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Merkel cell polyomavirus (MCPyV) infection is a known to be a critical risk factor for the development of Merkel cell carcinoma (MCC). Various reports on cutaneous MCC have shown that the differences in clinicohistopathological characteristics depend on the presence of MCPyV, but the situation in eyelid MCC is unknown. This study aimed to assess the prevalence of MCPyV in patients with eyelid MCC and examine the clinicohistopathological characteristics of MCPyV-associated eyelid MCC.Retrospective observational case series with laboratory investigations METHODS: Ten patients treated for eyelid MCC were included. Histopathological characteristics were examined by immunohistochemical staining using 12 antibodies. MCPyV infection was evaluated by PCR using primer set targeting large T antigen of MCPyV genome and by immunohistochemical staining using CM2B4 and Ab3 monoclonal antibodies. MCPyV viral load was also quantified by PCR using three primer sets.All patients (4 males and 6 females) were Japanese with mean age of 79 (range: 63 to 87) years. One patient died due to distant metastasis 8 months after surgery for MCC. Immunohistochemical studies showed typical MCC findings in all cases, including CK20 and neuroendocrine marker positivity. PCR and immunohistochemistry with CM2B4 and Ab3 detected MCPyV antigen in all tumors. Quantitative PCR using sT, LT4 and TAg primers yielded 0.94, 1.72 and 1.05 copies per cell, respectively.Clinical and histopathological characteristics of ten patients with eyelid MCC were elucidated. MCPyV infection was detected in all the eyelid MCC studied. These results provide insight for understanding the tumorigenesis of eyelid MCC.

Fragmentation of forest habitat has negative effects on arboreal mammals, compromising their natural dispersal and foraging movements. This paper describes an evolving series of mitigation measures aimed at creating cost-effective continuity pathways for arboreal mammals in Japan. The projects have focused on the endemic Japanese dormouse (Glirulus japonicus) a scarce, but popular and iconic species which provides an effective vehicle for environmental education and public engagement.

A 7-year-old American short-haired cat was presented with blepharospasm in the right eye. The case was finally performed with orbital exenteration, leading to the diagnosis of feline restrictive orbital myofibroblastic sarcoma. Adjuvant chemotherapy with toceranib was given for one month after surgery. However, the case died four months after surgery.

ObjectiveTo establish a metagenomic profiling method using long-read sequencing for clinical diagnosis of ocular inflammation and detect the etiologic virus of herpetic uveitis.DesignA retrospective, cross-sectional study.ParticipantsThe participants were 44 uveitis patients with a suspected infectious etiology and 22 controls with cataract.MethodsThe anterior aqueous humor (10-20 µl) was subjected to DNA purification, followed by whole genome amplification. The Nanopore MinION™ using the Flongle Flow Cell was used to perform rapid long-read sequencing and the phylogenetic composition of the microorganisms in the specimen was evaluated.Main Outcomes and MeasuresThe detection of the DNA sequence reads of the etiologic virus of herpetic uveitis in the generated FASTQ files from nanopore sequencing and the evaluation of the limits of detection (LOD) of metagenomic analysis compared to multiplex polymerase chain reaction (mPCR) testing for etiologic virus detection of herpetic uveitis.ResultsThe detection rate of nanopore metagenomic analysis was approximately 59.0% as a result of validation against 22 mPCR-positive cases. The LOD was between 103.6and 106copies of virus DNA. The undetectable cases tended to have significantly lower copy numbers by mPCR, suggesting the lower metagenomic analysis sensitivity compared to mPCR. The nine pathogenic microorganisms evaluated by mPCR were also not detected by nanopore in all mPCR-negative cases and controls. The minimum time to obtain analysis results using this method was approximately 190 minutes.Conclusions and RelevanceOur established sequencing protocol from the anterior aqueous humor detected the DNA fragments of etiologic viruses in patients with herpes virus uveitis. Conversely, nanopore metagenomic results contained considerable noise and were found to be less sensitive compared to the conventional mPCR tests for ocular infections.

ImportanceTorque teno virus positivity in the aqueous humor of uveitis patients could be associated with systemic immunodeficiency.ObjectiveWe explored the correlation between the presence of torque teno virus in the aqueous humor of uveitis patients and clinical information, including immunodeficiency history.DesignThis was a retrospective, cross-sectional study.SettingAll participants were recruited at Nagoya University Hospital, Tokyo Medical University Hospital, or Yokkaichi Municipal Hospital between April 2017 and March 2022.ParticipantsThe participants were 58 uveitis patients with a suspected infectious etiology and 24 controls with cataract or age-related macular degeneration.Main Outcomes and MeasuresWe used quantitative polymerase chain reaction to test all subjects for torque teno virus and multiplex polymerase chain reaction to test uveitis subjects for common ocular pathogens. When possible, both serum and aqueous humor samples were tested. Ocular torque teno virus positivity was compared with age, sex, and a history of systemic immunodeficiency with logistic analysis.ResultsTorque teno virus positivity was found in 7 of 31 cases (23%) with herpetic uveitis, 3 of 27 cases (11%) with nonherpetic uveitis, and 0 of 24 controls (0%). Among patients with herpes infection, positivity for torque teno virus was found in 3 of 7 patients (43%) with cytomegalovirus retinitis, 1 of 12 (8%) patients with iridocyclitis, 1 of 7 patients (14%) with acute retinal necrosis, and 2 of 4 patients (50%) with Epstein–Barr virus–related uveitis. Cytomegalovirus retinitis patients showed a significantly higher rate of ocular torque teno virus infection than controls (P= .008). Serum analysis revealed torque teno virus positivity in 9 of 10 cases (90%) with uveitis and in all 8 controls (100%). Age- and gender-adjusted logistic analysis revealed a correlation between ocular torque teno virus positivity and systemic immunodeficiency (P= .01), but no correlations between ocular torque teno virus and age, gender, or viral pathogenic type.Conclusion and RelevanceThis study found that positivity for ocular torque teno virus was correlated with a clinical history of systemic immunodeficiency. This suggests that ocular torque teno virus is a biomarker of systemic immunity.Key pointsQuestionWhat is the correlation between torque teno virus (TTV) in the aqueous humor of patients with uveitis and the clinical characteristics of these patients?FindingsIn this retrospective, cross-sectional study that included 82 patients, ocular TTV was found to be present in 39% of uveitis patients with underlying immunodeficiency and 8% of patients without underlying immunodeficiency; these findings showed statistical significance.MeaningIn patients with uveitis, the presence of ocular TTV may represent systemic immunodeficiency.

Information on the biodistribution (BD) of cell therapy products (CTPs) is essential for prediction and assessment of their efficacy and toxicity profiles in non-clinical and clinical studies. To conduct BD studies, it is necessary to understand regulatory requirements, implementation status, and analytical methods. This review aimed at surveying international and Japanese trends concerning the BD study for CTPs and the following subjects were investigated, which were considered particularly important: 1) comparison of guidelines to understand the regulatory status of BD studies in a global setting; 2) case studies of the BD study using databases to understand its current status in cell therapy; 3) case studies on quantitative polymerase chain reaction (qPCR) used primarily in non-clinical BD studies for CTPs; and 4) survey of imaging methods used for non-clinical and clinical BD studies. The results in this review will be a useful resource for implementing BD studies.

Coronavirus disease-2019 (COVID-19) has affected more than 220 million individuals since the global pandemic began. There is an urgent need for safe and effective vaccines, and vaccinations, such as mRNA vaccines, have been initiated worldwide. However, the adverse effects of these vaccines remain unclear. We herein present a case of an 80-year-old female on maintenance hemodialysis who developed takotsubo cardiomyopathy 4 days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. There was no obvious trigger for the onset of takotsubo cardiomyopathy other than the COVID-19 vaccination, which was the most significant event preceding her presentation. Echocardiograms obtained during her admission allowed us to monitor and show the recovery of left ventricular wall motion. We confirmed the diagnosis of takotsubo cardiomyopathy based on the findings, including transient left ventricular dysfunction, electrocardiographic abnormalities, an elevated troponin level, and the absence of occlusive coronary artery disease. In the present case, the vaccination may have triggered emotional or physical stress. Although difficulties are associated with proving the causal relationship in the present case, the temporal relationship between the vaccination and the onset of takotsubo cardiomyopathy is highly suggestive. The adverse effects associated with the vaccine are typical of COVID-19 vaccines administered to date, most of which are acceptable. Therefore, despite our experience of the present case, we still recommend the vaccination for COVID-19 because takotsubo cardiomyopathy induced by the COVID-19 vaccine is extremely rare and the prognosis of the patient was good. We herein present the first case of a patient on hemodialysis who developed takotsubo cardiomyopathy after receiving COVID-19 vaccination.

A 79-year-old man with chest pain and dyspnea underwent emergency percutaneous coronary intervention for acute myocardial infarction. However, he died 17 days later due to refractory heart failure. An autopsy revealed cardiac strangulation caused by herniation of the apical heart through a pericardial defect due to partial absence of the pericardium. (Level of Difficulty: Advanced.), Central Illustration

Ocular sarcoidosis is an inflammatory disease that manifests as uveitis, and is often difficult to distinguish from other forms of uveitis based on nonspecific findings alone. Comprehensive proteomic analyses of vitreous humor using LC-MS/MS were performed in each patient with ocular sarcoidosis, vitreoretinal lymphoma (VRL), and controls with epiretinal membrane or macular hole. Differential expression proteins (DEPs) were identified by comparing with VRL and controls, and functional pathway analysis was performed. The candidate biomarker proteins for ocular sarcoidosis were validated using enzyme-linked immunosorbent assay. A total of 1590 proteins were identified in all samples. Of these, 290 and 174 DEPs were detected in vitreous of ocular sarcoidosis compared with controls and VRL, respectively. Enrichment pathway analysis revealed that pathways related to the immune system were most upregulated. Validation of two candidate biomarkers for ocular sarcoidosis, neutrophil gelatinase-associated lipocalin (NGAL) and junctional adhesion molecules B (JAMB), confirmed upregulated NGAL and JAMB protein expressions in ocular sarcoidosis compared to controls and VRL. The results of this study revealed that altered vitreous protein expression levels may discriminate ocular sarcoidosis from other uveitis diseases. Vitreous NGAL and JAMB are potential biomarkers and may serve as an auxiliary tool for the diagnosis of ocular sarcoidosis.

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein 2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

In the pharmaceutical field, a technique to level the surface of powdered medicines is important in the dispensing process because the flatness of the powder surface affects the packaging accuracy directly. This paper investigates a method for leveling of the surface profile of powder using ultrasound vibration on a plate. The system used comprises a V-shaped plate and two ultrasound transducers, and the plate configuration required was determined from the results of simulations performed by finite element analysis. The resonant longitudinal vibration of the transducers generated the resonant flexural vibration mode of the plate at 27.4 kHz, which resulted in transportation and leveling of the powder. The powder was aggregated at the nodal positions of the flexural standing wave, and a correlation was observed between the sound pressure distribution over the plate and the surface profile of the powder. The powder leveling accuracy was investigated by varying the driving phase difference between the transducers, and it was found that a smaller standing wave ratio for the flexural vibration produced higher leveling accuracy. When the input voltage to the transducers was increased, the leveling time decreased and the leveling accuracy improved; the highest leveling accuracy obtained was 2.2 mm at 130 V

A 7.5‐year‐old intact male Japanese macaque was presented for evaluation of vision loss. After a complete ophthalmic examination, the patient was diagnosed with hypermature cataract in both eyes. After the cataract surgery, it was able to locate food and walk in a straight line., This is the first report on cataract surgery in a Japanese macaque. Good vision was restored postoperatively by calculating the intraocular lens power and performing the surgery properly even if there was a hypermature cataract.

The present AOP describes the inhibition of calcineurin activity resulting in impaired T-Cell Dependent Antibody Response (TDAR). Calcineurin (CN), a protein phosphatase, is known to impair immune function when its phosphatase activation is inhibited. CN inhibitors (CNIs) inhibit CN phosphatase activity to suppress many kinds of immune functions and have been used in the medical domain to prevent hyper immune reactions. However, CNIs are reported to also induce immunosuppression-derived adverse effects such as increased frequency and/or severity of infections and increased tumor incidences. CNIs might affect several T-cell derived immune functions to induce compromised host. Among the affected immune functions, T-cell dependent antibody response (TDAR) is an important factor to resist infections and thought to be the useful endpoint on evaluating immunotoxicity of chemicals; therefore, this AOP describes the linkage between the inhibition of CN activity and impairment of TDAR.

To clarify the incidence and demographic characteristics of malignant eyelid tumors diagnosed in a single institute in Japan.Retrospective, observational case series METHODS: Patients with malignant eyelid tumors diagnosed histopathologically at Tokyo Medical University Hospital between 1995 and 2019 were reviewed retrospectively. The incidence and demographic profile of malignant eyelid tumors were analyzed. The number of benign eyelid tumors diagnosed histopathologically during the same period was also counted.A total of 412 patients with histopathologically proven malignant eyelid tumors were included. The most common malignant eyelid tumor was sebaceous carcinoma (n = 180, 44%), followed by basal cell carcinoma (n = 148, 36%), squamous cell carcinoma (n = 35, 9%), lymphoma (n = 28, 7%), Merkel cell carcinoma (n = 11, 3%) and others (n = 10, 2%). Mean age of all patients with malignant eyelid tumor at the time of diagnosis was 71.0 ± 13.0 years. For sebaceous carcinoma, the proportion of female patients was significantly higher than that of male patients (P = 0.0283) and the proportion of involvement of upper eyelid was significantly higher than that of lower eyelid (P = 0.0001). On the other hand, there was no sex predominance in basal cell carcinoma and squamous cell carcinoma. The proportion of involvement of lower eyelid was significantly higher than of upper eyelid in basal cell carcinoma (P = 0.001) and squamous cell carcinoma (P = 0.0012). There were 1433 patients with benign eyelid tumors accounting for 78% of all eyelid tumors during the study period.Sebaceous carcinoma is the major malignant eyelid tumor in Japan and is more frequent in women than in men. Epidemiology of malignant eyelid tumors may be affected by the trend of population age structure associated with the recent population aging.

Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse.This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors.Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively).The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.

Patients with immune thrombocytopenia have increased risks of bleeding and thrombosis. The acute‐phase treatment for venous thromboembolism complicated with severe immune thrombocytopenia involves a “platelet dilemma” in therapeutic decision‐making.

The effect of molecular crowding on macromolecular reactions has been revealed by many researchers. In this study, we investigate the complexation of metal ions (Zn, Co, and Cd) with 8-quinolinol-5-sulfonic acid as a model of small-molecular reactions in molecular crowding. The complexation constants for 1:1, 1:2, and total complexation in the presence of polyethylene glycol (PEG, a molecular crowding reagent) are evaluated based on the increase in the reactant activity by volume exclusion and the decrease in the water activity due to the change in osmotic pressure. All complexation constants are enhanced by increasing the concentration of PEG. Its mechanisms differ for 1:1, 1:2, and total complexation. The 1:1 complexation is promoted only by the influence of the water activity, while the reactant and water activities influence the increase in the 1:2 complexation constant. Increasing the molecular weight of PEG further increases the complexation constants, as dehydration of the complex is promoted by a higher hydration number of PEG. Because this study gives the fundamental knowledge for the protein-metal interaction, in which solvation is an important factor, in molecular crowding, it provides new insights into molecular crowding studies and should attract the attention of a broad spectrum of biochemistry researchers.

The objective of this work was to assess multi-stage separation processes for CO2 capture based on semi-clathrate hydrate (SCH) adsorption media. Phase equilibria were determined for CO2 + tetra-n-butyl ammonium bromide (TBAB), N2 + TBAB and CO2 + N2 + TBAB SCH and correlated with a modified van der Waals–Platteeuw model. Experimental CO2 separation factors ranged from 5 to 10, whereas calculated values were all around 18 implying inhomogeneous absorption in the slurries. For simulation conditions, hydrate mass fractions less than 0.09 were estimated to prevent aggregation of the hydrate solids. A two-stage batch separation process allowed enrichment of CO2 to more than 90 mol% from a 20 mol% CO2 feed. A three-stage continuous countercurrent separation process allowed a CO2 recovery of about 90%. Separation performance of semi-clathrate hydrates ranked favorably among the CO2 separation methods, showing that SCH adsorption media have excellent potential for carbon capture applications.

The objective of this work was to investigate diffusion phenomena in methane clathrate hydrates during depressurization that lead to their dissociation. A thermodynamic mass transfer model is proposed that considers cage occupancy in structure I clathrate hydrates and methane diffusion from both S-cages (dodecahedron: 12 pentagons) and M-cages (tetradecahedron: 12 pentagons, 2 hexagons). Methane occupancies during dissociation were measured in situ with Raman spectroscopy with a newly-constructed optical system and data were estimated with Langmuir constants calculated by assuming a spherically symmetric cell potential. Model results were in agreement with experimentally-measured changes in average occupancy with time, so that dissociation kinetics at the interface were concluded to be strongly related to both methane diffusion and cage occupancy. Dissociation kinetics of methane hydrate can be reliably estimated with the proposed model. The proposed model is applicable to the study of methane hydrate dissociation-limited mechanisms or to larger-scale geological systems being used to estimate gas production rates.

Background/Aims: Uric acid (UA) levels are affected by changes in dialysis; however, the relationship between the pre- and postdialysis UA difference (UAD) and mortality remains unclear. Methods: A total of 1,073 patients receiving maintenance hemodialysis (HD) were enrolled in this cohort study and followed up for 5 years. Patients were divided into quartile categories according to baseline UAD. Cox’s regression analyses were used to investigate the relationship between UAD categories and all-cause and cardiovascular (CV) mortalities while adjusting for potential confounders. Results: A total of 280 patients died of all causes, including 121 CV deaths, during the follow-up. In the analysis for all-cause mortality, hazard ratios were significantly higher in the lowest UAD group (< 4.7 mg/dL) than in the highest UAD group (> 6.2 mg/dL). A correlation was not observed with CV mortality. Conclusion: UAD correlated with all-cause mortality. UAD may be the most appropriate reference for controlling UA in HD patients.

Purpose To describe the clinical and histopathological features of a case of choroidal melanocytoma treated by local resection. Observations A 73-year-old man was referred to our hospital with a clinical diagnosis of choroidal melanoma. His best corrected visual acuity at presentation was 20/20 OU. Ocular fundus examination of his right eye showed a pigmented intraocular tumor. Local resection of the tumor was performed under general anesthesia. Histopathological examination of the excised tumor showed proliferation of round to ovoid cells with abundant cytoplasm containing many melanosomes and uniform nuclei and these histopathological findings were compatible with a diagnosis of choroidal melanocytoma. Visual acuity of 20/200 OD has been maintained for over 4 years without local recurrence. Conclusions and Importance Clinical diagnosis of choroidal melanocytoma, especially differentiation from melanoma, is difficult and challenging. Local resection of the tumor allowed study of the histopathological features of the choroidal melanocytoma and maintained tolerable vision in the current case.

To clarify the incidence, demography and clinical features of orbital tumors diagnosed in a single institute in Japan. Retrospective, observational case series. Patients with primary orbital tumors including tumor-like lesions diagnosed clinically or histopathologically at Tokyo Medical University Hospital between 1995 and 2019 were analyzed. Incidence of all orbital tumors, demographic profile and clinical features of major benign and malignant tumors were reviewed retrospectively. Totally 1000 cases of primary orbital tumor were diagnosed clinically or histopathologically during the study period. Benign tumors accounted for 72% and malignant tumors 28%. 55% of benign tumors and 99% of malignant tumors were proven histopathologically. The most common benign orbital tumor was idiopathic orbital inflammation (27%), followed by IgG4-related ophthalmic disease (17%), cavernous venous malformation (13%) and pleomorphic adenoma (9%). The most common malignant tumor was lymphoma (70%), followed by adenoid cystic carcinoma (7%) and solitary fibrous tumor (5%). Epidemiology of orbital tumors has changed by the improvement of imaging techniques, establishment of novel clinical and histopathological criteria, and changes in population age structure associated with the aging society. Currently, lymphoproliferative diseases including lymphoma and IgG4-related ophthalmic diseases form the major orbital tumors in Japan.

Polypharmacy (PP) is common in end-stage chronic renal disease patients largely due to the presence of multiple comorbid conditions. Although PP is potentially harmful, its relationship with mortality and morbidity in hemodialysis patients currently remains unclear. Study design: cohort study. Setting: participants: one hundred and fifty-two initial hemodialysis patients (male, 88 patients; mean age, 70.3 years) were enrolled between February 2015 and March 2018 at Nobeoka Prefectural Hospital and Chiyoda Hospital. Predictor: patients were divided into 2 groups according to PP (6 or more drug prescriptions or less) during admission and discharge for the initiation of hemodialysis. Outcomes: all-cause mortality and hospitalization during the mean 2.8-year follow-up. Measurements: hazard ratios (HRs) were estimated using Cox’s model for the relationships between PP and clinical outcomes and adjusted for potential confounders. The group with 5 or less drug prescriptions was set as a reference. The number of prescribed drugs per patient averaged 7.4 at admission and 7.0 at discharge for initial hemodialysis. One hundred (65.8%) and 94 patients (61.8%) had PP at admission and discharge, respectively. During the follow-up, 20 patients died and 71 were hospitalized. PP at admission did not correlate with outcomes, whereas that at discharge correlated with all-cause hospitalization. PP at discharge may be associated with clinical outcomes. However, it remains unclear whether PP is the direct cause of outcomes or is simply a marker for an increased risk of outcomes.

Purpose To identify tissue metabolomic profiles in biopsy specimens with IgG4-related ophthalmic disease (IgG4-ROD) and mucosa-associated lymphoid tissue (MALT) lymphoma and investigate their potential implication in the disease pathogenesis and biomarkers. Methods We conducted a comprehensive analysis of the metabolomes and lipidomes of biopsy-proven IgG4-ROD (n = 22) and orbital MALT lymphoma (n = 21) specimens and matched adjacent microscopically normal adipose tissues using liquid chromatography time-of-flight mass spectrometry. The altered metabolomic profiles were visualized by heat map and principal component analysis. Metabolic pathway analysis was performed by Metabo Analyst 4.0 using differentially expressed metabolites. The diagnostic performance of the metabolic markers was evaluated using receiver operating characteristic curves. Machine learning algorithms were implemented by random forest using the R environment. Finally, an independent set of 18 IgG4-ROD and 17 orbital MALT lymphoma specimens were used to validate the identified biomarkers. Results The principal component analysis showed a significant difference of both IgG4-ROD and orbital MALT lymphoma for biopsy specimens and controls. Interestingly, lesions in IgG4-ROD were uniquely enriched in arachidonic metabolism, whereas those in orbital MALT lymphoma were enriched in tricarboxylic acid cycle metabolism. We identified spermine as the best discriminator between IgG4-ROD and orbital MALT lymphoma, and the area under the receiver operating characteristic curve of the spermine to discriminate between the two diseases was 0.89 (95% confidence interval, 0.803-0.984). A random forest model incorporating a panel of five metabolites showed a high area under the receiver operating characteristic curve value of 0.983 (95% confidence interval, 0.981-0.984). The results of validation revealed that four tissue metabolites: N1,N12-diacetylspermine, spermine, malate, and glycolate, had statistically significant differences between IgG4-ROD and orbital MALT lymphoma with receiver operating characteristic values from 0.708 to 0.863. Conclusions These data revealed the characteristic differences in metabolomic profiles between IgG4-ROD and orbital MALT lymphoma, which may be useful for developing new diagnostic biomarkers and elucidating the pathogenic mechanisms of these common orbital lymphoproliferative disorders.

We are focusing on the practical use of methane hydrate. For recovery and use of it as an energy resource, it is necessary to consider the possibility of clogging in the recovery pipe due to the rehydration of bubbles. The purpose of this research was to observe experimentally and evaluate theoretically the decomposition behavior of hydrate sedimentary layer and the rising behavior of bubbles generated by hydrate decomposition. Chlorodifluoromethane was used as a low pressure model gas of methane. Hydrate sedimentary layer was produced by cooling and pressurizing water in countercurrent contact with gas using a hydrate formation recovery device. The recovered hydrate was decomposed by the heating or depressurization method, without flowing water. Two theoretical rising velocities were derived from the theoretical value with using the Navier-Stokes equation or the values in consideration of the bubble shape and hydrate film existence. The experimental rising velocities of small spherical bubbles radius agreed well with the theoretical value by the Navier-Stokes equation. The relatively large elliptical bubbles showed a behavior close to the theoretical value of bubble with hydrate film. Under the pressure and temperature conditions closer to the hydrate equilibrium line, almost no generated bubbles could be identified visually.

Background and Aims Polypharmacy (PP) is common in end-stage chronic renal disease patients, largely because of the existence of multiple comorbid conditions. PP has the potential for harm and benefits, and the association between PP and mortality and morbidity in hemodialysis patients currently remains unclear. We examined the association of PP and the risk of clinical outcomes, such as all-cause mortality, all-cause hospitalization and cardiovascular events, in initial hemodialysis patients at admission and discharge. Method Study design: Cohort study. Setting: Participants: One hundred and fifty-two initial hemodialysis patients (female vs. male, 88 vs. 64; mean age, 70.3 years) were enrolled between February 2015 and March 2018 at the Nobeoka Prefectural Hospital and Chiyoda Hospital. Predictor: Patients were divided into 2 groups according to PP (6 or more drug prescriptions, or less) during admission and discharge for the initiation of hemodialysis. Outcomes: All-cause mortality, all-cause hospitalization and cardiovascular events (hospitalization due to stroke, ischemic heart disease or peripheral artery disease) during the mean 2.8-year follow-up. Measurements: Hazard ratios (HRs) were estimated using Cox’s model for the relationships between PP and the clinical outcomes, and adjusted for potential confounders, including age, sex, body mass index, systolic and diastolic blood pressure, Charlson comorbidity risk index, hemoglobin, serum levels of albumin, albumin-corrected Ca, phosphate, parathyroid hormone, C-reactive protein and NT-proBNP; and use of erythropoietin stimulating agents. The group with 5 or less drug prescriptions was set as reference. Results Among the patients in this cohort study, the number of prescribed drugs per patient averaged 7.4 at admission and 6.9 at discharge for initial hemodialysis. One hundred (65.8%) and 94 patients (61.8%) had PP at admission and discharge, respectively. During follow-up, 20 patients died, 71 patients were hospitalized and 25 patients had cardiovascular events. PP at admission is significantly associated with cardiovascular events (HR 8.50, 95%CI 1.45-49.68). Furthermore, PP at discharge is significantly associated with all-cause hospitalization and cardiovascular events (HR 1.95, 95%CI 1.01-3.70; HR 53.16, 95%CI 2.70-104.62, respectively). However, PP is not significantly associated with all-cause mortality at admission or discharge. Conclusion Among Japanese patients starting hemodialysis, PP may be associated with clinical outcomes. However, it remains unclear whether PP is the direct cause of the outcomes or is simply a marker for increased risk of outcomes.

Purpose To determine whether the CD27/CD70 pathway plays a significant role in corneal allograft rejection by investigating the effect of blocking the CD27/CD70 pathway by anti-CD70 antibody on corneal allograft survival. Methods Orthotopic penetrating keratoplasty was performed using C57BL/6 donor grafts and BALB/c recipients. Expression of CD27 and CD70 on rejected cornea was examined by immunohistochemistry. Corneal transplant recipients received intraperitoneal injection of anti-CD70 antibody (FR70) or control rat IgG. Alloreactivity was measured by mixed lymphoid reaction (MLR) in recipients administered control rat IgG and those administered anti-CD70 antibody. Corneal expression of IFN-γ and IL-12 was also examined in both groups. Graft opacity was assessed over an 8-week period and graft survival was evaluated using Kaplan-Meier survival curves. Proportion of CD4+CD44+ memory T cells in lymph nodes was measured by flow cytometry. Results CD4+CD27+ cells and CD11c+CD70+ cells were present in rejected cornea. Anti-CD70 antibody administration suppressed alloreactivity in corneal allograft recipients, and inhibited IFN-γ expression in recipient cornea (p Conclusion The CD27/CD70 pathway plays a significant role in corneal allograft rejection by initiating alloreactive Th1 cells and preserving memory T cells. Anti-CD70 antibody administration prolongs corneal allograft survival indicating the potential therapeutic effect of CD27/CD70 pathway blockade on corneal allograft rejection.