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Introduction: Single distant metastases after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) are rare. There are no guidelines for treating patients without liver tumors after resecting lung metastases. Case Presentation: Here, we report a patient with HCC recurring as a single lung metastasis 14 months after RFA. A 76-year-old woman with primary biliary cholangitis without hepatitis B virus or hepatitis C virus infection had been treated by RFA for a single 16-mm-sized HCC lesion in liver S8. Fourteen months thereafter, despite lack of intrahepatic recurrence, a single new 26-mm-sized mass was found in S10 of the right lung. The patient underwent right lower lobectomy. The histopathological diagnosis was HCC metastasis. Because no residual disease could be found, she was followed up without any additional treatment after surgery. She remains alive with no signs of recurrence 3 years later. Conclusion: HCC patients who relapse with lung metastases but without intrahepatic recurrence after RFA are extremely rare, especially when RFA is used to treat HCC lesions

Abstract Background Meningiomas and unruptured cerebral aneurysms (UCAs) rarely coexist. However, the treatment strategy remains to be fully elucidated. This report is a first report that UCA related to the tumor feeder intraoperatively ruptured when the meningioma was resected. Case presentation Herein, we present a case of meningioma coexisting with contralateral UCA related to a tumor feeder. Immediately after the meningioma was resected, intraoperative acute brain swelling due to rupture of the contralateral aneurysm appeared. The swollen brain protruding into the epidural space was resected, following contralateral ruptured aneurysm was performed by endovascular surgery. Intensive neurological treatment was administered and the patient gradually recovered. Conclusion This report highlights the possibility of intraoperative UCA rupture related to the tumor feeder when the meningioma is resected.

A 77-year-old man was referred to our hospital because of a hepatic tumor. Blood biochemistry showed elevated serum alfa-fetoprotein, protein induced by vitamin K absence-II, and carbohydrate antigen 19-9 levels. Gd-EOB-DTPA-enhanced magnetic resonance imaging revealed a 95-mm-sized tumor in liver S7. The tumor showed heterogeneous hyperintensity in the arterial phase, slightly washed out from the portal vein phase, and hypointensity in the hepatocellular phase. Post-enlargement segmental resection was performed, and the pathological diagnosis was combined hepatocellular cholangiocarcinoma. Seven months after surgery, multiple liver tumors were found, and biopsy revealed combined hepatocellular-cholangiocarcinoma. Hepatic arterial infusion chemotherapy with cisplatin was initiated. However, the patient developed a pulmonary abscess, which was treated with antibiotics. He then underwent treatment with lenvatinib, 11 months after surgery. At 8 weeks follow-up, a complete response (according to the modified Response Evaluation Criteria in Solid Tumors [RECIST]) and a partial response (RECIST version 1.1) was noted. To the best of our knowledge, thus far, only a single case of lenvatinib treatment of unresectable mixed liver cancer has been reported. In that case, lenvatinib was used as a third-line treatment. The present report is the first to describe lenvatinib as a first-line therapy for unresectable combined hepatocellular-cholangiocarcinoma, which resulted in a meaningful response. This case provides useful insights into the choice of appropriate drug treatment in this disease in the absence of randomized controlled trials of drug treatment.

Abstract Background and Aim Reliable predictors for hepatocellular carcinoma (HCC) are urgently needed. The psoas muscle index (PMI) is a simple and rapid method for evaluating muscle atrophy. Furthermore, the neutrophil/lymphocyte ratio (NLR) is a prognostic factor that is easy to calculate in everyday clinical practice. We aimed to investigate the value of the PMI and NLR as prognostic factors for patients receiving nonsurgical HCC therapy, hepatic arterial infusion chemotherapy (HAIC), transcatheter arterial chemoembolization (TACE), or molecular targeted drugs such as sorafenib (SOR) and lenvatinib (LEN). Methods We enrolled 87 patients with HCC who were treated with HAIC, TACE, SOR, or LEN. The primary endpoint was overall survival (OS) with variable PMI or NLR status. For Barcelona Clinic Liver Cancer (BCLC)‐B patients, useful prognostic factors were examined by comparing the OS between stratified groups. Prognostic factors including PMI and NLR were evaluated by univariate and multivariate analysis. Results Analysis of HAIC or TACE (HAIC/TACE) and SOR or LEN (SOR/LEN) patients showed significant differences in OS between low and high PMI. In patients treated with TACE, there was a significant difference in OS between low and high NLR. For BCLC‐B and low PMI, the prognosis was significantly worse for SOR/LEN than for TACE, although there was no difference for high PMI, suggesting that PMI may be useful for treatment selection. In addition, the prognostic formula composed of PMI, NLR, and up‐to‐seven criteria developed in the present study may be useful. Conclusion PMI and NLR are considered to be independent prognostic factors for HCC.

Background: Spinal hemangioblastomas (HBs) are rare spinal cord tumors that often involve syringomyelia, which induce various neurological symptoms. The timing of surgical therapy for symptomatic spinal HB that is associated with a better neurological prognosis has not yet been established. Case description: We report a case of cervical spinal HB with extensive syringomyelia. The symptoms gradually worsened to McCormick grade IV over the course of 17 years. The patient underwent preoperative endovascular therapy followed by surgical resection. Postoperative neurological function after 3 months and 1 year improved to McCormick grade III and grade II, respectively. Conclusion: This case may be the longest documented neurological dysfunction due to spinal HB with syringomyelia. Surgical treatment of spinal HB with very long-term neurological symptoms may improve neurological symptoms.

In order to validate a previously inferred function of the lateral prefrontal cortex (LPFC)-caudate nucleus (CdN) pathway in humans in inhibitory control and working memory, Oguchi et al used pathway-selective chemogenetic manipulation of neural activity in macaques. By suppressing pathway-specific neural activity and observing resultant behavioural changes, they provided evidence that the LPFC-CdN pathway does indeed play a role in inhibitory control.

Background: Herein, we report a case of cerebral hemorrhage in a 21-year-old nulliparous, primi gravida woman caused by posterior reversible encephalopathy syndrome (PRES), which may be associated with reversible cerebral vasoconstriction syndrome (RCVS). Case: The patient’s medical history was unremarkable, apart from the mother having had a cerebral infarction. She had been examined by a local doctor, and showed good progress; however, her blood pressure (BP) was 143/97 mmHg, she had findings of proteinuria (3+) and she had a headache on the 35th week with multiple vomiting episodes. She was admitted to our hospital after poor responsiveness and a consciousness level of GCS14, E4V4M6, a BP of 143/97 mmHg, a pulse rate of 77/min, bilateral abduction of the eyes, and left hemiplegia. Cranial computed tomography (CT) revealed cerebral hemorrhage with ventricular puncture in the right caudate nucleus. Emergency caesarean section was performed on the same day with priority given to maternal lifesaving. Acute cerebral infarction findings and PRES were observed on head magnetic resonance imaging (MRI) on the admission day 1. Head MR angiography on the 4th hospital day showed narrowing of the entire main artery trunk, suspected as RCVS. Short-term memory deficits were diagnosed post-extubation, but gradually improved. Although it became possible and hematoma in the ventricles were absorbed, left paresis and higher dysfunction were observed, and she was discharged on the 21st hospital day. Conclusion: PRES and RCVS occur simultaneously quite frequently, but require opposing treatment approaches. Both cases are reversible, but if they occur simultaneously, RCVS, which progresses slowly, may cause irreversible symptoms, thereby requiring careful treatment.

Abstract It is sometimes difficult to distinguish between multiple cancers and metastases using only diagnostic imaging, particularly when multiple hypervascular tumors are found in multiple organs. We present a case in which the preoperative histological evaluation was essential to determine the management of a hypervascular pancreatic tumor and liver tumor.

Abstract Non-alcoholic steatohepatitis (NASH)-related HCC is associated with oxidative stress. However, the mechanisms underlying the development of NASH-related HCC is unclear. MUTYH is one of the enzymes that is involved in repair of oxidative DNA damage. The aim of this study was to investigate the association between MUTYH and NASH-related hepatocarcinogenesis. MUTYH wild-type (Mutyh +/+), heterozygous (Mutyh +/−), and MUTYH-null (Mutyh −/−) mice were fed a high-fat high-cholesterol (HFHC) diet or HFHC + high iron diet (20 mice per group) for 9 months. Five of 20 Mutyh −/− mice fed an HFHC + high iron diet developed liver tumors, and they developed more liver tumors than other groups (especially vs. Mutyh+/+ fed an HFHC diet, P = 0.0168). Immunohistochemical analysis revealed significantly higher accumulation of oxidative stress markers in mice fed an HFHC + high iron diet. The gene expression profiles in the non-tumorous hepatic tissues were compared between wild-type mice that developed no liver tumors and MUTYH-null mice that developed liver tumors. Gene Set Enrichment Analysis identified the involvement of the Wnt/β-catenin signaling pathway and increased expression of c-Myc in MUTYH-null liver. These findings suggest that MUTYH deficiency is associated with hepatocarcinogenesis in patients with NASH with hepatic iron accumulation.

Abstract A 50‐year‐old woman with adrenal Cushing's syndrome and chronic hepatitis C developed an acute exacerbation of chronic hepatitis C before adrenectomy. After administration of glecaprevir/pibrentasvir was started, her transaminase levels normalized promptly and a rapid virological response also was achieved. Laparoscopic left adrenectomy was then performed safely.

Automated generation of reasonable atomic-level interface models, for example, at a grain boundary, is generally computationally intensive partly because of the three degrees of freedom in a rigid-body translation (RBT) of one side of the interface against the other. We propose an algorithm to obtain reasonable interface models using as few first-principles calculations as possible. The valence charge densities of two surface slabs constituting the interface are calculated using first-principles calculations. The surface charge densities are filtered with an exponential function using a parameter λ to obtain the reaction front. Models where the overlap of filtered charge densities between the two slabs takes a local maximum are adopted as initial models with desirable RBTs, which are then relaxed using first-principles calculations to obtain a reasonable interface model. The proposed algorithm successfully generated reasonable initial models for three out of three orientations in 75% of homointerfaces of body-centered cubic, face-centered cubic, and hexagonal close-packed non-magnetic elementary metals. For the Al {001} Σ5 twist grain boundary, the present algorithm also reproduced γ-surface features of RBTs showing correct displacement shift complete lattice periodicity. Further modifications and improvements to this method are expected to accelerate automated interface model generation from a previously unexplored approach.

Abstract Our pathological study of a case of poorly differentiated lymphocyte‐rich hepatocellular carcinoma suggested that immune checkpoint inhibitor may be an effective therapy. The histological type is an important factor in determining treatment choices.

Rewards that require high effort tend to be preferred over those that require low effort. Here, the authors show how the effort of obtaining rewards affects reward-related activity of dopamine neurons, and in turn the speed of learning stimulus-reward associations.

Abstract Background Portal annular pancreas (PAP) is a rare congenital anatomical abnormality of the pancreas in which the portal vein is encircled by aberrant parenchyma, and special attention is needed for pancreatic resections. This is the first report of central pancreatectomy (CP) in a PAP for metastatic renal cell carcinoma (RCC). Case presentation A 76-year-old man who had a history of left nephrectomy for renal cancer not otherwise specified 36 years earlier and radical cystectomy for bladder cancer 4 years earlier was incidentally found to have a pancreatic tumor and a liver tumor. The pancreatic tumor was diagnosed as metastasis of clear cell RCC, and the liver tumor was diagnosed as moderately differentiated hepatocellular carcinoma (HCC) on preoperative histological evaluation. Preoperative computed tomography imaging showed a type 3A PAP, in which the main pancreatic duct (MPD) ran ventral to the portal vein (anteportal type), and the aberrant parenchyma was located cranial to the confluence of the portal vein and splenic vein (suprasplenic type). After adhesiotomy and partial liver resection, CP was performed. With intraoperative ultrasound guidance, the aberrant parenchyma of the PAP could be preserved, avoiding additional resection. Thus, two pancreatic transections were performed, creating a single-cut margin that contained the MPD in the distal pancreas. Oncologically safe margins were confirmed by intraoperative pathological diagnosis. The distal pancreas was reconstructed by pancreatojejunostomy in the routine procedures. The pathological diagnosis of the surgical specimens was identical to the preoperative diagnosis. A postoperative pancreatic fistula (POPF) developed from the proximal stump of the head of the pancreas, necessitating no specific treatment other than drainage. The patient showed no signs or symptoms of recurrent RCC or abnormal pancreatic function for 2 years after the operation, although a histologically proven new HCC lesion developed distant from the initial site 8 months after the operation. Conclusions Precise preoperative evaluation of the tumor features and PAP allowed adequate surgical strategies to be planned. Intraoperative ultrasound was useful to minimize parenchymal resections of the PAP. CP is still a challenging procedure in terms of the development of POPF.

Introduction: Liver transplantation for hepatocellular carcinoma (HCC) has been established as a curative therapy of underlying liver disease and cancer. However, the role of liver transplantation remains controversial for patients with HCC beyond Milan criteria. Case Presentation: A man in his 50s who was diagnosed as having two foci of HCC and advanced liver cirrhosis was referred to our hospital for further examination and treatment. Both foci of HCC were located in segment 8 of the liver and measured 39 and 9 mm. Endoscopy showed esophageal varices that had a high risk of bleeding. After endoscopic ligation of the esophageal varices, he underwent transcatheter arterial chemoembolization (TACE) for downstaging of the advanced HCCs. No further liver deterioration was observed after TACE, and HCC staging was successfully downstaged to within the Milan criteria. One hundred ten days after TACE, he underwent liver transplantation; at 2.5 years after transplantation, he remains alive without HCC recurrence. Discussion/Conclusion: There are only a few treatment options available for patients with advanced HCC and severe liver damage. Multidisciplinary treatment such as locoregional treatments and prophylaxis of variceal bleeding may result in tumor downstaging, enabling radical liver transplantation without further exacerbation of liver damage.

Liquid crystalline epoxy resins have been reported to show superior mechanical and thermal properties. This high functionality is attributed to their meso- or macroscopic layered domain structure and their molecular scale ordering; hence, elucidation of the mechanism of layer formation during curing reactions is necessary for material development. In this study, the layer formation process has been investigated by the reactive coarse-grained molecular dynamics method. A mesogenic liquid crystalline epoxy and a typical non-mesogenic epoxy (diglycidyl ether of bisphenol A), mixed with a curing agent 4,4′-DDS (diaminodiphenyl sulfone), were considered. The results clearly showed that the mesogenic epoxy molecules formed a layer structure, whereas the non-mesogenic epoxy molecules remained as the amorphous structure even after the curing reactions. This difference was assumed to be caused by the straight structure of the mesogenic epoxy molecules and the strong attractive interactions between mesogenic parts. The interlayer spacing calculated by the simulation was in close agreement with the X-ray measurement. The details of the curing reaction process, e.g. the conversion and the molecular size in the mesogenic epoxy system, were also investigated. A large layer structure covered the simulation system after the stage in which the first reaction of the amine group was dominant, but the molecules were not large: the molecules were mainly attracted by the non-bond interactions. With the progress of the second reaction of the amine group, by which the tertiary amine was formed from the secondary amine, the molecular size became large and a rigid layer structure was formed over the whole simulation system. These results clearly indicated the role of the curing reactions: the first reaction produced small molecules from monomers and made them align in a layer form, and the second reaction connected them by cross-linking bonds and that produced rigid and large domains.

We calculate the stable atomic and electronic states of vanadium-substituted trirutile-type LixFeF3 (LixFe1−yVyF3) and discuss the effect of V substitution in LixFe1−yVyF3 based on the relative energy, Bader charge, and density of states. We find that the x = 0.50 configurations are the most stable for all y values studied here. In the cases where Fe and V coexist, we found that the compositions where Li insertions (x) were the same as the Fe substitutions (1 − y) were energetically stable. Our results suggest that Fe (or V) in LixFe1−yVyF3 preferentially decreases (or increases) its formal valence state with Li insertion (or extraction). This result will lead to the elucidation of the mechanism for the smooth transition from Li insertion to conversion reaction to solve the critical problem of FeF3 positive electrode material.

A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached the distant part. Therefore, complete removal of the glioma is impossible. Recently, research on the involvement of the tumor microenvironment in glioma invasion has advanced. Local hypoxia triggers cell migration as an environmental factor. The transcription factor hypoxia-inducible factor (HIF) -1α, produced in tumor cells under hypoxia, promotes the transcription of various invasion related molecules. The extracellular matrix surrounding tumors is degraded by proteases secreted by tumor cells and simultaneously replaced by an extracellular matrix that promotes infiltration. Astrocytes and microglia become tumor-associated astrocytes and glioma-associated macrophages/microglia, respectively, in relation to tumor cells. These cells also promote glioma invasion. Interactions between glioma cells actively promote infiltration of each other. Surgery, chemotherapy, and radiation therapy transform the microenvironment, allowing glioma cells to invade. These findings indicate that the tumor microenvironment may be a target for glioma invasion. On the other hand, because the living body actively promotes tumor infiltration in response to the tumor, it is necessary to reconsider whether the invasion itself is friend or foe to the brain.

Hepatic iron accumulation is generally increased in the chronic hepatitis C (CHC) liver; however, the precise mechanism of such accumulation remains unclear. We evaluated iron absorption from the gastrointestinal tract of patients with CHC and control participants. We measured the expression of a panel of molecules associated with duodenal iron absorption and serum hepcidin levels to determine the mechanism of iron accumulation in the CHC liver. We enrolled 24 patients with CHC and 9 patients with chronic gastritis without Helicobacter pylori infection or an iron metabolism disorder as control participants. An oral iron absorption test (OIAT) was administered which involved a dosage of 100 mg of sodium ferrous citrate. Serum level of hepcidin-25 was measured by liquid chromatography-tandem mass spectrometry. Ferroportin 1 (FPN) mRNA was measured by RT-PCR and FPN protein was analyzed by western blot. Samples were obtained from duodenum biopsy tissue from each CHC patient and control participant. Caco-2/TC7 cells were incubated in Costar transwells (0.4 μm pores). The OIAT showed significantly greater iron absorption in CHC patients than control participants. Serum hepcidin-25 in the CHC group was significantly lower than in the control group. Compared with control participants, duodenal FPN mRNA expression in CHC patients was significantly upregulated. The FPN mRNA levels and protein levels increased significantly in Caco-2/TC7 cell monolayers cultured in transwells with hepcidin. Lower serum hepcidin-25 levels might upregulate not only FPN protein expression but also mRNA expression in the duodenum and cause iron accumulation in patients with CHC.

Workload in the human brain can be a useful marker of internal brain state. However, due to technical limitations, previous workload studies have been unable to record brain activity via conventional electroencephalography (EEG) and magnetoencephalography (MEG) devices in mobile participants. In this study, we used a wearable EEG system to estimate workload while participants walked in a naturalistic environment. Specifically, we used the auditory steady-state response (ASSR) which is an oscillatory brain activity evoked by repetitive auditory stimuli, as an estimation index of workload. Participants performed three types of N-back tasks, which were expected to command different workloads, while walking at a constant speed. We used a binaural 500 Hz pure tone with amplitude modulation at 40 Hz to evoke the ASSR. We found that the phase-locking index (PLI) of ASSR activity was significantly correlated with the degree of task difficulty, even for EEG data from few electrodes. Thus, ASSR appears to be an effective indicator of workload during walking in an ecologically valid environment.

The aggregation of Au atoms onto a Au dimer (Au2) on a MgO (001) surface was calculated by restricted (spin-un-polarized) and unrestricted (spin-polarized) density functional theory calculations with a plane-wave basis and the approximate spin projection (AP) method. The unrestricted calculations included spin contamination errors of 0.0⁻0.1 eV, and the errors were removed using the AP method. The potential energy curves for the aggregation reaction estimated by the restricted and unrestricted calculations were different owing to the estimation of the open-shell structure by the unrestricted calculations. These results show the importance of the open-shell structure and correction of the spin contamination error for the calculation of small-cluster-aggregations and molecule dimerization on surfaces.

To precisely understand how higher cognitive functions are implemented in the prefrontal network of the brain, optogenetic and pharmacogenetic methods to manipulate the signal transmission of a specific neural pathway are required. The application of these methods, however, has been mostly restricted to animals other than the primate, which is the best animal model to investigate higher cognitive functions. In this study, we used a double viral vector infection method in the prefrontal network of the macaque brain. This enabled us to express specific constructs into specific neurons that constitute a target pathway without use of germline genetic manipulation. The double-infection technique utilizes two different virus vectors in two monosynaptically connected areas. One is a vector which can locally infect cell bodies of projection neurons (local vector) and the other can retrogradely infect from axon terminals of the same projection neurons (retrograde vector). The retrograde vector incorporates the sequence which encodes Cre recombinase and the local vector incorporates the "Cre-On" FLEX double-floxed sequence in which a reporter protein (mCherry) was encoded. mCherry thus came to be expressed only in doubly infected projection neurons with these vectors. We applied this method to two macaque monkeys and targeted two different pathways in the prefrontal network: The pathway from the lateral prefrontal cortex to the caudate nucleus and the pathway from the lateral prefrontal cortex to the frontal eye field. As a result, mCherry-positive cells were observed in the lateral prefrontal cortex in all of the four injected hemispheres, indicating that the double virus vector transfection is workable in the prefrontal network of the macaque brain.

The Skyrme-Faddeev-Niemi (SFN) model which is an O(3) σ model in three dimensional space up to fourth-order in the first derivative is regarded as a low-energy effective theory of SU(2) Yang-Mills theory. One can show from the Wilsonian renormalization group argument that the effective action of Yang-Mills theory recovers the SFN in the infrared region. However, the theory contains an additional fourth-order term which destabilizes the soliton solution. We apply the perturbative treatment to the second derivative term in order to exclude (or reduce) the ill behavior of the original action and show that the SFN model with the second derivative term possesses soliton solutions.