Search Results (62)

Background: Prescribing antiviral agents for severe acute respiratory syndrome coronavirus 2 requires careful consideration based on the patient’s risk factors for severe disease progression and their vaccination status. However, effective interventions ensuring the appropriate use of antiviral agents by physicians have yet to be fully established. Thus, this study evaluated the impact of an educational film on antiviral prescription rates for coronavirus disease 2019 (COVID-19). Methods: This prospective, nationwide, web-based survey enrolled 1500 physicians. They were instructed to view a short educational film and assess the necessity of prescribing antiviral agents in 16 fictitious scenarios featuring adult patients with COVID-19 with varying risk factors for severe disease and vaccination statuses. We compared the antiviral prescription rates before and after viewing the educational film. Results: There was a significant increase in the antiviral prescription rates after viewing the educational film, particularly nirmatrelvir/ritonavir prescribed in cases involving immunocompromised patients (from 31.3% to 49.4%) and those with obesity (from 15.1% to 33.7%) who were unvaccinated and had no risk of drug interactions. However, viewing the educational film made little to no impact on the prescription rates for the patients with hypertension and hyperlipidemia or those with no underlying conditions. Conclusions: Short educational films may promote the appropriate use of antiviral agents for COVID-19. However, their impact on altering prescription behavior appears limited and varies according to the clinical context. Full article

Background/Objectives: In a recent study, we investigated anti-VEGF treatment strategies for three subtypes of neovascular age-related macular degeneration (nAMD)—typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)—among a large cohort of Japanese patients. To further explore these findings, we conducted a post hoc analysis of this cohort to identify factors associated with the discontinuation of anti-VEGF therapy for nAMD in a real-world clinical setting. Methods: We collected medical records of patients newly diagnosed with nAMD who initiated intravitreal anti-VEGF antibody injection therapy. Patients were divided into two groups: those who continued anti-VEGF therapy for one year and those who discontinued treatment. Baseline best-corrected visual acuity, optical coherence tomography (OCT) findings, injection regimen, and the type of anti-VEGF antibody drug used were analyzed using univariate and multivariate analyses. Results: A total of 667 treatment-naïve nAMD patients initiated anti-VEGF agents and followed the therapy for 1 year. The one-year dropout rate in this study was 13%. Logistic regression analysis revealed that poor initial visual acuity and a PRN treatment regimen were significantly associated with higher odds of dropout. Age, gender, systemic factors, and the choice of intravitreal injection did not show any significant differences. Conclusions: Poor initial visual acuity and PRN treatment regimens may increase the risk of treatment dropout and should be carefully monitored. Full article

The appearances of Schisandrae Sphenantherae Fructus (SSF) and Schisandrae Chinensis Fructus (SCF) are very similar. Thus, being able to distinguish between SSF and SCF is useful for the quality control of these herbal medicines. In this study, two kinds of electrochemical fingerprint analyses using voltammetry or HPLC with electrochemical detection (HPLC-ECD) were developed in combination with multivariate analysis for discriminating between SSF and SCF. The data sets of the oxidation current values from voltammograms of SSF and SCF samples ranging from +0.5 to +1.0 V were applied to perform a partial least squares discriminant analysis (PLS-DA). Moreover, the data sets of the current heights of the characteristic target peaks on the chromatograms at an applied potential of +0.9 V were also applied to perform PLS-DA. In each PLS-DA obtained from the voltammograms and chromatograms, the scores for the SSF samples were plotted on a different region compared with the scores for the SCF samples. Considering the results of the cross-validation, the HPLC-ECD clearly discriminated between the SSF and SCF samples when compared with the voltammetry. In conclusion, our results show that the present electrochemical fingerprint analyses coupled with PLS-DA are useful as a means for discriminating between the SSF and SCF samples. Full article

Background: Frailty increases the risk of needing nursing care and significantly affects the life and functional prognosis of older individuals. Early detection and tailored interventions are crucial for maintaining and enhancing their life functions. Recognizing distinct clinical phenotypes is essential for devising appropriate interventions. This study aimed to explore diverse frailty phenotypes, focusing on poor nutrition in older Japanese individuals through observational research. Methods: Twenty-one nursing home residents underwent a comprehensive survey covering physical, blood, dietary, cardiac, cognitive, nutritional, nursing care, frailty, agitated behavior, and gut microbiome assessments (high-throughput 16S rRNA gene sequencing). Using clustering analysis with 239 survey items (excluding gut microbiome), participants were classified into subgroups based on clinical phenotypes, and group characteristics were compared through analysis. Results: Individuals with moderate or severe frailty and suspected dementia formed subgroups with distinct clinical phenotypes based on nutritional, defecation, and nursing care statuses. The gut microbiome significantly varied among these groups (p = 0.007), indicating its correlation with changes in clinical phenotype. Nutritional status differences suggested poor nutrition as a differentiating factor in the core clinical phenotype. Conclusions: This study proposes that the gut microbiome differs based on the clinical phenotype of Japanese older individuals with frailty, and targeted interventions addressing the gut microbiome may contribute to preventing frailty in this population. Full article

Sensory disturbances and central nervous system symptoms are important in patients with Minamata disease. In the peripheral nervous system of these patients, motor nerves are not strongly injured, whereas sensory nerves are predominantly affected. In this study, we investigated the mechanisms underlying the sensory-predominant impairment of the peripheral nervous system caused by methylmercury. We found that the types of cell death in rat dorsal root ganglion (DRG) neurons caused by methylmercury included apoptosis, necrosis, and necroptosis. Methylmercury induced apoptosis in cultured rat DRG neurons but not in anterior horn neurons or Schwann cells. Additionally, methylmercury activated both caspase 8 and caspase 3 in DRG neurons. It increased the expression of tumor necrosis factor (TNF) receptor-1 and the phosphorylation of receptor-interacting protein kinase 3 (RIP3) and mixed-lineage kinase domain-like pseudokinase (MLKL). The expression of TNF-α was increased in macrophage-like RAW264.7 cells by methylmercury. The increase was suggested to be mediated by the NF-κB pathway. Moreover, methylmercury induced neurological symptoms, evaluated by a hindlimb extension response, were significantly less severe in TNF-α knockout mice. Based on these results and our previous studies, we propose the following hypothesis regarding the pathogenesis of sensory nerve-predominant damage by methylmercury: First, methylmercury accumulates within sensory nerve neurons and initiates cell death mechanisms, such as apoptosis, on a small scale. Second, cell death triggers the infiltration of macrophages into the sensory fibers. Third, the macrophages are stimulated by methylmercury and secrete TNF-α through the NF-κB pathway. Fourth, TNF-α induces cell death mechanisms, including necrosis, apoptosis through the caspase 8/3 pathway, and necroptosis through the TNFR1-RIP1-RIP3-MLKL pathway, activated by methylmercury in sensory neurons. Consequently, methylmercury exhibits potent cytotoxicity specific to the DRG/sensory nerve cells in the peripheral nervous system. This chain of events caused by methylmercury may contribute to sensory disturbances in patients with Minamata disease. Full article

Background/Objectives: Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular age-related macular degeneration (nvAMD). While proactive and adequate treatment generally leads to better visual outcomes, various factors, including the disease type, ocular findings, lifestyle, and systemic status, affect the visual prognosis in clinical settings. This study aimed to identify the factors that affect the visual prognosis in patients with nvAMD treated with anti-VEGF therapy. Methods: We conducted a multicenter retrospective cohort study at eight tertiary referral centers in Japan, where we reviewed the medical records of patients newly diagnosed with nvAMD between January 2014 and December 2019. These patients had started treatment with either ranibizumab (0.5 mg) or aflibercept (2.0 mg) and were followed for at least 1 year. We evaluated the impact of the disease type, systemic factors, and initial fundus findings on the best-corrected visual acuity (BCVA) at 1 year. Results: This study included 182 patients (129 men, 53 women), with a mean age of 75.0 ± 8.6 years. The disease types were categorized as typical AMD (53%), polypoidal choroidal vasculopathy (PCV) (43%), and retinal angiomatous proliferation (RAP) (4%). Univariate analysis identified age, the baseline logarithm of the minimum angle of resolution BCVA, intraretinal fluid (IRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM). Multivariate analysis identified the following significant risk factors associated with vision worsening: age, smoking history, diabetes, and the presence of IRF and PED. Conclusions: The presence of IRF, PED, and SHRM at the start of treatment and a history of smoking and diabetes may be associated with a poor visual prognosis in patients with nvAMD. Full article

Some Corynebacterium strains produce toxins that are similar to those produced by Corynebacterium diphtheriae, leading to human infections that are often transmitted through zoonotic diseases. A novel species, which is formerly classified as Corynebacterium ulcerans lineage II, was recently re-evaluated and renamed “Corynebacterium ramonii sp. nov.”. We isolated C. ramonii from a human skin ulcer in Japan in 2023 (KCU0303-001) and identified it as ST344 using a genomic analysis. In addition, C. ramonii KPHES-18084 (ST344) and six strains of C. ulcerans (ST337/ST1011) were isolated from the oral cavities of 7/208 rescued cats (3.4%). The human ulcer strain KCU0303-001 and the rescued cat strain KPHES-18084 were found to be ST344 and closely related clones by core-genome and pan-genome analyses, suggesting that ST344 may be endemic to both clinical and companion animals in Japan. In support of this finding, another clinical isolate of ST344 (TSU-28 strain) was reported in Japan in 2019. Although ST337 is the most common C. ulcerans infection, the second most recent clinical isolate of C. ramonii, ST344, might be increasing; therefore, further genomic surveillance is required to monitor C. ramonii and C. ulcerans infections. Full article

Gastric cancer is one of the most common cancers worldwide, and new therapeutic strategies are urgently needed. Ferroptosis is an intracellular iron-dependent cell death induced by the accumulation of lipid peroxidation, a mechanism different from conventional apoptosis and necrosis. Therefore, induction of ferroptosis is expected to be a new therapeutic strategy. Glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) have been identified as the major inhibitors of ferroptosis. Herein, we performed immunohistochemistry for GPX4, FSP1, and 4-HNE using tissues from patients with gastric cancer and investigated the relationship between these factors and prognosis. Patients with high GPX4 expression or high GPX4 expression and low 4-HNE accumulation tended to have a poor prognosis (p = 0.036, 0.023), whereas those with low FSP1 expression and high 4-HNE accumulation had a good prognosis (p = 0.033). The synergistic induction of cell death by inhibiting GPX4 and FSP1 in vitro was also observed, indicating that the cell death was non-apoptotic. Our results indicate that the expression and accumulation of lipid peroxidation-related factors play an important role in the clinicopathological significance of gastric cancer and that novel therapeutic strategies targeting GPX4 and FSP1 may be effective in treating patients with gastric cancer who have poor prognosis. Full article

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

Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study’s findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation. Full article

Background: Diffusion-weighted images (DWI) obtained by echo-planar imaging (EPI) are frequently degraded by susceptibility artifacts. It has been suggested that DWI obtained by fast advanced spin-echo (FASE) or reconstructed with deep learning reconstruction (DLR) could be useful for image quality improvements. The purpose of this investigation using in vitro and in vivo studies was to determine the influence of sequence difference and of DLR for DWI on image quality, apparent diffusion coefficient (ADC) evaluation, and differentiation of malignant from benign head and neck tumors. Methods: For the in vitro study, a DWI phantom was scanned by FASE and EPI sequences and reconstructed with and without DLR. Each ADC within the phantom for each DWI was then assessed and correlated for each measured ADC and standard value by Spearman’s rank correlation analysis. For the in vivo study, DWIs obtained by EPI and FASE sequences were also obtained for head and neck tumor patients. Signal-to-noise ratio (SNR) and ADC were then determined based on ROI measurements, while SNR of tumors and ADC were compared between all DWI data sets by means of Tukey’s Honest Significant Difference test. Results: For the in vitro study, all correlations between measured ADC and standard reference were significant and excellent (0.92 ≤ ρ ≤ 0.99, p < 0.0001). For the in vivo study, the SNR of FASE with DLR was significantly higher than that of FASE without DLR (p = 0.02), while ADC values for benign and malignant tumors showed significant differences between each sequence with and without DLR (p < 0.05). Conclusion: In comparison with EPI sequence, FASE sequence and DLR can improve image quality and distortion of DWIs without significantly influencing ADC measurements or differentiation capability of malignant from benign head and neck tumors. Full article

Background: Bone morphogenetic protein-2 (bmp-2) has a high potential to induce bone tissue formation in skeletal muscles. We developed a bone induction system in skeletal muscles using the bmp-2 gene through in vivo electroporation. Natural bone tissues with skeletal muscles can be considered potential candidates for biomaterials. However, our previous system using plate-type electrodes did not achieve a 100% success rate in inducing bone tissues in skeletal muscles. In this study, we aimed to enhance the efficiency of bone tissue formation in skeletal muscles by using a non-viral bmp-2 gene expression plasmid vector (pCAGGS-bmp-2) and needle-type electrodes. Methods: We injected the bmp-2 gene with pCAGGS-bmp-2 into the skeletal muscles of rats’ legs and immediately placed needle-type electrodes there. Skeletal tissues were then observed on the 21st day after gene transfer using soft X-ray and histological analyses. Results: The use of needle-type electrodes resulted in a 100% success rate in inducing bone tissues in skeletal muscles. In contrast, the plate-type electrodes only exhibited a 33% success rate. Thus, needle-type electrodes can be more efficient and reliable for transferring the bmp-2 gene to skeletal muscles, making them potential biomaterials for repairing bone defects. Full article

Introduction: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. Methods: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). Results: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. Conclusions: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response. Full article

We previously showed that upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in vascular endothelial cells promotes tumor angiogenesis. In the present study, we aimed to clarify the role of stromal AEBP1/ACLP expression in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis showed that ACLP is abundantly expressed in cancer-associated fibroblasts (CAFs) in primary OSCC tissues and that upregulated expression of ACLP is associated with disease progression. Analysis using CAFs obtained from surgically resected OSCCs showed that the expression of AEBP1/ACLP in CAFs is upregulated by co-culture with OSCC cells or treatment with TGF-β1, suggesting cancer-cell-derived TGF-β1 induces AEBP1/ACLP in CAFs. Collagen gel contraction assays showed that ACLP contributes to the activation of CAFs. In addition, CAF-derived ACLP promotes migration, invasion, and in vivo tumor formation by OSCC cells. Notably, tumor stromal ACLP expression correlated positively with collagen expression and correlated inversely with CD8+ T cell infiltration into primary OSCC tumors. Boyden chamber assays suggested that ACLP in CAFs may attenuate CD8+ T cell migration. Our results suggest that stromal ACLP contributes to the development of OSCCs, and that ACLP is a potential therapeutic target. Full article

This experiment to search for the one of the charged lepton flavor-violating processes, muon-electron conversion, DeeMe, is being conducted at the J-PARC MLF H-Line in Japan. This experiment utilizes a pulsed proton beam from the Rapid Cycling Synchrotron (RCS). A graphite target is bombarded with a pulsed proton beam, negative pion production and pion-in-flight-decay to negative muon; then, the creation of muonic atoms is caused in the same pion production target. A converted electron is expected to be emitted after 1 ∼ 2 micro second-delayed timing. And two-body reaction of the new process, ${\mu }^{-}+(\mathrm{A},\mathrm{Z})\to e^{-}+(\mathrm{A},\mathrm{Z})$, results in 105 MeV monoenergetic electron. Thus, 1 ∼ 2 micro second-delayed 105 MeV monoenergetic electron is a searched signal. Electrons around 105 MeV are transported by the H-Line and analyzed using the dipole magnet (0.4 T) and four multi-wire proportional chambers (MWPCs). However, the burst pulse reaching ${10}^8$ charged particles/pulse attributable to the RCS pulse leads to significant dead time for the MWPC. Thus, the HV switching scheme is introduced to handle the prompt burst. The target single event sensitivity is ${10}^{-13}$. The H-Line construction was completed, and commissioning went well. The overview of the experiment and the current status are described in this article. Full article