tbuckley/cabot-search huggingface dataset:
The interplay of demography and selection during maize domestication and expansion
Authors: Li Wang, Timothy M. Beissinger, Anne Lorant, Claudia Ross-Ibarra, Jeffrey Ross-Ibarra, Matthew B. Hufford
Journal: Genome biology (2017)

The history of maize has been characterized by major demographic events, including population size changes associated with domestication and range expansion, and gene flow with wild relatives. The interplay between demographic history and selection has shaped diversity across maize populations and genomes.We investigate these processes using high-depth resequencing data from 31 maize landraces spanning the pre-Columbian distribution of maize, and four wild teosinte individuals (Zea mays ssp. parviglumis). Genome-wide demographic analyses reveal that maize experienced pronounced declines in effective population size due to both a protracted domestication bottleneck and serial founder effects during post-domestication spread, while parviglumis in the Balsas River Valley experienced population growth. The domestication bottleneck and subsequent spread led to an increase in deleterious alleles in the domesticate compared to the wild progenitor. This cost is particularly pronounced in Andean maize, which has experienced a more dramatic founder event compared to other maize populations. Additionally, we detect introgression from the wild teosinte Zea mays ssp. mexicana into maize in the highlands of Mexico, Guatemala, and the southwestern USA, which reduces the prevalence of deleterious alleles likely due to the higher long-term effective population size of teosinte.These findings underscore the strong interaction between historical demography and the efficiency of selection and illustrate how domesticated species are particularly useful for understanding these processes. The landscape of deleterious alleles and therefore evolutionary potential is clearly influenced by recent demography, a factor that could bear importantly on many species that have experienced recent demographic shifts.
Abstract 14733: Influence of High Risk Adrenergic Receptor Genotypes on Outcome in Infants With Single Ventricle
Authors: Ronand Ramroop, Dorin Manase, George Manase, Cory Simmons, Jane W Newburger, J William Gaynor, Mark W Russell, Seema Mital
Journal: Circulation (2015)

Introduction: Variants in adrenergic receptor (ADR) genes are associated with adverse clinical outcomes in patients with heart failure. We evaluated the association of variants in ADR receptor genes with outcomes in infants with single ventricle lesions. Methods: Infants with single ventricle lesions participating in the Pediatric Heart Network Single Ventricle Reconstruction Trial (randomized to Norwood with modified Blalock-Taussig shunt versus right ventricle-pulmonary artery shunt) underwent genotyping for 4 single nucleotide polymorphisms (SNPs) in 3 ADR genes: ADRB1-A/G (rs1801252), ADRB1-C/G (rs1801253), ADRB2-C/G (rs1042714) and ADRA2A-C/T (rs553668). Linear and logistic regression, deviance tests, t-tests and F-tests were used to analyze association of genotype with clinical outcomes including hospital length of stay (LOS) at Norwood, occurrence of serious adverse events (SAE), and transplant-free survival during 14 months follow-up using a dominant model. Results: The study included 347 eligible patients (62% male; 83% white). The mean age at Norwood procedure was 6±3.6 days and median Norwood LOS was 8 days. During 14 months follow-up, 147 patients had SAEs, 94 patients died and 14 were transplanted. ADRB1 AA (rs1801252) genotype was associated with longer Norwood LOS. The difference in LOS between AA vs AG/GG was 7.99 days (confidence intervals, 0.27, 15.71; p=0.043). ADRA2A CC (rs553668) genotype was associated with higher odds of SAEs i.e. 103/216 (47.6%) in CC compared to 36/106 (34%) in CT/TT [Odds ratio 1.77 (confidence intervals, 1.09, 2.87), p=0.018]. Transplant-free survival was not different between genotype groups. Combined analysis of risk genotypes did not confer an additive risk of adverse outcomes. Conclusions: ADR genotypes known to cause adrenergic upregulation were associated with prolonged Norwood hospitalization and/or serious adverse events in infant single ventricles. This may be secondary to adverse effects of adrenergic overexpression on cardiac function and systemic hemodynamics. Analysis is ongoing to replicate these findings for utility as predictive markers for outcomes in infant single ventricles.
FRI0033 QUANTIFERON GOLD-PLUS AND TUBERCULIN SKIN TEST REACTIVITY PREDICTORS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Juan Pablo Carrizales-Luna, Dionicio Ángel Galarza-Delgado, Luis Adrián Rendón-Pérez, Griselda Serna-Peña, Gisela García-Arellano, Mayra Alexandra Rendón-Medina, Berenice Soto-Monciváis, Leticia Santoyo-Fexas, Juan Manuel Muñoz-Ayala
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> RA patients have high latent tuberculosis(LTBI)prevalence(20-37%)<sup>1</sup>. In Mexico,ranges from 21.7% to 31.3% using tuberculin skin test (TST)<sup>2</sup>. The methods to detect LTBI are TST and IGRAs. QuantiFERON Gold-Plus (QTF-Plus)uses an antigen tube (TB1) that stimulates CD4+T cells and an additional tube (TB2) that also stimulates CD8+T cells<sup>3</sup>. <h3>Objectives:</h3> Determine the LTBI prevalence,variables that predict QTF-Plus and TST results and the concordance between TST and QTF-Plus in RA patients. <h3>Methods:</h3> A cross-sectional study in RA patients from the rheumatology department of the University Hospital "José E. González" in Mexico between October 2017 and June 2018. RA patients with ACR/EULAR 2010 classification criteria without a history of tuberculosis (TB) were included.QFT-Plus was performed according to manufacturer instructions.TST was applied with the Mantoux technique; a ≥5mm cutoff was used.The square chi and Fisher test were used for proportions, Mann-Whitney to compare means,trend analysis using linear trend test and a binary logistic regression model for variables related to positivity to both tests. <h3>Results:</h3> We included 111 patients (table 1), the mean age was 51.9 years, 92.3% were women,disease duration 8.7±8.8 years. QTF-Plus was positive in 46 (44.6%) patients. TST was positive in 31(27.9%) patients.Agreement between tests was 73.7% (kappa=0.45, p&lt;0.001).The majority of patients were using conventional DMARDs (86.7%), none of the patients were using biologic DMARDs. In the linear-to-linear association analysis,there was a trend towards TST negative result with the use of ≥2DMARDs (p=0.049 for trend) (figure 1).In the logistic regression model we found a significant relationship between a positive TST active TB exposure(OR 8.5,CI 95% 1.4-51.7; p=0.01)and an inverse relationship between the positive TST and antimalarials (OR 0.11, CI 95% 0.001-0.8),none of the variables interfered with QTF-Plus results. <h3>Conclusion:</h3> The LTBI prevalence in RA patients in our study is similar to countries with a high TB burden.We recommend considering RA patients as a high-risk population for LTBI.An intermediate agreement between TST and QTF-Plus was found.The use of antimalarials and ≥2DMARDs influence the TST reactivity,none of the variables altered the QTF-Plus results.Based on the results, we recommend the QuantiFERON Gold Plus over TST for the LTBI screening in RA patients. <h3>References:</h3> [1] Sester M,et al.Am J Respir Crit Care Med.2014;190(10):1168–76. [2] Pérez-Barbosa L,et al.Rheumatol Int.2015;35(9):1555–9. [3] Takasaki J,et al.J Infect Chemother.2018;24(3):188–92. <h3>Disclosure of Interests:</h3> None declared
Prognostic significance of baseline <i>FLT3</i>‐ITD mutant allele level in acute myeloid leukemia treated with intensive chemotherapy with/without sorafenib
Authors: Fevzi Yalniz, Iman Abou Dalle, Hagop Kantarjian, Gautam Borthakur, Tapan Kadia, Keyur Patel, Sanam Loghavi, Guillermo Garcia‐Manero, Koji Sasaki, Naval Daver, Courtney DiNardo, Naveen Pemmaraju, Nicholas J. Short, Musa Yilmaz, Prithviraj Bose, Kiran Naqvi, Sherry Pierce, Graciela M. Nogueras González, Marina Konopleva, Michael Andreeff, Jorge Cortes, Farhad Ravandi
Journal: American Journal of Hematology (2019)

Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 gene (FLT3) confer a poor prognosis in adult AML. Studies have reported that a higher mutant allelic burden is associated with a worse prognosis. Adult patients with FLT3-ITD mutated AML treated at our institution were identified. Patients were assigned into 2 groups; patients who received idarubicin and cytarabine (IA, group one) containing induction, and who received sorafenib in addition to IA containing regimens at induction (group two). The optimal FLT3-ITD mutant allele cut-off was defined as the cut-off to divide the whole cohort with the highest statistical significance. A total of 183 patients including 104 (57%) in group one and 79 (43%) in group two were identified. The complete remission (CR)/CR with incomplete hematologic recovery (CRi) for group one and group two were 85% and 99%, respectively (P = .004). The median relapse free survival (RFS) for group one and two were 12 and 45 months, respectively (P = .02). The median overall survival (mOS) was 17 months in group one, and has not been reached in group two (P = .008). The optimal FLT3-ITD mutant allele cut-off for OS was 6.9% in group one, there was no optimal cut-off in group two. On multivariate analysis, poor performance status (PS) (P = .003), sorafenib (P = .01), and presenting white blood cells (WBC) (P < .001) were independent predictors of OS. Higher FLT3-ITD allele burden is associated with a worse outcome in patients treated with IA-based chemotherapy. Addition of sorafenib to chemotherapy not only nullifies the negative prognostic impact of higher allele burden, but also improves outcome of FLT3-ITD mutated AML patients regardless of the allele burden.
SP0032 HOW TO MEASURE REHABILITATION
Authors: Alison Hammond
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Measuring outcomes is fundamental to rehabilitation. A wide range of subjective and objective outcome are available to health professionals, with patient reported outcomes (PROs) being widely used. Fundamental to their use is understanding how to select appropriate measures and interpret results. <h3>Objectives:</h3> This talk addresses: how to identify and select patient reported outcomes measures; the COSMIN taxonomy; understanding measurement properties; evaluating fitness for purpose; and understanding cross-cultural and linguistic validation of PROs, to enable PROs to be used across countries. This will be illustrated with an example of a Swedish – English-Dutch-German PRO, the Evaluation of Daily Activity Questionnaire. <h3>Disclosure of Interests:</h3> None declared
Abstract 2243: Real-Time Computed Tomography (RT-CT) for Guidance of Catheter Navigation, Transseptal Puncture and Anatomically Targeted Radiofrequency Ablation
Authors: Timm Dickfeld, Martin Engelhardt, Katrina Read, Christopher Kocher, Jagan Akella, Anthony Johnson, Robert Peters, Magdi Saba, Stephen Shorosfsky, Thorsten Fleiter
Journal: Circulation (2007)

Background: Recent ablation strategies for complex arrhythmias such as atrial fibrillation or ischemic ventricular tachycardia are increasingly based on anatomic considerations. While fluoroscopy and 3D-mapping systems are widely used to guide these ablations, they are limited by poor soft tissue visualization and the lack of real-time anatomic data. Therefore, this study sought to evaluate if real-time computed tomography (RT-CT) could overcome these limitations and guide catheter navigation, transseptal puncture and anatomically targeted ablation. Methods: Catheter real-time guidance was assessed in 5 swine (40kg) using a 40-slice RT-CT. First, right/left heart catheterization was performed from the femoral vein and artery with the goal to access all cardiac chambers and the great cardiac vessels. Second, transseptal puncture was attempted with targeted ablations at pre-specified locations at the left lateral wall. Third, targeted ablation at the pulmonary vein (PV) orifice and repeat ablations at the right lateral wall were created to assess accuracy and precision, respectively. Fourth, creation of a straight ventricular four-point line was attempted. Necropsy was performed to assess possible complications and to compare the location of the ablation sites with the CT images. Results: Catheter navigation was performed safely from the femoral vein to the pulmonary artery and the femoral artery to the left ventricle. Misguided catheters to the renal vein, jugular vein, and carotid artery were correctly identified and removed. Transseptal puncture using a Brocken-brough needle was successfully performed and confirmed with anatomically targeted ablations at the left lateral atrial wall. Accuracy as assessed by PV ablations was in the range of 1–3mm. Repeat ablations in the right atrial wall revealed a precision of 2–3mm. Maximum deviation from a straight 4-point ventricular line was 2.8mm. No complications were seen at necropsy. Conclusions: Catheter navigation (in all four cardiac chambers) as well as transseptal puncture can be performed guided exclusively by RT-CT. Anatomically targeted ablations can be created with good accuracy and precision under real-time guidance. This suggests a possible role of RT-CT to guide ablation procedures.
Abstract 1483: The Role of Genetically Programmed Biases in Th1 and Th2 Immune Responses in Atherogenesis
Authors: Stephanie Schulte, Galina Sukhova, Peter Libby
Journal: Circulation (2006)

Background: Inflammation occupies a central position in all phases of atherosclerosis. Atherosclerotic lesions contain predominantly CD4+ T lymphocytes. In response to the local cytokine milieu, CD4+ T cells differentiate into a Th1 or Th2 lineage. The influence of Th1 and Th2 helper cell subsets on atherogenesis was studied in two ApoE−/− mouse strains, C57Bl/6 and Balb/c, displaying opposite T cell subset polarization.n Methods and Results: ApoE−/− Bl/6 mice showed Th1-like immune responses. Splenic CD4+ T cells isolated from these mice produced substantial IFNγ upon polyclonal stimulation (2207.0 +/− 512.0 pg/ml), but low levels of IL-4 (48.8 +/− 16.4 pg/ml). ApoE−/− Bl/6 mice had IgG2a antibodies to oxidized LDL, a disease-specific antigen. In contrast, ApoE−/− Balb/c mice displayed predominant Th2 responses with lower IFNγ (622.1 +/− 76.6 pg/ml) and higher IL-4 production (185.9 +/− 40.8 pg/ml) by CD4+ T cells compared to ApoE−/− Bl/6 mice and an IgG1 isotype response towards oxidized LDL. ApoE−/− Bl...
Phenotypic Features of Oguchi Disease and Retinitis Pigmentosa in Patients with S-Antigen Mutations
Authors: Koji M. Nishiguchi, Yasuhiro Ikeda, Kosuke Fujita, Hiroshi Kunikata, Makoto Akiho, Kazuki Hashimoto, Katsuhiro Hosono, Kentaro Kurata, Yoshito Koyanagi, Masato Akiyama, Takefumi Suzuki, Ryo Kawasaki, Yuko Wada, Yoshihiro Hotta, Koh-Hei Sonoda, Akira Murakami, Mitsuru Nakazawa, Toru Nakazawa, Toshiaki Abe
Journal: Ophthalmology (2019)
Abstract O.41: Assessment of Kawasaki Disease Risk Scores for Predicting Coronary Artery Aneurysms at a North American Center
Authors: Mary Beth F Son, Kimberlee Gauvreau, Susan Kim, Alexander Tang, Fatma Dedeoglu, David R Fulton, Mindy S Lo, Robert P Sundel, Jane W Newburger
Journal: Circulation (2015)

Aim: To assess the performance of established Japanese risk scores (RS) to identify patients (pts) with Kawasaki disease (KD) at high-risk for developing coronary artery aneurysms (CAA). Methods: We reviewed clinical, laboratory and echocardiographic (echo) data for pts with KD treated with IVIG from 1/2006 to 5/2014. We defined CAA as z score ≥2.5 in the right coronary artery (RCA) or left anterior descending artery (LAD) at 4-8 weeks of illness. Relationships with Kobayashi, Sano, Egami and Harada RS and CAA were examined. The maximum z score of LAD or RCA (zMax) at baseline was a covariate in logistic regression. The discrimination of each model was assessed using the c statistic. Results: Of 268 pts with complete data, 173 (65%) were male and median age was 3.1 y (range 0.1-14.1 y). At diagnosis, 74 (28%) had ≤3 classical criteria for KD, and 70 pts (26%) received IVIG retreatment. On baseline echo, 75 pts (27%) had a zMax ≥ 2.0. CAA occurred in 15 pts (5.6%). The Harada RS predicted development of CAA (low risk = 0% (0/80), high risk=9% (12/140), p=0.005), but the Kobayashi, Sano, and Egami RS were not associated with CAA. CAA were associated with baseline zMax ≥2.0 vs. &lt;2.0 (12 [16%] vs. 3 [2%], respectively, p&lt;0.001) and as a covariate in logistic regression (Table 1). Conclusions: With the exception of the Harada score, established RS were ineffective at predicting the development of CAA at a cosmopolitan center. Baseline z scores were highly associated with CAA. However, adding baseline z scores to a logistic regression model did not improve discrimination of the RS.
AB0451 PROSPECTIVE STUDY OF REASONS FOR DISCONTINUATION OF TOFACITINIB IN SELF-FUNDED PATIENTS WITH RHEUMATOID ARTHRITIS FROM A SINGLE CENTRE
Authors: Ramakrishna Rao Uppuluri, Maryam Younis, Archana Rani, Shashikala Arava, Shivanand Jonnada, Kumar Datta, Challa Satyavati
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Tofacitinib is an oral Janus kinase inhibitor for the treatment of Rheumatoid Arthritis (RA). There can be potential differences in the adherence and compliance to therapies in real world compared to clinical trials especially in a non-reimbursable setup. Hence, it is very important to see the patient persistence to Tofacitinib therapy in a real world practice. <h3>Objectives:</h3> To evaluate the reasons for discontinuation of Tofacitinib in RA patients in real world set-up. <h3>Methods:</h3> Data of RA patients treated with Tofacitinib 5mg BID from a rheumatology center in South India was collected from September 2016 to January 2019 using standardized formats at baseline, 1, 3, 6 and 12 months. Efficacy was evaluated by DAS28-ESR and safety by listing of Adverse Events (AE). Reasons for discontinuation were objectively recorded. Concomitant RA treatment type/dose adjustments were as per the clinician's discretion. Analysis was based on observed values without imputation for missing data. For calculating persistence at a time point, the patients still taking the drug with treatment duration lower than that particular time point were excluded from the calculation. <h3>Results:</h3> Fifty seven RA patients were treated with Tofacitinib. Average age and disease duration were 50 (20-77) years, 9 (1-22) years respectively. Most patients were females (88%); seropositive (89%) and all had erosive disease. Tofacitinib was used as a second line drug after inadequate response with conventional Disease Modifying Anti Rheumatic Drugs. Average Tofacitinib follow up was 6 (1-16) months. Thirty nine patients who discontinued Tofacitinib were analyzed. Eighteen patients were at various stages of therapy including 8 patients completing 12 months. Persistence with Tofacitinib at 3, 6 and 12 months was 85, 50 and 17 percent respectively. Details of the reasons for discontinuation are given in Table and Figure. <h3>Conclusion:</h3> Tofacitinib was effective and well tolerated in Indian patients. However, majority of patients (80%) discontinued at various time points after feeling better. Only 13% discontinued due to AEs and 7% due to inadequate response. This data brings into light the difficulties faced by health providers for implementing 'treat to target' approach in real world practice. <h3>References</h3> [1] Marchesoni et al, Ann NY Acad Sci 2009, 1173: 837–846 <h3>Disclosure of Interests:</h3> Ramakrishna Rao Uppuluri Grant/research support from: Pfizer Inc, Maryam Younis: None declared, Archana Rani: None declared, Shashikala Arava: None declared, Shivanand Jonnada: None declared, Kumar Datta: None declared, Challa Satyavati: None declared
Multi-drug resistance and breast cancer: A meta-analysis of MDR1 and its functional significance
Authors: B. Trock, F. Leonessa, R. Clarke
Journal: Journal of Clinical Oncology (2007)

11010 Background: The clinical significance of MDR1 as a mechanism of multidrug resistance in breast cancer has not been established. We conducted a meta-analysis examining MDR1/gp170 in breast cancer, significantly updating a meta-analysis we performed in 1997. Methods: Published papers on MDR1/gp170 and breast cancer were identified by searching literature databases and bibliographies of published papers. Pooled relative risks (RR) for association between MDR1/gp170 expression and clinical outcomes were estimated with the Mantel-Haenszel method. Results: 84 studies were included in analysis: 63 measured MDR1/gp170 expression, 21 measured response to chemotherapy, 11 used sestamibi imaging, and 11 evaluated multidrug resistance reversing agents. MDR1 expression was detected in 45.9% of breast tumors prior to treatment and 66.8% of tumors after treatment (p&lt;0.0001). There were no significant differences in gp170 expression by antibody type (p=0.567). In 11 studies, MDR1/gp170 expression after chemotherapy was associated with a significant risk of non-response, RR=1.79 (95% CI=1.35, 2.35), p&lt;0.0001. This effect was lower in 13 studies with MDR1/gp170 assessed prior to chemotherapy, RR=1.28 (1.06, 1.55), p=0.009. Only 7 of 16 studies showed significant associations with decreased progression-free or overall survival. Of 11 sestamibi imaging studies, 10 showed a significant association between shorter retention and higher levels of MDR1/gp170, suggesting active protein pumping of contrast agent. None of 11 studies of multidrug reversing agents found &gt;25% of refractory patients improving to partial clinical response, but most studies did not confine treatment to patients with MDR1/gp170 expression. Conclusions: This meta-analysis includes nearly 3 times as many studies as our 1997 analysis. MDR1 is expressed in approximately half of breast cancer patients, and is induced by chemotherapy. MDR1 after chemotherapy is associated with RR=1.8 for failure to achieve a clinical response, and RR=1.3 without induction by chemotherapy. Sestamibi gives the strongest support for active efflux of agent by gp170, but studies with MDR reversing agents have shown little success, which may partly reflect poor study design. [Table: see text]