Search

Abstract Purpose To investigate the role of estrogen receptors (ERs) in high‐grade serous carcinoma (HGSC) and clear cell carcinoma (CCC) of the ovary and evaluate ERs as prognostic biomarkers for ovarian cancer. Methods This study included 79 patients with HGSC (n = 38) or CCC (n = 41) treated at our institution between 2005 and 2014. Immunohistochemistry examined protein expression of ERα, ERβ, and G protein‐coupled estrogen receptor‐1 (GPER‐1); relationships between ERα, ERβ, and GPER‐1 with patient survival were evaluated. Additionally, cell proliferation assay and phosphokinase proteome profiling were performed. Results In HGSC patients, expression of ERα, cytoplasmic GPER‐1, or nuclear GPER‐1 was associated with poor progression‐free survival (PFS) (P = .041, P = .010, or P = .013, respectively). Cytoplasmic GPER‐1 was an independent prognostic factor for PFS in HGSC patients (HR = 2.83, 95% CI = 1.03‐9.16, P = .007). ER expressions were not associated with prognosis in CCC patients. GPER‐1 knockdown by siRNA reduced the cells number to 60% of siRNA‐control‐treated cells (P

Abstract Background Synchronous oligometastatic non-small cell lung cancer (NSCLC) is generally characterised by the limited number of metastases at the time of diagnosis. Several clinical trials have shown that local ablative therapy (LAT) at all sites of the disease might be beneficial for patients with oligometastatic NSCLC. In recent years, the combination of programmed cell death 1 (PD-1) inhibitors or programmed cell death ligand 1 with cytotoxic chemotherapy has become a new standard treatment for patients with metastatic NSCLC. Furthermore, multisite LAT would inherently reduce the overall tumour burden, and this could promote T cell reinvigoration to enhance the efficacy of PD-1 inhibitors. Few studies have evaluated the efficacy of the combination of PD-1 inhibitors with LAT at all sites of disease. The aim of the present multicentre single-arm phase II study is to evaluate the efficacy of LAT at all sites of disease following standard platinum doublet chemotherapy with pembrolizumab in patients with oligometastatic NSCLC. Methods Thirty patients with synchronous oligometastatic NSCLC will be enrolled in the trial. All patients will receive 2–4 cycles of a systemic treatment including pembrolizumab and chemotherapy as induction therapy. Patients who will receive LAT will be determined by a multidisciplinary tumour board, including medical oncologists, radiation oncologists, and thoracic surgeons. LAT will be administered at all sites of disease within 21–56 days of the last dose of induction therapy and will be followed by maintenance therapy within 42 days of the last day of LAT. The primary endpoint is the progression-free survival (PFS) rate of 24 months from the date of initiation of LAT. The secondary endpoints are toxicity, response to induction therapy, PFS, overall survival, and the frequency of LAT. Discussion This study will provide novel data on the efficacy and safety profile of the combination of LAT and chemotherapy plus immune-checkpoint inhibitors in patients with synchronous oligometastatic NSCLC. If the primary endpoint of this study is met, extensive phase III studies further assessing this strategy will be recommended. Trial registration jRCT identifier: jRCTs041200046 (date of initial registration: 28 October 2020).

Real drive emissions (RDE) regulation were introduced from Euro6-d regulation. In order to achieve the regulation value of PM(Particulate Matter) emission in the RDE regulation, it is effective to install GPF(Gasoline Particulate Filter) system. To prevent GPF corruption , GPF system needs “PM emission amount estimation model” that estimates PM emission amount from direct injection gasoline engine to estimate PM corrected amount. Some models, for example packet model and map-based model, have been proposed as PM emission amount estimation model. However, these models have problems in terms of calculation load and accuracy for On-board calculation. Purpose of this research is to study On-board PM emission amount estimation model . We proposed a new model method of physical quantities that dominate PM production. Developed model uses probability density function of mixture fraction space so that mixture and fuel adhesion can be treated uniformly as a fuel distribution in cylinder. Also, variance of mixture-derived probability density function and fuel adhesion ratio are functionalized by a second-order polynomial of engine control parameters, and can be applied to multiple operating conditions. The developed model was verified by comparison with measurement data. Under 25 degC of coolant temperature(19 operation points), the estimated error was during 0% and 59% and average estimated error was 19%.

Oral microbiota is associated with human diseases including cancer. Emerging evidence suggests that proton pump inhibitors (PPIs), which allow the oral microbiome to translocate into the gut, negatively influence the efficacy of immune checkpoint blockade (ICB) in cancer patients. However, currently there is no effective treatment that restores the decreased efficacy. To address this issue, we retrospectively evaluated 118 advanced or recurrent non-small cell lung cancer (NSCLC) patients treated with ICB and analyzed 80 fecal samples of patients with lung cancer by 16S metagenomic sequencing. Clostridium butyricum therapy using C. butyricum MIYAIRI 588 (CBM588), a live biotherapeutic bacterial strain, was shown to improve the ICB efficacy in lung cancer. Thus, we investigated how CBM588 affects the efficacy of ICB and the gut microbiota of lung cancer patients undergoing PPI treatment. We found that PPI treatment significantly decreased the efficacy of ICB in NSCLC patients, however, CBM588 significantly restored the diminished efficacy of ICB and improved survival. In addition, CBM588 prolonged overall survival in patients receiving PPIs and antibiotics together. The fecal analysis revealed that PPI users had higher abundance of harmful oral-related pathobionts and lower abundance of beneficial gut bacteria for immunotherapy. In contrast, patients who received CBM588 had lesser relative abundance of potentially harmful oral-related bacteria in the gut. Our research suggests that manipulating commensal microbiota by CBM588 may improve the therapeutic efficacy of ICB in cancer patients receiving PPIs, highlighting the potential of oral-related microbiota in the gut as a new therapeutic target for cancer immunotherapy.

The Bronze Age—Iron Age transition in Central Asia (ca. 800 BCE) was a period of significant cultural change that was heavily influenced by greater population interaction and mobility. Indeed, scholars have increasingly emphasized the role that “food globalization in prehistory” has played in defining this period. In the mountain foothills of Kazakhstan, culinary traditions from across Eurasia were combined through the use of Southwest Asian wheat, barley, and livestock (cattle, sheep, and goats) with East Asian foxtail and broomcorn millets. The development of food cultures during this period has been investigated by archaeobotanical and isotopic analysis, yet lipid residues from pottery, which directly represent culinary practices, have not been adequately examined. In this study, lipid residue analysis was conducted on 72 pottery sherds, excavated from three burial mounds and one non-burial, ritual site located in Kazakhstan, dating to ca. 700–200 BCE. A particularly informative observation was the frequency of miliacin, a biomarker of broomcorn millet, detected in residues that corresponded well with previously published regional differences observed in carbon isotope ratios of human remains that indicate the consumption of C4 plants. This study also demonstrates continuity of Bronze Age dairying traditions into the Iron Age. Finally, this study sheds new light on the diversity of food cultures and mortuary practices in this region, which were not uniform across either space or time.

We report a rare case of a vertebro-vertebral arteriovenous fistula (VVAVF) manifesting as amyotrophic lateral sclerosis (ALS). A 76-year-old female patient presented with progressive weakness, muscle atrophy, fasciculation, and preserved deep tendon reflexes in the right upper limb. Electrophysiological testing showed lower motor neuron dysfunction. The patient was suspected to have ALS, but cervical magnetic resonance imaging (MRI) revealed enlarged blood vessels in the spinal canal, which compressed the cervical spinal cord and nerve roots. Angiography showed a shunt from the right vertebral artery to the right intervertebral vein and the vertebral venous plexus; therefore, the patient was diagnosed with VVAVF. Transarterial embolization was performed to obliterate the shunt, and weakness in the patient’s right upper limb subsequently improved. It is worth considering VVAVF as a differential diagnosis of ALS-like diseases.

We examine the changing importance of wild starch rich plant staples, predominantly tree nuts, in early agricultural societies in East Asia and Europe, focusing on Korea, Japan, and Britain. A comparative review highlights variations in the importance of wild plant staples compared to domesticated crops. The Korean Middle to Late Chulmun periods (c. 3,500–1,500 BC) was characterized by a high reliance on nuts alongside millet. This declines with the transition to rice agriculture, but remains significant during the Mumun period (c. 1,500–300 BC). In Japan, the arrival of rice and millets in the Yayoi Period (c. 1,000 BC−250 AD) saw continued evidence for high levels of reliance on wild resources, which declines only in the Kofun and early historical periods. In Early Neolithic Britain (c. 4,000–3,300 BC) cereal agriculture is accompanied by high evidence for wild plant foods. But during the Middle to Late Neolithic (3,300–c. 2,400/2,200 BC) cereals were abandoned on the mainland with hazelnuts becoming a prominent plant staple. Agriculture returned in the second half of the 3rd millennium BC, followed by a strong decline in wild plant food use during the Middle to Late Bronze Age (1,700–700 BC). Such patterns have previously been attributed to the slow adoption of farming by indigenous peoples, with a continued reliance on wild resources. In light of evidence demonstrating that the dispersal of agriculture was largely driven by a mixture of demic-diffusion and introgression of hunter-gatherers into agricultural groups, a reinterpretation of the role of wild foods is needed. It is argued that the relative importance of wild plant staples provides an indicator of the stability and dependability of agricultural and social systems. A heavy reliance on wild foods in early agricultural societies is tied to the slow adaptation of domesticated crops to new environments, where agricultural and social landscapes are yet to be firmly established, and social systems that could mitigate for poor harvests and storage were often absent. The retained lengthy persistence of wild plant staples in East Asian subsistence systems compared to the British Isles likely reflects differences in the ecological and labor demands for rice compared to Western Asiatic cereals.

Abstract Background There are few cases of anaphylaxis after local application of fibrin sealant diagnosed by skin tests. Case presentation A 49-year-old woman underwent partial lung resection under general anesthesia. Anesthesia was induced uneventfully. Shortly after applying absorbable suture reinforcement felt that contained fibrin sealant, her systolic blood pressure fell to approximately 70 mmHg, along with facial flushing. Anaphylaxis was diagnosed based on the clinical symptoms and high serum tryptase levels. Three months after the event, skin tests were performed with all agents and were positive only for fibrin sealant vial no. 2, whose main component is aprotinin. Subsequently, basophil activation tests using fibrin sealant vial no. 2 and pure aprotinin demonstrated that the causative agent was likely aprotinin. Conclusions We diagnosed aprotinin-induced anaphylaxis using skin tests and basophil activation tests. The occurrence of anaphylaxis should be considered when changes in vital signs are observed after the use of fibrin sealant.

Identifying the factors that contribute to individual differences in mid-level intensity neuromuscular fatigue is essential to improve performance and effective exercise in training and rehabilitation. This study investigated factors affecting individual differences in knee extensor fatigue induced by sustained isometric mid-level contractions. Twenty-six healthy young men performed a sustained fatiguing contraction to task failure at 40% maximal voluntary contraction (MVC) torque of the knee extensors. The MVC torque (TQMVC), evoked triplet torque (TQTRI), and voluntary activation (VA%) of the knee extensors were determined before and after the fatiguing task. Differences in TQMVC, TQTRI, and VA% before and after the fatiguing task were examined, and the relationship between TQMVC and TQTRI or VA% after the fatiguing task normalized to baseline was examined using Pearson product-moment correlation analysis. TQMVC and TQTRI decreased significantly after the fatiguing task (31.1% decrease for TQMVC, 38.8% decrease for TQTRI, p < 0.001), whereas VA% did not change significantly (4.2% increase for VA%, p = 0.057). After the fatiguing task, the normalized TQMVC was significantly correlated with the normalized TQTRI (r = 0.617, p < 0.001), but not with the normalized VA% (r = 0.348, p = 0.082). Individual differences in knee extensor fatigue induced by sustained mid-level contraction were more affected by peripheral fatigue than by central fatigue. Therefore, focusing on fatigue resistance in peripheral areas is important to improve endurance in moderate-intensity exercises.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

Ionic liquids (ILs) are being considered as novel lubricant additives to improve the friction and anti-wear characteristics of sliding surfaces. Because ILs consist of only cations and anions, their physical and chemical properties can be easily tailored by modifying their combination. These features enable to design of specific ILs for a given tribological system. However, there are few reports on the effect of ILs used as lubricant additives on the friction and anti-wear characteristics of sliding surfaces. Moreover, it is necessary to investigate the synergism between ILs and other lubricant additives to achieve high practical efficiency. Therefore, in this study, two ILs with different cations but similar anions were used in combination with an anti-wear additive, zinc dialkyldithiophosphate (ZDDP), and the resultant wear and friction characteristics of the worn surfaces were analyzed. We found that the tribological performance under steel/steel sliding conditions was dependent on the chemical composition of the ILs. In addition, mixed ZDDP and IL solutions exhibited lower friction and wear when compared to ZDDP alone. It is considered that the excellent lubrication and frictional performance observed with the mixed lubricant solutions is due to the formation of tribofilms comprising of ZDDP and IL on the sliding surface.

Abstract Background There is a well-established relationship between 12-lead electrocardiogram (ECG) and age and mortality. Furthermore, there is increasing evidence that ECG can be used to predict biological age. However, the utility of biological age from ECG for predicting mortality remains unclear. Methods This was a single-center cohort study from a cardiology specialized hospital. A total of 19,170 patients registered in this study from February 2010 to March 2018. ECG was analyzed in a final 12,837 patients after excluding those with structural heart disease or with pacing beats, atrial or ventricular tachyarrhythmia, or an indeterminate axis (R axis > 180°) on index ECG. The models for biological age were developed by principal component analysis (BA) and the Klemera and Doubal’s method (not adjusted for age [BAE] and adjusted for age [BAEC]) using 438 ECG parameters. The predictive capability for all-cause death and cardiovascular death by chronological age (CA) and biological age using the three algorithms were evaluated by receiver operating characteristic analysis. Results During the mean follow-up period of 320.4 days, there were 55 all-cause deaths and 23 cardiovascular deaths. The predictive capabilities for all-cause death by BA, BAE, and BAEC using area under the curves were 0.731, 0.657, and 0.685, respectively, which were comparable to 0.725 for CA (p = 0.760, 0.141, and 0.308, respectively). The predictive capabilities for cardiovascular death by BA, BAE, and BAEC were 0.682, 0.685, and 0.692, respectively, which were also comparable to 0.674 for CA (p = 0.775, 0.839, and 0.706, respectively). In patients aged 60–74 years old, the area under the curves for all-cause death by BA, BAE, and BAEC were 0.619, 0.702, and 0.697, respectively, which tended to be or were significantly higher than 0.482 for CA (p = 0.064, 0.006, and 0.005, respectively). Conclusion Biological age by 12-lead ECG showed a similar predictive capability for mortality compared to CA among total patients, but partially showed a significant increase in predictive capability among patients aged 60–74 years old.

Abstract The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

A 77-year-old man presented to our hospital with epigastric pain. He had previously undergone hepatic left lateral segmentectomy, cholangiojejunostomy, and Roux-en-Y reconstruction at 42 years of age for intrahepatic stones and liver abscesses. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed bile duct stones and intrahepatic bile duct dilation of the caudate lobe. Bile duct drainage for the caudate lobe was necessary; however, the volume of his caudate lobe was very small, making percutaneous transhepatic biliary drainage (PTBD) or endoscopic ultrasound-guided biliary drainage (EUS-BD) difficult. Therefore, we attempted laparotomy-assisted endoscopic biliary drainage. Under general anesthesia, an incision was made on the jejunum approximately 15 cm from the Y-leg anastomosis. An esophagogastroduodenoscope was directly inserted into the common hepatic duct anastomosed with the jejunum. The caudate lobe branch had severe stenosis, and the area upstream of the stenosis was filled with stones, sludge, and pus. The biliary stenosis was dilated using a balloon, and the stones were completely removed using a basket and a balloon catheter. There are various methods of biliary and pancreatic surgery and gastrointestinal reconstruction, and there are cases in which PTBD, EUS-BD, and endoscopic retrograde cholangiopancreatography (ERCP) with an enteroscope are difficult. In such cases, ERCP under laparotomy could be a good treatment option.

Objective: Predicting outcomes after intracerebral hemorrhage (ICH) may help improve patient outcomes. We developed and validated a machine learning prediction model for post-rehabilitation functional outcomes after ICH. Patient selection and explanatory variable settings were based on clinical significance. Functional outcomes were predicted using ternary classification. Methods: The subjects were patients aged > 18 years without pre-onset severe disability who developed primary putaminal and/or thalamic hemorrhage and underwent an inpatient rehabilitation program. As explanatory variables, 43 values related to patient background, imaging-related findings, systemic conditions, neurological findings, and blood tests were acquired within 10 days of onset. As an objective variable, the functional outcome at discharge to home or nursing home was acquired using a ternary classification. The dataset consisting of the collected information was split into a training dataset and a test dataset with a ratio of 2:1. A predictive model using a balanced random forest algorithm was created using supervised learning from the training dataset. The predictive performance was validated using a test dataset. Results: Between January 2018 and June 2019, 100 consecutive patients were included in the study. The areas under the receiver operating characteristic curves for predictions of good, moderate, and poor outcomes were 0.952, 0.790, and 0.921, respectively. Conclusions: The predictive performance of the model was comparable to that of previous models. Patient selection and variable settings from a clinical perspective may contribute to accurate and detailed predictions. These study designs are based on design thinking and may meet the needs of clinical practice.

Background The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population.Methods We stratified 177 individuals who participated in the Japanese Alzheimer’s Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)tau and AT(N)NfL). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles.Results We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer’s disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)tau and AT(N)NfL classifications. When we used t-tau as the N marker (AT(N)tau), those who had T− were more frequently assigned to (N)−, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)NfL). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)tau and AT(N)NfL classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)tau classification, but not in the AT(N)NfL classification.Conclusions AT(N)tau and AT(N)NfL in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.

The Inner Asian Mountain Corridor (IAMC) has been identified as a major pathway for the westward dispersal of millet from Northern China, where it was initially cultivated. Cross-disciplinary investigations are necessary to distinguish cultivated millet taxa from their wild relatives and to clarify the social context underlying millet adoption in novel environments. Despite the ambiguity in distinguishing Setaria italica from Panicum miliaceum or other Setaria species using conventional analysis of charred macro remains, recent attention has focused on the time gap between the introduction of S. italica to IAMC following P. miliaceum. Here, we employed a pottery impression casting method on materials from four Bronze Age sites in eastern/southeastern Kazakhstan to investigate the surface textures of grain impressions on the surface of pottery containers. We successfully identified both millets (Setaeria and Panicum) from three of the sites, Begash, Tasbas, and Dali in the IAMC. Based on our findings, two species of millet were introduced to the region within a much shorter range of time than previously estimated. In addition, the current evidence supports the premise that these cereals were likely utilized for human consumption.

Alcohol is a major risk factor of liver cirrhosis (LC). This study aimed to elucidate a surrogate marker of sarcopenia in patients with LC of different etiology. Out of 775 patients with LC, 451 were assessed for handgrip strength and skeletal muscle mass (by computed tomography). They were then divided into two groups: alcoholic cirrhosis (AC; n = 149) and nonalcoholic cirrhosis (NAC; n = 302). Endotoxin activity (EA) levels were measured with an EA assay. Group AC showed significantly higher platelet counts (p = 0.027) and lower blood urea nitrogen levels and fibrosis-4 index than group NAC (p = 0.0020 and p = 0.038, respectively). The risk factors of sarcopenia were age ≥ 65 years, female sex, CP-C LC, Hb levels < 12 g/dL, and EA level > 0.4 in all patients with LC; hemoglobin (Hb) levels < 12 g/dL and EA level > 0.4 in group AC; and age ≥ 65 years, CP-C LC, and Hb levels < 12 g/dL in group NAC. The prediction accuracy of Hb for sarcopenia in group AC, group NAC, and all patients was 83.6%, 75.9%, and 78.1% (sensitivity: 92.0%, 69.0%, and 80.2%; specificity: 66.4%, 71.0%, and 64.0%), respectively. Although not significant, the predictive performance was better when using the combination of Hb and EA measurements than when using Hb alone in group AC but was comparable in all patients. Hb levels can predict sarcopenia in patients with LC, but in those with AC, the combination of Hb and EA improves the prediction performance.

Abstract Background Sugammadex is a synthetic γ-cyclodextrin derivative designed to selectively bind to steroidal neuromuscular blocking agents and reverse their effects. Although many cases of sugammadex-induced anaphylaxis have been reported, few studies have investigated the underlying mechanism. Case presentation A 55-year-old Japanese man underwent a laryngectomy under general anesthesia. One month before laryngectomy, he had undergone laryngoscopy under general anesthesia and received sugammadex administration without causing hypersensitivity. He had no history of allergies. The operation was finished without complications. Shortly after sugammadex administration, his blood pressure dropped to approximately 70 mmHg, and his heart rate increased to 110 beats/minute with systemic erythema. Suspecting anaphylaxis, he was treated with the intravenous injection of phenylephrine, d-chlorpheniramine, and hydrocortisone. After these treatments, his cardiovascular condition stabilized. Eight months after the event, skin prick tests and intradermal tests with all agents used during general anesthesia were performed. Intradermal tests showed positive results only for sugammadex. Subsequently, basophil activation tests with CD203c were performed using sugammadex, γ-cyclodextrin, and positive controls (anti-immunoglobulin-E and formyl-methionyl-leucyl-phenylalanine). In addition to both controls, sugammadex, but not γ-cyclodextrin, induced significant upregulation of CD203c expression. We performed additional basophil activation tests with wortmannin, an inhibitor of phosphoinositide 3-kinase, to investigate the mechanism underlying sugammadex-induced basophil activation. The inhibitory effect of wortmannin on basophil activation due to sugammadex was similar to that of anti-immunoglobulin-E, suggesting an immunoglobulin-E-dependent mechanism. Although the patient showed no hypersensitivity after the first exposure of sugammadex, anaphylaxis appeared after the second administration. Because most cases of sugammadex-induced anaphylaxis reportedly appeared after first administration, this seems to be a rare case. Conclusions In the present case, sugammadex-induced anaphylaxis might have occurred through an immunoglobulin-E-dependent mechanism and not involve γ-cyclodextrin as an epitope. Physicians should pay attention to the occurrence of sugammadex-induced anaphylaxis even when the patient has a history of safe administration of sugammadex.

Abstract We previously found that N‐89 and its derivative, N‐251, which are being developed as antimalarial compounds, showed multiple antiviral activities including hepatitis C virus (HCV). In this study, we focused on the most characterized anti‐HCV activity of N‐89(N‐251) to clarify their antiviral mechanisms. We first prepared cells exhibiting resistance to N‐89(N‐251) than the parental cells by serial treatment of HCV–RNA‐replicating parental cells with N‐89(N‐251). Then, we newly generated HCV–RNA‐replicating cells with the replacement of HCV–RNAs derived from N‐89(N‐251)‐resistant cells and parental cells. Using these cells, we examined the degree of inhibition of HCV–RNA replication by N‐89(N‐251) and found that the host and viral factors contributed almost equally to the resistance to N‐89(N‐251). To further examine the contribution of the host factors, we selected several candidate genes by cDNA microarray analysis and found that the upregulated expression of at least RAC2 and CKMT1B genes independently and differently contributed to the acquisition of an N‐89(N‐251)‐resistant phenotype. For the viral factors, we selected several mutation candidates by the genetic comparative analysis of HCV–RNAs and showed that at least one M414I mutation in the HCV NS5B contributed to the resistance to N‐89. Moreover, we demonstrated that the combination of host factors (RAC2 and/or CKMT1B) and a viral factor (M414I mutation) additively increased the resistance to N‐89. In summary, we identified the host and viral factors contributing to the acquisition of N‐89(N‐251)‐resistance in HCV–RNA replication. These findings will be useful for clarification of the antiviral mechanism of N‐89(N‐251).

Abstract Background Solitary fibrous tumor (SFT) is a relatively rare mesenchymal tumor that mainly affects adults. Its prognosis is good after curative resection, but distant recurrences after 10 years or longer have been reported. Recurrent SFT usually arises as a local lesion; distant metastasis is rarely reported. Here, we report lung metastases that recurred a decade after excising a retroperitoneal primary SFT. Case presentation A 44-year-old woman had an SFT resected from her right retroperitoneum at our hospital. Ten years later, at age 54, she underwent a lung resection after CT showed three suspected metastases in her left lung. All three were histologically diagnosed as lung metastases from the retroperitoneal SFT. However, whereas the primary SFT had 1–2 mitotic cells/10 high power fields (HPF), the metastatic lesion increased malignancy, at 50/10 HPF. Conclusion Patients who have had resected SFTs should be carefully followed up, as malignancy may change in distant metastasis, as in this case.

Background: The impact of anemia on the safety and efficacy of anticoagulants in elderly patients with atrial fibrillation (AF) has not been elucidated. Method and Results: The J-ELD AF Registry is a large-scale, multicenter prospective observational study, of the one-year outcomes after administration of on-label doses of apixaban in Japanese patients with non-valvular AF aged ≥ 75 years. The entire cohort (3,015 patients from 110 institutions) was divided into three subgroups according to the WHO classification of anemia: normal (hemoglobin ≥ 13.0 g/dL in men and ≥ 12.0 g/dL in women, n = 1733, 57.5%), mild anemia (11.0 ≤ hemoglobin

In order to improve handling and stability not only in autonomous vehicles but also in manual vehicles, research had been conducted to appropriately control the two state quantities of vehicle body slip angle and yaw rate. By constructing a state feedback system that centrally controls these two states and applying the walking control technology of a biped robot, natural, smooth and good handling and stability was realized regardless of the driver. In addition, by setting the feedback gain that does not depend on the coefficient of friction of the road surface, it was possible to construct a relatively simple control system without considering the case classification according to the condition of the road surface.

Abstract Background Solid pseudopapillary neoplasm of the pancreas is a rare tumor in young women, metastasizing in only 5–15% of cases, and most commonly to the liver. Although treatment guidelines have not been established, surgical resection is usually performed. We report a rare case of repeat hepatectomy for liver metastases after distal pancreatectomy with solid pseudopapillary neoplasm. Case presentation The patient was a 71-year-old woman who underwent distal pancreatectomy for solid pseudopapillary neoplasm, and liver metastasis occurred 4 years after the first surgery. Partial liver resection was performed for four liver metastases, and histopathological examination revealed a diagnosis of liver metastasis from solid pseudopapillary neoplasm. However, 18 months later, liver metastases were detected again; three tumors were identified, and partial resection was performed, which has provided 18 months’ recurrence-free survival. Conclusions Long-term prognosis can be expected following R0 resection for resectable liver metastasis from solid pseudopapillary neoplasm.

When various sliding components of combustion engines protected with hard coatings are slid with automotive lubricants, unexpected interfacial phenomena may occur because typical automotive lubricants have been formulated with additives suitable for steel/steel sliding components. Therefore, understanding the effects of hard coatings on the performance of lubricant additives is crucial for further improving the lubrication properties of fully formulated oils through the optimization of additive formulations for hard coatings. In this study, friction tests were performed with a steel surface against steel surfaces coated with two ceramic materials and two diamond-like carbon materials under lubrication with a fully formulated oil. Atomic force microscopy and X-ray photoelectron spectroscopic (XPS) investigation of the steel surfaces after the friction tests revealed that the tribofilms comprised a bottom layer composed of calcium compounds and a top layer composed of phosphorous, zinc, and sulfur compounds. The thickness of each layer, which is closely related to the wear property, depends on the hard coating material. Moreover, XPS analysis focusing on the molybdenum element suggested that rate of chemical kinetics to form MoS2 differs among the hard coating materials, and dominantly affects the frictional property.

A pulmonary carcinoid tumor is a rare tumor that lacks a validated therapeutic approach for unresectable disease. Understanding the intersite tumor‐immune heterogeneity is essential to harness the immune system for cancer therapy. However, little is known about the tumor‐immune microenvironment (TIME). Here, we describe a patient who had heterogeneous TIME between primary and metastatic carcinoid tumors which differentially responded to chemoimmunotherapy. A 72‐year‐old man was diagnosed with an advanced pulmonary carcinoid tumor. CT‐guided biopsies of lung and scapular tumors confirmed typical carcinoid (PD‐L1, 1%–24%) and atypical carcinoid tumors (PD‐L1, negative), respectively. Although the primary lung carcinoid tumor showed a partial response, the scapular tumor was significantly enlarged after two cycles of anti‐PD‐L1 antibody therapy in combination with carboplatin plus etoposide. We performed quantitative pathology imaging analysis with fluorescent multiplex immunohistochemistry. CD8+ T cell infiltration was detected in the PD‐L1‐positive primary lung tumor nest; however, it was mostly restrained in the stroma in a PD‐L1‐negative metastatic scapular tumor. Treg infiltrations into both tumor nests and stroma were detected in the lung tumor, which were not detected in the metastatic scapular tumor. This study provides the first evidence of coexistence of heterogeneous TIME within a single individual with a pulmonary carcinoid tumor. This study may provide new insights into the mechanism of primary resistance to chemoimmunotherapy in pulmonary carcinoid tumors.

Abstract Background Renal cell carcinoma (RCC) is a primary tumor with the highest frequency of pancreatic metastasis. Although surgical resection can improve the prognosis of some patients with pancreatic metastasis of RCC (PM-RCC), the role of palliative surgery remains unclear. Herein, we described a case of jejunal limb occlusion caused by a tumor thrombus arising from a PM-RCC which was treated by surgical resection. Case presentation A 75-year-old, male patient with metastatic RCC was admitted to our hospital with new-onset dysphagia and weight loss. Twenty years earlier he underwent a right nephrectomy with an adrenalectomy for the first surgical resection of RCC, and 12 years ago he underwent a left partial nephrectomy for metachronous primary RCC. Nine years later, multiple pancreatic metastases were detected. After discontinuing interferon therapy, he was followed up at his request without anticancer treatment. Multiple, pulmonary metastases developed 3 years ago, and resection of a brain metastasis was performed 6 months ago. He had also undergone a total gastrectomy with Roux-en Y reconstruction and splenectomy for gastric cancer 23 years ago. Computed tomography revealed a metastatic lesion in the pancreatic tail extending into the jejunal limb, which was obstructed by a tumor thrombus. Jejunal limb resection was performed concomitantly with a distal pancreatectomy as palliative surgery. The jejunal limb remnant was approximately 30 cm long and was re-anastomosed to the esophagus using a circular stapler. Blood perfusion at the anastomotic site was confirmed by indocyanine green fluorescence imaging. He was discharged on postoperative day 24 and was followed in the outpatient clinic. He achieved sufficient oral intake at 8 months postoperatively. Conclusions PM-RCC can invade the gastrointestinal tract and cause tumor thrombus formation resulting in bowel occlusion requiring surgical intervention.

Abstract Background The bacterial density of Pseudomonas aeruginosa is closely related to its pathogenicity. We evaluated the effect of airway P. aeruginosa density on the clinical course of mechanically ventilated patients and the therapeutic efficacy of antibiotics. Methods We retrospectively analyzed data of mechanically ventilated ICU patients with P. aeruginosa isolated from endotracheal aspirates. Patients were divided into three groups according to the peak P. aeruginosa density during ICU stay: low (≤ 104 cfu/mL), moderate (105‒106 cfu/mL), and high (≥ 107 cfu/mL) peak density groups. The relationship between peak P. aeruginosa density and weaning from mechanical ventilation, risk factors for isolation of high peak density of P. aeruginosa, and antibiotic efficacy were investigated using multivariate and propensity score-matched analyses. Results Four-hundred-and-sixty-one patients were enrolled. Patients with high peak density of P. aeruginosa had higher inflammation and developed more severe respiratory infections. High peak density of P. aeruginosa was independently associated with few ventilator-free days on day 28 (P

Abstract Background Resting 12-lead electrocardiography is widely used for the detection of cardiac diseases. Electrocardiogram readings have been reported to be affected by aging and, therefore, can predict patient mortality. Methods A total of 12,837 patients without structural heart disease who underwent electrocardiography at baseline were identified in the Shinken Database among those registered between 2010 and 2017 (n = 19,170). Using 438 electrocardiography parameters, predictive models for all-cause death and cardiovascular (CV) death were developed by a support vector machine (SVM) algorithm. Results During the observation period of 320.4 days, 55 all-cause deaths and 23 CV deaths were observed. In the SVM prediction model, the mean c-statistics of 10 cross-validation models with training and testing datasets were 0.881 ± 0.027 and 0.927 ± 0.101, respectively, for all-cause death and 0.862 ± 0.029 and 0.897 ± 0.069, respectively for CV death. For both all-cause and CV death, high values of permutation importance in the ECG parameters were concentrated in the QRS complex and ST-T segment. Conclusions Parameters acquired from 12-lead resting electrocardiography could be applied to predict the all-cause and CV deaths of patients without structural heart disease. The ECG parameters that greatly contributed to the prediction were concentrated in the QRS complex and ST-T segment.

The effect of molecular structure on the traction properties of polyglycol oils was investigated using a traction tester, and in-situ observation of the oil film was performed with a micro-Fourier transform infrared spectrometer under elastohydrodynamic lubrication conditions. The sample oils used were polypropylene glycol (PPG) diol, PPG triol, PPG dimethyl ether, PPG diester, PPG diamine, PPG triamine, and poly-α-olefin. The traction coefficient and oil film thickness of the sample oils were sensitive to the functional group at the terminal of the molecule. The sample oil containing polar functional group is larger in oil film thickness and traction coefficient than non-polar hydrocarbon oil, poly-α-olefin. These results suggest that the hydrogen bonding of functional groups was strengthened by high pressure in the Hertzian contact region. Moreover, the effect of water in the sample oils on the traction behavior was discussed. Water was dissolved into the sample oils from the atmosphere during the lubrication test, and it is implied that water in PPG diamine affect the traction coefficient.

GPF system is expected as a solution for PN/PM regulation which is becoming stricter in gasoline engines. The management system of GPF temperature and residual soot amount in GPF is necessary for the GPF system to execute GPF regeneration control safely and effectively. Therefore, in this study, logics were investigated for GPF temperature and amount of residual soot, and the logics were verified by a test vehicle. This paper describes the development process and verification results.

For semen suppliers, predicting the low fertility of service bull candidates before artificial insemination would help prevent economic loss; however, predicting bull fertility through in vitro assessment of semen is yet to be established. In the present study, we focused on the methylated CpG sites of sperm nuclear DNA and examined methylation levels to screen new biomarkers for predicting bull fertility. In frozen-thawed semen samples collected from Japanese Black bulls, for which the sire conception rate (SCR) was recorded, the methylation level of each CpG site was analyzed using human methylation microarray. According to regression analysis, 143 CpG sites related to SCR were significantly differentially methylated. Whole genome bisulfite sequence data were obtained from three semen samples and the differentially methylated regions (DMRs) that included the target CpG sites selected by human methylation microarray were confirmed. Using combined bisulfite restriction analysis, fertility-related methylation changes were detected in 10 DMRs. With the exception of one DMR, the methylation levels of these DMRs were significantly different between groups with high fertility (> 50%) and low fertility (< 40%). From multiple regression analysis of methylation levels and SCR, three DMRs were selected that could effectively predict bull fertility. We suggest that these fertility-related differences in spermatozoal methylation levels could be new epigenetic biomarkers for predicting bull fertility.

Surface electromyographic activity (sEMG) of the biceps brachii (BB) during weak elbow flexion has been reported to immediately increase after strong elbow flexion even while exerting consistent force; this phenomenon is called “post-contraction potentiation” (PCP). To determine whether the central nervous system is involved in PCP, we investigated the effect of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) during PCP. Initially, the participants were instructed to perform successive muscle contraction tasks with different forces: 2% (Test 1); then 25%, 50%, or 100% (conditioning contraction [CC]); and again 2% (Test 2) of maximum voluntary contraction (MVC). In subsequent experiments, the CC intensity was set at 50% MVC, and tDCS (anodal, cathodal, and sham) was applied to the M1 before the task. In the last experiment, TMS was applied to M1 to evaluate the excitability of the corticospinal tract during Tests 1 and 2. The CC intensity at 50% or 100% MVC generated PCP, but didn’t at 25% MVC. Anodal tDCS significantly decreased the magnitude of PCP, while cathodal tDCS showed an increase in magnitude compared to sham tDCS. The BB motor-evoked potential amplitude during Test 2 was lower compared to that during Test 1. These findings suggest that changes in the excitability of the corticospinal tract and resultant changes in the activation pattern of motor unit activity play a role in generating PCP.

The fifty-year progress of faster-than-Nyquist (FTN) signaling is surveyed. FTN signaling exploits non-orthogonal dense symbol packing in the time domain for the sake of increasing the data rate attained. After reviewing the system models of both the conventional Nyquist-based and FTN signaling transceivers, we survey the evolution of FTN techniques, including their low-complexity detection and channel estimation. Furthermore, in addition to the classic FTN signaling philosophy, we introduce the recent frequency-domain filtering and precoding aided schemes. When relying on precoding, the information rate of FTN signaling becomes related to the eigenvalues of an FTN-specific intersymbol interference matrix, which provides a unified framework for the associated information-theoretic analysis and simplifies the associated power allocation specifically designed for increasing the information rate attained. We show that the FTN signaling scheme combined with bespoke power allocation employing a realistic raised-cosine shaping filter achieves the Shannon capacity associated with ideal rectangular shaping filters.

This paper proposes a buffer-aided relay selection that is capable of exploiting both half-duplex and virtual full-duplex (VFD) transmissions in a hybrid manner. In the proposed scheme, we consider a two-hop cooperative network where each node is equipped with a single antenna, and no direct link between the source to the destination exists. The proposed scheme consists of five relay selection modes: two unicast modes, a broadcast mode, a cooperative beamforming mode, and a VFD mode. Owing to the broadcast mode, multiple relay nodes can seamlessly have a common packet; this mode is capable of solving the inter-relay interference problem imposed on the VFD mode. The proposed scheme’s theoretical performance bounds on the throughput, the outage probability, and the delay are derived. It is demonstrated in our simulations that the proposed scheme attains higher performance in terms of a throughput and an outage probability than the conventional schemes while maintaining an acceptable average end-to-end delay profile.

Abstract Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients.

Abstract HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype–phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype–phenotype correlations are unclear in NMOSD.

One of the most severe side effects of photoimmunotherapy (PIT) for head and neck cancer is pain. As there are presently no detailed reports on pain and pain management in PIT, we conducted a retrospective case series study. We conducted a retrospective study of five patients who had received PIT at the National Cancer Center Hospital East between January 2021 and June 2022 using medical chart data. All patients experienced pain, evidenced by an increased numerical rating scale (NRS) after PIT, regardless of the illumination method. The daily change in mean NRS rating shows that the pain was highest on the day of PIT, with ratings of 6.8 and 7.8 for the frontal and cylindrical diffuser methods, respectively; it dropped the following day quickly. Four of the five patients received fentanyl injections for postoperative pain management beginning on postoperative day (POD) 0. All patients who underwent therapy using a cylindrical diffuser required postoperative pain management with opioid drugs. Pain after PIT tended to be most intense immediately after or one hour after illumination and declined the following day, suggesting the need to have a pain relief plan in place in advance.

Introduction Cross‐fused renal ectopia is a rare congenital malformation, and few cases of urolithiasis have been treated by retrograde ureteroscopic lithotripsy. We report a case of urolithiasis in right‐to‐left and superior‐type cross‐fused renal ectopia, successfully treated by the retrograde approach. Case presentation A 69‐year‐old woman with two 14‐mm renal stones in cross‐fused renal ectopia underwent retrograde ureteroscopic lithotripsy. Although we did not recognize the anomaly preoperatively, we could diagnose urolithiasis in the ectopic kidney intraoperatively. The patient had no complication, and follow‐up computed tomography after 3 months showed only a 5‐mm renal stone. Conclusion Although urolithiasis in patients with cross‐fused renal ectopia is a challenging condition for the urologist, the retrograde approach is a safe and effective treatment method. It is necessary to carefully examine the urinary tract especially in a patient with a history of unidentified solitary kidney.