tbuckley/cabot-search huggingface dataset:
AB0129 ULTRA-MICROSCOPIC ANALYSIS OF NURSING PHENOMENON IN SYNOVIAL TISSUE OF RHEUMATOID ARTHRITIS
Authors: Rie Kurose, Takahiro Ochi, Takashi Satoh, Miwa Uzuki, Kenya Murakami, Akira Kurose, Yo-Ichi Satoh, Yasuyuki Ishibashi, Kinji Ishida, Katsutoshi Ogasawara, Akinari Morikawa, Takashi Sawai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Applying recent advances in electron microscope technology, cells and cell-cell interactions are observable using virtual slides, three-dimensional (3D) imaging, and serial sections of ultrathin thickness. Inflammation in rheumatoid arthritis (RA) is caused by multiple cell types, including infiltrating inflammatory cells, such as lymphocytes, neutrophils, macrophages, and spindle-shaped fibroblasts. Especially, we are focusing on fibroblast-like synoviocytes (FLSs). These cells have been reported to be positive for multiple markers including CD14, CD68, HLA-DR and vimentin, and we have shown that these cells are dendritic cells in our previous study using electron microscopy. Therefore, FLSs are presumed to function as dendritic cells. and these cells involved in the nursing phenomenon. <h3>Objectives:</h3> The objective of this study is to investigate the chronicity mechanism of immunological inflammation in RA by using electron microscopy. <h3>Methods:</h3> Synovial tissues collected from RA patients undergoing elbow or knee joint surgery were prepared for this study. Using wide field of view images of the synovial tissue, areas containing the nursing phenomenon were selected by using multiscale electron microscopy. 3D structures of the features were constructed from series of micrographs obtained by using focused ion beam-scanning electron microscopy and those by using transmission electron microscopy with double-axis electron tomography (DA-ET). <h3>Results:</h3> From multiscale electron microscopy, many synovial dendritic cells and plasma cells were present in various areas of the lymphnodular infiltration. Serial cross-sectional observation with an FIB-SEM and 3D images revealed that synovial dendritic cells patronized the plasma cells, wrapping around the plasma cells, by the long slender axes. A tomogram of an ultra-thin sliced section created by using DA-ET revealed that synovial dendritic cells formed a membranous fusion with the plasma cells. <h3>Conclusion:</h3> The nursing phenomenon involves characteristic histopathological features, which may be a factor in the chronicity of the inflammation mechanism in RA synovial tissue. <h3>References</h3> [1] Ochi T, Yoshikawa H, Toyosaki-Maeda T, Lipsky PE. Mesenchymal stromal cells. Nurse-like cells reside in thesynovial tissue and bone marrow in rheumatoid arthritis. Arthritis Research&amp;amp;Therapy2007; 9(1): 201. [2] Ochi T, Sawai T, Murakami K, Kamataki A, Uzuki M, Tomita T, et al. Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between the cell types. Mod Rheum2018; 29: 1-5. <h3>Disclosure of Interests:</h3> None declared
Comprehensive Liquid Profiling of Circulating Tumor DNA and Protein Biomarkers in Long-Term Follow-Up Patients with Hepatocellular Carcinoma
Authors: Zhixiong Cai, Geng Chen, Yongyi Zeng, Xiuqing Dong, Zhenli Li, Yanbing Huang, Fuli Xin, Liman Qiu, Haipo Xu, Wei Zhang, Xiaoping Su, Xiaolong Liu, Jingfeng Liu
Journal: Clinical Cancer Research (2019)

Circulating tumor DNA (ctDNA) provides a novel approach for detecting tumor burden and predicting clinical outcomes of hepatocellular carcinoma (HCC). Here, we performed a thorough evaluation of HCC circulating genetic features and further fully integrated them to build a robust strategy for HCC monitoring and prognostic outcome assessment.We performed target sequencing and low-coverage whole-genome sequencing on plasma samples collected from 34 long-term follow-up patients with HCC to capture tumor somatic SNVs and CNVs, respectively. Clinical information was also obtained to evaluate the prognostic performance of ctDNA comparing with clinically applied protein biomarkers.All plasma samples before surgery showed somatic genetic variations resembling corresponding tumor tissues. During follow-up, SNVs and CNVs dynamically changed correlating to patients' tumor burden. We integrated the comprehensive ctDNA mutation profiles to provide a robust strategy to accurately assess patients' tumor burden with high consistence comparing with imaging results. This strategy could discover tumor occurrence in advance of imaging for an average of 4.6 months, and showed superior performance than serum biomarkers AFP, AFP-L3%, and Des-Gamma-Carboxy Prothrombin (DCP). Furthermore, our strategy could precisely detect minimal residual disease (MRD) in advance and predict patients' prognostic outcomes for both relapse-free survival (P = 0.001) and overall survival (P = 0.001); further combining ctDNA with DCP could increase the sensitivity for MRD detection.We demonstrated that plasma CNV and SNV levels dynamically correlated with patients' tumor burden in HCC. Our strategy of comprehensive mutation profile integration could accurately and better evaluate patients' prognostic risk and detect tumor occurrence in advance than traditional strategies.
Activity and duration of chemotherapy (CT) in different biologic subtype (BS) in metastatic breast cancer (MBC) patients (P).
Authors: Claudia Bighin, Lucia Del Mastro, Beatrice Dozin, Sara Giraudi, Alessia Levaggi, Alessia D'Alonzo, Matteo Lambertini, Francesca Poggio, Giuseppina Iacono, Loredana Miglietta, Paolo Pronzato
Journal: Journal of Clinical Oncology (2013)

1036 Background: In MBC P the benefit of CT after the 1st line (L) is poorly defined. We evaluated activity of subsequent L of CT in different BS of MBC. Methods: MBC P treated in our center from 2007 to 2012 with ER, PgR and HER2 on primary tumor and at least 1 L of CT for MBC were evaluated. P were classified as Luminal A (ER and/or PgR +, HER2 -, Ki67≤14%), Luminal B (ER and/or PgR +, HER2 -, Ki67&gt;14%), HER2+ (HER2+, any ER/PgR) and Triple-Negative ( ER-, PgR- and HER2-). Time on CT was calculated from the start of the 1st L to the end of the last L. Statistical analyses included Chi-square and Kruskal-Wallis tests, Kaplan-Meier curves and log-rank tests, and multivariate logistic regressions. Results: 207 P were identified, 52 were excluded because HER2 was unknown (19) or they did not receive any CT (33). Median follow-up was 31.4 months (m). The median number (N) of CT L was 2 (range 1-10). N of CT L and clinical benefit (CB) for every BS were reported in table. CB was inferior in TN P as compared with the other ones in 1st and in 2nd L ( p=.068 and p=.084 respectively in 1st and 2nd L). From 3rd L onward all P showed the same CB independently from BS. Time on CT related to median survival (S) for every BS was the same. At multivariate analysis the characteristics independently associated with a greater probability of receiving more than 4 CT L were age &lt; 50 years (p=.021), HER2+ or TN disease (p=.027) and site of metastasis other than lung (p=.047). Conclusions: Our analysis showed that, despite the same time spent on CT, TN P received less benefit from 1st and 2nd L CT than other BS. On the other hand, young HER2+ P were more likely to receive multiple L of CT with a significant impact on median S (p=.044). [Table: see text]
Abstract 897: Alliance of Blood Derived Endothelial Cells and Adipose Stromal Cells in Human Vasculogenesis
Authors: Dmitry O Traktuev, Daniel N Prater, Aravind R Sanjeevaiah, Stephanie Merfeld-Clauss, Brian H Johnstone, David A Ingram, Keith L March
Journal: Circulation (2007)

Introduction Both Endothelial progenitor cells (EPC) and adipose stromal cells (ASC) are under investigation as therapies for cardiovascular diseases. Both cell types are capable of modulating vascular assembly and are, thereby, capable of directly promoting revascularization of ischemic tissues. We have shown that EPC differentiate into endothelial cells to form small vessels, whereas ASC have pericytic properties and naturally stabilize vessels. In this study we tested the possibility that ASC would interact with EPC to assemble de novo vessels in collagen in an in vivo chimeric implant. Methods and Results Collagen implants embedded with either umbilical cord blood EPC or adult ASC or a 4:1 mixture of both (2x10 6 cells/ml) were implanted subcutaneously into NOD/SCID mice. After 14 d implants were harvested and evaluated by immunohistochemistry. There was a pronounced difference among the groups in vascular network assembly. The majority of vessels formed in the EPC and ASC monocultures were small capillaries bounded by a single endothelial layer. Conversely, 100% of the plugs embedded with both cell types were highly invaded with multilayered arteriolar vessels. The density of the CD31 + vessels in the EPC and co-culture plugs was 26.6 ± 5.8 and 122.4 ± 9.8 per mm 2 , respectively. No CD31 + cells of human origin were detected in the ASC monocultures, indicating that ASC, which do not express this EC-specific marker, engage murine EC or form pseudovessels in this system. The density of α-SMA + vessels with lumens per mm 2 was 13.1 ± 3.6 (EPC), 10.2 ± 3.5 (ASC) and 124.7 ± 19.7 (co-culture). The total overlap of CD31 + and SMA + vessels demonstrates that mature, multilayered conduits were formed with the co-culture. Moreover, the majority of these vessels were filled with erythrocytes (92.5 ± 16.2 per mm 2 ), indicating inosculation with the native vasculature, which was confirmed by ultrasound with echogenic microbubbles and persisted to at least 4 months. Conclusion This study is the first to demonstrate that non-transformed human EPC and ASC cooperatively form mature and stable vasculature with subsequent functional integration into a host vasculature system.
A novel AR translational regulator lncRNA LBCS inhibits castration resistance of prostate cancer
Authors: Peng Gu, Xu Chen, Ruihui Xie, Weibin Xie, Li Huang, Wen Dong, Jinli Han, Xiaodong Liu, Jihong Shen, Jian Huang, Tianxin Lin
Journal: Molecular Cancer (2019)

Progression to a castration resistance state is the main cause of deaths in prostate cancer (PCa) patients. Androgen Receptor (AR) signaling plays the central role in progression of Castration Resistant Prostate Cancer (CRPC), therefore understanding the mechanisms of AR activation in the milieu of low androgen is critical to discover novel approach to treat CRPC.Firstly, we explore the CRPC associated lncRNAs by transcriptome microarray. The expression and clinical features of lnc-LBCS are analyzed in three independent large-scale cohorts. The functional role and mechanism of lnc-LBCS are further investigated by gain and loss of function assays in vitro.The expression of Lnc-LBCS was lower in CRPC cells lines and tissues. LBCS downregulation was correlated with higher Gleason Score, T stage and poor prognosis of PCa patients. LBCS overexpression decreases, whereas LBCS knockdown increases, the traits of castration resistance in prostate cancer cells under androgen ablated or AR blocked condition. Moreover, knockdown of LBCS was sufficient to activate AR signaling in the absence of androgen by elevating the translation of AR protein. Mechanistically, LBCS interacted directly with hnRNPK to suppress AR translation efficiency by forming complex with hnRNPK and AR mRNA.Lnc-LBCS functions as a novel AR translational regulator that suppresses castration resistance of prostate cancer by interacting with hnRNPK. This sheds a new insight into the regulation of CRPC by lncRNA mediated AR activation and LBCS-hnRNPK-AR axis provides a promising approach to the treatment of CRPC.
Infographic. Useful steps in the prevention of illnesses during international athletics championships
Authors: Pascal Edouard, Danny Glover, Andrew Murray, Toomas Timpka, Marine Sorg, Frédéric Depiesse, Pedro Branco, Astrid Junge
Journal: British Journal of Sports Medicine (2019)

Illnesses can impair sports participation and performance in athletics training or competition (including major championships).1 Travel, jet lag, changes in climatic/environmental conditions and changes in food habits, in addition to the competition per se, could predispose athletes to illness in major championships context.2–4 

During international athletics championships, an incidence of illnesses between 20 and 68 per 1000 registered athletes have been reported.2 3 5 6 However, extended and deeper epidemiological analyses are needed to develop effective illness prevention strategies. Therefore, this study aimed to describe the occurrence and characteristics of illnesses at international athletics championships with regards to sex (male and female athletes), disciplines (explosive and endurance) and championships type (indoor and outdoor).

In major athletics championships between 2009 …
AB0555 POTENTIAL ROLE OF PAROTID ELASTOGRAPHY IN DIAGNOSIS AND CLASSIFICATION OF PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME
Authors: Hasan Satış, Betül Nur Demir, Reyhan Bilici Salman, Esra Temel, Hakan Babaoglu, Nuh Atas, Aslıhan Avanoglu Güler, Hazan Karadeniz, Emetullah Cingil, Abdurrahman Tufan, Mehmet Akif Ozturk, Seminur Haznedaroglu, Berna Göker
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Despite the improvements in classifying patients with primary Sjögren's syndrome with usage of the new 2016 ACR/EULAR classification criteria, there remains to be a need for improvement and investigating the value of new modalities in diagnosing as well as classifiying these patients. Objectives: to investigate potential role of parotid elastography in diagnosis and classification of patients with primary Sjögren's syndrome (pSs) <h3>Methods:</h3> This is a cross sectional analysis of patients with primary Sjögren's syndrome followed up in our out-patient Rheumatology clinic. We performed chart reviews and retrospectively investigated the available data on files to search whether or not our clinically diagnosed patients satisfied the 2002 AEG and/or 2016 ACR/EULAR criteria sets. Ultrasonographic and elastographic evaluation of parotid and submandibular glands bilaterally were performed on consecutive patients with clinical diagnosis of pSs and contributions of these findings to classification criteria sets were interpereted <h3>Results:</h3> There were 95 pSs patients and 30 healthy gender and age matched controls. Strain ratio, shearwave velocity and Pascal values of the glands were examined. Parotid strain ratio, submandibular velocity and submandibular pascal values were statistically significantly different compared to healthy controls (Table).%86 of patients considered clinically as Sjögren syndrome satisfied 2016 ACR/EULAR (criteria patients) and%84 satisfied 2002 AER classification criteria. We grouped patients with respect to parotid strain ratio taking 1.0875 as the cut-off value. Those patients who did not satisfy 2016 ACR/EULAR criteria, but clinically diagnosed as pSs (non criteria pSs patients), also had significantly higher parotid strain ratio and submandibular velocity compared to healthy controls (p:0,016 and p&lt;0,001 respectively). Interestingly, both criteria and non-criteria pSs patients had similar parotid strain ratio and submandibular velocity value (p:0,892 and p:0,260, respecitively) <h3>Conclusion:</h3> Parotid shear elastography is an easy and nonivasive method and can be a useful tool for the diagnosis and classification of patients with pSs (1). <h3>References</h3> [1] Mossel E, Delli K, van Nimwegen JF, Stel AJ, Kroese FGM, Spijkervet FKL, Vissink A, Arends S, Bootsma H; EULAR US-pSS Study Group. Ultrasonography of major salivary glands compared with parotid and labial gland biopsy and classification criteria in patients with clinically suspected primary Sjögren's syndrome Ann Rheum Dis. 2017 Nov;76(11):1883-1889. doi: 10.1136/annrheumdis-2017-211250 <h3>Disclosure of Interests:</h3> None declared
PF444 IDENTIFICATION OF T‐CELL RECEPTORS FROM THE ALLOGENEIC‐HLA REPERTOIRE SPECIFIC FOR MELANOMA‐ASSOCIATED ANTIGENS
Authors: M. de Rooij, M. van der Meent, D. van der Steen, D. Remst, R. Hagedoorn, A. Wouters, M. Kester, P. van Veelen, F. Falkenburg, M. Heemskerk
Journal: HemaSphere (2019)

Background: Melanoma‐associated antigens (MAGE) are highly expressed in multiple myelomas as well as solid tumors, but silent in normal cells except for male germ line cells. This tumor‐restricted expression makes it an excellent target for adoptive T cell therapy. However, due to thymic selection high‐affinity T cells against self‐antigens presented in the context of self‐HLA are deleted from the T‐cell repertoire of a patient. To overcome this problem, we identify T‐cell receptors (TCRs) from the allogeneic‐HLA repertoire instead of the autologous‐HLA repertoire. Aims: To identify high‐affinity T‐cell receptors from the allogeneic‐HLA repertoire specific for melanoma‐associated antigens. Methods: In this study we selected MAGE peptides by peptide elution experiments from HLA class I and subsequent mass spectrometric analysis of tumor cells. Only peptides binding in the most frequently occurring HLA‐alleles were selected. From the identified peptides, HLA‐tetramers were formed to isolate peptide specific CD8 + T cells from healthy allogeneic donors. Avidity of the selected T‐cell clones was determined by stimulation assays including a broad range of MAGE expressing tumor cell lines. To examine off‐target recognition, T‐cell clones were stimulated with MAGE negative cell lines and EBV‐transformed B lymphoblastic cells expressing all prevalent HLA molecules. Results: MAGE peptides were eluted from multiple myelomas, EBV‐transformed lymphoblastic cells, acute myeloid leukemia and ovarium carcinomas. For MAGE‐A1, T‐cell clones specific for four different epitopes presented in the context of HLA‐A ∗ 01:01, HLA‐A ∗ 03:01, HLA‐B ∗ 07:02 and HLA‐C ∗ 07:02 were selected. For MAGE‐A3, T‐cell clones specific for one epitope presented in the context of HLA‐A ∗ 01:01 and HLA‐B ∗ 35:01 were identified. The selected T‐cell clones demonstrated efficient recognition of MAGE‐A1 or MAGE‐A3 positive multiple myeloma and solid tumor cell lines without detectable cross‐reactivity. Summary/Conclusion: MAGE‐A1 and MAGE‐A3 specific T‐cell clones were isolated from the allogeneic‐HLA repertoire of healthy individuals. The identified clones were activated upon exposure to MAGE‐A1 or MAGE‐A3 positive tumor cell lines and showed limited off‐target recognition. These newly identified TCRs could potentially be used for TCR‐gene therapy strategies targeting MAGE‐A1 or MAGE‐A3 positive tumors.
SAT0507 EVALUATION OF THE NEW CLASSIFICATION CRITERIA FOR PFAPA SYNDROME
Authors: Fabio Crimi, Manel Mejbri, Véronique Hentgen, Glory Dingulu, Isabelle Koné-Paut, Sophie Georgin-Lavialle, Pascal Pillet, Michael Hofer
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Modified Marshall criteria used for PFAPA syndrome have never been validated and are little used by the experts because the symptoms of monogenic fevers often overlap with PFAPA ones. A new set of classification criteria based on an international survey and a consensus conference in Genoa was developed in 2018. <h3>Objectives:</h3> Evaluate the performance of the new criteria in a real-life setting <h3>Methods:</h3> This is a multicentric, prospective and descriptive cohort study, through the recurrent fever module of the JIRcohorte platform. 417 patients diagnosed with PFAPA (187), monogenic fever syndromes (167) or unclassified recurrent fever syndrome (UPF=63) from Swiss and French centers were enrolled in the study. The new classification criteria were applied to this cohort and we calculated their performance. We then analyzed which of the criteria performed the less well. <h3>Results:</h3> One hundred fourteen from 187 (61%) PFAPA patients met the new criteria, as well as 20/230 non-PFAPA patients (FMF: 3, MKD: 4, UPF: 13); 73 PFAPA patients did not meet the criteria. We calculated a specificity of 91.3% and a sensitivity of 60.9%. The least satisfied criterion among PFAPA patients not meeting the criteria was “absence of skin rash”. By removing this criterion, the sensitivity improved (81.2%), but the specificity decreased slightly to 86%. <h3>Conclusion:</h3> Genoa 2017 classification criteria for PFAPA syndrome showed a good specificity but an insufficient sensitivity. Excluding the less satisfied criterion, the set reaches a sensitivity and specificity around 80% which could be a fair compromise for PFAPA classification criteria. Our study highlights the difficulty in establishing classification criteria due to the lack of gold standard for PFAPA diagnosis. <h3>References</h3> [1] Vanoni F, Federici S, Antón J, Barron K, Brogan P, De Benedetti F, Dedeoglu F, Demirkaya E, Hentgen V, Kallinich T, Laxer R, Russo R, Toplak N, Uziel Y, Martini A, Ruperto N, Gattorno M, Hofer M. An international Delphi survey for the definition of the variables for the development of new classification criteria for Periodic Fever Aphthous stomatitis Pharyngitis Cervical Adenitis (PFAPA). Pediatr Rheumatol Online J. 2018, 16(1):27. <h3>Disclosure of Interests:</h3> Fabio Crimi: None declared, Manel Mejbri: None declared, Véronique Hentgen Consultant for: SOBI, Novartis, Abbvie, Speakers bureau: Novartis, Glory Dingulu: None declared, Isabelle Koné-Paut Grant/research support from: SOBI has supported drug product (anakinra) for the presented study, Consultant for: SOBI, Novartis, Pfizer, Abbvie, UCB, CHUGAI, ROCHE, Sophie Georgin-Lavialle Consultant for: novartis, sobi, Speakers bureau: novartis, sobi, Pascal Pillet: None declared, michael hofer Grant/research support from: novartis, SOBI, Consultant for: Novartis, SOBI
PB1969 CYP2D6 ALLELIC CHARACTERIZATION ON SPANISH TYPE 1 GAUCHER DISEASE PATIENTS
Authors: L. López de Frutos, P. Alfonso, C. Lahoz, P. Irún, P. Giraldo
Journal: HemaSphere (2019)

Background: Cytochrome p450 is the main drug metabolic pathway mostly by CYPIIIA4 and CYPIID6 enzymes. The second one is the responsible for the clearance from 20% of most common drugs as paracetamol or codeine and presented four different metabolizer phenotype: normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM) or ultra‐rapid metabolizer (UM). CYP2D6 (MIM∗608902) is a highly polymorphic gene that encodes CYPIID6. The different metabolizer capabilities are caused by different alleles on CYP2D6 due to entire gene deletions or duplications or 19 SNPs. This is the pathway to metabolize one of the Gaucher disease (GD) treatments, which dose administration is regulated according to the metabolizer phenotype being this one of the administration limitations Aims: With this background we consider interesting stablish the metabolizer and allelic frequency from CYP2D6 on our GD population and compare it with the general Spanish population and a Gaucher disease patients cohort. Methods: We select 109 type 1 GD patients genetically confirmed and we used the xTAG®CYP2D6 kit to identify the CYP2D6 gene alleles. This group was compared with a control group obtained from the completed Spanish reports on the pharmagkb database and with a worldwide type 1 GD patients enrolled on the ENCORE trial. Statistical significance was considered if p‐value&lt;0.05 Results: As a result, 87 patients were classified as normal, 14 as intermediate, 6 as poor and 2 as ultra‐rapid metabolizers. The allelic frequencies were 5.5% for duplication and 4.5% for deletion. The most common allele was wild type and the second one was the null allele ∗4. Alleles ∗6, ∗9 and ∗35 presented a higher frequency than expected. There was no relationship between the patients’ gender or GBA1 genotype and the allelic or phenotypic frequencies on CYPIID6 enzyme and CYP2D6 gene. This results were different than expected for Spanish population but agrees with the ENCORE Gaucher cohort. Summary/Conclusion: To sum up, our Spanish GD series shows an unexpected distribution of alleles that encode for an enzyme with a reduced or absent activity than the results previously reported in the Spanish population. This is important due to the pharmacological interactions and the impact of unexpected secondary effect that can be higher on this population.