Development and validation of a 13-item short version of the inflammatory bowel disease self-efficacy scale.

BACKGROUND: The inflammatory bowel disease self-efficacy scale (IBD-SES) is an instrument used across many countries to measure important health outcomes of patients with inflammatory bowel disease (IBD). We aimed to develop and validate a substantially shorter version of this scale to reduce patients' response burden. METHODS: A total of 919 patients with IBD, 482 recruited from an IBD clinic and 437 recruited online, completed the Japanese version of the original, 29-item IBD-SES. These data were then used to develop a shorter version of the scale. The original 29 items of the IBD-SES were reduced with three analytic steps: assessing ceiling and floor effect, testing correlation between items, and assessing test-retest reliability. The resulting 13-item IBD-SES was evaluated for construct validity by confirmatory factor analysis, criterion validity by Pearson correlation coefficients with original version, and internal consistency by item-total correlations and the Cronbach's α coefficient. RESULTS: The short version consisted of the same four subscales "managing stress and emotions," "managing medical care," "managing symptoms and disease," and "maintaining remission" as the original scale. The fit indices of the final model were as follows: normed chi-square, 7.18 (p < 0.001); comparative fit index, 0.94; goodness-of-fit index, 0.93; adjusted goodness-of-fit index, 0.89; parsimony goodness-of-fit index, 0.60; and root mean square error of approximation, 0.084. Correlation of each subscale with the original scale was high (0.97-0.98). Cronbach's α for each subscale ranged from 0.68 to 0.86. CONCLUSIONS: A short version of the IBD-SES was developed. The results confirmed the improved validity, reliability, and psychometric properties of the IBD-SES. TRIAL REGISTRATION: Not applicable.

Repeated Fluid Accumulation around a Breast Implant Related to Synovial Metaplasia of the Capsule.

We must take special care when treating postoperative fluid accumulation around breast implants (BIs) to exclude any serious complications, including BI-associated anaplastic large cell lymphoma. However, most late-onset fluid accumulation is caused by other conditions, such as traumatic hematoma and residual postoperative seroma. Surgeons must choose whether to conservatively observe or remove such BIs, while also determining whether to perform partial capsulectomy or total capsulectomy to solve the problem of fluid accumulation. We treated a 72-year-old woman who noticed swelling in her right breast 4 years after undergoing bilateral BI reconstruction. Before she was referred to our hospital, the fluid had been drained by needle aspiration five times, but the swelling returned to a similar size within a month. No malignant findings were observed by needle-aspirated cytology or flow cytometry. The patient requested the simultaneous removal of the left BI. Therefore, we performed both BI removal with total capsulectomy on the right side and partial capsulectomy of the superficial layer on the left side. A pathological examination of the capsule on the right side indicated a chronic expanding hematoma and synovial metaplasia characterized by papillary projections rich in CD68-positive cells, thus indicating reactive synovial cells. In contrast, the left superficial capsule was much thinner and showed less synovial metaplasia. Our findings indicate the advantages of total capsulectomy to solve the problem of repeated serous fluid accumulation around BIs, according to histological changes in the capsule.

A Deep Learning-Based Assay for Programmed Death Ligand 1 Immunohistochemistry Scoring in Non-Small Cell Lung Carcinoma: Does it Help Pathologists Score?

Several studies have developed various artificial intelligence (AI) models for immunohistochemical analysis of programmed death ligand 1 (PD-L1) in patients with non-small cell lung carcinoma; however, none have focused on specific ways by which AI-assisted systems could help pathologists determine the tumor proportion score (TPS). In this study, we developed an AI model to calculate the TPS of the PD-L1 22C3 assay and evaluated whether and how this AI-assisted system could help pathologists determine the TPS and analyze how AI-assisted systems could affect pathologists' assessment accuracy. We assessed the 4 methods of the AI-assisted system: (1 and 2) pathologists first assessed and then referred to automated AI scoring results (1, positive tumor cell percentage; 2, positive tumor cell percentage and visualized overlay image) for final confirmation, and (3 and 4) pathologists referred to the automated AI scoring results (3, positive tumor cell percentage; 4, positive tumor cell percentage and visualized overlay image) while determining TPS. Mixed-model analysis was used to calculate the odds ratios (ORs) with 95% CI for AI-assisted TPS methods 1 to 4 compared with pathologists' scoring. For all 584 samples of the tissue microarray, the OR for AI-assisted TPS methods 1 to 4 was 0.94 to 1.07 and not statistically significant. Of them, we found 332 discordant cases, on which the pathologists' judgments were inconsistent; the ORs for AI-assisted TPS methods 1, 2, 3, and 4 were 1.28 (1.06-1.54; P = .012), 1.29 (1.06-1.55; P = .010), 1.28 (1.06-1.54; P = .012), and 1.29 (1.06-1.55; P = .010), respectively, which were statistically significant. For discordant cases, the OR for each AI-assisted TPS method compared with the others was 0.99 to 1.01 and not statistically significant. This study emphasized the usefulness of the AI-assisted system for cases in which pathologists had difficulty determining the PD-L1 TPS.

Bqt4 affects relative movement between SPB and nucleolus in fission yeast.

Movement dynamics in the nucleus involve various biological processes, including DNA repair, which is crucial for cancer prevention. Changes in the movement of the components of the nucleus indicate the changes in movement dynamics in the nucleus. In Schizosaccharomyces pombe, the inner nuclear membrane protein Bqt4 plays an essential role in attaching telomeres to the nuclear envelope. We observed that the deletion of bqt4+ caused a significant decrease in the mean square displacement (MSD) calculated from the distance between the nucleolar center and spindle pole body (SPB), hereafter referred to as MSD(SPB-Nucleolus). The MSD(SPB-Nucleolus) decrease in bqt4Δ was microtubule-dependent. The Rap1-binding ability loss mutant, bqt4F46A, and nonspecific DNA-binding ability mutants, bqt43E-A, did not exhibit an MSD(SPB-Nucleolus) decrease compared to the WT. Moreover, the bqt43E-Arap1Δ double mutant and 1-262 amino acids truncated mutant bqt4ΔN (263-432), which does not have either Rap1-binding or nonspecific DNA-binding abilities, did not exhibit the MSD(SPB-Nucleolus) decrease to the same extent as bqt4Δ. These results suggest that the unknown function of Bqt4 in the C-terminal domain is essential for the maintenance of the pattern of relative movement between SPB and the nucleolus.

Dietary Perceptions among Patients with Crohn's Disease in Clinical Remission: Comparison with an Era Preceding the Availability of Biologic Therapy.

Introduction: Dietary temperance significantly affects the quality of life of patients with Crohn's disease (CD) and remains a major concern. However, perceptions of diet in remission may have changed from the era when treatment options were limited. Therefore, we compared the dietary perceptions and treatment of patients with CD in remission with previously published data from the time biologic therapy was not introduced. Methods: We compared the data of 254 patients with CD in remission who completed a questionnaire survey in 2022 with those of 76 patients with CD in remission collected in 2003, when biologics were not used for maintenance therapy in Japan. Remission was defined as a CD activity index of 150 or less in both studies. Perceptions of diet (degree of eating whatever one likes) were assessed using single-item nominal scale responses. Results: The percentage of patients receiving enteral nutrition therapy had decreased (past vs. present: 43.4 vs. 12.6%), while the proportion of patients receiving biologic therapy increased (0 vs. 88.6%, respectively). The percentages of patients who responded "not at all," "sometimes," and "mostly" when asked if they could eat whatever they liked had changed, respectively, from 9.2%, 46.1%, and 44.7% in the past to 4.3%, 25.2%, and 70.5% in the present. Conclusion: The proportion of those who ate whatever they liked and the mean body mass index increased in comparison with the corresponding values 20 years ago. With the advent of biologic therapies, the number of patients with CD who can enjoy eating has increased.

Expression of AQP-10, -11 and -12 in the rat stria vascularis.

BACKGROUND: Water homeostasis is essential for inner ear function. Several aquaporins (AQPs), which are water transport proteins in the cell or plasma membrane, have been reported in the lateral wall of the rat inner ear (cochlea). However, the presence of AQP-10, -11 and -12 has not been reported in the rat stria vascularis (SV) to date. AIMS/OBJECTIVES: We have aimed to clarify the expression of AQP-10, -11 and -12 in the cochlea lateral wall. MATERIALS AND METHODS: Using Wistar rats, we examined the expression of AQP-10, -11 and -12 in the cochlea lateral wall using molecular approaches and immunohistochemistry. RESULTS: AQP-11 was molecular biologically expressed, but the expression of AQP-10 and -12 was not observed. Immunohistochemically, AQP-11 was diffusely localized in the basal cells and marginal cells of the rat SV but was not expressed at the apical site of marginal cells with double staining. The expression of AQP-10 and -12 was not observed. CONCLUSIONS AND SIGNIFICANCE: Only AQP-11 was expressed in the basal cells and marginal cells, but it was not expressed at the apical site of marginal cells. Based on this study, AQP-11 may not have an important role in water flux between the perilymph and endolymph.

Surgical results of 29 ears with congenital middle ear anomalies; Microscopic vs. endoscopic ear surgery.

OBJECTIVE: Although congenital middle ear anomalies include various types of ossicular anomalies, all of these can be treated by ossiculoplasty or stapes surgery. Transcanal endoscopic ear surgery (TEES) is a minimally invasive surgical method for middle ear disease with an excellent surgical view that has been widely adopted worldwide. To determine the efficacy of TEES for middle ear anomalies, we describe the surgical results and compare the hearing outcomes between patients treated by TEES and microscopic ear surgery (MES). METHODS: A total of 39 ears with congenital middle ear anomalies were treated surgically at the University Hospital of Kochi Medical School between January 2011 and December 2021. In total, 29 ears of 23 patients were included in the study. Demographics, type of anomaly, surgical methods, pre- and postoperative hearing thresholds, and surgical complications were investigated by retrospective chart review. RESULTS: Of the 29 ears, 11 were treated by MES and 18 were treated by TEES. There were no differences in sex, age, preoperative hearing thresholds, or rate of stapes surgery between the two groups. The mean air-bone gap improvement was 20.6 dB in the MES group and 28.8 dB in the TEES group; these values were not significantly different. The median operation time was not significantly different between the MES and TEES groups (125 and 130 min, respectively). The improvements of air conduction in class 1 and 2 (stapes surgery) and class 3 (ossiculoplasty) cases were also not different between the groups. CONCLUSIONS: TEES achieved comparable hearing outcomes to MES without postauricular or endaural incisions. Further, class 1 and 2 anomalies demonstrated hearing improvement similar to class 3 without major complications. Since the surgical field limited around the ossicular chain, coupled with the fact that the middle ear anomaly itself does not exhibit inflammation leading to unfavorable bleeding, TEES is a feasible surgical procedure for all types of congenital ossicular anomalies.

Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis.

BACKGROUND: In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. METHODS: Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. RESULTS: Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. CONCLUSIONS: Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.

Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens.

BACKGROUND: Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a pathological examination. While diagnostic criteria for this disease have already been proposed, we established more quantitative criteria for evaluating islet morphology. METHODS: We measured the number, maximum diameter, total area, and circularity (representing how closely islets resemble perfect spheres) of islets contained in representative sections of ANHH (n = 4) and control cases (n = 5) using the NIS-Elements software program. We also measured the average cell size, percentage of cells with enlarged nuclei, and percentage of cells with recognizable nucleoli for each of three representative islets. We also assessed the interobserver diagnostic concordance of ANHH between five experienced and seven less-experienced pathologists. RESULTS: There was no significant difference in the number, maximum diameter, or total area of islets between the two groups, even after correcting for these parameters per unit area. However, the number of islets with low circularity (< 0.71) per total area of the pancreatic parenchyma was significantly larger in ANHH specimens than in controls. We also found that the percentage of cells with recognizable nucleoli was significantly higher in the ANHH group than in the controls. There were no significant differences in the average cell size or the number of cells with enlarged nuclei between the groups. The correct diagnosis rate with the blind test was 47.5% ± 6.12% for experienced pathologists and 50.0% ± 8.63% for less-experienced pathologists, with no significant differences noted. CONCLUSIONS: Low circularity, which indicates an irregular islet shape, referred to as "irregular shape and occasional enlargement of islets" and "lobulated islet structure" in a previous report, is a useful marker for diagnosing ANHH. An increased percentage of recognizable nucleoli, corresponding to "macronucleoli in ß-cells," has potential diagnostic value.

Lateral Transport of Domains in Anionic Lipid Bilayer Membranes under DC Electric Fields: A Coarse-Grained Molecular Dynamics Study.

Dynamic lateral transport of lipids, proteins, and self-assembled structures in biomembranes plays a crucial role in diverse cellular processes. In this study, we perform coarse-grained molecular dynamics simulations on a vesicle composed of a binary mixture of neutral and anionic lipids to investigate the lateral transport of individual lipid molecules and the self-assembled lipid domains upon an applied direct current (DC) electric field. Under the potential force of the electric field, a phase-separated domain rich in anionic lipids is trapped in the opposite direction of the electric field. The subsequent reversal of the electric field induces unidirectional domain motion. During the domain motion, the domain size remains constant, but a considerable amount of the anionic lipids is exchanged between the anionic-lipid-rich domain and the surrounding bulk. While the speed of the domain motion (collective lipid motion) shows a significant positive correlation with the electric field strength, the exchange of anionic lipids between the domain and bulk (individual lipid motion) exhibits no clear correlation with the field strength. The mean velocity field of the lipids surrounding the domain displays a two-dimensional (2D) source dipole. We revealed that the balance between the potential force of the applied electric field and the quasi-2D hydrodynamic frictional force well explains the dependence of the domain motions on the electric field strengths. The present results provide insight into the hierarchical dynamic responses of self-assembled lipid domains to the applied electric field and contribute to controlling the lateral transportation of lipids and membrane inclusions.

Clinical Significance of Surgical Intervention to Restore Swallowing Function for Sustained Severe Dysphagia.

Owing to rapid population aging, patients with dysphagia are significantly increasing in society. Dysphagia treatment is aimed at the restoration of the swallowing function and the prevention of recurrent aspiration-induced pulmonary infection. However, despite intensive rehabilitation, oral food intake remains inadequate in many patients with severe dysphagia, which results in the deterioration of patients' quality of life and joy of living. Surgical intervention may serve as a useful therapeutic strategy to restore swallowing function in these patients. The study included 25 patients (mean, 70.4 years; male/female ratio, 20:5) with chronic dysphagia. Dysphagia was associated with cerebrovascular diseases in sixteen patients; with age-induced physiological deterioration in five patients; and with miscellaneous etiologies in four cases. Cricopharyngeal and infrahyoid myotomies were performed in all patients. Laryngeal elevation and the medialization of the paralyzed vocal fold were performed in 15 and 3 patients, respectively. The Food Intake Level Scale (FILS) and videoendoscopic examination score (VEES) were used to evaluate swallowing function. The FILS showed a restoration of oral food intake alone in 72% of patients, and 64% of patients maintained this improvement at their last follow-up visit. We observed significantly improved VEES scores postoperatively. However, patients with cognitive impairment or advanced age showed poor outcomes. In conclusion, surgical intervention may be an effective therapeutic option to restore swallowing function in cases of sustained severe dysphagia; however, surgical indications require careful consideration.

Full genome-based characterization of an Asian G3P[6] human rotavirus strain found in a diarrheic child in Japan: Evidence for porcine-to-human zoonotic transmission.

Human rotavirus strains having the unconventional G3P[6] genotype have been sporadically detected in diarrheic patients in different parts of the world. However, the full genomes of only three human G3P[6] strains from Asian countries (China, Indonesia, and Vietnam) have been sequenced and characterized, and thus the exact origin and evolution of G3P[6] strains in Asia remain to be elucidated. Here, we sequenced and characterized the full genome of a G3P[6] strain (RVA/Human-wt/JPN/SO1199/2020/G3P[6]) found in a stool sample from a 3-month-old infant admitted with acute gastroenteritis in Japan. On full genomic analysis, strain SO1199 was revealed to have a unique Wa-like genogroup configuration: G3-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1. VP6 genotype I5 and NSP1 genotype A8 are commonly found in porcine rotavirus strains. Furthermore, phylogenetic analysis demonstrated that all 11 genes of strain SO1199 were closely related to those of porcine and/or porcine-like human rotaviruses and thus appeared to be of porcine origin. Thus, strain SO1199 was shown to possess a porcine-like genomic backbone and thus is likely to be the result of interspecies transmission of a porcine rotavirus strain. Of note is that all 11 genes of strain SO1199 were phylogenetically located in clusters, distinct from those of the previously identified porcine-like human G3P[6] strains from around the world including Asia, suggesting the occurrence of independent porcine-to-human zoonotic transmission events. To our knowledge, this is the first report on full genome-based characterization of a human G3P[6] strain that has emerged in Japan. Our findings revealed the diversity of unconventional human G3P[6] strains in Asia, and provide important insights into the origin and evolution of G3P[6] strains.

Deep Learning for Predicting Effect of Neoadjuvant Therapies in Non-Small Cell Lung Carcinomas With Histologic Images.

Neoadjuvant therapies are used for locally advanced non-small cell lung carcinomas, whereby pathologists histologically evaluate the effect using resected specimens. Major pathological response (MPR) has recently been used for treatment evaluation and as an economical survival surrogate; however, interobserver variability and poor reproducibility are often noted. The aim of this study was to develop a deep learning (DL) model to predict MPR from hematoxylin and eosin-stained tissue images and to validate its utility for clinical use. We collected data on 125 primary non-small cell lung carcinoma cases that were resected after neoadjuvant therapy. The cases were randomly divided into 55 for training/validation and 70 for testing. A total of 261 hematoxylin and eosin-stained slides were obtained from the maximum tumor beds, and whole slide images were prepared. We used a multiscale patch model that can adaptively weight multiple convolutional neural networks trained with different field-of-view images. We performed 3-fold cross-validation to evaluate the model. During testing, we compared the percentages of viable tumor evaluated by annotator pathologists (reviewed data), those evaluated by nonannotator pathologists (primary data), and those predicted by the DL-based model using 2-class confusion matrices and receiver operating characteristic curves and performed a survival analysis between MPR-achieved and non-MPR cases. In cross-validation, accuracy and mean F1 score were 0.859 and 0.805, respectively. During testing, accuracy and mean F1 score with reviewed data and those with primary data were 0.986, 0.985, 0.943, and 0.943, respectively. The areas under the receiver operating characteristic curve with reviewed and primary data were 0.999 and 0.978, respectively. The disease-free survival of MPR-achieved cases with reviewed and primary data was significantly better than that of the non-MPR cases (P<.001 and P=.001), and that predicted by the DL-based model was almost identical (P=.005). The DL model may support pathologist evaluations and can offer accurate determinations of MPR in patients.

Effects of CuO nanoparticles in composted sewage sludge on rice-soil systems and their potential human health risks.

The release of metal-based nanoparticles (MNPs) into sewage systems is worrisome due to their potential impact on crop-soil systems that are amended with sewage sludge. This study aimed to investigate the effects of copper oxide nanoparticles (CuO NPs) in composted sewage sludge (CSS) on rice-soil systems and to assess the health risks associated with consuming CuO NP-contaminated rice produced by CSS amendment. CSS was treated with three doses of CuO NPs, resulting in Cu levels below the sludge limits (1500 mg Cu kg-1) for reuse as a soil amendment. Results showed that CuO NPs in CSS at environmentally acceptable levels had no negative effect on rice growth and yield. In fact, they enhanced biomass production, tillering capacity, and soil fertility by increasing N and K levels in the soil. In addition, CuO NPs in CSS (450-1450 mg Cu kg-1) promoted the accumulation of macro- and micro-minerals in rice grains, thereby improving the nutritional value of rice. However, Cu contamination in CSS led to elevated levels of toxic metals, especially As, in rice grains, posing potential health risks to both adults and children. In the presence of higher CuO NPs contamination in CSS, the hazard quotient of As exceeded one, indicating an increased risks of toxic metal exposure via rice consumption. This study raises concerns about potential long-term threats to human health posed by MNPs contamination in CSS and highlights the need to reevaluate the permissible limits of hazardous elements in sludge to ensure its safe reuse in agriculture.

Determination of esophageal squamous cell carcinoma and gastric adenocarcinoma on raw tissue using Raman spectroscopy.

BACKGROUND: Cancer detection is a global research focus, and novel, rapid, and label-free techniques are being developed for routine clinical practice. This has led to the development of new tools and techniques from the bench side to routine clinical practice. In this study, we present a method that uses Raman spectroscopy (RS) to detect cancer in unstained formalin-fixed, resected specimens of the esophagus and stomach. Our method can record a clear Raman-scattered light spectrum in these specimens, confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue. AIM: To evaluate the use of Raman-scattered light spectrum for detecting endoscop-ically resected specimens of esophageal squamous cell carcinoma (SCC) and gastric adenocarcinoma (AC). METHODS: We created a Raman device that is suitable for observing living tissues, and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues. We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility, ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions. Furthermore, a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed. RESULTS: We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens. After data capture, the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations. Based on data analysis of molecular-level substrates, we established cut-off values for the diagnosis of esophageal SCC and gastric AC. By analyzing specific Raman shifts, we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses. CONCLUSION: Our technique provides qualitative information for real-time morphological diagnosis. However, further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.

Coarse-grained molecular dynamics simulation of cation distribution profiles on negatively charged lipid membranes during phase separation.

Revealing the ion distributions on a charged lipid membrane in aqueous solution under the influence of long-range interactions is essential for understanding the origin of the stability of the bilayer structure and the interaction between biomembranes and various electrolytes. However, the ion distributions and their dynamics associated with the phase separation process of the lipid bilayer membrane are still unclear. We perform coarse-grained molecular dynamics simulations to reveal the Na+ and Cl- distributions on charged phospholipid bilayer membranes during phase separation. During the phase separation, cations closely follow the position of negatively charged lipids on a microsecond timescale and are rapidly redistributed parallel to the lipid bilayer. In the homogenous mixture of zwitterionic and negatively charged lipids, cations weakly follow negatively charged lipids, indicating the strong interaction between cations and negatively charged lipids. We also compare cation concentrations as a function of surface charge density obtained by our simulation with those obtained by a modified Poisson-Boltzmann theory. Including the ion finite size makes the statistical results consistent, suggesting the importance of the ion-ion interactions in aqueous solution. Our simulation results advance our understanding of ion distribution during phase separation.

Natural attenuation and remobilization of arsenic in a small river contaminated by the volcanic eruption of Mount Iou in southern Kyushu Island, Japan.

The active volcano Mount Iou, in the southern part of Japan, erupted in 2018 for the first time in approximately 250 years. Geothermal water discharged from Mount Iou had high concentrations of toxic elements, such as arsenic (As), which could seriously contaminate the adjacent river. In this study, we aimed to clarify the natural attenuation of As in the river through daily water sampling for approximately eight months. The risk of As in the sediment was also evaluated using the sequential extraction procedures. The highest As concentration (2000 µg/L) was observed upstream but typically remained below 10 µg/L downstream. Dissolved As was the main form in the river water on non-rainy days. Arsenic concentration in the river naturally decreased through dilution and sorption/coprecipitation with Fe, Mn, and Al (hydr)oxides during flow. However, peaks in As concentration were frequently observed during rainfall events, possibly due to sediment resuspension. Furthermore, the range of pseudo-total As in the sediment was 4.62-14.3 mg/kg. Total As content was highest upstream before decreasing further along the flow. When using the modified Keon method, 44-70% of the total As existed as more reactive fractions associated with (hydr)oxides.

Real-world effectiveness of nivolumab and subsequent therapy in Japanese patients with metastatic renal cell carcinoma (POST-NIVO study): 36-month follow-up results of a clinical chart review.

OBJECTIVES: To examine the long-term effectiveness of nivolumab monotherapy and following subsequent therapies for metastatic renal cell carcinoma (mRCC) in Japanese real-world settings. METHODS: This was a multicenter, retrospective, observational study, with a 36-month follow-up, and conducted in Japanese patients with mRCC who initiated nivolumab monotherapy between 1 Feb 2017 and 31 Oct 2017. Endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: Of the 208 patients, 36.5% received nivolumab monotherapy as second-line, 30.8% as third-line, and 31.7% as fourth- or later-line therapy. By 36 months, 12.0% of patients continued nivolumab monotherapy; 88.0% discontinued, mainly because of disease progression (66.7%). The median (m) OS was not reached irrespective of treatment line, with a 36-month OS rate of 54.3% (second-line, 57.4%; third-line, 52.6%; fourth- or later-line, 52.9%). The ORR was 24.2% and five patients achieved complete response. The OS from first-line therapy was 8.9 years. In the 95 patients receiving therapy after nivolumab, 87.4% received vascular endothelial growth factor receptor-tyrosine kinase inhibitors, with mOS and mPFS of 27.4 and 8.1 months, respectively. Irrespective of treatment line, the mOS was not reached in patients with International Metastatic RCC Database Consortium (IMDC) favorable or intermediate risk at mRCC diagnosis. CONCLUSIONS: This 36-month real-world follow-up analysis showed a survival benefit of nivolumab monotherapy for patients with mRCC. The long-term effectiveness of sequential therapy from first-line therapy to therapy after nivolumab was also demonstrated. Additionally, nivolumab monotherapy was beneficial for patients with favorable IMDC risk at the time of mRCC diagnosis.

Content of Telephone Consultations of Patients With Inflammatory Bowel Disease: A Single-Center Descriptive Study.

This study aimed to analyze the specific contents of telephone consultations of patients with inflammatory bowel disease. A medical record survey was conducted at a clinic in Japan for 1 year. Telephone consultation sheets recorded by nurses for calls with the patients or their relatives were reviewed. Content analysis was used to summarize the telephone consultation content. Consultations were categorized into 8 categories. Coding was conducted by 2 independent researchers. Concordance rates were evaluated using kappa coefficients. We analyzed 476 sheets. A total of 229 participants consulted the clinic at least once. The mean number of consultations per person was 2.1. Of these patients, 96 (40.9%) had ulcerative colitis. The kappa coefficient was 0.89. The most frequent consultation was "Consultation on worsening health: Inflammatory bowel disease is likely to have worsened" (42.0%). The second most frequent response was "Consultation or progress report on a worsening health condition: The disease is unlikely to have worsened" (19.8%). For consultations related to worsening the disease, it would be useful to assess symptoms over the phone using a disease activity index to ascertain the degree of worsening and to develop a screening tool for determining whether patients can continue remote support or require face-to-face consultation.

Two-dimensional hydrodynamic simulation for synchronization in coupled density oscillators.

A density oscillator is a fluid system in which oscillatory flow occurs between different density fluids through the pore connecting them. We investigate the synchronization in coupled density oscillators using two-dimensional hydrodynamic simulation and analyze the stability of the synchronous state based on the phase reduction theory. Our results show that the antiphase, three-phase, and 2-2 partial-in-phase synchronization modes spontaneously appear as stable states in two, three, and four coupled oscillators, respectively. The phase dynamics of coupled density oscillators is interpreted with their sufficiently large first Fourier components of the phase coupling function.