tbuckley/cabot-search huggingface dataset:
Abstract B40: EWS-FLI1 orchestrates Ewing sarcoma plasticity through a post-translational modification cascade regulating FOXM1 stability
Authors: Jozef Ban, Dave Aryee, Lisa Bierbaumer, Heinrich Kovar
Journal: Cancer Research (2020)

Abstract Oscillations between proliferative and migratory/invasive cell states are at the core of the metastatic process. Transition between these states involves reversible shifts in transcriptional programs that orchestrate cytoskeletal remodeling. Ewing sarcoma pathogenesis depends on EWS-FLI1, an aberrant ETS transcription factor that drives cellular transformation and proliferation of presumably mesenchymal progenitor cells. Recently, it has been reported that transient modulation of EWS-FLI1 expression results in an epithelial-to-mesenchymal transition-like phenotype of Ewing sarcoma cells and in increased metastasis (Chaturvedi et al., 2014; Franzetti et al., 2016). It has been proposed that EWS-FLI1 low cells exist in small amounts in primary Ewing sarcoma tumors and thus provide a potential source for tumor dissemination, leading to adverse prognosis. In our studies, we investigate the mechanistic basis of EWS-FLI1 dose-dependent Ewing sarcoma plasticity and recently reported on the activation of an MRTFB/TEAD transcriptional module promoting cytoskeletal reprograming in response to low EWS-FLI1 levels (Katschnig et al., 2016). Here, we show that the proliferative state depends on the activity of nuclear beta-catenin complexed to FOXM1. We find that EWS-FLI1 not only drives FOXM1 expression on the RNA level, but also sustains nuclear FOXM1 stability by a mechanism involving FOXM1 protein demethylation by lysine-specific demethylase 1 (LSD1/KDM1A). Experimental evidence suggests that EWS-FLI1 regulates LSD1 protein stability in Ewing sarcoma cells by directly activating a ubiquitin-specific protease. Modulation of EWS-FLI1 led to loss of expression of the deubiquitinting enzyme (DUB), and consequently to rapid depletion of LSD1 and FOXM1 proteins and subcellular redistribution of beta-catenin to the cytoplasm. Genetic (siRNA) and pharmacologic inhibition of the DUB or LSD1 recapitulated the destabilizing effect on FOXM1 in EWS-FLI1-high Ewing sarcoma cells, blocking tumor cell proliferation. In addition, they led to complete loss of beta-catenin expression by a mechanism that is currently under investigation. Therefore, our study identifies targetable enzymatic activities downstream of EWS-FLI1 that are required to sustain Ewing sarcoma proliferation. Citation Format: Jozef Ban, Dave Aryee, Lisa Bierbaumer, Heinrich Kovar. EWS-FLI1 orchestrates Ewing sarcoma plasticity through a post-translational modification cascade regulating FOXM1 stability [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B40.
AB0084 TNF RECEPTORS PROFILE CHANGES ON CYTOTOXIC T CELLS SUBSETS IN RHEUMATOID ARTHRITIS ARE ASSOCIATED WITH EFFECTIVE TREATMENT
Authors: A. Alshevskaya, J. Lopatnikova, J. Zhukova, F. Kireev, O. Chumasova, N. Shkaruba, A. Sizikov, V. Gladkikh, S. Sennikov
Journal: Annals of the Rheumatic Diseases (2020)

Background: Previous studies of co-expression profile of receptors to tumor necrosis factor alpha (TNF) in rheumatoid arthritis (RA) have revealed a number of indicators associated with diseases activity with 93% sensitivity and 90% specificity. However, the ratio of receptors to cytokines remains poorly understood. However, the question of therapy effect and its effectiveness in various alteration of cytokine receptors balance remains under investigated. Objectives: To evaluate the dynamics of co-expression and quantitative expression of type 1 and 2 receptors for TNF in the subpopulations of CD3+CD8+ cells associated with changes in disease severity before and after effective basic therapy. Methods: Subanalysis of patients with high disease activity level successfully treated with methotrexate and oral glucocorticoids (n = 9) was performed. As a control group, we used data from 43 healthy donors, comparable by sex and age distribution. Subpopulations of cytotoxic T cells were studied, which were included in the final diagnostic models for differentiating different degrees of severity of RA: naive T cells and memory T cells. The dynamics of changes in the indicators of receptors number and proportion of cells expressing the corresponding receptor were compared. Results: For naïve cytotoxic T cells, the main revealed feature was the relative stability of the number of expressed receptors (both TNFR1 and TNFR2), regardless of the therapy, while this number did not significantly differ from healthy ones for TNFR1 and was significantly lower for TNFR2 (p &lt;0.05 for all three fractions). At the same time, in terms of cell percentage, on the contrary, the therapy led to a change in total proportion of TNFR1 + cells closer to healthy donors indicators, and the proportion of TNFR2 + cells in the opposite direction. For cytotoxic T memory cells, it was demonstrated that after successful treatment a significant increase in the number of type 1 receptors was observed, with a decrease in TNFR1+ cells proportion, while these indicators were close to the values of healthy donors. At the same time, healthy donors were characterized by a significantly higher expression of type 2 receptors in terms of cell density of receptors. It is noteworthy that with successful therapy, a slight increase in the number of TNFR2 was observed with a sharp decrease in the proportion of TNFR2+ cells (p = 0.043). Conclusion: The balance of TNF receptor expression on cells actively involved in immunopathological processes affects both the density distribution of receptors on cells and co-expression in a subpopulation. Effective treatment of RA leads to equalization of the expression profile either by the percentage of cells or by the number of receptors, approaching the indicators of healthy donors, but not simultaneously. Disclosure of Interests: None declared
Abstract 12361: Cytoglobin Regulates Cilia Length, Function and Organ System Laterality During Development
Authors: Elizabeth R Rochon, Jianmin Xue, Manush Saydmohammed, Cecilia W Lo, Michael Tsang, Mark T Gladwin, Paola Corti
Journal: Circulation (2019)

Introduction: Cytoglobin is a heme protein known to be expressed at relatively low concentrations in a variety of tissues throughout development and highly conserved in all vertebrates. While cytog...
Abstract 14044: Financial Hardship Due to Medical Bills Amongst Families of Children With Congenital Heart Disease
Authors: Avital B Ludomirsky, Emily Bucholz, Jane W Newburger
Journal: Circulation (2019)

Introduction: Congenital heart disease (CHD) carries significant healthcare costs and out of pocket expenses for families. Little is known about how financial hardship from medical bills (FHMB) aff...
Implications of SARS-CoV-2 infection for patients with rheumatic disease
Authors: Changsong Lin, Ziyu Wang, Jie Li, Xinyi Xia, Yun Liu, Qianghu Wang
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the letter by Mathian et al in the Annals of the Rheumatic Diseases . In the letter, the authors reported that hydroxychloroquine (HCQ) did not protect patients with systemic lupus erythematosus (SLE) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the clinical treatment. We report similar results from our study of treatment of patients with SLE on HCQ. We wish to add supplemental evidence to some of the points not adequately addressed in Mathian et al ’s1 letter.

Mathian et al did not report the incidence rate of COVID-19 in patients with SLE. We agree with Mathian et al. that it is not practical to assess the actual incidence rate of SARS-CoV-2 in patients with SLE. However, we observed that during the outbreak, 6 (0.2%) cases had SLE in 3057 patients with COVID-19 who were admitted to Wuhan Huoshenshan Hospital (China). Taking that the prevalence of SLE is approximately 0.05%–0.1% in China, this may suggest that patients with SLE are susceptible to SARS-CoV-2 …
The Great Coronavirus Pandemic of 2020—7 Critical Lessons
Authors: Lawrence O. Gostin
Journal: JAMA (2020)

The world is experiencing a once-in-a-lifetime pandemic, causing untold human suffering and death, unraveling of social relationships, and robbing individuals of livelihoods and countries of prosperity. The coronavirus pandemic has strained health systems, revealed unconscionable inequalities, and upended international institutions. Here are 7 critical lessons.
SAT0208 The predictive role of bone scintigraphy in osteoarhtritis, relationship with age and severity of the disease
Authors: S Bal, H Erturk, M Aydin, O Ugur, R Celiker
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Osteoarthritis (OA) is the most common cause of musculoskeletal diseases in the developed countries. The diagnosis of OA is usually dependent on clinical and radiological evaluations which have some limitations in measuring the outcome. <h3>Objectives</h3> The aims of this study were to evaluate the predictive role of bone scintigraphy in OA, and to study the relationship with age and severity of the disease. <h3>Methods</h3> Ninety-nine female subjects were included in this study. Conventional x-rays of the hand, knee, hip and lumbar regions were obtained from each subjects. According to Kellgren and Lawrence Grading System the radiological score of the joint which had the highest grade was accepted as the Maximum Radiological Score (MRS). A bone scan was performed for each subjects 4 h after the injection of 740 MBq of technetium ? 99m-MDP. Spot images of hand, knee, lumbar vertabrae and pelvis were acquired using a gamma camera (Toshiba GCA 601). Besides the increased or normal uptake of activity at the affected joints, the ratios of lesion/non-lesion were also calculated. In the areas where the increased uptake of activity were present, the maximum lesion/non-lesion ratio was accepted as Maximum Scintigraphic Score (MSS). According to the American College of Rheumatology- clinical and radiological ? criteria for diagnosis of OA 46 patients were included in OA group (Group 1) and 53 patients were included in control group (Group 2). The Lequesne Index was used to determine the severity of the disease. <h3>Results</h3> All patients in group 1 and 31 patients in group 2 had knee pain and the mean duration of pain was 51.6+77.5 months in group 1 and 23.4+46.5 months in group 2. The mean Body Mass Index (BMI) was 31.7+5.0 in group 1 and 36.7+4.0 in group 2. According to the results of scintigraphic evaluation, healthy controls were separated into two groups. In group 2A patients who had an increase in uptake at least one joint and in group 2B patients who had no uptake. The mean MSS was 4.2+1.4 in group 1 and 3.3+1.6 in group 2A. Also the mean MRS of the patients in group 1 were 2.9+0.9 and 0.6+0.5, 0.2+0.4 in group 2A and 2B respectively. The mean score of the Lequesne Index was 8,9+3,6 in group 1 patients. There was a positive correlation between age and MSS (p &lt; 0,05) and BMI and MRS (p &lt; 0,05). Also there was a strong correlation between Lequesne OA Severity Index Score the age of the patients in group 1 but no correlation with the MSS. According to the clinical and/or radiological criteria sensitivity of bone scintigraphy was 98.2%, specifity was 57.1%, positive predictive value was 76% and negative predictive value was 96%. <h3>Conclusion</h3> Our results suggest that 99 m technetium scintigraphy is a better quantifying method in assessing the changes of OA especially in early cases.
THU0235 Treatment of refractory posterior uveitis with anti-tnf-alfa (infliximab)
Authors: A Banares, E Pato, L Abasolo, P Macarron, C Hernandez, JA Jover, B Fernandez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> There is a group of patients with non-infectious posterior uveitis (PU) who are refractory to corticosteroid or immunosuppressive (IS) regimens. The important role played by TNF-a in experimental uveitis models, and the efficacy shown by the various anti-TNF-a agents in autoimmune diseases have been reported. <h3>Objectives</h3> To demonstrate the usefulness of infliximab in the treatment of non-infectious PU. <h3>Methods</h3> Open, non-controlled trial, including 7 patients with corticosteroid-refractory PU who were receiving one or more of the following IS agents for a minimum of 2 years: CsA, AZA, MTX. Treatment was administered on a compassionate use basis, after EC approval at our institution and patient informed consent. All IS agents except MTX were discontinued one month prior to the start of treatment. Prednisone dose was adjusted to 0.5 mg/kg/day and decreased by 5 mg/day every week in the absence of posterior pole inflammation. Three doses of 5 mg/kg infliximab were administered IV at weeks 0, 2, and 6. Visits including a full ophthalmological assessment took place at weeks 1, 3, 4, 5, 7, 8, and 12; fluorescein angiographies (FAG) and retinograms were performed at baseline and week 16. <h3>Results</h3> No adverse effects, and no ocular or systemic exacerbations were observed. Final prednisone dose was = or &lt; 7.5 mg for six patients, and 15 mg for patient 2. Vitreous haze improved in all patients except patient 7. Measurable improvement of visual acuity was documented in patients 2, 3, 4, 5, and 6. FAGs and retinograms confirmed vitreous clearance in all patients, showing improvement of active retinal bleeding in patient 4 and disappearance of a macular oedema (which had been present for years) in patient 5. Only patient 7, with chronic multifocal choroiditis, had no improvement. <h3>Conclusion</h3> In this preliminary open trial, infliximab treatment appears to be a useful option in the short term for the management of refractory PU patients with retinal vasculitis.
Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial
Authors: P. Grimison, A. Mersiades, A. Kirby, N. Lintzeris, R. Morton, P. Haber, I. Olver, A. Walsh, I. McGregor, Y. Cheung, A. Tognela, C. Hahn, K. Briscoe, M. Aghmesheh, P. Fox, E. Abdi, S. Clarke, S. Della-Fiorentina, J. Shannon, C. Gedye, S. Begbie, J. Simes, M. Stockler
Journal: Annals of Oncology (2020)
A retrospective study on the clinicopathologic features of IgG/IgA pemphigus
Authors: Maressa C. Criscito, Jeffrey M. Cohen, Siavash Toosi, Lauren A. Penn, Casey L. Ross, Joyce Park, Elyse M. Love, Julia S. Lehman, Nooshin K. Brinster
Journal: Journal of the American Academy of Dermatology (2020)
Abstract PR05: Similarities in molecular subtypes and subtype immune patterns between naturally occurring canine and human invasive bladder cancer
Authors: Deepika Dhawan, Breann C. Sommer, José A. Ramos-Vara, Noah M. Hahn, Deborah W. Knapp
Journal: Clinical Cancer Research (2020)

Abstract Relevant animal models are needed to study treatment strategies related to the molecular subtypes of bladder cancer and the immune response between these subtypes. The purpose of the study was to characterize the molecular subtypes and immune features in naturally occurring canine invasive urothelial carcinoma (InvUC). Canine InvUC is already known to mimic the human condition in pathologic features, metastatic behavior, and chemotherapy response. Molecular subtyping could further increase the utilization of the canine model. RNA-seq data from canine InvUC (n=56) and normal canine bladder mucosa (n=4) were analyzed using Strand NGS (Strand Genomics, San Francisco, CA). Data were normalized (DESeq, TMM), and DEGs selected (2FC, pcorr &amp;lt;0.05) using DESeq2 and edge R, respectively. Following unsupervised clustering that identified two groups of tumors, supervised clustering was performed in which the data were interrogated using a panel of genes known to classify human bladder cancer subtypes (TCGA), as well as multiple gene panels that classify human bladder cancer as immune hot (infiltrated) or immune cold (noninfiltrated, immune-suppressor features). Infiltrating immune cells were observed in histologic sections with CD3 immunohistochemistry. Distinct luminal (n=28) and basal (n=28) subtypes were identified in the canine InvUC samples, with subclassifications emerging in both subtypes. There was anticipated heterogeneity between the samples, but of the 28 basal tumors, all had hot immune features, with 10 being exceptionally hot. Of the luminal tumors, 22 of 28 were notably immune cold. In conclusion, canine InvUC mimics human invasive bladder cancer in regard to molecular subtypes and immune patterns within subtypes. This expands the value of the canine bladder cancer model and offers opportunities to study strategies for individualized therapy and to develop strategies to enhance the tumor immune environment in order to improve treatment outcomes. Support: NIH/NCI P30CA023168 Supp (Knapp, Ratliff). This abstract is also being presented as Poster A26. Citation Format: Deepika Dhawan, Breann C. Sommer, José A. Ramos-Vara, Noah M. Hahn, Deborah W. Knapp. Similarities in molecular subtypes and subtype immune patterns between naturally occurring canine and human invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr PR05.
Negative tests for SARS‐CoV‐2 infection do not rule out its responsibility for chilblains
Authors: G. Battesti, V. Descamps
Journal: British Journal of Dermatology (2020)

We read with great interest the report of Le Cleach et al discussing chilblains as a manifestation of COVID-19 pandemic. They reported 311 patients with acral lesions occurring during the COVID-19 lockdown in France. The most frequent clinical presentation of these acral lesions was typical chilblains. Among the 150 patients with RT-PCR testing and/or serology, only 10 had confirmed COVID-19. They concluded that there is no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions. They hypothesized that the situation could be due to the media stating that chilblains were caused by SARS-CoV-2 infection and leading to a higher rate of consultation or the lockdown leading to more inactivity and long periods at home barefoot on a cold floor.
Single-cell landscape of immunological responses in patients with COVID-19
Authors: Ji-Yuan Zhang, Xiang-Ming Wang, Xudong Xing, Zhe Xu, Chao Zhang, Jin-Wen Song, Xing Fan, Peng Xia, Jun-Liang Fu, Si-Yu Wang, Ruo-Nan Xu, Xiao-Peng Dai, Lei Shi, Lei Huang, Tian-Jun Jiang, Ming Shi, Yuxia Zhang, Alimuddin Zumla, Markus Maeurer, Fan Bai, Fu-Sheng Wang
Journal: Nature Immunology (2020)

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.
Occupational dermatology in the time of the COVID‐19 pandemic: a report of experience from London and Manchester, UK
Authors: F.J. Ferguson, G. Street, L. Cunningham, I.R. White, J.P. McFadden, J. Williams
Journal: British Journal of Dermatology (2020)

The Covid-19 pandemic has resulted in healthcare systems responding to rapidly rising demand. Simultaneously, increased infection prevention measures for staff, which includes additional personal protective equipment (PPE) and more rigorous hand hygiene procedures, has resulted in an increased incidence of occupational skin disease in frontline staff (1).
Refining Hellström-Lindberg Score: Which Patients Could Benefit from Standard Dose EPO?
Authors: Marta Riva, Gianluigi Reda, Emanuele Ravano, Ramona Cassin, Mariarita Sciumè, Pierangelo Spedini, Giambattista Bertani, Michele Nichelatti, Agostino Cortelezzi, Roberto Cairoli, Alfredo Molteni
Journal: Blood (2017)
Health-related quality of life indicators and overall quality of life: Results from a cluster analysis on baseline EORTC QLQ-C30 data from 6,739 cancer patients
Authors: C. Coens, F. Martinelli, C. Quinten, C. S. Cleeland, E. Greimel, M. King, J. Ringash, J. Schmucker-Von Koch, Q. Shi, A. Bottomley
Journal: Journal of Clinical Oncology (2009)

e20576 Background: Increasingly randomized controlled trials in cancer research include Health-related Quality of Life (HRQoL) alongside traditional biomedical outcome measures. The majority of these trials focus on a general cancer HRQoL measure. The objective of this meta-analysis was to identify which HRQoL indicators influence a patient's overall quality of life, in order to better understand the changes in such a generic scale. Methods: Retrospective pooling of 29 European Organisation for Research and Treatment of Cancer (EORTC) clinical trials, among 10 cancer sites, yielded baseline EORTC QLQ-C30 data for a total of 6,739 patients. A cluster analysis, using Ward's method, was performed to determine how the 15 HRQoL indicators, and the Global Health scale (GH) in particular, cluster overall and by cancer characteristics. Cronbach's alpha coefficient (α) was used to measure internal consistency. Dendrograms of the HRQoL indicators were plotted for each cancer type. Results: Three main clusters emerged: a physical function related cluster (physical functioning, role functioning, fatigue and pain, α = 0.83), a psychological function related cluster (emotional functioning, cognitive functioning and insomnia, α = 0.64) and a gastrointestinal cluster (nausea and vomiting and appetite loss, α = 0.68). The GH scale was found to be part of the physical function cluster in the overall dataset (α = 0.85). This result was reproduced for both metastatic and non-metastatic patients. When looking across the 10 different cancer sites, the GH scale was mainly linked with a physical component in brain, head and neck, lung, melanoma, ovarian, pancreatic and prostate cancer. However, in breast and testicular cancer, GH was more strongly associated with the emotional scales. Conclusions: This study shows that the GH scale of the EORTC QLQ-C30 is most strongly linked with a patient's physical status. This result is consistent across stage of disease and most cancer sites. The different results seen in patients with breast and testicular cancer deserve additional investigation. No significant financial relationships to disclose.