tbuckley/cabot-search huggingface dataset:
Abstract 4317: Cell-type specific epigenetic effects of tobacco smoking on the immune cell methylome
Authors: Xuting Wang, Ma Wan, Brian D. Bennett, Gary S. Pittman, Michelle Campbell, Dan Su, Isabel J. Thompson, Suzanne N. Martos, Douglas A. Bell
Journal: Cancer Research (2018)

Abstract Exposure to tobacco smoke dramatically alters DNA methylation in blood cells and this immune cell modulation may mediate smoking-associated complex diseases. To identify cell-type specific, smoking-associated differentially methylated regions (SM-DMRs) in hematopoietic cells from smokers and non-smokers, we used Illumina 450/850K arrays, reduced representation (RRBS) and whole genome bisulfite sequencing (WGBS) to measure methylation on DNA extracted from whole blood and 7 leukocyte subtypes (CD4+, CD8+, CD14+ monocytes, CD15+ granulocytes, B cells, NK cells and CD34+ progenitor cells). SM-DMRs preferentially occurred at enhancers (H3K27ac), and/or CpG island shores and were enriched for transcription factor (TF) binding suggesting crosstalk between TFs, DNA methylation, and tobacco smoke exposure. SM-DMRs in or near genes AHRR, ALPPL2, and GFI1 were highly significant in CD34+, CD14+, CD15+, B cells and NK cells but were absent in CD4+ and CD8+ T cells. We also identified genomic regions with distinct cell-type and lineage-specific differences in smoking-associated methylation and gene expression. AHRR displayed increased levels of both noncoding RNA and mRNA gene expression only in CD14+ monocytes. The SM-DMR in GPR15 was highly significant in CD4+ and CD8+ T cells, B cells, and NK cells but absent in myeloid cells. To explore possible links between smoking, DNA methylation/gene expression and immune cell functions, we carried out pathway analysis on smoking-affected methylomes and transcriptomes in each cell type. The smokers' transcriptome of CD56+ NK cells showed perturbation of genes either altered in leukemias, linked with leukemia GWAS SNPs, or under various types of innate immune stimulation. In particular, the locus containing HLA-DQA1 and HLA-DQB1 is highly significantly linked with chronic lymphocytic leukemia and these genes were strongly down-regulated in NK cells of smokers. The NK cell methylome of smokers also displayed perturbation of genes altered in leukemia cell lines. To identify and characterize rare blood cells among cell-type subsets that have smoking-altered transcriptomes, we are carrying out single cell RNA-seq. These studies may reveal new biological connections between tobacco smoke exposure and smoking-associated disease etiology. Citation Format: Xuting Wang, Ma Wan, Brian D. Bennett, Gary S. Pittman, Michelle Campbell, Dan Su, Isabel J. Thompson, Suzanne N. Martos, Douglas A. Bell. Cell-type specific epigenetic effects of tobacco smoking on the immune cell methylome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4317.
Abstract 2247: Accelerating cancer research using big data with BioKDE platform
Authors: Xiaodong Pang, Mayassa J. Bou-Dargham, Yuhang Liu, Zihan Cui, Linlin Sha, Tingting Zhao, Jinfeng Zhang
Journal: Cancer Research (2018)

Abstract Large volumes of data have been generated in biomedical field every day and made publicly accessible. A significant portion of the data are highly under-analyzed. On the other hands, biomedical researchers having problems that can be solved by these data do not have the expertise to access and analyze the data. The BioKDE (Biomedical Knowledge Discovery Engine) platform aims to bridge this gap by accelerating biomedical discovery through integration and mining of large volumes of public genomic data. We have integrated a large volume of genomics data from TCGA (the Cancer Genome Atlas) and GEO (Gene Expression Omnibus) database, which are linked with patient clinical information. Powerful and versatile query functions were built for the integrated data. Basic and advanced analysis tools have been implemented with user-friendly interfaces. Pipelines can be built by chaining the query tools with analysis tools to perform sophisticated data acquisition and analysis tasks very conveniently. Pipelines can be saved and shared among researchers to quickly replicate certain analyses using the same dataset or different datasets. A large number of novel discoveries have been made, which can be used directly to write scientific research papers using these discoveries alone or by combining with additional experimental validation studies. We will present a few case studies published recently to illustrate the power of the BioKDE. We are looking for collaborators to write papers together for the discoveries we made. The platform can be accessed at http://www.insilicom.com. Citation Format: Xiaodong Pang, Mayassa J. Bou-Dargham, Yuhang Liu, Zihan Cui, Linlin Sha, Tingting Zhao, Jinfeng Zhang. Accelerating cancer research using big data with BioKDE platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2247.
Abstract 1044: Establishment and characterization of rare breast patient-derived xenograft models as a potential resource for personalized medicine
Authors: Hellen Kuasne, Paul Savage, Constanza Martinez Ramirez, Leah Liu, Valentina Muñoz-Ramos, Virginie Pilon, Anie Monast, Radia Johnson, Nicholas Bertos, Jamil Asselah, Nathaniel Bouganim, Kevin Petrecca, Sarkis Meterissian, Atilla Omeroglu, Mark Basik, Morag Park
Journal: Cancer Research (2018)

Abstract Breast cancer (BC) exhibits a wide range of morphologic phenotypes and gene expression profiles. Most of the studies that led to the identification of intrinsic molecular subtypes in BC were limited to invasive ductal carcinomas of the breast and did not take rare histopathologic subtypes into account. Rare histopathologic BC subtypes (collectively less than 2% of all breast cancer) have particular prognostic and clinical characteristics. There is no current established treatment that takes into account the specificity of rare BC subtypes. This is mainly due to the absence of clinical trials to determine the optimal management of these rare pathologies. The establishment of relevant preclinical models and molecular characterization of rare BC subtypes is essential for identifying directed and suitable therapeutic regimens for BC patients diagnosed with these rare histopathologic variants. Patient-derived xenograft (PDX) has been recognized as a valuable method to evaluate the clinical diversity of breast cancer. These models were shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. We developed a cohort of eight BC rare histopathologic subtypes, including four metaplastic, one adenoid cystic, one IDC pleomorphic, one neuroendocrine, and one mucinous BC subtype. These PDXs and their primary tumors were submitted to whole-genome sequencing (WGS) and RNA sequencing. We also evaluated a total of 255 proteins by reverse phase protein array (RPPA) in these PDX samples. We are currently performing conditional reprogramming experiments to generate cell lines from these rare BC PDXs. Our preliminary results indicate that pathways related to PI3K/AKT, ERK/MAPK, mTOR, HGF, ERBB, AMPK and IL3 signaling are disrupted in rare BC subtypes. Several genes belonging to these pathways are dysregulated in rare BC tumors, and therefore represent potential therapeutic targets for personalized treatment. Citation Format: Hellen Kuasne, Paul Savage, Constanza Martinez Ramirez, Leah Liu, Valentina Muñoz-Ramos, Virginie Pilon, Anie Monast, Radia Johnson, Nicholas Bertos, Jamil Asselah, Nathaniel Bouganim, Kevin Petrecca, Sarkis Meterissian, Atilla Omeroglu, Mark Basik, Morag Park. Establishment and characterization of rare breast patient-derived xenograft models as a potential resource for personalized medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1044.
Comparison of Ion-Channel Subunit Expression in Canine Cardiac Purkinje Fibers and Ventricular Muscle
Authors: WeiHan, WeishengBao, ZhiguoWang, StanleyNattel
Journal: Circulation Research (2002)

Although Purkinje fibers (PFs) play an important role in cardiac electrophysiology, almost nothing is known about the expression of ion-channel subunits in PFs. We applied competitive reverse transcription–polymerase chain reaction, Western blotting, and immunocytochemistry to compare the expression of ion-channel subunit mRNA and protein in canine PFs versus ventricular muscle (VM). For transient outward current–related subunits, Kv4.2 was not detected, and Kv1.4 expression was extremely low. Kv4.3 expression was of the same order for VM and PFs. The tetraethylammonium chloride–sensitive subunit Kv3.4 was expressed much more strongly in PFs than in VM, and Kv channel–interacting protein transcript expression was 25-fold stronger in VM than in PFs. For delayed rectifiers, ERG and KvLQT1 expression was lower in PFs at both mRNA and protein levels. Although minK transcripts were more numerous in PFs, minK protein was significantly more strongly expressed in VM. L-type Ca2+ current α-subunit (CaV1.2) and Na+...
ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up
Authors: F. Honecker, J. Aparicio, D. Berney, J. Beyer, C. Bokemeyer, R. Cathomas, N. Clarke, G. Cohn-Cedermark, G. Daugaard, K.-P. Dieckmann, K. Fizazi, S. Fosså, J.R. Germa-Lluch, P. Giannatempo, J.A. Gietema, S. Gillessen, H.S. Haugnes, A. Heidenreich, K. Hemminki, R. Huddart, M.A.S. Jewett, F. Joly, J. Lauritsen, A. Lorch, A. Necchi, N. Nicolai, C. Oing, J. Oldenburg, D. Ondruš, A. Papachristofilou, T. Powles, A. Sohaib, O. Ståhl, T. Tandstad, G. Toner, A. Horwich
Journal: Annals of Oncology (2018)

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
Sotalol-Induced Beta Blockade in Cardiac Patients
Authors: Haroldbrooks, Johnbanas, Stevenmeister, Murrillszucs, Jamesdalen, Lewisdexter
Journal: Circulation (1970)

Sotalol (MJ 1999), a beta-adrenergic blocking agent found to have no significant intrinsic myocardial depressant effects, was administered intravenously to 20 patients with heart disease. Eight of the patients had clinical and hemodynamic evidence of chronic heart failure. Doses ranged from 0.2 to 0.6 mg/kg. In all studies, heart rate decreased significantly, accompanied by comparable decreases in cardiac index and tension-time index. There were, however, no significant changes in stroke index, mean blood pressure, or left ventricular end-diastolic pressure—even in those patients with advanced heart failure, indicating that the changes noted were primarily rate-related and could not be ascribed to myocardial depression. To confirm this, further studies were performed in which heart rate was held constant by atrial pacing in normal and catecholamine-depleted dogs. Sotalol, at doses much higher than the minimal beta-blocking dose, did not change stroke index, blood pressure, left ventricular end-diastolic p...
Left Atrial Size and Atrial Fibrillation in Mitral Stenosis
Authors: Peterprobst, Noragoldschlager, Arthurselzer
Journal: Circulation (1973)

In a series of 135 patients with mitral valvular stenosis, three groups were identified: those in sinus rhythm, those with intermittent atrial fibrillation, and those with longstanding, established atrial fibrillation. Examination of the relationships between atrial fibrillation, hemodynamic findings and radiologic data in mitral stenosis was undertaken. Analysis of clinical and hemodynamic factors in the three groups revealed that: 1) age is an etiological factor in the production of atrial fibrillation, as suggested by the age distribution among the three groups; 2) left atrial enlargement may be the result, rather than the cause, of atrial fibrillation; and 3) severity of mitral stenosis is not invariably related to the incidence of atrial fibrillation. Hemodynamic measurements were not significantly different among the three groups, with the single exception of lower cardiac outputs found in patients with established atrial fibrillation. Since no single consequence of mitral stenosis always produces a...
Correlates of the Built Environment and Active Travel: Evidence from 20 US Metropolitan Areas
Authors: Huyen T.K. Le, Ralph Buehler, Steve Hankey
Journal: Environmental Health Perspectives (2018)

Background: Walking and bicycling are health-promoting and environmentally friendly alternatives to the automobile. Previous studies that explore correlates of active travel and the built environment are for a single metropolitan statistical area (MSA) and results often vary among MSAs. Objectives: Our goal was to model the relationship between the built environment and active travel for 20 MSAs spanning the continental United States. Methods: We sourced and processed pedestrian and bicycle traffic counts for 20 U.S. MSAs (n=4,593 count locations), with 1–17 y of data available for each count location and the earliest and latest years of data collection being 1999 and 2016, respectively. Then, we tabulated land use, transport, and sociodemographic variables at 12 buffer sizes (100–3,000m) for each count location. We employed stepwise linear regression to develop predictive models for morning and afternoon peak-period bicycle and pedestrian traffic volumes. Results: Built environment features were significant predictors of active travel across all models. Areas with easy access to water and green space, high concentration of jobs, and high rates of active commuting were associated with higher bicycle and pedestrian volumes. Bicycle facilities (e.g., bike lanes, shared lane markings, off-street trails) were correlated with higher bicycle volumes. All models demonstrated reasonable goodness-of-fit for both bicyclists (adj-R2: 0.46–0.61) and pedestrians (adj-R2: 0.42–0.72). Cross-validation results showed that the afternoon peak-period models were more reliable than morning models. Conclusions: To our knowledge, this is the first study to model multi-city trends in bicycling and walking traffic volumes with the goal of developing generalized estimates of the impact of the built environment on active travel. Our models could be used for exposure assessment (e.g., crashes, air pollution) to inform design of health-promoting cities. https://doi.org/10.1289/EHP3389
Abstract 3721: MMP9 responsive molecular beacon-loaded nanovesicles for imaging and therapy for triple negative breast cancer
Authors: Amalendu P. Ranjan, Rafal Fudala, Sunil Shah, Andrew Gdowski, Piyush Kumar, Ignacy Grycznski, Zygmunt Grycznski, Jamboor K. Vishwanatha
Journal: Cancer Research (2018)

Abstract African American women are disproportionately affected by triple negative breast cancer (TNBC). Combination of tumor chemotherapy and imaging in an ‘all-in-one system' provides a useful multi-modal approach in the battle against metastatic breast cancer. A promising imaging technique, time gated molecular beacon probes, is a noninvasive and painless method for detection and monitoring. Molecular beacon probe-based theranostic nanoparticles is a novel concept in next-generation medicine that combines simultaneous diagnostics and therapeutics to radically change the way we diagnose, image and treat breast cancer. In this study, we formulated pH sensitive nanovesicles containing molecular beacons specific to MMP-9 for imaging tumor microenvironment along with an anticancer drug, thereby enabling visualization of the tumor together with therapy at the tumor site. This theranostic nanosystem will provide an exciting new tool for breast cancer diagnosis and therapy. Formulation of novel pH responsive nanovesicles were carried out using DMPC and DSPE-PG-8CH. Molecular beacons specific to MMP-9, along with cabazitaxel were encapsulated within the nanovesicles. Characterization of the formulated nanovesicles along with intracellular uptake studies were carried out in breast cancer cell lines. The hydrodynamic diameters of the vesicles were measured using a dynamic light scattering (DLS) instrument (Malvern Zetasizer Nano-ZS) and found to be ~65nm. The zeta potential varied between -55 to -60 mV. Validation of molecular beacon loading in liposome and its stability were done using spectroscopy. Results indicated a molecular beacon loading of ≈29 % in the liposomes and the liposomes were stable for atleast 2 weeks. Comparison of cleavage sequence with time MB and MB-loaded liposome showed that even after 72 hours, molecular beacon released from the liposomes were able to cleave MMP-9 and elicit an effect. This unique and innovative combinatorial theranostic strategy can improve the accuracy of imaging and therapy, provide better assessment of the severity of disease and even monitor the response to drug therapy. This innovative proposal of combining an imaging technique together with delivery of anticancer drug at the tumor site will enhance their clinical potential for diagnosis and therapy in metastatic breast cancer therapy. Citation Format: Amalendu P. Ranjan, Rafal Fudala, Sunil Shah, Andrew Gdowski, Piyush Kumar, Ignacy Grycznski, Zygmunt Grycznski, Jamboor K. Vishwanatha. MMP9 responsive molecular beacon-loaded nanovesicles for imaging and therapy for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3721.
Abstract P275: Food Insecurity is Associated with Increased Cardiovascular Risk in US Adults
Authors: Elisabeth L Sattler, Vibha Bhargava
Journal: Circulation (2016)

Background: Food insecurity has been associated with hypertension, hyperlipidemia, and diabetes in US adults; however, our knowledge of the association between food security status and overall cardiovascular risk in US adults is limited. Objective: To examine the association between food security status and cardiovascular risk in US adults. Methods: We performed cross-sectional analysis on 7,439 adults aged ≥ 20 years (mean age 44.12±12.97 years, 52% male, 73% Non-Hispanic White) using data from the National Health and Nutrition Examination Survey 2007-2012. Food security was measured using the validated 18-item US Household Food Security Survey Module. Cardiovascular risk was measured using the American Heart Association’s Life’s Simple 7 (LS7) criteria, with each component being categorized as poor, intermediate, or ideal. Ideal vs. non-ideal levels of each component and the total number of ideal LS7 components (0-4 and 5-7) were compared by food security status. Multivariate logistic regression models were used and adjusted for sociodemographic, economic, and health characteristics. Results: A total of 13% of adults were food insecure and 16% attained ideal scores on 5-7 LS7 components. Compared to food secure, food insecure adults were less likely to be non-Hispanic White, have college education, married, have health insurance coverage, and report excellent health. Food insecure adults were significantly less likely to have ideal scores on 5-7 LS7 components than food secure adults (14.5% vs. 17.7%, p=0.04). In logistic regression models, food insecure had significantly lower odds of attaining ideal scores on 5-7 LS7 components [OR=0.72 (95% CI 0.56-0.92)]. Food insecure were also less likely to have ideal scores on total cholesterol [OR=0.78 (0.62-0.98)], blood glucose [OR=0.77 (0.64-0.92)], BMI [OR=0.82 (0.70-0.97)], and smoking [OR=0.60 (0.47-0.74)]. Conclusion: Food insecure adults are at increased cardiovascular risk. Prevention efforts should be emphasized in this vulnerable population.