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Abstract Background Regulatory T (Treg) cells reportedly play crucial roles in tumor angiogenesis as well as antitumor immunity. In order to explore their therapeutic potential, we investigated the precise prognostic impact of Treg markers in endometrial carcinoma. Methods We performed multiplexed immunofluorescence and quantitative image analyses of CD25, FOXP3, CTLA4, and CD45RA in tumor specimens from 176 consecutive patients treated at our institution for primary endometrial carcinomas. Bioinformatics analyses were further conducted to corroborate the findings. Results High CD25+, FOXP3+, and CD25+FOXP3+CD45RA− stromal cell counts correlated with better overall survival (OS) (p = 0.00019, 0.028 and 0.0012) and MSI-high (p = 0.015, 0.016 and 0.047). High CD45RA+ stromal cell count was associated with superficial myometrial invasion (p = 0.0038). Bioinformatics survival analysis by Kaplan-Meier plotter showed that high CD25, FOXP3, CTLA4, and CD45RA mRNA expressions correlated with better OS (p = 0.046, 0.00042, 0.000044, and 0.0022). Univariate and multivariate analyses with various clinicopathologic prognostic factors indicated that high CD25+ or CD25+FOXP3+CD45RA− stromal cell count was significant and independent for favorable OS (p = 0.0053 and 0.0015). We subsequently analyzed the correlations between the multiplexed immunofluorescence results and treatment-free interval (TFI) after primary chemotherapy in recurrent cases, finding no significant associations. Further analysis revealed that high ratio of CD25+ : CD8+ cell count or CD25+FOXP3+CD45RA− : CD8+ cell count correlated with longer TFI (p = 0.021 and 0.021). Conclusion The current observations suggest that the balance between CD25+ or CD25+FOXP3+CD45RA− cells and CD8+ cells, corresponding to promoting or inhibiting effect on tumor angiogenesis, affect tumor chemosensitivity leading to prognostic significance. CD25+FOXP3+CD45RA− effector Treg tumor infiltration may serve as a useful prognostic biomarker and a potential target for immunotherapeutic manipulation of tumor chemosensitivity by novel management for advanced/recurrent endometrial carcinomas.

To determine the characteristics of pediatric patients 0–19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1–September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were

Abstract Single‐nucleotide polymorphisms (SNP) of ATP2B1 gene are associated with essential hypertension but their association with resistant hypertension (RHT) remains unexplored. The authors examined the relationship between ATP2B1 SNPs and RHT by genotyping 12 SNPs in ATP2B1 gene of 1124 Japanese individuals with lifestyle‐related diseases. Patients with RHT had inadequate blood pressure (BP) control using three antihypertensive drugs or used ≥4 antihypertensive drugs. Patients with controlled hypertension had BP controlled using ≤3 antihypertensive drugs. The association between each SNP and RHT was analyzed by logistic regression. The final cohort had 888 (79.0%) and 43 (3.8%) patients with controlled hypertension and RHT, respectively. Compared with patients homozygous for the minor allele of each SNP in ATP2B1, a significantly higher number of patients carrying the major allele at 10 SNPs exhibited RHT (most significant at rs1401982: 5.8% vs. 0.8%, p = .014; least significant at rs11105378: 5.7% vs. 0.9%, p = .035; most nonsignificant at rs12817819: 5.1% vs. 10%, p = .413). After multivariate adjustment for age, sex, systolic BP, and other confounders, the association remained significant for rs2681472 and rs1401982 (OR: 7.60, p

Introduction Small cell bladder cancer is a relatively rare tumor, representing

Introduction Radiation therapy is used as primary, adjuvant, and salvage therapy for prostate cancer. When using radiation therapy, the SpaceOAR® system is considered easy to use and useful for reducing the irradiated dose and toxicity to the rectum. Although SpaceOAR® system have been reported some adverse event including death. Case presentation A 74‐year‐old male was diagnosed with prostate cancer of clinical stage cT2aN0M0 and intermediate risk by the National Comprehensive Cancer Network guidelines. We inserted the SpaceOAR® Hydrogel before performing intensity‐modulated radiation therapy, as the patient had ulcerative colitis. We did not recognize any complications during or after the procedure, although magnetic resonance imaging revealed hydrogel in the bladder retrospectively. Fourteen months after the procedure, the patient was presented with macrohematuria and we found a bladder stone including hydrogel. Conclusion We report the first case of a bladder stone after use of SpaceOAR® Hydrogel. We must be careful of taking place it.

In Japan, periodic measles outbreaks occurred mainly among young children under the routine immunization program with one dose of the measles-containing vaccine (MCV). A second dose of MCV was introduced in 2006. During a nationwide measles resurgence in 2007–2008, the most affected age group was teenagers. The national serological surveillance for vaccine-preventable diseases made it clear that there was a measles immunity gap among teenagers who had not received a second dose of MCV. To fill this immunity gap, nationwide non-selective supplementary immunization activities (SIAs) were carried out as a five-year program from April 2008 to March 2013 by providing an opportunity to be vaccinated with the measles and rubella vaccine during the first year of junior high school (12–13 years old) and the last year of high school (17–18 years old). The SIA was conducted with the strong involvement of local governments in charge of vaccination delivery and collaboration between the health and education sectors. Japan was verified as achieving measles elimination in 2015 and this has been sustained to date. The challenge of rubella elimination following a similar strategy of a serological diagnosis of an immunity gap and targeted vaccination is also discussed.

Benign notochordal cell tumor (BNCT) is a benign lesion derived from notochordal cells. Although it is relatively common in intraosseous lesion, pulmonary BNCT is extremely rare. We present a case of 54-year-old male with multiple pulmonary nodules, in which were considered to be metastatic chordomas initially. For 20 months follow-up without any therapy, most of the nodules had no remarkable change but some nodules showed cystic change. We consulted with pathologists specializing in chordoma and the final diagnosis of the nodules was considered as BNCT rather than chordoma. We herein report the case of multiple pulmonary BNCTs with cystic change, comparing with previous reports.

Introduction Obstruction of a ureteroileal anastomosis after urinary diversion is an unpleasant situation for patients and clinicians alike. Case presentation A 48‐year‐old man who underwent a radical cystectomy for muscle‐invasive bladder cancer and urinary diversion using the Wallace technique complained of right back pain. Computed tomography showed right hydronephrosis. Cystoscopy via the ileal conduit revealed complete obstruction of the ureteroileal anastomosis. We performed a bilateral approach (antegrade and retrograde) to use the cut‐to‐the‐light technique. A guidewire and 7Fr single J catheter could be inserted. Conclusion The cut‐to‐the‐light technique was useful for complete obstruction of the ureteroileal anastomosis, the length of which was

Background and Objectives: Omega-3 fatty acids have potent lipid-lowering and antiplatelet effects; however, randomized controlled trials have yet to examine the effect of high-dose omega-3 fatty acid administration on peripheral artery disease (PAD) in hemodialysis patients with dyslipidemia. Therefore, this study aimed to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the ankle–brachial index (ABI) and remnant-like lipoprotein cholesterol (RLP-C) levels, which are indicators of PAD severity. Materials and Methods: Thirty-eight participants (mean age: 73.6 ± 12.7 years) were randomly assigned using stratified block randomization to either conventional therapy alone or conventional therapy supplemented with high-dose EPA/DHA (EPA: 1860 mg; DHA: 1500 mg) for a three-month intervention period. Patients in the conventional therapy alone group who opted to continue were provided with a low-dose EPA/DHA regimen (EPA: 930 mg; DHA: 750 mg) for an additional three months. The baseline and 3-month values for RLP-C, an atherogenic lipid parameter, and the ABI were recorded. Results: The results of the 3-month assessments revealed that the mean RLP-C changes were −3.25 ± 3.15 mg/dL and 0.44 ± 2.53 mg/dL in the EPA/DHA and control groups, respectively (p < 0.001), whereas the changes in the mean ABI values were 0.07 ± 0.11 and −0.02 ± 0.09 in the EPA/DHA and control groups, respectively (p = 0.007). In the EPA/DHA group, a significant negative correlation was found between the changes in RLP-C levels and the ABI (r = −0.475, p = 0.04). Additionally, the change in the RLP-C levels independently influenced the change in the ABI in the EPA/DHA group, even after adjusting for age, sex, and statin use (p = 0.042). Conclusions: Add-on EPA/DHA treatment improved the effectiveness of conventional therapy (such as statin treatment) for improving the ABI in hemodialysis patients with dyslipidemia by lowering RLP-C levels. Therefore, clinicians involved in dialysis should focus on RLP-C when considering residual cardiovascular disease risk in hemodialysis patients and should consider screening patients with elevated levels.

Even though SARS-CoV-2 was declared by WHO as constituting no longer a public health emergency, the development of effective treatments against SARS-CoV-2 infection remains a critical issue to prevent complications, particularly in fragile patients. The protease inhibitor nafamostat, currently used in Japan and Korea for pancreatitis, owing to its anticoagulant properties for disseminated intravascular coagulation (DIC), is appealing for the treatment of COVID-19 infection, because it potently inhibits the transmembrane protease serine 2 (TMPRSS2) that, after virus binding to ACE-2, allows virus entry into the cells and replication. Moreover, it could prevent the DIC and pulmonary embolism frequently associated with COVID-19 infection. The goal of the RAndomized Clinical Trial Of NAfamostat (RACONA) study, designed as a prospective randomized, double-blind placebo-controlled clinical trial, was to investigate the efficacy and safety of nafamostat mesylate (0.10 mg/kg/h iv for 7 days), on top of the optimal treatment, in COVID-19 hospitalized patients. We could screen 131 patients, but due to the predefined strict inclusion and exclusion criteria, only 15 could be randomized to group 1 (n = 7) or group 2 (n = 8). The results of an ad interim safety analysis showed similar overall trends for variables evaluating renal function, coagulation, and inflammation. No adverse events, including hyperkalemia, were found to be associated with nafamostat. Thus, the RACONA study showed a good safety profile of nafamostat, suggesting that it could be usefully used in COVID-19 hospitalized patients.

Background Nutcracker syndrome is a compression of the left renal vein between the superior mesenteric artery and aorta, resulting in thrombogenesis. While renal vein thrombosis caused by renal disease is more common, solitary left renal vein thrombosis with nutcracker syndrome is rare. Case Presentation We present the case of a patient with trauma‐associated left renal vein thrombosis with nutcracker syndrome. A 24‐year‐old woman with low body mass index taking oral contraceptives was admitted for trauma. She had multiple injuries, including thoracolumbar fractures, for which elective spinal fusion surgery was scheduled. As the D‐dimer level elevated to 82.5 μg/dL preoperatively, enhanced computed tomography was performed, which revealed a solitary left renal vein thrombus. Conclusion This is the report of solitary left renal vein thrombosis in a patient with nutcracker syndrome after trauma. Patients with low body mass index and coagulopathy might have solitary left renal vein thrombosis associated with nutcracker syndrome.

Abstract The concentrations of polycyclic aromatic hydrocarbons (PAHs) in aerosol were measured in Shinjuku, which is central Tokyo, Japan, for 10 years from 2007 to 2016. The effects of changes in emission sources and their degradation by reaction with ozone were assessed in this study. There was no significant increasing or decreasing trend of the PAH concentrations during 10 years (P > 0.05). The average selected seven the PAH concentrations (0.88 ng m−3) during 10 years was lower than those in New York and Paris. However, the trend of ozone concentrations is increasing in central Tokyo. This inconsistency raises a question. Did the fact that the ozone concentration was higher than the PAH concentrations promote PAH degradation? To apportion the PAH sources, we used PAH concentration profiles and positive matrix factorization analysis. The contribution of vehicle emissions to the PAHs ranged from 40 to 80%. Ozone concentrations increased by 3.70%/year during 10 years. The theoretical degradation rates of PAHs by ozone, which were calculated using a pseudo-first-order rate equation, suggested that the lifetimes of benzo[a]pyrene (BaP) decreased by 1 min from 2007 to 2016. We investigated the aging of BaP using the profile of the isomer ratios. We found that the aging of BaP at the urban and roadside sites were nearly identical indicating aging regardless of the season. Although the decomposition of BaP is promoted by the photochemical oxidation reaction, this result suggests that a certain threshold value exists as the degree of the decomposition. This degradation of PAH can improve chemical loss processes in air quality model.

Background: Notifications of novel coronavirus infections increased in early 2020 in Japan. We described characteristics of novel coronavirus infection cases and analyzed risk factors for severe outcomes. Methods: Cases were persons with laboratory-confirmed novel coronavirus infection reported under national surveillance between January and March 2020. Clinical characteristics were described, and risk factors of (1) intensive care unit [ICU] admission and (2) invasive ventilation/death were analyzed using Poisson regression. Results: Among the 516 cases analyzed, median age was 60 years (range: 1–97 years) and 285 (55%) were male. Common symptoms/signs were fever (375/475, 79%), cough (353/465, 76%), and pneumonia (245/387, 63%). Ten (2%) cases died. Of the 348 cases with data, 50 (14%) required invasive ventilation. Adjusted for each other, male gender and 1-year increase in age were associated with ICU admission (risk ratio [RR] 4.18; 95% confidence interval [CI], 1.69–10.32 and RR 1.05; 95% CI, 1.03–1.08, respectively) and invasive ventilation/death (RR 2.79; 95% CI, 1.49–5.21 and RR 1.06; 95% CI, 1.04–1.08, respectively). Diabetes, dyslipidemia, hyperuricemia, and lung diseases were also associated with severe outcomes. Of the 80 cases asymptomatic at hospitalization, 40 developed symptoms and five of them >70 years of age required invasive ventilation. Conclusions: The early stage of the novel coronavirus epidemic in Japan disproportionately affected the elderly. Older age, male gender, and underlying conditions were associated with severe outcomes. Notably, some elderly case-patients who were asymptomatic at diagnosis and promptly hospitalized still went on to develop severe disease, indicating the importance of careful monitoring of certain populations.

Abstract Background Obesity has been considered as a risk factor influencing operative difficulty. It was reported that body mass index (BMI; kg/m2) did not always properly reflect the degree of a patient’s visceral fat. The purpose of this study is to retrospectively investigate the association of operative outcomes and obesity indices including visceral fat area (VFA; cm2) and BMI in retroperitoneoscopic nephrectomy (RN). Methods We retrospectively reviewed consecutive 96 RN procedures performed from September 2016 to June 2020. We divided patients into BMI obese group (BMI ≥ 25, n = 25) and BMI normal group (BMI

To provide insight into the mortality burden of coronavirus disease (COVID-19) in Japan, we estimated the excess all-cause deaths for each week during the pandemic, January–May 2020, by prefecture and age group. We applied quasi-Poisson regression models to vital statistics data. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the 1-sided prediction interval. A total of 208–4,322 all-cause excess deaths at the national level indicated a 0.03%–0.72% excess in the observed number of deaths. Prefecture and age structure consistency between the reported COVID-19 deaths and our estimates was weak, suggesting the need to use cause-specific analyses to distinguish between direct and indirect consequences of COVID-19.

Abstract We investigated the impact of basal dietary sodium intake on the dapagliflozin-induced changes in albuminuria and blood pressure (BP) measured at home in patients with diabetic kidney disease (DKD).This was a secondary analysis of the Y-AIDA Study, in which DKD patients with estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine were administered dapagliflozin for 24 weeks, and dapagliflozin significantly improved albuminuria levels and home BP profiles. The effects on UACR, home-measured BP, and eGFR were compared between high- and low-sodium intake groups (HS and LS groups), which were created using baseline urinary sodium-to-creatinine ratio of 84 participants with available basal sodium-to-creatinine ratios. At baseline, clinic-/home-measured BPs, UACR, and eGFR, were comparable in the two groups. After 24 weeks, the reductions from baseline in ln-UACR were comparable in the two groups. In contrast, the reductions in evening home systolic BP and eGFR from baseline were larger in HS than in LS (BP: − 13 ± 2.08 vs. − 6 ± 1.88, P = 0.020; eGFR: − 3.33 ± 1.32 vs. 0.37 ± 1.29, P = 0.049). The home BP-lowering effects of dapagliflozin are larger in HS than LS, concomitant with a larger reduction in eGFR, suggesting a dapagliflozin-induced improvement in glomerular relative hyperfiltration in HS.

Background: The Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is a rare disorder characterized by congenital vaginal defects and uterine traces. Because of its rarity, standardized management for MRKH syndrome is unavailable. This study reviewed the management of the patients with MRKH syndrome in our institution. Methods: Using medical records, we retrospectively reviewed the surgical techniques, outcomes, postoperative management methods, and outpatient follow-up of 17 patients with MRKH syndrome in Keio University Hospital. Results: Of the 14 patients who requested vaginoplasty, 12 underwent surgery with Davydov’s modified procedure after the Frank method, and it took 17 months to 34 months (median two years) for the vaginal cavity to enlarge by 5–6 cm. The Frank method is a non-surgical dilation with instrumental stretching of the vaginal vestibular mucosa. Davydov’s procedure is a surgical vaginoplasty in which the vesicoureteral space is coated by the peritoneum. Although one patient lost 3800 mL of bleeding from the plexus vein and four needed to remove the prosthesis under anesthesia about one month after surgery, all patients achieved anatomic success with a vaginal cavity length of 6 cm or more and could have sexual intercourse with their sexual partners. However, two patients interrupted their preoperative hospital visits, and three were lost to follow-up postoperatively. Two of the three patients who did not accept vaginoplasty presented myoma at uterine trace and underwent myomectomy. Another one was scheduled for surgery through psychological support. Conclusions: Davydov’s modified procedure is effective, and dilating the vaginal cavity adequately using the Frank method before surgery is needed to ensure sufficient vaginal length with less perineum. During the operation, attention is required to care for the plexus vein. Comprehensive psychological support, providing appropriate information to the patient for mental maturity, and planning surgery according to their life stages are essential for successful treatment.

Abstract Background The number of cases of novel coronavirus disease 2019 (COVID-19) in Japan have risen since the first case was reported on January 24, 2020, and 6225 infections have been reported as of June 30, 2020. On April 8, 2020, our hospital began screening patients via pre-admission reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and chest computed tomography (CT). Although no patients exhibited apparent pneumonia, treatment delay or changes in treatment plans were required for a few patients based on the results of screening tests. During an emerging infectious disease pandemic, the likelihood of being infected, as well as the disease itself, affects clinical decision making in several ways. We summarized and presented our experience. Case presentation After the introduction of pre-admission screening, RT-PCR and CT were performed in 200 and 76 patients, respectively, as of June 30, 2020. The treatment of five patients, including two patients with cervical cancer, two patients with ovarian tumors, and one patient with ovarian cancer, was affected by the results. Two asymptomatic RT-PCR-positive patients did not develop COVID-19, but their treatment was delayed until the confirmation of negative results. The other three patients were RT-PCR-negative, but abnormal CT findings suggested the possibility of COVID-19, which delayed treatment. The patients receiving first-line preoperative chemotherapy for ovarian cancer had clinically evident exacerbations because of the treatment delay. Conclusion During the epidemic phase of an emerging infectious disease, we found that COVID-19 has several other effects besides its incidence. The postponing treatment was the most common, therefore, treatment of ovarian tumors and ovarian cancer was considered to be the most likely to be affected among gynecological diseases. Protocols that allow for easy over-diagnosis can be disadvantageous, mainly because of treatment delays, and therefore, the protocols must be developed in light of the local infection situation.

Abstract Background Regardless of patients’ baseline renal function, worsening renal function (WRF) during hospitalization is associated with poor outcomes. In individuals with acute heart failure (AHF), one predictor of WRF is an early drop in systolic blood pressure (SBP). Few studies have investigated WRF in elderly AHF patients or the influence of these patients’ heart rate (HR) at admission on the relationship between an early SBP drop SBP and the AHF. Methods We measured the SBP and HR of 245 elderly AHF inpatients (83 ± 6.0 years old, females 51%) at admission and another six times over the next 48 h. We defined ‘WRF’ as a serum creatinine increase ≥0.3 mg/dL by Day 5 post-admission. We calculated the ‘early SBP drop’ as the difference between the admission SBP value and the lowest value during the first 48 h of hospitalization. Results There were significant differences between the 36 patients with WRF and the 209 patients without WRF: early SBP drop (51 vs. 33 mmHg, p

In early 2020, Japan repatriated 566 nationals from China. Universal laboratory testing and 14-day monitoring of returnees detected 12 cases of severe acute respiratory syndrome coronavirus 2 infection; initial screening results were negative for 5. Common outcomes were remaining asymptomatic (n = 4) and pneumonia (n = 6). Overall, screening performed poorly.

We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013–2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided.

This article proposes a new kind of map for mobile robot localization and its generation method. We call the map a highlighted map, on which uniquely shaped objects (landmarks) in monotonous environments are highlighted. By using this map, robots can use such landmarks as clues for localization, and thus, their localization performance can be improved without having to update their sensors or online computation. Furthermore, this map can be easily combined with many other existing localization algorithms. We formulate the problem of making a highlighted map and propose a numerical optimization method based on reinforcement learning. This optimization method automatically identifies and emphasizes the important landmarks on the map. The generated highlighted map is adapted to situations such as the sensor characteristics and robot dynamics because this method uses the actual sensor measurement data. It is proven that the optimization converges under certain technical assumptions. We performed a numerical simulation and real-world experiment showing that the highlighted map provides better localization accuracy than a conventional map.

Photosynthesis generates reactive oxygen species that can damage cells. Here, the authors show that unicellular predators of photosynthetic prey have shared responses to photosynthetic oxidative stress and these may also have been important for the evolution of endosymbiosis.

The dynamic contact behavior of a minute liquid droplet upon the collision with a high temperature solid is investigated using total internal reflection imaging. An inkjet water droplet collides with a high temperature surface of sapphire and quartz glass prisms then splashes away. Contact behaviors captured from back using a nanosecond lighting stroboscope vary dramatically with the contact temperature Tc based on the heat conduction theory rather than the solid temperature Ts and are classified into four regions, (I) film evaporation, (II) nucleate boiling, (III) spontaneous nucleation and (IV) supercritical state regions. Contact area decreases significantly in the region (II) to show a minimum at a temperature close to the limit of liquid superheat, then increases in the region (III) to reach a maximum at a temperature close to the critical temperature before decreasing at higher temperatures. Even at a contact temperature so high as to exceed the critical temperature, liquid still contacts the solid surface over a significant area for several microseconds before drying up of the surface. The fine bubbles generated due to spontaneous nucleation hinders the contact due to the formation of the local dried area as the contact temperature approaches the superheat limit, whereas the contact is rather enhanced at further higher temperatures due to the dynamic action of spontaneous nucleation. Similar behaviors are observed for the quartz glass prism in the same range of the contact temperature.

Abstract Background The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. Methods We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0–10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. Results Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P

Mitochondrial uncoupling is a treatment strategy for metabolic diseases that reduces the efficiency of mitochondrial oxidative phosphorylation and ATP generation. Here the authors characterize the pharmacokinetic and therapeutic properties of the liver-localized mitochondrial uncoupler OPC-163493, which leads to amelioration of diabetes and hypertension in several rodent disease models.

The World Health Organization recommends that countries or organizations that host mass gatherings plan ahead and prepare for possible public health events to ensure a safe environment for local residents, participants and travellers.1 Public health events during mass gatherings can also affect non-host countries. There are numerous reports of the spread of infectious diseases by travellers returning from mass gatherings,2 which can potentially pose the risk of an outbreak of new infectious diseases to travellers’ home countries. With more frequent travel across borders, it is prudent that non-host countries prepare for mass gathering events.

Background: The carotid bulb has a high density of baroreceptors that play an important role in maintaining blood pressure. We hypothesized that atherosclerosis of the carotid bulb would reflect the severity of orthostatic hypotension more accurately than would atherosclerosis of other carotid artery segments. Methods: This cross-sectional study included 198 non-diabetic adults. We measured the cardio-vascular ankle index as an index of arterial stiffness, intima-media thickness in each carotid artery segment (internal carotid artery, carotid bulb, distal and proximal portions, respectively, of the common carotid artery) as a measure of atherosclerosis, and heart rate variability as a measure of cardiac autonomic function. The sit-to-stand test was used to assess severity of orthostatic hypotension. Results: Intima-media thickness of the carotid bulb was correlated with orthostatic systolic blood pressure change (r = −0.218, p = 0.002), cardio-ankle vascular index (r = 0.365, p < 0.001) and heart rate variability parameters. Multivariate regression analysis revealed that among all of the segments, only intima-media thickness of the carotid bulb was an independent predictor of orthostatic systolic blood pressure change (p = 0.022). Conclusion: Atherosclerosis of the carotid bulb was associated with severity of orthostatic hypotension, arterial stiffening and cardiac autonomic dysfunction than that of other carotid artery segments.

In this paper, the authors report a unique short circuit failure mechanism of a 1.2 kV silicon carbide (SiC) SBD-wall-integrated trench MOSFET (SWITCH-MOS), using numerical simulations and experimental validation. When the Schottky barrier height in the SWITCH-MOS was set at 1.20 eV, the short-circuit withstand time was roughly half that of a conventional SiC trench MOSFET. This is because, in the SWITCH-MOS, the thermionic-field emission electrons passing through the embedded SBD continue flowing into the high electric field in the n- drift region, even after the gate is turned off. This causes heat generation in the device, resulting in thermal runaway. Using a novel methodology for improving the short-circuit capability, it was confirmed that metal with a high Schottky barrier height of 1.75 eV can significantly improve the SWITCH-MOS short-circuit capability, making it comparable to that of conventional SiC trench MOSFETs, and suggesting SWITCH-MOS devices may be superior power devices for use in high frequency inverters.

Outbreaks of infectious diseases can occur after natural disasters as vital services are disrupted and populations move into evacuation centres. National notifiable disease surveillance may be inadequate in these situations because of resource-consuming disease confirmation or system interruptions. Although syndromic surveillance has been used as an alternative in post-disaster situations, no systematic evaluations of it have been published. We evaluated the ad hoc paper-based syndromic surveillance system implemented in evacuation centres in Ibaraki prefecture after the 2011 Great East Japan Earthquake and Tsunami. We assessed the simplicity, acceptability, data quality, timeliness and portability of this system and reviewed its usefulness. We concluded that the system was simple, acceptable, portable and useful. The documentation and monitoring of disease events and trends were useful for developing interventions in evacuation centres and have since been used to improve post-disaster infectious disease and surveillance knowledge in Japan. We believe timeliness was a challenge due to the chain of data transmission and communication passing through an intermediary. Future implementations of this system could consider a more direct chain of data transmission and communication from collectors to analysers. Too few key informant interviewees and the inability to obtain original paper-based data from evacuation centres limited our findings; we conducted this evaluation four years after the response occurred. Future evaluations should be completed closer to when operations cease. The usefulness of the system suggests adopting it in future disasters. A simple, plain-language manual should be developed to improve future employment.

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) encodes an enzyme that catalyzes de novo purine biosynthesis. Although PAICS has been implicated as a potential therapeutic target in several cancers, its clinical and prognostic significance in colorectal cancer (CRC) is not fully understood. To elucidate the roles of PAICS in CRC, we investigated PAICS expression in four cohorts consisting of a total of 1659 samples based on quantitative RT-PCR, microarray and RNA-seq analysis. Despite upregulated PAICS levels in tumor compared to those of normal mucosa, we found a decreasing trend of PAICS expression during tumor progression and metastasis. We conducted immunohistochemistry on 252 specimens, showing that PAICS protein was strongly expressed in the majority of CRCs, but not in adjacent mucosa. Notably, 29.0% of tumors lacked PAICS staining, and PAICS-negative expression in tumor had significant prognostic impact on poor cancer-specific survival in stage III CRC. Correspondingly, decreased levels of PAICS transcript were also correlated with poor relapse-free survival particularly in stage III patients, and this finding was robustly confirmed in three microarray datasets of a total of 802 stage II-III patients. Bioinformatics analysis of CRC tissues and cell lines consistently indicated a correlation between decreased PAICS expression and copy number loss of chromosome arm 4q. In conclusion, our results suggest that PAICS expression is downregulated during tumor progression due to genetic deletion of chromosome 4q in microsatellite stable but chromosomally unstable tumors. Furthermore, decreased expression of PAICS transcript or loss of PAICS protein may provide prognostic stratification for postoperative patients with stage III CRC.

In the field of drug repurposing, the use of statins for treating dyslipidemia is considered promising in ovarian cancer treatment based on epidemiological studies and basic research findings. Biomarkers should be established to identify patients who will respond to statin treatment to achieve clinical application. In the present study, we demonstrated that statins have a multifaceted mode of action in ovarian cancer and involve pathways other than protein prenylation. To identify biomarkers that predict the response to statins, we subjected ovarian cancer cells to microarray analysis and calculated Pearson’s correlation coefficients between gene expression and cell survival after statin treatment. The results showed that VDAC1 and LDLRAP1 were positively and negatively correlated with the response to statins, respectively. Histoculture drug response assays revealed that statins were effective in clinical samples. We also confirmed the synergistic effects of statins with paclitaxel and panobinostat and determined that statins are hematologically safe to administer to statin-treated mice. Future clinical trials based on the expression of the biomarkers identified in this study for repurposing statins for ovarian cancer treatment are warranted.

Japan has reported 26 cases of coronavirus disease 2019 (COVID-19) linked to cruise tours on the River Nile in Egypt between March 5 and 15, 2020. Here, we characterized the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome of isolates from 10 travelers who returned from Egypt and from patients possibly associated with these travelers. We performed haplotype network analysis of SARS-CoV-2 isolates using genome-wide single-nucleotide variations. Our analysis identified two potential Egypt-related clusters from these imported cases, and these clusters were related to globally detected viruses in different countries.

Replication of the circular bacterial chromosome is initiated at a unique origin (oriC) in a DnaA-dependent manner in which replication proceeds bidirectionally from oriC to ter. The nucleotide compositions of most bacteria differ between the leading and lagging DNA strands. Thus, the chromosomal DNA sequence typically exhibits an asymmetric GC skew profile. Further, free-living bacteria without genomes encoding dnaA were unknown. Thus, a DnaA-oriC-dependent replication initiation mechanism may be essential for most bacteria. However, most cyanobacterial genomes exhibit irregular GC skew profiles. We previously found that the Synechococcus elongatus chromosome, which exhibits a regular GC skew profile, is replicated in a DnaA-oriC-dependent manner, whereas chromosomes of Synechocystis sp. PCC 6803 and Nostoc sp. PCC 7120, which exhibit an irregular GC skew profile, are replicated from multiple origins in a DnaA-independent manner. Here we investigate the variation in the mechanisms of cyanobacterial chromosome replication. We found that the genomes of certain free-living species do not encode dnaA and such species, including Cyanobacterium aponinum PCC 10605 and Geminocystis sp. NIES-3708, replicate their chromosomes from multiple origins. Synechococcus sp. PCC 7002, which is phylogenetically closely related to dnaA-lacking free-living species as well as to dnaA-encoding but DnaA-oriC-independent Synechocystis sp. PCC 6803, possesses dnaA. In Synechococcus sp. PCC 7002, dnaA was not essential and its chromosomes were replicated from a unique origin in a DnaA-oriC independent manner. Our results also suggest that loss of DnaA-oriC-dependency independently occurred multiple times during cyanobacterial evolution and raises a possibility that the loss of dnaA or loss of DnaA-oriC dependency correlated with an increase in ploidy level.

Iodonium ylides have recently attracted much attention on account of their synthetic applications. However, only a limited number of reports concerning the properties and reactivity of iodonium ylides exist, which is partly due to their instability. In this study, we synthesized several iodonium ylides that bear both an electron-withdrawing group and an aromatic ring with an ortho-t-BuSO2 group. Based on the crystal structures of the synthesized iodonium ylides in combination with natural-bond-orbital (NBO) calculations, we estimated the strength of the intra- and intermolecular halogen-bonding interactions. In addition, we investigated the reactivity of the iodonium ylides under photoirradiation.

Repeated high-impact ground forces can lead to injury and decreased performance. While increasing flexor hallucis longus (FHL) muscle activity is known to increase stiffness and elasticity, it is unknown if this also decreases ground reaction forces by shock absorption during landing. This study aimed to determine whether increasing FHL muscle activity affects ground reaction force during landing in healthy subjects. Eight subjects performed single-leg steps onto a force platform for five trials, with and without flexion of the metatarsophalangeal (MTP) joint at the moment of landing. Integrated surface electromyography (sEMG) of the FHL and medial gastrocnemius (MG) and ground reaction forces (GRFs) were measured. sEMG and GRF during the 50 ms before and 100 ms following initial ground contact were analyzed and compared. Flexion of the MTP joint condition significantly decreased the vertical and mediolateral force peaks of GRF, and FHL muscle activity increased. Flexion of the MTP joint at the moment of landing reduces GRF in healthy subjects through force dissipation in the foot, by increased FHL muscle activity. The results suggest that this may contribute to injury prevention by reducing the impact force through flexing the MTP joint at the moment of landing.

Gynecologic melanomas are rare and have a poor prognosis. Although immunotherapy (immune checkpoint inhibitors) and targeted therapy has greatly improved the systemic treatment of cutaneous melanoma (CM) in recent years, its efficacy in gynecologic melanomas remains uncertain because of the rarity of this malignancy and its scarce literature. This review aimed to evaluate the literature of gynecologic melanomas treated with immunotherapy and targeted therapy through a PubMed search. We identified one study focusing on the overall survival of gynecologic melanomas separately and five case series and nine case reports concentrating on gynecologic melanomas treated with an immune checkpoint inhibitor and/or targeted therapy. Furthermore, the KIT mutation has the highest rate among all mutations in mucosal melanoma types. The KIT inhibitors (Tyrosine kinase inhibitors: TKIs) imatinib and nilotinib could be the treatment options. Moreover, immune checkpoint inhibitors combined with KIT inhibitors may potentially treat cases of resistance to immune checkpoint inhibitors. However, because of the different conditions and a small number of cases, it is difficult to evaluate the efficacy of immunotherapy and targeted therapy for gynecologic melanoma rigorously at this time. Further prospective cohort or randomized trials of gynecologic melanoma alone are needed to assess the treatment with solid evidence.

Since the 1970s, Earth-observing satellites collect increasingly detailed environmental information on land cover, meteorological conditions, environmental variables and air pollutants. This information spans the entire globe and its acquisition plays an important role in epidemiological analysis when in situ data are unavailable or spatially and/or temporally sparse. In this paper, we present the development of Japan Aerospace Exploration Agency’s (JAXA) Public-health Monitoring and Analysis Platform available from JAXA, a user-friendly, web-based system providing environmental data on shortwave radiation, rainfall, soil moisture, the normalized difference vegetation index, aerosol optical thickness, land surface temperature and altitude. This system has been designed so that users should be able to download and utilize data without the need for additional data processing. The website allows interactive exchange and users can request data for a specific geographic location and time using the information gained for epidemiological analysis.

Background. Surgery for gynecologic cancer with lymphadenectomy and pelvic radiotherapy can produce lymphoceles that sometimes complicate with infection, resulting in abscesses. The true pathogenic bacteria of abscesses are not always found because of false-negative results due to administered antibiotics and difficulty with detection, including for anaerobic bacteria. Analyzing bacteria flora by next-generation sequencing (NGS) using 16S ribosomal DNA may reveal the true pathogenic bacteria in abscesses. This is the first report on causative pathogens for infectious lymphocele using this technology. Methods. The subjects were patients who developed infectious lymphocele after surgery for gynecologic cancer at our hospital from July 2015 to September 2016. NGS analyses of bacterial flora were performed using specimens preserved at -80°C. Two steps of PCR were performed for purified DNA samples to obtain sequence libraries. Processing of sequence data, including operational taxonomic unit (OTU) definition, taxonomy assignment, and an OTU BLAST search were performed. All patients gave written informed consent and the study was approved by the institutional research ethics committee. Results. Six patients underwent puncture and drainage. The result in most cases indicated a single causative pathogen, including Staphylococcus lugdunensis, Streptococcus dysgalactiae, Streptococcus equinus, Enterococcus saccharolyticus, and Escherichia coli. Conclusions. NGS revealed that the causative bacteria in lymphocele infection are normally a single strain, such as a surface Gram-positive coccus or enteric bacteria. Antibiotics should be chosen as appropriate for elimination of these respective bacteria.

Pelvic inflammatory disease (PID) sometimes develops after intrauterine insemination (IUI). We herein present a case of PID which developed after IUI performed after abdominal modified radical trachelectomy (AmRT) and was treated with laparoscopic surgery. To our knowledge, this is the first case report of laparoscopic surgery for PID that occurred after AmRT in Japan. A 39-year-old woman who was diagnosed with cervical cancer stage IA1 with lymphovascular invasion underwent AmRT and pelvic lymphadenectomy. At 3 years and 6 months after the surgery, she had fever and pain in her left lower abdomen 10 days after IUI. She was diagnosed with PID with left ovarian cyst infection and underwent laparoscopic left ovarian cystectomy. Before surgery, bilateral ureteral catheters were inserted because of possible difficulty identifying the ureters. During surgery, severe adhesion was seen in the pelvic cavity. By moving the catheters manually back and forth from outside the body, we were able to identify the ureters visually. A uterine manipulator was inserted during surgery, rather than before surgery, to avoid the risk of uterine perforation. Laparoscopic surgery with ureteral catheters and a uterine manipulator can be applied safely for such cases after AmRT even when severe intraperitoneal adhesion is present.

We examined whether water-hydroxyapatite (HAP) images improve the diagnostic accuracy of bone metastasis compared with non-contrast CT alone. We retrospectively evaluated dual-energy computed tomography (DECT) images of 83 cancer patients (bone metastasis, 31; without bone metastasis, 52) from May 2018 to June 2019. Initially, two evaluators examined for bone metastasis on conventional CT images. In the second session, both CT and CT images plus water-HAP images on DECT. The confidence of bone metastasis was scored from 1 (benign) to 5 (malignant). The sensitivity, specificity, positive predictive values, and negative predictive values for both modalities were calculated based on true positive and negative findings. The intra-observer area under curve (AUC) for detecting bone metastasis was compared by receiver operating characteristic analysis. Kappa coefficient calculated the inter-observer agreement. In conventional CT images, sensitivity, specificity, positive predictive value, and negative predictive value of raters 1 and 2 for the identification of bone metastases were 0.742 and 0.710, 0.981 and 0.981, 0.958 and 0.957, and 0.864 and 0.850, respectively. In water-HAP, they were 1.00 and 1.00, 0.981 and 1.00, 0.969 and 1.00, and 1.00 and 1.00, respectively. In CT, AUCs were 0.861 and 0.845 in each observer. On water-HAP images, AUCs were 0.990 and 1.00. Kappa coefficient was 0.964 for CT and 0.976 for water-HAP images. The combination of CT and water-HAP images significantly increased diagnostic accuracy for detecting bone metastasis. Water-HAP images on DECT may enable accurate initial staging, reduced radiation exposure, and cost.

The first catalytic asymmetric synthesis of the key intermediate for beraprost has been achieved through an enantioselective intramolecular oxa-Michael reaction of an α,β-unsaturated amide mediated by a newly developed benzothiadiazine catalyst. The Weinreb amide moiety and bromo substituent of the Michael adduct were utilized for the C–C bond formations to construct the scaffold. All four contiguous stereocenters of the tricyclic core were controlled via Rh-catalyzed stereoselective C–H insertion and the subsequent reduction from the convex face.

Oxyresveratrol and gnetol are naturally occurring stilbene compounds, which have diverse pharmacological activities. The water-insolubility of these compounds limits their further pharmacological exploitation. The glycosylation of bioactive compounds can enhance their water-solubility, physicochemical stability, intestinal absorption, and biological half-life, and improve their bio- and pharmacological properties. Plant cell cultures are ideal systems for propagating rare plants and for studying the biosynthesis of secondary metabolites. Furthermore, the biotransformation of various organic compounds has been investigated as a target in the biotechnological application of plant cell culture systems. Cultured plant cells can glycosylate not only endogenous metabolic intermediates but also xenobiotics. In plants, glycosylation reaction acts for decreasing the toxicity of xenobiotics. There have been a few studies of glycosylation of exogenously administrated stilbene compounds at their 3- and 4′-positions by cultured plant cells of Ipomoea batatas and Strophanthus gratus so far. However, little attention has been paid to the glycosylation of 2′-hydroxy group of stilbene compounds by cultured plant cells. In this work, it is described that oxyresveratrol (3,5,2′,4′−tetrahydroxystilbene) was transformed to 3-, 2′-, and 4′-β-glucosides of oxyresveratrol by biotransformation with cultured Phytolacca americana cells. On the other hand, gnetol (3,5,2′,6′−tetrahydroxystilbene) was converted into 2′-β-glucoside of gnetol by cultured P. americana cells. Oxyresveratrol 2′-β-glucoside and gnetol 2′-β-glucoside are two new compounds. This paper reports, for the first time, the glycosylation of stilbene compounds at their 2′-position by cultured plant cells.

The magnetic response of the storage modulus for bimodal magnetic elastomers containing magnetic particles with a diameter of 7.0 μm and plastic beads with a diameter of 200 μm were investigated by varying the volume fraction of plastic beads up to 0.60 while keeping the volume fraction of the magnetic particles at 0.10. The storage modulus at 0 mT for monomodal magnetic elastomers was 1.4 × 104 Pa, and it slightly increased with the volume fraction of plastic beads up to 0.6. The storage modulus at 500 mT for bimodal magnetic elastomers at volume fractions below 0.25 was constant, which was equal to that for the monomodal one (=7.9 × 104 Pa). At volume fractions of 0.25−0.40, the storage modulus significantly increased with the volume fraction, showing a percolation behavior. At volume fractions of 0.40-0.60, the storage modulus was constant at 2.0 × 105 Pa, independently of the volume fraction. These results indicate that the enhanced increase in the storage modulus was caused by the chain formation of the magnetic particles in vacancies made of plastic beads.

A magnetic-responsive elastomer consisting of magnetic elastomer and zinc oxide with a tetrapod shape and long arms was fabricated mimetic to the tissue of sea cucumber in which collagen fibrils are dispersed. Only the part of magnetic elastomer is active to magnetic fields, zinc oxide plays a role of reinforcement for the chain structure of magnetic particles formed under magnetic fields. The magnetic response of storage modulus for bimodal magnetic elastomers was measured when the magnetic particle was substituted to a nonmagnetic one, while keeping the total volume fraction of both particles. The change in storage modulus obeyed basically a mixing rule. However, a remarkable enhancement was observed at around the substitution ratio of 0.20. In addition, the bimodal magnetic elastomers with tetrapods exhibited apparent change in storage modulus even at regions with a high substitution ratio where monomodal magnetic elastomers consist of only magnetic particles with less response to the magnetic field. This strongly indicates that discontinuous chains of small amounts of magnetic particles were bridged by the nonmagnetic tetrapods. On the contrary, the change in storage modulus for bimodal magnetic elastomers with zinc oxide with irregular shape showed a mixing rule with a substitution ratio below 0.30. However, it decreased significantly at the substitution ratio above it. The structures of bimodal magnetic elastomers with tetrapods and the tissue of sea cucumber with collagen fibrils are discussed.

Environmental surveillance supplements the surveillance of acute flaccid paralysis by monitoring wastewater for poliovirus circulation. Building on previous work, we analysed wastewater flow to optimise selection and placement of sampling sites with higher digital surface model (DSM) resolution. The newly developed 5-m mesh DSM from the panchromatic, remote-sensing instruments for stereo mapping on-board the Japanese advanced land observing satellite was used to estimate catchment areas and flow of sewage water based on terrain topography. Optimal sampling sites for environmental surveillance were identified to maximise sensitivity to poliovirus circulation. Population data were overlaid to prioritise selection of catchment areas with dense populations. The results for Kano City, Nigeria were compared with an analysis based on existing 30- and 90-m mesh digital elevation model (DEM). Analysis based on 5-m mesh DSM was also conducted for three cities in Niger to prioritise the selection of new sites. The analysis demonstrated the feasibility of using DSMs to estimate catchment areas and population size for programme planning and outbreak response with respect to polio. Alternative sampling points in Kano City that would cover a greater population size have been identified and potential sampling sites in Niger are proposed. Comparison with lower-resolution DEMs suggests that the use of a 5-m mesh DSMs would be useful where the terrain is flat or includes small-scale topographic changes not captured by 30-m data searches.