tbuckley/cabot-search huggingface dataset:
PB1727 OUTCOME OF CORE BINDING FACTOR ACUTE MYELOID LEUKEMIA IN ADULT PATIENTS
Authors: M. El Gammal, A. Mahmoud, M. Samra, A. Elnagar, N. El Shakankiry
Journal: HemaSphere (2019)

Background: Core binding factor acute myeloid leukemia (CBF AML) encodes two recurrent cytogentic abnormalities, t(8;21) and inv (16) and carries an overall good prognosis, yet some cases relapse . Aims: is to define unfavorable group of CBF AML by analysis of (C‐KIT and FLT3‐ITD) and to correlate with outcome of therapy. Methods: Prospective study started at Jan 2015 till June 2017, and included 70 patients CBF AML diagnosed and managed at medical oncology department of National Cancer Institute (NCI), Cairo University. All patients received standard of care protocol at NCI (“3+7”induction followed by 3‐4 courses of high dose cytarabine consolidation. The study was approved by the Institutional Review Board (IRB), of NCI, Egypt. Results: the median age was 31 years (18‐60, with a male/female ratio of 4/3. 42(60%) patients had t(8;21) and 28 patients had inversion 16(40%). C‐KIT mutations (exon 8 and exon 17) were detected in 10/52 tested patients and FLT3‐ITD was detected in 3/70 patients. While patients with Inv.16 had more lymphadenopathy and splenomegaly, median initial leucocytic count and exclusive gum hyperplasia, HCV‐Ab positivity (8/42) was exclusively present in patients with t(8;21). Clinically, lymphadenopathy, pallor and dyspnea were associated with worse overall survival (OS)(&lt;0.05). BM cellularity at day 28 of induction had a significant impact on survival (P = 0.002). Median OS was 19.5 month while median disease free survival (DFS) was not reached for the whole group. Patients with Inv.16 had non‐significant better DFS than patients with t(8;21)(P = 0.07). Neither C‐ KIT D816 V mutation nor FLT3‐ITD mutation had significant impact on OS or DFS, but when taken together (either C‐KIT or FLT3‐ITD mutant) had negative impact on DFS (P = 0.04). Summary/Conclusion: C‐KIT or FLT3‐ITD mutation had negative effect on DFS but not OS. HCV‐Ab positivity may be associated with t(8;21)AML, while Inv.16 is associated with more extramedullary disease image
Bronchodilator reversibility in asthma and COPD: findings from three large population studies
Authors: Christer Janson, Andrei Malinovschi, Andre F.S. Amaral, Simone Accordini, Jean Bousquet, A. Sonia Buist, Giorgio Walter Canonica, Barbro Dahlén, Judith Garcia-Aymerich, Louisa Gnatiuc, Marek L Kowalski, Jaymini Patel, Wan Tan, Kjell Torén, Torsten Zuberbier, Peter Burney, Deborah Jarvis
Journal: European Respiratory Journal (2019)

Bronchodilator response (BDR) testing is used as a diagnostic method in obstructive airway diseases. The aim of this investigation was to compare different methods for measuring BDR in participants with asthma and chronic obstructive pulmonary disease (COPD) and to study to the extent to which BDR was related to symptom burden and phenotypic characteristics.Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured before and 15 min after 200 μg of salbutamol in 35 628 subjects aged ≥16 years from three large international population studies. The subjects were categorised in three groups: current asthma (n=2833), COPD (n=1146) and no airway disease (n=31 649). Three definitions for flow-related reversibility (increase in FEV1) and three for volume-related reversibility (increase in FVC) were used.The prevalence of bronchodilator reversibility expressed as increase FEV1 ≥12% and 200 mL was 17.3% and 18.4% in participants with asthma and COPD, respectively, while the corresponding prevalence was 5.1% in those with no airway disease. In asthma, bronchodilator reversibility was associated with wheeze (OR 1.36, 95% CI 1.04-1.79), atopy (OR 1.36, 95% CI 1.04-1.79) and higher exhaled nitric oxide fraction, while in COPD neither flow- nor volume-related bronchodilator reversibility was associated with symptom burden, exacerbations or health status after adjusting for pre-bronchodilator FEV1Bronchodilator reversibility was at least as common in participants with COPD as those with asthma. This indicates that measures of reversibility are of limited value for distinguishing asthma from COPD in population studies. However, in asthma, bronchodilator reversibility may be a phenotypic marker.
CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data
Authors: Jonathan Cairns, Paula Freire-Pritchett, Steven W. Wingett, Csilla Várnai, Andrew Dimond, Vincent Plagnol, Daniel Zerbino, Stefan Schoenfelder, Biola-Maria Javierre, Cameron Osborne, Peter Fraser, Mikhail Spivakov
Journal: Genome biology (2016)

Capture Hi-C (CHi-C) is a method for profiling chromosomal interactions involving targeted regions of interest, such as gene promoters, globally and at high resolution. Signal detection in CHi-C data involves a number of statistical challenges that are not observed when using other Hi-C-like techniques. We present a background model and algorithms for normalisation and multiple testing that are specifically adapted to CHi-C experiments. We implement these procedures in CHiCAGO ( http://regulatorygenomicsgroup.org/chicago ), an open-source package for robust interaction detection in CHi-C. We validate CHiCAGO by showing that promoter-interacting regions detected with this method are enriched for regulatory features and disease-associated SNPs.
PF317 ELEVATION OF SERUM IL‐10 IS ASSOCIATED WITH ADVERSE CLINICAL OUTCOMES IN PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMA WHO WERE TREATED WITH R‐CHOP
Authors: J.H. Yi, S.E. Yoon, Y.H. Ko, W.S. Kim, S.J. Kim
Journal: HemaSphere (2019)

Background: Cytokines are one of the major non‐cellular component of tumor microenvironment, and they act as messengers between malignant cells and the cellular component of tumor microenvironment to promote cancer cell proliferation and to evade immune surveillance. While the role of cytokine had been widely investigated in patients with DLBLC, their impacts on secondary CNS involvement had rarely been reported. Aims: To address prognostic roles of serum cytokines regarding the OS and CNS events in DLBCL patients. Methods: Patients out of our prospective cohort study (NCT#00822731) who met the following criteria were included in the present study. 1) Patients with newly diagnosed, histologically confirmed DLBCL, other than primary CNS lymphoma; 2) Patients who were treated with R‐CHOP as the first‐line treatment; 3) Patients whose serum samples were collected. The clinical data of patients were collected. Serum levels of IL‐2, IL‐6, IL‐10, IL‐21, CXCL10, CCL3, CCL5, PAI‐1, survivin, and TNFα were measured. The primary end‐point of the current study was estimated 3‐year overall survival (OS) rate, and the secondary end‐point was time to secondary CNS involvement Results: A total of 313 patients were eligible for the analysis. The median age was 56 years (range, 16 to 86 years) and 177 patients (57%) were male. The 3‐year OS rate was 73.6% ( ± 2.5%), and all the factors in IPI significantly discriminated the OS. Six cytokines were correlated with the 3‐year OS rate (FIGURE). Time to CNS involvement was assess in 294 patients, and 16 events (5.4%) of secondary CNS involvement were detected. Only one cytokine could predict it, as patients with elevated IL‐10 was associated with significantly short time to CNS involvement compared to patients without IL‐10 elevation (p = 0.012). While only 1 out of 99 patients (1.0%) without IL‐10 elevation developed secondary CNS involvement, 15 out of 195 patients (7.7%) with IL‐10 elevation developed secondary CNS involvement (p = 0.017). Of note, among 19 patients who initially had CNS involvement, 14 patients (74%) had elevated serum IL‐10. Summary/Conclusion: We have found that elevation of CCL3, CCL5, CXCL10, IL‐6, IL‐10, and survivin were associated with inferior 3‐year OS rate, and elevation of IL‐10 was associated with short time to secondary CNS involvement. Considering their biologic roles in lymphomagenesis, further studies are required to incorporate these results to conventional prognostic factors to better predict outcomes of patients with DLBCL image
PB2186 IMPACT OF CYTOGENETIC ABNORMALITIES ON RESPONSE IN A COHORT OF INDIAN MULTIPLE MYELOMA PATIENTS–IS 13Q DELETION THE NEW 17P IN DISGUISE?
Authors: S. P. Mirgh, M. Mahapatra, T. Seth, R. Dhawan, M. Aggarwal, R. Saxena, H. Pati, S. tyagi, S. Kothari, R. Halder
Journal: HemaSphere (2019)

Background: R‐ISS (Revised International Staging System) incorporates cytogenetic abnormalities for risk stratification of multiple myeloma. High‐risk cytogenetic abnormalities in R‐ISS include 17p deletion, t(4;14),t(14;16). Detection of these abnormalities by interphase FISH (Fluorescence in‐situ hybridisation) has become a popular modality owing to its targeted detection ability in non‐mitotic cells. Aims: The aim of this study was to observe the frequency of cytogenetic abnormalities in the Indian setting and their co‐relation with treatment outcomes. Methods Retrospective single‐centre study conducted at a single tertiary care centre from North India. Multiple myeloma FISH panel comprising of 5 abnormalities ‐ 13q deletion, 17p deletion, t(4;14), t(11;14), t(14;16) were done in all patients with multiple myeloma, either at diagnosis or when they were referred for relapse or progression of disease. Records of patients in the last two years (January 2016 ‐July 2018) were analysed. Results: Over a period of 30months, myeloma FISH panel was done in 49 patients. Of these, abnormalities were detected in 52% (n = 25) patients. 90% patients belonged to ISS stage‐3. FISH panel was done at diagnosis, first relapse and disease progression in 77.5% (n = 38), 7.3% (n = 3) and 19.5% (n = 8), respectively. The most common abnormality was 13q deletion (36.7%). 17p deletion,t(4;14) and t(11;14) were seen in 8.2%(n = 4),4%(n = 2) and 2.4% (n = 1) patients, respectively. Response to treatment could be evaluated in 46 patients which was graded as per IMWG (International Myeloma Working Group) response criteria. The overall response rate (CR/VGPR/PR) of patients in different groups–Normal, 13q deletion, 17p deletion was 79.2%, 50%, 50% respectively. This implied that nearly half of the patients (n = 8) in 13q deletion group did not respond to therapy. Of these, 4 patients (50%) had 13q deletion at baseline. The possible reasons for this may be ‐ detection of 13q deletion in relapsed/refractory patients, concomitant t(4;14) on FISH panel, associated 13q deletion detection on conventional karyotyping and lack of 1q amp detection in our panel which could have let to an unfavourable outcome. Summary/Conclusion: IgH translocations are rare in Indian patients. 13q deletions, akin to the 17p group, are associated with high beta‐2 microglobulin levels (ISS‐3), poor responses to bortezomib based therapy and are seen on disease progression.
PB1731 ELEVATED FETAL HEMOGLOBIN (HBF) IN ELDERLY AML PATIENTS RECEIVING HYPOMETHYLATING AGENTS: ENHANCEMENT OF HBF INDUCTION BY RETINOIC ACID?
Authors: J. Stomper, E. Bissé, M. Lübbert
Journal: HemaSphere (2019)

Background: We recently reported elevation of fetal hemoglobin (HbF) as a potential predictor of outcome in elderly AML/MDS patients treated with DNA‐hypomethylating agents (HMA). HbF elevation prior to decitabine (DAC) treatment (Lübbert et al., Br. J. Haematol. 2017; 176:609‐617) as well as HbF induction following 2 courses of DAC treatment (Stomper et al., Haematologica 2019; 104:59‐69) were associated with superior outcome of AML/MDS patients. Interestingly, HbF elevation was shown to be associated with cytogenetic remissions and to be reversed at relapse, suggesting that HbF is preferentially induced in non‐clonal erythroid cells during HMA therapy. Preclinical work suggests that epigenetically active agents such histone deacetylase inhibitors (HDACi) can be combined with retinoic acid to induce HbF. Aims: We now investigated the effect of the add‐on drugs all‐ trans retinoic acid (ATRA) and valproic acid (VPA, an HDACi) on HbF induction during DAC treatment in AML patients. Methods: The DECIDER trial addresses the effects of the add‐on of ATRA or VPA to DAC (Grishina et al., BMC Cancer 2015; 15:430). We serially studied HbF levels in 16 AML patients ≥60 years old that received &gt;2 cycles of treatment within the DECIDER trial. Four patients received only DAC, 5 patients DAC+VPA, 5 patients DAC+ATRA, and 2 patients DAC+VPA+ATRA. HbF levels were measured in peripheral blood erythrocytes by HPLC before treatment and sequentially, i.e. after the end of each treatment course. HbF &gt;1.0% was considered induced. Results: In this albeit small cohort, continued treatment appeared to result in variations in maximally attained levels of HbF depending on the type of drug add‐on. As to VPA, the median peak HbF level attained was 1.5% (range, 0.4 ‐ 5.0%) in 9 patients not having received VPA compared to 1.0% (range, 0.2 ‐ 4.8%) in 7 patients having received VPA. The median peak HbF level in the absence of ATRA (9 patients) was 0.8% (range, 0.2 ‐ 2.8%) compared to 2.1% (range, 0.3 ‐ 5.0 %) in 7 patients having received ATRA. Summary/Conclusion: Given that the add‐on of ATRA (but not VPA) to DAC resulted in superior outcome (Lübbert et al., ASH 2016), these preliminary results suggesting a higher induction of HbF in the presence of ATRA warrant prospective, serial HbF determinations in a planned randomized validation trial. Also, RNA‐sequencing studies in AML cell lines treated with DAC ‐/+ ATRA are addressing de‐repression of the gamma‐globin locus in vitro.
AB1272 TREATMENT OF RHEUMATOID ARTHRITIS WITH EXTENSION OF THE ANTI-TNF INTERDOSE INTERVALS. A MONOCENTRIC OFF-LABEL STUDY
Authors: Evripidis Kaltsonoudis, Eleftherios Pelechas, Paraskevi V. Voulgari, Alexandros Drosos
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Since the advent of anti-TNFs a revolution has been established in the treatment of Rheumatoid Arthritis (RA). <h3>Objectives:</h3> To evaluate the ability to safely extend the interdose intervals of the anti-TNFs in RA patients. <h3>Methods:</h3> Eighty-six patients with early RA fulfilling the ACR/EULAR classification criteria were included and followed-up at predefined times. All patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) plus an anti-TNF. At every visit, the disease activity score using the 28-joint count (DAS-28) as well as all the drug-related laboratory parameters were recorded. Clinical remission was defined as DAS-28 &lt;2.6 for ≥12 months. RA patients in clinical remission had the possibility to extend interdose intervals. <h3>Results:</h3> A total number of 57 females and 29 males (mean age: 62.7±4.1 years; disease duration: 14.9±2.4 months) were included. 76 patients were in clinical remission, while 10 were in low disease activity. From those in clinical remission, 40 patients received adalimumab (ADA), 23 etanercept (ETN) and 13 golimumab (GOL). Regarding the extension of the interdose intervals, 29 patients were on ADA every 21 days, 11 every 30 days. Regarding the extension of the interdose intervals in patients receiving ETN: 15 patients were on ETN every 10 days, 8 every 15 days. Finally, 6 patients were on GOL at a dose interval of 35 days, 4 every 40 days, 3 every 45 days. Young, female and seronegative patients treated early with an anti-TNF had more chances of extending the interdose interval. <h3>Conclusion:</h3> We found that the extension of the interdose intervals of the anti-TNFs is a feasible option in early RA patients and it reflects not only significant clinical benefits for the patient but also economic benefits for the healthcare systems. <h3>Disclosure of Interests:</h3> None declared
Distinct subtypes of diffuse large B-cell lymphoma defined by hypermutated genes
Authors: Amjad Alkodsi, Alejandra Cervera, Kaiyang Zhang, Riku Louhimo, Leo Meriranta, Annika Pasanen, Suvi-Katri Leivonen, Harald Holte, Sirpa Leppä, Rainer Lehtonen, Sampsa Hautaniemi
Journal: Leukemia (2019)
Programmed Death-1 or Programmed Death Ligand-1 Blockade in Patients with Platinum-resistant Metastatic Urothelial Cancer: A Systematic Review and Meta-analysis
Authors: Scot A. Niglio, Rachel Jia, Jiayi Ji, Samuel Ruder, Vaibhav G. Patel, Alberto Martini, John P. Sfakianos, Kathryn E. Marqueen, Nikhil Waingankar, Reza Mehrazin, Peter Wiklund, William K. Oh, Madhu Mazumdar, Bart S. Ferket, Matthew D. Galsky
Journal: European Urology (2019)
AB0588 GASTROINTESTINAL INVOLVEMENT OF BEHCET’S DISEASE IN RUSSIA
Authors: Regina Goloeva, Zemfira Alekberova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Behcet's disease (BD) is a multisystem vasculitis with unknown etiology and a unique geographical distribution. Intestinal manifestations of BD (IBD) are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. <h3>Objectives:</h3> To analyze the severity and clinical features IBD in Russia <h3>Methods:</h3> The study included 250 patients (male – 177, female – 73) with BD (according to ISGBD 1990 and ICBD criteria 2014). The male-to-female ratio was 2,4:1, the mean age was 31,5±9,3 yrs, the age of disease onset - 21.8±9.62 yrs, the median of disease duration - 10.25±8.32 yrs. All those with gastrointestinal symptoms were subject to a gastroscopy and/or colonoscopy through which Crohn's disease and ulcerative colitis were excluded by the proctologists. <h3>Results:</h3> Patients with gastrointestinal symptoms were 63 of 250 - 25.2% pts, (male – 40, female – 23). Symptoms of IBD include the abdominal pain in 62% pts, distension –55%, diarrhea – 14%, nausea – 13%, blood in the bowel movement – 4,7%. The examination revealed: esophageal ulcers (1.6%, four cases), gastric ulcers (3.2%, eight cases), and duodenal ulcers (1.2%, three cases) were found using endoscopy. Also, 6.8% (17 patients) had gastro duodenal ulcers and 14.3% (nine patients) combined gastrointestinal involvement including esophageal and had gastro duodenal ulcers. Colonic ulcers were detected in 9.2% (23 cases) by colonoscopy, two patients had multisegmental diffuse ulceration, three patients had in the sigmoid colon and of everyone else in the ileum. Ccolitis without ulcers found in 5,6% (14 cases). Two patients had a clinic of appendicitis, the operation found that the appendix is not inflamed. Two patients were 0.8% (were on treatment) urgently operated due to perforation of ulcers of the ileum, the woman held suturing of perforated ulcer, and a man - hemicolectomy. The last patient has a relaparotomy after 1 month and removal of the entire colon. <h3>Conclusion:</h3> The IBD in Russia is affected in 1/4 of patients, but heavy refractory forms not often. <h3>Disclosure of Interests:</h3> None declared
Abstract 17173: Impact of Geometry and Cell Density on Structural and Functional Maturation in Large-format Mesh Engineered Cardiac Tissues Generated From Human iPS Cells
Authors: Takeichiro Nakane, Hidetoshi Maumoto, Joseph P Tinney, Fangping Yuan, William J Kowalski, Fei Ye, Kenji Minakata, Tadashi Ikeda, Ryuzo Sakata, Jun K Yamashita, Bradley B Keller
Journal: Circulation (2016)

Background: Linear-shaped engineered cardiac tissues (ECTs) from human iPSC-derived cardiovascular cells demonstrate therapeutic and myocardial regenerative potential in rat MI models; however, thi...
Reanalysis of Clinical Exome Sequencing Data
Authors: Pengfei Liu, Linyan Meng, Elizabeth A Normand, Fan Xia, Xiaofei Song, Andrew Ghazi, Jill Rosenfeld, Pilar L Magoulas, Alicia Braxton, Patricia Ward, Hongzheng Dai, Bo Yuan, Weimin Bi, Rui Xiao, Xia Wang, Theodore Chiang, Francesco Vetrini, Weimin He, Hanyin Cheng, Jie Dong, Charul Gijavanekar, Paul J Benke, Jonathan A Bernstein, Tanya Eble, Yasemen Eroglu, Deanna Erwin, Luis Escobar, James B Gibson, Karen Gripp, Soledad Kleppe, Mary K Koenig, Andrea M Lewis, Marvin Natowicz, Pedro Mancias, LaKeesha Minor, Fernando Scaglia, Christian P Schaaf, Haley Streff, Hilary Vernon, Crescenda L Uhles, Elaine H Zackai, Nan Wu, V Reid Sutton, Arthur L Beaudet, Donna Muzny, Richard A Gibbs, Jennifer E Posey, Seema Lalani, Chad Shaw, Christine M Eng, James R Lupski, Yaping Yang
Journal: New England Journal of Medicine (2019)

Reanalysis of Clinical Exome Data and Diagnostic Yield As knowledge about genetic causes of disease improves, periodic reanalysis of clinical exome sequence could yield new genetic information. Thi...
Mid‐regional pro‐atrial natriuretic peptide for the early detection of non‐acute heart failure
Authors: Aisha Gohar, Frans H. Rutten, Hester den Ruijter, Johannes C. Kelder, Stephan von Haehling, Stefan D. Anker, Martin Möckel, Arno W. Hoes
Journal: European Journal of Heart Failure (2019)
MATCHER: manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics
Authors: Joshua D. Welch, Alexander J. Hartemink, Jan F. Prins
Journal: Genome biology (2017)

Single cell experimental techniques reveal transcriptomic and epigenetic heterogeneity among cells, but how these are related is unclear. We present MATCHER, an approach for integrating multiple types of single cell measurements. MATCHER uses manifold alignment to infer single cell multi-omic profiles from transcriptomic and epigenetic measurements performed on different cells of the same type. Using scM&T-seq and sc-GEM data, we confirm that MATCHER accurately predicts true single cell correlations between DNA methylation and gene expression without using known cell correspondences. MATCHER also reveals new insights into the dynamic interplay between the transcriptome and epigenome in single embryonic stem cells and induced pluripotent stem cells.
The European Alpha-1 antitrypsin Deficiency Research Collaboration (EARCO). A new ERS Clinical Research Collaboration to promote research in alpha-1 antitrypsin deficiency
Authors: Marc Miravitlles, Joanna Chorostowska-Wynimko, Ilaria Ferrarotti, Noel G McElvaney, Karen O’Hara, Jan Stolk, Robert A Stockley, Alice Turner, Marion Wilkens, Timm Greulich
Journal: European Respiratory Journal (2019)
Mutational Biases Influence Parallel Adaptation
Authors: Arlin Stoltzfus, David M. McCandlish
Journal: Molecular Biology and Evolution (2017)

While mutational biases strongly influence neutral molecular evolution, the role of mutational biases in shaping the course of adaptation is less clear. Here we consider the frequency of transitions relative to transversions among adaptive substitutions. Because mutation rates for transitions are higher than those for transversions, if mutational biases influence the dynamics of adaptation, then transitions should be overrepresented among documented adaptive substitutions. To test this hypothesis, we assembled two sets of data on putatively adaptive amino acid replacements that have occurred in parallel during evolution, either in nature or in the laboratory. We find that the frequency of transitions in these data sets is much higher than would be predicted under a null model where mutation has no effect. Our results are qualitatively similar even if we restrict ourself to changes that have occurred, not merely twice, but three or more times. These results suggest that the course of adaptation is biased by mutation.