tbuckley/cabot-search huggingface dataset:
Insights Into the Mechanism of Zymogen Protein C Protection Against Cancer Progression
Authors: Julie M Crudele, Geerte L. Van Sluis, Paris Margaritis, Joshua I Siner, Michael Sliozberg, Jenna Maurer, Armida Faella, Shangzhen Zhou, Katherine A. High, Charles T Esmon, C. Arnold Spek, Valder R Arruda
Journal: Blood (2012)
Effects of a New Pathogen-Reduction Technology (Mirasol PRT) on Platelet Function.
Authors: Maribel Diaz-Ricart, Silvia Perez-Pujol, Raul Tonda, Miguel Lozano, Berta Fuste, Irene Lopez-Vilchez, Ana M. Galan, Junzhi Li, Raymond Goodrich, Gines Escolar
Journal: Blood (2004)
P2.03a-028 Phase I/II Trial of Carboplatin, nab-Paclitaxel and Bevacizumab for Advanced Non-Squamous Non-Small Cell Lung Cancer: Results of Phase I Part
Authors: Satoshi Ikeo, Naoyuki Nogami, Hiromoto Kitajima, Hiroshige Yoshioka, Akihiro Bessho, Kyoichi Kaira, Toshio Kubo, Shuji Murakami, Koshiro Watanabe, Katsuyuki Kiura
Journal: Journal of Thoracic Oncology (2017)
P2.06-002 Phase I Study of DS-6051b, a ROS1/NTRK Inhibitor, in Japanese Subjects with Advanced Solid Tumors Harboring Either a ROS1 or NTRK Fusion Gene
Authors: Kaname Nosaki, Yutaka Fujiwara, Masayuki Takeda, Noboru Yamamoto, Kazuhiko Nakagawa, Chihiro Abe, Ryota Shiga, Kenji Nakamaru, Takashi Seto
Journal: Journal of Thoracic Oncology (2017)
P1.05-048 Effect of Adjuvant Chemotherapy on the Patterns and Dynamics of Recurrences in Resected Stage II(N1) Lung Adenocarcinoma
Authors: Byung Jo Park, Yong Soo Choi, Jung Hee Lee, Hong Kwan Kim, Jong Ho Cho, Jae Ill Zo, Young Mog Shim, Sumin Shin, Myung-Ju Ahn, Jin Seok Ahn, Keunchil Park, Jhingook Kim
Journal: Journal of Thoracic Oncology (2017)
Types of Myocardial Infarction Among Human Immunodeficiency Virus–Infected Individuals in the United States
Authors: Heidi M. Crane, Pathmaja Paramsothy, Daniel R. Drozd, Robin M. Nance, J. A. Chris Delaney, Susan R. Heckbert, Matthew J. Budoff, Greer A. Burkholder, James H. Willig, Michael J. Mugavero, William C. Mathews, Paul K. Crane, Richard D. Moore, Joseph J. Eron, Sonia Napravnik, Peter W. Hunt, Elvin Geng, Priscilla Hsue, Carla Rodriguez, Inga Peter, Greg S. Barnes, Justin McReynolds, William B. Lober, Kristina Crothers, Matthew J. Feinstein, Carl Grunfeld, Michael S. Saag, Mari M. Kitahata
Journal: JAMA Cardiology (2017)

The Second Universal Definition of Myocardial Infarction (MI) divides MIs into different types. Type 1 MIs result spontaneously from instability of atherosclerotic plaque, whereas type 2 MIs occur in the setting of a mismatch between oxygen demand and supply, as with severe hypotension. Type 2 MIs are uncommon in the general population, but their frequency in human immunodeficiency virus (HIV)-infected individuals is unknown.
Organophosphorus Xenobiotic Toxicology
Authors: John E. Casida
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Originally, organophosphorus (OP) toxicology consisted of acetylcholinesterase inhibition by insecticides and chemical threat agents acting as phosphorylating agents for serine in the catalytic triad, but this is no longer the case. Other serine hydrolases can be secondary OP targets, depending on the OP structure, and include neuropathy target esterase, lipases, and endocannabinoid hydrolases. The major OP herbicides are glyphosate and glufosinate, which act in plants but not animals to block aromatic amino acid and glutamine biosynthesis, respectively, with safety for crops conferred by their expression of herbicide-tolerant targets and detoxifying enzymes from bacteria. OP fungicides, pharmaceuticals including calcium retention agents, industrial chemicals, and cytochrome P450 inhibitors act by multiple noncholinergic mechanisms, often with high potency and specificity. One type of OP-containing fire retardant forms a highly toxic bicyclophosphate γ-aminobutyric acid receptor antagonist upon combustion. Some OPs are teratogenic, mutagenic, or carcinogenic by known mechanisms that can be avoided as researchers expand knowledge of OP chemistry and toxicology for future developments in bioregulation.
P1.05-010 Aberrant Promoter Methylation of ESR1 and CDH13 Gene Are an Independent Prognostic Marker in Surgically Resected Non-Small Cell Lung Cancer
Authors: Milica Kontic, Dragana Jovanovic, Svetlana Bojic, Heather Nelson, Simona Ognjanovic
Journal: Journal of Thoracic Oncology (2017)
P3.02a-004 NSCLC Patients Harboring ALK Translocation: Clinical Characteristics and Management in Real World Setting. EXPLORE GFPC 02-14
Authors: Isabelle Monnet, Jean Bernard Auliac, Radj Gervais, Anne Marie Chiappa, Nathalie Baize, Suzanna Bota, Helene Doubre, Chrystele Locher, Acya Bizieux, Gilles Robinet, Christos Chouaid
Journal: Journal of Thoracic Oncology (2017)
Pharmacological Inhibition of PIM Kinases In Chronic Lymphocytic Leukemia Cases with Unfavorable Prognosis Markers
Authors: Beatriz Herreros, James R. Bischoff, Maria E. Rodriguez, Margarita Sanchez-Beato, Elena Domenech, Carmen Blanco, Cristina I. Gomez-Abad, Raul Cordoba, Julio Delgado, Jose A Garcia-Marco, Juan F. Garcia, José Francisco Tomás, Joaquín Martínez-López, Antonia Rodriguez, Raquel Villuendas, Miguel A. Piris
Journal: Blood (2010)
Unsupervised Clustering of Quantitative Image Phenotypes Reveals Breast Cancer Subtypes with Distinct Prognoses and Molecular Pathways
Authors: Jia Wu, Yi Cui, Xiaoli Sun, Guohong Cao, Bailiang Li, Debra M. Ikeda, Allison W. Kurian, Ruijiang Li
Journal: Clinical Cancer Research (2017)

Abstract Purpose: To identify novel breast cancer subtypes by extracting quantitative imaging phenotypes of the tumor and surrounding parenchyma and to elucidate the underlying biologic underpinnings and evaluate the prognostic capacity for predicting recurrence-free survival (RFS). Experimental Design: We retrospectively analyzed dynamic contrast–enhanced MRI data of patients from a single-center discovery cohort (n = 60) and an independent multicenter validation cohort (n = 96). Quantitative image features were extracted to characterize tumor morphology, intratumor heterogeneity of contrast agent wash-in/wash-out patterns, and tumor-surrounding parenchyma enhancement. On the basis of these image features, we used unsupervised consensus clustering to identify robust imaging subtypes and evaluated their clinical and biologic relevance. We built a gene expression–based classifier of imaging subtypes and tested their prognostic significance in five additional cohorts with publically available gene expression data but without imaging data (n = 1,160). Results: Three distinct imaging subtypes, that is, homogeneous intratumoral enhancing, minimal parenchymal enhancing, and prominent parenchymal enhancing, were identified and validated. In the discovery cohort, imaging subtypes stratified patients with significantly different 5-year RFS rates of 79.6%, 65.2%, 52.5% (log-rank P = 0.025) and remained as an independent predictor after adjusting for clinicopathologic factors (HR, 2.79; P = 0.016). The prognostic value of imaging subtypes was further validated in five independent gene expression cohorts, with average 5-year RFS rates of 88.1%, 74.0%, 59.5% (log-rank P from &amp;lt;0.0001 to 0.008). Each imaging subtype was associated with specific dysregulated molecular pathways that can be therapeutically targeted. Conclusions: Imaging subtypes provide complimentary value to established histopathologic or molecular subtypes and may help stratify patients with breast cancer. Clin Cancer Res; 23(13); 3334–42. ©2017 AACR.
S47 Pneumolysin promotes neutrophil: platelet aggregation in vitro
Authors: JG Nel, C Durandt, AJ Theron, GR Tintinger, TJ Mitchell, C Feldman, R Anderson
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> The pneumococcal cholesterol-binding, pore-forming toxin, pneumolysin (Ply), appears to be a key mediator not only of the acute lung injury, but also myocardial damage, associated with severe pneumococcal disease. Although direct Ply-mediated cardiopulmonary toxicity has been implicated, the neutrophil- and platelet-targeted pro-inflammatory activities of the toxin are also believed to contribute to the pathogenesis of these adverse events, albeit by poorly characterised mechanisms. To test the hypothesis that Ply promotes neutrophil: platelet networking, we have investigated the effects of the toxin on the induction of heterotypic aggregation of these cells <i>in vitro.</i> <h3>Methods</h3> Neutrophil: platelet-enriched buffy coat suspensions were prepared from the heparinised blood of healthy, adult humans by sedimentation (at 37°C) and diluted 1:50 in Hanks’ balanced salt solution. Following 5 min of preincubation, recombinant Ply (10–80 ng/ml), or the pneumolysoid, delta 6Ply (attenuated with respect to pore-forming activity, negative control), or adenosine 5’-diphosphate (ADP, 100 μM, positive control) were added to the cell suspensions. After a further 5 min period of incubation at 37°C, samples were stained with 5 μl of each of the following murine, anti-human, fluorochrome-labelled monoclonal antibodies: CD16-APC (neutrophils), CD42a-PE (platelets), and CD45-Krome Orange, and incubated for 15 min at room temperature in the dark. This was followed by analysis of samples at a slow rate using a Gallios flow cytometer. The relative numbers of platelets interacting with a single neutrophil were determined using the relative mean fluorescence intensities of CD16+/CD42a+/CD45+ neutrophils. <h3>Results</h3> These are shown in the accompanying table. Addition of Ply to the mixed cell suspension resulted in statistically significant dose-related formation of neutrophil:platelet aggregates which was maximal at 80 ng/ml and greater in magnitude to that observed with ADP, while delta6Ply was ineffective. <h3>Conclusion</h3> Ply, at pathologically-relevant concentrations, promotes neutrophil:platelet aggregation <i>in vitro</i>, an activity which is dependent on the pore-forming properties of the toxin. Given the increasing recognition of the role played by platelets in driving neutrophilic inflammation, this activity of Ply may exacerbate pulmonary and myocardial injury in severe pneumococcal disease.
Augmented Effects on Neovascularization by Mixing the Conditioned Medium from Early EPCs into Late EPCs Derived from Human Cord Blood.
Authors: Eun-Sun Yoo, Jee-Young Ahn, Yun-Kyung Bae, Jee Hyun Kong, Sang Min Lee, Yeung-Chul Mun, Kyoung-Eun Lee, Chu-Myong Seong
Journal: Blood (2006)
S121 The occupations at increased copd risk in the large population-based uk biobank cohort
Authors: S De Matteis, D Jarvis, A Darnton, L Rushton, P Cullinan
Journal: Thorax (2016)

<h3>Background</h3> Occupational exposures are important and preventable causes of COPD. In a cross-sectional study of current occupation among over 220,000 workers in the UK Biobank cohort (over 500,000 subjects) we previously reported that 14 jobs were associated with increased COPD risk (De Matteis S, et al., OEM, 2016). To progress these findings we developed OSCAR, a new web-based tool for efficient self-reporting and automatic coding of job-histories in large population-based studies. Our aim was to identify the occupations at increased COPD risk taking into account lifetime job-histories in the UK general population. <h3>Methods</h3> We administered OSCAR to all UK Biobank participants with an available email address (n = 324,653) between June-February 2016. Paid jobs held for at least six months were collected and coded by OSCAR using the UK Standard Occupational Classification (SOC), v.2000. COPD was defined as FEV1/FVC&lt;LLN based on spirometry performed at recruitment. Prevalence ratios (PRs) for ever-exposure to each of the 353 SOC-coded jobs using lifetime office workers as reference category were estimated using Poisson regression with adjustment for age, sex, recruitment centre and lifetime tobacco smoking. In addition, we used lifetime cumulative job durations to test for exposure-response trends. <h3>Results</h3> Among the 116,375 participants who completed OSCAR (response rate: 34%), 94,551 had acceptable and repeatable spirometry data (according to ERS/ATS criteria) and smoking information and were included in the analyses. Taking into account individual lifetime job-histories, 19 jobs significantly increased COPD risk (e.g. ‘fishing and agriculture related occupations’: PR: 1.69; 95% confidence interval (CI): 1.18–2.42, and ‘food, drink and tobacco process operatives’: PR: 1.42; 95% CI: 1.02–1.97). The majority were also confirmed by positive exposure-response trends for cumulative years of employment in each job/lifetime. <h3>Conclusions</h3> Compared to our previous cross-sectional study, some jobs were confirmed (e.g. ‘food, drink and tobacco process operatives’, and ‘horticultural trades’) while others were not (e.g. ‘coal miners’), likely due to the few employed in these jobs among the OSCAR responders. OSCAR is still collecting job-histories in the UK Biobank cohort; further analyses on a larger sample, as well analyses restricted to never-smokers and never-asthmatics to investigate the possibility of residual confounding, are planned.
Firearm Violence as a Disease—“Hot People” or “Hot Spots”?
Authors: Charles C. Branas, Sara Jacoby, Elena Andreyeva
Journal: JAMA Internal Medicine (2017)

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RASGRP1/APTX Ratio Strongly Correlates with Clinical Response and Survival in AML Patients Treated with Tipifarnib-Bortezomib Combination.
Authors: Stefania Paolini, Emanuela Ottaviani, Sarah Parisi, Federica Salmi, Barbara Lama, Antonio Curti, Daniela Cilloni, Anna Candoni, Ernesto Vigna, Cristina Clissa, Carlo Finelli, Ilaria Iacobucci, Claudio Laterza, Cristina Papayannidis, Pier Paolo Piccaluga, Nicola Vianelli, Giuseppe Saglio, Renato Fanin, Fortunato Morabito, Alfonso Zaccaria, Francesco Lauria, Marco Gobbi, Dino Amadori, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2009)
Phase 1/ 2 Study of Sapacitabine and Decitabine Administered Sequentially in Elderly Patients with Newly Diagnosed AML,
Authors: Farhad Ravandi, Stefan Faderl, Jorge E. Cortes, Guillermo Garcia-Manero, Elias Jabbour, Patricia Ann Boone, Tapan Kadia, Gautam Borthakur, William G. Wierda, Meir Wetzler, Parameswaran Venugopal, Judy Chiao, Hagop M. Kantarjian
Journal: Blood (2011)
P2.03b-049 Molecular &amp; Clinical Status of Current Biomarkers: EGFR, ALK, ROS, MET of Lung Cancer in North Indian Patients
Authors: Moushumi Suryavanshi, Dushyant Kumar, Manoj Panigrahi, Meenakshi Choudhary, Anurag Mehta
Journal: Journal of Thoracic Oncology (2017)
BMA will no longer be lone representative of doctors in contract negotiations in England
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Two unions will represent hospital, staff specialist, and junior doctors in contract negotiations in England in future, after the Hospital Consultants and Specialists Association became the first NHS trade union in decades to win national collective bargaining rights.

Previously the HCSA, formed in 1948, has been limited to representing its members at a local level and in grievance procedures. It has campaigned for decades for collective bargaining rights, which since the inception of the NHS have been limited to the BMA. Relations between the BMA and the government became strained last year during the protracted strike by junior doctors, with England’s health secretary, Jeremy Hunt, accusing the BMA of being “irresponsible” and “misleading its members.”1

In an interview the HCSA’s president, Ross Welch, told The …
Role of Pleckstrin 2 in Improved Erythropoiesis of Transferrin-Treated Beta-Thalassemic Mice
Authors: Maria Feola, Andrea Zamperone, Weili Bao, Tenzin Choesang, Huihui Li, Guiyuan Li, Antonia Follenzi, Shilpa M Hattangadi, Christopher Mason, Peng Ji, Yelena Ginzburg
Journal: Blood (2015)
P3.02c-030 Use of a 200-Mg Fixed Dose of Pembrolizumab for the Treatment of Advanced Non–Small Cell Lung Cancer (NSCLC)
Authors: Edward Garon, Martin Reck, Delvys Rodríguez-Abreu, Andrew Robinson, Rina Hui, Csőszi Tibor, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, David Turner, Julie Stone, Reshma Rangwala, Julie Brahmer
Journal: Journal of Thoracic Oncology (2017)
IKAROS expression in distinct bone marrow cell populations as a candidate biomarker for outcome with lenalidomide‐dexamethasone therapy in multiple myeloma
Authors: Arnold Bolomsky, Wolfgang Hübl, Stefano Spada, Ercan Müldür, Karin Schlangen, Daniel Heintel, Alberto Rocci, Adalbert Weißmann, Veronique Fritz, Martin Willheim, Niklas Zojer, Antonio Palumbo, Heinz Ludwig
Journal: American Journal of Hematology (2017)

Immunomodulatory drugs (IMiDs) are a cornerstone in the treatment of multiple myeloma (MM), but specific markers to predict outcome are still missing. Recent work pointed to a prognostic role for IMiD target genes (e.g. CRBN). Moreover, indirect activity of IMiDs on immune cells correlated with outcome, raising the possibility that cell populations in the bone marrow (BM) microenvironment could serve as biomarkers. We therefore analysed gene expression levels of six IMiD target genes in whole BM samples of 44 myeloma patients treated with lenalidomide-dexamethasone. Expression of CRBN (R = 0.30, P = .05), IKZF1 (R = 0.31, P = .04), IRF4 (R = 0.38, P = .01), MCT-1 (R = 0.30, P = .05), and CD147 (R = 0.38, P = .01), but not IKZF3 (R = -0.15, P = .34), was significantly associated with response. Interestingly, IKZF1 expression was elevated in BM environmental cells and thus selected for further investigation by multicolor flow cytometry. High IKAROS protein levels in total BM mononuclear cells (median OS 83.4 vs. 32.2 months, P = .02), CD19+ B cells (median OS 71.1 vs. 32.2 months, P = .05), CD3+ CD8+ T cells (median OS 83.4 vs 19.0 months, P = .008) as well as monocytes (median OS 53.9 vs 18.0 months, P = .009) were associated with superior overall survival (OS). In contrast, IKAROS protein expression in MM cells was not predictive for OS. Our data therefore corroborate the central role of immune cells for the clinical activity of IMiDs and built the groundwork for prospective analysis of IKAROS protein levels in distinct cell populations as a potential biomarker for IMiD based therapies.
IGHV Gene Replacement in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Occurs at a Frequency Similar to That in Normal B Cells and May Augment Clonal Expansion by Permitting Autogenic/Microbial Clonal Stimulation.
Authors: Katerina Hatzi, Sophia Yancopoulos, Emilia Albesiano, Max D. Cooper, Zhixin Zhang, Manlio Ferrarini, Nicholas Chiorazzi
Journal: Blood (2006)
Cross Reactivity of Rabbit Anti-Recothrom (Human Recombinant Thrombin) Antibodies with Molecular Variants of Human Thrombin, and Various Bovine Thrombin Preparations
Authors: Nasir Sadeghi, Josephine Cunanan, Debra Hoppensteadt, Indermohan Thethi, Rakesh Wahi, Jawed Fareed
Journal: Blood (2010)
P136 Relationship between progression of lung disease in alpha-1 antitrypsin deficiency and cardiovascular risk
Authors: C Hall, S Samanta, N Verma, B Gooptu, JR Hurst
Journal: Thorax (2016)

<h3>Introduction</h3> Patients with alpha-1 antitrypsin deficiency (AATD) who are homozygous for the mutated Z allele (PiZZ) typically present with emphysema and liver cirrhosis, caused by the uncontrolled action of neutrophil elastase in the lungs and toxic gain-of-function AAT polymer aggregates in the ER of hepatocytes. The link between cardiovascular disease and COPD is widely accepted, but is less well understood in AATD. This study aimed to investigate how markers of lung function severity and the rate of disease progression are associated with cardiovascular risk in a cohort of PiZ patients. <h3>Methods</h3> Cardiovascular (CV) risk was determined by the degree of arterial stiffness, measured using aortic pulse wave velocity (aPWV). This was recorded with the Vicorder device which uses the transcutaneous distance between the common carotid and femoral arteries, and the time delay between the feet of the 2 diastolic pulse waveforms to calculate the pulse velocity. Cardiovascular risk was additionally assessed using the QRISK2 algorithm. Pulmonary function was evaluated using FEV1, KCO and RV%TLC, and the degree of AATD disease progression used previous pulmonary function test (PFT) data to determine the rate of lung function decline. <h3>Results</h3> We enrolled 48 PiZZ AATD patients (mean (SD) age 52.9 (15.9) years, 19 male) and found significant relationships (denoted by: **p &lt; 0.01 and *p &lt; 0.05) between both aPWV and QRISK2 and the degree of airflow obstruction (FEV1: r = −0.470**, rho = −0.325*), emphysema (KCO: r = −0.493**, r = −0.411**) and hyperinflation (RV%TLC: r = 0.550**, r = 0.433**). Including only patients with ≥3 PFT results, we found a significant relationship between emphysema progression and calculated but not measured cardiovascular risk: KCO change vs. QRISK2 (r = −0.549, p = 0.015, n = 19). <h3>Conclusions</h3> Reduced lung function was associated with a greater magnitude of measured and calculated cardiac risk in the AATD cohort. However AATD-mediated lung disease progression was not significantly related to measured CV risk – an exception being a significant relationship between the rate of decline of KCO and QRISK2.
The Combination of Interferon-Alpha with Imatinib in Early Chronic Phase Chronic Myeloid Leukemia Patients Induces a Significant Improvement of the Molecular Responses in the First Two Years of Treatment: Results From Three Studies From the GIMEMA CML Working Party.
Authors: Francesca Palandri, Fausto Castagnetti, Ilaria Iacobucci, Marilina Amabile, Gabriele Gugliotta, Angela Poerio, Massimo Breccia, Enrico Gottardi, Bruno Martino, Ivana Pierri, Fabrizio Quarantelli, Franca Radaelli, Giorgina Specchia, Fabrizio Pane, Giuseppe Saglio, Giovanni Martinelli, Gianantonio Rosti, Michele Baccarani
Journal: Blood (2009)