tbuckley/cabot-search huggingface dataset:
PB2417 SPECTRUM OF HAEMOGLOBINOPATHIES;A TERTIARY CARE HOSPITAL EXPERIENCE
Authors: N. Fareed, G. Fatima, M. Quraishy
Journal: HemaSphere (2019)

Background: Inherited abnormalities of hemoglobin synthesis include a myriad of disorders ranging from thalassemia syndromes to structurally abnormal hemoglobin variants. Identification of these disorders is immensely important epidemiologically and aid in prevention of more serious hemoglobin disorders. Aims: This study presents the pattern of haemoglobinopathies amongst the referred patients of anaemia in a 1 year period, it helps to identify the cases of different hemoglobin disorders. Methods: Inherited abnormalities of hemoglobin synthesis include a myriad of disorders ranging from thalassemia syndromes to structurally abnormal hemoglobin variants. Identification of these disorders is immensely important epidemiologically and aid in prevention of more serious hemoglobin disorders. Results: Out of 747 cases, 558 (74.6%) were normal and 189 (25.3%) cases had abnormal haemoglobin pattern. 356 (47.6%) were males and 391 (52.3%) were females. Of all cases of Anaemia 278 (49.8%) were microcytic hypochromic, 22 (3.9%) macrocytic and the rest 258 (46.2%) had normocytic normochromic picture. Of the 189 abnormal cases, Spectrum of haemoglobinopathies prevalent were Beta Thalassemia trait 117 (61.9%), followed by Beta thalassaemia major 27 (14.2%). Other haemoglobinopathies in descending order of frequency were sickle cell disease 15 (7.9%), Hb D Disease 16 (8.4%), sickle cell trait 01 (0.5%), Sickle/beta thalassaemia in 02 (1.0%) and Hb E in 04 (2.1%). Summary/Conclusion: Our study showed higher frequency of Beta Thalassaemia trait. It is suggested that detection of HbA2 should be carried out in all the high‐risk groups with anaemia. Further larger studies are needed to screen our population to detect thalassaemia carrier state and Iron deficiency Anaemia.
Abstract 15350: Dietary Omega-3 Fatty Acids and Fiber Intake Increase Adiponectin Levels in African American Adults With Metabolic Syndrome
Authors: Erin P Ferranti, Brittany Butts, Carolyn M Reilly, Sandra B Dunbar
Journal: Circulation (2015)

Introduction and Purpose: Adiponectin is a key peptide involved in the relationship between adiposity, insulin resistance and inflammation. Lower plasma levels are associated with metabolic syndrome (MetS), type 2 diabetes mellitus, and coronary artery disease. African Americans (AA) have lower levels of adiponectin compared to other racial/ethnic groups. While clinical trials have examined the effects of dietary intake of omega-3 fatty acids, fiber, and other nutrients on adiponectin levels and metabolic risk, few studies have examined these relationships in AA adults. The purpose of this study is to examine the relationship between dietary factors and adiponectin in AA adults with MetS. Methods: This analysis is of baseline data from a larger, longitudinal lifestyle intervention study in AA adults with metabolic syndrome. Dietary intake was assessed with the 2005 Block Food Frequency Questionnaire. Plasma adiponectin was measured by ELISA. Analysis included descriptive statistics, correlations and multiple regression. Results: Seventy-four participants, 50.5±9.1 years of age, 77% female, were included in this analysis. Most participants (N=62, 85%) were obese, with mean BMI 35.6±6.3 and mean waist-hip ratio (W:H) 0.95±.05 for males and 0.88±.08 for females. Mean omega-3 intake was .77±0.5g and fiber intake was 15.47±7.9g. Adiponectin was higher in females than males (7.7±4.0 vs 5.4±3.3, t=-2.8, p=.007) and negatively associated with W:H (r=-.20, p=.03). Adiponectin had a positive linear relationship with omega-3 (R2=.235, p=.003) and fiber (R2=.201, p=.015) intake, controlling for gender and W:H. These relationships are consistent with studies in other ethnic groups. Conclusion: Higher adiponectin levels are protective with metabolic risk factors, particularly central adiposity. Increased consumption of omega-3 fatty acids and fiber is associated with higher levels of adiponectin and may confer risk protection in AA adults with MetS. Culturally tailored strategies aimed at improved dietary quality, particularly focused on increasing dietary intake of omega-3 fatty acids and fiber are warranted.
Characterization of the cellular immune response in hepatitis C virus infection
Authors: Xinjian Zhang, Jun Dou, Markus W. Germann
Journal: Medicinal Research Reviews (2009)

Abstract Hepatitis C virus (HCV), a hepatotropic RNA virus, is a major causative agent of chronic hepatitis, liver cirrhosis, and hepatocellular carcinomas. The host immune responses, especially cellular immune responses, play an important role in viral clearance, liver injury, and persistent HCV infection. A thorough characterization of the HCV cellular immune responses is important for understanding the interplays between host immune system and viral components, as well as for developing effective therapeutic and prophylactic HCV vaccines. Recent advances that provide better understanding the cell immune responses in HCV infection are summarized in this article. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 6, 843–866, 2009
Abstract 15191: Left Atrial Volume as an Independent Predictor of Congestive Heart Failure in Patients With Atrial Fibrillation
Authors: Yoshinobu Suwa, Yoko Miyasaka, Satoshi Tsujimoto, Hirofumi Maeba, Ichiro Shiojima
Journal: Circulation (2015)

Backgound: Left atrial (LA) enlargement has been proposed as a barometer of diastolic dysfunction and a predictor of congestive heart failure (CHF) in patients with sinus rhythm. Whether LA volume predicts CHF in patients with atrial fibrillation (AF) is not well known. Methods: To determine the clinical importance of LA volume in the prediction of CHF in patients with AF, AF patients referred for clinically-indicated echocardiogram, without a history of significant mitral valve disease, congenital heart disease, pacemaker, or cardiac surgery, in 2007-2008 were prospectively included and followed forward them up to September 2014. LA volume was measured using the biplane area-length formula. CHF was ascertained using the Framingham criteria. Cox proportional hazards modeling was used to assess the risk factors of CHF development. Results: Of 456 AF patients who met all study criteria (mean 70 ± 10 year-old, 67% men, 62% hypertension, 26% diabetes, LV ejection fraction 68 ± 13%, LA volume 52 ± 24 mL/m 2 ), 46 (10%) developed CHF events during a mean follow-up of 44 ± 31 months. CHF events were significantly increased with advancing age (HR 1.4, 95%CI 1.0-2.0, P&lt;0.05), but not with sex. In a multivariate Cox proportional hazards model, greater indexed LA volume (per 10 mL/m 2 ; HR 1.2, 95% CI 1.1-1.3, P&lt;0.01) was independent of age (HR 1.04, 95% CI 1.01-1.07, P=0.03), sex (P=0.77), history of CHF (P=0.58), hypertension (P=0.38), diabetes (P=0.89), and LV ejection fraction (HR 0.95, 95% CI 0.93-0.96, P&lt;0.001) for the prediction of CHF development. The Kaplan-Meier estimate of cumulative CHF-free survival by indexed LA volume was shown (Fig.). Conclusions: In our cohort with AF, LA volume predicted CHF developments, independent of LV systolic function and other cardiovascular comorbidities, which appears to be clinically useful information for risk stratification.
PB1854 MYELOFIBROSIS DUE TO SEVERE VITAMIN D DEFICIENCY RICKETS
Authors: Y. El Chazli, B. Eldomiaty, N. Balbaa, E. Hassan, N. Mikhael, S. Elsayed, Y. Abdelmeguid, D. Fawzy
Journal: HemaSphere (2019)

Background: The association between severe active infantile rickets and myelofibrosis has been reported as Von Jaksch's anemia since 1937. Vitamin D deficiency rickets is a common condition in infants and children of developing countries including Egypt. Despite this fact only 26 patients with myelofibrosis due to severe vitamin D deficiency rickets have been reported in the literature worldwide and none from Egypt. Aims: To report cases of myelofibrosis due to severe vitamin D deficiency rickets and to highlight the importance of considering this rare condition in the differential diagnosis of hypochromic microcytic anemia with splenomegaly in infants. Methods: retrospective description of patients diagnosed as myelofibrosis due to severe vitamin D deficiency rickets for a 6 month period at the Alexandria University Children's Hospital. After taking informed consent from their legal guardians, patients have been subjected to history taking, clinical examination, and laboratory investigations including bone marrow biopsy (BMB). Results: Five patients have been included. Four males and one female, with an age ranging from 6 to 22 months at presentation. They presented with clinical signs of active rickets (wide anterior fontanel, frontal bossing, rachitic rosaries, and hypotonia). They all had an enlarged spleen by examination, confirmed by ultrasonography. Their blood picture showed a hypochromic microcytic anemia (Hb 5 to 8.6 g/dL) with normoblasts, anisopoikilocytosis, teardrops and pencil cells, thrombocytopenia (platelet count 25 to 132 x10 3 cell/cmm, normal in one patient) and a normal white cell count showing monocytosis and immature forms (promyelocytes, myelocytes and band cells). Their chemistry was significant for low calcium, low phosphorus and very high alkaline phosphatase (ALP 922 ‐ 4678 U/L). Bone marrow was done and showed thickened trabeculae and increased bone marrow fibrosis using reticulin stain (picture). Unfortunately, the patients presenting with a symptomatic anemia had a packed red cells transfusion. All patients have been started on therapeutic doses of Vitamin D with rapid correction of their blood counts and gradual normalization of their chemistry parameters. Summary/Conclusion: It is important to raise clinicians’ awareness to such a rare but yet easy to diagnose condition to avoid unnecessary transfusions and investigations and delays in treatment. The treatment of myelofibrosis due to severe vitamin D deficiency rickets is very simple and effective. image
Abstract 17651: Increased Dipeptidyl Peptidase-4 Accelerates Diet-Related Vascular Aging and Atherosclerosis in ApoE-Deficient Mice under Chronic Stress
Authors: Yanna Eli, Guang Yang, Aiko Inoue, Limei Piao, Takeshi Sasaki, Masafumi Kuzuya, Xian Wu Cheng
Journal: Circulation (2017)

Background: Exposure to psychosocial stress is a risk factor for cardiovascular disease. Objectives: Given that dipeptidyl peptidase-4 (DPP4) regulates several intracellular signaling pathways asso...
PF254 RESULTS FROM THE FIRST‐IN‐HUMAN STUDY OF MIVEBRESIB (ABBV‐075), A PAN‐INHIBITOR OF BROMODOMAIN AND EXTRA TERMINAL PROTEINS, IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA
Authors: G. Borthakur, O. Odenike, J.E. Wolff, I. Aldoss, D. Rizzieri, T. Prebet, B. Hu, M.H. Dinh, X. Chen, D.A. Modi, K.J. Freise, B.A. Jonas
Journal: HemaSphere (2019)

Background: Bromodomain and extra‐terminal (BET) proteins bind to acetyllysines and upregulate oncogenic target genes. Mivebresib (ABBV‐075) is a pan‐BET inhibitor with antitumor activity in vitro and xenograft models of AML. This 2‐part phase 1 study evaluates the safety and pharmacokinetics of mivebresib at monotherapy or combination dosing schedules in patients with solid tumors (part 1) and acute myeloid leukemia (AML; part 2) (NCT02391480). Aims: Here, we report preliminary data from part 2 in patients with relapsed/refractory (RR) AML. Methods: Mivebresib monotherapy (MIV‐mono), or combined with venetoclax (MIV‐VEN), were administered daily to adult patients with AML. The dose‐limiting toxicity (DLT) period was 28 d. Results: As of Dec 2018, 41 patients (median age: 69 y [range, 29–84]; 19 patients had &gt;2 prior therapies) were enrolled: 19 in MIV‐mono (5 of whom switched to MIV‐combo) and 22 who began treatment in MIV‐VEN cohorts. 23 patients had high cytogenetic risk. Median time on treatment was 28 d (range, 8–562). There were no DLTs. All patients experienced a treatment‐emergent adverse event (AE), most commonly (≥40% patient incidence), fatigue (56%), dysgeusia (46%), decreased appetite (44%), diarrhoea (42%), nausea (42%), vomiting (42%). 40 patients had grade ≥3 AEs (febrile neutropenia (37%), anemia (34%) and thrombocytopenia (32%). 33 patients had serious AEs, most commonly febrile neutropenia (19%). 25 deaths were reported; 15 patients died of causes unrelated to mivebresib and 10 patients due to AML progression. The median best % bone marrow blast change for 26 evaluable patients was −20% (range, −98% to +300%). Gene expression analysis in pre‐ and post‐treatment peripheral blood samples showed that HEXIM1, DCXR and CD93 genes were reliable PD biomarkers of ABBV‐075 which were consistently modulated in a dose‐dependent manner. At the cutoff date, median overall survival for all patients was 2.6 m. Summary/Conclusion: Mivebresib was well tolerated and showed antileukemic effects in patients with RR AML.
AB0623 ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS AND RISK OF CEREBROVASCULAR ACCIDENT: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Patompong Ungprasert, Karn Wijarnpreecha, Wisit Cheungpasitporn
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> An increased risk of cardiovascular disease, including cerebrovascular accident (CVA), among patients with chronic inflammatory immune-mediated disorders is well-recognized, especially among patients with rheumatoid arthritis and systemic lupus erythematosus [1]. Patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) may be at an increased risk of CVA as well although the data are still inconclusive as most studies addressing this association were small in size. <h3>Objectives:</h3> The current systematic review and meta-analysis was conducted with the aims to comprehensively identify all relevant studies and summarize their results together to better characterize the risk of CVA among patients with aAV. <h3>Methods:</h3> Two investigators independently searched for published studies indexed in MEDLINE and EMBASE database from inception to October 2018 using the search strategy that included the terms for anti-neutrophil cytoplasmic antibody-associated vasculitis and cerebrovascular accident. Eligible studies must be cohort studies (either retrospective or prospective) that compared the risk of incident CVA between patients with aAV and individuals without aAV. They must also report the relative risk or hazard ratio with 95% confidence interval (CI) of this comparison. Point estimates and standard errors from each study were extracted and combined together using the random effect, generic inverse variance technique of DerSimonian and Laird. <h3>Results:</h3> A total of 5 studies fulfilled the inclusion criteria and were included in this meta-analysis. The risk of incident CVA among patients with aAV was significantly higher than individuals without aAV with the pooled risk ratio of 1.49 (95% CI, 1.06–2.10). The statistical heterogeneity was insignificant with an I<sup>2</sup> of 11%. The forest plot of this meta-analysis is shown as figure 1. The funnel plot of this study was relatively symmetric and did not suggest the presence of publication bias. <h3>Conclusion:</h3> A significantly increased risk of CVA among patients with aAV was demonstrated by this meta-analysis. Physicians who take care of patients with aAV should be aware of this risk and focus on interventions to modify other conventional risk factors for CVA may be warranted. <h3>References</h3> [1] Hintenberger R, et al. Cardiovascular disease in patients with autoinflammatory syndromes. Rheumatol int. 2018;38:37-50. <h3>Disclosure of interests:</h3> None declared
FRI0045 CHANGES IN LEFT VENTRICULAR SYSTOLIC FUNCTION ARE PREDICTED BY DISEASE SEVERITY IN PATIENTS WITH RHEUMATOID ARTHRITISWITHOUT PRIOR CARDIOVASCULAR DISEASE
Authors: Alessandro Giollo, Giovanni Cioffi, Giovanni Orsolini, Luca Idolazzi, Antonio Carletto, Andrea Dalbeni, Federica Ognibeni, Elena Fracassi, Davide Gatti, Maurizio Rossini, Ombretta Viapiana
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Occult left ventricular (LV) systolic dysfunction (LVSD) is associated with worse cardiovascular outcomes in asymptomatic patients with arterial hypertension and/or diabetes mellitus. In these patients, LV systolic function may worsen or improve overtime. However, little is known about the changes in LV function during follow up of patients with rheumatoid arthritis (RA). <h3>Objectives</h3> This prospective study analyzed incidence and factors associated with changes in LV systolic function in patients with RA without known cardiovascular disease. <h3>Methods</h3> One-hundred-forty outpatients with RA without overt cardiac disease were recruited between March and December 2014. Patients underwent clinical and echocardiographic evaluation at baseline and after a median period [min-max] of 35 [23-47] months of follow up. Stress-corrected midwall fractional shortening (sc-MFS) was used as measure of LVSD and considered impaired if &lt;86.5%. Disease activity was assessed with the clinical disease activity index (CDAI). <h3>Results</h3> Impaired sc-MFS at follow up (sc-MFS-FU) was detected in 60/140 (43%) patients who were compared with 80 patients with normal sc-MFS-FU. Baseline sc-MFS did not differ significantly between the two groups, which appeared to diverge significantly soon after 1-year of follow up (figure). Baseline anti-citrullinated protein antibodies (ACPA) positivity, high disease activity (CDAI&gt;10) and duration of RA were independently associated with impaired sc-MFS-FU at multiple logistic regression analysis. Among these parameters, ACPA had the highest sensitivity (80%) whereas high disease activity had the highest specificity (89%) for sc-MFS-FU. A predictive score including all three predictors (ACPA status, CDAI&gt;10 and duration of RA) detected impaired sc-MFS-FU with a sensitivity of 78% and specificity of 82% (AUC 0.80 [IC 0.72-0.88], p&lt;0.0001). <h3>Conclusion</h3> This study supports the hypothesis that changes overtime in LVSF in patients with RA are associated with ACPA, high disease activity and duration of disease. <h3> Disclosure of Interests: </h3> Alessandro Giollo: None declared, Giovanni Cioffi: None declared, Giovanni Orsolini Speakers bureau: Grunenthal, Luca Idolazzi: None declared, Antonio Carletto Speakers bureau: Roche, Novartis, MSD, Abbvie, Bristol, Jannsen, Celgene, Pfizer, Andrea Dalbeni: None declared, Federica Ognibeni: None declared, Elena Fracassi Speakers bureau: Novartis, Davide Gatti Speakers bureau: Abiogen, Amgen, Janssen-Cilag, Mundipharma, Pfeizer, Maurizio Rossini: None declared, Ombretta Viapiana Speakers bureau: Novartis, Abbvie, Eli-Lilly, Sanofi Genzyme
The healthy ageing gene expression signature for Alzheimer’s disease diagnosis: a random sampling perspective
Authors: Laurent Jacob, Terence P. Speed
Journal: Genome biology (2018)

In a recent publication, Sood et al. (Genome Biol 16:185, 2015) presented a set of 150 probe sets that could be used in the diagnosis of Alzheimer’s disease (AD) based on gene expression. We reproduce some of their experiments and show that their signature is indeed able to discriminate between AD and control patients using blood gene expression in two cohorts. We also show that its performance does not stand out compared to randomly sampled sets of 150 probe sets from the same array.
The m6A demethylase ALKBH5 controls trophoblast invasion at the maternal-fetal interface by regulating the stability of <i>CYR61</i> mRNA
Authors: Xiao-Cui Li, Feng Jin, Bei-Ying Wang, Xiang-Jie Yin, Wei Hong, Fu-Ju Tian
Journal: Theranostics (2019)

N 6 -Methyladenosine (m 6 A) is the most prevalent internal modification in mammalian mRNAs.Although m 6 A is important in many biological processes, its roles in the placenta are unclear.Methods: Levels of global mRNA m 6 A methylation and ALKBH5 expression in recurrent miscarriage (RM) patients were determined using quantitative reverse transcription-PCR (qRT-PCR), m 6 A RNA methylation quantification, and immunohistochemical methods.Using ALKBH5 overexpression and knockdown methods, we determined the role of ALKBH5 in trophoblast invasion at the maternal interface through trophoblasts and an extravillous explant culture experiments.Furthermore, the regulation of CYR61 by ALKBH5 was explored by RNA-sequencing coupled with methylated RNA immunoprecipitation. Results:We found that the level of global mRNA m 6 A methylation was significantly decreased in placental villous tissue from RM patients, while ALKBH5 expression was specifically unregulated.Furthermore, we demonstrated that ALKBH5 knockdown in human trophoblast promoted trophoblast invasion.Conversely, overexpression of ALKBH5 inhibited cell invasion.ALKBH5 knockdown promoted trophoblast invasion in villous explant culture experiments, while overexpression of ALKBH5 repressed these effects.Furthermore, we clarified that ALKBH5 inhibited trophoblast invasion by regulating CYR61 mRNA stability, and this RNA regulation is m 6 A dependent.Mechanistic analyses showed that decreased ALKBH5 in trophoblast increased the half-life of CYR61 mRNA and promoted steady-state CYR61 mRNA expression levels.Conclusions: We elucidated the functional roles of ALKBH5 and mRNA m 6 A methylation in trophoblast and identified a novel RNA regulatory mechanism, providing a basis for further exploration of broad RNA epigenetic regulatory patterns in RM diseases.