroke, and 3.3 × 102 N and 19 W kg-1 at upstroke, respectively. Our results point out the importance of asymmetric kinematics in burst acceleration of dolphin, which may be a useful mechanism for biomimetic design of high-performance underwater robots.

Animal wings are lightweight and flexible; hence, during flapping flight their shapes change. It has been known that such dynamic wing morphing reduces aerodynamic cost in insects, but the consequences in vertebrate flyers, particularly birds, are not well understood. We have developed a method to reconstruct a three-dimensional wing model of a bird from the wing outline and the feather shafts (rachides). The morphological and kinematic parameters can be obtained using the wing model, and the numerical or mechanical simulations may also be carried out. To test the effectiveness of the method, we recorded the hovering flight of a hummingbird (Amazilia amazilia) using high-speed cameras and reconstructed the right wing. The wing shape varied substantially within a stroke cycle. Specifically, the maximum and minimum wing areas differed by 18%, presumably due to feather sliding; the wing was bent near the wrist joint, towards the upward direction and opposite to the stroke direction; positive upward camber and the ‘washout’ twist (monotonic decrease in the angle of incidence from the proximal to distal wing) were observed during both half-strokes; the spanwise distribution of the twist was uniform during downstroke, but an abrupt increase near the wrist joint was found during upstroke.

Phosphorylation of hormone-sensitive lipase (HSL) and perilipin by protein kinase A (PKA) promotes the hydrolysis of lipids in adipocytes. Although activation of lipolysis by PKA has been well studied, inactivation via protein phosphatases is poorly understood. Here, we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a binding partner for protein phosphatase 1 and protein phosphatase 2A (PP2A), is involved in lipolysis by regulating phosphatase activity. PRIP knockout (PRIP-KO) mice displayed reduced body-fat mass as compared with wild-type mice fed with standard chow ad libitum. Most other organs appeared normal, suggesting that mutant mice had aberrant fat metabolism in adipocytes. HSL in PRIP-KO adipose tissue was highly phosphorylated compared to that in wild-type mice. Starvation of wild-type mice or stimulation of adipose tissue explants with the catabolic hormone, adrenaline, translocated both PRIP and PP2A from the cytosol to lipid droplets, but the translocation of PP2A was significantly reduced in PRIP-KO adipocytes. Consistently, the phosphatase activity associated with lipid droplet fraction in PRIP-KO adipocytes was significantly reduced and was independent of adrenaline stimulation. Lipolysis activity, as assessed by measurement of non-esterified fatty acids and glycerol, was higher in PRIP-KO adipocytes. When wild-type adipocytes were treated with a phosphatase inhibitor, they showed a high lipolysis activity at the similar level to PRIP-KO adipocytes. Collectively, these results suggest that PRIP promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of HSL and perilipin A, thus reducing PKA-mediated lipolysis.

Class V myosin (myosin-V) is a cargo transporter that moves along an actin filament with large (approximately 36-nm) successive steps. It consists of two heads that each includes a motor domain and a long (23 nm) neck domain. One of the more popular models describing these steps, the hand-over-hand model, assumes the two-headed structure is imperative. However, we previously succeeded in observing successive large steps by one-headed myosin-V upon optimizing the angle of the acto-myosin interaction. In addition, it was reported that wild type myosin-VI and myosin-IX, both one-headed myosins, can also generate successive large steps. Here, we describe the mechanical properties (stepsize and stepping kinetics) of successive large steps by one-headed and two-headed myosin-Vs. This study shows that the stepsize and stepping kinetics of one-headed myosin-V are very similar to those of the two-headed one. However, there was a difference with regards to stability against load and the number of multisteps. One-headed myosin-V also showed unidirectional movement that like two-headed myosin-V required 3.5 k(B)T from ATP hydrolysis. This value is also similar to that of smooth muscle myosin-II, a non-processive motor, suggesting the myosin family uses a common mechanism for stepping regardless of the steps being processive or non-processive. In this present paper, we conclude that one-headed myosin-V can produce successive large steps without following the hand-over-hand mechanism.