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Objective Li-Fraumeni syndrome (LFS) is a pan-cancer predisposition syndrome caused by germline pathogenic variants in the gene TP53. The interpretation of TP53 variants in clinical scenarios outside the classic LFS criteria may be challenging. Here, we report a patient affected by 2 primary cancers at later ages, who harbored a likely pathogenic TP53 at low allele frequency detected in a blood sample. Methods The Molecular Tumor Board committee at our institution revisited the case of a patient who was enrolled in a research protocol for the investigation of genetic conditions associated with neuroendocrine tumors. Clinical, familial, and molecular data were reviewed. The patient received germline testing using a next generation sequencing multi-gene panel and was incidentally found to harbor a TP53 likely pathogenic variant, with 22% of variant allele fraction. Additional samples, including a second blood sample, oral swab, and saliva, were collected for DNA analysis. A new TP53 sequencing round was performed with the attempt to distinguish between a true constitutional germline variant and a somatically acquired variant due to aberrant clonal expansion of bone marrow precursors. Results Patient’s personal and familial history of cancer did not meet classic nor Chompret LFS criteria. Environmental risk factors for cancer were identified, such as alcohol abuse and tobacco exposure. The TP53 variant initially found in the next-generation sequencing was confirmed by Sanger sequencing in the previous DNA sample extracted from blood for the first analysis and in a second blood sample collected 6 years later. The TP53 variant was not detected in the DNA extracted from the oral swab and saliva samples. Conclusion Considering the low TP53 variant allele fraction in blood, absence of variant detection in oral swab and saliva samples, the lack of LFS clinical criteria, and history of exposure to environmental risk factors for cancer, the main hypothesis for this case was aberrant clonal expansion due to clonal hematopoiesis. Oncologists should interpret TP53 findings during germline testing with caution.

SynopsisIn the field of organismal biology, as in much of academia, there is a strong incentive to publish in internationally recognized, highly regarded, English-language journals to promote career advancement. This expectation has created a linguistic hegemony in scientific publishing, whereby scholars for whom English is an additional language face additional barriers to achieving the same scientific recognition as scholars who speak English as a first language. Here, we surveyed the author guidelines of 230 journals in organismal biology with impact factors of 1.5 or greater for linguistically inclusive and equitable practices and policies. We looked for efforts that reflect first steps toward reducing barriers to publication for authors globally, including the presence of statements that encouraged submissions from authors of diverse nationalities and backgrounds, policies regarding manuscript rejection based on perceived inadequacies of the English language, the existence of bias-conscious reviewer practices, whether translation and editing resources or services are available, allowance for non-English abstracts, summaries, or translations, and whether journals offer license options that would permit authors (or other scholars) to translate their work and publish it elsewhere. We also directly contacted a subset of journals to verify whether the information on their author guidelines page accurately reflects their policies and the accommodations they would make. We reveal that journals and publishers have made little progress toward beginning to recognize or reduce language barriers. Counter to our predictions, journals associated with scientific societies did not appear to have more inclusive policies compared to non-society journals. Many policies lacked transparency and clarity, which can generate uncertainty, result in avoidable manuscript rejections, and necessitate additional time and effort from both prospective authors and journal editors. We highlight examples of equitable policies and summarize actions that journals can take to begin to alleviate barriers to scientific publishing.

Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

Background Cardiopulmonary arrest (CPA) is the most serious presentation of acute myocardial infarction (AMI). However, the frequency and prognostic impact of CPA in young patients with AMI have been still unclear. Objectives This study aimed to characterize AMI in young patients who underwent primary percutaneous coronary intervention using large-scale nationwide all-comer registry data in Japan (J-PCI registry). Methods Data on risk factor profiles, clinical features, post-procedural complications, and in-hospital outcomes were reviewed within the J-PCI registry between 2014 and 2018. Results Among 213,297 patients with AMI, 23,985 (11.2%) were young (age, 20–49 years). Compared with the older group (age, 50–79 years; n=189,312), the young group included a higher number of men, smokers, patients with dyslipidemia, and patients with single-vessel disease, and a lower number of patients with hypertension and diabetes. Despite favorable clinical profiles, younger age was associated with a higher rate of presentation with CPA (Figure 1). Further, concomitant CPA was strongly associated with in-hospital mortality in the young group (Table 1). Conclusions Young patients with AMI presented a higher risk of CPA than older patients, which was strongly associated with in-hospital mortality. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI

Charge acceleration during an intense light field application to solids attracts much attention as elementary processes in high-harmonic generation and photoelectron emission. For manipulating such attosecond dynamics of charge, carrier-envelope-phase (CEP: relative phase between carrier oscillation of light field and its envelope function) control has been employed in insulators, nanometal and graphene. In superconducting materials, collective control of charge motion is expected because of its strongly coherent nature of quasi-particles. Here we report that, in a layered organic superconductor, a non-linear petahertz current driven by a single-cycle 6 femtosecond near infrared field shows up as second harmonic generation (SHG), which is in contrast to the common belief that even harmonics are forbidden in the centrosymmetric system. The SHG represents a CEP sensitive nature and an enhancement near the superconducting temperature. The result and its quantum many-body analysis indicate that a polarized current is induced by non-linear acceleration of charge, which is amplified by superconducting fluctuations. This will lead to petahertz functions of superconductors and of strongly correlated systems., Here the authors show second harmonic generation (SHG) from a centrosymmetric organic superconductor κ-(BEDT-TTF)2Cu[N(CN)2]Br. They find unusual temperature dependence and CEP-sensitive nature of the SHG which are explained in terms of nonlinear current.

In a honeycomb-lattice Mott insulator α-RuCl3, an ultrafast magnetization is induced by circularly polarized excitation of spin-orbit excitons. An ultrafast 6-fs measurement clarifies that the orbital moment emerges from a coherent inter-orbital charge motion.

Background Large-scale registries have demonstrated that in-hospital mortality after percutaneous coronary intervention (PCI) varies widely across institutions; however, the underlying reasons are not fully understood. Bleeding has been regarded as one of the most serious PCI-related complications associated with increase in mortality. To date, reducing bleeding complications have tended to be addressed, though appropriate care for patients who developed bleeding complications may be also important. Therefore, we sought to investigate which was more involved in the inter-institutional variations in in-hospital mortality. Methods We analyzed 388,866 procedures at 718 hospitals performed from 2017 to 2018, using data from a representative nationwide PCI registry in Japan. A bleeding complication was defined as post-procedural bleeding that required a blood transfusion. We first divided the hospitals into quintiles according to their risk-adjusted in-hospital mortality (very low, low, medium, high, and very high). Then, the bleeding complication rate and in-hospital mortality rate among patients who developed bleeding complications were calculated for each quintile. Results In total, 4,048 (1.04%) in-hospital deaths and 1,535 (0.39%) bleeding complications occurred. In-hospital mortality varied widely from 0.22% to 2.46% in very-low- to very-high-mortality hospitals. The bleeding complication rate also increased modestly from 0.27% to 0.57% (odds ratio, 1.95; 95% confidence interval, 1.58–2.39). However, the mortality rate among patients who developed bleeding complications markedly increased by quintile; the mortality rate of very-high-morality hospitals was 6-fold higher than that of very-low-mortality hospitals (29.0% vs. 4.8%, respectively; odds ratio, 12.2; 95% confidence interval, 6.9–21.7). Conclusions Wide variation in in-hospital mortality was observed within the Japanese nationwide PCI registry, and this variation was largely driven by differences in mortality among patients with bleeding complications, rather than crude incidence of bleeding complications. These results underscore the importance of efforts toward reducing not only bleeding complications but also, even more importantly, mortality once bleeding has occurred. Funding Acknowledgement Type of funding sources: None.

Background Fractional flow reserve (FFR) is a gold standard method to evaluate functional lesion severity in daily clinical practice. Recently, the resting full-cycle ratio (RFR) was Previous studies showed the better diagnostic performance of RFR comparing with FFR. It is well known that patients with chronic kidney disease (CKD) have poor prognosis. Therefore, we should carefully assess the functional lesion severity in CKD patients. However, it is unclear whether the diagnostic performance of RFR for detecting functional ischemia is similar regardless of the degree of renal function. The aim of this study is to compare the diagnostic performance of RFR based on renal function. Method This study was a prospectively enrolled observational study. A total of 265 consecutive patients with 373 intermediate lesions were enrolled in this study. There were classified into three groups according to renal function (Group 1: eGFR ≥60 mL/min/1.73m2; Group 2: 30 mL/min/1.73m2 ≤eGFR Results Of 373 lesions, the median age was 70.1±11.0 years. Functional significance was observed in 153 lesions (41.0%) of all lesions. RFR showed a significant correlation with FFR in each group (Group 1; r2=0.63 [p Conclusion The diagnostic performance of RFR was different based on renal function. During RFR acquisition, the degree of renal function could influence concordance with FFR, and should be taken into account when interpreting RFR. Funding Acknowledgement Type of funding sources: None.

Jensen (Can. J. Phys. 98, 506 (2020). doi: 10.1139/cjp-2019-0395 ) presents theoretical justification for the claim that linear triatomic molecules are necessarily observed to be bent. The basis of the assertion is that the expectation value of the supplement of the bending angle, [Formula: see text] used in Jensen’s paper, is calculated to be positive. In this comment, we examine the interpretation of the expectation values of [Formula: see text] in stationary states, and indicate that Jensen’s claim contradicts a basic principle of quantum mechanics that the energy and geometrical variables cannot have definite values at the same time.

Background Current evidence regarding COVID‐19 convalescent plasma (CCP) transfusion practices is limited and heterogeneous. We aimed to determine the impact of the use of CCP transfusion in patients with previous circulating neutralizing antibodies (nAbs) in COVID‐19. Methods Prospective cohort including 102 patients with COVID‐19 transfused with ABO compatible CCP on days 0–2 after enrollment. Clinical status of patients was assessed using the adapted World Health Organization (WHO) ordinal scale on days 0, 5, and 14. The nAbs titration was performed using the cytopathic effect‐based virus neutralization test with SARS‐CoV‐2 (GenBank MT126808.1). The primary outcome was clinical improvement on day 14, defined as a reduction of at least two points on the adapted WHO ordinal scale. Secondary outcomes were the number of intensive care unit (ICU)‐free days and the number of invasive mechanical ventilation‐free days. Results Both nAbs of CCP units transfused (p

We examined whether eccrine sweat glands ion reabsorption rate declined with age in 35 adults aged 50-84 years. Aerobic fitness (VODuring a passive heating protocol (lower leg 42 °C water submersion) the maximum ion reabsorption rates from the chest, forearm and thigh were measured, alongside other thermophysiological responses. The maximum ion reabsorption rate was defined as the inflection point in the slope of the relation between galvanic skin conductance and sweat rate.The maximum ion reabsorption rate at the forearm, chest and thigh (0.29 ± 0.16, 0.33 ± 0.15, 0.18 ± 0.16 mg/cmThe eccrine sweat glands' maximum ion reabsorption rate is not affected by age, spanning 50-84 years. Aldosterone concentration in an aged cohort does not appear to modulate the ion reabsorption rate. We provide further support for maintaining cardiorespiratory fitness to attenuate any decline in sudomotor function.

We demonstrate temperature insensitive operation of an active optical package substrate comprising of silicon waveguide, two micro-mirrors and polymer waveguide. Transmission of 112-Gb/s PAM4 optical signal was performed without noticeable penalty at 85 °C.

INTRODUCTIONCOVID-19 convalescent plasma (CCP) transfusion has emerged in the past months as an alternative approach to treat pneumonia cases of SARS-CoV-2. Current evidence regarding characteristics of the plasma product, the titer of neutralizing antibodies (nAbs) in the transfused units, time to onset of intervention, and impact of nAbs produced by the patient are limited and heterogeneous.MATERIAL AND METHODSWe describe the preliminary results of 104 patients with severe pneumonia due to SARS-CoV-2 transfused with CCP at three medical centers in Brazil. All enrolled patients were transfused with doses between 200 mL through 600mL of ABO compatible CCP on days 0-2 after enrolment. Clinical parameters were monitored and nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBankMT126808.1).RESULTSForty-one patients achieved clinical improvement on day 14, and multivariable logistic regression showed that nAbs T (from CCP units transfused) (p= 0.001), nAbs P0 (on day of enrolment) (p=0.009) and use of other supportive therapies (pDISCUSSION/CONCLUSIONDespite the study limitations, our data have shown an association between patients’ previously acquired nAbs and clinical outcomes. The potential value of timely administration of CCP transfusion before day 10 of disease onset was demonstrated and nAbsP0, but not nAbsT, were associated with ICU LOS, and duration of mechanical ventilation on the improvement of clinical outcomes was also demonstrated. In conclusion, we consider these data are useful parameters to guide future CPP transfusion strategies to COVID-19.

BackgroundDecreased regulatory T cells (Tregs) and Treg dysfunction are hallmarks of a various autoimmune and inflammatory diseases. While low-dose IL-2 therapy induces Treg expansion in vivo and has clinical benefits in some diseases (e.g., SLE and chronic graft-versus-host disease [GvHD]), there are many concerns about adverse events due to low Treg-selectivity. Furthermore, frequent dosing is needed due to the short half-life.ObjectivesWe discovered a novel site-specific PEGylated IL-2 variant, KKC80, with high Treg selectivity and a long half-life in vivo, which overcomes the issues of low-dose IL-2 therapy.MethodsBased on the co-crystal structure of wild-type IL-2 and its heterotrimeric receptor (PBD ID: 2ERJ), amino acid residues that were to be PEGylation sites were substituted with oAzZLys, an azide-containing lysine derivative. The PEG molecule was site-specifically attached to oAzZLys-incorporated IL-2 by copper-free click chemistry. The binding property to the IL-2 receptors were measured by surface plasmon resonance (SPR). In vitro, Treg selectivity was evaluated by the IL-2-dependent proliferation activity of Tregs and NK cells from human peripheral blood mononuclear cells (PBMCs). In vivo pharmacological activity after the single subcutaneous administration in cynomolgus monkeys was measured by changes in Treg count and Treg activation status in peripheral blood by flow cytometry. Pharmacokinetic parameters were calculated according to serum PEGylated IL-2 concentration. Efficacy in mouse xenogeneic GvHD model using human PBMC-transplanted NOG mice and in monkey DTH model were evaluated.ResultsA novel PEGylated IL-2, KKC80 (human IL-2 desA1/C125S /I129oAzZLys_W-shaped 80 kDa PEG) was discovered by optimizing the PEGylation site and PEG structure based on Treg selectivity and PK. SPR analysis showed that the binding affinity of KKC80 to CD25 was moderately decreased from wild-type IL-2, while binding affinity of KKC80 to IL-2Rβγ was remarkably decreased due to a significant change of the association rate constant. In vitro, wild-type IL-2 activated both Tregs and NK cells in the same concentration range, whereas KKC80 selectively activated Tregs. The Treg selectivity of KKC80 was comparable to another IL-2 mutein, Fc.IL-2 V91K. KKC80, but not Fc.IL-2 V91K, retained its biological activity, even in the presence of a large amount of recombinant soluble CD25, which mimicked the endogenous decoy receptor for IL-2. In monkeys, KKC80 selectively increased peripheral blood Tregs in a dose-dependent manner; the average maximum rate of increase of Treg count in animals treated with 0.01, 0.03, 0.1, 0.3 and 1 mg/kg was 1.5, 3.5, 28, 50 and 154-fold, respectively. In contrast to Tregs, the rates of increase of conventional CD4+ T, CD8+ T and NK cells were low. The Treg increase peaked on day 8 or 11 and lasted for over day 29. KKC80 showed a more sustained upregulation of functional Treg markers (e.g., Foxp3 and CD25) in comparison to Fc.IL-2 V91K. The half-life of KKC80 was calculated as 83.5 to 150 h. At high doses, inflammation-related adverse effects, including increased CRP (≥0.3 mg/kg) and deterioration of general conditions (1 mg/kg) were observed. In the mouse xenogenic GvHD model, KKC80 ameliorated GvHD symptoms and suppressed multiple tissue inflammation markers. Decreased soluble CD25 and IFN-γ were also confirmed, suggesting Treg-mediated anti-inflammatory effect by KKC80 administration were exerted in vivo. In the monkey DTH model, KKC80 suppressed skin inflammation and antibody production.ConclusionAmong next-generation IL-2 variants, KKC80 showed a best-in-class biological profile for Treg activation. A drastic and sustained increase of Tregs with high Treg-selectivity and anti-inflammatory effects were observed in vivo. These data suggest that in comparison to current IL-2 therapy, KKC80 provides superior therapeutic index and efficacy in patients with autoimmune and inflammatory diseases.Figure 1.Disclosure of InterestsMasahiro Ikeda Employee of: Kyowa Kirin Co., Ltd., Shinpei Yamaguchi Employee of: Kyowa Kirin Co., Ltd., Masumi Murakami Employee of: Kyowa Kirin Co., Ltd., Shigeki Takaoka Employee of: Kyowa Kirin Co., Ltd., Yasuko Sakaguchi Employee of: Kyowa Kirin Co., Ltd., Shunki Yasui Employee of: Kyowa Kirin Co., Ltd., Kousuke Iijima Employee of: Kyowa Kirin Co., Ltd., Kenichiro Nanya Employee of: Kyowa Kirin Co., Ltd., Hideyuki Onodera Employee of: Kyowa Kirin Co., Ltd., Toru Amano Employee of: Kyowa Kirin Co., Ltd.

Introduction Phosphodiesterase (PDE) 5 inhibitors induce relaxation of endothelial cells. Tadalafil, one of PDE 5 inhibitors, has been applied for the treatments of erectile dysfunction (ED) and benign prostate hyperplasia (BPH). Under continuous treatments with PDE 5 inhibitor for BPH, it is significant to investigate the relationship between endothelial and sexual functions by comparing the brachial-ankle pulse wave velocity (baPWV).and the sexual health inventory for men (SHIM) score. Objectives Total 89 BPH patients who consulted our clinic with a complaint of urinary symptoms were enrolled in this prospective study. They were treated with a daily dose of 5mg tadalafil. Methods The Institutional Review Board (IRB) approved this clinical study and informed consents had been obtained from 89 BPH patients. Their vessels endothelial function was assessed by baPWV and erectile function was evaluated by SHIM score. International prostate symptom score (IPSS) was obtained as male lower urinary symptoms (LUTS) parameters. However, we focused on the relationship between vessels endothelial and erectile function in this sub-analysis report. Therefore, the SHIM scores were compared with baPWV and IPSS at 0, 3, 6, 12, 24, 36, 48, 60, 72 and 84 months after PDE5 inhibitor treatment. Results The mean age of 89 patients was 66.7 +/- 11.1 years old. Their prostate size was 29.8 +/- 21.2 ml. Initial SHIM, baPWV and IPSS score were 7.4 +/- 5.6, 1742.5 +/- 393.0 cm/sec and 17.5+/- 7.5, respectively. Before tadalafil treatment, baPWV and SHIM were significantly correlated (p=0.0025) which indicated patients with low vessels endothelial function vessels endothelial function suffered from erectile dysfunction. F4rthere06re, all the data of baPWV and SHIM including after tadalafil treatment from 3 to 84 months (n=472) were significantly co-related each other (p Conclusions Our previous paper (Aging Male 21, 2018) reported that PDE5 inhibitors improved ED, male LUTS and baPWV from 3 to 12 months. The present data also suggested that endothelial function and male LUTS strongly related to ED in BPH patients. However, baPWV and SHM score levels returned to the baseline levels after 24 and 36 months, respectively. Thus, tadalafil can delay vessels endothelial and erectile dysfunction in BPH patients. In addition, erectile dysfunction seems to be occurred after vessels endothelial dysfunction. Hence, baPWV might be a predictive factor for ED in BPH patients with tadalafil treatments. Disclosure Work supported by industry: no.

Summary Purpose Table tennis is a popular physical activity offering several health benefits. However, the physiological responses to table tennis, relative to other exercise types, have not been fully investigated. A comparison between different exercise types, based on ratings of perceived exertion (RPE), would offer a better physiological characterization of table tennis. We therefore investigated cardiorespiratory and thermoregulatory responses to table tennis relative to cycling at a similar RPE. Methods Eight healthy table tennis players performed 2 sets of 5 minutes simulated table tennis exercise separated by a 5 minutes break by returning a ball ejected from a machine at light (30 balls/min) and moderate (45 balls/min) intensities, respectively. RPE (range, 6–20) was assessed at the end of exercise. On the second visit, they cycled for 5 minutes to meet similar RPE reported during table tennis trial. Physiological responses were assessed during table tennis and cycling trials. Results There was no significant reported difference in RPE between the two exercise types at light (12.9 ± 2.0 and 11.5 ± 1.9 for table tennis and cycling, respectively) and moderate (14.5 ± 0.9 and 14.0 ± 1.4, respectively) intensities, respectively (exercise type effect and interaction, all P ≥ 0.134). Heart rate and oxygen consumption were greater in table tennis than in cycling at both light and moderate intensities (all P ≤ 0.047). No difference in core body temperature was recorded between the exercise types (P = 0.227), but skin temperature was lower in table tennis than in cycling in both intensities (both P ≤ 0.034). Chest sweat rate was slightly greater in table tennis than in cycling at moderate intensity (P = 0.060). Conclusion These results suggest that the cardiopulmonary and thermoregulatory responses of table tennis were greater than those of cycling even at similar RPE.

Intense light-field application to solids produces enormous/ultrafast non-linear phenomena such as high-harmonic generations 1, 2 and attosecond charge dynamics 3, 4. They are distinct from conventional photonics. However, main targets have been limited to insulators and semiconductors, although theoretical approaches have been made also for correlated metals and superconductors 5. Here, in a layered organic superconductor, a non-linear charge oscillation driven by a nearly single-cycle strong electric field of >10 megavolts /cm is observed as a stimulated emission. The charge oscillation is different from a linear response and ascribed to a polar charge oscillation with a period of 6 fs. This non-linear polar charge oscillation is enhanced by critical fluctuations near a superconducting transition temperature and a critical end point of first order Mott transitions. Its observation on an ultrafast timescale of 10 fs clarifies that the Coulomb repulsion plays an essential role in superconductivity of organic superconductors., 5 Figs. for main text, 3 Figs for supplementary information

Background The number of elderly patients with inflammatory bowel disease (IBD) is increasing, but the outcomes of patients with elderly onset (EO) IBD treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Methods This was a multicenter retrospective observational study including bio-naïve patients with IBD who started anti-TNF treatment from, 2010 to, 2019 at, 18 hospitals of the Osaka Gut Forum. Elderly patients were defined as those, 60 years and older, and elderly patients with IBD were further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). The clinical symptoms were evaluated by partial Mayo score (pMayo) for UC and Harvey-Bradshaw index (HBI) for CD, and the clinical remission rate at, 52 weeks after the start of treatment was analyzed retrospectively. Clinical remission was defined as pMayo ≤, 2 and each subscore ≤, 1 for UC and HBI ≤, 4 for CD. Results A total of, 432 patients were enrolled, comprising, 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and, 352 under age, 60 (Non-elderly, 81.5%). After, 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and, 60.8%; P = 0.001, and, 35.9% and, 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission [Odds ratio (OR), 0.49, 95% confidence interval (CI), 0.25–0.96] and steroid-free remission [OR, 0.51, 95%CI, 0.26–0.99] after, 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly lower in Elderly-EO than in Non-elderly (P = 0.007), but comparable between Elderly-NEO and Non-elderly. Conclusion Anti-TNF treatment is less effective for bio-naïve EO-IBD than for elderly patients with younger onset and non-elderly, and may raise safety concerns in this group of patients.

Background:Dysphagia (swallowing disorder) is an important health concern among the elderly that is associated with a poor prognosis [1]. Rheumatic diseases such as dermatomyositis are thought to represent an important risk factor for dysphagia, but few studies have described the association between dysphagia and rheumatoid arthritis (RA), and details on the prevalence of dysphagia in RA patients is not known [2] [3].Objectives:The present study aimed to determine the prevalence of dysphagia and associated risk factors among elderly patients with rheumatoid arthritis.Methods:We conducted a cross-sectional study including 93 patients with RA and osteoarthritis (OA) over 65 years of age. OA patients were included in the study as healthy controls. Patients with a history of stroke, neuromuscular disease, or head and neck tumors were excluded from the study. From July to November 2019, the water swallowing test (WST) and repetitive saliva swallowing test (RSST) were performed to evaluate the presence or absence of dysphagia in the patients. We also checked oral conditions, hoarseness, temporomandibular joint symptoms, cervical range of motion limitations, and grip strength. In addition, interviews were conducted to investigate swallowing ability and aspiration history. We compared the prevalence of dysphagia between RA and OA patients and explored potential risk factors for dysphagia in RA patients using logistic regression models.Results:Our study subjects comprised 63 RA patients (mean age, 73.8 years; 86.5% female) and 30 OA patients (mean age, 75.8 years; 82.3% female). The WST and RSST revealed that RA patients had a significantly higher prevalence of dysphagia than OA patients (23.8% vs 6.7%, pConclusion:Dysphagia was more prevalent among RA patients than in OA patients, suggesting an association with temporomandibular involvement, cervical disorder, and muscle weakness. Subclinical dysphagia should be assessed and monitored carefully in the clinical course of elderly patients with RA.References:[1] KW Altman et al. Consequence of dysphagia in the hospitalized patient: impact on prognosis and hospital resources. Arch Otolaryngol Head Neck Surg. 2010 Aug; 136 (8):784-9.[2] Gilheaney Ó et al. The Prevalence of Oropharyngeal Dysphagia in Adults Presenting with Temporomandibular Disorders Associated with Rheumatoid Arthritis: A Systematic Review and Meta-analysis. Dysphagia. 2017 Oct; 32 (5):587-600.[3] Mugii N et al. Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies. PLoS One. 2016 May 11;11 (5):e0154746.Disclosure of Interests:None declared

Pericardial effusion with cardiac tamponade is an uncommon metastatic manifestation of ovarian tumors, with only one previously reported case involving a borderline ovarian tumor (BOT).A 50-year-old woman was diagnosed and treated for a primary Stage IIc BOT. The disease recurred as an emergency pericardiocentesis eight years later, which was resected following pericardial effusion with a cardiac tamponade. This occurred two more times, and on the last occasion, drainage failed to relieve her symptoms. However, her symptoms resolved after the creation of a pericardium pleural window together with a pericardiectomy.For patients with a metastatic BOT, the creation of a pericardium pleural window and pericardiectomy is effective for recurrent pericardial tamponade, if the pericardial space is posteriorly located and/or segmented.

Gayal (Bos frontalis) is a semi domesticated and endangered bovine species in Bangladesh. This study was conducted to know the present distribution, performances and utility of gayal in the home tract. Bandarban Hill district was found the home tract of gayal in Bangladesh. Gayals were reared under extensive management system in the forest of Bandarban Hill district. They browsed forest herbs and grass freely in the forest and came to human dwelling for salt licking. Total number of gayal was counted between 800- 900. The average number of gayal per farmer was 5.01. The coat color of adult gayal was black. White stocking was very prominent in adult gayal. The height at wither and weight for adult males ranged from 126 to 136 cm and 490 to 577 kg, respectively. Reproductive efficiency was high and calving interval was 402 days. They exhibited high disease resistant. The PVC (Pack Cell Volume) and hemoglobin value was 33.5±5.71% and 13.43±2.9 g/dl, respectively. Gayal was used only as meat animal. The high growth rate and reproductive efficiency of gayal in the home tract indicates that this species can be utilized economically if proper breeding plan and sound extension service can be adopted.DOI: http://dx.doi.org/10.3329/bjas.v44i1.23147Bang. J. Anim. Sci. 2014. 44 (1): 75-84

The effects of crystallographic orientation on the ferroelectric properties of Pb(Zr,Ti)O3 (PZT) thin films grown on (111) and (100)-oriented Pt substrates are investigated. The effects of doping PZT with species X (forming PXZT) thin films (Pb:X:Zr:Ti, 113:3:30:70; X = La, Nb, or Y) using chemical solution deposition were studied. The crystallinity of all PXZT films was almost identical. The remnant polarisation of the un-doped, La-, Nb-, and Y-doped PZT capacitors with Pt(111) bottom electrodes were 133.4, 64.7, 60.2, and 98.4 µC/cm2, respectively. In ferroelectric capacitors with Pt(100) bottom electrodes, the remnant polarisations were 185.6, 148.1, 103.1, and 135.7 µC/cm2, respectively. The remnant polarisation was larger with Pt(100) than with Pt(111). The initial remnant polarisation of the un-doped PZT capacitors was larger than that of PXZT.

Leptospirosis is considered one of the most important zoonosis worldwide. The activation of the Complement System is important to control dissemination of several pathogens in the host. Only a few studies have employed murine models to investigate leptospiral infection and our aim in this work was to investigate the role of murine C5 during in vivo infection, comparing wild type C57BL/6 (B6 C5+/+) and congenic C57BL/6 (B6 C5−/−, C5 deficient) mice during the first days of infection. All animals from both groups survived for at least 8 days post-infection with pathogenic Leptospira interrogans serovar Kennewicki strain Fromm (LPF). At the third day of infection, we observed greater numbers of LPF in the liver of B6 C5−/− mice when compared to B6 C5+/+ mice. Later, on the sixth day of infection, the LPF population fell to undetectable levels in the livers of both groups of mice. On the third day, the inflammatory score was higher in the liver of B6 C5+/+ mice than in B6 C5−/− mice, and returned to normal on the sixth day of infection in both groups. No significant histopathological differences were observed in the lung, kidney and spleen from both infected B6 C5+/+ than B6 C5−/− mice. Likewise, the total number of circulating leukocytes was not affected by the absence of C5. The liver levels of IL-10 on the sixth day of infection was lower in the absence of C5 when compared to wild type mice. No significant differences were observed in the levels of several inflammatory cytokines when B6 C5+/+ and B6 C5−/− were compared. In conclusion, C5 may contribute to the direct killing of LPF in the first days of infection in C57BL/6 mice. On the other hand, other effector immune mechanisms probably compensate Complement impairment since the mice survival was not affected by the absence of C5 and its activated fragments, at least in the early stage of this infection.

442 Background: Despite optimal management of NMIBC with transurethral resection of bladder tumor (TURBT) and intravesical BCG therapy, a significant proportion of patients (pts) will eventually present with disease recurrence or progression. To date, there is no validated predictive biomarker to guide patient selection for the most appropriate therapy in this setting. Methods: We retrospectively identified pts with high-risk NMIBC treated with TURBT, repeat TUR and intravesical BCG (≥ 6 instillations) from 2009 to 2016. Patients were classified as BCG-responsive (BCG-R) and BCG-unresponsive (BCG-UR) based on the International Bladder Cancer Group criteria. Whole exome sequencing was performed using archival FFPE tumor tissue from pre-BCG TURBT samples. Association of genomic variables and outcomes was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Thirty-five patients were included (BCG-R = 17, BCG-UR = 18). Median follow-up was 46 months for BCG-R and 52 months for BCG-UR pts. The majority of pts was male (91.4%), former smoker (60%), and presented with high-grade urothelial carcinoma (85.7%) and/or T1 staging (71.4%). Median time for relapse and progression was 10.5 and 19 months, respectively, in the BCG-UR group. In this cohort, TMB was significantly different in BCG-R and BCG-UR groups, with a median TMB of 5.53 +- 4.60 and 3.17 +- 1.82 mutations/Mb, respectively ( P= 0.045). TMB was also associated with relapse-free survival (RFS), with a median RFS of 38 and 15 months in high versus low TMB groups, respectively ( P= 0.0092). Intratumoral genetic heterogeneity assessed by mutant-allele tumor heterogeneity (MATH) was not statistically different between the groups, with a median MATH score of 31.8 and 21.9 for BCG-R and BCG-UR ( P= 0.14), respectively. On multivariate analysis, age and TMB were independently associated with RFS. Conclusions: In this exploratory biomarker study, high TMB was associated with benefit from immunotherapy with BCG for NMIBC. The identification of predictive biomarkers in this setting is an important unmet need and integrative analysis of TMB with other potential predictive biomarkers should be assessed in larger datasets.

We present a theoretical study of an electronic state in the semiconductor Wannier-Stark ladder (WSL) driven by an intense THz laser. Numerical calculations based on the R-matrix Floquet theory have revealed that the dynamic localization (DL) is unstable against the Fano resonance-like interminiband decay mechanism caused by the THz-mediated coupling, termed here the dynamic Fano resonance (DFR). The obtained result is sharply contrasted with the conventional understanding without the introduction of DFR that the degree of stability of the DL would be comparable to or more than that of the WSL with no THz laser (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

High-temperature oxidation behavior of Al2O3-forming heat-resisting alloys with noble metal (palladium, platinum, gold) and rare earth (yttrium) additions was studied in oxidizing atmospheres (oxygen, oxygen-water vapor) for 18 ks at 1473, 1573, and 1673 K, by mass gain measurements, amount of spalled oxide, observation of surface appearance, X-ray diffraction (XRD), scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and transmission electron microscopy (TEM). Mass gains of all the Al2O3-forming Fe-20Cr-4Al alloys increased with increasing oxidation temperatures in both oxidation conditions. After oxidation in oxygen, the mass gains of the alloys with noble metal were almost the same values after any oxidation temperature. The mass gain of the alloys with yttrium decreased with increase in yttrium addition up to 0.1 mass%, and then tended to increase with 0.5 mass% yttrium addition at all oxidation temperatures studied. The amount of spalled oxide from the Fe-20Cr-4Al (A4) alloy showed the biggest value at 1573 K-oxidation, and then decreased in the order of 1473 K, 1673 K. On the other hand, the amount of spalled oxide from the other alloys decreased compared with the A4 alloy. No spalled oxide from 0.5Pt, 0.05Y, and 0.5Y alloys was observed at any oxidation temperature. After oxidation in an oxygen-water vapor mixture (dew point: 353 K), the mass gain of all the alloys showed similar values to that obtained in oxygen after any oxidation temperature. The amount of spalled oxide from the A4 alloy was about the same after oxidation at 1473 and 1573 K in oxygen, but then was higher when oxidized at 1673 K. The amount of spalled oxide from the other alloys obtained in oxygen–water vapor increased compared with those obtained in oxygen. On the other hand, the amount of spalled oxide from the 0.5Y alloy was zero after any oxidation temperature, and that from the 0.5Pt alloy was also zero after 1673 K-oxidation.