tbuckley/cabot-search huggingface dataset:
Abstract 18645: Female Sex is Associated With Developement of Lower Limb Ischemia During Extracorporeal Life Support
Authors: Duk Won Bang, Byoung-Won Park, Min Su Hyon, Min Ho Lee, Won Ho Chang
Journal: Circulation (2017)

Introduction: Percutaneous cannulation of femoral vessels has been widely used for rapid deployment of extracorporeal life support (ECLS). Limb ischemia is a devastating complication in patients re...
PB2380 PROGNOSTIC EVALUATION OF MULTIPLE MYELOMA PATIENTS SUBMITTED TO UP‐FRONT AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FROM A SINGLE BRAZILIAN CENTER
Authors: Y. Vivas, V. Hungria, K. Santos, A. Chaoubah, M. Bustamante‐Teixeira, L. Vivas, L. Costa, A. Neto
Journal: HemaSphere (2019)

Background: Although autologous hematopoietic stem cell transplantation (AHSCT) has been performed in the context of multiple myeloma since the end of the 90's, response to therapy and patient survival are not homogeneous between different patients. Aims: In order to understand the factors involved in therapy response degree and survival on AHSCT performed as first‐line therapy, we conducted a retrospective analysis of myeloma multiple patients from asingle Brazilian center. Methods: All patients treated with AHSCT between May 2004 and October 2017were evaluated, excluding patients with prior transplant therapies or insufficient records data.Variables related to the International Staging System (ISS), Durie‐Salmon staging, clinical presentation at diagnosis, regimen used for induction, number of treatment cycles, induction and transplant treatment response assessmentwere studied.Event free survival (EFS) and overall survival (OS) were calculated and associated to analyzed factors. Results: Altogether, 137 patients were included in the study, with an average age of 52 years, 59,1% of them were male and 86,9% nonblack. Fifty two patients (38%) died, 6 (4,4%) of these during AHSCT. OS was 63,8% and EFS was 25,1% in 5 years.OS univariate analysis, as confirmed by multivariate analysis, was smaller in patients with anemia at diagnosis (p = 0,006).EFS, submitted to multivariate analysis, was smaller in patients treated with more than one line of induction chemotherapy.A positive response to induction therapy was the main factor related to a very good partial response and complete response to AHSCT (p = 0,001). Summary/Conclusion: Notwithstanding the great gap in knowledge over the successful myeloma multiple AHSCT factors, our data is similar to the ones found in literature, with anemia as an important independent prognostic factor to OS.
Abstract 14623: Impact of Secondary Chordal Cutting on Functional Mitral Regurgitation Due to Tethering During Aortic Valve Replacement in Patients With Severe Aortic Stenosis
Authors: Tomohiro Tsunekawa, Ryuhei Tanaka, Takayoshi Kato, Itta Kawamura, Yusuke Motoji, Tatsuomi Kinoshita, Yasuhide Okawa, Shinji Tomita
Journal: Circulation (2017)

Introduction: Functional mitral regurgitation (MR) in aortic stenosis (AS) may improve after aortic valve replacement (AVR) and tethering of anterior mitral leaflet (AML) is a strong predictor of p...
Addressing confounding artifacts in reconstruction of gene co-expression networks
Authors: Princy Parsana, Claire Ruberman, Andrew E. Jaffe, Michael C. Schatz, Alexis Battle, Jeffrey T. Leek
Journal: Genome biology (2019)

Gene co-expression networks capture biological relationships between genes and are important tools in predicting gene function and understanding disease mechanisms. We show that technical and biological artifacts in gene expression data confound commonly used network reconstruction algorithms. We demonstrate theoretically, in simulation, and empirically, that principal component correction of gene expression measurements prior to network inference can reduce false discoveries. Using data from the GTEx project in multiple tissues, we show that this approach reduces false discoveries beyond correcting only for known confounders.
Bystander responses impact accurate detection of murine and human antigen-specific CD8+ T cells
Authors: Matthew D. Martin, Isaac J. Jensen, Andrew S. Ishizuka, Mitchell Lefebvre, Qiang Shan, Hai-Hui Xue, John T. Harty, Robert A. Seder, Vladimir P. Badovinac
Journal: Journal of Clinical Investigation (2019)

Induction of memory CD8 T cells is important for controlling infections such as malaria HIV/AIDS, and for cancer immunotherapy. Accurate assessment of antigen (Ag)-specific CD8 T-cells is critical for vaccine optimization and defining correlates of protection. However, conditions for determining Ag-specific CD8 T-cell responses ex-vivo using ICS may be variable, especially in humans with complex antigens. Here, we used an attenuated whole parasite malaria vaccine model in humans and various experimental infections in mice to show that the duration of antigenic stimulation and timing of brefeldin A (BFA) addition influences the magnitude of Ag-specific and bystander T cell responses. Indeed, following immunization with an attenuated whole sporozoite malaria vaccine in humans, significantly higher numbers of IFN-γ producing memory CD8 T-cells comprised of antigen specific and bystander responses were detected by increasing the duration of Ag-stimulation prior to addition of BFA. Mechanistic analyses of virus-specific CD8 T-cells in mice revealed that the increase in IFNg producing CD8 T-cells was due to bystander activation of Ag-experienced memory CD8 T-cells, and correlated with the proportion of Ag-experienced CD8 T-cells in the stimulated populations. Incubation with anti-cytokine antibodies (ex. IL-12) improved accuracy in detecting bona-fide memory CD8 T-cell responses suggesting this as the mechanism for the bystander activation. These data have important implications for accurate assessment of immune responses generated by vaccines intended to elicit protective memory CD8 T-cells.
THU0251 ASSOCIATION OF SMOKING STATUS AND TOTAL AND INDIVIDUAL DAMAGE INDEX IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Romy Kallas, LI Jessica, Michelle A Petri
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Smoking is a risk factor for systemic lupus erythematosus (SLE). It has been associated with increased disease activity and decreased effectiveness of hydroxychloroquine in cutaneous lupus. <h3>Objectives:</h3> The objective of the study was to determine the association between smoking status and total and individual damage items in SLE. <h3>Methods:</h3> We analyzed data from the Hopkins Lupus Cohort. Damage was recorded using the Systemic Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index. Fisher's exact test and Wilcoxon test were used in exploratory analysis. Logistic regression was used to estimate the association between damage and smoking status (ever/never). Odds ratios and 95% confidence intervals were reported. Stratification by ethnicity was done for individual damage items that were found to be significantly associated with smoking. <h3>Results:</h3> The prevalence of ever smokers in our cohort was 36%. SLE patients who ever smoked had higher odds of total damage with higher mean total damage index scores (p &lt;0.0001). Data for individual damage items significantly associated with smoking are presented in Table 1. The association between cataract and smoking was still present after adjusting for ethnicity, diabetes, and prednisone use in a multivariate regression model (OR= 1.4, p= 0.0083). Stratification by ethnicity showed that African- American SLE patients who ever smoked were more likely to have cataract, scarring chronic alopecia, extensive scarring, skin ulceration, pulmonary hypertension, cerebrovascular events, cardiomyopathy, and diabetes compared to non-smokers. Caucasian SLE patients who ever smoked were more likely to have extensive scarring, gastrointestinal infarction and resection, and muscle atrophy (Table 1). N/C: data are not sufficient for calculating odds ratio <h3>Conclusion:</h3> Smoking is a modifiable factor for organ damage in SLE. It is already known that it interferes with the efficacy of hydroxychloroquine. Now we are able to prove that smokers have more cutaneous damage (scarring) even after stratification for ethnicity. As expected, smokers had more cardiovascular damage. New findings include associations with gastrointestinal damage, cataracts, pulmonary hypertension, pancreatitis and diabetes. Disclosure of Interests: Romy Kallas: None declared, Jessica Li: None declared, Michelle A Petri Shareholder of: Pfizer, Merck, Grant/research support from: AstraZeneca, Exagen, Consultant for: Eli Lilly, GSK, Merck EMD Serono, Janssen, Amgen, Novartis, Quintiles, Exagen, Inova Diagnostics, AstraZeneca, Blackrock, Glenmark, UCB, and the Annenberg Center for Health Sciences
Complex Admixture Preceded and Followed the Extinction of Wisent in the Wild
Authors: Karolina Węcek, Stefanie Hartmann, Johanna L. A. Paijmans, Ulrike Taron, Georgios Xenikoudakis, James A. Cahill, Peter D. Heintzman, Beth Shapiro, Gennady Baryshnikov, Aleksei N. Bunevich, Jennifer J. Crees, Roland Dobosz, Ninna Manaserian, Henryk Okarma, Małgorzata Tokarska, Samuel T. Turvey, Jan M. Wójcik, Waldemar Żyła, Jacek M. Szymura, Michael Hofreiter, Axel Barlow
Journal: Molecular Biology and Evolution (2016)

Retracing complex population processes that precede extreme bottlenecks may be impossible using data from living individuals. The wisent (Bison bonasus), Europe's largest terrestrial mammal, exemplifies such a population history, having gone extinct in the wild but subsequently restored by captive breeding efforts. Using low coverage genomic data from modern and historical individuals, we investigate population processes occurring before and after this extinction. Analysis of aligned genomes supports the division of wisent into two previously recognized subspecies, but almost half of the genomic alignment contradicts this population history as a result of incomplete lineage sorting and admixture. Admixture between subspecies populations occurred prior to extinction and subsequently during the captive breeding program. Admixture with the Bos cattle lineage is also widespread but results from ancient events rather than recent hybridization with domestics. Our study demonstrates the huge potential of historical genomes for both studying evolutionary histories and for guiding conservation strategies.
Retrospective analysis of the addition of cetuximab to induction chemotherapy (IC) with docetaxel, cisplatin, and 5-fluorouracil (TPF-C) for locally advanced squamous cell carcinoma of the head and neck (LA-HNSCC)
Authors: D. I. Kuperman, B. Nussenbaum, W. Thorstad, B. Haughey, J. Lewis, D. Adkins
Journal: Journal of Clinical Oncology (2007)

6072 Background: Achievement of a partial (PR) or complete (CR) tumor response at the primary site to IC has been used to predict for tumor sensitivity to definitive radiation (RT)-based treatment approaches in patients with LA-HNSCC. Three randomized trials of IC showed that TPF resulted in superior tumor response rates at the primary site in comparison to PF (TAX 323, TAX 324, and GORTEC). Based on the improved tumor response rate with the addition of cetuximab to cisplatin in metastatic HNSCC, TPF-C is a rational approach to improving tumor response rate to IC in LA-HNSCC. Methods: Between 2/06–12/06, 23 consecutive patients with LA-HNSCC were treated with IC that included TPF + cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly dose) for 1–3 cycles, followed by a standardized clinical assessment of tumor response at the primary site and at the regional nodes. TPF (docetaxel and cisplatin both 75 mg/m2 on day 1; 5-FU 750 mg/m2/d for 3 days) was given at every 3 week intervals. PR was defined as = 50% decrease and CR as complete resolution of tumor at the primary site. This is a retrospective analysis of the efficacy and the adverse effects (AE) of TPF-C in these patients. Results: Of 23 patients, 21 were evaluable for tumor response rate (RR). During IC, there were no deaths and grade 3–4 AE included: neutropenic fever (4), sepsis (1), and infusion reactions (4). Patients with favorable (PR or CR) tumor response to IC were treated with definitive RT-based therapy; whereas others were treated with surgery first. Conclusions: In this population of patients with LA-HNSCC with mostly (74%) T3 and T4 primary tumors, the tumor RR at the primary site to TPF-C was 71%. The addition of cetuximab to TPF was feasible. No significant financial relationships to disclose. [Table: see text]
Decreasing Trends in Mean HbA1c Are Not Associated With Increasing Rates of Severe Hypoglycemia in Children: A Longitudinal Analysis of Two Contemporary Population-Based Pediatric Type 1 Diabetes Registries From Australia and Germany/Austria Between 1995 and 2016
Authors: Aveni Haynes, Julia M. Hermann, Helen Clapin, Sabine E. Hofer, Beate Karges, Timothy W. Jones, Elizabeth A. Davis, Reinhard W. Holl
Journal: Diabetes Care (2019)

To investigate temporal trends in glycemic control and severe hypoglycemia rates for pediatric patients with type 1 diabetes from 1995 to 2016 by analyzing data from the longitudinal, prospective, population-based German/Austrian (Diabetes Patient History Documentation [DPV]) and Western Australian (Western Australian Children's Diabetes Database [WACDD]) diabetes registries.Patients diagnosed with type 1 diabetes aged <15 years were identified from the DPV (N = 59,883) and WACDD (N = 2,595) registries and data extracted for all clinic visits occurring between 1995 and 2016, inclusive. Mean HbA1c and severe hypoglycemia (self-reported loss of consciousness/convulsion) rates were calculated per 100 patient-years.Between 1995 and 2016, the annual mean HbA1c decreased from 8.3 to 7.8% in the DPV cohort and from 9.2 to 8.3% in the WACDD cohort. Over the same period, the severe hypoglycemia rate decreased by an annual average of 2% (relative risk 0.983 [95% CI 0.981, 0.986]) in the DPV cohort and 6% (relative risk 0.935 [95% CI 0.934, 0.937]) in the WACDD cohort. Concomitant decreasing trends in both HbA1c and severe hypoglycemia rates were observed in boys and girls, all age-groups, and injection therapy/pump regimen groups.Over the past two decades, there have been concurrent improvements in HbA1c and decreasing severe hypoglycemia rates in two contemporary, longitudinal, population-based pediatric cohorts of type 1 diabetes. Translation of these data into clinical practice and patient education may reduce fear of hypoglycemia and enable better glycemic control.
Closing the Loop on the Role of Multiparametric Magnetic Resonance Imaging–Targeted Prostate Biopsy
Authors: Ahmad Shabsigh, Cheryl T. Lee
Journal: JAMA Surgery (2019)

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A method to perform pharmacokinetic sampling through a single lumen catheter following drug administration
Authors: Jeffrey M. Skolnik, Dominique A. Paccaly, Jeffrey S. Barrett, Peter C. Adamson
Journal: Cancer Research (2006)

3113  Introduction: The ability to use a single indwelling catheter for both dosing and sampling purposes can enhance enrollment in pharmacokinetic studies, especially in children. Objective: To develop a procedure for pharmacokinetic sampling from a single indwelling central catheter following drug dosing. Material and Methods: An in vitro model system for drug dosing through a central venous catheter using a variety of commercial catheters (Cook® and CR Bard®) was used for method development. A 3-way stopcock was fitted with both a waste and sample syringe, and was connected to the catheter via a needless access hub. Actinomycin-D (Act-D, 0.5 mg/mL) and vincristine (VCR, 1 mg/mL), two drugs to be studied in an upcoming pharmacokinetic-pharmacodynamic study, were dosed through the catheter. Sampling occurred from drug-free whole blood. The effect of flush volume and composition, as well as catheter type and lumen size, on residual drug concentration was studied. Concentration profiles were fitted to simple exponential decay models, and were incorporated into models to explore the potential for clinically influential contamination. Results: Limited residual Act-D and VCR concentrations were found in samples obtained after four rinse waste cycles interrupted by a 2 mL saline flush. Mean residual concentrations of Act-D were 0.6±0.6 ng/mL and of VCR were 0.3±0.4 ng/mL, at or below the limit of quantitation, reflecting a six log decrease from initial infusion concentration. Conclusion: We have developed a procedure to efficiently reduce drug contamination during pharmacokinetic sampling from a single lumen catheter. Further evaluation of in vivo validation is ongoing and the proposed configuration will soon be evaluated in a prospective clinical trial currently underway at our institution.
Abstract 19907: GWAS Incorporating Gene-Social Support Interactions Identifies Novel Lipid Loci in African Americans
Authors: Solomon K Musani, Melissa A Richard, Mario Sims, Myriam Fornage
Journal: Circulation (2017)

Emotionally supportive relationships have been found to be cardio protective. To identify new genetic loci that influence serum lipid levels, we searched genome-wide for gene-social support interac...
Abstract 20350: Exercise and Cognitive Re-Training as a Strategy to Improve Cognitive Outcomes in Heart Failure
Authors: Rebecca Gary, Drenna Waldrop-Valverde, Sudeshna Paul
Journal: Circulation (2017)

Background: Persons with heart failure (HF) are up to 50% more likely to develop mild to moderate cognitive impairment compared to age-matched healthy adults. Aerobic exercise is well established t...
PF156 SINGLE-CELL TRANSCRIPTIONAL HETEROGENEITY SUGGESTS NOVEL FINGERPRINT OF RELAPSE IN ACUTE MYELOID LEUKEMIA
Authors: Z. Wang, R. Wang, C. Yang, Y. liu, C. Zhang, L. Gao, X. Zhang
Journal: HemaSphere (2019)

Background: Some rare subgroups of leukemia cells harboring relapse-inducing genes were selected after chemotherapy. Tounravel intra-tumoral heterogeneity and selective drug-resistance, single-cell RNA sequencing (scRNA-seq) was already performed on many solid tumors and blood cancer to achieve the high-resolutiontranscriptome profiling on individual cells from a larger heterogeneous population. However,the comprehensive investigation on cancer heterogeneityduring cancer development at single-cell resolution is still rare. Aims: To identify diverse subsets and molecular characteristics of acute myeloid leukemia (AML) relapse Methods: Since single-cell suspension was obtainedfrom bone marrow of acute myeloid leukemia samples, we used the 10x GenomicsChromium platform to capture transcriptomes of singlecells on barcoded mRNA capture beadsfor massively parallel scRNA-seq. Data processing followed by the Cell Ranger software pipelineto demultiplex cellularbarcodes, and map reads to the genome and transcriptome hg38 using the STAR aligner. Uniquemolecular identifier (UMI) count matrix and quality control were performed using Seurat. The t-SNE map was calculated using Rtsne package Results: We analyzed transcriptome data from near 50K single leukemia bone marrow cells across 3 patients during newly diagnosed, complete remission and relapse stages. To define the landscape of cellular heterogeneity and its association with outcome in an unbiased manner, we performed unsupervised machine learning algorithm on near 50K single cells from leukemia bone marrow and identify one robust 14-cluster solution (from 0 to 13, Figure 1A) and the hallmark genes within each clusters (Figure 1B). The pattern exhibits distinct distribution on different stages (Figures 1C), indicating intra-tumoral heterogeneity during leukemia progression. Within cluster 0, the subgroups expressing such as LILRB2, TNFAIP2 or PTAFR were chemotherapy sensitive (Figure 2A). While the subgroups expressing such as APOC1, CDKN2A, KLF1 or GATA1 were chemotherapy resistant (Figure 2B). These chemotherapy resistant subgroups may play some key roles in leukemia relapse.Summary/Conclusion: We identify novel relapse subgroups in highly heterogeneous leukemia, which could not be found using traditional bulk RNA-seq.
AB0116 BROMODOMAIN INHIBITOR, I-BET762 INHIBITS PRODUCTION OF PRO-INFLAMMATORY MEDIATORS BY DOWN-REGULATING BROMODOMAIN AS AN EPIGENETIC READER IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES
Authors: Ra Ham Kim, Hyun Jung Yoo, Shin Eui Kang, Ji Soo Park, Seon Uk Kim, Eun Young Lee, Jin Kyun Park, Yeong Wook Song
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a chronic autoimmune disorder, characterized by joint inflammation and bone destruction. The fibroblast-like synoviocyte contributes to the pathogenesis of RA through proliferation and production of cytokines. Recently, blockade of the bromodomain and extra-terminal domain (BET) family protein was reported to be a potential therapeutic target by inhibiting epigenetics interaction between bromodomains and acetylated histones. <h3>Objectives:</h3> We aimed to investigate the effects of bromodomain-containing protein 4 (BRD4) inhibition on tumor necrosis factor (TNF)-α-stimulated rheumatoid arthritis fibroblast-like synoviocyte (RA-FLS) using BRD4 inhibitor, I-BET762. <h3>Methods:</h3> We examined the effects of BET protein inhibitor on cytokine production and cellular proliferation in RA-FLS. RA-FLSs were treated with TNF-α (10 ng/ml) in the presence of I-BET762 for 48 h. The cell viability and proliferation were measured after 24, 48, and 72 h in I-BET762-treated RA-FLS using CCK-8 colorimetric assay. We then screened pro-inflammatory mediators by using the human inflammation antibody array (Abcam). The levels of interleukin (IL)-6 and IL-8 in culture supernatants of TNF-α-stimulated RA-FLS were measured by enzyme-linked immunosorbent assays (ELISA). <h3>Results:</h3> I-BET762 had no significant effect on cytotoxicity and proliferation of RA-FLS. I-BET762 reduced the secretion of CXCL-10 and regulated upon activation, normal T cell expressed, and secreted (RANTES) from RA-FLS while increased the secretion of tissue inhibitor of metalloproteinase 2 (TIMP-2) in the antibody array. In addition, ELISA showed significantly decreased level of IL-6 and IL-8 in culture supernatant after treatment with I-BET762. <h3>Conclusion:</h3> Inhibition of BRD4 by I-BET762 leads to down-regulation of pro-inflammatory cytokines and chemokines in RA-FLS. I-BET762 may have anti-inflammatory properties and provide a therapeutic target molecule in RA. <h3>References</h3> [1] Sahai V, et al. Oncotarget 2016;6;7(33):53997-54009. [2] Klein K, et al. Ann Rheum Dis2016;75: 422–429. <h3>Disclosure of Interests:</h3> None declared