tbuckley/cabot-search huggingface dataset:
PB1959 THE ROLE OF FLOW CYTOMETRY IN DIFFERENTIAL DIAGNOSIS OF CMML AND REACTIVE MONOCYTOSIS. THE LIPID SIGNAL PATHWAY CHARACTERISTICS IN CLONAL MONOCYTOSIS
Authors: A. Sevoyan, A. Sevoyan
Journal: HemaSphere (2019)

Background: Myelodysplastic syndrome (MDS) is a heterogeneous group of diseases characterized by ineffective erythropoiesis and dysplasia. MDS and its subtype CMML is highly associated with chronic inflammatory and autoimmune diseases; however the combination of MDS with other bone marrow neoplasms is not a common entity. Only few cases of MDS combined with other blood malignancies have been described. The pathogenesis and mechanisms of two different clones evolution in MDS is an unclear multistep process involving molecular genetic instability, epigenetic factors and innate immune response deregulation. The role of plasma lipid signaling pathway have been also defined in recent years. Aims: Is to investigate the role of immunophenotyping in differential diagnosis of CMML and reactive monocytosis and clarify the possible significance of phosphoinositides in diagnosis of CMML. Methods: Blood samples of patient with CMML combined with plasma cell disorder, patient with CMML and blood samples of 2 patients with monocytosis were examined in our laboratory. Peripheral blood CBC, bone marrow smear cytological examination, pathohistology, flow cytometry and PCR were performed for the diagnostic purposes. In parallel with classic diagnostic work‐up the chromatograph method was used to investigate the cytoplasmatic mono and di‐phosphoinositides in patients with CMML. Results: CBC reveal monocytosis &gt;1000 less than 1 month duration, PCR analysis were negative for BCR ABL in all 4 cases. Case N = 1 histology examination Results: &gt;30% of plasma cells express CD56 and CD138, atypical cells express MPO and CD14 and epithelioid granulomas. In case N = 1 Immuntophenotype results were the following: (CD64+)‐52%, (CD16+)‐44%, (CD14‐). In case N = 2 the dysplasia, megakaryocytes and monocytes were observed by histology examination. Immunophenotype Results: (CD14+/CD16)‐31.1%, (CD14+/‐CD16+)‐49.3%, (CD14‐/CD16‐)‐4.3%. There were monocytosis and secondary changes of hematopoietic tissue in histology examination of cases N = 3 and N = 4. Immunophenotype showed: (CD14‐/16‐)‐13%, (CD64+)15%, (CD56‐)‐3%. High level of mono and di‐phosphoinositides were registered in first 2 cases in compare with cases N3 and N4. The flow cytometry revealed monocyte specific markers in all 4 cases with certain variations. Summary/Conclusion: The exact immunophenotype markers for clonal monocytosis must be defined. Lipid signaling pathway components, such as cytoplasmatic mono and di‐phosphoinositides must be investigated in the context of clonal monocytosis and diagnostic purposes.
Transcriptional network analysis implicates altered hepatic immune function in NASH development and resolution
Authors: Joel T. Haas, Luisa Vonghia, Denis A. Mogilenko, An Verrijken, Olivier Molendi-Coste, Sébastien Fleury, Audrey Deprince, Artemii Nikitin, Eloïse Woitrain, Lucie Ducrocq-Geoffroy, Samuel Pic, Bruno Derudas, Hélène Dehondt, Céline Gheeraert, Luc Van Gaal, Ann Driessen, Philippe Lefebvre, Bart Staels, Sven Francque, David Dombrowicz
Journal: Nature Metabolism (2019)
Annals Consult Guys - Length of Stay After Myocardial Infarction: How Low Can We Go?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2019)

Web Exclusives18 June 2019Annals Consult Guys - Length of Stay After Myocardial Infarction: How Low Can We Go?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author and Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0045 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 June 2019Volume 170, Issue 12Page: CG1KeywordsDiagnostic techniquesDisclosureLength of stayMuscular dystrophiesMyocardial infarctionResearch grantsResearch reporting guidelines ePublished: 18 June 2019 Issue Published: 18 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Parvovirus outbreak in a kindergarten in a municipality in the north of Portugal, April-June 2008
Authors: G Gonçalves, M Dias
Journal: Eurosurveillance (2008)

In response to an alert raised due to epidemic exanthematous rashes in children in a kindergarten, an outbreak investigation was carried out in a municipality in the north of Portugal in late spring 2008. The intention was to establish an aetiological diagnosis and take corrective measures if necessary. The warden at the kindergarten was interviewed, and a self-administered questionnaire was given to parents and staff. Blood samples from seven children with facial erythema were collected for serological investigation. Seventeen cases of erythema infectiosum, due to infection with parvovirus B19, were identified and classified as "confirmed". No cases occurred among the eight adult staff members. An overall attack rate of 38% was observed among the 45 children (born in 2002 and 2003). All cases were mild and without fever. This parvovirus B19 outbreak made it possible to estimate the basic reproduction number (R0) at between 6 and 8 (or above). Staff members, parents and local clinicians were informed that the infection could pose a risk when caught by people with special clinical conditions. All children had received one dose of measles-mumps-rubella vaccine and 60% had received two doses. The seven children with serologically confirmed parvovirus B19 infection were immune to measles and rubella. All seven were negative for measles- or rubella-specific IgM.
Abstract 13795: Gene Expression Profiles in Engineered Cardiac Tissues Respond to Mechanical Loading and Inhibition of Tyrosine Kinase
Authors: Fei Ye, Fangping Yuan, Xiaohong Li, Nigel Cooper, Joseph P Tinney, Bradley B Keller
Journal: Circulation (2013)

Engineered cardiac tissues (ECTs) rapidly mature in vitro to form functional cardiac muscle and respond to mechanical load with increased proliferation and maturation. Little is known regarding the...
AB1334 AN OPEN-SOURCE WEB-BASED ANALYTICS PLATFORM FOR THE HUMAN IMMUNE ATLAS
Authors: Martin Wasser, Joo Guan Yeo, Pavanish Kumar, Thaschawee Arkachaisri, Su LI Poh, Fauziah Ally, Jing Yao Leong, Kee Thai Yeo, Salvatore Albani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Mass cytometry (CyTOF) measures the expression of many proteins (currently up to 40) in single cells. TII applies CyTOF to characterise cellular diversity of the immune system in peripheral blood and other tissues. Using a growing collection of CyTOF data acquired from blood of clinically and demographically diverse human subjects, we have built our version of the immune atlas, called EPIC (Extended Poly-dimensional Immunome characterisation). <h3>Objectives:</h3> We will discuss two main objectives of this project. To integrate CyTOF data, metadata, cell annotations or other inferred data into the immune atlas, we developed a novel data analytics pipeline. To provide a user-friendly gateway that helps researchers explore the immune atlas and gain new insights about their own CyTOF data, we implemented a web-based data analytics application using the R Shiny programming environment. <h3>Methods:</h3> The core components of the atlas are 'immune maps', which comprise CyTOF data of samples labeled with identical antibody panels and grouped according to a common biological theme. Besides protein expression patterns, immune maps contain contain clinical and demographic metadata, as well as phenotypic information inferred from clustering and cell type annotation. To intuitively analyse these complex multi-dimensional data, we developed a Shiny/R web application that has two main objectives. First, clients can explore the immunome at different levels of details using a wide range of interactive visualisation methods, such as bar charts comparing the abundance of all or subsets of immune cell types in different age groups, or tSNE/UMAP scatter plots providing global perspectives of expression domains. Second, users can upload their own CyTOF data and, through pattern matching, obtain instant estimates about the abundance of selected immune cell populations in their own samples. <h3>Results:</h3> We tested our system using immune maps constructed from healthy paediatric samples. Manually gated ground truth data along with interactive visualisation techniques were used to measure the accuracy of our pipeline in detecting and annotating homogenous cell populations. In addition, we will demonstrate how immune maps can be applied to classify uploaded CyTOF data. <h3>Conclusion:</h3> Our interactive immune atlas platform promises to improve our understanding of the changing immunome landscape in response to disease, treatment and ageing. <h3>References</h3> NA <h3>Disclosure of Interests:</h3> Martin Wasser: None declared, Joo Guan Yeo: None declared, Pavanish Kumar: None declared, Thaschawee Arkachaisri Speakers bureau: Abbvie Pte, Ltd, Su Li Poh: None declared, Fauziah Ally: None declared, Jing yao Leong: None declared, Kee Thai Yeo: None declared, Salvatore Albani: None declared
AB0110 RITUXIMAB INDUCED GRANULOMATOUS HEPATITIS WITH A SARCOIDOSIS LIKE REACTION: A BLINDED TRIAL IN MICE
Authors: sultan almogairen, Ahmed Alhumaidi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rituximab is useful in patients with rheumatoid arthritis (RA) with persistently active disease despite adequate trials with other disease-modifying antirheumatic drugs (DMARDs). <h3>Objectives</h3> To determine whether the inhibition of the B cell CD20 receptor by rituximab results in acute hepatitis in BALB/c mice. <h3>Methods</h3> Twenty BALB/c mice were studied. Ten mice received subcutaneous (SC) injection of rituximab (0.31mg per 25g body weight per 0.03 ml normal saline) at 0, 1, 2 and 4 weeks. For the control group, 10 mice received a SC injection of normal saline (NS) (0.03 ml). At the 10th week post injection, the mice were sacrificed, and histopathological studies were conducted <h3>Results</h3> Of the rituximab-treated group, 1/10 mice died. Liver histology for the rituximab -treated group showed that 7/9 displayed histopathological changes in the lobular cellular infiltrates of eosinophils, lymphocytes and histocytes, in addition to granuloma formation. In contrast, only minimal inflammation was observed in 3/10 mice in the control group (p=0.051). <h3>Conclusion</h3> To our knowledge this is the first experimental controlled study demonstrating rituximab may play a role in inducing granulomatous hepatitis with a sarcoidosis-like reaction. <h3>References</h3> [1] Soliman MM, Hyrich KL, Lunt M, Watson KD, Symmons DP, Ashcroft DM. Rituximab or a second anti-tumor necrosis factor therapy for rheumatoid arthritis patients who have failed their first anti-tumor necrosis factor therapy? Comparative analysis from the British Society for Rheumatology Biologics Register. Arthritis Care Res (Hoboken)2012;64:1108-15. [2] Reuben A. Hepatotoxicity of immunosuppressive drugs. In:Kaplowitz N, DeLeve LD, eds.Drug-induced liver disease. 3rd ed.Amsterdam: Elsevier;2011:569-91. [3] Nard FD, Todoerti M, Grosso V, Monti S, Breda S, Rossi S, et al. Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs. World J Hepatol2015;7:344-361. [4] Greenwald M, Tesser J, Sewell KL. Biosimilars Have Arrived: Rituximab. Arthritis2018;2018. <h3>Disclosure of Interests</h3> None declared
PS1322 ASTX660, A NON‐PEPTIDOMIMETIC ANTAGONIST OF CIAP1/2 AND XIAP, INDUCES APOPTOSIS IN T CELL LYMPHOMA BY ENHANCING IMMUNE MEDIATED AND DEATH RECEPTOR DEPENDENT KILLING
Authors: M. Sims, G. Ward, J. Munck, S. Jueliger, M. Davis, C. Gewinner, R. Ferraldeschi, J. Lyons
Journal: HemaSphere (2019)

Background: ASTX660 is a potent, non‐peptidomimetic antagonist of the cellular and X‐linked inhibitors of apoptosis proteins (cIAP1/2 and XIAP), which is currently being tested in a first in human phase I‐II study in patients with advanced solid tumors and lymphomas (NCT02503423). IAP antagonists enhance tumor necrosis factor (TNF) receptor superfamily mediated apoptosis and are potent anti‐tumor immune enhancers. Aims: Herein, we describe the profile of ASTX660 in a range of T cell lymphoma (TCL) cell lines and evaluate ASTX660's ability to enhance immune mediated killing of tumor cells. Methods: A panel of human and mouse T‐cell lymphoma cell lines were tested in proliferation (Alamar blue or CellTiterGlo) or apoptosis assays (activated caspase‐3 substrate assays by IncuCyte or FACS) for sensitivity to ASTX660 alone or in combination with recombinant Death Receptor ligands (TNFα, FASL or TRAIL). Additionally, we used a novel co‐culture system of tumor cell lines with anti‐CD3 activated human peripheral blood mononuclear cells (PBMC) to assess ASTX660 effects on immune mediated cell killing. Target engagement and induction of apoptosis markers were analysed by Western blotting. Results: ASTX660 antagonises IAPs in TCL cell lines, as indicated by a decrease in cIAP1 protein levels. This ASTX660‐dependent decrease in cIAP was associated with an increase in TNFα‐dependent apoptosis in the EL4 and L5178 TCL cell lines. Several T‐cell lymphoma models, including HuT‐78, HH and My‐La expressed low levels of TNFR1 and therefore did not respond to ASTX660 in the presence of TNFα. However, in these cell lines, ASTX660 conferred a significant increase in FASL or TRAIL‐dependent apoptosis, indicating that ASTX660 sensitises TCL cells to various death receptor ligands and response correlates with receptor expression levels. In addition to this direct effect on TCL cell lines, ASTX660 also enhances anti‐CD3 stimulated PBMC‐dependent killing of multiple tumour cell lines, including TCL lines, via induction of caspase activity. Additional preclinical experiments (both in vitro and in vivo) are underway to further characterise the mode of action of ASTX660 in TCL. Summary/Conclusion: The combination of both direct and indirect effects of ASTX660 on TCL lines, described here, supports the ongoing clinical testing of ASTX660 in TCL (NCT02503423). Preliminary clinical efficacy and safety data of ASTX660 in relapsed/refractory (r/r) peripheral T cell lymphoma and cutaneous T cell lymphoma is the subject of a separate abstract.
Clinical Outcomes of Anti PD-1 Immunotherapy in Patients with Relapsed/Refractory Non Hodgkin Lymphomas
Authors: Mitchell E. Hughes, Christopher Jensen, Jakub Svoboda, Lauren Elizabeth Strelec, Matthew R. Youngman, Stephen J. Schuster, Daniel J. Landsburg, Sunita Dwivedy Nasta, Donald Edward Tsai, David Michael Mintzer, Jennifer Gill, Colleen Dorsey, Kaitlin Kennard, Elizabeth T Chatburn, Joanna Rhodes, Krista Isaac, Kristy Walsh, Tanya Latorre, Kaley Piersanti, Evan Bannister, Colleen Timlin, Donna Capozzi, Anthony R. Mato
Journal: Blood (2017)
OP0247 EFFECT OF IMMUNOSUPPRESSIVE DRUG WITHDRAWAL ON DAMAGE PROGRESSION AND FLARE OCCURRENCE IN SLE PATIENTS IN REMISSION
Authors: Margherita Zen, Francesca Saccon, Mariele Gatto, Maddalena Larosa, Francesco Benvenuti, Luca Iaccarino, Andrea Doria
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with Systemic Lupus Erythematosus (SLE) are often treated with prolonged maintenance therapy with immunosuppressants (ISs) after remission achievement, with the aim of avoiding disease flares and subsequent organ damage. Data on the risk of flare after IS discontinuation and the effect of IS discontinuation on damage accrual are scanty. <h3>Objectives</h3> Our aims were to analyze damage progression in remitted SLE patients who did or did not discontinued ISs, to assess flare rate after IS withdrawal and to compare damage accrual in patients who did or did not flare after IS discontinuation. <h3>Methods</h3> We considered all SLE patients included in our lupus database, diagnosed between 1990 and 2018 (ACR criteria), treated with immunosuppressants over their disease course, who discontinued IS due to remission. IS discontinuation was defined as complete withdrawal of any immunosuppressive drug, and remission as clinical SLE Disease Activity Index (SLEDAI)-2K=0. Flares were defined according to SLEDAI Flare Index, and damage according to SLICC damage Index (SDI). <h3>Results</h3> Eligible patients ever treated with ISs were 319 out of 456 (69.9%) currently in follow-up. Remission lasting at least 6 months was achieved by 206 patients treated with IS (64.6%) (Table 1); among them 105 (51%) discontinued ISs during the follow-up. Mean±SD follow-up after IS withdrawal was 91±71 months (range 6-372). No difference in damage accrual between remitted patients who discontinued or did not discontinue ISs was observed at the end of follow-up, after adjusting for disease duration: median (range) SDI 1 (0-6) and 0 (0-4), respectively. Accordingly, the proportion of remitted patients who accrued damage during the follow-up was similar between those who did or did not discontinue ISs (55% vs. 48%). Among patients who discontinued ISs, 26 (24.7%) experienced a flare after a median (range) of 57 (6-264) months from IS discontinuation. Flares were severe in 50% of cases (Table 2). No difference in damage progression between patients who flared and did not flare after IS withdrawal was found at the end of follow-up: median (range) SDI 1 (0-5) and 1 (0-6), respectively. Moreover, the proportion of patients with damage accrual was similar among patients with and without flare after IS discontinuation (56% vs. 54%). <h3>Conclusion</h3> In our SLE cohort, the withdrawal of IS therapy in remitted patients did not seem to influence damage progression in the medium-term. <h3>Disclosure of Interests:&nbsp;</h3> None declared
Patterns of Polymorphism at the Self-Incompatibility Locus in 1,083 Arabidopsis thaliana Genomes
Authors: Takashi Tsuchimatsu, Pauline M. Goubet, Sophie Gallina, Anne-Catherine Holl, Isabelle Fobis-Loisy, Hélène Bergès, William Marande, Elisa Prat, Dazhe Meng, Quan Long, Alexander Platzer, Magnus Nordborg, Xavier Vekemans, Vincent Castric
Journal: Molecular Biology and Evolution (2017)

Although the transition to selfing in the model plant Arabidopsis thaliana involved the loss of the self-incompatibility (SI) system, it clearly did not occur due to the fixation of a single inactivating mutation at the locus determining the specificities of SI (the S-locus). At least three groups of divergent haplotypes (haplogroups), corresponding to ancient functional S-alleles, have been maintained at this locus, and extensive functional studies have shown that all three carry distinct inactivating mutations. However, the historical process of loss of SI is not well understood, in particular its relation with the last glaciation. Here, we took advantage of recently published genomic resequencing data in 1,083 Arabidopsis thaliana accessions that we combined with BAC sequencing to obtain polymorphism information for the whole S-locus region at a species-wide scale. The accessions differed by several major rearrangements including large deletions and interhaplogroup recombinations, forming a set of haplogroups that are widely distributed throughout the native range and largely overlap geographically. "Relict" A. thaliana accessions that directly derive from glacial refugia are polymorphic at the S-locus, suggesting that the three haplogroups were already present when glacial refugia from the last Ice Age became isolated. Interhaplogroup recombinant haplotypes were highly frequent, and detailed analysis of recombination breakpoints suggested multiple independent origins. These findings suggest that the complete loss of SI in A. thaliana involved independent self-compatible mutants that arose prior to the last Ice Age, and experienced further rearrangements during postglacial colonization.