Melanoma is a severe and life-threatening malignancy derived from melanocytes. The traditional treatment for melanoma could not sustain satisfactory outcomes long term; however, the recent immune ...checkpoint treatment has made a breakthrough in these problems. Nivolumab is a representative immune checkpoint treatment, and this PD-1-targeted therapy has evolutionally developed and improved the clinical outcome in a recent decade. On the other hand, the clinical application of immune checkpoint treatment presents clinicians with novel questions, especially how to obtain additional efficacy and overcome the disadvantage by using this treatment. To answer these problems, we first investigated the distribution of PD-L1 in various organs to clarify the organs most affected by anti-PD-1 antibody treatment. Among various organs, lung, placenta, spleen, heart, and thyroid highly expressed PD-L1, while skin, thalamus, hippocampus, ovary, stomach, testis, and prostate showed lower expressions of PD-L1. Furthermore, the immune profiles were also examined in tumors and peripheral blood in patients with melanoma. PD-1 was highly expressed in CD8 and CD4 cells, and B cells also highly expressed PD-1 compared with NK cells. However, there was no significant difference in Th1/Th2/Th17 cytokines and inhibitory cytokine IL-10. Although nevus showed a low expression of PD-L1 compared with healthy skin, PD-L1 expression was increased in growth-phase melanoma. Finally, we analyzed the peripheral blood profiles in patients treated with nivolumab. PD-1-bearing dendritic cells (DCs) were increased during nivolumab treatment and Lin-CD11c+HLA-DR+ cells were highly increased during nivolumab treatment. These findings indicate a clue to answering the problems during nivolumab treatment and suggest to us the importance of multiple aspect observation during immune checkpoint treatment.
The global outbreak of COVID-19 is now putting enormous pressure on society to change our traditional social behavior. Government officials are also forced to make short-term decisions based on ...limited information for public health, and investor sentiment about the infection situation in each country has a significant impact on the stock market. In this paper, we attempt to visualize the time series of indexed social sentiment in Japan under the COVID-19 pandemic by using a neural network approach, and clarify changes in the sensitivity of citizens to the coronavirus. The sentiment was classified for Twitter tweets that matched the keywords for which the government was asked to restrict action, and sentiment trends were identified for the period from before the outbreak to the fifth wave of infection in Tokyo, Sapporo, Osaka, and Fukuoka. The indices obtained show a correlation with the number of infected cases by region and with national and local events, and in global cities such as Tokyo and Osaka as they experienced waves of infections and emergency declarations, sensitivity gradually became paralyzed, and parallel trends in sentiment waveforms were observed among regions.
Introduction: Peer support programs are mainly studied by hospitals and medical professionals, and further research is needed on their impact on quality of life (QOL). The purpose of this study was ...to investigate the type of community-based peer support program that is effective for improving the QOL of cancer survivors. Method: A systematic review was performed using the following procedures: (1) randomized controlled trials aimed at improving QOL were searched from PubMed and Igaku Chuo Zasshi, (2) papers that met the inclusion criteria were selected, and (3) the papers were assessed for quality by using the revised Cochrane risk-of-bias tool for randomized trials.Results: Results showed that four studies met the eligibility criteria, and three of them showed statistically significant improvements in QOL. The peers instructed in programs were breast cancer survivors who had been diagnosed one to three years earlier. Furthermore, peers received special training for approximately eight hours per session for a total of two to seven days before providing support to the participants.Conclusion: Few programs have been fully applied in Japan. In terms of program effectiveness and risk of bias, programs that include obtaining support and managing activities that affect mood may be effective. Furthermore, the importance of taking enough time to help cancer survivors trust each other and provide support according to the patient's wishes and available community resources was demonstrated.
Abstract Feline morbillivirus (FmoPV) has recently been identified in Hong Kong and Japan. FmoPV is considered to belong to the genus Morbillivirus, in the family Paramyxoviridae . In this study, the ...complete nucleotide sequences of three strains of FmoPV detected in cats in Japan were determined. Among the six genes in FmoPV; N, P/V/C, M, F, H and L, the P gene showed the highest polymorphism in the nucleotide and putative amino acid sequences among the FmoPV strains. There was no geographical association in terms of the FmoPV phylogeny; however, from extensive phylogenetic and recombination analyses, we found that one Japanese FmoPV strain, MiJP003, was a probable recombinant between two virus strains in the independent lineages found in Japan and Hong Kong, respectively. The recombination was considered to have occurred within the F and H genes. Such recombination is thought to be involved in the evolution of FmoPV.
Feline morbillivirus (FmoPV) is a novel paramyxovirus found to infect domestic cats. FmoPV has been isolated in several countries in Asia and Europe and is considered to have genetic diversity. Also, ...it is suspected to be associated with feline renal diseases including tubulointerstitial nephritis (TIN), which affects domestic cats with a high incidence rate.
To clarify the state of FmoPV infection among domestic cats in Japan, an epidemiological survey was conducted. Twenty-one out of 100 cats were found to have serum antibodies (Ab) against FmoPV-N protein by indirect immunofluorescence assay (IF) using FmoPV-N protein-expressing HeLa cells. Twenty-two of the cats were positive for FmoPV RNA in the urine and/or renal tissues. In total, 29 cats were positive for Ab and/or viral RNA. These FmoPV-infected cats were classified into three different phases of infection: RNA+/Ab + (14 cats), RNA+/Ab- (8 cats) and RNA-/Ab + (7 cats). In immunohistochemistry (IHC), 19 out of 29 cats were positive for FmoPV-N protein in kidney tissues; however, the FmoPV-N protein was located in the inflammatory lesions with severe grade in only four out of the 19 cats. Since 15 out of 29 infected cats were positive for viral RNA and Ab, approximately half of the infected cats were persistently infected with FmoPV.
A statistically significant difference was observed between infection of FmoPV and the presence of inflammatory changes in renal lesions, indicating a relationship between FmoPV infection and feline renal diseases. However, we could not obtain histopathological evidence of a relationship between FmoPV infection and TIN.
Melanoma is a malignant tumor of the melanocytes with an unfavorable clinical behavior. Nivolumab, a representative anti‐programmed death 1 (PD‐1) antibody, has recently been used for the treatment ...of metastatic malignant melanoma. However, there have been few appropriate biomarkers predicting the effect of nivolumab before the administration. Furthermore, the detailed characteristics of peripheral blood mononuclear cell (PBMC) profiles during nivolumab treatment remains unclear. In this study, we investigated fluctuations of PBMC profile during nivolumab treatment. PBMC analysis showed T‐helper (Th)2‐dominant conditions after a first course of nivolumab treatment. In a favorable case treated with nivolumab, a Th1/T‐cytotoxic 1 shift was observed after nivolumab was administrated. These results suggest that flow cytometric analysis of PBMC may be helpful for the treatment of nivolumab.
A 73‐year‐old woman with lung adenocarcinoma (cT4N3M1a: Stage IVA) was treated with atezolizumab as the eighth line of therapy. Four weeks after the fourth dose of atezolizumab, the prothrombin time ...(PT) and activated thromboplastin time (APTT) were prolonged. Coagulation factor V (FV) activity was decreased, and FV inhibitors were observed. There was no history of PT or APTT prolongation or bleeding before the use of atezolizumab. Atezolizumab‐induced coagulation FV inhibitor was diagnosed. After 2 weeks, the PT and APTT spontaneously normalized. FV activity improved and the FV inhibitors disappeared after 6 and 9 weeks, respectively.
In recent years, the use of immune checkpoint inhibitors (ICIs) for the treatment of various carcinomas has increased, which have been associated with immune‐related adverse events (irAEs) that are often diverse. Haematological immune‐related adverse events (hem‐irAEs) are rare, and only a few cases of ICI‐induced coagulation factor inhibitors have been reported. Here, we report a rare case of ICI‐induced factor V inhibitor.
For the safe storage of zeolite wastes generated by the treatment of radioactive saline water at the Fukushima Daiichi Nuclear Power Station, this study investigated the fundamental properties of ...herschelite adsorbent and evaluated its adsorption vessel for hydrogen production and corrosion. The hydrogen produced by the herschelite sample is oxidized by radicals as it diffuses to the water surface and thus depends on the sample's water level and dissolved species. The hydrogen production rate of herschelite submerged in seawater or pure water may be evaluated by accounting for the water depth. From the obtained fundamental properties, the hydrogen concentration of a reference vessel (decay heat = 504 W) with or without residual pure water was evaluated by thermal-hydraulic analysis. The maximum hydrogen concentration was below the lower explosive limit (4%). The steady-state corrosion potential of a stainless steel 316L increased with the absorbed dose rate, but the increase was repressed in the presence of herschelite. The temperature and absorbed dose at the bottom of the 504 W vessel were determined as 60 °C and 750 Gy/h, respectively. Under these conditions, localized corrosion of a herschelite-contacted 316L vessel would not immediately occur at Cl
−
concentrations of 20,000 ppm.
In most animals, avoiding pathogenic bacteria is crucial for better health and a long life span. For this purpose, animals should be able to quickly sense the presence or uptake of pathogens. The ...intestine could be a candidate organ to induce escape behaviors; however, the intestinal signaling mechanism for acute regulation of neuronal activity is not well understood. Here, we show that adult Caenorhabditis elegans can respond to the pathogenic bacterium Pseudomonas aeruginosa within 30 min of exposure. This behavior was much faster than previously observed avoidance behaviors in response to P. aeruginosa. By genetic screening, we isolated a mutant defective in this quick avoidance behavior and found that the novel F‐box protein FBXC‐58 is involved. FBXC‐58 is expressed in several tissues, but defective avoidance was rescued by expression of the protein in the intestine. Interestingly, we also found that some but not all mutants in the p38‐MAPK and insulin‐like signaling pathways, which function in the immune response to pathogens in the intestine, were defective in the quick avoidance behavior to P. aeruginosa. These results suggest that a novel signaling pathway in the intestine exists to regulate neuronal activity for a quick behavioral response.
We show that adult Caenorhabditis elegans can respond to the pathogenic bacterium Pseudomonas aeruginosa within 30 min of exposure. This behavior was much faster than previously observed avoidance behaviors in response to P. aeruginosa. Our results suggest that a novel signaling pathway in the intestine exists to regulate neuronal activity for a quick behavioral response.
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