Identification of heparin-binding proteins expressed on Trichosporon asahii cell surface.

Trichosporon asahii is a pathogenic yeast that cause trichosporonosis. T. asahii exhibits several colony morphologies, such as white (W)- or off-white (O)-type, which may affect virulence. In this study, we compared the expression pattern of heparin-binding proteins in various colony morphologies and identified heparin-binding protein in T. asahii. Surface plasmon resonance analysis revealed that cell surface molecules attached more strongly to heparin in W- than O-type cells. We purified and identified a heparin-binding protein strongly expressed in W-type cells using heparin-Sepharose beads, named it heparin-binding protein 1 (HepBP1), and expressed Flag-tagged HepBP1 in mammalian cells. The heparin-binding ability of Flag-tagged HepBP1 was confirmed by pulldown assay using heparin-Sepharose beads. Thus, HepBP1 is a heparin-binding protein on T. asahii cell surface. These results suggest that several T. asahii cell surface proteins interact with glycosaminoglycans; therefore, they could contribute to infection.

Automated evaluation of masseter muscle volume: deep learning prognostic approach in oral cancer.

BACKGROUND: Sarcopenia has been identified as a potential negative prognostic factor in cancer patients. In this study, our objective was to investigate the relationship between the assessment method for sarcopenia using the masseter muscle volume measured on computed tomography (CT) images and the life expectancy of patients with oral cancer. We also developed a learning model using deep learning to automatically extract the masseter muscle volume and investigated its association with the life expectancy of oral cancer patients. METHODS: To develop the learning model for masseter muscle volume, we used manually extracted data from CT images of 277 patients. We established the association between manually extracted masseter muscle volume and the life expectancy of oral cancer patients. Additionally, we compared the correlation between the groups of manual and automatic extraction in the masseter muscle volume learning model. RESULTS: Our findings revealed a significant association between manually extracted masseter muscle volume on CT images and the life expectancy of patients with oral cancer. Notably, the manual and automatic extraction groups in the masseter muscle volume learning model showed a high correlation. Furthermore, the masseter muscle volume automatically extracted using the developed learning model exhibited a strong association with life expectancy. CONCLUSIONS: The sarcopenia assessment method is useful for predicting the life expectancy of patients with oral cancer. In the future, it is crucial to validate and analyze various factors within the oral surgery field, extending beyond cancer patients.

Analysis of Feeding Behavior Characteristics in the Cu/Zn Superoxide Dismutase 1 (SOD1) SOD1G93A Mice Model for Amyotrophic Lateral Sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a progressive disease affecting upper and lower motor neurons. Feeding disorders are observed in patients with ALS. The mastication movements and their systemic effects in patients with ALS with feeding disorders remain unclear. Currently, there is no effective treatment for ALS. However, it has been suggested that treating feeding disorders and improving nutritional status may prolong the lives of patients with ALS. Therefore, this study elucidates feeding disorders observed in patients with ALS and future therapeutic agents. We conducted a temporal observation of feeding behavior and mastication movements using an open-closed mouth evaluation artificial intelligence (AI) model in an ALS mouse model. Furthermore, to determine the cause of masticatory rhythm modulation, we conducted electrophysiological analyses of mesencephalic trigeminal neurons (MesV). Here, we observed the modulation of masticatory rhythm with a prolonged open phase in the ALS mouse model from the age of 12 weeks. A decreased body weight was observed simultaneously, indicating a correlation between the prolongation of the open phase and the decrease observed. We found that the percentage of firing MesV was markedly decreased. This study partially clarifies the role of feeding disorders in ALS.

Association between home-based exercise using a pedometer and clinical prognosis after endovascular treatment in patients with peripheral artery disease.

BACKGROUND: Exercise therapy following endovascular treatment (EVT) is important for patients with peripheral artery disease (PAD); however, continuous exercise therapy is difficult to be performed in clinical practice. This study aimed to investigate the association between the implementation of home-based exercise using pedometers after EVT and 1-year clinical outcomes. METHODS: This multicenter observational prospective cohort registry included patients with PAD complaining of intermittent claudication who underwent EVT for aortoiliac and/or femoropopliteal artery lesions between January 2016 and March 2019. Patients were instructed to perform home-based exercises using a specific pedometer after EVT. The study population was divided into good and poor recording groups according to the frequency of the pedometer measurements. The good recording group was defined as those who completed ≥50 % of the prescribed daily pedometer recording during the follow-up period. The poor recording group was defined as those with an inability to use a pedometer and/or who completed <50 % of the prescribed daily pedometer recordings. The primary outcome was 1-year major adverse events (MAE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, target vessel revascularization, and major amputation of the target limb. RESULTS: The mean age was 74.4 years; 78 % were male. A total of 623 lesions were analyzed (58.7 % aortoiliac, 41.3 % femoropopliteal). At 1 year, a lower cumulative incidence of MAE was observed in the good recording group compared to that in the poor recording group [10/233 (4.3 %) vs. 35/267 (13.7 %) patients, respectively; p < 0.001]. Multivariate Cox regression analysis showed that patients in the good recording group had a lower hazard ratio for 1-year MAE (0.33; 95 % confidence interval, 0.16-0.68; p = 0.004) than that in the poor recording group. CONCLUSIONS: Good self-recording of pedometer measurements was associated with favorable prognosis in patients with PAD following EVT.

Prediction of cervical lymph node metastasis from immunostained specimens of tongue cancer using a multilayer perceptron neural network.

BACKGROUND: Although cervical lymph node metastasis is an important prognostic factor for oral cancer, occult metastases remain undetected even by diagnostic imaging. We developed a learning model to predict lymph node metastasis in resected specimens of tongue cancer by classifying the level of immunohistochemical (IHC) staining for angiogenesis- and lymphangiogenesis-related proteins using a multilayer perceptron neural network (MNN). METHODS: We obtained a dataset of 76 patients with squamous cell carcinoma of the tongue who had undergone primary tumor resection. All 76 specimens were IHC stained for the six types shown above (VEGF-C, VEGF-D, NRP1, NRP2, CCR7, and SEMA3E) and 456 slides were prepared. We scored the staining levels visually on all slides. We created virtual slides (4560 images) and the accuracy of the MNN model was verified by comparing it with a hue-saturation (HS) histogram, which quantifies the manually determined visual information. RESULTS: The accuracy of the training model with the MNN was 98.6%, and when the training image was converted to grayscale, the accuracy decreased to 52.9%. This indicates that our MNN adequately evaluates the level of staining rather than the morphological features of the IHC images. Multivariate analysis revealed that CCR7 staining level and T classification were independent factors associated with the presence of cervical lymph node metastasis in both HS histograms and MNN. CONCLUSION: These results suggest that IHC assessment using MNN may be useful for identifying lymph node metastasis in patients with tongue cancer.

Machine Learning Analysis of Gaze Data for Enhanced Precision in Diagnosing Oral Mucosal Diseases.

The diagnosis of oral mucosal diseases is a significant challenge due to their diverse differential characteristics. Risk assessment of lesions by visual examination is a complex process due to the lack of definitive guidelines. This study aimed to improve this process by creating a diagnostic algorithm using gaze data acquired during oral mucosal disease examinations. A total of 78 dentists were included in this study. Tobii Pro Nano® (Tobii Technology) was used to acquire gaze data during clinical photographic visual examinations. Advanced analysis tools such as support vector machines and heatmaps were used to visualize the gazing tendencies of a group of skilled oral surgeons, focusing on the number of gazes per region and the gazing time ratios. The preliminary findings showed the possibility of visualizing gazing tendencies and identifying areas of importance for diagnosis. The classification of intraoral photographs based on gross features revealed the existence of an optimal examination method for each category and diagnostically significant areas. This novel approach to analyzing gaze data has the potential to refine diagnostic techniques and increase both accuracy and efficiency.

Bending Angle Sensor Based on Double-Layer Capacitance Suitable for Human Joint.

Goal: To develop bending angle sensors based on double-layer capacitance for monitoring joint angles during cycling exercises. Methods: We develop a bending angle sensor based on double-layer capacitive and conducted three stretching, bending, and cycling tests to evaluate its validity. Results: We demonstrate that the bending angle sensor based on double-layer capacitance minimizes the change in the capacitance difference in the stretching test. The hysteresis and root mean square error (RMSE) compared with the optical motion capture show hysteresis: 8.0% RMSE and 3.1° in the bending test. Moreover, a cycling experiment for human joint angle measurements confirm the changes in accuracy. The RMSEs ranged from 4.7° to 7.0°, even when a human wears leggings fixed with the developed bending-angle sensor in the cycling test. Conclusion: The developed bending angle sensor provides a practical application of the quantitative and observational evaluation tool for knee joint angles.

High platelet reactivity is a predictor of left ventricular remodelling in patients with acute myocardial infarction.

AIMS: Acute myocardial infarction (AMI) is associated with left ventricular remodelling (LVR), which leads to progressive heart failure. Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses during the complex process of myocardial wound healing or repair following AMI. This study aimed to investigate the impact of platelet reactivity immediately after primary percutaneous coronary intervention (PCI) on LVR in AMI patients with ST-segment (STEMI) and non-ST-segment elevation (NSTEMI). METHODS AND RESULTS: This prospective, single-centre, observational study included 182 patients with AMI who underwent primary PCI (107 patient with STEMI and 75 patients with NSTEMI). Patients were administered a loading dose of aspirin plus prasugrel before the procedure, and platelet reactivity was assessed using the VerifyNow P2Y12 assay immediately after PCI. Echocardiography was performed before discharge and during the chronic phase (8 ± 3 months after discharge). LVR was defined as a relative ≥20% increase in left ventricular end-diastolic volume index (LVEDVI). LVR in chronic phase was found in 34 patients (18.7%) whose platelet reactivity was significantly higher than those without LVR (259.6 ± 61.5 and 213.1 ± 74.8 P2Y12 reaction units [PRU]; P = 0.001). The occurrence of LVR did not differ between patients with STEMI and patients with NSTEMI (21.5% and 14.7%; P = 0.33). The optimal cut-off value of platelet reactivity for discriminating LVR was ≥245 PRU. LVEDVI significantly decreased at chronic phase in patients without high platelet reactivity (<245 PRU) (from 49.2 ± 13.5 to 45.4 ± 15.8 mL/m2 ; P = 0.02), but not in patients with high platelet reactivity (≥d245 PRU) (P = 0.06). Multivariate logistic analysis showed that high platelet reactivity was an independent predictor of LVR after adjusting for LVEDVI before discharge (odds ratio, 4.13; 95% confidence interval, 1.85-9.79). CONCLUSIONS: High platelet reactivity measured immediately after PCI was a predictor of LVR in patients with AMI during the chronic phase. The role of antiplatelet therapy on inflammation in the myocardium is a promising area for further research.

Recurrent Fever due to Helicobacter cinaedi Infection during R-CHOP Chemotherapy in Diffuse Large B-Cell Lymphoma: Case Report and Literature Review.

Fever due to Helicobacter cinaedi bacteremia under chemotherapy has not been widely recognized among clinicians. We experienced a 72-year-old man with diffuse large B-cell lymphoma, who was complicated with H. cinaedi bacteremia-induced fever under R-CHOP chemotherapy. We summarized 6 cases including ours, suggesting that fever without neutropenia developing around day 6 from starting chemotherapy is a possible symptom caused by H. cinaedi bacteremia. We should discriminate fever due to H. cinaedi bacteremia if fever emerged before myelosuppression in the course of chemotherapy.

Successful Nonsurgical Treatment of Acute Peritonitis Caused by a Large Thrombosis of the Superior Mesenteric Vein in a 25-year-old Woman.

Superior mesenteric venous thrombosis (SMVT), which results from various etiologies, including coagulation disorders, can be diagnosed early using advanced imaging technology. However, few reports have described the nonsurgical treatment of acute peritonitis caused by SMVT. We encountered a young woman whose history included abdominal pain and daily oral contraceptives and who presented with acute peritonitis caused by SMVT. We administered nonsurgical treatment that included thrombolysis and anticoagulation for the peritonitis (without mesenteric ischemia as confirmed by contrast-enhanced computed tomography). In addition, we showed the importance of investigating persistent risk factors for thromboembolism in young patients to determine the duration of anticoagulation.

[Identification of Heparin-binding Proteins on the Cell Surface of Cryptococcus neoformans].

Interactions between virulence factors of pathogens and host responses play an important role in the establishment of infection by microbes. We focused on interactions between Cryptococcus neoformans proteins and heparin, which is abundant on host epithelial cells. Surface proteins were extracted and analyzed. Fractions from anion-exchange column chromatography interacted with heparin in surface plasmon resonance analyses. Heparin-binding proteins were purified and then separated by gel electrophoresis; and were identified as transaldolase, glutathione-disulfide reductase, and glyoxal oxidase. These results imply that multifunctional molecules on C. neoformans cells, such as those involved in heparin binding, may play roles in adhesion that trigger responses in the host.

Clinical Outcome After Permanent Pacemaker Implantation in Patients With a High Percentage of Ventricular Pacing.

Previous reports have suggested that right ventricular apical pacing may lead to cardiac dysfunction. Septal pacing is thought to be superior to apical pacing in the prevention of cardiac dyssynchrony, however, there have been no reports on the contribution of septal pacing to improving clinical outcome.We retrospectively evaluated factors associated with cardiac events in patients with right ventricular pacing.The study population consisted of 256 consecutive patients newly implanted with permanent pacemakers and followed-up for 29 ± 18 months. Cardiac events, consisting of cardiac death or heart failure requiring hospitalization, occurred in 22 patients. Kaplan-Meier curves revealed that patients with a high percentage of ventricular pacing (> 90%, n = 101, group H) had a higher incidence of cardiac events than patients with a low percentage of ventricular pacing (< 10%, n = 83, group L) (P = 0.002). In group H, multivariate analysis showed that age (HR: 1.174, 95%CI: 1.066-1.291, P = 0.001), ejection fraction (EF) (HR: 0.898, 95%CI: 0.836-0.964, P = 0.003), QRS duration during cardiac pacing (HR: 1.059, 95%CI: 1.017-1.103, P = 0.006), and existing basal cardiac diseases (HR: 13.080, 95%CI: 2.463-69.479, P = 0.003) were significant predictors of cardiac events, although pacing site had no significant association with prognosis (P = 0.56).Higher age, lower EF, longer QRS duration during cardiac pacing, and existing basal cardiac diseases are associated with poor prognosis in patients with a high percentage of ventricular pacing.

Analysis of DNA methylation landscape reveals the roles of DNA methylation in the regulation of drug metabolizing enzymes.

BACKGROUND: Drug metabolizing enzymes (DMEs) exhibit dramatic inter- and intra-individual variability in expression and activity. However, the mechanisms determining this variability have not been fully elucidated. The aim of this study was to evaluate the biological significance of DNA methylation in the regulation of DME genes by genome-wide integrative analysis. RESULTS: DNA methylation and mRNA expression profiles of human tissues and hepatoma cells were examined by microarrays. The data were combined with GEO datasets of liver tissues, and integrative analysis was performed on selected DME genes. Detailed DNA methylation statuses at individual CpG sites were evaluated by DNA methylation mapping. From analysis of 20 liver tissues, highly variable DNA methylation was observed in 37 DME genes, 7 of which showed significant inverse correlations between DNA methylation and mRNA expression. In hepatoma cells, treatment with a demethylating agent resulted in upregulation of 5 DME genes, which could be explained by DNA methylation status. Interestingly, some DMEs were suggested to act as tumor-suppressor or housekeeper based on their unique DNA methylation features. Moreover, tissue-specific and age-dependent expression of UDP-glucuronosyltransferase 1A splicing variants was associated with DNA methylation status of individual first exons. CONCLUSIONS: Some DME genes were regulated by DNA methylation, potentially resulting in inter- and intra-individual differences in drug metabolism. Analysis of DNA methylation landscape facilitated elucidation of the role of DNA methylation in the regulation of DME genes, such as mediator of inter-individual variability, guide for correct alternative splicing, and potential tumor-suppressor or housekeeper.

Predictive factors of cervical spondylotic myelopathy in patients with lumbar spinal stenosis.

OBJECTIVE: To analyze cervical spondylotic myelopathy (CSM) predictive factors in patients with lumbar spinal stenosis (LSS). METHODS: Two hundred thirty-seven patients who visited for low back pain, lower limb pain and/or lower limb numbness and who were diagnosed with LSS were enrolled in this study. The ratio of males to females was 117-120, and the mean age was 68.8 years (range 45-87 years). LSS and CSM were diagnosed by characteristic symptoms, physical findings and MRI. We examined gender, age, Torg-Pavlov ratio (TPR), spondylolisthesis or spondylosis, LSS symptom types and number of stenosis segments with LSS to clarify predictive factors for CSM. RESULTS: There were 21 (8.86%) patients with coexistent CSM among 237 LSS patients. CSM morbidity was significantly more common among males compared with females. TPR was 0.71 ± 0.09 in the CSM patients and 0.81 ± 0.10 in the non-CSM patients. TPR of the CSM patients was significantly smaller than that of the non-CSM patients. We analyzed to determine the predictive factors of CSM and TPR was identified. The predictive value of TPR for CSM was 0.78. CONCLUSION: Torg-Pavlov ratio was the most important predictive factor of CSM in patients with LSS.

Angioscopic evaluation of stabilizing effects of an antilipemic agent, bezafibrate, on coronary plaques in patients with coronary artery disease: a multicenter prospective study.

To evaluate the stabilizing effects of an antilipemic agent, bezafibrate, on coronary plaques, we carried out a prospective angioscopic and angiographic open trial. From April 1997 to December 1998, 24 patients underwent coronary angioscopy of plaques in non-targeted vessels during coronary interventions and then again 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrate (14 patients, 21 plaques) groups. Oral administration of bezafibrate (400 mg/day) was started immediately after the intervention and was continued for 6 months. The vulnerability score was determined based on the angioscopic characteristics of plaques and compared before and 6 months later. Six months later, the vulnerability score was reduced (from 1.6 to 0.8; P<0.05) in the bezafibrate group and unchanged (from 1.4 to 1.3; NS) in the control group. In the bezafibrate group, the changes in the vulnerability score were not correlated with those in % stenosis or minimal lumen diameter. The plasma total cholesterol level (T-C) was unchanged, triglyceride level (TG) was decreased, and high density lipoprotein cholesterol level (HDL-C) was increased in the bezafibrate group, but were unchanged in the control group. In the bezafibrate group, T-C and TG were decreased and HDL-C was increased in patients with a reduced vulnerability score but were unchanged in those with an unchanged score. These results indicate that 6 month administration of bezafibrate stabilizes coronary plaques and that the stabilization is not correlated with angiographic changes.