tbuckley/cabot-search huggingface dataset:
AB0815 CHANGES IN BODY COMPOSITION, BONE MINERAL DENSITY AND BONE REMODELING MARKERS DURING INTERLEUKIN 12/23 INHIBITION IN PSORIATIC ARTHRITIS
Authors: J. Paccou, W. Bavière, R. Chapurlat, E. Sornay-Rendu, P. Szulc, B. Cortet, R. M. Flipo
Journal: Annals of the Rheumatic Diseases (2020)

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by multiple comorbid conditions including cardiovascular comorbidities, diabetes, obesity and osteoporosis. Little is known about body composition in patients with PsA and no data are available regarding body composition changes under DMARDs. Objectives: We investigated the effects of ustekinumab (UST), a humanized anti-interleukin 12/23 antibody, on body composition, bone mineral density (BMD) and bone remodeling markers in patients treated for PsA. Methods: Thirty patients with active PsA treated with UST were included in a 6 months open follow-up study. Body mass index, DAS28-CRP, bone remodeling markers, serum levels of leptin, BMD and body composition (dual-energy X-ray absorptiometry) were measured at baseline and 6 months of treatment. At baseline, PsA patients were compared with 60 non-PsA controls matched for age, sex and body mass index. Results: Compared with controls, we observed lower total and appendicular lean mass (53.1 ±13.1 vs. 56.7 ±11.9 kg, p=0.013 and 21.6 ±6.3 vs. 23.4 ±5.0 kg, p=0.010 respectively) and greater fat mass in PsA (32.5 ±10.8 vs. 25.2 ±8.9 kg, p&lt;0.001). Among PsA patients, 30% had a skeletal muscle mass index below the cut-off point for sarcopenia (Baumgartner’s criteria: men 7.26 kg/m2, women 5.5 kg/m2) whereas no case was observed in the control group. After 6 months of treatment with UST, there was not a significant change of BMI, while there was a tendency for reaching the significant level for fat mass (+1.75 ±3.60 kg, p=0.054), and fat mass index (+0.59 ±1.25 kg/m 2 , p=0.061). In contrast, a decrease in total lean mass was observed (-1.57 ±3.10 kg, p=0.046) without a significant change in appendicular lean mass and skeletal muscle mass index. No changes for bone remodeling markers, leptin and BMD were observed at 6 months. Conclusion: Patients with active PsA required biologic therapy had increased fat mass and decreased lean mass. Moreover, ustekinumab might worsen the decrease in lean mass with no significant change in fat mass. Disclosure of Interests: Julien Paccou Grant/research support from: Janssen, Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, Sanofi, UCB, Wallis Bavière: None declared, Roland Chapurlat: None declared, Elisabeth Sornay-Rendu: None declared, Pawel Szulc: None declared, Bernard Cortet Consultant of: Aptissen, René-Marc Flipo Consultant of: Johnson and Johnson, MSD France, Novartis, Sanofi, Speakers bureau: Johnson and Johnson, MSD France, Novartis, Sanofi
SAT0436 PATIENTS WITH PSORIATIC ARTHRITIS WHO ACHIEVE THE MDA RESPONSE SHOW LESS SUBCLINICAL ATHEROSCLEROSIS THAN THOSE IN DAPSA REMISSION
Authors: J. A. Lorenzo Martín, E. Pardo Campo, L. C. Charca Benavente, M. Pino Martínez, S. Alonso Castro, S. Fernández, L. M. Arboleya Rodríguez, M. Alperi-López, R. Queiró Silva
Journal: Annals of the Rheumatic Diseases (2020)

Background: Although the MDA response and DAPSA remission are treatment objectives proposed by EULAR for a proper management of psoriatic arthritis (PsA), there is no clear consensus on which of the two is the most advisable in clinical practice. Some studies suggest that patients who reach a sustained MDA have less subclinical atherosclerosis, but whether the same applies to DAPSA remission is unknown at present. Objectives: To compare the frequency of subclinical atherosclerosis in patients with PsA that reach the MDA response versus those who achieve DAPSA remission. Methods: One hundred-forty consecutive patients with PsA (CASPAR criteria) treated with biological and non-biological systemic agents were included. SCORE risk charts were used to estimate cardiovascular risk (CVR). The presence of plaques and / or carotid intima-media thickness (cIMT) &gt; 0.9 mm in carotid ultrasound defined subclinical atherosclerosis. These findings were analyzed in patients in MDA and in those in DAPSA remission. Results: According to the SCORE tables, 42.8%, 35.7% and 21.5%, had low, moderate and high-very high CVR, respectively. There was a linear association between cIMT values and the SCORE risk categories (p &lt;0.0005). The best cut-off point to define a high CVR (by SCORE plus carotid plaques) corresponded to a cIMT &gt; 0.63 mm, with an area under the ROC curve of 0.75 (0.66-0.82), sensitivity 85.7%, specificity 56.1% (Figure 1). Ninety-seven of the 140 patients (69.3%) were in MDA situation, while 60 (42.8%) were in DAPSA remission. The average value of the cIMT was 0.64 ± 0.12 mm. One in 4 patient had atheroma plaques, while 19 (13.6%) had a cIMT&gt; 0.9 mm. There were no differences in cIMT values of patients with (0.66 ± 0.12 mm) and without (0.63 ± 0.12 mm) DAPSA remission. An identical percentage (25%) of patients with and without DAPSA remission had carotid atheroma plaques. On the other hand, there were differences between patients with (6.2%) and without (30.2%) MDA in terms of cIMT values &gt; 0.9 mm, p &lt;0.05. 32.6% of non-MDA and 23.7% of MDA patients had carotid plaques, p NS. Conclusion: Patients who achieve an MDA response show less subclinical atherosclerosis than those in DAPSA remission. These findings suggest that the MDA response better discriminates the presence of subclinical atherosclerosis, and therefore, it could be a more complete therapeutic target than DAPSA remission. Disclosure of Interests: None declared
Abstract PHB01: The zebrafish as a mechanical filter: Using zebrafish xenografts to model Ewing sarcoma metastasis in vivo
Authors: Dagan Segal, Bo-Jui Chang, Hanieh Mazloom-Farsibaf, Reto Fiolka, James Amatruda, Gaudenz Danuser
Journal: Cancer Research (2020)

Abstract Ewing Sarcoma (ES), a pediatric cancer driven by the oncogenic fusion protein EWS-FLI1, recurs or metastasizes in 1 in 3 patients with no clear correlation to accumulation of secondary mutations, raising the possibility that environmental cues may drive metastasis. Previous work in the field has observed distinct cellular morphologies of ES cells in cell culture as a function of EWS-FLI1 level and posited the idea that this may correlate with distinct functional cellular states. In this work, we use zebrafish xenografts to investigate the effect of variable microenvironments on cellular morphologies of ES cells. We use high resolution light-sheet microscopy to focus on specific recurring seeding sites within the 3-day old zebrafish larvae. We then implement a unique cell-shape classification method to distinguish discrete 3D cellular morphologies in these datasets. Using this workflow, we observe a variety of cellular morphologies within the fish, including elongated cellular protrusions, blebbing, and rounded cells. We demonstrate that ES cells take on distinct morphological states as a function of the region in which they reside. We find cell proliferation, but not cell death, vary greatly in the different regions, suggesting differences in the functional state of the ES cells. Interestingly, knockdown of EWS-FLI1 in xenografted cells leads to discrete switches between cellular morphologies, but only as a function of seeding site within the fish, suggesting a previously undescribed environmental cue that modulates cellular effects of EWS-FLI1. Overall, the xenograft model for ES in zebrafish embryos can be viewed as a “mechanical filter”, which provides unique, complex 3-dimensional environments to study cell behavior within an organism, while leveraging the advantages of the zebrafish system, namely higher throughput and high resolution in vivo imaging capabilities. This work establishes a pipeline for classification and distinction of morphological states within a living organism, and, more specifically, helps our understanding of cellular plasticity of ES cells in response to microenvironment. Citation Format: Dagan Segal, Bo-Jui Chang, Hanieh Mazloom-Farsibaf, Reto Fiolka, James Amatruda, Gaudenz Danuser. The zebrafish as a mechanical filter: Using zebrafish xenografts to model Ewing sarcoma metastasis in vivo [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr PHB01.
AB0477 OVARIAN RESERVE IN PATIENTS WITH RHEUMATIC DISEASES
Authors: Z. Alekberova, R. Goloeva, M. Cherkasova, A. Lila
Journal: Annals of the Rheumatic Diseases (2020)

Background: Access to assays of circulating anti-Mullerian hormone (AMH) levels has opened a new page in the assessment of ovarian function and fertility in various diseases, including rheumatic diseases (RDs). The definition of AMH as a marker of ovarian reserve significantly simplified its interpretation as well as measuring the contribution of the disease itself to the patients’ infertility. Objectives: To evaluate the effects of the disease and it’s treatment on serum AMH levels for Behcet’s disease (BD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic scleroderma (SSD). Methods: The study included 73 patients with RDs from 18 to 40 years: 42 patients with BD, 12 with SLE, 11 with RA, 8- with SSD, the control group consisted of 15 healthy women. Enzyme-linked immunosorbent assay (ELISA) was used to measure AMH levels. Parametric and nonparametric statistical methods of Statistica 8.0 package were used for statistical processing of data. Results: Mean age in BD patients was 30.0 years, in SLE and RA -33.5 years, in SSD - 35.0 years, and 32.0 years in the control group. The average disease duration was 4.5 years, 11.5 years, 4.0 years and 6.0 years, respectively. BD, n=42 SLE, n=12 RA, n=11 SSD, n=8 Control, n=15 Mean age, years 30,0 [26;35] 33.5 [29;38] 33,5 [24;36] 35,0 [28;40] 32,0 [26;35] Average disease duration, years 4,5 [2,6;9,0] 11,5 [2,8;18] 4,0 [4,0;6,0] 6,0 [2,0-10,0] - Mean AMH level, ng/ml 2,5 [1,1;3,7] 3,5 [0,4-7,1] 3,35 [2,0;7,6] 2,5 [0,3;7,1] 3,1 [1,9;5,4] There were no significant differences in the mean AMH levels between the groups. No association between AMG levels and clinical manifestations, disease activity or duration of rheumatic disease was found. Baseline AMH – in treatment-naïve patients before initiation of any DMARDs was assessed in 11 BD patients. A significant ( p &gt;0.05) decrease of AMH levels was established in patients with high SLE activity treated with CP. Of notice, all examined patients were additionally receiving a GEBD -Rituximab. Conclusion: Decreased ovarian function was found in patients with high SLE activity treated with CP with Rituximab. Disclosure of Interests: None declared
Cortical reactivations of recent sensory experiences predict bidirectional network changes during learning
Authors: Arthur U. Sugden, Jeffrey D. Zaremba, Lauren A. Sugden, Kelly L. McGuire, Andrew Lutas, Rohan N. Ramesh, Osama Alturkistani, Kristian K. Lensjø, Christian R. Burgess, Mark L. Andermann
Journal: Nature Neuroscience (2020)
Blood mitochondrial DNA as a biomarker of clinical outcomes in idiopathic pulmonary fibrosis
Authors: Hee-young Yoon, Kwanghun Choi, Miae Kim, Hak-Su Kim, Jin Woo Song
Journal: European Respiratory Journal (2020)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown aetiology [1] with ageing being one of the major risk factors [2]. Several ageing-related changes, such as the overproduction of mitochondrial reactive oxygen species, low adenosine triphosphate production, reduced mitochondrial biogenesis and inadequate mitochondrial (mt)DNA repair [3] have also been reported in the IPF lungs [4, 5] and in a bleomycin-induced mouse model [6]. Plasma cell-free DNA, including mtDNA, is released from dying cells into the circulatory system in response to injury [7]. Since circulating mtDNA contains CpG-rich sequences similar to bacterial DNA, disengaged mtDNA can activate the innate immune system by functioning as a damage-associated molecular pattern [8] and contribute to the stimulation of the profibrotic pathway [9]. Plasma mtDNA level could serve as a potential marker for disease progression and acute exacerbation in idiopathic pulmonary fibrosis <https://bit.ly/2XoXsAv> We would like to thank Ye-Jee Kim (Dept of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea) for their advice on statistical analysis.
Abstract IA18: Molecular signatures of circulating tumor cells
Authors: Daniel Haber, Xin Hong, Richard Ebright, Doug Micalizi, Aditya Bardia, Ryan Sullivan, Mehmet Toner, Shyamala Maheswaran
Journal: Clinical Cancer Research (2020)

Abstract Circulating tumor cells (CTCs) are shed from primary cancers, as well as from metastatic deposits, into the blood circulation, where they may travel either as single cells or as CTC clusters, facing both mechanical and oxidative stress. Only a small subset of CTCs remain sufficiently viable to initiate metastatic growth upon dissemination to distant organs; their detection in patients with localized invasive cancer may present an opportunity for early detection, while their analysis in advanced cases provides a “whole cell biomarker,” enabling single-cell DNA, RNA, and protein studies, as well as functional drug-sensitivity testing using cultured CTCs. We have applied microfluidic technologies to deplete normal hematopoietic cells from blood specimens of patients with cancer, enhancing the ability of unmanipulated CTCs to proliferate ex vivo and recapitulating features of metastatic-competent cancer cells. Cultured CTCs from patients with either breast cancer or melanoma are highly tumorigenic when injected orthotopically at low inoculum into immunosuppressed mice. However, they display sensitivity to ROS and appear to upregulate compensatory mechanisms that are not commonly observed in primary tumors. In addition, they may undergo prolonged dormancy when lodged within distant organs. By combining single-cell RNA seq of patient-derived CTCs together with CRISPR and other genome-wide screens for modulators of metastasis phenotypes, we have sought to identify novel vulnerabilities in these cellular initiators of metastasis. While CTCs transit only very briefly through the blood circulation, these exceptional conditions may present new therapeutic opportunities to suppress the metastatic recurrence of cancer. Citation Format: Daniel Haber, Xin Hong, Richard Ebright, Doug Micalizi, Aditya Bardia, Ryan Sullivan, Mehmet Toner, Shyamala Maheswaran. Molecular signatures of circulating tumor cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA18.
Baseline requirements for novel agents being considered for phase II/III brain cancer efficacy trials: conclusions from the Adult Brain Tumor Consortium’s first workshop on CNS drug delivery
Authors: Stuart A Grossman, Carlos G Romo, Michelle A Rudek, Jeffrey Supko, Joy Fisher, L Burt Nabors, Patrick Y Wen, David M Peereboom, Benjamin M Ellingson, William Elmquist, Fred G Barker, David Kamson, Jann N Sarkaria, William Timmer, Ranjit S Bindra, Xiaobu Ye
Journal: Neuro-Oncology (2020)

Author(s): Grossman, Stuart A; Romo, Carlos G; Rudek, Michelle A; Supko, Jeffrey; Fisher, Joy; Nabors, L Burt; Wen, Patrick Y; Peereboom, David M; Ellingson, Benjamin M; Elmquist, William; Barker, Fred G; Kamson, David; Sarkaria, Jann N; Timmer, William; Bindra, Ranjit S; Ye, Xiaobu
Comparison of MS score and HScore for the diagnosis of adult-onset Still’s disease-associated macrophage activation syndrome
Authors: Lei Zhang, Xiaopei Yang, Tian-Fang Li, Xiaojun Liu, Shengyun Liu
Journal: Annals of the Rheumatic Diseases (2020)

The best cut-off value of HScore was 169, with a sensitivity of 93% and a specificity of 86% when it was developed. 6The cutoff was set at 190.5 and yielded a sensitivity of 96.7% and a specificity of 98.4% when tested in a group of Turkish patients with MAS. 7 Our results indicate that HScore is suitable for detecting AOSD-MAS but with a lower cut-off value.Indeed, different patients' selection criteria, different disease status and different underlying diseases may result in quite different conclusions.Further studies are needed to validate these different scoring tools.
Fcγ Receptor I–Coupled Signaling in Peripheral Nociceptors Mediates Joint Pain in a Rat Model of Rheumatoid Arthritis
Authors: Fan Liu, Xinhua Shen, Si Su, Huan Cui, Yehong Fang, Tao Wang, Lianfeng Zhang, Yuguang Huang, Chao Ma
Journal: Arthritis & Rheumatology (2020)

Rheumatoid arthritis (RA) is often accompanied by joint pain and inflammation. Previous studies have demonstrated that functional Fcγ receptor I (FcγRI) is expressed in dorsal root ganglion (DRG) neurons and might contribute to pain in rodent models of antigen-induced arthritis (AIA). This study was undertaken to elucidate the roles of nociceptive neuronal FcγRI-coupled signaling in the development of joint pain in AIA.RNA sequencing was used to investigate the transcriptome profile changes in the DRG in a rat model of AIA. A primary sensory neuron-specific Fcgr1a conditional-knockout (CKO) rat was established by crossing rats carrying a loxP-flanked Fcgr1a with a Pirt-specific Cre line. Behavioral, morphologic, and molecular studies were conducted to evaluate the differences between wild-type (WT) and CKO rats after AIA.We first showed that AIA induced a transcriptome profile change in the DRG, involving a number of key proteins downstream of the FcγRI-related signaling pathway. Compared to the WT rats, both the IgG immune complex-induced acute pain and AIA-induced pain were alleviated in CKO rats. Moreover, the AIA-induced activation of FcγRI-related signaling in DRGs was significantly reduced in CKO rats. In addition, CKO rats showed attenuated joint swelling after AIA.These results indicate that activation of FcγRI-coupled signaling in DRG neurons plays an important role in the development of joint pain in AIA. Our findings may provide novel insights into the interactions between the peripheral nervous system and the immune system in pathologic conditions and might suggest potential biotargets for the treatment of pain in RA.
Is innate immunity our best weapon for flattening the curve?
Authors: Leonard Angka, Marisa Market, Michele Ardolino, Rebecca C. Auer
Journal: Journal of Clinical Investigation (2020)

The COVID-19 pandemic is a stern reminder not to take our immune system for granted. The fact that some individuals contract and clear the SARS-CoV-2 virus without apparent symptoms stands in sharp contrast to the damage that this virus has brought upon more vulnerable populations, including the elderly and patients with chronic conditions or cancer. While the differences in severity of infection between these populations are multifactorial, it is likely that innate immunity provides the underpinning, given its central role in the early response to viral infections. Within two decades, there have been three known coronavirus zoonoses (SARS-CoV-1, MERS, and SARS-CoV-2), all of which have taken a devastating toll on the human and economic health of affected societies. Unfortunately, with the frequency and diffusion of novel zoonoses, this is unlikely to be our last battle. As we begin the long and daunting recovery from this pandemic, we must take the opportunity to think about how to exploit our innate immune system to better prepare us to fight the next virus.
THU0102 DENDRITIC CELLS AS A PREDICTOR OF GOOD CLINICAL RESPONSE IN RHEUMATOID ARTHRITIS PATIENTS
Authors: M. Korolev, Y. Kurochkina, N. Banshhikova, V. Omelchenko, E. Letyagina, A. Akimova, A. Lykov, O. Poveschenko
Journal: Annals of the Rheumatic Diseases (2020)

Background: Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through presentation of cartilage glycoprotein, production of proinflammatory cytokines and activation of Th1/Th17 responses. DCs are a heterogeneous population and can be divided into groups: myeloid (mDCs) and plasmacytoid (pDCs). DCs can induce both immune response and tolerance. Objectives: To investigate the subpopulations of peripheral blood DCs (myeloid and plasmacytoid) in patients with early RA as a predictor of responsibility to disease-modifying antirheumatic drugs (DMARDs) treatment. Methods: Fifty two patients with early RA (duration of the disease up to 12 months) were included in the study. All patients fullfield ACR/EULAR criteria (2010) and received methotrexate, leflunomide, sulfasalazine or their combination. Fifty five patients with osteoarthritis (OA) used as a control group. Analysis of the content of the B-lymphocytes, myeloid and plasmacytoid DCs was carried out by flow cytometry. B-lymphocytes, subtypes of peripheral blood DCs were characterized by the following phenotypes: myeloid DCs (CD3-CD14-CD19-HLA-DR + CD11c + CD123-), plasmacytoid DCs (CD3-CD14-CD19-HLA-DR + CD11c-CD123 +), B-lymphocytes (CD19 +). Analyses were performed before treatment and after 3 and 6 months. Results: Patients with early RA are characterized by significant evaluation of the population of myeloid DCs in comparison of patients with osteoarthritis (26.6% vs 23.5, p=0.0007). Furthermore, the difference was found in the number of cells with the phenotype B-lymphocytes: 5.4% vs 3%, p = 0.0005). No significant differences were observed in the number of plasmocytoid DCs. After 3 and 6 month of observation we detected reducing amount of myeloid DCs 26.6% vs 21.1% vs 18.4% respectively. Also we revealed reducing B-cells in treatment (5.4% vs 3 % vs 2%). Disease activity according to DAS28 droped to low (4.32 to3.06, p=0.03). We also revealed a reliable negative correlation between both the activity of the disease and the B- cells (rS=-0.4, p=0.05, n=52) and myeloid DCS (rS=-0.6, p=0.0004, n=52). A reducing of the immune cells during the DMARDS therapy suggests that they are an attractive marker for good clinical response to therapy. Conclusion: The data obtained confirm the determining role of myeloid DC and B lymphocytes in maintaining systemic inflammation in rheumatoid arthritis. In addition, these cells are a target of DMARDs therapy and a predictor of a good clinical response. Disclosure of Interests: None declared