tbuckley/cabot-search huggingface dataset:
PS1006 INHIBITORS OF HOXA9 LEUKEMOGENIC TRANSCRIPTION FACTOR ARE EFFICIENT ON HUMAN AML CELL MODELS BUT NOT ON NORMAL HUMAN BONE MARROW CD34+ HEMATOPOIETIC CELLS
Authors: M. Lambert, S. Depauw, S. Jambon, M. Bellart, L. Lutchmee, L. Louis‐Thérèse, R. Nhili, M.‐H. David‐Cordonnier
Journal: HemaSphere (2019)

Background: The HOXA9 protein is a transcription factor associated with normal hematopoiesis and which expression on hematopoietic stem cells and progenitor cells decreases in the course of blood cell differentiation. The expression of HOXA9 is however maintained at high level in several subtypes of acute myeloid leukemia (AML) such as mll ‐rearranged leukemias, NPM1‐mutated AMLs and AML presenting MYST3‐CREBP, NUP98‐NSD1 or RUNX/EVI1 translocations. The over‐expression of HOXA9 in these AML subtypes is associated with the maintenance of cell proliferation and the blockade of cell differentiation. It is well known that HOXA9 exerts its leukemic potential through DNA interaction and, therefore, we selected direct inhibitors of HOXA9/DNA interaction to block its activity and evaluate them on a murine leukemia cell model (Depauw et al., 2019). Aims: In order to go further, we aim at evaluating them on human AML cell models expressing or not HOXA9 and on normal human CD34+ hematopoietic cells to address any potential effect of our inhibitors on normal hematopoiesis. Methods: The expression level of HOXA9 was quantified by qRT‐PCR on a series of human AML cell lines. The sensitivity of those cell lines regarding two selected inhibitors was seen addressed using global cell survival analysis using MTS reaction. Methylcellulose clonogenic assays were performed on a series of human AML cell lines and on normal human bone marrow CD34+ hematopoietic cells. Knock‐down of HOXA9 expression was performed as a control using lentiviral delivery of HOXA9‐specific or control shRNAs. Results: A strong correlation between HOXA9 expression and the sensitivity to two of our inhibitors was evidenced in a series of 14 human AML cell lines with linear determination coefficients of R of ∼0.75 and ∼0.8. Clonogenic assays evidenced a decrease in the number and size of the colony forming units of treated related to untreated AML cell models. The relevance of HOXA9 expression in the clonogenicity is addressed by use of lentivirally transduced shHOXA9 in some of the AML cell models. By contrast, no difference were observed on either the number, the size and the differentiation subtypes of the colonies obtained from treated versus untreated normal human CD34+ hematopoietic cells. Summary/Conclusion: In conclusion, we selected inhibitors of HOXA9/DNA interaction that alter cell proliferation and clonogenic activity in a series of HOXA9‐positive AML cell models but that do not affect the progenitor cell number from normal bone marrow CD34+ cells.
Association of interleukin-18 (IL-18), tumor necrosis factor-'alfa' (TNF-'alfa') and interferon-'gama' (IFN-'gama) genes polymorphisms with severity of liver fibrosis in brazilian patients with chronic hepatitis B
Authors: S. C. Ferreira, S. G. F. Chacha, F. F. Souza, A. Teixeira, Neifi Hassan Saloum Deghaide, Celso Teixeira Mendes Júnior, E. C. Castelli, Marie Secaf, S. Rodrigues, M. G. Villanova, Leandra Naíra Zambelli Ramalho, Sergio Zucoloto, Eduardo Antonio Donadi, Ana de Lourdes Candolo Martinelli
Journal: Journal of Hepatology (2010)
SP0208 UNDERSTANDING THE IMPACT OF PAIN, SLEEP AND FATIGUE ON PATIENTS LIVES
Authors: Savia de Souza
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Pain is well known to be a common dominant symptom in people with rheumatic musculoskeletal diseases (RMDs). Perhaps less well acknowledged by healthcare professionals are fatigue and sleep disturbances in these patients. Individually these symptoms are problematic but when combined their effect and impact on patients' lives is greatly amplified; often leaving people in a vicious cycle whereby being in pain results in poor sleep leading to fatigue the next day, which lowers patients' pain tolerance resulting in a poorer night"s sleep, more fatigue and increased pain. Pain, fatigue and sleep disturbance greatly reduce quality of life for people with RMDs. Patients have to adapt their daily and leisure activities, or give them up altogether with negative psychological consequences such as anxiety and depression. Patients can end up feeling helpless and sometimes suicidal. Relationships with partners and friends are often altered affecting their sexual and social lives. Major life decisions, such as having a baby, can be put on hold or shelved. People with RMDs may also have to reduce their working hours or stop working, which has financial repercussions for them and their families. This can exacerbate stress, anxiety and depression leading to poorer health outcomes. It is therefore of great importance that healthcare professionals understand the extent to which pain, fatigue and sleep difficulties impact on patients' lives so that priority can be given to addressing these distressing symptoms as part of any management strategy. <h3>Disclosure of Interests:</h3> None declared
Abstract #5104: General down-regulation of the DWNN gene in human cancers
Authors: Zodwa Dlamini, Zukile Mbita
Journal: Cancer Research (2009)

Background:  DWNN gene is a gene that is also known as RbBP6 and has been implicated in cell cycle regulation and apoptosis. RbBP6 gene has been reported to possess a novel DWNN domain coding sequence at its 5\#8217; end; hence it is also called the DWNN gene. A mouse homologue of this gene has been implicated in mitotic apoptosis. In this study, the expression of the DWNN gene and its role in apoptosis was explored.  Methodology:  DWNN domain gene products were localized using  in situ  hybridization (ISH) and immunocytochemistry (ICC) to detect the DWNN mRNAs and proteins respectively. Polymerase Chain reaction was used to investigate the DWNN genotype in human cancers cell lines (MCF7, HeLa and HepG2 cells) in order to determine mutations in the gene. Western blotting was used to determine the nature of the DWNN in human cell lines. RNA interference and DWNN over-expression was used to determine the involvement of the DWNN in apoptosis and cell cycle regulation.  Results and Conclusion:  ISH and ICC showed that the DWNN is down-regulated in human cancers at both mRNA and protein levels respectively although cells showed that the expression of the DWNN gene products was high during the G2/Mitosis transition. Knocking down the DWNN domain did not sensitise the Hek 293 cells to Camptothecin-induced apoptosis. Also overexpression of the DWNN domain did not sensitise these cells to Camptothecin induced apoptosis. These results suggest that the DWNN gene is involved in cell cycle control. Up-regulation in mitotic cells and down-regulation in cancers also suggest that RbBP6 gene products are involved in cell cycle arrests. Down-regulation in cancers also suggests the lost of its function which correlates with loss of cell cycle control in this disease.     Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5104.
OP0338 LOW-DOSE IL-2 SELECTIVELY RESTORES REGULATORY T CELLS IN PATIENTS WITH BEHCET’S DISEASE
Authors: Xiaoqing Liu, Gaiqin Chai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The lack of CD4+CD25+Foxp3+ T regulatory cell (Treg) has been associated with human systemic autoimmune diseases, such as rheumatoid arthritis (RA). IL-2 is an essential growth and survival factor for Treg cells. However, the significance of Treg cells in the pathogenesis and the effect of low dose IL-2 on Behcet's disease (BD) are rarely reported. <h3>Objectives</h3> To investigate the significance of Treg cells and the effect of low dose IL-2 on BD. <h3>Methods</h3> Eighty patients with BD and seventy healthy donors were enrolled. CD4<sup>+</sup>T cell subsets in peripheral blood mononuclear cells from these people were measured by multicolour flow cytometry. Twenty-six patients were treated daily with subcutaneous injections of 0.5 million IU of human IL-2 for five consecutive days, CD4<sup>+</sup>T cell subsets were analysed before and after treatment by flow cytometry. <h3>Results</h3> Compared to health control, the absolute counts of circulating Treg cells were significantanty decreased in patients with BD (median:29.93 cells/ul VS median:33.16 cells/ul, <i>P</i>=0.039) and it is negative correlation with disease activity. While the ratios of Th17/Treg in patients with BD (median:0.29) were significantly higher than those of health control (median:0.2). No diffrernce in the absolute counts of circulating Th17 cells (CD4<sup>+</sup>IL-17<sup>+</sup>) between patients with BD and health control. Treatment of patients with BD with a low-dose IL-2 selectively increased the absolute counts of Treg cells, from a median of 18.97 cells/ul to 74.68 cells/ul (at 5 days) (<i>P&lt;</i>0.001). No significant difference was observed in the absolute counts of circulating Th17, Th1 and Th2 cells after IL-2 treatment. <h3>Conclusion</h3> Th17/Treg cells may play a role in the pathogenesis of patients with BD, low-dose IL-2 proposes a selective biological treatment strategy by restoring immune tolerance. <h3>References</h3> [1] Zeidan M J, Saadoun D, Garrido M, et al. Behcet's disease physiopathology: a contemporary review[J]. Auto Immun Highlights,2016,7(1):4. [2] Malek T R, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity[J]. Immunity,2010,33(2):153-165. [3] Klatzmann D, Abbas A K. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases[J]. Nat Rev Immunol,2015,15(5):283-294. <h3>Disclosure of Interests</h3> None declared
Cardiomyopathy Associated with Worsening Intravascular Hemolysis in Transgenic Knock-in Mouse Model of Sickle Cell Disease
Authors: Maureen Mburu, Rafey Feroze, Daniel Whitehurst, Xucai Chen, Samit Ghosh, Solomon Fiifi Ofori-Acquah, Flordeliza S Villanueva
Journal: Blood (2017)
Rapid expansion of immune-related gene families in the house fly, <i>Musca domestica</i>
Authors: Timothy B. Sackton, Brian P. Lazzaro, Andrew G. Clark
Journal: Molecular Biology and Evolution (2016)

The house fly, Musca domestica, occupies an unusual diversity of potentially septic niches compared with other sequenced Dipteran insects and is a vector of numerous diseases of humans and livestock. In the present study, we apply whole-transcriptome sequencing to identify genes whose expression is regulated in adult flies upon bacterial infection. We then combine the transcriptomic data with analysis of rates of gene duplication and loss to provide insight into the evolutionary dynamics of immune-related genes. Genes up-regulated after bacterial infection are biased toward being evolutionarily recent innovations, suggesting the recruitment of novel immune components in the M. domestica or ancestral Dipteran lineages. In addition, using new models of gene family evolution, we show that several different classes of immune-related genes, particularly those involved in either pathogen recognition or pathogen killing, are duplicating at a significantly accelerated rate on the M. domestica lineage relative to other Dipterans. Taken together, these results suggest that the M. domestica immune response includes an elevated diversity of genes, perhaps as a consequence of its lifestyle in septic environments.
Assessment of Machine Learning Detection of Environmental Enteropathy and Celiac Disease in Children
Authors: Sana Syed, Mohammad Al-Boni, Marium N. Khan, Kamran Sadiq, Najeeha T. Iqbal, Christopher A. Moskaluk, Paul Kelly, Beatrice Amadi, S. Asad Ali, Sean R. Moore, Donald E. Brown
Journal: JAMA Network Open (2019)

Duodenal biopsies from children with enteropathies associated with undernutrition, such as environmental enteropathy (EE) and celiac disease (CD), display significant histopathological overlap.To develop a convolutional neural network (CNN) to enhance the detection of pathologic morphological features in diseased vs healthy duodenal tissue.In this prospective diagnostic study, a CNN consisting of 4 convolutions, 1 fully connected layer, and 1 softmax layer was trained on duodenal biopsy images. Data were provided by 3 sites: Aga Khan University Hospital, Karachi, Pakistan; University Teaching Hospital, Lusaka, Zambia; and University of Virginia, Charlottesville. Duodenal biopsy slides from 102 children (10 with EE from Aga Khan University Hospital, 16 with EE from University Teaching Hospital, 34 with CD from University of Virginia, and 42 with no disease from University of Virginia) were converted into 3118 images. The CNN was designed and analyzed at the University of Virginia. The data were collected, prepared, and analyzed between November 2017 and February 2018.Classification accuracy of the CNN per image and per case and incorrect classification rate identified by aggregated 10-fold cross-validation confusion/error matrices of CNN models.Overall, 102 children participated in this study, with a median (interquartile range) age of 31.0 (20.3-75.5) months and a roughly equal sex distribution, with 53 boys (51.9%). The model demonstrated 93.4% case-detection accuracy and had a false-negative rate of 2.4%. Confusion metrics indicated most incorrect classifications were between patients with CD and healthy patients. Feature map activations were visualized and learned distinctive patterns, including microlevel features in duodenal tissues, such as alterations in secretory cell populations.A machine learning-based histopathological analysis model demonstrating 93.4% classification accuracy was developed for identifying and differentiating between duodenal biopsies from children with EE and CD. The combination of the CNN with a deconvolutional network enabled feature recognition and highlighted secretory cells' role in the model's ability to differentiate between these histologically similar diseases.
PB1847 CONGENITAL COMBINED DEFECTS OF COAGULATION FACTORS FVII AND FX: ABOUT A TUNISIAN FAMILY.
Authors: S. Maalej, F. Megdiche, M. Ghorbel, S. Kacem, O. Kassar, Y. Fakhfakh, F. Kotti, H. Chaabane, L. Mbarek, M. Elloumi, C. Kallel
Journal: HemaSphere (2019)

Background: Combined factor VII (FVII) and factor X (FX) deficiency is considered as an extremely rare bleeding disorder. Only a few cases have been reported all over the world. According to the WFH (World Federation of Hemophilia) 2014, the global populations’ prevalence of combined defects of coagulation factors (CDCF) is close to 1:2 000 000. These recessively inherited coagulation disorders, are usually associated with a high consanguinity's rate. Unfortunately, diagnosis is still underestimated, mainly due to the important heterogeneity of clinical and biological phenotypes which may induce difficulties in the disease's management in patients. Aims: The aim of this study was to report two cases presenting a combined FVII‐FX deficiency diagnosed in the South of Tunisia. Methods: Biological investigation included prothrombin time (PT), activated partial thromboplastin time, FVII and FX analysis by coagulometric methods and fibrinogen by the Clauss method. Results: An 11‐year‐old female was referred to our laboratory to realize routine screening tests before a tonsillectomy. Haemostasis has been checked and results showed a prolonged PT (PT = 45%, normal range:70‐100%) (aPTT and fibrinogen were normal), which prompted to realize further tests. Our patient, offspring of a consanguineous marriage, reported, since an early age, recurrent epistaxis and abundant gingivorrhagia. Laboratory analyses showed a combined FVII and FX deficiency with a mild decrease of both FVII and FX coagulant activities as follows: (FVII:C = 52%, normal range: 55‐170%) and FX:C = 36%, normal range: 70‐120%) which required a family screening. It was then revealed that she had an older sister (17 years old) with a combined FVII and FX deficiency (FVII:C = 53%, FX:C = 47%). Clinically, the sister presented gingivorrhagia since an early age. With regard to the parents, the plasma levels of the father revealed that he was probably a carrier of FX deficiency (FX:C = 51%) and he complained about gingivorrhagia and epistaxis too. However, the mother and two other sisters had normal coagulant activities and didn’t suffer from any abnormal bleeding disorder. Summary/Conclusion: In accordance with the recent reports, the presence of two clotting defects in a patient may cause diagnostic difficulties. For that, firstly, an acquired vitamin K deficiency should be excluded by getting normal clotting activities of both factors II and IX. Secondly, to avoid a misdiagnosis, it's recommended to investigate both FVII and FX in cases with prolonged PT, especially that patients belonging to the South of Tunisia are known by high rates of consanguineous marriages. Added to that, it's important to explore the mutational spectrum of F7 and F10 and its associated phenotypes in order to attest the combined defects and to guarantee a better genetic counselling.
Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts
Authors: Ela Elyada, Mohan Bolisetty, Pasquale Laise, William F. Flynn, Elise T. Courtois, Richard A. Burkhart, Jonathan A. Teinor, Pascal Belleau, Giulia Biffi, Matthew S. Lucito, Santhosh Sivajothi, Todd D. Armstrong, Dannielle D. Engle, Kenneth H. Yu, Yuan Hao, Christopher L. Wolfgang, Youngkyu Park, Jonathan Preall, Elizabeth M. Jaffee, Andrea Califano, Paul Robson, David A. Tuveson
Journal: Cancer Discovery (2019)

Cancer-associated fibroblasts (CAF) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we use single-cell RNA sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human and mouse PDAC tumors. We corroborate the presence of myofibroblastic CAFs and inflammatory CAFs and define their unique gene signatures in vivo. Moreover, we describe a new population of CAFs that express MHC class II and CD74, but do not express classic costimulatory molecules. We term this cell population "antigen-presenting CAFs" and find that they activate CD4+ T cells in an antigen-specific fashion in a model system, confirming their putative immune-modulatory capacity. Our cross-species analysis paves the way for investigating distinct functions of CAF subtypes in PDAC immunity and progression. SIGNIFICANCE: Appreciating the full spectrum of fibroblast heterogeneity in pancreatic ductal adenocarcinoma is crucial to developing therapies that specifically target tumor-promoting CAFs. This work identifies MHC class II-expressing CAFs with a capacity to present antigens to CD4+ T cells, and potentially to modulate the immune response in pancreatic tumors.See related commentary by Belle and DeNardo, p. 1001.This article is highlighted in the In This Issue feature, p. 983.
Abstract 14912: A Randomized Trial Using Mobile Short-Text Messaging to Improve Cardiovascular Risk Profile in Poorly Controlled Diabetes in Kenya
Authors: Gurveen Soin, Nancy Kunyiha, Jasmit Shah, Kinita Patel, Christopher Arisi, Erick Njenga, Mohamed Jeilan, Shaheed Sorathia, Leonard M Ngunga, Anders L Barasa
Journal: Circulation (2018)

Introduction: Cardiovascular disease (CVD) is a major cause of death in the diabetic population. Prevention strategies that target high-risk individuals are the most effective means of preventing a...
PB2171 THE COMPARISON OF THE RELATIONSHIP BETWEEN POLYNEUROPATHY FREQUENCY AND CLINICAL AND LABORATORY FINDINGS IN MULTIPLE MYELOMA CASES
Authors: A. Senturk Yikilmaz, S. Akinci, S. Bakanay, I. Dilek
Journal: HemaSphere (2019)

Background: Multiple myeloma (MM) patients compose approximately 10% of patients with hematological malignancies. Polyneuropathy (PN) is one of the most important complications related to the disease and treatment. Aims: Multiple myeloma (MM) patients compose approximately 10% of patients with hematological malignancies. Polyneuropathy (PN) is one of the most important complications related to the disease and treatment. Methods A total of 121 MM cases followed in the Hematology Clinic of Atatürk Training and Research Hospital between 2010‐2018 were included in the study. Electromyography results were evaluated retrospectively and clinical and laboratory findings were compared. Five cases with diabetes mellitus were excluded from the study. Chi‐square method was accepted as statistically significant p &lt;0.05. Results: The median age of the patients was 64.5 (min 39 max: 88), and Female/Male ratio was 51/65 (44%/65%). Demographic data of 28 (24.3%) patients with PN and 87 (75.7%) patients without PN were presented in Table 1. Renal function tests were normal in 64 (55.7%) of 87 patients without polyneuropathy (p = 0.005). There were 28 (23%) cases with extramedullary plasmacytoma larger than 1.5 cm which were detected by MR imaging at the time of diagnosis. In cases with extramedullary plasmacytoma, the prevalence of polyneuropathy was higher at the initial diagnosis (p = 0.012). Summary/Conclusion: There are publications in the literature showing that PN is associated with perineural and perivascular monoclonal immunoglobulin accumulation in MM. In our cases, there was no correlation between the presence of PN during diagnosis and the immunoglobulin subtype, but it was found to be related to the presence of renal dysfunction and the presence of extramedullary plasmacytoma. And we think that this result is the considerable. image