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Equivalent doses for the eye lenses, thyroid, and mammary glands were measured and compared between one adult and three pediatric anthropomorphic phantoms during chest computed tomography (CT) using 40 mm volume helical scan on the Aquilion ONE GENESIS Edition CT equipment. Placing an optically stimulated luminescence dosemeter (OSLD) on the eye lenses, thyroid, and mammary gland, we measured and compared the equivalent dose of OSLD among different phantoms during chest CT using a helical scan. Compared with adults, the equivalent doses to the eye lens, thyroid, and mammary glands were ~81%, 77%, and 63% lower in newborns, 1-year-olds, and 5-year-olds using comparable image noise during chest CT., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM)., Patients and Methods: We retrospectively examined clinical features and status of anti-Ro52 Ab in patients with PM/DM admitted at the University of Tsukuba Hospital between January 2019 and February 2023. We compared anti-Ro52 Ab-positive and -negative groups., Results: A total of 40 patients were selected and analyzed. Median age at diagnosis was 61.5 (48.8-69.3) years and 34 cases were female. Twenty-three cases were PM and 17 cases were DM (including 6 clinically amyopathic dermatomyositis: CADM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease (ILD) was detected in 29 cases, 9 of which were rapidly progressive. Glucocorticoid (GC)-resistant cardiomyopathy was detected in 6 cases, malignancy in 3 cases, and Sjögren's syndrome (SS) in 4 cases. Of the 22 anti-Ro52 Ab positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and -negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), ILD (95.5% vs. 44.4%), GC-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein (CRP) were significantly higher in the anti-Ro52 Ab-positive group (p<0.05). The frequencies of PM/DM, positivity of anti-MDA5 Ab, malignancies, and SS were comparable between groups., Conclusion: Anti-Ro52 Ab were frequently positive in PM/DM and anti-Ro52 Ab-positive patients showed significantly higher rates of anti-ARS Ab positivity and ILD, GC-resistant cardiomyopathy, concomitant use of immunosuppressants, and higher levels of CRP. Anti-Ro52 Ab may be useful as a severity marker in PM/DM., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Endoscopic resection (ER) of esophageal squamous cell carcinoma (ESCC) is evaluated pathologically, and additional treatment is recommended for cases resulting in non-curative resection, defined as pMM with lymphovascular invasion (LVI), pSM, or positive vertical margin. This study aimed to assess long-term outcomes and risk factors for recurrence in patients with ESCC treated with non-curative ER followed by additional chemoradiotherapy (CRT). We retrospectively reviewed the clinical courses of patients who underwent non-curative ER followed by additional CRT for ESCCs between August 2007 and December 2017. Recurrence rates and risk factors for recurrence were analyzed. Among 97 patients with non-curative ER, 73 underwent additional CRT. With a median follow-up period of 71 months, recurrences were observed in 10 (14%) of 73 patients, with a median interval of 24.5 (1-59 months). The 3- and 5-year recurrence-free survival were 89 and 85%, respectively, and the 3- and 5-year overall survival rates were 96 and 91%, respectively. Multivariate analysis showed that lymphatic invasion was an independent risk factor for recurrence in patients with non-curative ESCC receiving additional CRT. Among the 10 patients with recurrence, 4, 3, 2, and 1 underwent surgery, chemotherapy, supportive care, and CRT, respectively. Notably, all four patients who underwent surgery survived, regardless of regional and/or distant lymph node metastasis. Lymphatic invasion is an independent risk factor for the recurrence of non-curative ESCCs. Careful follow-up is required for at least 5 years after ER with additional CRT., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In addition to treatment with antituberculosis drugs, complete surgical excision is important for the cure of chest wall tuberculosis. However, surgery is often challenging to perform due to different factors such as the strong adhesion of tuberculous lesions to the surrounding normal tissue, growth of neovascularization and presence of fragile necrotic tissues. Firm adhesions, bleeding and fragile tissue make it difficult to determine the boundary with normal tissue and completely excide the lesion. Moreover, ingenuity is required. Herein, we report the identification of the boundary between the lesion and normal tissue by injecting indigo carmine into the abscess to completely excide the lesion, which is considered an intuitive and safe method., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

To determine whether using lower-tube voltage reduces the scattered dose for the lens during paediatric thoracic computed tomography (CT). Two paediatric anthropomorphic phantoms (ATOM Phantom, CIRS, Norfolk, Virginia, USA) representing a newborn and 5-year-old were placed on the gantry of CT scanner, and optically stimulated luminescence dosemeters were placed on the left and right lenses, in front of the left and right thyroid glands, in front of the left and right mammary glands, and in front of and behind the mammary gland level and we measured scattered dose of the optically stimulated luminescence dosemeter was compared for each phantom between 80 and 120 kVp. Significant differences were observed in the scatter doses for the lens between 80 and 120 kVp (p < 0.01). Compared with the 120 kVp scan, the scatter doses for the lens were ~15-40% lower in newborn and 5-year-olds using the 80 kVp scan during paediatric CT., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A 'genomically' humanized animal stably maintains and functionally expresses the genes on human chromosome fragment (hCF; <24 Mb) loaded onto mouse artificial chromosome (MAC); however, cloning of hCF onto the MAC (hCF-MAC) requires a complex process that involves multiple steps of chromosome engineering through various cells via chromosome transfer and Cre-loxP chromosome translocation. Here, we aimed to develop a strategy to rapidly construct the hCF-MAC by employing three alternative techniques: (i) application of human induced pluripotent stem cells (hiPSCs) as chromosome donors for microcell-mediated chromosome transfer (MMCT), (ii) combination of paclitaxel (PTX) and reversine (Rev) as micronucleation inducers and (iii) CRISPR/Cas9 genome editing for site-specific translocations. We achieved a direct transfer of human chromosome 6 or 21 as a model from hiPSCs as alternative human chromosome donors into CHO cells containing MAC. MMCT was performed with less toxicity through induction of micronucleation by PTX and Rev. Furthermore, chromosome translocation was induced by simultaneous cleavage between human chromosome and MAC by using CRISPR/Cas9, resulting in the generation of hCF-MAC containing CHO clones without Cre-loxP recombination and drug selection. Our strategy facilitates rapid chromosome cloning and also contributes to the functional genomic analyses of human chromosomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: During restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis-associated colorectal cancer or dysplasia, ileal pouch-anal handsewn anastomosis (IAA) is preferred to avoid the risk of cancer development in the remaining rectal mucosa. However, there is a risk of the ileal pouch not reaching the anus with this procedure. Here, we created deformable 3-dimensional (3D) models for simulation., Method: Six patients who underwent IAA without vessel ligation and 5 patients who underwent ileal pouch-anal canal double-stapled anastomosis (IACA) because the ileal pouch did not reach the anus were studied. A 3D printer was used to create deformable 3D models from the data obtained from computed tomography scans. The positional relationship among the mesenteric arteries, pubis, and coccyx were evaluated., Result: The distance between the superior mesenteric artery root and the tip of the ileal artery was longer in the IAA group than that in the IACA group (IAA vs IACA: 26.2 ± 2.1 cm vs 20.9 ± 1.6cm). The distance from the tip of the ileal artery to the coccyx (IAA vs IACA: 6.7 ± 1.7 cm vs 12.1 ± 2.1 cm) and the distance from the tip of the ileal artery to the lower edge of the pubis (IAA vs IACA; 8.1 ± 1.3 cm vs 12.7 ± 2.4 cm) were longer in the IACA group than those in the IAA group., Conclusions: We established a method for creating 3D deformable models of patients with ileal pouch-anal anastomosis. These 3D models may be useful for preoperative simulation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

With the recent increase in the frequency of duodenal tumor detection, significant progress has been made in endoscopic diagnosis and treatment. Although the first guidelines were issued in Japan, patient treatment varies widely among institutions. There is a need for improving the quality of endoscopic diagnosis and more curative and safer treatments. Biopsy is the standard diagnostic method; however, the diagnostic accuracy of endoscopic biopsy is not so high. Therefore, the differentiation of superficial non-ampullary duodenal epithelial tumors from non-neoplastic lesions is being developed. The incidence of lymph node and distant metastases of duodenal epithelial tumors is extremely rare in intramucosal carcinomas, and they are considered good candidates for endoscopic treatment if the technical difficulties can be resolved. Adverse events associated with endoscopic treatment are greatly reduced at advanced facilities through novel resection and closure methods, and further improvements are expected in the future. Clarifying the risk of metastatic recurrence may lead to the development of more appropriate treatments and curative resection criteria., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

High population density and tourism in Southeast Asia increase the risk of mpox due to frequent interpersonal contacts. Our wastewater surveillance in six Southeast Asian countries revealed positive signals for Monkeypox virus (MPXV) DNA, indicating local transmission. This alerts clinicians and helps allocate resources like testing, vaccines and therapeutics in resource-limited countries., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Arbuscular mycorrhizal (AM) fungi establish mutualistic symbiosis with a wide range of terrestrial plants, including rice. However, the mechanisms underlying the initiation of AM symbiosis are yet to be elucidated, particularly in nonleguminous plants. We previously demonstrated that chitin elicitor receptor kinase 1 (OsCERK1), a lysin motif receptor-like kinase essential for chitin-triggered immunity, also plays a key role in AM symbiosis in rice. However, the mechanisms underlying the regulation of switching between immunity and symbiosis by OsCERK1 are yet to be fully elucidated. SYMBIOSIS RECEPTOR-LIKE KINASE (SYMRK)/DOES NOT MAKE INFECTIONS 2 (DMI2) is a leucine-rich repeat receptor-like kinase associated with both root nodule symbiosis and AM symbiosis in legumes. The homolog of SYMRK in rice, OsSYMRK, has a shorter form than that in legumes because OsSYMRK lacks a malectin-like domain (MLD). The MLD reportedly contributes to symbiosis in Lotus japonicus; however, the contribution of OsSYMRK to AM symbiosis in rice remains unclear. Phylogenetic analyses indicated that the MLD of SYMRK/DMI2 is widely conserved even in mosses and ferns but absent in commelinids, including rice. To understand the function of OsSYMRK, we produced an Ossymrk knockout mutant using genome editing technology. AM colonization was mostly abolished in Ossymrk with a more severe phenotype than Oscerk1. Ca2+ spiking against chitin tetramer was also diminished in Ossymrk. In contrast, comparable defense responses against chitin heptamer to the wild type were observed in Ossymrk. Bimolecular fluorescence complementation studies demonstrating an interaction between OsSYMRK and OsCERK1 indicate that OsSYMRK may play an important role in switching from immunity to symbiosis through the interaction with OsCERK1 in rice., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Our study aimed to compare the treatment outcomes between endoscopic submucosal dissection (ESD) with an insulated-tip knife (ESD-IT) and a needle-type knife (ESD-N) for large superficial esophageal neoplasms, as no study of this kind has been previously reported. We used the dataset of a multicenter, randomized controlled trial that compared conventional ESD (C-ESD) and traction-assisted ESD (TA-ESD) for superficial esophageal neoplasms. We compared the procedural outcomes between ESD-IT and ESD-N in a post hoc analysis and conducted sub-analyses based on traction assistance and electrical knife type. We included 223 (EST-IT, n = 169; ESD-N, n = 54) patients with no significant differences in baseline characteristics. The operator handover rate due to ESD difficulties was significantly higher in ESD-N (ESD-IT = 0.6% vs. ESD-N = 13.0%, P = 0.001), while the injection volume was significantly higher in ESD-IT than in ESD-N (40.0 vs. 20.5 mL, P < 0.001). Other outcomes were comparable between both groups (procedural time: 51.0 vs. 49.5 minute, P = 0.89; complete resection: 90.5% vs. 90.7%, P > 0.99; and complication rate: 1.8% vs. 3.7%, P = 0.60 for ESD-IT and ESD-N, respectively). In the sub-analyses, the handover rate was significantly lower with TA-ESD than with C-ESD for ESD-N (3.2% vs. 26.1%, P = 0.034), and a significantly smaller injection volume was used in TA-ESD than in C-ESD for ESD-IT (31.5 vs. 47.0 mL, P < 0.01). ESD with either endoscopic device achieved favorable treatment outcomes with low complication rates. The handover rate in ESD-N and the injection volume in ESD-IT improved with the traction method., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA)., Materials and Methods: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed., Results: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients., Conclusion: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Background: Noninvasive detection of early stage cancers with accurate prediction of tumor tissue-of-origin could improve patient prognosis. Because miRNA profiles differ between organs, circulating miRNomics represent a promising method for early detection of cancers, but this has not been shown conclusively., Methods: A serum miRNA profile (miRNomes)-based classifier was evaluated for its ability to discriminate cancer types using advanced machine learning. The training set comprised 7931 serum samples from patients with 13 types of solid cancers and 5013 noncancer samples. The validation set consisted of 1990 cancer and 1256 noncancer samples. The contribution of each miRNA to the cancer-type classification was evaluated, and those with a high contribution were identified., Results: Cancer type was predicted with an accuracy of 0.88 (95% confidence interval [CI] = 0.87 to 0.90) in all stages and an accuracy of 0.90 (95% CI = 0.88 to 0.91) in resectable stages (stages 0-II). The F1 score for the discrimination of the 13 cancer types was 0.93. Optimal classification performance was achieved with at least 100 miRNAs that contributed the strongest to accurate prediction of cancer type. Assessment of tissue expression patterns of these miRNAs suggested that miRNAs secreted from the tumor environment could be used to establish cancer type-specific serum miRNomes., Conclusions: This study demonstrates that large-scale serum miRNomics in combination with machine learning could lead to the development of a blood-based cancer classification system. Further investigations of the regulating mechanisms of the miRNAs that contributed strongly to accurate prediction of cancer type could pave the way for the clinical use of circulating miRNA diagnostics., (© The Author(s) 2022. Published by Oxford University Press.)

Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337-450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09-6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93-3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The diagnosis of colitis-associated cancer or dysplasia is important in the treatment of ulcerative colitis. Immunohistochemistry of p53 along with hematoxylin and eosin (H&E) staining is conventionally used to accurately diagnose the pathological conditions. However, evaluation of p53 immunohistochemistry in all biopsied specimens is expensive and time-consuming for pathologists. In this study, we aimed to develop an artificial intelligence program using a deep learning algorithm to investigate and predict p53 immunohistochemical staining from H&E-stained slides., Methods: We cropped 25 849 patches from whole-slide images of H&E-stained slides with the corresponding p53-stained slides. These slides were prepared from samples of 12 patients with colitis-associated neoplasia who underwent total colectomy. We annotated all glands in the whole-slide images of the H&E-stained slides and grouped them into 3 classes: p53 positive, p53 negative, and p53 null. We used 80% of the patches for training a convolutional neural network (CNN), 10% for validation, and 10% for final testing., Results: The trained CNN glands were classified into 2 or 3 classes according to p53 positivity, with a mean average precision of 0.731 to 0.754. The accuracy, sensitivity (recall), specificity, positive predictive value (precision), and F-measure of the prediction of p53 immunohistochemical staining of the glands detected by the trained CNN were 0.86 to 0.91, 0.73 to 0.83, 0.91 to 0.92, 0.82 to 0.89, and 0.77 to 0.86, respectively., Conclusions: Our trained CNN can be used as a reasonable alternative to conventional p53 immunohistochemical staining in the pathological diagnosis of colitis-associated neoplasia, which is accurate, saves time, and is cost-effective., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Little is known about the time course of mortality reduction following smoking cessation in Asians who have smoking behaviours distinct from their Western counterparts. We evaluated the level of reduction in all-cause, cardiovascular disease (CVD) and lung cancer mortality by years since quitting smoking, in Asia., Methods: Using Cox regression, we analysed individual participant data (n = 709 151) from 16 prospective cohorts conducted in China, Japan, Korea/Singapore, and India/Bangladesh, separately by cohorts. Cohort-specific hazard ratios (HRs) were combined using a random-effects meta-analysis., Results: During a mean follow-up of 12.0 years, 108 287 deaths were ascertained-35 658 from CVD and 7546 from lung cancer. Among Asian men, a dose-response relationship of risk reduction in deaths from all causes, CVD and lung cancer was observed with an increase in years after smoking cessation. Compared with never smokers, however, all-cause and CVD mortality among former smokers remained elevated 10-14 years after quitting [multivariable-adjusted HR (95% confidence interval (CI) = 1.25 (1.13-1.37) and 1.20 (1.02-1.41), respectively]. Lung cancer mortality stayed almost 2-fold higher than among never smokers 15-19 years after smoking cessation [1.97 (1.41-2.73)], particularly among former heavy smokers [2.62 (1.71-4.00)]. Women who quitted for ≥5 years retained a significantly elevated mortality from all causes, CVD and lung cancer. Overall patterns of the cessation-mortality associations were similar across countries., Conclusions: Our findings suggest that adverse effects of tobacco smoking persist for an extended time period, even for more than two decades, which is beyond the time windows defined in current clinical guidelines for risk assessment of lung cancer and CVD., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Water containing ultrafine/nano bubbles (UFBs) promoted the growth of tomato (Solanum lycopersicum) in soil damaged by cultivation of tomato in the previous year or bacterial wilt-like disease and also promoted the growth of lettuce (Lactuca sativa) when lettuce was grown in the soil damaged by repeated cultivation of lettuce. On the other hand, UFB supply did not affect plant growth in rock wool or healthy soil. Furthermore, the growth of lettuce was not affected by UFB water treatment in the soil damaged by the cultivation of tomato. UFB water partly suppressed the growth of the pathogen of bacteria wilt disease, Ralstonia solanacearum in vitro. These data suggest that UFB water is effective to recover the plant growth from soil damage., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Objectives: The primary objective is to reveal the effect of hydroxychloroquine (HCQ) treatment on corrected QT (QTc) interval in patients with systemic lupus erythematosus (SLE). The secondary objective is to investigate factors that affect QTc prolongation., Methods: SLE patients who had electrocardiograms between 2015 and 2020 were recruited and assigned to two groups based on whether they were treated with HCQ (HCQ group) or not (control group). Change of QTc before and after HCQ administration in the HCQ group was measured and compared with the control group. Patients treated with HCQ were further divided into two groups based on presence or absence of QTc prolongation and the characteristics were compared., Results: In total, 126 patients were recruited, of whom 42 were treated with HCQ. In the HCQ group, the mean QTc significantly increased ( p  < .001), while there was no significant difference of mean QTc in the control group. Moreover, those in the HCQ group with QTc prolongation showed a significantly higher proportion of hypertension and longer SLE duration compared to those without QTc prolongation. However, the multiple logistic regression analysis showed that there were no significant differences among them., Conclusion: HCQ could induce QTc prolongation in SLE patients. It might be better that the possibility of QTc prolongation was taken into consideration when HCQ was administered in the patients with longer disease duration of SLE and coincidence of hypertension.

Temperature corrections are necessary to account for the varying mass of air in the cavity volume of a vented ionization chamber. The temporal response resulting from temperature changes in a cylindrical and/or Farmer-type ionization chamber, which is the standard dosimeter, has been thoroughly discussed by some researchers. The purpose of this study was to characterise and analyse the dependence of the cavity air temperature of the parallel-plate-type ionization chamber on changes in the ambient temperature. Ionization chambers NACP-02 (IBA Dosimetry, GmbH) and Advanced Markus TN34045 (PTW, Freiburg) were modelled using thermal analysis software to present the temperature equilibrium time and the entire ionization chamber temperature distribution. The temporal response of each ionization chamber was measured for comparing the calculation results of the thermal analysis. The ionization chamber cavities of NACP-02 and TN34045 reached complete equilibrium in 670 and 750 s, respectively. Heat transfer occurred faster at the centre of the front wall of TN34045 than at the outside of the centre except for the edges. Further, the non-uniformity of temperature in the cavity was in the range of 24.2-24.8°C for NACP-02 and 23.7-24.4°C for TN34045 at 200 s after the ionization chamber was installed in the water phantom. The previous proposal to wait for about 15 mins after submerging the chamber in a water phantom before the measurement is demonstrated to be appropriate for parallel-plate-type ionization chambers., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: We aimed to report the 2-year results of stereotactic body radiation therapy for prostate cancer and identify the clinical and dosimetric factors that predict acute genitourinary toxicities., Methods: We retrospectively reviewed the medical records of patients with non-metastatic prostate cancer treated at Toyota Memorial Hospital between 2017 and 2020. The patients were treated with stereotactic body radiation therapy with a total dose of 36.25 Gy in five fractions on consecutive weekdays. While low-risk patients received radiotherapy alone, intermediate- to high-risk patients also received androgen deprivation therapy., Results: We analysed a total of 104 patients, including 10, 60 and 34 low-, intermediate- and high-risk patients, respectively. The median follow-up duration was 2 years. We did not observe biochemical/clinical recurrence, distant metastasis or death from prostate cancer. One patient died of another cause. Grade 2 acute genitourinary toxicity was observed in 40 (38%) patients. Age (P = 0.021), genitourinary toxicity of grade ≥1 at baseline (P = 0.023) and bladder mean dose (P = 0.047) were significantly associated with the incidence of grade 2 acute genitourinary toxicity. The cut-off value of 65 years for age and 10.3 Gy for the bladder mean dose were considered the most appropriate. Grade 2 acute gastrointestinal toxicity was observed in five (5%) patients. None of the patients experienced grade ≥3 acute or late toxicity., Conclusions: Stereotactic body radiation therapy is feasible for Japanese patients with prostate cancer, with acceptable acute toxicity. Age, genitourinary toxicity at baseline and bladder mean dose predict grade 2 acute genitourinary toxicity., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The liverwort Marchantia polymorpha possesses oil bodies in idioblastic oil body cells scattered in its thallus. Oil bodies are subcellular organelles in which specific sesquiterpenes and bisbibenzyls are accumulated. Therefore, a specialized system for the biosynthesis and accumulation of these defense compounds specifically in oil bodies has been implied. A recent study on M. polymorpha genome sequencing revealed 10 genes that shared high similarities with fungal-type terpene synthases (TPSs). Eight of these fungal-type TPS-like genes in M. polymorpha (MpFTPSL1-6, -9 and -10) are located within a 376-kb stretch on chromosome 6 and share similarities of over 94% at the nucleotide level. Therefore, these genes have likely originated from recent gene duplication events. The expression of a subset of MpFTPSLs was induced under non-axenic growth on vermiculite, which increased the amounts of sesquiterpenes and number of oil bodies. The tdTomato fluorescent protein-based in-fusion reporter assay with MpFTPSL2 promoter revealed fluorescent signals specifically in oil body cells of the thallus, indicating that MpFTPSL2 functions in oil body cells. Recombinant MpFTPSL2 expression in Escherichia coli led to sesquiterpene synthesis from farnesyl pyrophosphate. Moreover, suppression of a subset of MpFTPSLs through RNA interference reduced sesquiterpene accumulation in thalli grown on vermiculite. Taken together, these results suggest that at least a subset of MpFTPSLs is involved in sesquiterpene synthesis in oil body cells., (� The Author(s) 2021. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hybrid endoscopy-assisted larynx-preserving esophagectomy is developed for cervical esophageal squamous cell carcinoma encroaching or extending above the upper esophageal sphincter. First, a cervical incision was surgically performed followed by cervical lymph node dissection. Second, the margin of cervical esophageal squamous cell carcinoma was endoscopically identified with iodine staining and marked endoscopically followed by semi-circumferential or circumferential endoscopic full-thickness excision around the lumen of the esophagus. The distal margin was surgically resected and reconstruction was performed. Among six consecutive patients with cervical esophageal squamous cell carcinoma undergoing hybrid endoscopy-assisted larynx-preserving esophagectomy, proximal surgical margin was histologically negative in five patients. During a median follow-up period of 15.5 months, all patients tolerated oral intake and were alive without evidence of recurrence. None of the patients experienced aspiration pneumonia, vocal disorder or postoperative anastomotic stricture. Hybrid endoscopy-assisted larynx-preserving esophagectomy could be a clinically feasible treatment for cervical esophageal squamous cell carcinoma providing accurate proximal resection margin with the benefit of laryngeal function preservation., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: This study aimed to conduct objective and subjective comparisons of image quality among abdominal computed tomography (CT) reconstructions with deep learning reconstruction (DLR) algorithms, model-based iterative reconstruction (MBIR), and filtered back projection (FBP)., Methods: Datasets from consecutive patients who underwent low-dose liver CT were retrospectively identified. Images were reconstructed using DLR, MBIR, and FBP. Mean image noise and contrast-to-noise ratio (CNR) were calculated, and noise, artifacts, sharpness, and overall image quality were subjectively assessed. Dunnett's test was used for statistical comparisons., Results: Ninety patients (67 ± 12.7 years; 63 males; mean body mass index [BMI], 25.5 kg/m 2 ) were included. The mean noise in the abdominal aorta and hepatic parenchyma of DLR was lower than that in FBP and MBIR ( p < .001). For FBP and MBIR, image noise was significantly higher for obese patients than for those with normal BMI. The CNR for the abdominal aorta and hepatic parenchyma was higher for DLR than for FBP and MBIR ( p < .001). MBIR images were subjectively rated as superior to FBP images in terms of noise, artifacts, sharpness, and overall quality ( p < .001). DLR images were rated as superior to MBIR images in terms of noise ( p < .001) and overall quality ( p = .03)., Conclusions: Based on objective and subjective comparisons, the image quality of DLR was found to be superior to that of MBIR and FBP on low-dose abdominal CT. DLR was the only method for which image noise was not higher for obese patients than for those with a normal BMI., Advances in Knowledge: This study provides previously unavailable information on the properties of DLR systems and their clinical utility.

En bloc resection is essential for accurate pathological evaluation in patients with superficial esophageal squamous cell carcinoma (SESCC). This retrospective study aimed to clarify optimal treatment selection of endoscopic resection according to lesion size. A total of 760 patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) between January 2011 and December 2015. Among them, this retrospective study included 196 solitary index SESCC lesions ≤20 mm, with the deepest invasion to the mucosa or superficial submucosa endoscopically. The lesions were classified according to size measured via endoscopy as follows; group A: lesions ≤10 mm, group B: lesions ≥11 mm but ≤15 mm, and group C: lesions ≥16 mm but ≤20 mm. The short- and long-term outcomes were investigated for EMR and ESD subgroups. In patients undergoing EMR and ESD, en bloc resection rates for group A and B were not different (98.8 vs. 100%, 93.3 vs. 100%, respectively). However, the en bloc resection rate was significantly lower in EMR than that in ESD for group C (64.3 vs. 100%, P < 0.001). Furthermore, the use of adjunctive ablative therapy rate was significantly higher in EMR than that in ESD in group C (35.7 vs. 0%, P < 0.001). The 5-year cumulative local recurrence rate of group C was significantly higher than that of group A + B after EMR (P < 0.01). EMR was an adequate treatment for SESCC lesions ≤15 mm. On the other hand, ESD could be necessary to achieve en bloc resection for lesions ≥16 mm to avoid local recurrence., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Humanized non-obese diabetic/severe combined immunodeficiency/interleukin-2 receptor-γ-null (NOD/SCID/IL2rγ null ) [humanized (huNSG)] mice engrafted with human hematopoietic cells have been used for investigations of the human immune system. However, the epigenetic features of the human regulatory T (T reg ) cells of huNSG mice have not been studied. The objective of this study was to clarify the characteristics of human T reg cells in huNSG mice, especially in terms of the epigenetic aspects. We compared the populations, inhibitory molecule expression and suppressive capacity of human T reg cells in spleens harvested from the huNSG mice 120 days after the engraftment of human umbilical cord blood CD34 + cells with human peripheral blood mononuclear cells (PBMCs). Histone modifications and enhancer of zeste homolog 2 (Ezh2), an H3K27 methyltransferase, of human T reg cells were quantified in huNSG mice and human PBMCs. The effect of Ezh2 inhibitor on human T reg cells exposed to interleukin (IL)-6 was also compared between them. Human T reg cells in the spleens of huNSG mice showed an increased proportion among CD4 + T cells, higher expressions of forkhead box protein 3 (FoxP3), cytotoxic T lymphocyte antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor-related protein (GITR), a higher production of IL-10 and enhanced suppressive capacity when compared with those in human PBMCs. H3K27me3 and Ezh2 were specifically up-regulated in human T reg cells of huNSG mice in comparison with those of human PBMCs. The decrease in T reg cells induced by IL-6 exposure was attenuated in huNSG mice when compared with human PBMCs, while the difference between them was cancelled by addition of Ezh2 inhibitor. In conclusion, huNSG mice exhibit functionally augmented human T reg cells owing to enzymatic up-regulation of H3K27me3., (© 2021 British Society for Immunology.)

Objectives: To investigate the clinical features and prognosis of nocardiosis complicated by connective tissue diseases (CTDs)., Methods: We examined patients with CTDs who were diagnosed with nocardiosis from October 2004 to 2019. We retrospectively investigated patient characteristics and therapeutic outcomes. We then performed a comparison between survivors and non-survivors., Results: Fourteen patients were examined. Underlying CTDs were systemic lupus erythematosus (28.6%), vasculitis syndrome (28.6%), rheumatoid arthritis (21.4%), adult Still disease (14.3%) and dermatomyositis (7.1%). Infected organs were lung (85.7%), brain (42.9%), skin/cutaneous lesions (28.6%) and muscle (7.1%). Disseminated infections were seen in nine patients (64.3%). At the onset of nocardiosis, all patients were given prednisolone (23.2 ± 11.9 mg/day). Only two patients (14.3%) were given TMP-SMX for prophylaxis of pneumocystis pneumonia. Relapse occurred in one patient (7.1%) and four patients (28.6%) died from nocardiosis for a cumulative survival rate at 52 weeks of 76.9%. In a comparison of survivors (71.4%) and non-survivors (28.6%), cutaneous lesions were significantly more frequent in the latter (10 vs 75%, p  = .04) with an odds ratio of 27.0 (95% CI: 1.7-453.4)., Conclusion: Cutaneous lesions as a result of dissemination might be a risk factor for nocardiosis mortality in patients with CTDs.

Background: In prostate cancer treatment, lower urinary tract symptoms significantly improve with luteinizing hormone-releasing hormone antagonists use compared with agonists. However, it is unclear whether luteinizing hormone-releasing hormone antagonists can decrease acute urinary tract toxicity during external beam radiotherapy. This study aimed to assess whether luteinizing hormone-releasing hormone antagonists used as neoadjuvant therapy reduced acute urinary tract toxicity during external beam radiotherapy compared with luteinizing hormone-releasing hormone agonists., Methods: The study included 78 patients who underwent intensity-modulated radiation therapy for intermediate- and high-risk prostate cancer between April 2013 and January 2020. Irradiation was initiated after 3-6 months of neoadjuvant therapy. Androgen deprivation therapy was given to the intermediate-risk group for 6 months and the high-risk group for 2-3 years. The European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group toxicity grading scale was used to evaluate the urinary tract system toxicity. Relevant clinical factors were used in matching patients based on propensity scores to enable comparison between the groups., Results: Each group had 27 matched patients. There was no reduction in urinary tract toxicity with the use of luteinizing hormone-releasing hormon antagonists (P = 0.624). For patients with an International Prostate Symptom Score of ≥11 at the start of treatment, 18 patients in each group were matched. Significantly lower scores were observed in the luteinizing hormone-releasing hormon antagonist group (P = 0.041)., Conclusions: Luteinizing hormone-releasing hormon antagonists may reduce acute urinary tract toxicity during prostate cancer external beam radiotherapy compared with luteinizing hormone-releasing hormon agonists, in particular in patients with moderate to severe symptoms at the start of treatment., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

In this study, we propose a methodology for temperature determination of the temperature and pressure correction factor, PTP, by analyzing the temperature distribution of the modeled ionization chamber taking into account the thermal effect of a water phantom on neighboring materials in the process. Additionally, we present an appropriate temperature-equilibrium time for conducting measurements. The temporal response in the cavity is acquired at 20-s intervals using a Farmer ionization chamber and an electrometer. The initial temperature of the water phantom is 20-25°C with continuous heating/cooling. The temporal response is measured until temperature equilibrium is confirmed, specifically when a temperature difference of 1-5°C is observed between the ionization chamber and the water phantom. Using an ionization-chamber model, temperature distribution is simulated between 20 and 25°C with various parameters set to receive heating and cooling from surrounding media. The results suggest that the temporal response of the ionization chamber essentially coincides with the temperature change at the tip and middle; moreover, the predicted temperature change for temporal response and the simulated temperature of water are different by ~0.16°C at the tip and ~0.79°C at the bottom. Overall, the temperature-equilibration time for absorbed dosimetry is affected by two factors: the cavity wall and the stem side of the cavity; moreover, 400 s is required to obtain complete temperature equilibrium in the water phantom. This analytical study supports the experimental value obtained in previous research. Therefore, analytical representation of the temperature distribution in the ionization chamber is possible., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: We previously reported that Rag1 -/- mice inoculated with splenocytes from M3 muscarinic acetylcholine receptor (M3R) knockout mice immunized with an M3R peptide mixture developed sialadenitis-like Sjögren's syndrome (M3R-induced sialadenitis [MIS]). We also found that intravenous administration of altered peptide ligand (APL) of N-terminal 1 (N1), which is one of the T-cell epitopes of M3R, suppressed MIS. In this study, we aimed to evaluate the suppressive ability and its mechanisms of rice seeds expressing N1-APL7 against MIS. Methods: Rice seeds expressing N1 and N1-APL7 were orally administered to MIS mice for 2 weeks. The changes in saliva flow and sialadenitis (salivary gland inflammation) were analyzed. The M3R-specific T-cell response in the spleen and the expression of regulatory molecules in the cervical lymph nodes and mesenteric lymph nodes were also analyzed. Results: Oral administration of N1-APL7-expressing rice seeds significantly recovered reduction in saliva flow and suppressed sialadenitis when compared with treatment with nontransgenic rice seeds and N1 rice seeds. IFNγ production from M3R-reactive T cells tended to decline in the N1-APL7 rice-treated group as compared with those in the other groups. In the N1-APL7 rice-treated group, the mRNA expression levels of Foxp3 in the cervical-lymph-node CD4 + T cells were higher than those in the other groups. Conclusion: Oral administration of N1-APL7-expressing rice suppressed MIS via suppression of M3R-specific IFNγ and IL-17 production and via enhancement of regulatory molecule expression.Key messagesWe generated N1-peptide- or N1-APL7-expressing rice seeds. Oral administration of N1-APL7-expressing rice seeds significantly recovered the reduction of saliva flow and suppressed sialadenitis via the suppression of M3R specific IFNγ and IL-17 production and via enhancement of regulatory T (Treg) cells.

Objectives: To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD). Methods: The protein expression levels of CCL18 in labial salivary glands (LSGs) assessed by immunofluorescence (IF) staining were compared among patients with IgG4-RD ( n  = 3), primary Sjögren's syndrome (pSS; n  = 4), and control subjects ( n  = 5). CCL18 expression levels in macrophages, CD11c + cells, B cells, and plasmacytes in LSGs were examined by double IF staining. The protein expression levels of CCR8 and expressing cells (T, B cells, and plasmacytes) in LSGs were also compared among patients with IgG4-RD, pSS, and control subjects by double IF staining. The effects of the CCL18-CCR8 axis on total IgG, IgG2, and IgG4 production by peripheral blood mononuclear cells (PBMCs) stimulated with CD40L, IL-4, IL-10, and IL-21 were examined by in vitro assays. Results: CCL18 was specifically upregulated in LSGs of patients with IgG4-RD, compared with only a few cells in pSS patients and none of the controls. The numbers of CCL18-producing macrophages, CD11c + cells, and plasmacytes in LSGs were significantly higher in IgG4-RD patients than in pSS patients and control ( p  < .05, each). Many T and B cells and some plasmacytes expressed CCR8 in LSGs of IgG4-RD and pSS patients. CCL18 specifically enhanced IgG4 production by stimulated PBMCs. Conclusion: CCL18-CCR8 axis was upregulated in LSGs of patients with IgG4-RD, suggesting possible roles of this axis in the pathogenesis of IgG4-RD.Key messagesThe CCL18-CCR8 axis in labial salivary glands (LSGs) and lacrimal glands of IgG4-RD patients was specifically upregulated compared with primary Sjögren's syndrome and control subjects.This axis might be a potentially novel therapeutic target in IgG4-RD, based on its important etiopathogenic roles, such as chemotaxis of various cells, induction of fibrosis, and enhancement of IgG4 production.

IgG4-related disease (IgG4-RD) is characterized by lympho-plasmacytic infiltration and fibrosis in multiple organs, accompanied by high serum IgG4 levels. Although both IgG4-RD and Sjögren's syndrome (SS) frequently affect salivary and lacrimal glands, the clinical and pathological features of these two conditions are different. In an attempt to delineate the pathomechanisms of IgG4-RD, we compared the gene expression patterns of various molecules in labial salivary glands (LSGs) between IgG4-RD and SS. First, using quantitative PCR, we demonstrated significantly higher mRNA expression levels of activation-induced cytidine deaminase (AID), IL-10, and TGFβ in LSGs of IgG4-RD than SS and healthy controls (HCs). We propose that the combination of AID and IL-10 contributes to IgG4-specific immunoglobulin class switch recombination, and that TGFβ induces LSGs fibrosis in IgG4-RD. Second, DNA microarray identified 2641 differentially expressed genes (DEGs) in LSGs; with 1321 up-regulated and 1320 down-regulated genes in IgG4-RD, relative to SS. Among the up-regulated DEGs in IgG4-RD, quantitative PCR confirmed significantly higher expression levels of chemokine (C-C motif) ligand 18 (CCL18) and lactotransferrin in LSGs of IgG4-RD than SS and HCs. The former has chemotactic activity on various types of lymphocytes and enhances collagen production from fibroblasts, while lactotransferrin is an iron-binding protein abundantly present in milk and has a wide range of functions, including fibroblast proliferation and maturation of dendritic cells (DCs). Third, immunofluorescence staining confirmed specific upregulation of CCL18 in macrophages, CD11c + and B cells, and plasmacytes of LSGs-IgG4-RD. These pathological findings could help in the identification of disease-specific biomarkers as well as development of novel therapeutic strategies.

A variety of polyphenols have been isolated from plants, and their biological activities have been examined. Sudachitin (5,7,4'-trihydroxy-6,8,3'-trimethoxyflavone) is a polymethoxyflavone that is isolated from the peel of Citrus sudachi. Although we previously reported that sudachitin possesses an anti-inflammatory activity, its other biological activities are not yet understood. In this study, we report a novel biological activity of sudachitin, which selectively induced apoptosis in human keratinocyte HaCaT cells. Another polymethoxyflavone, nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), promoted autophagy but not apoptosis in HaCaT cells. On the other hand, 3'-demethoxysudachitin (5,7,4'-trihydroxy-6,8-dimethoxyflavone) failed to induce apoptosis and autophagy. These results show that three polymethoxyflavones have different effects on apoptosis and autophagy in HaCaT cells. Understanding the structure and biological activity of polymethoxyflavones may lead to the discovery of potential candidates for cancer drug development without significant toxic side effects. Abbreviations: ROS: reactive oxygen species; DMSO: dimethyl sulfoxide; MTT: 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; PARP: poly(ADP-ribose) polymerase; PI: propidium iodide; MAPK: mitogen-activated protein kinase.

Endoscopic submucosal dissection (ESD) has evolved into a viable treatment modality for superficial esophageal cancer. ESD offers a distinct advantage given the ability to perform en bloc resection enabling accurate histopathologic assessment. Data from published literature has established ESD as the preferred option in the treatment of superficial squamous cell carcinoma with complete resection rates of 78-100%, and a low rate recurrence of 0-2.6%. En bloc resection for esophageal SCC is curative for tumors with M1 (intrapethelial) or M2 (invasion into the lamina propria) involvement with no lymphovascular invasion. Tumors that contain lymphovascular invasion or submucosal invasion greater than 200 μm should be treated as advanced carcinomas due to the increased risk of lymph node metastasis. In contrast, the role of ESD in Barrett's esophagus is more limited due to the high rate of efficacy of EMR. A randomized control trial comparing EMR and ESD strategies found a higher R0 resection rate for ESD, but no significant difference in complete remission from neoplasia at 3 month follow up. Endoscopic ultrasound (EUS) has a limited role in the evaluation of superficial esophageal cancer. Alternatively, detailed endoscopic assessment along with magnification endoscopy or narrow band imaging, may provide greater utility than EUS. The most common adverse events of ESD in the esophagus include perforation and stricture. Perforation can often be managed by defect closure along with non-operative conservative management. Steroid administration with either topical or local injection can be effective management in stricture prevention. Continued refinement of ESD technique and innovation will overcome some of the current limitations of ESD and enable curative resection of superficial esophageal cancer as an alternative to invasive surgery.

Background: The intravascular compartment is known as the plasma volume, and the extravascular compartment represents fluid within the interstitial space. Plasma volume expansion is a major symptom of heart failure. The aim of the current study was to investigate the impact of plasma volume status on the prognosis of acute heart failure syndromes., Methods and Results: We analyzed 1115 patients with acute heart failure syndromes who were admitted to our hospital. These patients were divided into three groups based on their plasma volume status at admission: first tertile (plasma volume status <41.9%, n = 371), second tertile (41.9%⩽ plasma volume status <49.0%, n = 372), and third tertile (49.0%⩽ plasma volume status, n = 372). Plasma volume status was defined as follows: actual plasma volume = (1 - hematocrit) × [ a + ( b × body weight)] ( a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal plasma volume = c × body weight ( c=39 in males and c=40 in females); and plasma volume status = [(actual plasma volume - ideal plasma volume)/ideal plasma volume] × 100 (%). In the Kaplan-Meier analysis, all-cause mortality, cardiac mortality and cardiac events increased progressively from the first to third tertile ( p <0.001, respectively). In the Cox proportional hazard analysis, after adjusting for potential confounding factors, plasma volume status was an independent predictor of all-cause mortality (hazard ratio 1.429, p < 0.001), cardiac mortality (hazard ratio 1.416, p = 0.001) and cardiac events (hazard ratio 1.207, p = 0.004)., Conclusion: Increased congestion is associated with increased morbidity and mortality in heart failure patients. Plasma volume status, which represents intravascular compartment and congestion, can identify poor prognosis in patients with acute heart failure syndromes.

Objectives: The objective of this study is to develop clinical practice guideline (CPG) for Sjögren's syndrome (SS) based on recently available clinical and therapeutic evidences., Methods: The CPG committee for SS was organized by the Research Team for Autoimmune Diseases, Research Program for Intractable Disease of the Ministry of Health, Labor and Welfare (MHLW), Japan. The committee completed a systematic review of evidences for several clinical questions and developed CPG for SS 2017 according to the procedure proposed by the Medical Information Network Distribution Service (Minds). The recommendations and their strength were checked by the modified Delphi method. The CPG for SS 2017 has been officially approved by both Japan College of Rheumatology and the Japanese Society for SS., Results: The CPG committee set 38 clinical questions for clinical symptoms, signs, treatment, and management of SS in pediatric, adult and pregnant patients, using the PICO (P: patients, problem, population, I: interventions, C: comparisons, controls, comparators, O: outcomes) format. A summary of evidence, development of recommendation, recommendation, and strength for these 38 clinical questions are presented in the CPG., Conclusion: The CPG for SS 2017 should contribute to improvement and standardization of diagnosis and treatment of SS.

The small Indian mongoose (Herpestes auropunctatus) is an invasive species in Okinawa and Amami-Oshima, Japan. Major strategies for their eradication have been the use of baited traps, which suffer from decreasing efficiency with declining populations and the bycatch of native animals. To address these concerns, mongoose-specific lures are required. In this study, we aimed to identify species- and/or sex-specific compounds from anal sac secretions of small Indian mongooses. Volatile compounds emitted from male and female mongoose anal sac secretions were analyzed by thermal desorption-gas chromatography-mass spectrometry. In addition to several fatty acids, 2-phenylethanol was identified as a minor compound, which is uncommon in mammalian secretions but a dominant odorant in roses. Female samples emitted higher levels of 2-phenylethanol than male samples did. These findings indicate that 2-phenylethanol is a female-specific volatile compound of anal sac secretions in small Indian mongooses, and it may be useful as an ingredient of mongoose-specific scent lures.

Objectives: To evaluate the scoring of whole-body magnetic resonance imaging (WBMRI) for efficacy assessment in rheumatoid arthritis (RA) patients receiving biological disease-modifying anti-rheumatic drugs (bDMARDs)., Methods: Thirty consecutive RA patients receiving bDMARDs were included in this retrospective study. Contrast WBMRI was performed before and 1 year after bDMARDs initiation., Results: At baseline, mean age was 57.1 years and mean disease duration was 3.0 years. Median disease activity score in 28 joints improved from 5.1 to 2.1. Treatment with bDMARDs improved mean whole-body synovitis score from 31.2 to 23.2 and median whole-body bone-edema score from 11 to 3. Whole-body bone-erosion score improved in seven patients and deteriorated in 17 patients. Logistic regression analysis identified whole-body synovitis score as a poor prognostic factor for whole-body bone-erosion progression. Bone-edema score in individual bones was identified as a poor prognostic factor for the progression of bone-erosion. Changes in hand synovitis score correlated with those of other joints, but neither changes in bone-edema nor erosion score of hands correlated with those of other joints in WBMRI., Conclusions: WBMRI scoring may be a novel useful tool to evaluate the efficacy of anti-rheumatic drugs, as well as a potential predictor of joint prognosis, in patients with RA.

Protamine peptide (PP) derived from salmon is a 14-mer with 10 arginine residues. We investigated the in vitro and in vivo antifungal activity of PP against Candida albicans PP showed a concentration-dependent dual mode of action, with fungicidal activity and inhibitory activity for hyphal development in vitro. At lethal concentrations of PP, intracellular accumulation of PP was energy-dependent but independent of endocytosis, and resulted in ATP efflux and the generation of reactive oxygen species in the cells. PP at sublethal concentrations inhibited hyphal development in C. albicans by binding to the cell surface. Though antifungal activity of PP was inactivated by high concentrations of NaCl, the antifungal activity of the synthetic cyclic (via a disulfide bond) form of PP (cyclic PP) was not. Cyclic PP also showed the concentration-dependent dual mode of action, and had five-fold greater antifungal activity than PP. The advantage of antifungal activity of cyclic PP compared with PP in vitro resulted in a high in vivo efficacy in a murine oral candidiasis model. Oral treatment with cyclic PP inhibited hyphal development of C. albicans on mouse tongues and protected against the development of severe candidiasis. This study shows the therapeutic potential of cyclic PP as an antifungal peptide against C. albicans., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We investigated whether the maintenance of routine assessment of patient index data 3 (RAPID3) remission for one year (RAPID3-MR) may predict good radiographic outcomes. We also compared radiographic progression to prognostic factors among patients with RAPID3-MR, with the maintenance of clinical disease activity index remission for one year (CDAI-MR) or with the maintenance of 28 joint count disease activity score remission for one year (DAS28-MR)., Methods: Of 1220 patients with available clinical data, 92 with RAPID3-MR, 80 with RAPID3-NMR (not satisfying RAPID3-MR), 45 with CDAI-MR, and 75 with DAS28-MR were retrospectively investigated. CDAI and DAS28 for clinical outcomes and the modified total Sharp score (mTSS) for radiographic joint damage were investigated for at least one year., Results: RAPID3, CDAI, DAS28, and their categories remained unchanged or significantly improved in RAPID3-MR patients but significantly deteriorated in RAPID3-NMR patients. The mean annual ΔmTSS was significantly lower in RAPID3-MR patients (0.12 ± 0.55) than in RAPID3-NMR patients (0.54 ± 1.27) (p = 0.025). There was no significant difference among RAPID3-MR patients, CDAI-MR patients (0.06 ± 0.85), and DAS28-MR patients (0.11 ± 0.89). The baseline mTSS (p = 0.038) and monotherapy with nonbiological disease-modifying antirheumatic drugs (p = 0.033) were good prognostic factors in RAPID3-MR patients., Conclusions: One-year RAPID3 remission maintenance may predict good radiographic outcomes.

Objective: To compare the effectiveness of three different biologics in anti-Ro/SSA antibody-positive and antibody-negative patients with rheumatoid arthritis (RA)., Methods: The study subjects were 110 biologics naïve patients with RA who started treatment with biologics and examined for anti-Ro/SSA antibody between December 2003 and March 2014. For patients treated with intravenous infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT), we compared the clinical characteristics and changes in composite disease activity index, such as DAS28, SDAI, and CDAI, for 12 months in anti-Ro/SSA antibody-positive and antibody-negative patients., Results: We examined 59 patients (nine were positive and 50 were negative for anti-Ro/SSA antibody) treated with IFX, 27 patients (5 positive and 22 negative) treated with TCZ, and 24 patients (13 positive and 11 negative) treated with ABT. For patients treated with IFX, parameters of disease activity did not change significantly from baseline in anti-Ro/SSA antibody-positive patients, whereas they improved in antibody-negative patients. On the other hand, treatment with TCZ and ABT significantly decreased disease activity, relative to baseline, in both anti-Ro/SSA antibody-positive and antibody-negative patients. Anti-Ro/SSA antibody-positive patients treated with IFX showed higher frequency of HACA and seroconversion of ANA, and lower serum TGF-β levels., Conclusions: Positivity to anti-Ro/SSA in RA seems to confer resistance to IFX via production of HACA and ANA, and low serum TGF-β levels, but not to TCZ and ABT.

Background: Although histone acetylation, an epigenetic modification, has been reported to be related to the progression of various diseases, its involvement in nephrosclerosis is unclear., Methods: Dahl salt-sensitive rats were used as a model of nephrosclerosis in this study. The rats were divided into three groups: (i) normal-salt diet group, (ii) high-salt diet group (HS), and (iii) HS administered daily with curcumin, a histone acetyltransferase inhibitor (HS+C). At 6 weeks after the treatment, the kidneys were dissected. Morphologic changes were assessed by Masson's trichrome staining. The number of macrophages, fibroblasts and the cells expressing acetylated histone H3 at Lys 9 (H3K9) were assessed by immunohistochemistry., Results: Although both HS and HS+C rats revealed a marked increase in systolic blood pressure, serum creatinine was increased only in HS rats at 6 weeks. In the HS rats, nephrosclerosis was induced, accompanying a significant accumulation of macrophages and fibroblasts. The inflammation and fibrosis was markedly suppressed in the HS+C group. The level of histone acetylation at Lys 9 was enhanced in the HS rats, whereas curcumin administration suppressed the histone acetylation. Moreover, in the HS rats, interleukin-6 gene expression was associated with acetylated H3K9, as revealed by chromatin immunoprecipitation assay., Conclusions: Our results suggested that curcumin ameliorates nephrosclerosis via suppression of histone acetylation, independently of hypertension., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Unlabelled: : Although isolation of oral mucosal stromal stem cells has been previously reported, complex isolation methods are not suitable for clinical application. The neurosphere culture technique is a convenient method for the isolation of neural stem cells and neural crest stem cells (NCSCs); neurosphere generation is a phenotype of NCSCs. However, the molecular details underlying the isolation and characterization of human oral mucosa stromal cells (OMSCs) by neurosphere culture are not understood. The purpose of the present study was to isolate NCSCs from oral mucosa using the neurosphere technique and to establish effective in vivo bone tissue regeneration methods. Human OMSCs were isolated from excised human oral mucosa; these cells formed spheres in neurosphere culture conditions. Oral mucosa sphere-forming cells (OMSFCs) were characterized by biological analyses of stem cells. Additionally, composites of OMSFCs and multiporous polylactic acid scaffolds were implanted subcutaneously into immunocompromised mice. OMSFCs had the capacity for self-renewal and expressed neural crest-related markers (e.g., nestin, CD44, slug, snail, and MSX1). Furthermore, upregulated expression of neural crest-related genes (EDNRA, Hes1, and Sox9) was observed in OMSFCs, which are thought to contain an enriched population of neural crest-derived cells. The expression pattern of α2-integrin (CD49b) in OMSFCs also differed from that in OMSCs. Finally, OMSFCs were capable of differentiating into neural crest lineages in vitro and generating ectopic bone tissues even in the subcutaneous region. The results of the present study suggest that OMSFCs are an ideal source of cells for the neural crest lineage and hard tissue regeneration., Significance: The sphere culture technique is a convenient method for isolating stem cells. However, the isolation and characterization of human oral mucosa stromal cells (OMSCs) using the sphere culture system are not fully understood. The present study describes the isolation of neural crest progenitor cells from oral mucosa using this system. Human OMSCs form spheres that exhibit self-renewal capabilities and multipotency, and are enriched with neural crest-derived cells. These oral mucosa sphere-forming cells can generate ectopic bone tissue in vivo. Therefore, the results of the present study show that the sphere culture system can be applied, without the need for complex isolation techniques, to produce multipotent spheres with the properties of neural crest stem cells. Furthermore, a convenient strategy is demonstrated for the isolation and culture of human OMSCs that could have clinical applications., (©AlphaMed Press.)