tbuckley/cabot-search huggingface dataset:
PS1358 POTENT ANTI‐MYELOMA EFFICACY OF DENDRITIC CELL THERAPY IN COMBINATION WITH POMALIDOMIDE AND PROGRAMMED DEATH‐LIGAND 1 BLOCKADE IN A PRECLINICAL MODEL OF MULTIPLE MYELOMA
Authors: S.‐H. Jung, T.‐H. Chu, M.‐C. Vo, H.‐S. Park, T.J. Lakshmi, S.‐Y. Ahn, H.‐J. Kim, J.‐J. Lee
Journal: HemaSphere (2019)

Background: Dendritic cell (DC)‐based vaccines are recognized as a promising immunotherapeutic strategy against cancer, and various combination approaches have been developed to enhance DC function by modulating immune responses and tumor microenvironment. Aims: In this study, we investigated the efficacy of DC vaccination in combination with pomalidomide and programmed death ligand‐1 (PD‐L1) blockade in a murine model of multiple myeloma (MM). Methods: MOPC‐315 cell lines were injected subcutaneously to establish MM bearing mice. Four test groups were used to mimic clinical protocol: (1) PBS control, (2) DCs + pomalidomide/dexamethasone, (3) Pomalidomide/dexamethasone + PD‐L1 blockade, and (4) DCs + pomalidomide/dexamethasone + PD‐L1 blockade. Results: The combination of DCs + pomalidomide with dexamethasone + PD‐L1 blockade inhibited more strongly tumor growth and prolonged survival of treated mice compared to the other groups. This effect was associated with a significant reduction in immune suppressor cells, such as myeloid‐derived suppressor cells, regulatory T cells, and M2 macrophages, and level of immunosuppressive factors, such as vascular endothelial growth factor, transforming growth factor‐β, and interleukin‐10, and with the significant induction of immune effector cells, such as CD4 + and CD8 + T cells, memory T cells, natural killer (NK) cells, and M1 macrophages, in the spleen and tumor microenvironment. Functional activities of cytotoxic T lymphocytes and NK cells in spleen were also enhanced by the combination of DCs + pomalidomide with dexamethasone + PD‐L1 blockade. Summary/Conclusion: The collective findings in the murine MM model suggest that DC vaccination combined with pomalidomide and PD‐L1 blockade synergistically enhance antitumor immunity through two‐way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response.
PB2136 DO FUNCTIONAL VARIANTS OF MIF AND MBL GENES INFLUENCE OUTCOME IN PATIENTS UNDERWENT AUTOLOGOUS STEM CELL TRANSPLANTATION FOR MULTIPLE MYELOMA?
Authors: M. Pehlivan, A. F. Nursal, I. Gündeş, Y. Oyacı, D. Kıvanç, S. Pehlivan
Journal: HemaSphere (2019)

Background: Multiple myeloma (MM) is a plasma cell malignancy, with wide survival range and multiple risk factors and staging systems linked to survival. Macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine. Mannose‐binding lectin (MBL) enhances opsonization and activates complement. Aims: This analysis was performed to evaluate the relationships of MIF ‐173G/C and MBL codon 54 variants with clinical feaures and susceptibility in patients underwent Autologous stem cell transplantation (ASCT) for MM. Methods A total of 155 patients (Female/Male:74/81) who underwent ASCT and 200 healthy subjects (Female/Male:99/101) were included. The median follow‐up period was 36 months. Genotyping of these variants was determined by PCR‐RFLP. Genotype and allele frequencies were compared between the study groups using χ 2 ‐test. Kaplan‐Meier curves for Progression‐free survival (PFS) and Overall survival (OS) were compared using a log‐rank test. Results: The median age at diagnosis is 55 years for patients. In all, median OS was 79 months in patients. OS showed that 16.1% patients died. PFS was associated with gender ( p = 0.049, 95% Cl:0.258‐0.998). Individuals with BB genotype showed a significant association with 10.607‐fold increased risk of MM ( p = 0.001 ). The genetic analysis association with survival was performed under a recessive genetic model (CC vs. GG/CG). MIF GC/GG genotype was significantly associated with longer OS (median 5 years) compared to CC genotypes (Log Rank p = 0.016 ). Summary/Conclusion: Our study indicated that the MBL codon 54 functional variant might contribute to MM susceptibility in Turkish population. Also our results imply that the OS in MM patients is associated with the ‐173G/C variant of MIF gene.
Krüppel-like factor 3 inhibition by mutated lncRNA<i>Reg1cp</i>results in human high bone mass syndrome
Authors: Mi Yang, Qi Guo, Hui Peng, Yu-Zhong Xiao, Ye Xiao, Yan Huang, Chang-Jun Li, Tian Su, Yun-Lin Zhang, Min-Xiang Lei, Hui-Ling Chen, Tie-Jian Jiang, Xiang-Hang Luo
Journal: The Journal of Experimental Medicine (2019)

High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp. Mutant Reg1cp increased the formation of the CD31hiEmcnhi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31hiEmcnhi vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and bone formation. Our findings revealed a specific mutation in lncRNA Reg1cp that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.
SP0196 IS THERE ROOM FOR OTHER IMAGING MODALITIES BEYOND CONVENTIONAL X-RAYS AND MRI?
Authors: C.J. van der Laken
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Early diagnosis of spondyloarthritis is still tempting since objective measures to assess disease activity are often negative. MRI provides highly sensitive visualization of inflammation, but detection levels in early spondyloarthitis are varying. Another clinical temptation is early treatment evaluation of spondyloarthritis. An important outcome measure is therapeutic efficacy on bone formation in vertebral column and sacro-iliac joints. Conventional X-rays only allow for assessment of bone formation over a time span of at least 2 years. In this presentation, opportunities with new upcoming imaging techniques to address above mentioned clinical issues will be discussed in relation to longer existing imaging techniques. <h3>Disclosure of Interests:</h3> None declared
Abstract 14804: Acute and 3-year Bleeding Risks: Comparing Drug-Eluting to Bare-Metal Stents in Old and Very Old Adults in a Community Population
Authors: Daniel E Forman, Samip Vasaiwala, Treacy S Silbaugh, Ann Lovettt, Sharon-Lise T Normand, Laura Mauri
Journal: Circulation (2010)

Introduction: The rapidly expanding population of older adults is highly susceptible to coronary artery disease, and also to revascularization-related bleeding complications. Although drug eluting ...
Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease
Authors: Sunaina Rengarajan, Emily E. Vivio, Miles Parkes, Daniel A. Peterson, Elisha D.O. Roberson, Rodney D. Newberry, Matthew A. Ciorba, Chyi-Song Hsieh
Journal: Gut Microbes (2019)

Aberrant immune responses against gut microbiota are thought to be key drivers of inflammatory bowel disease (IBD) pathogenesis. However, the extent and targets of immunoglobulin (Ig) A versus IgG responses to gut bacteria in IBD and its association with IBD severity is not well understood. Here, we address this by analyzing fecal samples from Crohn's disease (CD), ulcerative colitis (UC), and Non-IBD patients by flow cytometry for the frequency of bacteria that were endogenously bound with IgA and/or IgG. Assessment of IBD patients from two geographically distinct cohorts revealed increased percentages of IgA- and IgG-bound fecal bacteria compared to non-IBD controls. Notably, the two major subsets of IBD showed distinct patterns of Ig-bound bacteria, with CD activity associated with increases in both IgA and IgG-bound bacteria, whereas UC activity correlated only with increases in IgG-bound bacteria. Analysis of the flow sorted Ig-bound bacterial repertoire by 16S rDNA sequencing revealed taxa that were Ig-bound specifically in IBD. Notably, this included bacteria that are also thought to reside in the oral pharynx, including Gemella, Peptostreptococcus, and Streptococcus species. These data show that the pattern of IgA and IgG binding to fecal bacteria is distinct in UC and CD. In addition, the frequency of Ig-bound fecal bacteria may have potential as a non-invasive biomarker for disease activity. Finally, our results support the hypothesis that immune responses to oral pharyngeal bacteria may play an important role in the pathogenesis of IBD.
Diversity of Translation Initiation Mechanisms across Bacterial Species Is Driven by Environmental Conditions and Growth Demands
Authors: Adam J Hockenberry, Aaron J Stern, Luís A N Amaral, Michael C Jewett
Journal: Molecular Biology and Evolution (2017)

The Shine-Dalgarno (SD) sequence motif is frequently found upstream of protein coding genes and is thought to be the dominant mechanism of translation initiation used by bacteria. Experimental studies have shown that the SD sequence facilitates start codon recognition and enhances translation initiation by directly interacting with the highly conserved anti-SD sequence on the 30S ribosomal subunit. However, the proportion of SD-led genes within a genome varies across species and the factors governing this variation in translation initiation mechanisms remain largely unknown. Here, we conduct a phylogenetically informed analysis and find that species capable of rapid growth contain a higher proportion of SD-led genes throughout their genomes. We show that SD sequence utilization covaries with a suite of genomic features that are important for efficient translation initiation and elongation. In addition to these endogenous genomic factors, we further show that exogenous environmental factors may influence the evolution of translation initiation mechanisms by finding that thermophilic species contain significantly more SD-led genes than mesophiles. Our results demonstrate that variation in translation initiation mechanisms across bacterial species is predictable and is a consequence of differential life-history strategies related to maximum growth rate and environmental-specific constraints.
Disease-specific primed human adult stem cells effectively ameliorate experimental atopic dermatitis in mice
Authors: Byung-Chul Lee, Jae-Jun Kim, Jin Young Lee, Insung Kang, Nari Shin, Seung-Eun Lee, Soon Won Choi, Je-Yoel Cho, Hyung-Sik Kim, Kyung-Sun Kang
Journal: Theranostics (2019)

Although human mesenchymal stem cells (hMSCs) hold considerable promise as an alternative therapeutic reagent for allergic disorders including atopic dermatitis (AD), the strategy for enhancing hMSC-based therapy remains challenging.We sought to investigate whether preconditioning with mast cell (MC) granules could enhance the therapeutic efficiency of human umbilical cord blood-derived MSCs (hUCB-MSCs) against AD.Methods: AD was experimentally induced in NC/Nga mice by repeated applications of 4% sodium dodecyl sulfate (SDS) and dermatophagoides farinae (Df) extract, and preconditioned hUCB-MSCs were subcutaneously injected.The therapeutic effect was determined by gross examination and additional ex vivo experiments performed using blood and skin samples to determine the resolution of allergic inflammation.To explore the underlying mechanisms, several co-culture assays with primary isolated immune cells and wound closure assays were conducted.Results: Pretreatment of MC granules enhanced the therapeutic effects of hUCB-MSCs by attenuating the symptoms of AD in an experimental animal model.MC granule-primed cells suppressed the activation of major disease-inducing cells, MCs and B lymphocytes more efficiently than naïve cells both in vitro and in vivo.Histamine-mediated upregulation of the COX-2 signaling pathway was shown to play a crucial role in suppression of the allergic immune response by MC-pretreated hUCB-MSCs.Moreover, MC pretreatment improved the wound healing ability of hUCB-MSCs.Conclusions: Our findings indicate that pre-exposure to MC granules improved the therapeutic effect of hUCB-MSCs on experimental AD by resolving the allergic immune reaction and accelerating the tissue regeneration process more efficiently than naïve cells, suggesting a potential enhancement strategy for stem cell-based therapy.
AB0436 ADHERENCE TO DISEASE-MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATIC DISEASES
Authors: Rita Angélica Pineda Sic, Iván de Jesús Hernández-Galarza, Marielva Castro-González, Dionicio Ángel Galarza-Delgado, Miguel Angel Villarreal-Alarcón, Rodolfo Allan Uriarte Botello, Octavio Ilizaliturri Guerra
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> There has been seen a low adherence to treatment in patients with rheumatic diseases, which can have important consequences in disease prognosis. Although literature in Latin-American population is scarce, a previous study evaluating medication adherence in this population reported a 16.4% prevalence of adherence in Rheumatoid Arthritis (RA) and 45.9% in Systemic Lupus Erythematosus (SLE) patients (1). It has been demonstrated better outcomes in patients with rheumatic conditions who have good adherence to treatment therapies (2). <h3>Objectives:</h3> To describe the adherence to synthetic Disease-Modifying Antirheumatic Drugs (DMARDs) in patients with rheumatic diseases from a Mexican outpatient rheumatology clinic. <h3>Methods:</h3> This study was conducted in the outpatient rheumatology clinic of University Hospital in Monterrey, México, cross-sectional, descriptive, self-report adherence study. Consecutive patients with RA, SLE, Inflammatory Myopathies, Psoriatic arthritis (PsA), Systemic Sclerosis (SSc) were approached during their normal routine rheumatology appointments, in the March 2018 to December 2018 period. They were asked how many days of the last month they forgot or took their DMARDs. We classified the adherence rate in 4 categories based on the days of the last month it took the indicated medication; good: 75%-100% (&gt; 21 days), regular 50-74% (21-15 days), bad 25-49% (14-8 days) and null: &lt;25% (&lt; 7 days). When adherence was not good we interrogated about the cause. Data was obtained from REPAIR ® (internal electronic patient record) and analyzed with the statistical package SPSS version 24. <h3>Conclusion:</h3> Adherence in this group of patients was good, for the definition used in our study. The method used (self-report) is very sensitive to detect non-adherence, but it overestimate good adherence, therefore the potential bias of results must be considered and confirmed whit objective measurement. The main reason for poor or no adherence was the economic, with the exception of the Ssc group it was their own decision and the patients with SLE that had the same percentage for economic and self-decision. <h3>References</h3> [1] - Resende Prudente L, Souza Diniz J, Matteucci Ferreira TXA, Marçal Lima D, Antônio Silva N, Saraiva G, et al. Medication adherence in patients in treatment for rheumatoid arthritis and systemic lupus erythematosus in a university hospital in Brazil. Patient Preference and Adherence. 2016:10 863–870 [2] - Waimann ChA, Marengo MF, de Achaval S, Cox VL, Garcia-Gonzalez A, Reveille JD. Electronic Monitoring of Oral Therapies in Ethnically Diverse and Economically Disadvantaged Patients With Rheumatoid Arthritis. Arthritis &amp; Rheumatism. 2013:6 1421-1429. <h3>Disclosure of Interests:</h3> None declared
PF512 NEXT‐GENERATION SEQUENCING‐BASED CLONALITY ASSESSMENT OF IMMUNOGLOBULIN GENE REARRANGEMENTS DISTINGUISHES RELAPSE FROM SECOND PRIMARY CLASSICAL HODGKIN LYMPHOMA
Authors: D. van Bladel, M. van den Brand, J. Rijntjes, A. Brinkman, T. Reigl, N. Darzentas, C. Hess, K. Hebeda, P. Groenen, H. van Krieken, B. Scheijen
Journal: HemaSphere (2019)

Background: Classic Hodgkin's lymphoma (cHL) has a high cure rate with current therapy, however relapse still occurs in 5%&gt;10% of early stage and 15%&gt;30% of advanced cHL. Interestingly, case reports and small series have shown that some of these relapses appear to be a new primary cHL. Assessment of clonal relationship between primary diagnosis and relapsed cHL samples after treatment will distinguish true relapse from second primary lymphoma. Clonality detection in cHL using conventional clonality assays has thus far been severely hampered by the low frequency of Hodgkin and Reed‐Sternberg (HRS) cells and limited DNA quality obtained from formalin‐fixed paraffin‐embedded (FFPE) material. Within the EuroClonality‐NGS Working Group, we have developed a novel approach to detect immunoglobulin (IG) heavy chain (IGH ) and k light chain (IGK) gene rearrangements. Aims: The objective or our study is to determine the clonal relationship between HL diagnosis and relapse samples to assess the incidence of second primary malignancies in HL recurrences. Methods: We have collected 70 paired primary and relapse cHL cases. In 38/70 cases relapse occurred within three years after diagnosis, in 32/70 cases relapse occurred later than three years after diagnosis. EuroClonality‐NGS gene‐specific IGH‐VJ‐FR3, IGH‐DJ, IGK‐VJ and Intron‐Kde primer sets for small amplicon sizes were used to perform next‐generation sequencing (NGS)‐based clonality analysis with Ion Torrent PGM. Bioinformatic analyses with the interactive web‐based immunoprofiler ARResT/Interrogate allowed run/sample quality control followed by accurate identification of clonotypes. Results: We show that NGS‐based clonality assessment is highly suitable for detecting IG rearrangements in FFPE tissue specimens, including HL tissue specimens. Our preliminary data analysis of 7 paired diagnosis and relapse samples demonstrates the presence of identical clonotypes in 2 cases, while distinct clonotypes were observed in 3 other cases suggesting a new primary lymphoma. In the remaining 2 cases no specific clonotype could be identified in either diagnosis and/or relapse. The analysis of additional cHL recurrences by NGS‐based clonality assessment will reveal the true incidence of clonally unrelated lymphoma in relapsed cHL. Summary/Conclusion: This study is an important step towards establishment of NGS‐based clonality assessment in clinical practice for cHL, and eventually the improvement of therapeutic management of second primary cHL.
Radiomic measures from chest high-resolution computed tomography associated with lung function in sarcoidosis
Authors: Sarah M. Ryan, Tasha E. Fingerlin, Margaret Mroz, Briana Barkes, Nabeel Hamzeh, Lisa A. Maier, Nichole E. Carlson
Journal: European Respiratory Journal (2019)

Introduction Pulmonary sarcoidosis is a rare heterogeneous lung disease of unknown aetiology, with limited treatment options. Phenotyping relies on clinical testing including visual scoring of chest radiographs. Objective radiomic measures from high-resolution computed tomography (HRCT) may provide additional information to assess disease status. As the first radiomics analysis in sarcoidosis, we investigate the potential of radiomic measures as biomarkers for sarcoidosis, by assessing 1) differences in HRCT between sarcoidosis subjects and healthy controls, 2) associations between radiomic measures and spirometry, and 3) trends between Scadding stages. Methods Radiomic features were computed on HRCT in three anatomical planes. Linear regression compared global radiomic features between sarcoidosis subjects (n=73) and healthy controls (n=78), and identified associations with spirometry. Spatial differences in associations across the lung were investigated using functional data analysis. A subanalysis compared radiomic features between Scadding stages. Results Global radiomic measures differed significantly between sarcoidosis subjects and controls (p&lt;0.001 for skewness, kurtosis, fractal dimension and Geary's C ), with differences in spatial radiomics most apparent in superior and lateral regions. In sarcoidosis subjects, there were significant associations between radiomic measures and spirometry, with a large association found between Geary's C and forced vital capacity (FVC) (p=0.008). Global radiomic measures differed significantly between Scadding stages (p&lt;0.032), albeit nonlinearly, with stage IV having more extreme radiomic values. Radiomics explained 71.1% of the variability in FVC compared with 51.4% by Scadding staging alone. Conclusions Radiomic HRCT measures objectively differentiate disease abnormalities, associate with lung function and identify trends in Scadding stage, showing promise as quantitative biomarkers for pulmonary sarcoidosis.
The HVEM-BTLA Axis Restrains T Cell Help to Germinal Center B Cells and Functions as a Cell-Extrinsic Suppressor in Lymphomagenesis
Authors: Michelle A. Mintz, James H. Felce, Marissa Y. Chou, Viveka Mayya, Ying Xu, Jr-Wen Shui, Jinping An, Zhongmei Li, Alexander Marson, Takaharu Okada, Carl F. Ware, Mitchell Kronenberg, Michael L. Dustin, Jason G. Cyster
Journal: Immunity (2019)

The tumor necrosis factor receptor superfamily member HVEM is one of the most frequently mutated surface proteins in germinal center (GC)-derived B cell lymphomas. We found that HVEM deficiency increased B cell competitiveness during pre-GC and GC responses. The immunoglobulin (Ig) superfamily protein BTLA regulated HVEM-expressing B cell responses independently of B-cell-intrinsic signaling via HVEM or BTLA. BTLA signaling into T cells through the phosphatase SHP1 reduced T cell receptor (TCR) signaling and preformed CD40 ligand mobilization to the immunological synapse, thus diminishing the help delivered to B cells. Moreover, T cell deficiency in BTLA cooperated with B cell Bcl-2 overexpression, leading to GC B cell outgrowth. These results establish that HVEM restrains the T helper signals delivered to B cells to influence GC selection outcomes, and they suggest that BTLA functions as a cell-extrinsic suppressor of GC B cell lymphomagenesis.
Colonoscopy-Naïve Raters Can Be Trained to Assess Colonoscopy Quality
Authors: Rajesh N. Keswani, Mark Benson, Claire Beveridge, Andrew J. Gawron, Adam B. Gluskin, Charles J. Kahi, Tonya R. Kaltenbach, Jessica McClure, Robert Schenck, Rena H. Yadlapati, Anna Duloy
Journal: Clinical Gastroenterology and Hepatology (2019)