tbuckley/cabot-search huggingface dataset:
Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
Authors: Molly Went, Amit Sud, Helen Speedy, Nicola J. Sunter, Asta Försti, Philip J. Law, David C. Johnson, Fabio Mirabella, Amy Holroyd, Ni Li, Giulia Orlando, Niels Weinhold, Mark van Duin, Bowang Chen, Jonathan S. Mitchell, Larry Mansouri, Gunnar Juliusson, Karin E Smedby, Sandrine Jayne, Aneela Majid, Claire Dearden, David J. Allsup, James R. Bailey, Guy Pratt, Chris Pepper, Chris Fegan, Richard Rosenquist, Rowan Kuiper, Owen W. Stephens, Uta Bertsch, Peter Broderick, Hermann Einsele, Walter M. Gregory, Jens Hillengass, Per Hoffmann, Graham H. Jackson, Karl-Heinz Jöckel, Jolanta Nickel, Markus M. Nöthen, Miguel Inacio da Silva Filho, Hauke Thomsen, Brian A. Walker, Annemiek Broyl, Faith E. Davies, Markus Hansson, Hartmut Goldschmidt, Martin J. S. Dyer, Martin Kaiser, Pieter Sonneveld, Gareth J. Morgan, Kari Hemminki, Björn Nilsson, Daniel Catovsky, James M. Allan, Richard S. Houlston
Journal: Blood Cancer Journal (2018)

Abstract The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown ( R g = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.
Abstract 16046: Clinical Action is Frequently Taken Following Detection of Previously Unknown Atrial Fibrillation by an Insertable Cardiac Monitor in High Risk Patients: The REVEAL AF Study
Authors: Atul Verma, Rolf Wachter, Peter R Kowey, Jonathan L Halperin, Bernard J Gersh, Mitchell S Elkind, Rachelle E Kaplon, Lou Sherfesee, James A Reiffel
Journal: Circulation (2017)

Introduction: The REVEAL AF study found a high incidence (40% at 30 months) of previously undetected atrial fibrillation (AF) episodes ≥6 minutes with long-term cardiac rhythm monitoring in patients at risk for AF and stroke. To determine if monitoring led to changes in therapy, we characterized new clinical actions (NCA) following AF detection. Methods: Patients with CHADS2 scores ≥3 (or =2 with ≥1 additional AF risk factor) but no history of AF received insertable cardiac monitors (ICM) and were followed 18-30 months. Physicians recorded NCA taken in response to detected AF of any duration at scheduled (every 6 months) and unscheduled follow-up visits. A NCA was defined as initiation of oral anticoagulation (OAC), rhythm or rate control medications, cardioversion, ablation, or referral for treatment. Descriptive statistics were used to summarize treatment decisions. Results: Among 387 subjects who met inclusion criteria and received an ICM, AF was found in 115 subjects at 239 visits. A NCA was taken in ...
Identifying Ultra-High Risk Smoldering Multiple Myeloma
Authors: Theresia Akhlaghi, Even H Rustad, Venkata D Yellapantula, Neha Korde, Sham Mailankody, Nikoletta Lendvai, Alexander M. Lesokhin, Hani Hassoun, Sergio Giralt, Heather J. Landau, Eric L. Smith, Gunjan L. Shah, Michael Scordo, David J. Chung, Khalid Mezzi, Monica Khurana, Megan Braunlin, Winifred Werther, Ola Landgren, Malin Hultcrantz
Journal: Blood (2018)
SP0084 Why physical activity exercise works
Authors: M.D. Iversen
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Pain, inflammation, and decreased physical function are consequences of musculoskeletal disorders (MSDs), limiting patients' daily activities and restricting their participation in society. Physical activity and exercise have positive health effects for the circulatory, digestive, endocrine, excretory, immune, integumentary, muscular, nervous, respiratory and skeletal systems. Given the benefits of physical activity and exercise, physical activity is a primary component of symptom management for individuals with musculoskeletal disorders. This presentation will review the short- and long-term effects of physical activity and exercise in general and specifically, for individuals with musculoskeletal disorders, with a focus on the cardiovascular, immune and musculoskeletal systems. <h3>Disclosure of Interest</h3> None declared
Fear Network Unresponsiveness in Women with Anorexia Nervosa
Authors: Simon Maier, Katharina Schneider, Carolin Stark, Almut Zeeck, Ludger Tebartz van Elst, Lukas Holovics, Armin Hartmann, Claas Lahmann, Katharina Domschke, Kathrin Nickel, Bernd Feige, Volkmar Glauche, Christian Fleischhaker, Oliver  Tüscher, Andreas Joos
Journal: Psychotherapy and Psychosomatics (2018)
The Role of Three‐Dimensional Magnetic Resonance Elastography in the Diagnosis of Nonalcoholic Steatohepatitis in Obese Patients Undergoing Bariatric Surgery
Authors: Alina M. Allen, Vijay H. Shah, Terry M. Therneau, Sudhakar K. Venkatesh, Taofic Mounajjed, Joseph J. Larson, Kristin C. Mara, Phillip J. Schulte, Todd A. Kellogg, Michael L. Kendrick, Travis J. McKenzie, Suzanne M. Greiner, Jiahui Li, Kevin J. Glaser, Michael L. Wells, Jun Chen, Richard L. Ehman, Meng Yin
Journal: Hepatology (2018)

The lack of reliable, noninvasive methods to diagnose early nonalcoholic steatohepatitis (NASH) is a major unmet need. We aimed to determine the diagnostic accuracy of three-dimensional magnetic resonance elastography (3D-MRE), with shear stiffness measured at 60 Hz, damping ratio at 40 Hz, and magnetic resonance imaging proton density fat fraction (MRI-PDFF) in the detection of NASH in individuals undergoing bariatric surgery. Obese adults at risk for NASH were enrolled between 2015 and 2017 (prospective cohort, n = 88) and 2010 and 2013 (retrospective cohort, n = 87). The imaging protocol consisted of multifrequency 3D-MRE (mf3D-MRE) with shear waves delivered at different frequencies to explore parameters that best correlated with histologic NASH, and MRI-PDFF to estimate steatosis. The prospective cohort was used to establish the optimal mf3D-MRE technical parameters for NASH detection. The two cohorts were then combined to derive predictive models of NASH and disease activity by nonalcoholic fatty liver disease activity score (NAS) using the three imaging parameters that correlated with NASH. A total of 175 patients (median age 45, 81% women, and 81 [46%] with histologic NASH) were used for model derivation. From the complex shear modulus output generated by mf3D-MRE, the damping ratio at 40 Hz and shear stiffness at 60 Hz best correlated with NASH. The fat fraction obtained from MRI-PDFF correlated with steatosis (P < 0.05 for all). These three parameters were fit into a logistic regression model that predicted NASH with cross-validated area under the receiver operating characteristic curve (AUROC) = 0.73, sensitivity = 0.67, specificity = 0.80, positive predictive value = 0.73 and negative predictive value = 0.74, and disease activity by NAS with cross-validated AUROC = 0.82. Conclusion: The mf3D-MRE allows identification of imaging parameters that predict early NASH and disease activity. This imaging biomarker represents a promising alternative to liver biopsy for NASH diagnosis and monitoring. The results provide motivation for further studies in nonbariatric cohorts.
Dermal fibroblast expression profiling implicates tumour microenvironment in the development of aggressive squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa
Authors: Y. Z. Ng, C. Pourreyron, C. Proby, J. Salas, D. F. Murrell, J. A. McGrath, E. B. Lane, I. M. Leigh, A. P. South
Journal: British Journal of Dermatology (2010)
Abstract 14957: Tristetraprolin and Poly(ADP-Ribose)-Polymerase-14 Post-Transcriptionally Regulate Macrophage Tissue Factor Expression: Novel Mechanisms for Regulating Thrombosis
Authors: M Bilal Iqbal, Michael Johns, Sheng-Chun Yu, Mark Boothby, Jonathan Dean, Felicity Gavins, Dorian O Haskard
Journal: Circulation (2012)

BACKGROUND Monocyte-derived tissue factor (TF) plays critical roles in atherothrombosis. Little is known about its post-transcriptional regulation. Tristetraprolin (TTP), the most widely studied mR...
Human Rhinovirus Inhibits Macrophage Phagocytosis of Bacteria in Chronic Obstructive Pulmonary Disease. More Than a Common Cold
Authors: Ian Sabroe, Antonia Ho, David H. Dockrell
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

More Than a Common ColdChronic obstructive pulmonary disease (COPD) results from chronic inflammation, tissue injury, and aberrant repair processes in the respiratory airways.Acute viral and/or bacterial infections cause acute exacerbations.Rhinovirus (RV) infection is the most common viral cause of acute exacerbations in COPD, accounting for approximately 60% of viral acute exacerbations (1).Secondary bacterial infections frequently follow viral infection, resulting in more severe clinical illness with a greater reduction in FEV 1 over FVC and greater length of hospitalization (2).In this issue of the Journal, Finney and colleagues (pp.1496-1507) provide an important advance by demonstrating that a type A human RV (HRV) infection, HRV16, impairs phagocytosis of two important pathogens in COPD: nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (3).The HRV-associated phagocytic defect was demonstrated for both bacteria in the case of monocyte-derived macrophages (MDMs), but only for NTHi in the case of alveolar macrophages (AMs).Of note, the authors were able to demonstrate viral uptake by AMs challenged ex vivo, with cytoplasmic localization of virions.The phagocytic defect was reprised with a Toll-like receptor 3 (TLR3) agonist (polyinosinic:polycytidylic acid) and was a delayed response, requiring approximately 6 hours of HRV incubation.The authors also showed that HRV16 decreased proinflammatory cytokines in COPD MDMs challenged with NTHi.MDMs and AMs from subjects with COPD showed reduced phagocytosis to NTHi and S. pneumoniae (in the absence of HRV challenge) as compared with those obtained from healthy donors, and the degree of AM phagocytosis was correlated with MDM phagocytosis and with FEV 1 % predicted for both pathogens.Other models of the interaction between HRV and macrophages are of potential interest.HRV also induces replication-independent activation of TLR2 in mouse macrophages with production of proinflammatory cytokines (4).Conversely, HRV1B reduces CXCL8 (C-X-C motif chemokine ligand 8) production in response to NTHi, with reduced bacterial clearance and prolonged neutrophilic inflammation in mouse lungs (5).In this case, replication-independent viral responses induce degradation of IRAK-1 (IL-1 receptor-associated kinase 1), a key adaptor required for MyD88-dependent TLR signaling, inducing tolerance to bacterial stimuli in AMs.
Abstract 14851: Oral Anticoagulation Continuation vs Heparin Bridging During Cardiac Rhythm Device Procedures: Less Pocket Hematomas - Meta-analysis of Randomized Trials
Authors: Georges El-Hayek, Abel Casso Dominguez, Matthew Pierce, Alexandre Benjo, Daniel Garcia, Eyal Herzog, Conor Barrett, Robert Altman, Jacqueline Suk Danik, Stephan Danik
Journal: Circulation (2014)

Background and Objectives: Management of patients with high thrombo-embolic (TE) risk on long-term oral anticoagulation (OAC) during cardiac rhythm devices procedures is controversial. Current guid...
Cluster and CART analyses identify large subgroups of adults with cystic fibrosis at low risk of 10-year death
Authors: Pierre-Régis Burgel, Lydie Lemonnier, Clémence Dehillotte, Jenna Sykes, Sanja Stanojevic, Anne L. Stephenson, Jean-Louis Paillasseur
Journal: European Respiratory Journal (2018)

Our goal was to identify subgroups of adults with cystic fibrosis (CF) at low risk of death within 10 years. Factor analysis for mixed data followed by Ward's cluster analysis was conducted using 25 variables from 1572 French CF adults in 2005. Rates of death by subgroups were analysed over 10 years. An algorithm was developed using CART (classification and regression tree) analysis to provide rules for the identification of subgroups of CF adults with low rates of death within 10 years. This algorithm was validated in 1376 Canadian CF adults. Seven subgroups were identified by cluster analysis in French CF adults, including two subgroups with low (∼5%) rates of death at 10 years: one subgroup (22% of patients) was composed of patients with nonclassic CF, the other subgroup (17% of patients) was composed of patients with classic CF but low rates of Pseudomonas aeruginosa infection and diabetes. An algorithm based on CART analysis of data in 2005 allowed us to identify most French adults with low rates of death. When tested using data from Canadian CF adults in 2005, the algorithm identified 287 out of 1376 (21%) patients at low risk (10-year death: 7.7%). Large subgroups of CF adults share low risk of 10-year mortality.
The long non-coding RNA LncHDAC2 drives the self-renewal of liver cancer stem cells via activation of Hedgehog signaling
Authors: Jiayi Wu, Pingping Zhu, Tiankun Lu, Ying Du, Yanying Wang, Luyun He, Buqing Ye, Benyu Liu, Liuliu Yang, Jing Wang, Yang Gu, Jie Lan, Yajing Hao, Lei He, Zusen Fan
Journal: Journal of Hepatology (2018)
Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis
Authors: Yixin Zhou, Chen Chen, Xuanye Zhang, Sha Fu, Cong Xue, Yuxiang Ma, Wenfeng Fang, Yunpeng Yang, Xue Hou, Yan Huang, Hongyun Zhao, Shaodong Hong, Li Zhang
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immune-checkpoint inhibitors plus chemotherapy are emerging as effective first-line treatment in advanced non-small-cell lung carcinoma (NSCLC), but little is known about the magnitude of benefits and potential clinical predictors. <h3>Methods</h3> We performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy in first line of treatment for advanced NSCLC. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. <h3>Results</h3> Six trials involving 3144 patients were included. PD-1/PD-L1 inhibitor plus chemotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.62; 95% CI 0.57–0.67; <i>P</i> &lt; .001), OS (HR, 0.68; 95% CI 0.53–0.87; <i>P</i> = .002) and ORR (relative ratio [RR], 1.56; 95% CI 1.29–1.89; <i>P</i> &lt; .001), irrespective of PD-L1 expression level. The significant predictor(s) for treatment benefit with combination therapy versus chemotherapy alone were PD-L1 expression level for PFS (<i>P</i> &lt; .001); types of checkpoint inhibitor for ORR (<i>P</i> &lt; .001); histology (<i>P</i> = .025), age (<i>P</i> = .038), gender (<i>P</i> &lt; .001), and types of checkpoint inhibitor (<i>P</i> &lt; .001) for OS. In safety analyses, PD-1/PD-L1 inhibitor plus chemotherapy had significantly higher incidence of adverse events (AEs) of grade 3 or higher (RR, 1.14; <i>P</i> = .007), AEs leading to treatment discontinuation (RR, 1.29; <i>P</i> = .022), serious AEs (RR 1.70; <i>P</i> = .006), immune mediated AEs of any grade (RR, 2.37; <i>P</i> &lt; .001), and immune mediated AEs of grade 3 or higher (RR, 3.71; <i>P</i> &lt; .001). <h3>Conclusions</h3> PD-1/PD-L1 inhibitor plus chemotherapy, compared with chemotherapy, is associated with significantly improved PFS, ORR, and OS in first-line therapy in NSCLC, at the expense of increased treatment-related AEs.
“Biomarker-guided clinical decisions: for patients, health economists or neither?” Jens-Ulrik Jensen.<i>Eur Respir J</i>2013; 42: 895–897.
Authors: Paul Robinson, Philipp Latzin, Sylvia Verbanck, Graham Hall, Alexander Horsley, Monika Gappa, Cindy Thamrin, Hubertus Arets, Paul Aurora, Susanne Fuchs, Gregory King, Sooky Lum, Kenneth Macleod, Manuel Paiva, Jane Pillow, Sarath Ranganathan, Felix Ratjen, Florian Singer
Journal: European Respiratory Journal (2013)
Cell-Intrinsic Depletion of AML1-ETO-Positive Pre-Leukemic HSCs By Kras Activating Mutation
Authors: Cristina Di Genua, Ruggiero Norfo, Alba Rodriguez-Meira, Roy Drissen, Christopher Booth, Benjamin Povinelli, Emmanouela Repapi, Nicki Gray, Joana Carrelha, Laura Kettyle, Lauren Jamieson, Wen Hao Neo, Claus Nerlov, Adam J Mead
Journal: Blood (2017)
Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Untreated AML: Results from a Phase 1 Dose Escalation and Expansion Study
Authors: Gail J. Roboz, Courtney D. DiNardo, Eytan M. Stein, Stephane de Botton, Alice S. Mims, Gabrielle T. Prince, Jessica K. Altman, Martha L. Arellano, William B. Donnellan, Harry P. Erba, Gabriel N. Mannis, Daniel A Pollyea, Anthony S. Stein, Geoffrey L. Uy, Justin M. Watts, Amir T. Fathi, Hagop M. Kantarjian, Martin S. Tallman, Sung Choe, David Dai, Bin Fan, Hongfang Wang, Vickie Zhang, Katharine E. Yen, Stephanie M. Kapsalis, Denice Hickman, Hua Liu, Samuel V. Agresta, Bin Wu, Eyal C. Attar, Richard M. Stone
Journal: Blood (2018)
Resource Utilization Early after Chimeric Antigen Receptor (CAR) T Cell Infusion for Hematologic Malignancies
Authors: Gunjan L. Shah, Jae H. Park, Craig S. Sauter, Elaine Duck, Elizabeth Halton, Maria Lia Palomba, Connie Lee Batlevi, Anas Younes, Mark Blaine Geyer, Eric L. Smith, Sham Mailankody, Elena Mead, Bianca Santomasso, Miguel-Angel Perales, Paul Sabbatini, Sergio Giralt, Renier J. Brentjens, Peter Bach
Journal: Blood (2018)
PI3Kα/δ inhibition promotes anti-tumor immunity through direct enhancement of effector CD8+ T-cell activity
Authors: Larissa S. Carnevalli, Charles Sinclair, Molly A. Taylor, Pablo Morentin Gutierrez, Sophie Langdon, Anna M. L. Coenen-Stass, Lorraine Mooney, Adina Hughes, Laura Jarvis, Anna Staniszewska, Claire Crafter, Ben Sidders, Elizabeth Hardaker, Kevin Hudson, Simon T. Barry
Journal: Journal for ImmunoTherapy of Cancer (2018)

PI3K inhibitors with differential selectivity to distinct PI3K isoforms have been tested extensively in clinical trials, largely to target tumor epithelial cells. PI3K signaling also regulates the immune system and inhibition of PI3Kδ modulate the tumor immune microenvironment of pre-clinical mouse tumor models by relieving T-regs-mediated immunosuppression. PI3K inhibitors as a class and PI3Kδ specifically are associated with immune-related side effects. However, the impact of mixed PI3K inhibitors in tumor immunology is under-explored. Here we examine the differential effects of AZD8835, a dual PI3Kα/δ inhibitor, specifically on the tumor immune microenvironment using syngeneic models. Continuous suppression of PI3Kα/δ was not required for anti-tumor activity, as tumor growth inhibition was potentiated by an intermittent dosing/schedule in vivo. Moreover, PI3Kα/δ inhibition delivered strong single agent anti-tumor activity, which was associated with dynamic suppression of T-regs, improved CD8<sup>+</sup> T-cell activation and memory in mouse syngeneic tumor models. Strikingly, AZD8835 promoted robust CD8<sup>+</sup> T-cell activation dissociated from its effect on T-regs. This was associated with enhancing effector cell viability/function. Together these data reveal novel mechanisms by which PI3Kα/δ inhibitors interact with the immune system and validate the clinical compound AZD8835 as a novel immunoncology drug, independent of effects on tumor cells. These data support further clinical investigation of PI3K pathway inhibitors as immuno-oncology agents.
Systems Biology Analysis Identifies Targetable Vulnerability Networks to Proteasome Inhibitors in Multiple Myeloma
Authors: Mark B. Meads, Rafael Renatino Canevarolo, Praneeth Reddy Sudalagunta, Paula S. Oliveira, Dario M. Magaletti, Bin Fang, Maria D Coelho Siqueira Silva, Amit Kulkarni, Hongyue Dai, William S. Dalton, Ion Petre, John M. Koomen, Ariosto Siqueira Silva, Kenneth H. Shain
Journal: Blood (2018)
Abstract 18805: Association of State Certificate of Need Regulations With the Appropriateness of PCI Procedures
Authors: Philip W Chui, Craig S Parzynski, Joseph S Ross, Vivian Ho, John A Spertus, Hitinder S Gurm, Jeptha P Curtis
Journal: Circulation (2015)

Introduction: Certificate of Need (CON) regulations are intended to limit healthcare infrastructure to control healthcare costs, prevent overuse, and improve quality of care. However, there is limited information about the impact of CON regulations on the use of invasive cardiac procedures. To address this gap, we examined the association of state CON regulations with the appropriateness of percutaneous coronary interventions (PCI). Methods: We used data from the ACC’s CathPCI Registry to analyze 1,143,402 PCIs performed at 1,297 hospitals between January 2010 and December 2011. We applied the 2012 Appropriate Use Criteria (AUC) to determine whether the procedure was considered appropriate, uncertain, or inappropriate, and we used chi-square analyses to assess whether the proportions of PCIs AUC categories differed depending on whether the procedure had been performed in a state with or without CON regulations. Analyses were repeated stratified by whether or not the procedure was performed in the setting of an acute coronary syndrome (ACS). Results: The characteristics and outcomes of patients undergoing PCI were similar in states with and without CON. The proportion of PCIs considered appropriate in non-CON states was slightly lower compared with CON states (85.5% versus 86.2%), and a higher proportion of procedures were considered inappropriate (4.6% versus 4.2%) [Table]. Absolute differences were larger among non-ACS PCI patients and were not statistically significant among ACS PCI patients. Conclusions: States with CON had a lower proportion of inappropriate PCIs as compared with states without CON. However, the absolute differences were small, suggesting that CON regulations alone may have a limited impact on preventing potential overuse of PCI procedures.