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Summary: Background & Aims: Branched-chain amino acids (BCAAs), and the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent physical decline in older people. However, their combined effect on physical function in heart failure (HF) is unclear. This study aimed to investigate the association of BCAAs and EPA/DHA with exercise tolerance in people with HF. Methods: In total, 124 patients with HF were prospectively enrolled, and their serum BCAA and EPA/DHA levels, dietary pattern, and 6-minute walking distance (6-MWD) were assessed. Results: Lower 6-MWD quantiles contained more female patients than higher 6-MWD quantiles. Patients with a shorter 6-MWD were older and had a smaller leg circumference, higher B-type natriuretic peptide concentrations, and lower BCAA and EPA/DHA levels than those with longer 6-MWD (all P < 0.05). Patients with a shorter 6-MWD had an imbalanced dietary pattern with low intakes of oily fish, soy products, and vegetables. Meanwhile, their estimated nutrient intakes were high in saturated fatty acids and sucrose and low in polyunsaturated fatty acids and dietary fiber (all P < 0.05). According to multivariate analysis, low EPA/DHA concentrations (per 50 μg/mL decrease) [odds ratio, 95% confidence interval: 1.479 (1.025–2.137)], low dietary fiber intake (per 1 g/1000kcal decrease) [1.524 (1.098–2.119)], and high sucrose intake (per 1 g/1000kcal increase) [1.170 (1.040–1.310)] were independently associated with short 6-MWD (the lowest quantile of 6-MWD,

Eosinophilic cholecystitis (EC) is a rare condition that is characterized by eosinophilic infiltration in the gallbladder wall. We report the case of a 35-year-old woman who presented with unremitting right upper quadrant pain for 1 month. Computed tomography showed a strongly enhanced inner layer of the gallbladder wall. Magnetic resonance imaging of the same area showed low signal intensity on T2-weighted imaging. Cholecystectomy was performed, and histological examination of the surgical specimen revealed >100 eosinophils per high-power field in the inner subserosal layer. The area of these histological findings corresponded to the strongly enhanced inner layer of the gallbladder wall identified on computed tomography.

Abstract Purpose While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r. Methods A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality. Results This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1–3.1]. Conclusions Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.

Ovarian mature teratomas are benign, but malignant transformation can occur infrequently, especially in women of advanced age. The tissue that undergoes malignant change is mostly squamous cell carcinoma, although adenocarcinoma has been reported in a small number of cases. The immunostaining results of adenocarcinoma usually show a cytokeratin (CK)7−/CK20+ expression profile, corresponding to lower gastrointestinal tract origin. In this report, we describe a case of mucinous carcinoma arising from an ovarian mature teratoma showing a CK7+/CK20+ profile and discuss its imaging features. A 40-year-old woman presented to her primary care physician with abdominal distension and poor oral intake, and she was referred to our hospital. She had been diagnosed with an ovarian mature teratoma at our institution 3 years earlier. At the current presentation, pelvic magnetic resonance imaging showed a large multilocular cystic mass with adipose tissue extending into the upper abdomen. Densely packed cysts were observed inside the mass, which showed weak contrast enhancement on contrast-enhanced imaging and a mildly high signal on diffusion-weighted imaging. A portion of the cysts also showed abnormal 18F-fluorodeoxyglucose uptake (maximum standardized uptake value, 13.2) on positron emission tomography/computed tomography. The patient was subsequently diagnosed with mucinous carcinoma showing a CK7+/CK20+ profile arising from a mature teratoma by pathologic examination. This mucinous carcinoma arising from a mature teratoma showed a CK7+/CK20+ profile and took the form of densely packed multilocular cysts. In this respect, it was similar to primary ovarian epithelial mucinous carcinoma on both magnetic resonance imaging and pathologic examination despite showing a much higher maximum standardized uptake value than that of primary ovarian mucinous carcinoma. When a large ovarian teratoma contains a large multilocular cyst, the presence of densely packed multilocular cysts should not be missed even in a mass without solid components. Clinicians should consider the possibility of mucinous carcinoma showing a CK7+/CK20+ profile arising from a mature teratoma in such cases.

In the few articles describing MRI findings of myxoid leiomyosarcoma (MLMS), high signal intensity (SI) on T2-weighted images (T2WI) due to myxoid change was believed to be one of the common features. However, we encountered an MLMS with low SI similar to uterine myometrium on T2WI that subsequently grew with extremely edematous change even after 3 cycles of gonadotropin-releasing hormone agonist (GnRHa) treatment. Here we present this atypical MLMS case with radiologic-pathologic correlation. The patient was a 46-year-old woman with a chief complaint of low abdominal pain. The tumor was a pedunculated mass arising from the right anterior wall of the uterus that included a low-SI tumor-like component that partially transitioned into a peripheral high-SI component on T2WI and was diagnosed as hydropic leiomyoma. After 3 cycles of GnRHa therapy, the tumor size increased along with the size of the peripheral high-SI component on T2WI, while the size of the low-SI tumor-like component decreased. A small markedly low-SI area on both T1 and T2WI and a subtle high-SI area on fat-saturated T1WI indicating hemorrhage were present within the tumor. Pathologically, not only the peripheral high-SI component but also the low-SI tumor-like component on T2WI corresponded to MLMS, and the high-SI component was associated mainly with edematous change rather than myxoid change. MLMS may initially show low SI on T2WI and change to high SI mainly due to edematous change with rapid growth. Intratumoral hemorrhage might be the only key feature to differentiates MLMS from hydropic leiomyoma.

Abstract Background With the aging of heart failure (HF) patients, collaboration between medical and nursing care facilities is essential for HF care. The aims of this study were: (1) to identify the factors that affect willingness of nursing care staffs to cooperate with HF care; (2) to test whether the internet video education is useful in improving their willingness to collaborate. Methods A web‐based questionnaire was e‐mailed to 417 registered medical corporations that operated nursing care facilities in the prefecture where the authors work. Medical and care staff working at each facility were asked their willingness to cooperate with HF care and their problems about collaboration. Machine learning analysis was used to assess the factors associated with unwillingness to cooperate. After watching a 6‐min YouTube video explaining HF and community collaboration, we reaffirmed their willingness to cooperate. Results We received responses from 76 medical and care staff members. Before watching the video, 32.9% of participants stated that they were unwilling to cooperate with HF care. Machine learning analysis showed that job types, perceived problems of collaboration, and low opportunities to learn about HF were associated with unwillingness to cooperation. After watching the video, we observed an increase from 67.1% to 80.3% (p

Abstract Background Hepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes mellitus (T2DM). HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. HIC is originally calculated by post-load insulin and C-peptide from the oral glucose tolerance test (OGTT). However, OGTT or meal tolerance tests are a burden for patients, and OGTT is not suitable for overt diabetes due to the risk of hyperglycemia. If we can calculate the HIC from the fasting state, it is preferable. We hypothesized that fasting HIC correlates with postprandial HIC in both participants with T2DM and without diabetes. We investigated whether fasting HIC correlates with postprandial HIC in overt T2DM and nondiabetes subjects (non-DM) evaluated by using glucose clamp and meal load. Methods We performed a meal tolerance test and hyperinsulinemic–euglycemic clamp in 70 subjects, 31 patients with T2DM and 39 non-DM subjects. We calculated the postprandial C-peptide AUC-to-insulin AUC ratio as the postprandial HIC and the fasting C-peptide-to-insulin ratio as the fasting HIC. We also calculated whole-body insulin clearance from the glucose clamp test. Results The fasting HIC significantly correlated with postprandial HIC in T2DM (r_S = 0.82, P

Renomedullary interstitial cell tumor (RMICT), referred to as a medullary fibroma, is almost always asymptomatic and incidentally identified either at autopsy or upon resection of the kidney for other reasons. Although a few cases of RMICTs that are large in size and clinically symptomatic have been reported, there are few reports of RMICTs contrasting imaging findings with pathological findings. In this report, we describe a relatively large RMICT case of 3 cm in size, focusing on the radiologic-pathologic correlation.

In recent years, environmental problems such as global warming and air pollution have been recognized more seriously. Soot in the combustion products is one of the causes of air pollution. Hydrogen is now attracting attention as an alternative fuel to fossil fuels because it can be carbon-neutral fuel synthesized from renewable energy sources. If hydrogen is mixed with hydrocarbon fuels, it is possible to reduce CO2 emission. In this study, we investigated the effect of hydrogen addition on a coaxial jet diffusion flame. We used methane and propane as main fuels, and soot region was visualized using a laser induced incandescence (LII) method. In experiments, two-dimensional distribution of the soot concentration was obtained, and the maximum soot volume fraction and the total soot volume were evaluated from the LII signal. In order to clarify the effect of hydrogen addition, nitrogen was also added to the main fuel, and both results were compared.

Since hydrogen does not emit carbon dioxide when it is burned, burning hydrogen directly is one option. However, as the hydrogen ratio in the total fuel increases, the visible flame emission becomes weaker. Therefore, when using fuels with hydrogen mixed with city gas, it is necessary to have a system that monitors incomplete combustion to ensure safe use of combustion equipment. In this study, we measured the C2 and CH chemiluminescence intensities of a laminar premixed flame of hydrogen and methane. These chemiluminescence intensities were evaluated using the ICCD camera, compared with flame images taken by the commercially available digital camera. Especially, we proposed a method to determine the C2 and CH chemiluminescence intensities simultaneously in terms of the signals composed of three primary colors of red (R), green (G), and blue (B) obtained by the digital camera images. The G signal of the flame obtained by the digital camera is almost proportional to the C2 chemiluminescence intensity. The B signal also shows a good linear relationship when data are divided into two groups according to the presence or the absence of the outer flame. We concluded that if the C2 and CH chemiluminescence intensities are predicted from the G signal and the B signal.

Abstract Background Optimised antithrombotic therapy requires clinical experience and an understanding of the current guidelines. This retrospective study aimed to evaluate whether pharmacist interviews and interventions with patients taking oral antithrombotic drugs in the pharmaceutical outpatient cardiology clinic had favourable clinical outcomes including decreased bleeding. Methods The participants included patients visiting the outpatient clinic of cardiovascular internal medicine at the Kobe University Hospital from January–December 2017, and were taking oral antithrombotic medication. The observation period was from the first visit to the outpatient clinic to October 2021 or death. Patients who received pharmacist intervention more than twice were defined as the pharmacist intervention group. Two control patients per one pharmacist intervention group individual were selected from the non-intervention pool matched for age, gender and antithrombotic medication type. Results Of the 895 eligible patients, 132 were in the pharmacist intervention group and 264 were selected for the matched non-intervention group. Bleeding events according to the Bleeding Academic Research Consortium criteria over type 2 were significantly lower in the pharmacist intervention group compared with the non-intervention group (17.4% versus 28.4%, P = 0.019). There were no significant differences in mortality and heart failure hospitalisation frequency, stroke, or cardiovascular events between the groups. Multivariate analysis identified age (≥ 65 years) and pharmacist intervention as factors associated with bleeding (odds ratio = 2.29 and 0.51, respectively). Conclusion Pharmacist intervention in the outpatient clinic of cardiovascular internal medicine was effective in reducing the risk of bleeding in patients undergoing antithrombotic therapy.

Currently, a power-to-gas technology that obtains electrolytic hydrogen from renewable energy sources, synthesizes it with carbon dioxide, and converts it to methane has received a great deal of attention. It is called methanation, but there are few studies examining alternative substances to replace the raw material of hydrogen. Since hydrogen does not exist naturally, it is important to find other substances that react with carbon dioxide. We focus on flammable gases formed in oil refineries and petrochemical plants. In this study, based on chemical equilibrium calculations of the so-called NASA-CEA, we tested several gases including flammable and nonflammable gases by reacting them with carbon dioxide. Some of them are included in flare stacks. The reactants in the present gas conversion were H2O, CH3OH, C2H5OH, NH3, CH3CN, CH3N2CH3, C3H8O (1-propanol), C3H8O (2-propanol), C2H6, C2H4, C3H8, C3H6, C3H4 (allene), C3H4 (propine), C6H5OH, (CH3COOH)2, HCOOH, HF, HCl, HBr, H2S, HNO3, and SiH4. The results show that substances with more hydrogen atoms per mol of reactant, such as C3H8, CH3N2CH3, and SiH4, can produce more synthetic methane. One more finding is that graphite due to coking increases proportionately to the number of carbon atoms in the chemical formula.

BackgroundRituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions (IRs), especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H1-receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce IRs. Multiple retrospective case-control studies indicate that the second generation of histamine H1-receptor antagonists might be more effective than the first generation in suppressing IRs caused by the rituximab infusion. ObjectiveThis study aimed to assess the efficacy of first- and second-generation histamine H1-receptor antagonists for preventing IRs resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma. MethodsThis is a phase II, double-blind, active-controlled randomized trial. It will be a multicenter study conducted across 3 facilities that aims to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will receive their initial rituximab infusion. Participating patients will be administered hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H1-receptor antagonists, respectively. This will be combined with 400-mg acetaminophen tablets taken approximately 30 minutes before the first infusion of rituximab. The primary end point of this trial is to assess severe IRs, equivalent to grade 2 or higher as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, that occur within a 4-hour period after the initiation of rituximab infusion. The secondary end points include assessing the severity of the initial IR, the maximum severity of the IR, and the duration between rituximab infusion initiation and the onset of the first IR within a 4-hour period. Additionally, the trial will evaluate histamine H1-receptor antagonist–induced drowsiness using the visual analogue scale, with each patient providing their individual response. ResultsThis study began with patient recruitment in April 2023, with 17 participants enrolled as of November 12, 2023. The anticipated study completion is set for February 2026. ConclusionsThis study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H1-receptor antagonists in preventing IRs induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase III study aimed at determining the standard premedication protocol for rituximab infusion. Trial RegistrationJapan Registry of Clinical Trials jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169 International Registered Report Identifier (IRRID)DERR1-10.2196/54882

Although imaging studies are not typically performed for clinical diagnosis of cervicitis, in this case magnetic resonance imaging (MRI) was performed because a lesion with a tumor-like gross appearance was found in the uterine cervix. We present a case of cervicitis in which clinical, imaging and pathological features overlapped with those of gastric-type mucinous adenocarcinoma (GAS). The patient, a 30-year-old woman, was referred to a gynecologist with a complaint of watery vaginal discharge. On visual examination, the uterine cervix was irregularly enlarged and bled easily, suggesting cervical cancer. The next day, the patient had a fever of 39°C and blisters appeared on her vulva due to herpes simplex virus type II infection. MRI showed a diffusely enlarged cervix with poorly marginated high signal intensity on T2-weighted imaging (WI) and apparent diffusion coefficient map as well as strong enhancement on contrast-enhanced T1WI, which are findings consistent with GAS. Although a punch biopsy showed only mild atypia of the cervical glands, this was not enough to completely rule out GAS. Consequently, laser conization of the lesion was performed for definitive diagnosis, and the diagnosis of cervicitis was made. Acute cervicitis can be difficult to differentiate from GAS based on symptoms, results of cervical biopsy and MR imaging because of their overlapping features. Even when a patient presents with a lesion with tumor-like gross appearance, acute cervicitis should be included in the differential diagnosis if the result of cervical biopsy is negative, especially when accompanied by infection-like fever.

Abstract This study aimed to determine the effects of pregnancy and ontogeny on risperidone and paliperidone pharmacokinetics by assessing their serum concentrations in two subjects and constructing a customized physiologically‐based pharmacokinetic (PBPK) model. Risperidone and paliperidone serum concentrations were determined in a pregnant woman and her newborn. PBPK models for risperidone and paliperidone in adults, pediatric, and pregnant populations were developed and verified using the Simcyp simulator. These models were then applied to our two subjects, generating their “virtual twins.” Effects of pregnancy on both drugs were examined using models with fixed pharmacokinetic parameters. In the neonatal PBPK simulation, 10 different models for estimating the renal function of neonates were evaluated. Risperidone was not detected in the serum of both pregnant woman and her newborn. Maternal and neonatal serum paliperidone concentrations were between 2.05–3.80 and 0.82–1.03 ng/ml, respectively. Developed PBPK models accurately predicted paliperidone's pharmacokinetics, as shown by minimal bias and acceptable precision across populations. The individualized maternal model predicted all observed paliperidone concentrations within the 90% prediction interval. Fixed‐parameter simulations showed that CYP2D6 activity largely affects risperidone and paliperidone pharmacokinetics during pregnancy. The Flanders metadata equation showed the lowest absolute bias (mean error: 22.3% ± 6.0%) and the greatest precision (root mean square error: 23.8%) in predicting paliperidone plasma concentration in the neonatal population. Our constructed PBPK model can predict risperidone and paliperidone pharmacokinetics in pregnant and neonatal populations, which could help with precision dosing using the PBPK model‐informed approach in special populations.

For a power-to-gas (PtG) system, methanation has attracted attention to synthesize methane from carbon dioxide and hydrogen. There is a problem that heat generated by the reaction causes thermal degradation of the catalyst. Then, we have proposed a methanation reactor with circulation (MeRCi), where the temperature of the catalyst bed is controlled by recycling a part of the product gas. In this study, a one-dimensional model of the MeRCi was developed, and the methanation process was numerically simulated for assessment of reaction characteristics. The catalyst amount, the recycle ratio, and the catalyst bed length were changed. For comparison, the simulation of a straight-tube fixed-bed reactor was also simulated. Based on the gas temperature distribution of the straight-tube reactor, the simulation results show a good agreement with the experimental data, and the validity of our numerical model was confirmed. Even for the higher recycle ratio, the methane conversion rate at the reactor outlet does not change much, showing the high conversion rate within the simulation conditions. The increase of the catalyst packing density as well as the catalyst bed length enlarges the methane conversion rate. By considering the fact that the methane conversion rate is sufficiently high when the catalyst packing density is over 500 kg/m3, the reaction rate must be kept at certain level to keep the high methane conversion rate. As for the catalyst bed length, there is a minimum value at which the methane conversion rate is unexpectedly dropped where unreacted hydrogen and carbon dioxide are retained in the products.

BackgroundAcute myocardial infarction (AMI) and acute ischemic stroke (AIS) are the leading causes of death globally. Cardio-cerebral infarction (CCI) is the rare occurrence of AMI and AIS, either simultaneously or one after the other. Treatment recommendations are not clear in case of the occurrence of AMI and AIS simultaneously, especially the strategy of primary percutaneous coronary intervention (PCI).Case presentationWe report consecutive seven case series of patients with CCI who underwent primary PCI in our institute. Comorbidities, strategy of primary PCI, and outcomes were investigated. All patients presented with the chief complaints associated with stroke. Atrial fibrillation (AF) was complicated in five of CCI patients, and four of AF patients were not anticoagulated. The major causes of stroke were cardiogenic and/or hemodynamic in this case series. All patients showed total occlusion in the culprit lesion, and six patients had other diseased vessels. Thrombus aspiration was mainly chosen as the reperfusion strategy in PCI. However, only two patients were diagnosed as definitive coronary embolism, and stenting was needed in six patients due to severe atherosclerotic lesion in culprit coronary artery. Final thrombolysis in myocardial infarction (TIMI) 3 flow was achieved only in four patients. Hemorrhagic complications occurred in three patients. Two patients died during in-hospital stay, and most had to be transferred for rehabilitation.ConclusionsCCI was a rare but fatal condition in patients who underwent primary PCI. Although CCI was associated with concomitant atrial fibrillation, organic coronary stenosis requiring stenting for revascularization was present in almost all the cases. Given the complexity of coronary artery lesions and high in-hospital mortality, further investigations are needed to determine the optimal treatment strategy.

Background: Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme involved in alcohol metabolism. ALDH2 polymorphism has been reported as a risk factor for type 2 diabetes mellitus (T2DM) and is associated with liver insulin resistance due to alcohol consumption in non-diabetic individuals. Herein, we investigated the association between ALDH2 polymorphisms and insulin resistance in patients with T2DM. Methods: We performed a meal tolerance test and the hyperinsulinemic-euglycemic clamp on 71 Japanese participants: 34 patients with T2DM, and 37 non-diabetic participants. We analyzed the ALDH2 polymorphism (ALDH2 rs67); GG type was defined as the T2DM high-risk group, compared with the low-risk AG and AA groups. Results: Glucose levels were similar in the high- and low-risk T2DM groups. The high-risk group for T2DM showed a significantly higher BMI (p

The third Gravitational-Wave Transient Catalog (GWTC-3) describes signals detected with Advanced LIGO and Advanced Virgo up to the end of their third observing run. Updating the previous GWTC-2.1, we present candidate gravitational waves from compact binary coalescences during the second half of the third observing run (O3b) between 1 November 2019, 15∶00 Coordinated Universal Time (UTC) and 27 March 2020, 17∶00 UTC. There are 35 compact binary coalescence candidates identified by at least one of our search algorithms with a probability of astrophysical origin p_{astro}>0.5. Of these, 18 were previously reported as low-latency public alerts, and 17 are reported here for the first time. Based upon estimates for the component masses, our O3b candidates with p_{astro}>0.5 are consistent with gravitational-wave signals from binary black holes or neutron-star–black-hole binaries, and we identify none from binary neutron stars. However, from the gravitational-wave data alone, we are not able to measure matter effects that distinguish whether the binary components are neutron stars or black holes. The range of inferred component masses is similar to that found with previous catalogs, but the O3b candidates include the first confident observations of neutron-star–black-hole binaries. Including the 35 candidates from O3b in addition to those from GWTC-2.1, GWTC-3 contains 90 candidates found by our analysis with p_{astro}>0.5 across the first three observing runs. These observations of compact binary coalescences present an unprecedented view of the properties of black holes and neutron stars.

Abstract Aims The aim of this study was to compare the diagnostic performance of the nutritional indicators, the mini nutritional assessment‐short form (MNA‐SF), the geriatric nutritional risk index (GNRI), and the controlling nutritional status (CONUT), in heart failure (HF) patients. Methods and results Nutritional status was prospectively assessed by the aforementioned three nutritional indicators in 150 outpatients with HF who were then followed for 1 year. The prevalence of patients with the nutritional risk as assessed by the MNA‐SF, GNRI, and CONUT scores was 50.0%, 13.3%, and 54.0%, respectively. There was slight agreement of nutritional risk assessment between the MNA‐SF and GNRI scores (κ coefficient = 0.16), as well as the GNRI and CONUT scores (κ = 0.11), but poor agreement between the MNA‐SF and CONUT scores (κ = −0.09). The CONUT score had the lowest area under the curve (AUC) for the identification of low body weight, low muscle mass, and low physical function among the three indicators (all P

Abstract Background Blunt traumatic diaphragmatic hernia (TDH) is a complication of blunt diaphragmatic injury. If missed, it could lead to critical presentations, such as incarceration or strangulation of the herniated intra-abdominal organs, and thus, early surgical repair is required. Methods of the operative approach against delayed TDH remain unclear. Even with the spread of the minimally invasive approach, laparotomy has been predominantly selected for cases with hemodynamic or gastrointestinal complaints. Literature on the use of laparoscopy for repair of such cases is limited, and no study has been conducted for those with intrathoracic gastric perforation. Case presentation A 55-year-old male patient with a history of multiple traumas presented with shock, followed by left hypochondrium pain and vomiting. The patient was admitted to the emergency department of our institution and diagnosed with delayed TDH complicated by intrathoracic gastric perforation, and tension empyema. Emergency surgery using laparoscopic approach was performed, despite unstable hemodynamics, considering orientation, exposure, and operativity compared with laparotomy. Repair of the diaphragm plus total gastrectomy was successfully performed by minimally invasive management. The patient made an uneventful recovery without recurrence after 8 months. Conclusion Unstable hemodynamic conditions and intrathoracic gastric perforation could not be contraindications to laparoscopic repair in treating delayed TDH.

Abstract Background Dipeptidyl peptidase 4 inhibitor (DPP4i) is an effective medicine for type 2 diabetes mellitus (T2DM). Some articles reported DPP4i improves insulin secretion and insulin resistance. However, these effects are not well established by glucose clamp test and test meal in Japanese. We investigated the effect of DPP4i on insulin resistance and insulin secretion by using the glucose clamp test and meal tolerance test (MTT). Methods We performed a MTT, and the hyperinsulinemic-euglycemic clamp in 8 Japanese patients with T2DM. This study was a single-arm study. We measured fasting and postprandial glucose, insulin, incretins, and glucagon levels. We also measured serum adiponectin levels. Results HbA1c was significantly decreased after 3 months. The fasting and postprandial glucose levels were significantly decreased. Fasting and postprandial insulin levels were not changed. The insulin resistance derived from the glucose clamp test was significantly improved. HOMA-IR was not significantly changed. GLP-1 and GIP were significantly increased but glucagon did not change. Adiponectin was not significantly changed. Conclusions Although the number of patients was very small, these results suggested that DPP4i treatment might improve insulin resistance without changing insulin secretion.

Abstract Herein, we describe a case of olmesartan‐related sprue‐like enteropathy in which improvement in villous atrophy was confirmed by small‐bowel capsule endoscopy (CE). We successfully treated a 66‐year‐old man with a chief complaint of loose diarrhea. The patient had persistent watery diarrhea 10 times a day and experienced a weight loss of 9 kg in 3 months. An abdominal computed tomography scan showed fluid retention in the small intestine. Blood test results revealed no inflammatory reaction. Esophagogastroduodenoscopy detected villous atrophy in the stomach and duodenum. Moreover, small‐bowel CE showed villous atrophy in about two‐thirds of the small intestine. Based on other examinations, hyperthyroidism, intestinal tuberculosis, intestinal amyloidosis, and intestinal malignant lymphoma were ruled out. Therefore, the patient was suspected of having an olmesartan‐related sprue‐like disease. Early after discontinuation of medication, diarrhea symptoms improved, and a repeat CE indicated improvements in small intestinal villous atrophy. Since the patient had been administered olmesartan for a long time and CE showed villous atrophy throughout the small bowel, we suspected him of having the olmesartan‐associated sprue‐like disease. The findings of gastric mucosa atrophy on esophagogastroduodenoscopy may lead to an early diagnosis of this disease. Olmesartan‐related sprue‐like enteropathy should be considered as a differential diagnosis in patients with chronic severe watery diarrhea.

So far, diesel particulate filters (DPFs) have been widely used to collect diesel particulates including soot in the exhaust after-treatment. However, as the soot is continuously collected in the porous filter, the exhaust pressure (pressure drop) increases. To optimize the filter design for reducing its pressure drop, we need a numerical simulation. In this study, we simulated the particle-laden flow across the DPF. Structure of SiC-DPF was obtained by an X-ray CT technique. We conducted the numerical simulation by changing the soot aggregation diameter (simply called soot size), and evaluated the time-variation of the pressure drop. For discussing the soot deposition process, the contributions of the Brownian diffusion and the interception effect were separately estimated. Especially, we focused on the soot deposition region which could affect the pressure drop, together with the soot cake permeability and the soot packing density. Results show that, as the soot size is smaller, more soot is trapped. As a result, the shift from the depth filtration to the surface filtration is observed earlier. Therefore, for discussing the pressure drop, it is important to consider where the soot deposition occurs as well as the deposited soot mass in the filter.

Endothelial nitric oxide synthase (eNOS) is a critical regulatory enzyme that controls vascular tone via the production of nitric oxide. Although thrombin also modulates vascular tone predominantly via the activation of protease-activated receptors (PARs), the time course and mechanisms involved in how thrombin controls eNOS enzymatic activity are unknown. eNOS enzymatic activity is enhanced by the phosphorylation of eNOS-Ser1177 and reduced by the phosphorylation of eNOS-Thr495. In this study, we hypothesized that thrombin regulates vascular tone through the differential phosphorylation of eNOS. Using rat descending aorta, we show that thrombin modulates vascular tone in an eNOS-dependent manner via activated PAR-1. We also show that thrombin causes a temporal biphasic response. Protein kinase C (PKC) is associated with second phase of thrombin-induced response. Western blot analysis demonstrated thrombin phosphorylated eNOS-Ser1177 and eNOS-Thr495 in human umbilical vein endothelial cells. A PKC inhibitor suppressed the thrombin-induced phosphorylation of eNOS-Thr495, but not that of eNOS-Ser1177. Our results suggest that thrombin induces a temporal biphasic vascular response through the differential phosphorylation of eNOS via activated PAR-1. Thrombin causes transient vasorelaxation by the phosphorylation of eNOS-Ser1177, and subsequent attenuation of vasorelaxation by the phosphorylation of eNOS-Thr495 via PKC, leading to the modulation of vascular tone.

Abstract Aims Increased left ventricular mass index (LVMI) disproportionate to electrocardiographic QRS voltage has been reported to be associated with cardiac fibrosis and amyloid infiltration to myocardium. This study aimed to assess whether the LVMI‐to‐QRS‐voltage ratio predicts clinical outcomes in heart failure with preserved ejection fraction (HFpEF). Methods and results The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of Japanese patients hospitalized with HFpEF (EF ≥ 50%). LVMI was assessed by echocardiography using the cube formula. QRS voltage was assessed by Sokolow–Lyon voltage criteria. We divided 290 patients in the registry who met inclusion criteria into five groups according to the quintile values of their LVMI‐to‐QRS‐voltage ratio. In the highest quintile group (≥71.8 g/m2/mV), approximately 50% of the patients had concentric hypertrophy and 30% had eccentric hypertrophy. These patients had the highest proportion of atrial fibrillation (61.4%) and history of pacemaker implantation (12.1%) among the five groups (P

Abstract Background Potentially inappropriate medications (PIMs) and polypharmacy in older adults lead to increase the risk of adverse drug events. This study aimed to evaluate the effectiveness of pharmacist intervention combining the criteria for detecting PIMs with the deprescribing algorithm on correcting PIMs, reducing the number of medications, and readmissions. Methods A prospective observational study was conducted at a Japanese University Hospital enrolling new inpatients aged ≥65 years prescribed ≥1 daily medication. Pharmacists detected PIMs based on the criteria combined the screening tool of older persons’ potentially inappropriate prescriptions criteria version 2 with the screening tool for older persons’ appropriate prescriptions for Japanese, examined changes using the deprescribing algorithm, and suggested changes to the physician. The proportion of patients whose number of medications was reduced at discharge and the rate of readmissions within 30 and 90 days were compared between patients without PIMs (without PIMs group), patients who were not suggested to change PIMs (no suggestions group), and patients who were suggested to change PIMs (suggested group). Results The study enrolled 544 patients (median age 75.0 years, 54.4% males, median number of medications 6.0/patient). The number of patients with PIMs was 240 (44.1%), and 304 patients had no PIMs (without PIMs group). Among the patients with PIMs, 125 (52.1%) patients received pharmacist suggestions to change ≥1 PIMs (suggested group), and 115 patients received no suggestions for change (no suggestions group). The total number of PIMs was 432, of which changes were suggested for 189 (43.8%). Of these 189 cases, 172 (91.0%) were changed. The proportion of patients whose number of medications was reduced was significantly higher in the suggested group than in the without PIMs group and the no suggestions group [56.8% (71/125) vs. 26.6% (81/304) and 19.1% (22/115), respectively; P

Gastric plexiform fibromyxoma is extremely rare. In our case, upper gastrointestinal endoscopy of a 41-year-old woman patient revealed a 1-cm submucosal tumor (SMT) in the greater curvature of the lower body of the stomach. On contrast-enhanced computed tomography, the tumor was hypervascular in the arterial phase with continuous enhancement in the post-venous phase. On endoscopic ultrasonography, it had a low echo pattern. The preoperative diagnosis was a gastric SMT with a rich vasculature; however because the biosy specimen did not contain tumor tissue, a malignant tumor could not be excluded. The patient underwent nonexposed endoscopic wall-inversion surgery (NEWS), and the tumor was completely resected. Immunohistochemical examination revealed that the tumor was positive for D2-40 and α-smooth muscle actin, but negative for c-kit, discovered on gastrointestinal stromal tumor-1, desmin, S100, Melan-A, signal transducer and activator of transcription 6, insulinoma-associated protein 1, CXCL13, ETS transcription factor, follicular dendritic cell, anaplastic lymphoma kinase, human melanoma black, h-caldesmon, and CD1a, 10, 21, 23, 31, 34, 68, and 163. Approximately, 1–2% of the tumor cell nuclei were Ki-67-positive. Finally, we diagnosed the tumor as a plexiform fibromyxoma. In conclusion, NEWS is an effective method for the treatment of SMTs with a diameter of

Abstract Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction.

Abstract Background Adenosarcoma is classified as a mixed epithelial and mesenchymal tumor composed of a benign epithelial component and a malignant stromal component. The stromal component in adenosarcoma is usually low grade, and consequently the prognosis is relatively favorable. While, adenosarcoma with sarcomatous overgrowth (SO) is defined as an adenosarcoma in which the sarcomatous component constitutes more than 25% of the tumor. The stromal component is also high-grade sarcoma showing greater nuclear pleomorphism and mitotic activity, thus, it is associated with worse prognosis. MRI findings of adenosarcoma without SO have been described in previous literatures but the imaging findings in adenosarcoma with SO may be poorly defined. Therefore we present two cases of uterine adenosarcoma with SO. Case presentation Patient 1 was a 76-year-old woman referred to our hospital with complaint of abdominal distension and postmenopausal bleeding. Patient 2 was a 57-year-old woman with complaint of lower abdominal pain and abnormal uterine bleeding. On magnetic resonance imaging (MRI), T2 weighted imaging showed a large, heterogeneous high-intensity mass with hyperintense tiny cysts that expanded the uterine cavity and extended into the cervical canal for both patients. On diffusion-weighted imaging (DWI), both masses appeared as high signal intensity. Patient 2 also had a right ovarian adult granulosa cell tumor that may have contributed to development of the adenosarcoma. Patient 1 recurred with peritoneal sarcomatosis 6 months after surgery and died of the disease. Patient 2 also recurred with a left upper lung metastasis 3 months after surgery. Conclusions DWI may depict pathological changes produced by SO of adenosarcoma as high signal intensity, even though SO does not seem to change MRI findings of adenosarcoma on other sequences. Therefore, DWI could potentially predict SO in presumptive adenosarcoma on MRI and the patient’s prognosis. It is also important for pathologists to know if SO can arise in adenosarcoma because they need to examine the tumor thoroughly to determine the percentage of SO component in the tumor volume when SO is present.

In this study, we have investigated turbulent premixed flames affected by local stretch in a swirl flow, measured by the simultaneous OH-PLIF/SPIV system. Evaluating the transient of burning velocity and stretch rate, the flow and the flame dynamics in a cyclone-jet combustor were discussed. The flame front was determined by the OH fluorescence signal. Results show that the axial mean velocity becomes the maximum around the center axis, whereas the axial or the radial rms velocity takes the maximum at the position far from the center axis. These could be caused by the velocity fluctuation due to the flame and flow interactions. According to the local burning velocity and the stretch rate, the estimated Markstein number (Ma) roughly matches the value of the laminar flame. With an increase of the swirl number (Sw), the rms velocity is enlarged. Interestingly, the probability of higher burning velocity increases at larger Sw. At the same time, the flame extinction occurs more frequently. Thus, it is derived that the swirl flow has a positive effect to increase the local burning velocity, but it simultaneously has a negative effect which causes the local flame extinction.

Abstract Background Surgeons sometimes have difficulty determining which result to favor when preoperative results (MRI + preoperative endometrial biopsy [pre-op EB]) differ from intraoperative frozen section histology (FS) results. Investigation of how FS can complement ordinary preoperative examinations like MRI and pre-op EB in identification of patients at high risk of lymph node metastasis (high-risk patients) could provide clarity on this issue. Therefore, the aim of this study is to assess the utility of pre-op EB, MRI and FS results and determine how to combine these results in identification of high-risk patients. Methods The subjects were 172 patients with endometrial cancer. Patients with a histological high-grade tumor (HGT), namely, grade 3 endometrioid cancer, clear cell carcinoma or serous cell carcinoma, or with any type of cancer invading at least half of the uterine myometrium were considered high-risk. Tumors invading at least half of the uterine myometrium were classified as high-stage tumors (HST). We compared (a) detection of HGT using pre-op EB versus FS, (b) detection of HST using MRI versus FS, and (c) identification of high-risk patients using MRI + pre-op EB versus FS. Lastly, we determined to what degree addition of FS results improves identification of high-risk patients by routine MRI + pre-op EB. Results (a) Sensitivity, specificity, and accuracy for detecting HGT were 59.6, 98.4 and 87.8% for pre-op EB versus 55.3, 99.2 and 87.2% for FS (P = 0.44). (b) These figures for detecting HST were 74.4, 83.0 and 80.8% for MRI versus 46.5, 99.2 and 86.0% for FS (P < 0.001). (c) These figures for identifying high-risk patients were 78.3, 85.4 and 82.6% for MRI + pre-op EB versus 55.1, 99.0 and 81.2% for FS (P < 0.001). The high specificity of FS improved the sensitivity of MRI + pre-op EB from 78.3 to 81.2%, but this difference was not statistically significant (P < 0.16). Conclusion Frozen section enables identification of high-risk patients with nearly 100% specificity. This advantage can be used to improve sensitivity for identification of high-risk patients by routine MRI + pre-op EB, although this improvement is not statistically significant.

Introduction Pancreatic and duodenal homeobox factor-1 (PDX-1) is an imperative gene for insulin secretion in maturity-onset diabetes of the young 4. PDX-1 gene polymorphism was associated with lower first-phase insulin secretion in a genome-wide association study of intravenous glucose tolerance test. It was not associated with type 2 diabetes risk and insulin secretion in a genome-wide oral glucose tolerance test study. However, there have been no reports of overt type 2 diabetes and insulin resistance evaluation using a glucose clamp. We investigated PDX-1 polymorphism, insulin secretion, and insulin resistance in overt type 2 diabetes.Research design and methods We performed a meal tolerance test (MTT) and hyperinsulinemic–euglycemic clamping on 63 Japanese subjects, 30 with type 2 diabetes and 33 non-diabetic. We analyzed the rs1124607 PDX-1 gene polymorphism and defined A/C and C/C as the high-risk group and A/A as the low-risk group.Results HOMA-beta (homeostatic model assessment beta-cell function) was significantly lower in the high-risk group than in the low-risk group for all subjects (72.9±54.2% vs 107.0±63.5%, p

Abstract Background A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. Methods A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. Results Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. Conclusions Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

Abstract Aims Trimethylamine N‐oxide (TMAO) is a metabolite derived from the gut microbiota. Elevated TMAO levels are associated with a poor prognosis in patients with heart failure with reduced ejection fraction. However, the prognostic effect of elevated TMAO levels on heart failure with preserved ejection fraction (HFpEF) remains unclear. Methods and results We consecutively enrolled 146 patients who were hospitalized and discharged from Tottori University Hospital with the primary diagnosis of HFpEF (ejection fraction ≥ 50%). High TMAO levels were defined as those greater than the median value in the patients (20.37 μmol/L). Patients with high TMAO levels had a significantly higher prevalence of prior hospitalization for heart failure and severe renal dysfunction than those with low TMAO levels. They also had a significantly higher acylcarnitine to free carnitine ratio than those with low TMAO levels, which indicated abnormal fatty acid metabolism and relative carnitine deficiency. After adjustment for differences in the patients' background in multivariate analysis, high TMAO levels remained independently associated with a high incidence of the composite endpoints of death due to cardiac causes and hospitalization for heart failure (adjusted hazard ratio, 1.91; 95% confidence interval, 1.01 to 3.62; P

To solve the global warming problem, it is necessary to minimize the use of fossil fuels such as coal and natural gas. As a power-to-gas technology, CO2 methanation has been focused on, which can produce the synthetic methane through the catalytic conversion of carbon dioxide and hydrogen, called methanation. However, it is better not to use catalysts, because the catalyst could be damaged due to the thermal degradation due to the exothermic reaction. In the present study, we have investigated the characteristics of the methanation reaction based on the chemical equilibrium calculations, NASA-CEA. We changed the reaction temperature, the ambient pressure and the ratio of carbon dioxide and hydrogen. Six various pressures of 1, 2, 5, 10, 15, 20 atm were applied, with the temperature range of 500 to 1500 K. The methane conversion rate is defined by the deficient reactant of carbon dioxide or hydrogen. Especially, a new parameter of the hydrogen reactivity factor (H.R.F.) is proposed to characterize the initial components in the mixture with the methane conversion rate. To promote the methanation reaction, we have tested to add oxygen as the secondary oxidizer. Results show that, in the case of no oxygen, the methane conversion rate is almost 100% for the excess of hydrogen (H.R.F. < 1). As more carbon dioxide is supplied at (H.R.F. > 1), the methane conversion rate is decreased. The methane conversion rate is reduced at higher reaction temperature or lower ambient pressure, which can be explained by the so-called Le Chatelier's principle. However, the methane conversion rate is enlarged by adding oxygen. This is the case when carbon dioxide is the excess species, and coking is observed with production of graphite through the pyrolysis of methane. Since the mass fraction of graphite is smaller when oxygen is added, oxygen can improve the methane conversion rate due to less coking. For developing the non-catalytic system, the methanation reactor with circulation (MeRCi) has been proposed, where the reactants in the flow are circulated to ensure the enough residence time and utilize the exothermic heat of the methanation reaction.

Two-dimensional axisymmetric numerical simulations were performed for a Bunsen flame to investigate the OH concentration and heat release rate of methane-hydrogen premixed flames. The OH production rate of the premixed flame increases as the hydrogen ratio in the fuel increases. Resultantly, the OH concentration in the premixed flame increases with the larger heat release rate, but the OH concentration in the diffusion flame remains almost unchanged. The higher the total equivalence ratio, the greater the change in OH concentration and the heat release rate. This could be due to the fact that most of the hydrogen in the fuel reacts in the premixed flame. Independent of the total equivalence ratio, the relationship between the maximum OH concentration in the premixed flame and the OH fluorescence intensity measured by the PLIF technique shows some similarity in both methane and methane-hydrogen flames. Since the same linearity between the maximum value of the heat release rate and the burning velocity is observed, it is derived that the heat release rate in the premixed flame can be estimated by the burning velocity.

In this study, we experimentally investigated soot and NOx in a diffusion flame on a coaxial burner. By applying a dielectric-barrier-discharge (DBD) plasma, we tried to reduce these emissions. When the DBD plasma was exposed to the air flow, the height of the luminous flame slightly decreased. By considering the fact that the flame height without the DBD plasma is proportional to the fuel flow rate, the DBD plasma surely affects the soot concentration of the luminous flame. Based on the LII image, the soot region identified by the LII signal corresponds to the luminous flame zone. This soot distribution is similar even when the DBD plasma is activated, but the soot concentration of the luminous flame zone is reduced. As the air flow rate increases, the reduction of the integrated LII signal by the DBD plasma is smaller. This could be because the plasma is only active at the exit of the air flow, and the effect of the plasma is relatively weaker when the air flow rate increases. As for NOx emission, it is confirmed that the EINOx without plasma increases by increasing the air flow rate, showing that the thermal NOx could increase. Overall, when the plasma is activated, the EINOx always increases at any air flow rate. That is, the simultaneous reduction of soot and NOx cannot be achieved.

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star–black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc^{−3} yr^{−1} and the neutron star–black hole merger rate to be between 7.8 and 140 Gpc^{−3} yr^{−1}, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc^{-3} yr^{-1} at a fiducial redshift (z=0.2). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to (1+z)^{κ} with κ=2.9_{-1.8}^{+1.7} for z≲1. Using both binary neutron star and neutron star–black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2_{-0.2}^{+0.1} to 2.0_{-0.3}^{+0.3}M_{⊙}. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3_{-0.5}^{+0.3} and 27.9_{-1.8}^{+1.9}M_{⊙}. While we continue to find that the mass distribution of a binary’s more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60M_{⊙}, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χ_{i}≈0.25. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum.

Recently, hydrogen is paid the most attention all over the world, because the CO2 emission can be reduced by an increase of its usage. In our previous study, hydrogen has been added in the premixed methane-air flame. The OH chemiluminescence intensity and the burning velocity were experimentally obtained, using a Bunsen burner. For further study, we investigated OH concentration by using the OH-PLIF technique. Especially, the OH fluorescence intensity was measured by keeping the burning velocity constant. The premixed gas velocity of CH4-H2-air mixture was 1.3 m/s. For comparison, OH chemiluminescence intensity was measured. Results showed that even when the hydrogen ratio in the total fuel of methane and hydrogen was changed, the OH fluorescence intensity was almost constant. On the other hand, OH chemiluminescence intensity decreased monotonically. Conclusively, different from the OH chemiluminescence intensity, the OH fluorescence intensity can be a good marker to evaluate the burning velocity in the combustion of mixed fuel of hydrogen and methane.

Ganglioneuroma, which arise from neural crest cells, typically occurs in adolescents and young adults. Most ganglioneuromas are clinically asymptomatic and hormonally silent, therefore may be diagnosed incidentally during imaging studies. Ganglioneuroma containing fat (lipomatous ganglioneuroma) is a rare variant of ganglioneuroma that is histologically characterized by a mature adipocytic component admixed with a conventional ganglioneuroma. Herein, we report the case of adrenal lipomatous ganglioneuroma with elevated urinary catecholamine level.

Abstract Background Oral mucositis frequently occurs in cancer patients treated with chemotherapy and chemoradiotherapy (CRT). This study examined the safety and efficacy of ibuprofen gargle in healthy volunteers and patients with chemotherapy- and concomitant CRT-induced oral mucositis. Methods We enrolled healthy volunteers and patients with chemotherapy- and CRT-induced oral mucositis. In cohort I, single and multiple doses of ibuprofen gargle (0.6% or 1.0%) were administered to healthy volunteers on day 1 and days 4–10. In cohort II, multiple doses of ibuprofen gargle (0.6%) were administered to patients with complicated grade 2–3 oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The primary endpoint of cohort I was the treatment-related adverse events (TRAEs) as defined by CTCAE version 4.0. The primary endpoint of cohort II was the change in the visual analogue scale (VAS) pain score from before to 15 min after gargle use on day 3. The incidence and severity of TRAEs were assessed based on the CTCAE version 4.0 and a subjective rating scale completed by healthy volunteers and patients. Results In cohort I, 9 of 10 healthy volunteers were evaluable for safety. All 9 healthy volunteers reported the TRAE of oral irritation with single or multiple use of the gargle. In cohort II, 10 patients were enrolled and evaluable for safety and 7 of 10 patients were evaluable for efficacy. The mean change in the VAS pain score from before to 15 min after using the gargle on day 3 was − 1.28 (95% confidence interval: − 2.06, − 0.51), and all patients experienced some degree of pain relief (range: − 0.2 to − 2.5). All 10 patients reported the TRAE of oral irritation. No other TRAEs of ibuprofen gargle were observed in the healthy volunteers and patients. Conclusion Despite oral irritation, the ibuprofen gargle appeared to be safe and effective for the pain related to chemo- or CRT-induced oral mucositis. However, ibuprofen-related oral irritation warrants further formulation improvement. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry ( UMIN000014433 ).

To avoid the proneness to degradation due to coking in the operation of solid oxide fuel cells (SOFCs) directly running on methane (CH4) fuels, a modified porous anode of the Ni1−XCoX/YSZ (yttria-stabilized zirconia) cermet prepared by an impregnation method is presented. The influence of the Co alloying content on the cermet microstructure, SOFC characteristics, and prolonged cell performance stability has been studied. Co was incorporated into Ni and formed a solid solution of Ni1−XCoX alloy connected with the YSZ as the cermet anode. The porous microstructure of the Ni1−XCoX/YSZ cermet anode formed by sintering exhibited a grain growth with an increase in the Co alloying content. The electrochemical performance of the cells consisting of the Ni1−XCoX/YSZ cermet anode, the YSZ electrolyte, and the LSM (La0.8Sr0.2MnO3) cathode showed an enhancement by the Ni1−XCoX impregnation treatment for the respective supply of H2 and CH4 to the anode. The cell using the Ni0.75Co0.25/YSZ cermet anode (the Ni0.75Co0.25 cell) showed the highest cell performance among the cells tested. In particular, the performance enhancement of this cell was found to be more significant for CH4 than that for H2; a 45% increase in the maximum power density for CH4 and a 17% increase for H2 at 750 °C compared with the performance of the cell using the Ni/YSZ cermet anode. Furthermore, the prolonged cell performance stability with a continuous CH4 supply was found for the Ni0.85Co0.15 and Ni0.75Co0.25 cells at least for 60 h at 750 °C. These enhancement effects were caused by the optimum porous microstructure of the cermet anode with the low anodic polarization resistance.

Abstract Aims The prognostic implication of left ventricular outflow tract velocity time integral (LVOT‐VTI) on admission in hospitalized heart failure with preserved ejection fraction (HFpEF) patients has not been determined. We sought to investigate whether LVOT‐VTI on admission is associated with worse clinical outcomes in hospitalized patients with HFpEF. Methods and results We studied consecutive 214 hospitalized HFpEF patients who had accessible LVOT‐VTI data on admission, from a prospective HFpEF‐specific multicentre registry. The primary outcome of interest was the composite of all‐cause death and readmission due to heart failure. During a median follow‐up period of 688 (interquartile range 162–810) days, the primary outcome occurred in 83 patients (39%). The optimal cut‐off value of LVOT‐VTI for the primary outcome estimated by receiver operating characteristic analysis was 15.8 cm. Lower LVOT‐VTI was significantly associated with the primary outcome compared with higher LVOT‐VTI (P = 0.005). Multivariable Cox regression analyses revealed that lower LVOT‐VTI was an independent determinant of the primary outcome (hazard ratio 0.94, 95% confidence interval 0.91–0.98). In multivariable linear regression, haemoglobin level was the strongest independent determinant of LVOT‐VTI among clinical parameters (β coefficient = −0.61, P = 0.007). Furthermore, patients with lower LVOT‐VTI and anaemia had the worst clinical outcomes among the groups (P < 0.001). Conclusions Lower admission LVOT‐VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT‐VTI on admission might be useful for categorizing a low‐flow HFpEF phenotype and risk stratification in hospitalized HFpEF patients.

PurposeTo evaluate whether reduced field-of-view (rFOV) DWI sequence improves the differentiation between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) using VI-RADS.Material and methodsEighty-nine patients underwent bladder MRI with full field-of-view (fFOV) DWI and rFOV DWI sequence. Images were independently evaluated by 2 radiologists. The sensitivities, specificities, accuracies, and areas under the curve (AUCs) for the differentiation between NMIBC and MIBC with fFOV DWI and with rFOV DWI sequence were calculated using VI-RADS. Apparent diffusion coefficients (ADC) values were measured for each patient and averaged.ResultsThe sensitivity, specificity, accuracy, and AUC by reader 1 were 92%, 78%, 82% and 0.905 with fFOV DWI, and 92%, 86%, 88% and 0.916 with rFOV DWI sequence, respectively. The sensitivity, specificity, accuracy and AUC by reader 2 were 96%, 76%, 82% and 0.900 with conventional DWI, and 96%, 81%, 85% and 0.907 with rFOV DWI sequence, respectively. The specificity and accuracy of reader 1 were significantly better with rFOV DWI sequence than with fFOV DWI, in contrast there was no significant difference for the others. The average of ADC values of fFOV DWI and rFOV DWI sequence were 1.004×10-6 mm2/s and 1.003×10-6 mm2/s, respectively.ConclusionThe diagnostic ability of rFOV DWI sequence may be better than that of fFOV DWI using VI-RADS for the differentiation between NMIBC and MIBC regardless of image-reading experience, it is controversial.

We search for gravitational-wave (GW) transients associated with fast radio bursts (FRBs) detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project, during the first part of the third observing run of Advanced LIGO and Advanced Virgo (2019 April 1 15:00 UTC–2019 October 1 15:00 UTC). Triggers from 22 FRBs were analyzed with a search that targets both binary neutron star (BNS) and neutron star–black hole (NSBH) mergers. A targeted search for generic GW transients was conducted on 40 FRBs. We find no significant evidence for a GW association in either search. Given the large uncertainties in the distances of our FRB sample, we are unable to exclude the possibility of a GW association. Assessing the volumetric event rates of both FRB and binary mergers, an association is limited to 15% of the FRB population for BNS mergers or 1% for NSBH mergers. We report 90% confidence lower bounds on the distance to each FRB for a range of GW progenitor models and set upper limits on the energy emitted through GWs for a range of emission scenarios. We find values of order 10 ^51 –10 ^57 erg for models with central GW frequencies in the range 70–3560 Hz. At the sensitivity of this search, we find these limits to be above the predicted GW emissions for the models considered. We also find no significant coincident detection of GWs with the repeater, FRB 20200120E, which is the closest known extragalactic FRB.

Oral lichen planus (OLP) is a type of chronic and refractory stomatitis characterized by abnormal keratinization, which is often painful. There is no consensus regarding treatment options for OLP, particularly in the presence of pain. The current study protocol focuses on the short-term efficacy and long-term safety of an ibuprofen gargle for pain management in patients with OLP. Patients (n = 24) with painful OLP will be enrolled. During a crossover study period, patients in the ibuprofen–placebo (IP) group will receive an ibuprofen gargle (0.6%) on day 1, a placebo gargle on day 2, and an ibuprofen gargle on days 3–5 at least once daily. Patients in the placebo–ibuprofen (PI) group will receive a placebo gargle on day 1, an ibuprofen gargle on day 2, and an ibuprofen gargle on days 3–5 at least once daily. The primary endpoint of the crossover study period is the change in pain level as measured by a visual analogue scale score from before gargle administration to 5 min after gargle administration on days 1 and 2. The primary endpoint of the long-term extension study is assessment of long-term safety. The results of this study may support existing evidence regarding the effectiveness of ibuprofen rinses in treating OLP.

Endoplasmic reticulum (ER) stress has been reported as a cause of Parkinson’s disease (PD). We have previously reported that the ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1) and its stabilizing factor suppressor/enhancer lin-12-like (SEL1L) participate in the ER stress. In addition, we recently demonstrated that neuronal cell death is enhanced in the cellular PD model when SEL1L expression is suppressed compared with cell death when HRD1 expression is suppressed. This finding suggests that SEL1L is a critical key molecule in the strategy for PD therapy. Thus, investigation into whether microRNAs (miRNAs) regulate SEL1L expression in neurons should be interesting because relationships between miRNAs and the development of neurological diseases such as PD have been reported in recent years. In this study, using miRNA databases and previous reports, we searched for miRNAs that could regulate SEL1L expression and examined the effects of this regulation on cell death in PD models created by 6-hydroxydopamine (6-OHDA). Five miRNAs were identified as candidate miRNAs that could modulate SEL1L expression. Next, SH-SY5Y cells were exposed to 6-OHDA, following which miR-101 expression was found to be inversely correlated with SEL1L expression. Therefore, we selected miR-101 as a candidate miRNA for SEL1L modulation. We confirmed that miR-101 directly targets the SEL1L 3′ untranslated region, and an miR-101 mimic suppressed the 6-OHDA–induced increase in SEL1L expression and enhanced cell death. Furthermore, an miR-101 inhibitor suppressed this response. These results suggest that miR-101 regulates SEL1L expression and may serve as a new target for PD therapy.

Autologous chondrocyte implantation (ACI) is a cell therapy to repair cartilage defects. In ACI a biopsy is taken from a non-load bearing area of the knee and expanded in-vitro. The expansion process provides the benefit of generating a large number of cells required for implantation; however, during the expansion these cells de-differentiate and lose their chondrocyte phenotype. In this review we focus on examining the de-differentiation phenotype from a mechanobiology and biophysical perspective, highlighting some of the nuclear mechanics and chromatin changes in chondrocytes seen during the expansion process and how this relates to the gene expression profile. We propose that manipulating chondrocyte nuclear architecture and chromatin organization will highlight mechanisms that will help to preserve the chondrocyte phenotype.