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Dynapenia and multimorbidity are common health problems affecting older adults. However, few studies have systematically reviewed the association between dynapenia and multimorbidity. Therefore, this systematic review aimed to provide a comprehensive overview of studies on the association between these conditions. We searched four electronic databases for relevant articles published in July 2023. The main inclusion criteria were the following: a description of dynapenia, which indicates loss of muscle strength, and a description of multimorbidity with two or more chronic diseases. Five studies met these inclusion criteria. In all five of these studies, the participants were community-dwelling older adults. All the studies showed an association between dynapenia and multimorbidity. The prevalence of dynapenia and multimorbidity ranged from 16% to 25.9%. The results of our systematic review demonstrated that dynapenia in older adults increases the risk of multimorbidity. We propose that interventions and reversible changes in dynapenia can prevent multimorbidity. (PROSPERO Registration No. CRD42023443282).

The combination of systemic amyloid A (AA) amyloidosis and xanthogranulomatous pyelonephritis (XGP) resulting from a chronic urinary tract infection is extremely rare. We herein report a case of systemic AA amyloidosis secondary to XGP for which clinical remission developed after nephrectomy. To our knowledge, this is the first case report describing the clinical improvement of systemic AA amyloidosis secondary to XGP after nephrectomy in Japan. Clinicians should be aware of this uncommon combination and search for amyloid depositions in cases of XGP.

The aluminous calcium-ferrite type phase (CF) and new aluminous phase (NAL) are thought to hold the excess alumina produced by the decomposition of garnet in MORB compositions in the lower mantle. The respective stabilities of CF and NAL in the nepheline-spinel binary (NaAlSiO 4 -MgAl 2 O 4 ) are well established. However with the addition of further components the phase relations at lower mantle conditions remain unclear. Here we investigate a range of compositions around the nepheline apex of the nepheline-kalsilite-spinel compositional join (NaAlSiO 4 -KAlSiO 4 -MgAl 2 O 4 ) at 28-78 GPa and 2000 K. Our experiments indicate that even small amounts of a kalsilite (KAlSiO 4 ) component dramatically impact phase relations. We find NAL to be stable up to at least 71 GPa in potassium-bearing compositions. This demonstrates the stabilizing effect of potassium on NAL, because NAL is not observed at pressures above 48 GPa on the nepheline-spinel binary. We also observe a broadening of the CF stability field to incorporate larger amounts of potassium with increasing pressure. For pressures below 50 GPa only minor amounts ( < 0.011 ( 1 ) K K + N a + M g ) of potassium are soluble in CF, whereas at 68 GPa, we find a solubility in CF of at least 0.088 ( 3 ) K K + N a + M g . This indicates that CF and NAL are suitable hosts of the alkali content of MORB compositions at lower mantle conditions. For sedimentary compositions at lower mantle pressures, we expect K-Hollandite to be stable in addition to CF and NAL for pressures of 28-48 GPa, based on our simplified compositions., Supplementary Information: The online version contains supplementary material available at 10.1007/s00410-024-02129-w., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s) 2024.)

Carbon nitrides featuring three-dimensional frameworks of CN 4 tetrahedra are one of the great aspirations of materials science, expected to have a hardness greater than or comparable to diamond. After more than three decades of efforts to synthesize them, no unambiguous evidence of their existence has been delivered. Here, the high-pressure high-temperature synthesis of three carbon-nitrogen compounds, tI14-C 3 N 4 , hP126-C 3 N 4 , and tI24-CN 2 , in laser-heated diamond anvil cells, is reported. Their structures are solved and refined using synchrotron single-crystal X-ray diffraction. Physical properties investigations show that these strongly covalently bonded materials, ultra-incompressible and superhard, also possess high energy density, piezoelectric, and photoluminescence properties. The novel carbon nitrides are unique among high-pressure materials, as being produced above 100 GPa they are recoverable in air at ambient conditions., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Eosinophilic granulomatous polyangiitis is a systemic vasculitis associated with bronchial asthma and eosinophilic sinusitis. Here, we describe an unusual presentation of eosinophilic granulomatous polyangiitis that initially manifested as swelling of the oral cavity floor and cervical soft tissue. A 58 year-old Japanese man was diagnosed with bronchial asthma during childhood but did not receive regular medication. Prior to this presentation, he had a persistent cough for over 1 month, and a local physician diagnosed him with bronchial asthma. However, 6 months later, his cough worsened, and a blood test revealed elevated eosinophil levels. Immediately afterward, swelling of the floor of the oral cavity and cervical soft tissue developed. Cellulitis was suspected and antimicrobial treatment was initiated; however, the symptoms persisted and abdominal pain developed. An endoscopic examination revealed duodenitis and a duodenal ulcer. The patient was diagnosed with eosinophilic granulomatous polyangiitis based on three items of the 2022 American College of Rheumatology/European College of Rheumatology classification criteria: obstructive airway disease, blood eosinophil count ≥1 × 109 cells/L, and extravascular eosinophilic infiltration with a score of 10. Oral prednisolone (70 mg/day), intravenous cyclophosphamide (500 mg/m2), and subcutaneous mepolizumab (300 mg every 4 weeks) were administered. The patient's symptoms improved after these treatments, and the eosinophil count and inflammatory marker levels declined. When swelling of the oral cavity floor and cervical soft tissue following an increase in eosinophilia and allergic symptoms occurs, it is crucial to consider the likelihood of eosinophilic granulomatous polyangiitis and collaborate with otolaryngologists and dentists to ensure its prompt identification., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: In bone scintigraphy, it is difficult to compare quantitative values, such as standardized uptake value (SUV), obtained from 2 different single-photon emission computed tomography combined with computed tomography (SPECT/CT) devices owing to differences of imaging acquisition and analysis methods. Therefore, the purpose of this study was to compare the SUV obtained from different SPECT/CT devices using the ratio to normal bone, and to analyze the correlation between them., Subjects and Methods: A total of 27 prostate cancer patients who underwent bone scintigraphy either using Symbia T16 or Symbia Intevo (Siemens Medical Solutions, Erlangen, Germany) were retrospectively analyzed. In each patient, spherical voxels of interest were placed on the following 5 reference points: humeral head (humerus), femoral neck (femur), lower part of the ilium (ilium), first lumbar vertebra (L1), fifth lumbar vertebra (L5), and the maximum SUV (SUV max ) and average SUV (SUV ave ) of these regions were measured., Results: The mean and variance of SUV ave (humerus) was the smallest on both SPECT/CT. To compare the SUV obtained from the 2 devices, the SUV ave ratio and SUV max ratio of each region were calculated as the SUV ave and SUV max of each region divided by the SUV ave of the humeral head in each patient. Median values of the SUV max ratio and SUV ave ratio of each region showed similar tendencies in both devices, with correlation coefficients between 0.93 and 1.19., Conclusion: Our results demonstrated that by expressing the quantitative value of SUV ave of each region as a ratio to the SUV ave of the humeral head, accumulation in the targeted bone can be compared even when the imaging acquisition and analysis methodsare different.

TAFRO syndrome, a rare systemic inflammatory disorder, commonly develops in an acute or subacute manner, with an aggressive clinical behavior. A substantial number of cases of TAFRO syndrome presenting with abdominal pain, and adrenal abnormalities on imaging have also been reported. A 54-year-old man developed severe acute abdominal pain. Bilateral adrenal swelling was detected on computed tomography. Although the abdominal pain resolved spontaneously, a fever and anasarca were observed. The patient was eventually diagnosed with TAFRO syndrome, and corticosteroid administration resulted in remission. TAFRO syndrome should be included in the differential diagnosis of acute abdomen and adrenal abnormalities.

Materials with an extremely low thermal and high electrical conductivity that are easy to process, foldable, and nonflammable are required for sustainable applications, notably in energy converters, miniaturized electronics, and high-temperature fuel cells. Given the inherent correlation between high thermal and high electrical conductivity, innovative design concepts that decouple phonon and electron transport are necessary. We achieved this unique combination of thermal conductivity 19.8 ± 7.8 mW/m/K (cross-plane) and 31.8 ± 11.8 mW/m/K (in-plane); electrical conductivity 4.2 S/cm in-plane in electrospun nonwovens comprising carbon as the matrix and silicon-based ceramics as nano-sized inclusions with a sea-island nanostructure. The carbon phase modulates electronic transport for high electrical conductivity, and the ceramic phase induces phonon scattering for low thermal conductivity by excessive boundary scattering. Our strategy can be used to fabricate the unique nonwoven materials for real-world applications and will inspire the design of materials made from carbon and ceramic.

Objectives: Although community studies have shown no difference between the sexes in the prevalence of fecal incontinence (FI), few direct comparisons of disease characteristics between male and female patients have been reported. The aim of this study was to determine whether characteristics of FI differ between male and female patients in Japan., Methods: Included in the study were 408 (149 men, 259 women) patients with FI who visited the Matsushima Hospital Coloproctology Center between October 2016 and September 2017. We retrospectively evaluated data on age, number of bowel movements, Bristol stool form scale, number of FI, incontinence scores, anorectal manometry, comorbidities, and history of anal surgery., Results: Maximum resting pressure and maximum squeeze pressure were found to be within normal range in significantly more male than female patients (34.9% vs. 12.4%, respectively; p < 0.0001). Irritable bowel syndrome (IBS, 20.1% vs. 9.3%; p = 0.003) and a history of anal surgery (29.5% vs. 17.5%; p = 0.02) were more prevalent among male patients than among female patients. Use of mepenzolate as treatment was significantly more common among male patients than among female patients (16.8% vs. 6.6%, respectively; p = 0.005). Responses to the various treatments were good, regardless of sex., Conclusions: FI appears to be more commonly accompanied by normal anal sphincter pressures in male patients than in female patients, and IBS and previous anal surgery appear to be more common among male patients than among female patients. FI appears to be controllable in most patients, regardless of sex., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2022 The Japan Society of Coloproctology.)

Metal nanowires (NWs) with a diameter of a few nanometers have attracted considerable attention as a promising one-dimensional nanomaterial due to their inherent flexibility and conductive properties and their weak plasmon absorption in the visible region. In a previous paper, we reported the synthesis of ultrathin 1.8 nm-diameter Au NWs using toluene-solubilized aqueous solutions of a long-chain amidoamine derivative (C18AA). This study investigates the effect of different organic solvents solubilized in C18AA aqueous solutions on the morphology of the Au products and demonstrates that solubilizing methylcyclohexane yields thick 2.7 nm-diameter Au NWs and 3.3 nm-diameter Au-Ag alloy NWs. Further, the surface-enhanced Raman scattering sensitivity of ultrathin Au NWs, thick Au NWs, and thick Au-Ag alloy NWs were assessed using 4-mercaptopyridine and found that their enhancement factors are 10 4 -10 5 and the order is Au-Ag NWs > thick Au NWs > ultrathin Au NWs., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Materials that can efficiently convert heat into electricity are widely utilized in energy conversion technologies. The existing thermoelectrics demonstrate rather limited performance characteristics at room temperature, and hence, alternative materials and approaches are very much in demand. Here, it is experimentally shown that manipulating an applied stress can greatly improve a thermoelectric power factor of layered p-type SnSe single crystals up to ≈180 µW K -2 cm -1 at room temperature. This giant enhancement is explained by a synergetic effect of three factors, such as: band-gap narrowing, Lifshitz transition, and strong sample deformation. Under applied pressure above 1 GPa, the SnSe crystals become more ductile, which can be related to changes in the prevailing chemical bonding type inside the layers, from covalent toward metavalent. Thus, the SnSe single crystals transform into a highly unconventional crystalline state in which their layered crystal stacking is largely preserved, while the layers themselves are strongly deformed. This results in a dramatic narrowing in a band gap, from E g = 0.83 to 0.50 eV (at ambient conditions). Thus, the work demonstrates a novel strategy of improving the performance parameters of chalcogenide thermoelectrics via tuning their chemical bonding type, stimulating a sample deformation and a band-structure reconstruction., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: The CpG island methylator phenotype of neuroblastoma (NBL) is strongly associated with poor prognosis and can be targeted by 5-aza-2'-deoxycytidine (5-aza-dC). Differentiation therapy is a standard maintenance therapy for high-risk NBLs. However, the in vivo effect of tamibarotene, a synthetic retinoic acid, and the efficacy of its combination with 5-aza-dC have not been studied. Here, we conducted a preclinical study to assess the in vivo tamibarotene effect and the combination., Methods: Treatment effects were analysed by in vitro cell growth and differentiation state and by in vivo xenograft suppression. Demethylated genes were analysed by DNA methylation microarrays and geneset enrichment., Results: Tamibarotene monotherapy induced neural extension and upregulation of differentiation markers of NBL cells in vitro, and tumour regression without severe side effects in vivo. 5-Aza-dC monotherapy suppressed tumour growth both in vitro and in vivo, and induced demethylation of genes related to nervous system development and function. Pre-treatment with 5-aza-dC in vitro enhanced upregulation of differentiation markers and genes involved in retinoic acid signaling. Pre-treatment with 5-aza-dC in vivo significantly suppressed tumour growth and reduced the variation in tumour sizes., Conclusions: Epigenetic drug-based differentiation therapy using 5-aza-dC and TBT is a promising strategy for refractory NBLs., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Canerpaturev (C-REV) is a highly attenuated, replication-competent, mutant strain of oncolytic herpes simplex virus type 1 that may be an effective new cancer treatment option. S-1, an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, is used as a key chemotherapeutic agent for metastatic recurrent breast cancer. Although the antitumor effects of oncolytic viruses combined with 5-FU in vivo have been reported, the detailed mechanisms are unknown. Here, we investigated the antitumor mechanism of the combination of C-REV and S-1 in triple-negative breast cancer (TNBC) in the context of tumor immunity. The combined effect of C-REV and S-1 was evaluated in a bilateral tumor model of murine TNBC 4T1 in vivo. S-1 enhanced the TNBC growth inhibitory effects of C-REV, and decreased the number of tumor-infiltrating, myeloid-derived suppressor cells (MDSCs), which suppress both innate and adaptive immune responses. Moreover, C-REV alone and in combination with S-1 significantly increased the number of CD8 + T cells in the tumor and the production of interferon γ (IFNγ) from these cells. Our findings indicate that C-REV suppresses TNBC tumor growth by inducing the expansion of effector CD8 + T cell subsets in tumors in which S-1 can inhibit MDSC function. Our study suggests that MDSCs may be an important cellular target for breast cancer treatment. The combination of C-REV and S-1 is a new approach that might be directly translated into future clinical trials against TNBC., Competing Interests: M.T. is an employee of Takara Bio Inc. The other authors declare no competing interests. The funding sponsor (Takara Bio, Inc.) had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish this paper.

Objectives: During laparoscopic right hemicolectomy, many surgeons make a small incision near the umbilicus after the routine intraperitoneal operation. In this study, we created a precursory small epigastric incision at the center of a line connecting the xiphoid process and umbilicus (the M point, an empirically determined position) at the start of surgery prior to laparoscopic manipulation. This study aimed to determine whether the small incision at the center of the M point was a suitable position through which the right hemicolon is extracted., Methods: The subjects included 148 patients who underwent laparoscopic right hemicolectomy at our hospital between January 2013 and December 2019. We measured the distance between the M point and the gastrocolic trunk (GCT) root at the base of the transverse mesocolon and the middle colic artery (MCA) root on preoperative contrast-enhanced computed tomography images., Results: We found that the GCT and MCA roots are located within a radius of 1.5 cm from the M point, suggesting that the base of the transverse mesentery was located almost directly below the M point. Comparisons based on sex differences and body mass index (BMI) also revealed that the transverse mesocolon root is closer to the M point in men and overweight patients., Conclusions: From these results, the placement of a precursory small epigastric midline incision not only allows for a safe insertion of the first laparoscopic port in a short period of time but also facilitates safe transection and anastomosis due to the proximity of the M point to the transverse mesocolon root., Competing Interests: Conflicts of Interest Drs. Ryuichi Oshima, Yukihito Kokuba, Tsukasa Shimamura, Kenta Katsumata, Yasuhito Hisatsune, Hiroyuki Negishi, Nobuyoshi Miyajima, and Takehito Otsubo have no conflicts of interest or financial ties to disclose., (Copyright © 2021 by The Japan Society of Coloproctology.)

Oncolytic viruses (OVs) remodel the tumor microenvironment by switching a "cold" tumor into a "hot" tumor with high CD8 + T-cell infiltration. CD8 + T-cell activity plays an essential role in the antitumor efficacy of OVs. However, the activity of T cells is impaired by the programmed cell death protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) interaction. To date, it remains unclear why OVs alone have a significant antitumor activity even when PD-L1 expression persists on tumor or immune cells. In this study, we found that canerpaturev (C-REV) treatment significantly suppressed tumor growth, even though it induced a significant increase in PD-L1 expression in tumors in vivo as well as persistence of high PD-L1 expression on antigen-presenting cells (macrophage and dendritic cells [DCs]). Surprisingly, we observed that C-REV treatment increased the abundance of activated CD8 + PD-1 - tumor-infiltrating lymphocytes (TILs) in the tumor on both the injected and contralateral sides, although infiltration of CD8 + PD-1 high TILs into the tumor was observed in the control group. Moreover, the difference in PD-1 expression was observed only in tumors after treatment with C-REV, whereas most CD8 + T cells in the spleen, tumor-draining lymph nodes and blood were PD-1-negative, and this did not change after C-REV treatment. In addition, changes in expression of T-cell immunoglobulin and mucin-domain containing-3 and T-cell immune-receptor with Ig and ITIM domains were not observed on CD8 + TILs after C-REV treatment. Taken together, our findings may reveal mechanisms that allow OVs to trigger an antitumor immune response, irrespective of a PD-L1-enriched tumor microenvironment, by recruitment of CD8 + PD-1 - TILs., (© 2021 Union for International Cancer Control.)

Oncolytic virus (OV) therapy is widely considered as a major breakthrough in anti-cancer treatments. In our previous study, the efficacy and safety of using C-REV for anti-cancer therapy in patients during stage I clinical trial was reported. The stimulator of interferon genes (STING)-TBK1-IRF3-IFN pathway is known to act as the central cellular host defense against viral infection. Recent reports have linked low expression levels of cGAS and STING in cancer cells to poor prognosis among patients. Moreover, downregulation of cGAS and STING has been linked to higher susceptibility to OV infection among several cancer cell lines. In this paper, we show that there is little correlation between levels of cGAS/STING expression and susceptibility to C-REV among human pancreatic cancer cell lines. Despite having a responsive STING pathway, BxPC-3 cells are highly susceptible to C-REV infection. Upon pre-activation of the STING pathway, BxPc-3 cells exhibited resistance to C-REV infection. However, without pre-activation, C-REV completely suppressed the STING pathway in BxPC-3 cells. Additionally, despite harboring defects in the STING pathway, other high-grade cancer cell lines, such as Capan-2, PANC-1 and MiaPaCa-2, still exhibited low susceptibility to C-REV infection. Furthermore, overexpression of STING in MiaPaCa-2 cells altered susceptibility to a limited extent. Taken together, our data suggest that the cGAS-STING pathway plays a minor role in the susceptibility of pancreatic cancer cell lines to C-REV infection.

The dehydration and decarbonation in the subducting slab are intricately related and the knowledge of the physical properties of the resulting C-H-O fluid is crucial to interpret the petrological, geochemical, and geophysical processes associated with subduction zones. In this study, we investigate the C-H-O fluid released during the progressive devolatilization of carbonate-bearing serpentine-polymorph chrysotile, with in situ electrical conductivity measurements at high pressures and temperatures. The C-H-O fluid produced by carbonated chrysotile exhibits high electrical conductivity compared to carbon-free aqueous fluids and can be an excellent indicator of the migration of carbon in subduction zones. The crystallization of diamond and graphite indicates that the oxidized C-H-O fluids are responsible for the recycling of carbon in the wedge mantle. The carbonate and chrysotile bearing assemblages stabilize dolomite during the devolatilization process. This unique dolomite forming mechanism in chrysotile in subduction slabs may facilitate the transport of carbon into the deep mantle.

Introduction: We validated a Japanese version of the Bladder Cancer Index (BCI) as a tool for measuring health-related quality of life (HRQOL) in bladder cancer patients treated with various surgical procedures., Methods: The reliability and validity of the Japanese BCI were examined in 397 Japanese patients with bladder cancer via cross-sectional analysis. The patients simultaneously completed the Short Form (SF)-12, EQ-5D, and the Functional Assessment of Cancer Therapy-General and Bladder (FACT-G and FACT-BL). The differences in BCI subscales among various treatment groups were analyzed., Results: This study involved 397 patients (301 males and 96 females), with a mean age of 70 years and a median disease duration of 29 months (IQR: 12-66 months). Of these patients, 221 underwent transurethral resection of a bladder tumor, and 176 patients underwent radical cystectomy (ileal conduit: 101 patients, ileal neobladder: 49, and ureterostomy: 26). Cronbach's alpha coefficient was ≥ 0.78 for all subscales, except the bowel bother subscale. Despite moderate correlations being detected between the function and bother score in urinary and bowel domains, the sexual function score was inversely correlated with the sexual bother score (r = - 0.19). A missing value percentage of > 15% was associated with old age (p < 0.05). The mean domain scores differed significantly among distinct clinically relevant treatment groups., Conclusions: Although revisions are needed to make it easier for elderly patients to comprehend, we confirmed the reliability and validity of the Japanese BCI. The Japanese BCI could be used for cross-cultural assessments of HRQOL in bladder cancer patients.

Determination of the chemical composition of the Earth's mantle is of prime importance to understand the evolution, dynamics, and origin of the Earth. However, there is a lack of experimental data on sound velocity of iron-bearing Bridgmanite (Brd) under relevant high-pressure conditions of the whole mantle, which prevents constraints on the mineralogical model of the lower mantle. To uncover these issues, we have conducted sound-velocity measurement of iron-bearing Brd in a diamond-anvil cell (DAC) up to 124 GPa using Brillouin scattering spectroscopy. Here we show that the sound velocities of iron-bearing Brd throughout the whole pressure range of lower mantle exhibit an apparent linear reduction with the iron content. Our data fit remarkably with the seismic structure throughout the lower mantle with Fe 2+ -enriched Brd, indicating that the greater part of the lower mantle could be occupied by Fe 2+ -enriched Brd. Our lower-mantle model shows a distinctive Si-enriched composition with Mg/Si of 1.14 relative to the upper mantle (Mg/Si = 1.25), which implies that the mantle convection has been inefficient enough to chemically homogenize the Earth's whole mantle., Competing Interests: The authors declare no competing interest.

Breast cancer (BC) is the most common malignant tumor in females. Development of novel biomarkers or therapeutic targets may contribute toward the improvement of a patient's prognosis. Marginal zone B and B1 cell-specific protein (MZB1) is an unfolded protein response-related chaperone and mainly exists in the endoplasmic reticulum of B lymphocytes, although little is known regarding its role in BC cells. The present study aimed to investigate the significance of MZB1 expression in BC. To begin with, MZB1 mRNA expression levels in 13 BC cell lines and two non-cancerous mammary cell lines were evaluated. Next, mRNA and protein expression of MZB1 in BC patient tumor specimens was evaluated to assess the association between expression and clinicopathological factors or prognosis. MZB1 mRNA expression levels were detectable in four estrogen receptor (ER)-positive BC cell lines. When ratios of MZB1 mRNA expression levels between BC and non-cancerous specimens were evaluated, patients with stage III disease exhibited a higher ratio than patients with stage 0/I/II disease (P=0.009). Using immunohistochemistry, patients with ER-positive BC more frequently expressed MZB1, compared with patients with ER-negative BC (P=0.003). In patients with ER-positive BC, patients with MZB1-positive BC experienced shorter disease-free survival (DFS) times than patients with negative BC (P=0.026). Multivariate analysis of DFS demonstrated that MZB1 positivity was an independent prognostic factor (P=0.022). The results of the present study suggested that MZB1 expression may be associated with a more advanced stage of BC. Furthermore, in patients with ER-positive BC, MZB1 may be a potential prognostic marker., (Copyright: © Watanabe et al.)

Although gas exsolution is a major driving force behind explosive volcanic eruptions, viscosity is critical in controlling the escape of bubbles and switching between explosive and effusive behavior. Temperature and composition control melt viscosity, but crystallization above a critical volume (>30 volume %) can lock up the magma, triggering an explosion. Here, we present an alternative to this well-established paradigm by showing how an unexpectedly small volume of nano-sized crystals can cause a disproportionate increase in magma viscosity. Our in situ observations on a basaltic melt, rheological measurements in an analog system, and modeling demonstrate how just a few volume % of nanolites results in a marked increase in viscosity above the critical value needed for explosive fragmentation, even for a low-viscosity melt. Images of nanolites from low-viscosity explosive eruptions and an experimentally produced basaltic pumice show syn-eruptive growth, possibly nucleating a high bubble number density., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Background: Neuromuscular and vascular hamartoma is a rare lesion of the small intestine, with only 26 cases reported since its initial description in 1982. No occurrence of hamartoma in the appendix has been reported until now., Case Presentation: A 60-year-old man had been suffering from longstanding right lower quadrant pain. Abdominal computed tomography showed a slight swelling of the appendix as the possible cause of his pain. Laparoscopic appendectomy with partial resection of the cecum was performed for diagnostic and therapeutic purposes. An 18 × 10-mm lesion located on the tip of the appendix was found in the resected specimen. Pathological examination showed that the lesion was covered with normal mucosa and consisted of adipose tissue, smooth muscle fibers, small vessels, and neural fibers. These findings were consistent with neuromuscular and vascular hamartoma of the appendix., Conclusion: This is the first report of neuromuscular and vascular hamartoma arising from the appendix.

Background: Frozen section of excised tissue is used to confirm removal of the etiology of primary hyperparathyroidism in the current era of intraoperative parathyroid hormone measurement and provides safeguards for surgeons. We recently reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LD) ratio in tissue suspension can accurately distinguish normal parathyroid tissue from other tissues. Therefore, we hypothesized that this ratio may also be applied to distinguish hyperfunctioning parathyroid tissue (HPT) from other tissues., Methods: We prospectively analyzed 22 patients who underwent parathyroidectomy for primary hyperparathyroidism (benign, 21; malignant, 1) from July 2018 to October 2019. In total, 27 specimens were examined. Approximately 1 mm3 of minced HPT as confirmed by frozen sections was suspended in 1 mL of normal saline and AST and LD levels were measured. The AST/LD ratios of other tissues (normal parathyroid tissue, thyroid gland, adipose tissue, and others; n = 94) were obtained from our previous report., Results: The AST/LD ratio of benign HPT was consistently higher than that of other tissues (P < 0.001). The optimal cut-off value was 0.36 according to the receiver operating characteristic curve, with 100% sensitivity and specificity. The AST/LD ratio in malignant HPT was also markedly lower than that in benign HPT., Conclusion: This method might be a new adjunct for intraoperative differentiation of HPT with an accuracy and turnaround time comparable with those of frozen sections, minimal cost, and no need for dedicated pathological staff. Additionally, this method might increase the treatment success rate in settings with limited medical resources., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tumor endothelial cells (TEC) lining tumor blood vessels actively contribute to tumor progression and metastasis. In addition to tumor cells, TEC may develop drug resistance during cancer treatment, allowing the tumor cells to survive chemotherapy and metastasize. We previously reported that TECs resist paclitaxel treatment via upregulation of ABCB1. However, whether TEC phenotypes are altered by anticancer drugs remains to be clarified. Here, we show that ABCB1 expression increases after chemotherapy in urothelial carcinoma cases. The ratio of ABCB1-positive TEC before and after first-line chemotherapy in urothelial carcinoma tissues ( n = 66) was analyzed by ABCB1 and CD31 immunostaining. In 42 cases (64%), this ratio increased after first-line chemotherapy. Chemotherapy elevated ABCB1 expression in endothelial cells by increasing tumor IL8 secretion. In clinical cases, ABCB1 expression in TEC correlated with IL8 expression in tumor cells after first-line chemotherapy, leading to poor prognosis. In vivo , the ABCB1 inhibitor combined with paclitaxel reduced tumor growth and metastasis compared with paclitaxel alone. Chemotherapy is suggested to cause inflammatory changes in tumors, inducing ABCB1 expression in TEC and conferring drug resistance. Overall, these findings indicate that TEC can survive during chemotherapy and provide a gateway for cancer metastasis. Targeting ABCB1 in TEC represents a novel strategy to overcome cancer drug resistance. SIGNIFICANCE: These findings show that inhibition of ABCB1 in tumor endothelial cells may improve clinical outcome, where ABCB1 expression contributes to drug resistance and metastasis following first-line chemotherapy., (©2020 American Association for Cancer Research.)

Background: Identification of parathyroid tissue during surgery is necessary for its preservation in situ or for autotransplantation to avoid postoperative hypoparathyroidism. Frozen sections are the gold standard for distinguishing parathyroid tissue from other tissues during thyroidectomy. Although frozen sections are very accurate, they are costly and require pathologists and technical staff. Parathyroid tissue is rich in mitochondria, which harbor Krebs-cycle enzymes such as aspartate aminotransferase. In contrast, lactate dehydrogenase is expressed ubiquitously. These 2 enzymes are measured routinely as "leaked" enzymes. We hypothesized that the aspartate aminotransferase-to-lactate dehydrogenase ratio in suspended tissue could distinguish parathyroid tissue from other tissues., Methods: We analyzed 94 specimens (43 parathyroid, 19 thyroid cancers, 13 normal lymph nodes, 10 adipose, 6 thyroid, and 3 miscellaneous tissues) from 55 patients who underwent thyroid or parathyroid surgery between March 2018 and June 2019 in our institution. Trace amounts of remnant parathyroid tissue from autotransplantation specimens were suspended in 1 mL of normal saline and measured for aspartate aminotransferase and lactate dehydrogenase. Approximately 1 mm 3 of apparently distinct tissue minced by scissors (eg, thyroid gland, metastatic lymph node, etc) or washouts of needles used for preoperative aspiration biopsy were also measured for comparison., Results: The aspartate aminotransferase-to-lactate dehydrogenase ratios in suspended parathyroid tissue specimens were consistently greater than those of other tissues (P < .001, Mann-Whitney test); 0.27 was the optimal cutoff value with 100% sensitivity and specificity., Conclusion: This method distinguished parathyroid tissue quickly and conveniently from other tissues intraoperatively with minimum cost and without dedicated pathologic staff. This methodology may serve useful in decreasing the incidence of postoperative hypoparathyroidism, especially in settings with limited access to pathologists., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Radical cystectomy (RC) is the gold standard for managing muscle-invasive and high-risknon-muscleinvasive bladder cancer, but is accompanied by non-negligible operative risk. The aim of this study is to identify preoperative variables to predict major perioperative complications after RC and to develop a nomogram using the cohort from multiple institutions in Japan. We retrospectively reviewed 668 patients who underwent open RC with ileal conduit or neobladder at Hokkaido University hospital and 20 affiliated institutions between 1997 and 2010. Complications occurring within 90 days of surgery were graded using modified Clavien classification system. We defined modified Clavien grade 3 or more as major complications and performed univariate and multivariate logistic regression analyses. Predictive accuracy of the nomogram was evaluated with the area under the receiver operating characteristics curve (AUC). A total of 528 men and 140 women were included in this study. There were a total of 160/668 patients (24%) with major perioperative complications. A multivariate model identified gender (OR : 1. 63, p=0. 04), cardiovascular comorbidity (OR : 1.48, p=0.03) and simultaneous nephroureterectomy (OR : 2.81, p=0. 01) as independent predictors. Using these 3 variables, a nomogram was developed with the AUC of 0.58. Predictive performance of our nomogram showed only fair performance ; but at least, we identified male, cardiovascular comorbidity and simultaneous nephroureterectomy as independent predictors of perioperative major complications.

Objective: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC)., Methods: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences., Results: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC., Conclusions: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control., (© The Author(s) 2019. Published by Oxford University Press.)

An unconscious 55-year-old man with a history of neurofibromatosis type 1 (NF1) was transported to the emergency department and was diagnosed with acute renal failure owing to a large bladder tumor. A submucosal tumor was also identified in the duodenum. The patient was diagnosed with a primary gastrointestinal stromal tumor (GIST) of the bladder and duodenum. After six cycles of regorafenib therapy, 18 F-fluorodeoxyglucose accumulation in the duodenal GIST on positron emission tomography-computed tomography (PET-CT) showed a partial metabolic response. Currently, no standard drug therapy for unresectable or relapsed NF1-associated GIST has been established. Regorafenib may thus be considered as and appropriate initial therapy.

The naturally occurring oncolytic herpes simplex virus canerpaturev (C-REV), formerly HF10, proved its therapeutic efficacy and safety in multiple clinical trials against melanoma, pancreatic, breast, and head and neck cancers. Meanwhile, patients with colorectal cancer, which has increased in prevalence in recent decades, continue to have poor prognosis and morbidity. Combination therapy has better response rates than monotherapy. Hence, we investigated the antitumor efficacy of cetuximab, a widely used anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and C-REV, either alone or in combination, in vitro and in an in vivo human colorectal xenograft model. In human colorectal cancer cell lines with different levels of EGFR expression (HT-29, WiDr, and CW2), C-REV exhibited cytotoxic effects in a time- and dose-dependent manner, irrespective of EGFR expression. Moreover, cetuximab had no effect on viral replication in vitro . Combining cetuximab and C-REV induced a synergistic antitumor effect in HT-29 tumor xenograft models by promoting the distribution of C-REV throughout the tumor and suppressing angiogenesis. Application of cetuximab prior to C-REV yielded better tumor regression than administration of the drug after the virus. Thus, cetuximab represents an ideal virus-associated agent for antitumor therapy, and combination therapy represents a promising antitumor strategy for human colorectal cancer.

Background/objectives: This historical control study examined the differences in the incidence of postoperative pneumonia between patients administered liquid and semi-solid nutrients after percutaneous endoscopic gastrostomy (PEG)., Subjects/methods: The medical records of adult patients who underwent PEG between March 1999 and March 2014 were investigated. The patients were administered either liquid or semi-solid nutrient and examined for gastroesophageal reflux via radiography after PEG. The study period was divided into periods I (liquid nutrient to all patients), II (semi-solid nutrient to patients with reflux and liquid nutrient to those without), and III (semi-solid nutrient to all patients). The patient characteristics and incidence of postoperative pneumonia were stratified by the periods. To assess the relationship between postoperative pneumonia and the periods, a logistic regression analysis was performed., Results: Of 370 patients enrolled, 149 were in period I, 64 in period II, and 157 in period III. Postoperative pneumonia was more frequently observed in period I (20.8%) than in periods II (7.8%) and III (10.2%). The odds ratios were higher in period I (period I vs. II: 3.10 [95% confidence intervals: 1.15-8.38]; period I vs. III: 2.32 [1.21-4.44]). The incidence of gastroesophageal reflux did not greatly differ between periods II (25.0%) and III (35.0%)., Conclusions: The incidence of postoperative pneumonia after PEG was lower in the patients administered semi-solid nutrient than in those administered liquid nutrient, suggesting that semi-solid nutrient administration to patients with PEG tubes is preferable to prevent postoperative pneumonia. Furthermore, it may be favored especially in those with gastroesophageal reflux.

Breast cancer (BC) is the most frequently diagnosed malignant tumor in women worldwide, and the development of new molecules associated with BC is essential for the management of this disease. RAS and EF-hand domain-containing ( RASEF ) encodes the GTPase enzyme that belongs to the Rab family. Although the effects of this gene have been reported in several malignant tumor types, the role of RASEF in BC has not been completely elucidated. The aim of the present study was to investigate the importance of RASEF expression in BC. RASEF mRNA expression levels were evaluated in BC and non-cancerous mammary cell lines. The association between RASEF mRNA expression levels and clinicopathological factors in 167 patients with BC were then determined. Among the 13 examined BC cell lines, ER-negative/HER2-negative cell lines expressed lower RASEF mRNA levels, when compared with the other examined cell lines (P=0.014). Of the 167 patients examined, patients with negative hormone receptor status exhibited significantly lower RASEF mRNA expression levels (P<0.001). In addition low RASEF expression in BC tissues was associated with negative estrogen receptor status (P<0.001), negative progesterone receptor status (P<0.001), and triple-negative status (P<0.001). Additionally, although the differences were not statistically significant, patients with low RASEF expression levels exhibited poorer disease-free survival (P=0.123) and overall survival (P=0.086) than other patients. The results of the present study indicate that RASEF mRNA expression levels are associated with hormone receptor status in BC.

Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic ® ) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev-C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials. Additionally, the safety of several OVs, such as pelareorep (Reolysin ® ), proved their safety and efficacy in combination with paclitaxel in breast cancer patients, but the outcomes of OVs as monotherapy against breast cancer have not provided a clear therapeutic strategy for OVs. The clinical trials of OVs against pancreatic cancer have not yet demonstrated efficacy as either monotherapy or as part of combination therapy. However, there are several oncolytic viruses that have successfully proved their efficacy in different preclinical models. In this review, we mainly focused on the oncolytic viruses that transitioned into clinical trials against melanoma, glioma, pancreatic, and breast cancers. Hence, we described the current status and future prospects of OVs clinical trials against melanoma, glioma, pancreatic, and breast cancers.

Background: Age is a prognostic factor for recurrent differentiated thyroid carcinoma (DTC) and may be related to radioactive iodine (RAI) nonavidity. Indications for molecular-targeted drugs (MTDs) are currently limited to RAI-refractory DTC. Demonstrating refractoriness to RAI, mainly indicated by RAI nonavidity, may be a barrier to the introduction of MTDs for elderly patients. The present study was conducted to evaluate the impact of age and histological type on the RAI avidity of recurrent lesions of DTC., Methods: Two hundred fifty-eight patients (189 patients with classic papillary thyroid carcinoma [cPTC], 8 patients with follicular variant of papillary thyroid carcinoma, and 61 patients with follicular thyroid carcinoma), who underwent their first RAI whole-body scanning for recurrent DTC at our institution between 2004 and 2013, were retrospectively studied. Radioactive iodine uptake was determined by visible uptake by metastatic lesion(s) in a diagnostic RAI-whole-body scan., Results: The prevalence of RAI-avid lung metastases in cPTC indicated a significant, inverse correlation with age (<55 years, 36.2%; ≥55 years, 3%; P < 0.001). By contrast, for follicular thyroid carcinoma, the prevalence of RAI avidity was not influenced by age. Similar tendencies were observed for lymph node metastases., Conclusions: Radioactive iodine avidity by metastatic lesions of cPTC in elderly patients, especially those older than 55 years, was seldom demonstrated. Adherence to a strategy of restricting MTD administration after confirmation of RAI refractoriness should be revisited for elderly patients. A strategy of omitting RAI treatment should be taken into account when considering age and histological type.

Background: Translocator protein (TSPO) imaging can be used to detect neuroinflammation (including microglial activation) after acute cerebral infarction. However, longitudinal changes of TSPO binding after mild ischemia that induces selective neuronal loss (SNL) without acute infarction are not well understood. Here, we performed TSPO imaging with [ 18 F]DPA-714 to determine the time course of neuroinflammation and SNL after mild focal ischemia., Results: Mild focal ischemia was induced by middle cerebral artery occlusion (MCAO) for 20 min. In MCAO rats without acute infarction investigated by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, in vitro ARG revealed a significant increase of [ 18 F]DPA-714 binding in the ipsilateral striatum compared with that in the contralateral side at 1, 2, 3, and 7 days after MCAO. Increased [ 18 F]DPA-714 binding was observed in the cerebral cortex penumbra, reaching maximal values at 7 days after MCAO. Activation of striatal microglia and astrocytes was observed with immunohistochemistry of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) at 2, 3, and 7 days after MCAO. SNL was investigated with Nissl staining and neuronal nuclei (NeuN) immunostaining and observed in the ischemic core region of the striatum on days 3 and 7 after MCAO. We confirmed that total distribution volume of [ 18 F]DPA-714 in the ipsilateral striatum was significantly increased at 2 and 7 days after MCAO using positron emission tomography (PET)., Conclusions: [ 18 F]DPA-714 binding measured with in vitro ARG was increased before SNL appeared, and this change was detected by in vivo PET. These findings suggest that TSPO PET imaging might be useful for detection of neuroinflammation leading to SNL after focal ischemia.

Laparoscopic adrenalectomy is the gold standard procedure for most adrenal tumors. Obesity is considered as a risk factor for surgical complications. This study aimed to evaluate whether obesity affects peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy using body mass index (BMI). This retrospective study included 98 patients who underwent transabdominal laparoscopic adrenalectomy between January 2011 and December 2016. We divided the patients into 2 groups: non-obese group (BMI < 25 kg/m2) and obese group (BMI ≥ 25 kg/m2). We assessed perioperative outcomes and postoperative complications between the groups. A total of 98 patients were analyzed (70 without obesity and 28 with obesity). There were no significant differences between the non-obese and obese groups regarding operative time (111 vs 107 min; p = 0.795), blood loss (3.5 vs 3.5 ml; p = 0.740), rate of placement of additional trocars (14.3% vs 17.9%; p = 0.657), rate of open conversion (2.6% vs 3.6%; p = 0.853), and postoperative length of hospital stay (6 vs 5 days; p = 0.237). Furthermore, obesity was not a significant risk factor for postoperative complications (postoperative bleeding, wound infection, and pneumonia). There are no significant differences in peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy in patients with obesity compared with those without obesity. Transabdominal laparoscopic adrenalectomy is feasible and safe for patients with obesity.

The analgesic mechanisms of mu opioid receptor (MOR) agonists, including receptor occupancy at the site of action, are not completely understood. The aims of the present study were to evaluate: (i) receptor occupancy in the rat brain after administration of MOR agonists; (ii) the relationship between occupancy and the antinociceptive effect. Morphine (2 or 4 mg/kg) or oxycodone (1 or 3 mg/kg) was subcutaneously administered to rats. The antinociceptive effect of these drugs was measured by the hot-plate test. MOR occupancy in the thalamus was assessed by conducting an ex vivo receptor binding assay using [ 3 H] [D-Ala 2 , N-MePhe 4 , Gly-ol]-enkephalin, followed by autoradiographic analysis. Both drugs produced antinociception in a dose-dependent manner, and these effects disappeared after the time point at which the maximal effect was elicited. Thalamic MOR occupancy was observed in a dose-dependent manner at the time point at which maximal antinociception was elicited, and relatively low occupancy was observed when the antinociceptive effect was decreasing. Good correlation between thalamic MOR occupancy and the antinociceptive effect was observed. These findings provide direct evidence for the receptor occupancy of MOR agonists at the site of action and its relationship with the analgesic effect., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Recent advance of genetic testing has contributed to the diagnosis of hereditary pheochromocytoma and paraganglioma (PPGL). The clinical characteristics of hereditary PPGL are varying among the types of mutational genes. It is still difficult to specify the pathognomonic symptoms in the case of rare genetic mutations. Here, we report the case of synchronous bilateral pheochromocytomas and paraganglioma with novel MYC associated factor X (MAX) gene mutation., Case Presentation: A 24-year-old female had hyperhidrosis and hypertension. Her urine test showed high normetanephrine and vanillylmandelic acid. Enhanced computed tomography revealed three enhanced masses in right adrenal gland, left adrenal gland, and left renal hilus. She was diagnosed with PPGL. Because 123 I-metaiodobenzylguanidine scintigraphy indicated the accumulations in the left adrenal gland mass and the left renal hilus mass and not in the right adrenal gland mass, we performed laparoscopic left adrenalectomy and extirpation of the left renal hilus mass to preserve the right adrenocortical function. However, her symptoms recurred shortly after the operation presumably due to unveiling of the activity of the right pheochromocytoma. Following right adrenalectomy as the second operation, the catecholamine levels declined to normal range. Her genetic testing indicated the novel germline mutation in MAX gene (c.70&#95;73 del AAAC/p.Lys24fs*40)., Conclusions: MAX germline mutation is recently identified as a rare cause of hereditary PPGL. The deletion mutation in MAX gene in this patient has never reported before. In the case of bilateral pheochromocytomas, the surgical indication should be decided considering each patient's genetic background. Due to the possibility for other types of malignant tumors, close follow-up is essential for MAX mutation carriers.

Breast cancer (BC) is the most common malignant tumor among women worldwide. Development of novel molecular targets is important to improve prognosis of BC patients. Derlin 3 (DERL3) gene is a member of derlin family, and its coding protein is critical to the endoplasmic reticulum-associated degradation mechanism. However, its oncological role in breast cancer remains unclear. This study evaluated DERL3 expression and function in BC. We analyzed DERL3 mRNA in 13 BC and two non-cancerous cell lines, and explored effects of DERL3 knockdown on BC proliferation, invasion and migration. We also evaluated correlation of DERL3 mRNA expression levels with clinicopathological factors and prognosis in 167 BC patients. DERL3 mRNA expression was detected in five (38%) BC cell lines. Inhibiting DERL3 expression significantly decreased proliferation and invasion in BC cells. Specimens from patients with lymph node metastasis had higher DERL3 mRNA expression than those without (P=0.030). Patients in the highest quartile for DERL3 mRNA expression (n=42) were more likely to experience shorter overall survival than other patients (P=0.032). These findings indicate that DERL3 promotes malignant phenotype in BC cells. DERL3 may serve as a potential prognostic marker and therapeutic target for BC.

Objective: To determine the characteristics of 90-day morbidity and mortality after radical cystectomy in Japanese octogenarians., Methods: A retrospective multi-institutional study. We reviewed the records of 834 patients treated by open radical cystectomy between 1997 and 2010. All complications within 90 days after surgery were sorted into the 11 categories proposed by the Memorial Sloan-Kettering Cancer Center and graded according to the modified Clavien-Dindo system. We compared the characteristics of complications between ≥80-year (n = 86) and <80-year (n = 748) groups. Multivariate regression models were used to determine the predictors of complications., Results: American Society of Anesthesiologists score III-IV was more frequent (14% vs. 6%, respectively, P < 0.0001), and ureterocutaneostomy was more frequently performed (30% vs. 21%, respectively, P = 0.0148) in the ≥80-year group compared with <80-year group. There were no significant differences in the rates of any complication, major (Grade 3-5) complication, or 90-day mortality between the two groups (≥80-year group: 70%, 21%, 3.5%, respectively, <80-year group: 68%, 22%, 2%, respectively). The ≥80-year group had fewer genitourinary complications (7% vs. 16%, respectively, P = 0.0131). Multivariate regression analyses revealed that bowel-using urinary diversion (P = 0.0031) and the operative time (P = 0.0269) were significant predictors of any grade of complications, and a male sex (P = 0.0167), annual cystectomy volume (P = 0.0284) and prior cardiovascular comorbidity (P = 0.0034) were significant predictors of major complications., Conclusions: In our experience, radical cystectomy in Japanese octogenarians caused similar perioperative comorbidities. Old age as a single criterion should not be used to abandon radical cystectomy; careful preoperative assessment is mandatory., (© The Author 2017. Published by Oxford University Press.)

Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56 , and latency-associated transcripts, and overexpresses UL53 and UL54 . In preclinical studies, HF10 replicated efficiently within tumor cells with extensive cytolytic effects and induced increased numbers of activated CD4 + and CD8 + T cells and natural killer cells within the tumor, leading to a significant reduction in tumor growth and prolonged survival rates. Investigator-initiated clinical studies of HF10 have been completed in recurrent breast carcinoma, head and neck cancer, and unresectable pancreatic cancer in Japan. Phase I trials were subsequently completed in refractory superficial cancers and melanoma in the United States. HF10 has been demonstrated to have a high safety margin with low frequency of adverse effects in all treated patients. Interestingly, HF10 antigens were detected in pancreatic carcinoma over 300 days after treatment with infiltration of CD4 + and CD8 + T cells, which enhanced the immune response. To date, preliminary results from a Phase II trial have indicated that HF10 in combination with ipilimumab (anti-CTLA-4) is safe and well tolerated, with high antitumor efficacy. Improvement of the effect of ipilimumab was observed in patients with stage IIIb, IIIc, or IV unresectable or metastatic melanoma. This review provides a concise description of the genomic functional organization of HF10 compared with talimogene laherparepvec. Furthermore, this review focuses on HF10 in cancer treatment as monotherapy as well as in combination therapy through a concise description of all preclinical and clinical data. In addition, we will address approaches for future directions in HF10 studies as cancer therapy.

An open question for solid-earth scientists is the amount of water in Earth's interior. The uppermost mantle and lower mantle contain little water because their dominant minerals, olivine and bridgmanite, have limited water storage capacity. In contrast, the mantle transition zone (MTZ) at a depth of 410 to 660 km is considered to be a potential water reservoir because its dominant minerals, wadsleyite and ringwoodite, can contain large amounts of water [up to 3 weight % (wt %)]. However, the actual amount of water in the MTZ is unknown. Given that water incorporated into mantle minerals can lower their viscosity, we evaluate the water content of the MTZ by measuring dislocation mobility, a property that is inversely proportional to viscosity, as a function of temperature and water content in ringwoodite and bridgmanite. We find that dislocation mobility in bridgmanite is faster by two orders of magnitude than in anhydrous ringwoodite but 1.5 orders of magnitude slower than in water-saturated ringwoodite. To fit the observed mantle viscosity profiles, ringwoodite in the MTZ should contain 1 to 2 wt % water. The MTZ should thus be nearly water-saturated globally.

Breast cancer (BC) is the most common malignancy among women. Identifying novel biomarkers to predict prognosis accurately is important in managing this disease. The regulatory factor X1 ( RFX1 ) gene is a member of the regulatory factor X gene family. Its protein reportedly downregulates the proto-oncogene c-myc , but its role in BC has been unclear. In this study, expression and methylation status of RFX1 were determined in BC cell lines. We then evaluated RFX1 mRNA expression levels with regard to clinicopathological factors including postoperative prognosis in 167 patients with BC. Expression of RFX1 was heterogeneous among cell lines, and we found no DNA methylation at the RFX1 promoter region. Patients were categorized into groups with high or low RFX1 expression, based on ratio of RFX1 mRNA expression in BC and adjacent non-cancerous tissues. The high RFX1 group was significantly associated with low T factor (P=0.028), earlier disease stage (P=0.015), positive expression of estrogen receptor (P=0.005) and progesterone receptor (P=0.011), negative expression of human epidermal growth factor receptor 2 (P=0.001). The high RFX1 group experienced more favorable disease-free survival (P=0.007) and overall survival (P=0.013). In multivariate analysis, RFX1 expression was an independent prognostic factor for disease-free survival. Our findings indicate that RFX1 may serve as a prognostic marker for BC.

Introduction: CT angiography has gained widespread acceptance for preoperative evaluation of blood supply in patients with colorectal cancer. However, there have been few reports that pertain to the splenic flexure, for which surgery is technically difficult. We used preoperative CT angiography and CT colonography to evaluate blood supply to the splenic flexure., Methods: We defined the splenic flexure as the junction of the distal third of the transverse colon and the proximal third of the descending colon. We reviewed 191 cases and considered the descending colon as divided into the proximal third and the distal two-thirds; we then determined which part of the descending colon the left colic artery (LCA) entered. We also considered the transverse colon as divided into the proximal two-thirds and the distal third, and evaluated which part of the transverse colon the left branch of the middle colic artery entered., Result: We classified blood supply to the splenic flexure into six types, described by the feeder vessels: type 1, the LCA (39.7%); type 2, the left branch of the middle colic artery (17.8%); type 3, the LCA and the left branch of the middle colic artery (9.9%); type 4, the accessory left colic artery (4.1%); type 5, the LCA and the accessory left colic artery (2.6%); and type 6, the marginal artery (25.6%)., Conclusion: We classified blood supply to the splenic flexure into more complex types than previous reports had. Because we dissect the lymph nodes according to the type of blood supply, knowing the type before splenic flexure surgery is crucial., (© 2016 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Aim: To clarify prognostic factors of metatstatic urothelial carcinoma treated by systemic chemotherapy in real-world clinical practice in the Japanese population., Materials and Methods: A total of 228 patients with metastatic urothelial carcinoma undergoing systemic chemotherapy between 2000 and 2013 were included in the present multi-institutional study. The gemcitabine plus cisplatin regimen was administered as first-line chemotherapy to 131 patients, whereas methotrexate, vinblastine, doxorubicin, and cisplatin or its modified regimen was given to 71 patients. Of the 228 patients, 119 received at least 2 different regimens and 22 underwent resection of metastases (metastasectomy). Multivariate survival analysis was performed using the Cox proportional hazards model. The characteristics included were age, sex, Eastern Cooperative Oncology Group performance status (PS), primary site, pathology of primary site, hemoglobin levels, lactate dehydrogenase levels, C-reactive protein levels, corrected calcium levels, estimated glomerular filtration rate levels, history of prior chemotherapy, metastatic sites, resection of primary site, number of metastatic organs, and metastasectomy., Results: The median overall survival (OS) time was 17 months. On multivariate analysis, female sex, good Eastern Cooperative Oncology Group PS at presentation, hemoglobin level≥10g/dl, and single organ metastasis were significant independent predictors of prolonged OS. For the survival effect of metastasectomy, the median OS time of the 22 patients with metastasectomy was 53 months, which was significantly longer when compared with patients not undergoing metastasectomy (15mo). After adjustment for the 4 aforementioned prognostic factors, metastasectomy still remained significant (hazard ratio: 0.364, P = 0.0008)., Conclusions: Female sex, more favorable PS at presentation, hemoglobin level>10g/dl, and single organ metastasis were favorable prognostic factors. In addition, metastasectomy was associated with long-term disease control., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Nowadays there is a high demand for specialized functional materials for specific applications in sensors or biomedicine (e.g. fMRI). For their implementation in devices, nanostructuring and integration in a composite matrix are indispensable. Spin crossover complexes are a highly promising family of switchable materials where the switching process can be triggered by various external stimuli. In this work, the synthesis of nanoparticles of the spin crossover iron(ii) coordination polymer [Fe(L)(bipy)] n (with L = 1,2-phenylenebis(iminomethylidyne)bis(2,4-pentanedionato)(2-) and bipy = 4,4'-bipyridine) is described using polystyrene-poly-4-vinylprididine blockcopolymer micelles as the template defining the final size of the nanoparticle core. A control of the spin crossover properties can be achieved by precise tuning of the crystallinity of the coordination polymer via successive addition of the starting material Fe(L) and bipy. By this we were able to synthesize nanoparticles with a core size of 49 nm and a thermal hysteresis loop width of 8 K. This is, to the best of our knowledge, a completely new approach for the synthesis of nanoparticles of coordination polymers and should be easily transferable to other coordination polymers and networks. Furthermore, the use of blockcopolymers allows a further functionalization of the obtained nanoparticles by variation of the polymer blocks and an easy deposition of the composite material on surfaces via spin coating.

Large-scale energy storage and the utilization of biomass as a sustainable carbon source are global challenges of this century. The reversible storage of hydrogen covalently bound in chemical compounds is a particularly promising energy storage technology. For this, compounds that can be sustainably synthesized and that permit high-weight% hydrogen storage would be highly desirable. Herein, we report that catalytically modified lignin, an indigestible, abundantly available and hitherto barely used biomass, can be harnessed to reversibly store hydrogen. A novel reusable bimetallic catalyst has been developed, which is able to hydrogenate and dehydrogenate N-heterocycles most efficiently. Furthermore, a particular N-heterocycle has been identified that can be synthesized catalytically in one step from the main lignin hydrogenolysis product and ammonia, and in which the new bimetallic catalyst allows multiple cycles of high-weight% hydrogen storage.

Background: Due to variations in location and size, laparoscopic surgery for paraaortic or paracaval neurogenic tumors is challenging. We evaluated the surgical outcomes, as well as surgical tips and tricks., Methods: Between 2000 and 2015, 25 procedures were performed in 24 patients. One patient underwent second surgery due to the recurrence of paraganglioma. Data were collected on the tumor diameter, tumor location, perioperative outcomes, pathology, and last-known disease status. Regarding the operative procedures, we reviewed the operative charts or videos to identify surgical tips and tricks., Results: The median tumor diameter was 5.0 cm (range 1.5-10). The tumor location was suprahilar in 10, hilar in 6, and infrahilar in 9 cases. Regarding the approach, a transperitoneal approach was selected in 24 cases and retroperitoneal approach in 1. The median operative time and blood loss were 208 min (range 73-513) and 10 mL (range 0-1020), respectively. No patient required blood transfusion or conversion to open surgery. Pathological examination revealed paraganglioma in 12, ganglioneuroma in 7, and schwannoma in 6 cases. At the last follow-up, 23 patients were free of disease, while one patient developed metastatic multiple recurrence of paraganglioma 54 months after the second laparoscopic surgery. A review of the surgical records revealed several tips and tricks, including taping the vena cava/renal vein (n = 2) being helpful for detaching a retrocaval tumor from these great vessels, or rotating the kidney to provide a favorable operative view of tumors behind the renal hilum (n = 2). In recent cases, 3D-CT was helpful for preoperative planning., Conclusions: Laparoscopic resection of paraaortic or paracaval neurogenic tumors is feasible in experienced hands. Surgeons should be familiar with detaching maneuvers around great vessels and the mobilization of adjacent organs. Careful preoperative planning is mandatory.