tbuckley/cabot-search huggingface dataset:
Abstract 2421: Factors associated with abnormal cervical cancer screening results among screening compliant women in the United States
Authors: Onyema Greg Chido-Amajuoyi, Sanjay Shete
Journal: Cancer Research (2019)

Abstract Introduction: Formal guidelines recommend routine cervical cancer screening using the Papanicolaou (Pap) test and / or screening for high risk Human Papillomavirus (HPV). This study aims to describe the factors associated with abnormal cervical cancer screening outcomes. Methods: We analyzed data from 7,716 women, aged 30 to 65 years, who were respondents of the 2015 Cancer Control Supplement (CCS) of the National Health Interview Survey (NHIS). Weighted multinomial logistic regression was used to examine the factors associated with i) abnormal Pap test, ii) positive high-risk HPV test, as well as iii) abnormal Pap and positive high-risk HPV tests. Results: Overall, 16.8% [95% CI, 15.6 to 18.0] of women who screened for cervical cancer in the last 3 years, had an abnormal result. Risk of abnormal cervical cancer screening results decreased as age increased. Compared to the younger age group (30-45 years), those aged 56-65 years had lower odds of an abnormal Pap test (aOR: 0.71, 95% CI: 0.55, 0.92), positive high-risk HPV test (aOR: 0.51, 95% CI: 0.27, 0.97) or abnormal Pap and positive high-risk HPV tests (aOR: 0.55, 95% CI: 0.35, 0.88). Similarly, women who were married or living with a partner were less likely to have an abnormal Pap test (aOR: 0.83, 95% CI: 0.69, 1.00), than unmarried women. On the contrary, geographic region, race and cigarette smoking were found increase the odds of an abnormal cervical cancer screening result. Blacks were more likely to have abnormal screening results compared to Whites. Current smokers had increased odds of abnormal Pap test (aOR: 1.33, 95% CI: 1.02, 1.73) and positive high-risk HPV test (aOR: 1.94, 95% CI: 1.13, 3.32), compared to never smokers. Discussion: Study findings call for continued surveillance of cancer screening outcomes. More so there is a need for further studies to examine factors promoting an increased likelihood of abnormal cervical cancer screening results in populations identified in this study. Note: This abstract was not presented at the meeting. Citation Format: Onyema Greg Chido-Amajuoyi, Sanjay Shete. Factors associated with abnormal cervical cancer screening results among screening compliant women in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2421.
On the road to universal health care in Indonesia, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
Authors: Nafsiah Mboi, Indra Murty Surbakti, Indang Trihandini, Iqbal Elyazar, Karen Houston Smith, Pungkas Bahjuri Ali, Soewarta Kosen, Kristin Flemons, Sarah E. Ray, Jackie Cao, Scott D. Glenn, Molly K. Miller-Petrie, Meghan D. Mooney, Jeffrey L. Ried, Dina Nur Anggraini Ningrum, Fachmi Idris, Kemal N Siregar, Robert S. Bernstein, Pandu Harimurti, Tikki Pangestu, Yuwono Sidharta, Mohsen Naghavi, Christopher J L Murray, Simon I Hay
Journal: The Lancet. Gastroenterology & hepatology (2018)
Abstract 48: Small Arteritis is the Basic Pathology of Kawasaki Disease
Authors: Zenshiro Onouchi, Akiko Okamoto, Chinatsu Suzuki, Kenji Hamaoka
Journal: Circulation (2015)

Introduction: Pathologic processes of two features in Kawasaki disease (KD) have not been elucidated. The one is the preponderance of aneurysms in the main coronary artery. The other is the discontinuity in the process of the vasculitis between those of microvessels and small arteries, and those of medium-sized to large arteries. Hypothesis: We assessed the hypothesis that arteritis of the vasa vasorum, which we described for the first time, plays a key role in the preponderance of aneurysms in the main coronary artery in KD. Methods: We examined the relationship between patient age at onset of KD and the distance ratio of the aneurysm in the left main coronary artery (LMCA) to clarify the role of arteritis of the coronary vasa vasorum, originated from the atrial and ventricular branches of the peripheral coronary artery, in the ischemia at the media of LMCA. The distance ratio Y was defined as D1/D2 х 100, where D1 and D2 are the distances from the left coronary ostium to the proximal point of the aneurysm and to the bifurcation into the left anterior descending and left circumflex artery, respectively. We then studied the relations between cardiogenic shock and extracardiac aneurysm, and coronary aneurysm in our cases and those of literatures. Results: The mean distance ratio of 56 aneurysms correlated with age, similar to the development of the coronary vasa vasorum: Y = 49.75383 - 3.3739X, P = 0.002987, R = 0.356. Cardiogenic shock which indicates severe interstitial myocarditis and severe arteritis of the coronary vasa vasorum occurs in the 1st week of the illness and is followed by aneurysm formation in LMCA. Extracardiac aneurysm due to severe arteritis of its vasa vasorum associates with severe arteritis of the coronary vasa vasorum originated from the aorta which may induce dilatation at the proximal portion of LMCA. Thus, aneurysm in LMCA complicated with extracardiac aneurysm reveals its proximal extension. In conclusion, these findings may contribute to understand morphogenesis and to investigate the treatment on KD.
Abstract 2694: A first-in-class small-molecule modulator of the p300/CBP interactome exhibits broad efficacy in xenograft models of solid tumors and hematologic malignancies
Authors: Bernd Hentsch, Valentino Cattori, Marc Labelle, Ulrich Kessler
Journal: Cancer Research (2019)

Abstract Background: Dysregulation of the cellular transcription machinery is a fundamental feature of cancer. E1A binding protein (p300) and CREB binding protein (CBP) are two closely related paralog transcription co-activators involved in the expression of oncogenic drivers in cancer cells. Methods: Small molecule ligands of the CH1/TAZ1 domain of p300/CBP were rationally designed and optimized for their anti-proliferative activity in vitro. Subsequent characterization focused on their ability to modulate downstream biological processes controlled by p300/CBP, including hormone-dependent androgen receptor signalling, the HIF-1 alpha/VEGF pathway and reactivation of p53 in HPV-positive carcinomas. The in vivo efficacy of this novel compound class was assessed in a variety of patient and cell line derived xenograft models, and pharmacodynamic effects were investigated. Results: Several modulators of p300/CBP exhibited anti-proliferative effects at low nanomolar concentrations in more than 60 cancer cell lines inducing both senescence and apoptosis in a highly context dependent manner. Transcriptome analyses revealed the downregulation of various drivers of cell cycle progression. Once daily oral administration triggered strong growth-inhibitory effects in several xenograft models up to complete tumor eradication at well tolerated doses. p300/CBP dependent biomarkers like VEGF (colon cancer) and PSA (prostate cancer) were significantly downregulated in the tumors of treated animals. In an orthotopic model of acute myeloid leukemia, the growth of primary tumors and metastasis was almost completely inhibited. Conclusions: Reprogramming the transcriptional profile of cancer cells by modulation of p300/CBP activity by targeting the CH1/TAZ1 domain represents a novel and broadly applicable approach for the treatment of cancer. The presented data illustrate the clinical potential of this new class of therapeutics against a broad variety of tumor types, including prostate and colon cancer as well as hematological malignancies. Citation Format: Bernd Hentsch, Valentino Cattori, Marc Labelle, Ulrich Kessler. A first-in-class small-molecule modulator of the p300/CBP interactome exhibits broad efficacy in xenograft models of solid tumors and hematologic malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2694.
Explaining variation in the burden of child and adolescent tuberculosis
Authors: Kathryn J. Snow, Susan M. Sawyer, Justin T. Denholm, Stephen M. Graham
Journal: European Respiratory Journal (2019)

<b>The burden of tuberculosis in children and&nbsp;young people depends greatly on the intensity of the TB epidemic, the demographics of the population, and the success of prevention efforts</b>http://bit.ly/2ETFTik
Abstract 18342: Development of Fibrotic Substrate for Atrial Fibrillation in Advanced Heart Failure is Driven Not by Inflammation but by Smad2/3 Dependent Replacement Fibrosis
Authors: Shin Yoo, Edward B Thorp, Aaron Kunamalla, Gary L Aistrup, Jason Ng, David Gordon, Bradley Knight, Rod Passman, Jeffrey Goldberger, Rishi Arora
Journal: Circulation (2015)

Introduction: Fibrosis is an important contributor to atrial fibrillation (AF) substrate in heart failure, with TGF-β signaling generating atrial fibrosis. Inflammation is also known to contribute to AF. However, it is not known: a) if inflammation underlies the development of atrial fibrosis, b) if TGF-β signaling is involved in the generation of atrial inflammation and c) what is the relative role of canonical SMAD2/3 versus non-canonical TGF-β-activated kinase 1 (TAK) signaling in the creation of atrial inflammation/fibrosis. Methods: 21 dogs underwent transfection in the posterior left atria of either a plasmid expressing a dominant negative TGF-β type II receptor (pUBC-TGFβ-DN-RII) (N=9) or control vector (pUBC-LacZ) (N=12), followed by 3-4 weeks of right ventricular tachypacing (VTP) (240 bpm). After 3-4 weeks of VTP, the following were assessed: AF by open-chest mapping. Atrial tissue was assessed for signaling (pSMAD2/3 and pTAK) by western blot, fibrosis by trichrome staining and iflammation by CD68 staining. Results: The interstitial fibrosis in LacZ atria was replacement in character (Fig 1A). TGFβ-RII-DN dogs had a significant decrease in replacement fibrosis leading to a decrease in duration of inducible AF (LacZ 63.64 ± 12.12 s vs. TGFβ 26.52 ± 3.79 s, p &lt; 0.05). While both groups demonstrated evidence of inflammation (CD68 staining), there was no difference in inflammation between the groups (Fig 1B). TGFβ-RII-DN dogs had a significant decrease in pSMAD2/3 but not pTAK, compared to pUBC-LacZ dogs. Conclusion: The development of fibrotic substrate for AF in advanced HF is driven not by inflammation but primarily by SMAD2/3 mediated myocardial replacement fibrosis. These findings may have important implications for mechanism-guided therapies for AF, with canonical TGF-β signaling appearing to be an attractive therapeutic target in AF.
Abstract LB-204: DNA vaccine co-expressing Her2/ErbB2 antigen, fused with LAMP, elicits strong antitumor effects in vivo by increasing tumor infiltration with CD8+ T cells
Authors: Renhuan Xu, Teri Heiland
Journal: Cancer Research (2019)

Abstract DNA vaccines have emerged as an attractive immunotherapeutic approach against infectious diseases and cancer due to its fast, efficient design and validation. It remains, however, a challenge in clinical settings due to historically low levels of immunogenicity in humans. In order to enhance the immunogenicity of DNA vaccines used as a cancer therapy, we have developed a nucleic acid platform, UNITE (UNiversal Intracellular Targeted Expression), which combines novel delivery methods and adjuvants which complement our lysosomal targeting technology. Fusing a tumor associated antigen (TAA) with the Lysosomal Associated Membrane Protein 1 (LAMP-1), we can activate Ag specific CD4+ T cells by targeting the major histocompatibility complex II compartment. In this study, we selected ErbB2/Her2 as the cancer target because it is a broadly overexpressed and well-characterized oncoantigen. Mice vaccinated with Her2-LAMP DNA demonstrate robust Her2-specific CD4+ and CD8+ T cells, in addition to antibody responses, which in turn have significant antitumor effect in murine breast and bladder tumor models. Moreover, we demonstrate that the Her2-LAMP vaccine promotes CD8+ T cell tumor infiltration to a greater degree than when compared to a traditional DNA vaccine without LAMP. In summary, we show that UNITE as a nucleic acid platform, can enhance antitumor immunity in vivo. Citation Format: Renhuan Xu, Teri Heiland. DNA vaccine co-expressing Her2/ErbB2 antigen, fused with LAMP, elicits strong antitumor effects in vivo by increasing tumor infiltration with CD8+ T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-204.
Abstract 10103: Improvement in Survival With Favorable Neurological Outcome in Elderly Japanese Patients With Out-of-Hospital Cardiac Arrest: A Nationwide Observational Cohort Study
Authors: Akira Funada, Yoshikazu Goto, Tetsuo Maeda, Ryota Teramoto, Masakazu Yamagishi
Journal: Circulation (2015)

Introduction: Although older age is associated with worse prognosis after cardiac arrest, little is known about the improvement in survival of very elderly patients with out-of hospital cardiac arrest (OHCA). Hypothesis: We aimed to evaluate the survival trends and predictors of favorable prognosis in this population. Method: We analyzed the records of 607,147 OHCA events obtained from a prospectively collected nationwide Utstein-style Japanese database from 2008 to 2012. The end-point was 1-month survival with favorable neurological outcome (Cerebral Performance Category Scale, category 1 or 2; CPC 1-2). Results: In total, 334,730 OHCA patients aged ≥75 years were eligible for analyses. The overall 1-month CPC 1-2 rate was 0.88% (2,933/334,730). OHCA aged 75-84 years had better 1-month CPC 1-2 rate than those ≥85years (1.18% [2,067/174,781] vs 0.54% [866/159,949], p &lt;0.0001). The 1-month CPC 1-2 rate improved in OHCA aged ≥75 years (0.73% [433/59,595] in 2008 to 0.96% [708/73,487] in 2012, p for trend &lt;0.001), even in only OHCA aged ≥85 years (0.42% [115/27,163] in 2008 to 0.65% [241/36,860] in 2012, p for trend &lt;0.0001). Multivariate logistic regression analysis indicated that bystander-witnessed arrest (adjusted odds ratio [aOR] 5.7, 95% confidential interval [CI] 5.2–6.3, p &lt;0.0001) and initial shockable rhythm (aOR 10.6, 95% CI 9.8–11.5, p &lt;0.0001) were significantly associated with 1-month CPC 1-2 rates of OHCA aged ≥75 years. OHCA with bystander witness and initial shockable rhythm had a higher 1-month CPC 1-2 rate than the others (11.14% [1,061/9,520] vs 0.58% [1,872/325,210], p &lt;0.0001, aOR 19.1, 95% CI 17.6–20.7, p &lt;0.0001). The 1-month CPC 1-2 rate of OHCA with initial unshockable rhythm also improved 0.42% (239/56,927) in 2008 to 0.60% (420/70,583) in 2012 (p for trend &lt;0.001); however, in OHCA without bystander witness, the 1-month CPC 1-2 rate did not improve between 2008 (0.19% [71/36,736]) and 2012 (0.28% [125/45,224]) (p for trend = 0.080). Conclusion: Data drawn from a large subset of elderly patients in Japanese registry suggest that rate of 1-month CPC 1-2 from OHCA have significantly improved during the study period; however, the OHCA outcome differed by bystander-witness and first documented rhythm.
Abstract 4127: RX-5902 exhibits direct and immunomodulatory anti-tumor activities in melanoma PDX models
Authors: Andrew Eisen
Journal: Cancer Research (2019)

Abstract Background: Nuclear β-catenin promotes deleterious processes in tumors and their microenvironment. Diminishing nuclear β-catenin attenuates these oncogenic processes. RX-5902 is an oral, small molecule inhibitor of β-catenin nuclear translocation mediated by phosphorylated p68 (DDX5). RX-5902 exhibits potent anti-cancer activity in many cancer cell lines, xenograft models in immunodeficient mice and immune competent mice and in patients. This study examines the relative contribution and context of the direct and immunomodulatory effects on the anti-tumor activities of RX-5902. Methods: Four patient-derived melanoma xenograft models were implanted into either immunodeficient nude mice or NOG mice “humanized” with HLA unmatched CD34+ stem cells with average humanization of 36%. The PDX models were derived from 2 tumors that were clinically unresponsive to an anti-PD-1 agent and 2 tumors obtained prior to any immune treatment. In each category one tumor had BRAF WT and one a V600E mutation. Mice were randomized to receive either vehicle or RX-5902 at 5, 15 or 50 mg/kg po QDx5/Off x2 when implanted tumors reached 100-120 mm3 and began treatment when tumors reached 200mm3. Treatment lasted for 28 days and animals were observed for an additional 14 off therapy. Results: The tumor growth inhibition data at 50 mg/kg is found in the table below. There was evidence of an immune contribution to the TGI in those tumors derived from subjects who did not benefit from I/O (Nivolumab) therapy. In each category the response was greater in tumors with WT BRAF. Conclusion: RX-5902 provided greater TGI in the two melanoma PDX models derived from subjects who were resistant to I/O therapy compared to the models from I/O naïve subjects and, regardless, is greater in BRAF WT vs mutant tumors. The RX-5902 immune-mediated anti-tumoral activity may benefit the majority of melanoma subjects with limited response to BRAF-directed and/or I/O therapy. Citation Format: Andrew Eisen. RX-5902 exhibits direct and immunomodulatory anti-tumor activities in melanoma PDX models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4127.
Abstract 1667: A robust human immune profiling assay using CyTOF technology and automated data analysis software
Authors: Stephen K. Li, Daniel Majonis, C. Bruce Bagwell, Benjamin C. Hunsberger, Vladimir I. Baranov, Olga I. Ornatsky
Journal: Cancer Research (2019)

Abstract Immune monitoring is an essential method for quantifying changes in immune cell population numbers and states over time in health and disease. A cornerstone in translational and clinical research, it is frequently used in the investigation of chronic inflammation, infectious disease, autoimmune diseases, and cancer. The diversity of immune cell populations demands a highparameter approach to more fully and efficiently quantify these changes. Mass cytometry, which utilizes CyTOF® technology, is a single-cell analysis platform that uses metal-tagged antibodies to resolve over 40 markers in a single tube of sample without the need for compensation. It is an ideal solution for routine enumeration of immune cell populations. However, development of a robust, highly multiplexed assay requires panel optimization as well as standardization of instrument setup and an analysis pipeline. We have developed a sample-to-answer solution for human immune profiling using mass cytometry. It includes an optimized 30-marker immune profiling panel provided in a lyophilized, single-tube format, validated SOPs for human whole blood and PBMC staining, an instrument data acquisition template, instructions for data acquisition on a Helios™ system, and automated software for data analysis. The software analyzes FCS 3.0 files generated with the kit; automatically reports cell counts, percentage calculations, and staining intensity; and produces graphical elements such as histograms, dot plots, and a Cen-se′™ (t-SNE variant) graph for 36 immune cell populations. Here we present assay analytical validation data on repeatability, reproducibility, software precision, and software accuracy. We also present a performance comparison of the lyophilized material and a liquid formulation of the same antibodies and clones used in the lyophilized format. This assay provides a robust, complete solution for broad immune profiling using mass cytometry that reduces sources of variability and subjectivity in sample preparation and data analysis. Citation Format: Stephen K. Li, Daniel Majonis, C. Bruce Bagwell, Benjamin C. Hunsberger, Vladimir I. Baranov, Olga I. Ornatsky. A robust human immune profiling assay using CyTOF technology and automated data analysis software [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1667.
Test Detects Prosthetic Joint Infection in Synovial Fluid
Authors: Rebecca Voelker
Journal: JAMA (2019)

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Bayesian bacterial detection using irregularly sampled optical endomicroscopy images
Authors: Ahmed Karam Eldaly, Yoann Altmann, Ahsan Akram, Paul McCool, Antonios Perperidis, Kevin Dhaliwal, Stephen McLaughlin
Journal: Medical Image Analysis (2019)

Pneumonia is a major cause of morbidity and mortality of patients in intensive care. Rapid determination of the presence and gram status of the pathogenic bacteria in the distal lung may enable a more tailored treatment regime. Optical Endomicroscopy (OEM) is an emerging medical imaging platform with preclinical and clinical utility. Pulmonary OEM via multi-core fibre bundles has the potential to provide in vivo, in situ, fluorescent molecular signatures of the causes of infection and inflammation. This paper presents a Bayesian approach for bacterial detection in OEM images. The model considered assumes that the observed pixel fluorescence is a linear combination of the actual intensity value associated with tissues or background, corrupted by additive Gaussian noise and potentially by an additional sparse outlier term modelling anomalies (bacteria). The bacteria detection problem is formulated in a Bayesian framework and prior distributions are assigned to the unknown model parameters. A Markov chain Monte Carlo algorithm based on a partially collapsed Gibbs sampler is used to sample the posterior distribution of the unknown parameters. The proposed algorithm is first validated by simulations conducted using synthetic datasets for which good performance is obtained. Analysis is then conducted using two ex vivo lung datasets in which fluorescently labelled bacteria are present in the distal lung. A good correlation between bacteria counts identified by a trained clinician and those of the proposed method, which detects most of the manually annotated regions, is observed.