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The influence of general anaesthetic agents on intra-operative neurophysiological monitoring in neonates and infants has rarely been reported. Propofol-based anaesthesia is recommended to avoid suppression of neurophysiological monitoring. However, the administration of propofol in children undergoing prolonged procedures, especially those younger than six months, should be carefully controlled due to the potential risk of propofol infusion syndrome. Adding a small dose of inhalational anaesthetic can be an option to reduce propofol requirements. Recent guidelines in Japan suggest limiting inhalational anaesthetics to less than 0.5 minimum alveolar concentrations when co-administered with low-dose propofol during intra-operative neuromonitoring. However, there is still insufficient evidence regarding the impact of sevoflurane on neurophysiological monitoring when co-administered with propofol in infants. This report describes a case of a three-month-old infant undergoing spinal lipoma resection in which there was a dramatic suppression of neurophysiological monitoring with the addition of 0.35-0.45% sevoflurane to propofol-based anaesthesia.
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INTRODUCTION: Dual-energy computed tomography (DECT) can generate virtual non-contrast (VNC) images. Herein, we sought to improve the accuracy of VNC images by identifying the optimal slope of contrast media (SCM) for VNC-image generation based on the iodine concentration and subject's body size. METHODS: We used DECT to scan a multi-energy phantom including four iodine concentration rods (15, 10, 5, and 2 mg/mL), and 240 VNC images (eight SCM ranging from 0.49 to 0.56 × three body sizes × ten scans) that were generated by three-material decomposition. The CT number of each iodine and solid water rod part was measured in each VNC image. The difference in the CT number between the iodine and the solid water rod part was calculated and compared using paired t-test or repeated measures ANOVA. RESULTS: The SCM that achieved an absolute value of the difference in CT number of <5.0 Hounsfield units (HU) for all body sizes simultaneously was greater at lower iodine concentration (SCM of 0.5, 0.51, and 0.53 at 10, 5, and 2 mg/mL iodine, respectively). At an iodine concentration of 15 mg/mL, no SCM achieved an absolute difference of <5.0 HU in CT number for all body sizes simultaneously. At all iodine concentrations, the SCM achieving the minimal difference in the CT number increased with the increase in body size. CONCLUSION: By adjusting the SCM according to the iodine concentration and body size, it is possible to generate VNC images with an accuracy of <5.0 HU. IMPLICATIONS FOR PRACTICE: Improving the accuracy of VNC images minimizing incomplete iodine subtraction would make it possible to replace true non-contrast (TNC) images with VNC images and reduce the radiation dose.
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Iodo , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Reprodutibilidade dos Testes , Imagens de FantasmasRESUMO
The atomic masses of ^{55}Sc, ^{56,58}Ti, and ^{56-59}V have been determined using the high-precision multireflection time-of-flight technique. The radioisotopes have been produced at RIKEN's Radioactive Isotope Beam Factory (RIBF) and delivered to the novel designed gas cell and multireflection system, which has been recently commissioned downstream of the ZeroDegree spectrometer following the BigRIPS separator. For ^{56,58}Ti and ^{56-59}V, the mass uncertainties have been reduced down to the order of 10 keV, shedding new light on the N=34 shell effect in Ti and V isotopes by the first high-precision mass measurements of the critical species ^{58}Ti and ^{59}V. With the new precision achieved, we reveal the nonexistence of the N=34 empirical two-neutron shell gaps for Ti and V, and the enhanced energy gap above the occupied νp_{3/2} orbit is identified as a feature unique to Ca. We perform new Monte Carlo shell model calculations including the νd_{5/2} and νg_{9/2} orbits and compare the results with conventional shell model calculations, which exclude the νg_{9/2} and the νd_{5/2} orbits. The comparison indicates that the shell gap reduction in Ti is related to a partial occupation of the higher orbitals for the outer two valence neutrons at N=34.
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Nêutrons , TitânioRESUMO
BACKGROUND: We conducted comprehensive clinical and molecular characterization of claudin 18.2 expression (CLDN18.2) in advanced gastric or gastroesophageal junction cancer (GC/GEJC). PATIENTS AND METHODS: Patients with advanced GC/GEJC who received systemic chemotherapy from October 2015 to December 2019 with available tumor specimens were analyzed. We evaluated clinicopathological features of CLDN18.2 expression with four molecular subtypes: mismatch repair deficient, Epstein-Barr virus-positive, human epidermal growth factor receptor 2-positive, and others. In addition, programmed death-ligand 1 (PD-L1) combined positive score (CPS), genomic alterations, and the expression of immune cell markers were assessed. Clinical outcomes of standard first- or second-line chemotherapy and subsequent anti-programmed cell death protein 1 (anti-PD-1) therapy were also investigated according to CLDN18.2 expression. RESULTS: Among 408 patients, CLDN18.2-positive (moderate-to-strong expression in ≥75%) was identified in 98 patients (24.0%) with almost equal distribution in the four molecular subtypes or CPS subgroups. CLDN18.2-positive was associated with Borrmann type 4, KRAS amplification, low CD16, and high CD68 expression. Overall survival with first-line chemotherapy was not significantly different between CLDN18.2-positive and -negative groups [median 18.4 versus 20.1 months; hazard ratio 1.26 (95% confidence interval 0.89-1.78); P = 0.191] regardless of stratification by PD-L1 CPS ≥5. Progression-free survival and objective response rates of first- and second-line chemotherapy, and anti-PD-1 therapy also showed no significant differences according to CLDN18.2 status. CONCLUSIONS: CLDN18.2 expression in advanced GC/GEJC was associated with some clinical and molecular features but had no impact on treatment outcomes with chemotherapy or checkpoint inhibition. CLDN18.2-positive also had no impact on overall survival. This information could be useful to interpret the results from currently ongoing clinical trials of CLDN18.2-targeted therapies for advanced GC/GEJC and to consider a treatment strategy for CLDN18.2-positive GC/GEJC.
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Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Antígeno B7-H1 , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/metabolismo , Neoplasias Gástricas/patologia , Junção Esofagogástrica/metabolismo , Junção Esofagogástrica/patologia , Claudinas/genética , Claudinas/uso terapêuticoRESUMO
Magnetic reconnection in laser-produced magnetized plasma is investigated by using optical diagnostics. The magnetic field is generated via the Biermann battery effect, and the inversely directed magnetic field lines interact with each other. It is shown by self-emission measurement that two colliding plasmas stagnate on a midplane, forming two planar dense regions, and that they interact later in time. Laser Thomson scattering spectra are distorted in the direction of the self-generated magnetic field, indicating asymmetric ion velocity distribution and plasma acceleration. In addition, the spectra perpendicular to the magnetic field show different peak intensity, suggesting an electron current formation. These results are interpreted as magnetic field dissipation, reconnection, and outflow acceleration. Two-directional laser Thomson scattering is, as discussed here, a powerful tool for the investigation of microphysics in the reconnection region.
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A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.
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There is a lack of evidence regarding the optimal intra-operative glycaemic level of patients with ornithine transcarbamylase deficiency to prevent cerebral oedema due to protein catabolism and hyperammonemia. We describe a case of a two-year-old girl with ornithine transcarbamylase deficiency who underwent cardiac surgery requiring cardiopulmonary bypass. A high-dose dextrose infusion to prevent protein catabolism was given throughout surgery, which caused uncontrollable hyperglycaemia unresponsive to high-dose insulin administration. Factors contributing to the hyperglycaemia may have included surgical stress, steroid administration and hypothermia. During invasive surgery, anaesthetists should carefully adjust the rates of dextrose and insulin infusions, guided by close monitoring of blood ammonia, glucose and lactate.
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OBJECTIVES: Contact tracing for COVID-19 relies heavily on the cooperation of individuals with authorities to provide information of contact persons. However, few studies have clarified willingness to cooperate and motivation to provide information for contact tracing. This study sought to describe willingness to cooperate and motivation to report contact persons for COVID-19 contact tracing among citizens in Japan, and to assess any associated sociodemographic factors. STUDY DESIGN: Cross-sectional study. METHODS: This was an online-based survey using quota sampling. Participants were asked about their willingness to cooperate in reporting contacts for COVID-19 contact tracing if they tested positive. Participants also responded to questions regarding their reasons for cooperating or not cooperating and provided sociodemographic data. Multiple logistic regression analysis was performed to clarify associations between sociodemographic factors and willingness to cooperate. RESULTS: This study included 2844 participants. The proportion of participants who were not willing to cooperate in reporting contacts was 27.6%, with their main reasons being concerns about causing trouble for the other person and being criticised for revealing their names. Willingness to cooperate was lower among men, young adults and those with an educational level less than a university degree. CONCLUSIONS: To improve the effectiveness of contact tracing, educational campaigns, such as reducing the fear and stigma associated with COVID-19, may be important. Furthermore, it is essential to understand that individuals may have contacts whom they do not wish to disclose to others and to be considerate when handling such situations.
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COVID-19 , Busca de Comunicante , COVID-19/epidemiologia , Estudos Transversais , Humanos , Japão/epidemiologia , Masculino , Inquéritos e Questionários , Adulto JovemRESUMO
Magnetic reconnection is a universal process in space, astrophysical, and laboratory plasmas. It alters magnetic field topology and results in energy release to the plasma. Here we report the experimental results of a pure electron outflow in magnetic reconnection, which is not accompanied with ion flows. By controlling an applied magnetic field in a laser produced plasma, we have constructed an experiment that magnetizes the electrons but not the ions. This allows us to isolate the electron dynamics from the ions. Collective Thomson scattering measurements reveal the electron Alfvénic outflow without ion outflow. The resultant plasmoid and whistler waves are observed with the magnetic induction probe measurements. We observe the unique features of electron-scale magnetic reconnection simultaneously in laser produced plasmas, including global structures, local plasma parameters, magnetic field, and waves.
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We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.
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BACKGROUND: In the randomized phase III KEYNOTE-181 study, pembrolizumab prolonged overall survival (OS) compared with chemotherapy as second-line therapy in patients with advanced esophageal cancer and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥10. We report a post hoc subgroup analysis of patients with esophageal squamous cell carcinoma (ESCC) enrolled in KEYNOTE-181 in Asia, including patients from the KEYNOTE-181 China extension study. PATIENTS AND METHODS: Three hundred and forty Asian patients with advanced/metastatic ESCC were enrolled in KEYNOTE-181, including the China cohort. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks for ≤2 years or investigator's choice of paclitaxel, docetaxel, or irinotecan. OS, progression-free survival, response, and safety were analyzed without formal comparisons. OS was evaluated based on PD-L1 CPS expression level. RESULTS: In Asian patients with ESCC, median OS was 10.0 months with pembrolizumab and 6.5 months with chemotherapy [hazard ratio (HR), 0.63; 95% CI 0.50-0.80; nominal P < 0.0001]. Median progression-free survival was 2.3 months with pembrolizumab and 3.1 months with chemotherapy (HR, 0.79; 95% CI 0.63-0.99; nominal P = 0.020). Objective response rate was 17.1% with pembrolizumab and 7.1% with chemotherapy; median duration of response was 10.5 months and 7.7 months, respectively. In patients with PD-L1 CPS <1 tumors (pembrolizumab versus chemotherapy), the HR was 0.99 (95% CI 0.56-1.72); the HR (95% CI) for death was better for patients with PD-L1 CPS cut-offs >1 [CPS ≥1, 0.57 (0.44-0.75); CPS ≥5, 0.56 (0.41-0.76); CPS ≥10, 0.53 (0.37-0.75)]. Treatment-related adverse events were reported in 71.8% of patients in the pembrolizumab group and 89.8% in the chemotherapy group; grade 3-5 events were reported in 20.0% and 44.6%, respectively. CONCLUSIONS: Pembrolizumab monotherapy demonstrated promising efficacy in Asian patients with ESCC, with fewer treatment-related adverse events than chemotherapy. PD-L1 CPS ≥1 is an appropriate cut-off and a predictive marker of pembrolizumab efficacy in Asian patients with ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/induzido quimicamente , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , HumanosRESUMO
Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324.
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Vacinas Anticâncer/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T Citotóxicos/imunologia , Idoso , Antígenos de Neoplasias/imunologia , Feminino , Antígeno HLA-A24/imunologia , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Linfócitos T Citotóxicos/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Vacinas de Subunidades Antigênicas/uso terapêuticoRESUMO
To identify the precise molecular processes to induce DNA lesions, we attempt a novel spectroscopy of X-ray induced luminescence (XIL) using soft X-ray synchrotron radiation, which is a non-destructive analysis of the reaction intermediates in the elementary reaction pathway of damage induction and self-organized restoration. Using a liquid micro-jet technique to introduce aqueous samples in a vacuum chamber, we measure UV-visible luminescence from nucleotide solution as a function of the soft X-ray energy from the nitrogen to oxygen K-edge region. The XIL intensities for the nucleotide solutions are significantly enhanced in the soft X-ray region (410-530 eV) which is ascribed to the K-shell excitation/ionization of nitrogen atoms in the nucleobases. Furthermore, the XIL spectra do not show any signature of X-ray absorption near-edge structure (XANES) of the nucleobases. This is because the luminescence intensities collected from the integral area of the micro-jet only reflect the quantum yield of luminescence of the absorbed X-ray into UV-visible light irrespective of the absorption cross sections, i.e. of XANES. Thus the present result is the first evidence of luminescence as a result of X-ray absorption of aqueous nucleotides.
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DNA/química , DNA/efeitos da radiação , Desoxirribonucleotídeos/química , Desoxirribonucleotídeos/efeitos da radiação , Desenho de Equipamento , Concentração de Íons de Hidrogênio , Luminescência , Nitrogênio/química , Oxigênio/química , Síncrotrons , Água/química , Espectroscopia por Absorção de Raios XRESUMO
BACKGROUND AND AIMS: Recent studies identified that metabolically abnormal non-overweight phenotype is a risk factor for cardiovascular diseases. However, only little is known about risk factors for the progression from metabolically healthy non-overweight (MHNO) to metabolically abnormal phenotype. In this study, we investigated the impact of respiratory function on the progression from MHNO to metabolically abnormal phenotype. METHODS AND RESULTS: In this retrospective cohort study, 8949 (3872 men and 5077 women) individuals with MHNO, who participated in a health-checkup program from 2004 to 2015, were enrolled. Four metabolic factors (high-normal blood pressure or hypertension, impaired fasting glucose or diabetes, hypertriglyceridemia, and low HDL cholesterol concentration) were used to define metabolically healthy (less than two factors) or metabolically abnormal (two or more factors) phenotypes. Respiratory function was measured by spirometry. Over a median 4.0 years of follow-up, 927 participants progressed to metabolically abnormal phenotype. The percentage of FVC for predicted values (HR 0.98, 95% CI 0.93-1.03, p = 0.418) was not associated with the progression to metabolically abnormal phenotype after adjusting for covariates, including age, sex, alcohol consumption, exercise, smoking status, and body mass index, whereas the percentage of FEV1 for predicted values (%FEV1) (HR 0.87, 95% CI 0.84-0.91, p < 0.001) and the FEV1/FVC ratio (HR 0.86, 95% CI 0.78-0.95, p = 0.004) were associated with the progression to metabolically abnormal phenotype. CONCLUSION: Decrease in respiratory function in terms of %FEV1 and the FEV1/FVC ratio is associated with the progression to metabolically abnormal phenotype in individuals with MHNO.
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Pulmão/fisiopatologia , Síndrome Metabólica/fisiopatologia , Obesidade Metabolicamente Benigna/fisiopatologia , Respiração , Adulto , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Japão/epidemiologia , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade Metabolicamente Benigna/diagnóstico , Obesidade Metabolicamente Benigna/epidemiologia , Fenótipo , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Capacidade VitalRESUMO
INTRODUCTION: Antithrombin resistance (ATR) is a novel thrombotic risk in abnormal prothrombins. A manual ATR assay using Oxyuranus scutellatus (Ox) venom as a prothrombin activator was established for detecting antithrombin-resistant prothrombin. However, this assay was limited because of Ox snake venom availability and its throughput capacity. Here, we have improved the ATR assay using bovine factors Xa and Va (FXa/Va) as prothrombin activators and have optimised assay conditions for an automated instrument (ACL TOP 500). METHODS: Diluted plasma was incubated with a prothrombin activator mix (phospholipids, CaCl2 , and bovine FXa/Va), followed by inactivation with antithrombin for 10, 20 and 30 minutes. We added a chromogenic substrate S-2238, and assessed changes in absorbance/min at 405 nm. We also adapted assay conditions for ACL TOP 500. RESULTS: Optimum conditions for FXa/Va treatment were 6.25% phospholipids, 5 mM CaCL2 , 0.01 µg/mL FXa and 0.1 µg/mL FVa. ATR assay kinetics with the FXa/Va activator was comparable with that with the Ox activator in heterozygous reconstituted plasma with the recombinant wild-type or antithrombin-resistant prothrombin. Using ACL TOP 500, optimum conditions for the FXa/Va treatment were 10.0% phospholipids, 5 mM CaCl2 , 0.02 µg/mL FXa and 0.2 µg/mL FVa. The automated ATR assay with the FXa/Va activator demonstrated good detectability for antithrombin-resistant prothrombin in plasma from a heterozygous carrier with prothrombin Yukuhashi or Belgrade. CONCLUSION: We optimised the ATR assay with the FXa/Va activator and adapted the assay for ACL TOP 500; the assay showed the ability to clearly detect antithrombin-resistant prothrombin in manual and automated procedures.