Search

Abstract Background Peritoneal metastasis, a major complication of colorectal cancer (CRC), often leads to poor quality of life and unfavorable outcomes. Despite numerous studies characterizing its biological features in CRC, intratumor heterogeneity and interactions between cancer cells and tumor microenvironment cells remain poorly understood. Methods To explore these aspects, we performed single-cell transcriptome analysis of matched primary tumor and peritoneal metastasis samples from a treatment-naïve patient. Results Our analysis revealed enrichment of “tip” endothelial cells in the primary tumor, driving angiogenic sprouting, whereas these cells were absent in peritoneal metastases. Moreover, cancer cells in peritoneal metastasis displayed a distinct expression signature associated with epithelial–mesenchymal transition and tumor invasiveness. Analysis of cell–cell communication between endothelial and tumor cells revealed decreased VEGF signaling and increased CXCL–ACKR1 interactions in peritoneal metastasis. Conclusions Although limited by its N-of-1 design and requiring further validation, our study provides preliminary observations suggesting that alterations in cancer-endothelial cell interactions could reduce dependence on VEGF signaling and influence immune cell infiltration in CRC peritoneal metastasis.

Objectives: Peritoneal metastasis indicates a poor prognosis in patients with colorectal cancer (CRC). Studies have shown improved prognosis in patients after removal of peritoneal dissemination, and this surgery is recommended if not excessively invasive. The aim of this study was to examine clinical outcomes and prognostic factors for R0 resected CRC with synchronous peritoneal metastasis. Methods: We analyzed data retrospectively from 250 patients with stage IV CRC who underwent R0 resection at our hospital. The patients were divided into three groups according to the type of surgery: non-resected (N), palliative primary tumor resection (P), and R0 resection (R0) groups. Overall survival (OS) and recurrence-free survival (RFS) were investigated and clinicopathological parameters were analyzed for prognostic significance. Results: The 3-year OS was 57.2% in the R0 group. The R0 group had a significantly higher 3-year OS than that in the other groups (p < 0.0001). Multivariate analysis revealed that histological type, lymphatic and venous invasion, liver metastasis, R0 resection, and perioperative chemotherapy were independent prognostic factors. The 5-year RFS in the R0 group was 26.5%. Multivariate analysis revealed that the number of peritoneal metastases and surgical procedure were independent prognostic factors. Laparoscopic surgery had better 5-year RFS in the R0 group compared with that in the open surgery group (p = 0.0044). Conclusions: R0 resection of colorectal cancer with synchronous peritoneal metastasis should be considered for improving long-term survival. The laparoscopic approach for this disease is another promising method to prolong survival in patients with R0 resection.

Abstract Background Cytoreductive surgery and chemotherapy reportedly improve the prognosis of patients with metachronous peritoneal metastases. However, the types of peritoneal metastases indicated for cytoreductive surgery remains unclear. Therefore, we aimed to clarify the category of cases for which cytoreductive surgery would be effective and report the prognosis associated with cytoreductive surgery for metachronous peritoneal metastases. Methods This study included 52 consecutive patients who underwent cytoreductive surgery for metachronous peritoneal metastases caused by colorectal cancer between January 2005 and December 2018 and fulfilled the selection criteria. The median follow-up period was 54.9 months. Relapse-free survival was calculated as the time from cytoreductive surgery of metachronous peritoneal metastases to recurrence. Overall survival was defined as the time from cytoreductive surgery of metachronous peritoneal metastases to death or the end of the follow-up period. Results The 5-year relapse-free survival rate was 30.0% and the 5-year overall survival rate was 72.3%. None of the patients underwent hyperthermic intraperitoneal chemotherapy. The analysis indicated no potential risk factors for 5-year relapse-free survival. However, for 5-year overall survival, the multivariate analysis revealed that time to diagnosis of metachronous peritoneal metastases of

Abstract Aim The aim of this study was to clarify the significance of resection of ovarian metastases from colorectal cancer and to identify the clinicopathologic characteristics. Methods In this multicenter retrospective study, we evaluated data on ovarian metastases from colorectal cancer obtained from patients at 20 centers in Japan between 2000 and 2014. We examined the impact of resection on the prognosis of patients with ovarian metastases and examined prognostic factors. Results The study included 296 patients with ovarian metastasis. The 3‐y overall survival rate was 68.6% for solitary ovarian metastases. In all cases of this cohort, the 3‐y overall survival rates after curative resection, noncurative resection, and nonresection were 65.9%, 31.8%, and 6.1%, respectively (curative resection vs noncurative resection [P

BackgroundLung subtraction iodine mapping (LSIM)-CT is a clinically useful technique that can visualize pulmonary mal-perfusion in patients with chronic thromboembolic pulmonary disease (CTEPD). However, little is known about the associations of LSIM images with hemodynamic parameters of patients with CTEPD. This study investigates a parameter of LSIM images associated with mean pulmonary arterial pressure (mPAP) and validates the association between pulmonary vascular resistance, right atrial pressure, cardiac index, and exercise capacity in patients with CTEPD.MethodsThis single-center, prospective, observational study involved 30 patients diagnosed with CTEPD using lung perfusion scintigraphy. To examine the correlation of decreased pulmonary perfusion area (DPA) with mPAP, areas with 0–10, 0–15, 0–20, and 0–30 HU in lung subtraction images were adopted in statistical analysis. The DPA to total lung volume ratio (DPA ratio, %) was calculated as the ratio of each DPA volume to the total lung volume. To assess the correlation between DPA ratios of 0–10, 0–15, 0–20, and 0–30 HU and mPAP, Spearman's rank correlation coefficient was used.ResultsThe DPA ratio of 0–10 HU had the most preferable correlation with mPAP than DPA ratios of 0–15, 0–20, and 0–30 HU (ρ = 0.440, P = 0.015). The DPA ratio of 0–10 HU significantly correlates with pulmonary vascular resistance (ρ = 0.445, P = 0.015). The receiver operating characteristic curve analysis indicated that the best cutoff value of the DPA ratio of 0–10 HU for the prediction of an mPAP of ≥30 mmHg was 8.5% (AUC, 0.773; 95% CI, 0.572–0.974; sensitivity, 83.3%; specificity, 75.0%). Multivariate linear regression analysis, which was adjusted for the main pulmonary arterial to ascending aortic diameter ratio and right ventricular to left ventricular diameter ratio, indicated that the DPA ratio of 0–10 HU was independently and significantly associated with mPAP (B = 89.7; 95% CI, 46.3–133.1, P

Objectives Sometimes, severe adhesion occurs between the rectus abdominis muscle and the ileal intestinal limbs after temporary diverting ileostomy. This can make ileostomy reversal difficult. The aim of the present study is to assess whether absorbable adhesion barrier made of oxidized regenerated cellulose (INTERCEED) could contribute to improved surgical outcomes in stoma reversal. Methods This was a single-institutional retrospective study. A total of 36 consecutive patients who underwent ileostomy reversal by a single surgeon were retrospectively reviewed. INTERCEED was inserted between the ileal limbs and the rectus abdominis muscle at the time of ileostomy creation in 12 patients. Surgical outcomes of the ileostomy reversal were compared between patients treated with and without INTERCEED. Results The degree of adhesion formation between the ileal limbs and the rectus abdominis muscles, operating time, and estimated blood loss were significantly reduced in patients treated with INTERCEED compared with those treated by the conventional approach. None of the patients in the INTERCEED group had postoperative complications after the initial surgery and ileostomy reversal. Conclusions INTERCEED is suitable for insertion between the ileal limbs and the rectus abdominis muscles because of its softness and flexibility. The use of INTERCEED for diverting ileostomy contributes to reduced adhesion formation, operative time, and blood loss in patients, and further research is needed to confirm our results.

BackgroundChronic kidney disease (CKD) impacts prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). While estimated glomerular filtration rate (eGFR) calculated from serum creatinine [eGFR (creatinine)] is affected by body muscle mass which reflects frailty, eGFR calculated from serum cystatin C [eGFR (cystatin C)] is independent of body composition, resulting in better renal function assessment.MethodsThis study included 390 consecutive patients with symptomatic severe aortic stenosis (AS) who underwent TAVI, and measured cystatin C-based eGFR at discharge. Patients were divided into two groups, with or without CKD estimated with eGFR (cystatin C). The primary endpoint of this study was the 3-year all-cause mortality after TAVI.ResultsThe median patient age was 84 years, and 32.8% patients were men. Multivariate Cox regression analysis indicated that eGFR (cystatin C), diabetes mellitus, and liver disease were independently associated with 3-year all-cause mortality. In the receiver-operating characteristic (ROC) curve, the predictive value of eGFR (cystatin C) was significantly higher than that of eGFR (creatinine). Furthermore, Kaplan–Meier estimates revealed that 3-year all-cause mortality was higher in the CKD (cystatin C) group than that in the non-CKD (cystatin C) group with log-rank p = 0.009. In contrast, there was no significant difference between the CKD (creatinine) and non-CKD (creatinine) groups with log-rank p = 0.94.ConclusionseGFR (cystatin C) was associated with 3-year all-cause mortality in patients who underwent TAVI, and it was superior to eGFR (creatinine) as a prognostic biomarker.

In Japan, major mumps outbreaks still occur every 4–5 years because of low mumps vaccine coverage (30–40%) owing to the voluntary immunization program. Herein, to prepare for a regular immunization program, we aimed to reveal the nationwide and long-term molecular epidemiological trends of the mumps virus (MuV) in Japan. Additionally, we performed whole-genome sequencing (WGS) using next-generation sequencing to assess results from conventional genotyping using MuV sequences of the small-hydrophobic (SH) gene. We analyzed 1,064 SH gene sequences from mumps clinical samples and MuV isolates collected from 25 prefectures from 1986 to 2017. The results showed that six genotypes, namely B (110), F (1), G (900), H (3), J (41), and L (9) were identified, and the dominant genotypes changed every decade in Japan since the 1980s. Genotype G has been exclusively circulating since the early 2000s. Seven clades were identified for genotype G using SH sequence-based classification. To verify the results, we performed WGS on 77 representative isolates of genotype G using NGS and phylogenetically analyzed them. Five clades were identified with high bootstrap values and designated as Japanese clade (JPC)-1, -2, -3, -4, -5. JPC-1 and -3 accounted for over 80% of the total genotype G isolates (68.3 and 13.8%, respectively). Of these, JPC-2 and -5, were newly identified clades in Japan through this study. This is the first report describing the nationwide and long-term molecular epidemiology of MuV in Japan. The results provide information about Japanese domestic genotypes, which is essential for evaluating the mumps elimination progress in Japan after the forthcoming introduction of the mumps vaccine into Japan’s regular immunization program. Furthermore, the study shows that WGS analysis using NGS is more accurate than results obtained from conventional SH sequence-based classification and is a powerful tool for accurate molecular epidemiology studies.

Objective:. This cohort study investigated short- and long-term postoperative outcomes of laparoscopic procedures for rectal cancer performed with versus without certified surgeons. Background:. In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) evaluates surgical skills deemed essential for laparoscopic surgery; however, it is unknown whether this certification contributes to procedural safety. Methods:. Outcomes of laparoscopic rectal resections for cStage II and III rectal cancer performed from 2014 to 2016 at 56 Japanese hospitals were retrospectively reviewed. The impact of having versus not having certified surgeons on postoperative complications and other short- and long-term outcomes were assessed. In cases with ESSQS-certified surgeons, surgeons attended surgery in the capacity of an operator, assistant, scope operator, or advisor. Results:. Overall, 3188 procedures were analyzed, with 2644 procedures performed with and 544 without ESSQS-certified surgeons. A multivariate logistic regression model showed that the adjusted odds ratio of postoperative complications after procedures performed with ESSQS-certified surgeons was 0.68 (95% confidence interval, 0.51–0.91; P = 0.009). The adjusted odds ratios for conversion and pathological R0 resection rates with ESSQS-certified surgeons were 0.20 (P < 0.001) and 2.10 (P = 0.04), respectively. Multiple linear regression analyses showed significantly shorter surgical duration and more harvested lymph nodes for operations performed with ESSQS-certified surgeons. Multivariate Cox regression showed that the adjusted hazard ratios for poor overall and recurrence-free survival after operations performed with ESSQS-certified surgeons were 0.88 (P = 0.35) and 1.04 (P = 0.71), respectively. Conclusions:. This study showed the superiority of the short-term postoperative results for laparoscopic rectal procedures performed with ESSQS-certified surgeons.

Anorectal melanoma (AM) is a rare and aggressive malignancy. Two main types of surgical approach for AM are abdominoperineal resection (APR) and wide local excision (WLE). Nine patients with AM underwent surgical treatment between July 2005 and October 2017 at our institution. Two of the patients were diagnosed with localized stage, four with regional stage, and three with distant stage. Laparoscopic APR was performed in six patients with localized and regional stages, whereas palliative APR and/or WLE were performed in those with distant metastasis. Both patients with localized stage lived without relapse for 6.8 years after surgery. One of the patients with regional stage had no relapse during 3.6 years of follow-up. The other three patients had recurrence and died between 6 and 32 months after surgery. The median overall survival (OS) of the cohort was 14.8 months, and the 5- and 10-year OS were 33.3% and 16.7%, respectively. The tumor at the regional stage could be removed through WLE, but preoperative diagnosis of lymph node metastasis is difficult in patients with AM. Further development of the diagnostic method is expected, and future tasks will be to establish the selection criteria to determine which surgical approach is optimal for this devastating disease.

In this study, strengthening of machinable zirconia/mica composites was attempted by exchanging interlayer ions of mica in composites for larger ions, like chemically strengthened glasses. So the sintering behavior and ion-exchange of the composites fabricated using swelling mica and the mechanical properties of the ion-exchanged composites were investigated. The dense composite was obtained by sintering at 1200°C for 1 min and was ion-exchanged in molten potassium salts at 800°C. Na+ ions in the interlayer of mica near surface of the composites were exchanged for K+ ions. However, K+ ions were not inserted in the interlayer of mica. Mica reacted with molten salts to form an amorphous phase near surface of the composites. Simultaneously with the reaction, Na+ ions in mica were discharged into molten salts and K+ ions in molten salts were penetrated into the amorphous phase. Then other crystalline phases were formed in the amorphous phase. By the ion-exchange, the cracks developed from Vickers indentation corners were obviously shortened, which is one of the evidence that the compressive stress was generated near surface. By the compressive stress, the fracture toughness (3.5 MPa・m0.5) and the bending strength (322 MPa) of the composites were increased to 5.6 MPa・m0.5 and 447 MPa, respectively.

Abstract In this study, we determined the alignment of the laser altimeter aboard Hayabusa2 with respect to the spacecraft using in-flight data. Since the laser altimeter data were used to estimate the trajectory of the Hayabusa2 spacecraft, the pointing direction of the altimeter needed to be accurately determined. The boresight direction of the receiving telescope was estimated by comparing elevations of the laser altimeter data and camera images, and was confirmed by identifying prominent terrains of other datasets. The estimated boresight direction obtained by the laser link experiment in the winter of 2015, during the Earth’s gravity assist operation period, differed from the direction estimated in this study, which fell on another part of the candidate direction; this was not selected in a previous study. Assuming that the uncertainty of alignment determination of the laser altimeter boresight was 4.6 pixels in the camera image, the trajectory error of the spacecraft in the cross- and/or along-track directions was determined to be 0.4, 2.1, or 8.6 m for altitudes of 1, 5, or 20 km, respectively.

Introduction Total mesorectal excision (TME) and postoperative adjuvant chemotherapy following neoadjuvant chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer (LARC). However, neoadjuvant CRT has no recognised impact on reducing distant recurrence, and patients suffer from a long-lasting impairment in quality of life (QOL) associated with TME. Total neoadjuvant therapy (TNT) is an alternative approach that could reduce distant metastases and increase the proportion of patients who could safely undergo non-operative management (NOM). This study is designed to compare two TNT regimens in the context of NOM for selecting a more optimal regimen for patients with LARC.Methods and analysis NOMINATE trial is a prospective, multicentre, randomised phase II selection design study. Patients must have clinical stage II or III (T3-T4Nany) LARC with distal location (≤5 cm from the anal verge or for those who are candidates for abdominoperineal resection or intersphincteric resection). Patients will be randomised to either arm A consisting of CRT (50.4 Gy with capecitabine) followed by consolidation chemotherapy (six cycles of CapeOx), or arm B consisting of induction chemotherapy (three cycles of CapeOx plus bevacizumab) followed by CRT and consolidation chemotherapy (three cycles of CapeOx). In the case of clinical complete response (cCR) or near cCR, patients will progress to NOM. Response assessment involves a combination of digital rectal examination, endoscopy and MRI. The primary endpoint is the proportion of patients achieving pathological CR or cCR≥2 years, defined as the absence of local regrowth within 2 years after the start of NOM among eligible patients. Secondary endpoints include the cCR rate, near cCR rate, rate of NOM, overall survival, distant metastasis-free survival, locoregional failure-free survival, time to disease-related treatment failure, TME-free survival, permanent stoma-free survival, safety of the treatment, completion rate of the treatment and QOL. Allowing for a drop-out rate of 10%, 66 patients (33 per arm) from five institutions will be accrued.Ethics and dissemination The study protocol was approved by Wakayama Medical University Certified Review Board in December 2020. Trial results will be published in peer-reviewed international journals and on the jRCT website.Trial registration number jRCTs051200121

Summary: Background/objective: Paraaortic lymph node (PALN) metastasis influences treatment strategy for colorectal cancer. The aims of this study were to elucidate the diagnostic value of computed tomography (CT) and positron emission tomography (PET) for PALN metastasis from left-sided colorectal cancer. Methods: A total of 108 patients who underwent radical surgery including PALN dissection were included. Size and morphology of PALN were evaluated using CT, and presence of higher FDG uptake was evaluated using PET. Findings of CT and PET were compared with pathological status. Results: The largest major axis ≥11 mm and heterogeneous internal density were predictive factors on multivariate analysis. Eighty five percent of the PALNs ≥11 mm with heterogeneous internal density were pathologically metastatic, whereas 94.1% without them were not metastatic. PET had an accuracy, sensitivity, and specificity of 85.7%, 66.7%, and 94.1%, respectively. In patients with PALNs

Abstract The precise orbit of the Hayabusa2 spacecraft with respect to asteroid Ryugu is dynamically determined using the data sets collected by the spacecraft’s onboard laser altimeter (LIght Detection And Ranging, LIDAR) and automated image tracking (AIT). The LIDAR range data and the AIT angular data play complementary roles because LIDAR is sensitive to the line-of-sight direction from Hayabusa2 to Ryugu, while the AIT is sensitive to the directions perpendicular to it. Using LIDAR and AIT, all six components of the initial state vector can be derived stably, which is difficult to achieve using only LIDAR or AIT. The coefficient of solar radiation pressure (SRP) of the Hayabusa2 spacecraft and standard gravitational parameter (GM) of Ryugu can also be estimated in the orbit determination process, by combining multiple orbit arcs at various altitudes. In the process of orbit determination, the Ryugu-fixed coordinate of the center of the LIDAR spot is determined by fitting the range data geometrically to the topography of Ryugu using the Markov Chain Monte Carlo method. Such an approach is effective for realizing the rapid convergence of the solution. The root mean squares of the residuals of the observed minus computed values of the range and brightness-centroid direction of the image are 1.36 m and 0.0270°, respectively. The estimated values of the GM of Ryugu and a correction factor to our initial SRP model are 29.8 ± 0.3 m3/s2 and 1.13 ± 0.16, respectively.

Background: Although intraplaque hemorrhage (IPH) has been identified as a key feature of rupture-prone plaques, noninvasive imaging-based features for its detection in coronary artery have not been clearly established. The aim of this study was to investigate the relationship of the ratio between the signal intensities of coronary plaque and cardiac muscle (PMR) on non-contrast T1-weighted imaging (T1WI) in magnetic resonance with IPH in the directional coronary atherectomy (DCA) specimens. Methods: Fifteen lesions from 15 patients, who underwent DCA and T1WI, were prospectively enrolled. The snap-frozen samples obtained by DCA were used for immunohistochemical staining against a protein specific to erythrocyte membranes (glycophorin A) and macrophages. The percentage of glycophorin A and macrophages was graded using a scale from 0 to 4, with higher scores indicating higher percentages. Results: PMR showed a strong positive correlation with glycophorin A scores (ρ = 0.772, p

In order to fabricate machinable zirconia ceramics for dental restorations, zirconia/mica composites were prepared by mixing zirconia and fine mica powders, compacting the powder mixtures and then conducting pressure-less sintering of green powder compacts. The composites containing 30–49 vol% mica reached approximately full density at 1150ºC. The sintering temperature was 150ºC lower than that of monolithic zirconia. The mica melted during firing at above 1000ºC and recrystallized during cooling. The melting of mica at above 1000ºC induced rearrangement of the zirconia particles and accelerated mass-transport of zirconia through the solution-precipitation, resulting in low-temperature sintering of zirconia. Dense composites containing 30–36 vol% mica were machinable using a drill made of hard metal, while those containing 49 vol% mica were sufficiently machinable with a conventional high-speed steel tool. The machinable composite containing 30 vol% mica had a bending strength of 552 MPa and a fracture toughness of 3.9 MPa·m°5.

P-glycoprotein, an ATP-binding cassette (ABC) transporter, extrudes a large variety of xenobiotics from the cell which protects tissues from toxins. Here authors solve a pair of X-ray structures of homodimeric P-glycoprotein and resolve structural elements proposed to participate in the mechanism of the transporter.

Advances in genetic sequencing and other diagnostic technologies have enabled the use of precision medicine in clinical cancer care, as well as the development of novel therapies that are targeted to specific molecular drivers of cancer. Developing these new agents and making them accessible to patients requires global clinical studies and regulatory review and approval by different national regulatory agencies. Whereas these global trials present challenges for drug developers who conduct them and regulatory agencies who oversee them, they also raise practical issues about patients with low-frequency cancers who need these therapies. A lack of uniform standards in both regulatory approval for marketing and reimbursement for approved agents across countries may make the newly developed agent either unavailable or inaccessible to patients in certain countries or regions, even if patients from those countries or regions participated in the clinical research that established the safety and efficacy of the agent. In an effort to further understand and address this need, we convened an international workshop in 2017 in North Bethesda, MD. After presentations of the individual regulatory pathways for marketing approval and reimbursement for individual nations, participants discussed expedited pathways and specific challenges for uncommon cancers. As a matter of justice, agents being developed for rare cancers, pediatric cancers, or uncommon molecular subsets of common cancers need a pragmatic, science-based regulatory policy framework to clearly specify the type and quantity of evidence needed to demonstrate efficacy from these trials and evidence to support accessibility.

Acceptor impurity doping is recognized as a functional tool to extend the capabilities and applications of β-Ga2O3. The effect of thermal annealing on photoexcited carriers was characterized by measuring the photocurrent spectra of nitrogen (N)-ion-implanted β-Ga2O3 crystals, where the N was found to cause less crystal damage to the crystal and much lower thermal diffusivity than Mg. The photocurrent intensity at 4.5–5.5 eV showed an increase with an increase in external bias, and the increase was attributed to the photo-generated non-equilibrium electrons and holes. The spectra under a positive external bias showed a distinct onset at 3.0–3.5 eV owing to optical transitions involving deep donor levels formed by the N-implantation. Spectrally integrated responsivity showed a significant change with the annealing temperature by reflecting the recovery of crystallinity and the thermal activation of N impurities. The results also indicate the formation of additional nonradiative recombination centers due to N-implantation.

Aims Acute decompensated heart failure (ADHF) can occur early after transcatheter aortic valve implantation (TAVI), but the risk factors or mechanisms associated with it have not been fully determined. This hypothesis-generating study aimed to investigate the clinical indices associated with the development of ADHF within 72 hours after TAVI and to improve procedural approaches for TAVI.Method and results In this single-centre hypothesis generating prospective observational study, we enrolled 156 consecutive patients with severe aortic stenosis who underwent TAVI between January 2016 and February 2018 at our institution. We set the primary endpoint as the new development of ADHF within 72 hours after TAVI, and clinical indices associated with it were evaluated using a multivariable logistic model. The median age of the patients was 83 (quartile range 80–86) years, 48 (30.8%) were men and the median Society of Thoracic Surgery-Predicted Risk of Mortality was 7.1 (range 5.2–10.4). Mitral stenosis (MS), defined as mean transmitral valve pressure gradient ≥5 mm Hg, was present in 15 (9.6%) patients. After TAVI, the invasive mean transaortic valve pressure gradient (mAVPG) decreased from 48 (36–66) to 7 (5–11) mm Hg, and 12 (7.7%) patients developed ADHF within 72 hours after TAVI. Multivariable logistic regression analysis showed that MS (adjusted OR, 14.227; 95% CI 2.654 to 86.698; p=0.002) and greater decreases in mAVPG (1.038; 1.003 to 1.080; p=0.044) were associated with ADHF.Conclusions MS and drastic improvement of mAVPG were associated with new development of ADHF within 72 hours after TAVI.

A-71-year-old woman was diagnosed as chronic thromboembolic pulmonary hypertension (CTEPH) accompanied by essential thrombocythemia (ET) with JAK2 V617F mutation. Blood test showed remarkable increase of platelet counts (132.9 × 10^4/μL) and elevated plasma BNP level (125.1pg/mL). Right heart catheterization (RHC) revealed remarkably high mean pulmonary arterial pressure (mPAP) of 43 mmHg. We gave her riociguat of 7.5mg, oral anticoagulants, oxygen inhalation for CTEPH, and anagrelide for ET. We performed 4 sessions of balloon pulmonary angioplasty (BPA) in 9 months RHC revealed successful hemodynamic improvement (mPAP = 21 mmHg) after final BPA procedure without riociguat. At six month later after final BPA procedure, RHC showed steadily improvement of mPAP (21 mmHg) without riociguat and oxygen inhalation. She lives well without oxygen inhalation and PH targeted therapy. This is the first report of successful treatment for a patient with CTEPH comorbid with ET with JAK2 V617F mutation by BPA.

This paper reports our experimental results on analyzing a human's goal finding process in continuous learning. The objective of this research is to make clear the mechanism of continuous learning. To fill in the missing piece of reinforcement learning framework for a learning robot, we focus on two human mental learning processes, awareness as pre-learning process and reflection as post-learning process. To observe mental learning processes of a human, we propose a new method for visualizing them by the reflection subtask for human to be aware of the goal finding process in continuous learning with invisible mazes. Two-layered task is introduced. The first layer is the main task of continuous learning designing the environmental mastery task to accomplish the goal for any environment. The second layer is the reflection subtask to make clear the goal finding process in continuous learning. The reflection cost is evaluated to analyze it.

Serial femtosecond crystallography (SFX) using X-ray free-electron lasers (XFELs) holds enormous potential for the structure determination of proteins for which it is difficult to produce large and high-quality crystals. SFX has been applied to various systems, but rarely to proteins that have previously unknown structures. Consequently, the majority of previously obtained SFX structures have been solved by the molecular replacement method. To facilitate protein structure determination by SFX, it is essential to establish phasing methods that work efficiently for SFX. Here, selenomethionine derivatization and mercury soaking have been investigated for SFX experiments using the high-energy XFEL at the SPring-8 Angstrom Compact Free-Electron Laser (SACLA), Hyogo, Japan. Three successful cases are reported of single-wavelength anomalous diffraction (SAD) phasing using X-rays of less than 1 Å wavelength with reasonable numbers of diffraction patterns (13 000, 60 000 and 11 000). It is demonstrated that the combination of high-energy X-rays from an XFEL and commonly used heavy-atom incorporation techniques will enable routine de novo structural determination of biomacromolecules.

Abstract Intracellular lipid droplets (LDs) are found in a wide variety of cell types and have been recognized as organelles with unique spherical structures. Although LDs are not stable lipid-depots, they are active sites of neutral lipid metabolism, and comprise neutral lipid or cholesterol cores surrounded by phospholipid monolayers containing specialized proteins. However, sizes and protein compositions vary between cell and tissue types. Proteins of the perilipin family have been associated with surfaces of LDs and all carry a conserved 11-mer repeat motif. Accumulating evidence indicates that all perilipins are involved in LD formation and that all play roles in LD function under differing conditions. In this brief review, we summarize current knowledge of the roles of perilipins and lipid metabolizing enzymes in a variety of mammalian cell types.

Fabrication processes have been developed to form the tunnel barriers in the suspended multi-wall carbon nanotubes (MWCNTs). Individual MWCNTs are positioned under the optical microscope to bridge them between the two metal electrodes. The tunnel barrier is formed by irradiating them with focused Ga ion beam (FIB), and its characteristics are evaluated with the resistance increase by the irradiation and the barrier height. It is found that those values depend not only on the dose of the Ga ions, but also on a diameter of the MWCNT. The single electron transistors (SETs) are fabricated by forming the double barriers in the suspended MWCNT. We find some devices show regular and stable SET behaviours.

We characterize the behavior caused by thermal annealing for C, O, Si and Mg ions implanted in GaN films by photothermal deflection spectroscopy (PDS) with respect to structural disorder and defect levels related to yellow luminescence. Although the implanted region damaged by ion bombardment is recovered by annealing, the FWHM values of ω(0002) evaluated by x-ray diffraction are almost independent of the temperature. However, the Urbach energy, as an index of structural disorder, evaluated by PDS is improved. Recovery of the structural disorder is likely to depend on the dose quantity rather than the acceleration voltage. Defect states in the band gap are reduced as well, though featured PDS signals related to the kind of implanted ion are hardly detected except for the carbon ion. The intensity of yellow luminescence at room temperature is enhanced according to the improvement of the Urbach energy and reduction of defect states in the band gap. PDS is useful for defect analysis of III-V nitride semiconductors that are electrically and optically inactive, such as ion-implantation samples, especially Mg-implanted GaN for achieving reliable p-type conduction.

We studied the emissive pits in InGaN films grown on compressive and strain-free GaN underlying layers. Pit density decreased with the full width at half maximum of ω(0002) of InGaN. The films grew on compressive and strain-free GaN underlying layers with spiral and step-flow modes, respectively. Carbon impurities accumulated inside the pits. Comparison of cathodoluminescence inside the pits and steady-state photocapacitance spectra showed that the energy level of the carbon impurities appeared at ∼2.8 eV below the conduction band (Ec) for both types of pits. Deep-level defects at Ec −2.4 eV resulting in green fluorescence emission were considered to originate from pits related to screw dislocations.

The investigation of the III-V nitride-based driving circuits is in demand for the development of GaN-based power electronic devices. In this work, we aim to grow high-quality InGaN/GaN heterojunctions on the n-channel AlGaN/GaN-on-Si high electron mobility transistor (HEMT) templates to pursue the complementary p-channel conductivity to realize the monolithic integrated circuits. As the initial step, the epitaxial growth is optimized and the structure properties are investigated by comparing with the InGaN/GaN heterojunctions grown on GaN/sapphire templates. It is found that both the In composition and relaxation degree are higher for the InGaN/GaN on the HEMT template than that on the sapphire substrate. The crystalline quality is deteriorated for the InGaN grown on the HEMT template, which is attributed to the poor-quality GaN channel in the HEMT template. Further analysis indicates that the higher In incorporation in the InGaN layer on the HEMT template may be caused by the higher relaxation degree due to the compositional pulling effect. An increase in the growth temperature by 20 °C with optimized growth condition improves the crystalline quality of the InGaN, which is comparable to that on GaN/sapphire even if it is grown on a poor-quality GaN channel.

Linear polystyrene-stabilized PdO nanoparticles (PS-PdONPs) were prepared by thermal decomposition of Pd(OAc)2 in the presence of polystyrene. X-ray diffraction (XRD) and transmission electron microscopy (TEM) indicated the production of PdO nanoparticles. The loading of palladium was determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). PS-PdONPs exhibited high catalytic activity for Mizoroki-Heck reactions under air in water and could be recycled without loss of activity.

Cellular lipid droplets (LD) are organelles involved in cellular lipid metabolism. When liver cellular components were fractionated using sucrose density gradient centrifugation, adipose differentiation-related protein (ADRP) was distributed in both the top and bottom fractions, which correspond to the LD and membranous fractions, respectively, in the mouse liver under normal feeding conditions. After overnight fasting, triacylglycerol and ADRP increased nearly 2.5-fold in the mouse liver, and a portion appeared in the intermediate-density LD (iLD) fractions. ADRP in the iLD fractions was also increased in a mouse nonalcoholic steatohepatitis model induced by methione/choline-deficient diet. When HuH-7 human hepatoma cells were incubated with oleic acid for 24 h, the amount of ADRP increased, and it was distributed in both the LD and membrane fractions. However, ADRP appeared in the iLD fractions upon treatment of HuH-7 cells with glucagon. This behavior of ADRP was cAMP-dependent, as the ADRP-positive iLD fractions were induced by dibutylyl cAMP and were blocked by protein kinase A inhibitors. A portion of ADRP colocalized microscopically with calnexin, which is present in the iLD fractions, by treatment of HuH-7 cells or human primary hepatocytes with oleic acid and glucagon, but not by treatment with oleic acid alone. Glucagon has a role in the reorganization of endoplasmic reticulum membranes to generate ADRP-associated lipid-poor particles in hepatic cells, which is related to LD formation during lipid storage.

Cytosolic lipid droplets (LDs), which are now recognized as multifunctional organelles, accumulate in leukocytes under various inflammatory conditions. However, little is known about the characteristic features of LDs in neutrophils. In this study, we show that perilipin-3 (PLIN3; formerly called TIP47) is involved in LD formation and the inflammatory response in HL-60-derived neutrophils. HL-60, a promyelocytic cell line, was differentiated into neutrophils via treatment with all-trans retinoic acid. After differentiation, cells were stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g-LPS), a major pathogen in adult periodontitis. When HL-60-derived neutrophils were stimulated with P.g-LPS, LDs increased in both number and size. In the differentiated cells, PLIN3 was induced while PLIN1, PLIN2 and PLIN5 were not detected. PGE2 production and the PLIN3 protein level were increased by the P.g-LPS treatment of the cells in a dose-dependent manner. When PLIN3 was down-regulated with siRNA treatment, LDs essentially disappeared and the level of PGE2 secreted in the cell culture medium decreased by 65%. In addition, the suppression of PLIN3 repressed the PGE2 producing enzymes; i.e., microsomal PGE synthase-1, -2 and cyclooxygenase-2. These findings indicate that PLIN3 has a pivotal role in LD-biogenesis in HL-60-derived neutrophils, and that PLIN3 is associated with the synthesis and secretion of PGE2.

BACKGROUND: Cholesterol metabolism is tightly regulated by both cholesterol and its metabolites in the mammalian liver, but the regulatory mechanism of triacylglycerol (TG) synthesis remains to be elucidated. Lipin, which catalyzes the conversion of phosphatidate to diacylglycerol, is a key enzyme involved in de novo TG synthesis in the liver via the glycerol-3-phosphate (G3P) pathway. However, the regulatory mechanisms for the expression of lipin in the liver are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Apolipoprotein E-knock out (apoE-KO) mice were fed a chow supplemented with 1.25% cholesterol (high-Chol diet). Cholesterol and bile acids were highly increased in the liver within a week. However, the amount of TG in very low-density lipoprotein (VLDL), but not in the liver, was reduced by 78%. The epididymal adipose tissue was almost eradicated in the long term. DNA microarray and real-time RT-PCR analyses revealed that the mRNA expression of all the genes in the G3P pathway in the liver was suppressed in the high-Chol diet apoE-KO mice. In particular, the mRNA and protein expression of lipin-1 and lipin-2 was markedly decreased, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), which up-regulates the transcription of lipin-1, was also suppressed. In vitro analysis using HepG2 cells revealed that the protein expression of lipin-2 was suppressed by treatment with taurocholic acid. CONCLUSIONS/SIGNIFICANCE: These data using apoE-KO mice indicate that cholesterol and its metabolites are involved in regulating TG metabolism through a suppression of lipin-1 and lipin-2 in the liver. This research provides evidence for the mechanism of lipin expression in the liver.

Many mammalian genes are clustered on the genomes, and hence the genes in the same cluster can be regulated through a common regulatory element. We indeed showed previously that the perilipin/PEX11α gene pair is transactivated tissue-selectively by PPARγ and PPARα, respectively, through a common binding site. In the present study, we identified a gene, named GSPA, neighboring a canonical PPAR target, acyl-CoA oxidase (AOX) gene. GSPA expression was induced by a peroxisome proliferator, Wy14,643, in the liver of wild-type mice, but not PPARα-null mice. GSPA and AOX share the promoter and two peroxisome proliferator-response elements. GSPA mRNA was also found in the heart and skeletal muscle, as well as 3T3-L1 cells. GSPA encodes a protein of 161 amino acids that is enriched in 3T3-L1 cells. Even other gene pairs might be regulated through common sequence elements, and conversely it would be interesting how each gene is aptly regulated in clusters.

Background: The Endoscopic Surgical Skill Qualification System (ESSQS) in Japan evaluates the surgical skills required for laparoscopic surgery as an operator as well as a supervisor. This study aimed to demonstrate the benefits of an ESSQS-certified surgeon's participation in laparoscopic rectal resections as a supervisor (assistant or advisor). Methods: We retrospectively reviewed laparoscopic resection results for cStage II and III rectal cancer performed at 56 Japanese hospitals between 2014 and 2016. We used propensity score matching to generate paired cohorts with or without an ESSQScertified supervisor at a one-to-one ratio. The impact of ESSQS-certified supervisors' participation on short-term outcomes was assessed. In the matched cohort, multivariable logistic regression analysis and multivariable regression analysis of postoperative complication rate and intraoperative blood loss were performed to further mitigate the impact of pathological factors. Results: Two groups (n = 399 each) with or without an ESSQS-certified supervisor were well matched by clinical factors. The group with an ESSQS-certified supervisor had lower blood loss (68 mL vs. 98 mL, P = 0.036) and a lower incidence of severe morbidities of Clavien- Dindo grade ≥IIIa (8.0% vs. 13.3%, P = 0.016). Multivariable logistic regression analysis and multivariable regression analysis confirmed that the attendance of ESSQS-certified supervisors reduced postoperative complication occurrence (adjusted odds ratio: 2.28, 95% confidence interval: 1.38 -- 3.80, P = 0.001) and intraoperative blood loss (estimated difference: -15.7 mL, P = 0.016). Conclusion: This study demonstrated the educational benefits of ESSQS-certified supervisors, including assistants and advisors, evidenced by their superior short-term outcomes. [ABSTRACT FROM AUTHOR]