tbuckley/cabot-search huggingface dataset:
Short‐term prognostic implications of serum and urine neutrophil gelatinase‐associated lipocalin in acute heart failure: findings from the AKINESIS study
Authors: Nicholas Wettersten, Yu Horiuchi, Dirk J. van Veldhuisen, Christian Mueller, Gerasimos Filippatos, Richard Nowak, Christopher Hogan, Michael C. Kontos, Chad M. Cannon, Gerhard A. Müeller, Robert Birkhahn, Pam Taub, Gary M. Vilke, Olga Barnett, Kenneth McDonald, Niall Mahon, Julio Nuñez, Carlo Briguori, Claudio Passino, Alan Maisel, Patrick T. Murray
Journal: European Journal of Heart Failure (2019)
Trends in Mental and Physical Health-Related Quality of Life in Low-Income Older Persons in the United States, 2003 to 2017
Authors: David H. Rehkopf, Frank F. Furstenberg, John W. Rowe
Journal: JAMA Network Open (2019)

This cross-sectional study of respondents to the Behavioral Risk Factor Surveillance System survey assesses trends between 2003 and 2017 in mental and physical health-related quality of life in low-income US individuals 60 years or older.
European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure
Authors: Petar M. Seferović, Andrew J.S. Coats, Piotr Ponikowski, Gerasimos Filippatos, Martin Huelsmann, Pardeep S. Jhund, Marija M. Polovina, Michel Komajda, Jelena Seferović, Ibrahim Sari, Francesco Cosentino, Giuseppe Ambrosio, Marco Metra, Massimo Piepoli, Ovidiu Chioncel, Lars H. Lund, Thomas Thum, Rudolf A. De Boer, Wilfried Mullens, Yuri Lopatin, Maurizio Volterrani, Loreena Hill, Johann Bauersachs, Alexander Lyon, Mark C. Petrie, Stefan Anker, Giuseppe M.C. Rosano
Journal: European Journal of Heart Failure (2019)
Abstract A24: Gene expression along the glycolysis-cholesterol synthesis axis and outcome in pancreatic cancer
Authors: Joanna M. Karasinska, James T. Topham, Steve E. Kalloger, Gun Ho Jang, Robert E. Denroche, Luka Culibrk, Laura M. Williamson, Hui-li Wong, Michael K.C. Lee, Grainne M. O'Kane, Richard A. Moore, Andrew J. Mungall, Malcolm J. Moore, Cassia Warren, Andrew Metcalfe, Faiyaz Notta, Jennifer J. Knox, Steven Gallinger, Janessa Laskin, Marco A. Marra, Steven J.M. Jones, Daniel J. Renouf, David F. Schaeffer
Journal: Cancer Research (2019)

Abstract Reprogramming of metabolic pathways allows cancer cells to survive and thrive in the tumor microenvironment. Glycolysis-inducing factors including oncogenic KRAS mutations, loss of function in TP53 and hypoxia are prevalent in PDAC. Cholesterol and its metabolites support tumor cell growth and the mevalonate pathway, which uses glycolysis products for de novo cholesterol synthesis, has been found to be upregulated in cancer. However, whether intertumoral heterogeneity in these metabolic networks influences outcome in pancreatic cancer has not been well established. We profiled the expression of glycolytic and cholesterogenic genes in 325 resected and metastatic pancreatic ductal adenocarcinoma (PDAC) tumors and identified four distinct subgroups: quiescent, glycolytic, cholesterogenic, and mixed. Glycolytic tumors were associated with the shortest median survival in resectable and metastatic disease settings. Patients with cholesterogenic tumors had the longest median survival. KRAS and MYC amplified tumors had higher expression of glycolytic genes than tumors with normal or lost copies of these oncogenes. The mitochondrial uptake of pyruvate, the end product of glycolysis, facilitates the generation of acetyl-CoA for cholesterol synthesis. PDAC tumors with a glycolytic gene signature had the lowest expression of mitochondrial pyruvate carriers MPC1 and MPC2. Glycolytic and cholesterogenic gene expression correlated with the expression of reported prognostic PDAC subtype classifier genes. Our results indicate that PDAC tumors have unique metabolic profiles that influence disease outcome and provide functional correlate to previously identified subtypes. The findings also raise the possibility of a shift in balance between the glycolytic and cholesterogenic pathways as a factor in PDAC progression and a potential target for therapy. Citation Format: Joanna M. Karasinska, James T. Topham, Steve E. Kalloger, Gun Ho Jang, Robert E. Denroche, Luka Culibrk, Laura M. Williamson, Hui-li Wong, Michael K.C. Lee, Grainne M. O'Kane, Richard A. Moore, Andrew J. Mungall, Malcolm J. Moore, Cassia Warren, Andrew Metcalfe, Faiyaz Notta, Jennifer J. Knox, Steven Gallinger, Janessa Laskin, Marco A. Marra, Steven J.M. Jones, Daniel J. Renouf, David F. Schaeffer. Gene expression along the glycolysis-cholesterol synthesis axis and outcome in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A24.
Abdominal Wall Granulomatous Inflammation Mimicking Malignancy on FDG PET/CT
Authors: Guohua Shen, Anren Kuang
Journal: Clinical Nuclear Medicine (2019)

An old woman with abdominal pain complained a palpable mass on the right anterior abdominal wall. On PET/CT images, the lesion presented as a soft tissue mass with irregular shape, invading adjacent peritoneum and showing intense FDG uptake. Based on imaging findings, a malignancy was suspected, and she underwent surgical resection. However, the abdominal wall mass was diagnosed as granulomatous inflammation with a little necrosis by pathological results. Awareness of this benign disease is helpful for an accurate diagnosis of abdominal wall mass.
Impact of digital patient monitoring (DPM) on quality of clinical care of cancer immunotherapy (CIT)-treated patients (pts) with advanced/metastatic non-small cell lung cancer (a/mNSCLC)
Authors: O.O. Schmalz, C. Jacob, J. Ammann, B. Liss, S. Iivanainen, M. Kammermann, J. Koivunen, M. Giger, A. Klein, R.A. Popescu
Journal: Annals of Oncology (2019)
Identification of Recurrent Genomic Alterations in the Apoptotic Machinery in CLL Patients Treated with Venetoclax Monotherapy
Authors: Brenda J Chyla, Relja Popovic, Charles Lu, Fengjiao Dunbar, Danjuma Quarless, Kenneth Robinson, Scott Warder, Amanda Jacobson, Lang Zhou, Andrew Souers, Jeffrey Waring, Anahita Bhathena, Joel D. Leverson, Su Young Kim
Journal: Blood (2019)
Response to R. Waldman <i>et al</i> .: ‘Does IL‐4 inhibition play a role in dupilumab‐associated conjunctivitis?’
Authors: M. Ardeleanu, B. Shumel, A.B. Rossi, N.M.H. Graham
Journal: British Journal of Dermatology (2019)

Linked Article: Waldman et al. Br J Dermatol 2020; 182:251. Bakker et al. Br J Dermatol 2019; 180:1248–9.
18F-FDG PET/CT-Guided Diagnosis and Evaluation of Treatment Response to Cyclosporine A in Maldistributed Subcutaneous Panniculitis-like T-Cell Lymphoma Without Typical Skin Rash
Authors: Yoshiaki Abe, Kentaro Narita, Hiroki Kobayashi, Akihiro Kitadate, Masami Takeuchi, Kosei Matsue
Journal: Clinical Nuclear Medicine (2019)

Abstract A 30-year-old woman presented with persistent fever and elevated lactate dehydrogenase levels without skin rash. 18 F-FDG PET/CT revealed FDG uptake in subcutaneous tissues in the forearm, buttocks, and lower limbs, whereas the trunk was unaffected. She was diagnosed with subcutaneous panniculitis-like T-cell lymphoma based on a PET/CT-guided subcutaneous tissue biopsy from the thigh. Although conventional cytotoxic agent–based chemotherapies failed to achieve disease remission, subsequent cyclosporine A treatment promptly resolved the fever and laboratory abnormalities. Remarkably, abnormal FDG uptake disappeared entirely on follow-up PET/CT, demonstrating its utility in the evaluations of responses to emerging cyclosporine A–based treatments in subcutaneous panniculitis-like T-cell lymphoma.
Exercise Attenuates Cardiotoxicity of Anthracycline Chemotherapy Measured by Global Longitudinal Strain
Authors: Benedict T. Costello, Timothy J. Roberts, Erin J. Howden, Ashley Bigaran, Steven J. Foulkes, Rhys I. Beaudry, Kristel Janssens, Mark J. Haykowsky, Yoland Antill, Sophie Nightingale, Sherene Loi, Andre La Gerche
Journal: JACC CardioOncology (2019)

Anthracycline-based chemotherapy (AC) is a common treatment for patients with breast cancer and has been associated with a dramatic improvement in breast cancer survivorship. Among patients with early-stage breast cancer, cardiovascular diseases represent the most common cause of mortality, and
Polyfunctional TEM cells in psoriatic arthritis synovium skewed towards Th17 cells
Authors: Smriti K Raychaudhuri, Christine Abria, Siba P Raychaudhuri
Journal: Annals of the Rheumatic Diseases (2019)

are skewed more towards the Th17 cells when compared with RA.At different time points of a disease process, it is expected that the kinetics of the polyfunctionality of these cells along with their cytokine profile would vary.Thus, this could be a possible explanation for treatment failure or variations in responsiveness to a specific anticytokine therapeutic agent in a patient with RA or in a patient with PsA.
NHS to fast track access to cannabis based treatment for epilepsy
Authors: Jacqui Wise
Journal: BMJ (2019)

NHS England is fast tracking access to the cannabis based treatment Epidyolex for two forms of severe epilepsy after negotiating a discount with the manufacturer.

From 6 January doctors will be able to prescribe Epidyolex with clobazam for children aged 2 and over with Lennox-Gastaut syndrome and Dravet syndrome.

The announcement follows recommendations from the National Institute for Health and Care Excellence (NICE) on 18 December that the NHS should pay for Epidyolex.12 It follows the findings of NICE’s final appraisal on cannabis based products which was published in November 2019.3 NICE initially rejected the use of cannabidiol in draft appraisal documents in August …
A Subset of Colorectal Cancers with Cross-Sensitivity to Olaparib and Oxaliplatin
Authors: Sabrina Arena, Giorgio Corti, Erika Durinikova, Monica Montone, Nicole M. Reilly, Mariangela Russo, Annalisa Lorenzato, Pamela Arcella, Luca Lazzari, Giuseppe Rospo, Massimiliano Pagani, Carlotta Cancelliere, Carola Negrino, Claudio Isella, Alice Bartolini, Andrea Cassingena, Alessio Amatu, Gianluca Mauri, Andrea Sartore-Bianchi, Gloria Mittica, Enzo Medico, Silvia Marsoni, Michael Linnebacher, Sergio Abrignani, Salvatore Siena, Federica Di Nicolantonio, Alberto Bardelli
Journal: Clinical Cancer Research (2019)

Defects in the homologous recombination (HR) repair pathway are of clinical interest due to sensitivity of HR-deficient cells to PARP inhibitors. We were interested in defining PARP vulnerability in patients with metastatic colorectal cancer (mCRC) carrying KRAS and BRAF mutations who display poor prognosis, have limited therapeutic options, and represent an unmet clinical need.We tested colorectal cancer cell lines, patient-derived organoids (PDO), and patient-derived xenografts (PDX) enriched for KRAS and BRAF mutations for sensitivity to the PARP inhibitor olaparib, and the chemotherapeutic agents oxaliplatin and 5-fluorouracil (5-FU). Genomic profiles and DNA repair proficiency of colorectal cancer models were compared with pharmacologic response.Thirteen of 99 (around 13%) colorectal cancer cell lines were highly sensitive to clinically active concentrations of olaparib and displayed functional deficiency in HR. Response to PARP blockade was positively correlated with sensitivity to oxaliplatin in colorectal cancer cell lines as well as patient-derived organoids. Treatment of PDXs with olaparib impaired tumor growth and maintenance therapy with PARP blockade after initial oxaliplatin response delayed disease progression in mice.These results indicate that a colorectal cancer subset characterized by poor prognosis and limited therapeutic options is vulnerable to PARP inhibition and suggest that PDO-based drug-screening assays can be used to identify patients with colorectal cancer likely to benefit from olaparib. As patients with mCRC almost invariably receive therapies based on oxaliplatin, "maintenance" treatment with PARP inhibitors warrants further clinical investigation.
PET/CT features of extrapulmonary tuberculosis at first clinical presentation: a cross-sectional observational<sup>18</sup>F-FDG imaging study across six countries
Authors: Jamshed Bomanji, Rajnish Sharma, Bhagwant R. Mittal, Sanjay Gambhir, Ahmad Qureshy, Shamim M.F. Begum, Diana Paez, Mike Sathekge, Mariza Vorster, Dragana Sobic Saranovic, Pawana Pusuwan, Vera Mann, Sobhan Vinjamuri, Alimuddin Zumla, Thomas N.B. Pascual
Journal: European Respiratory Journal (2019)

A large proportion of the huge global burden of extrapulmonary tuberculosis (EPTB) cases are treated empirically without accurate definition of disease sites and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 2-deoxy-2-(fluorine-18) fluoro-d-glucose (18F-FDG) in tuberculosis could be a useful imaging technique for localising disease sites and extent of disease.We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across eight centres located in six countries: India, Pakistan, Thailand, South Africa, Serbia and Bangladesh, to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/computed tomography (CT) scans were performed within 2 weeks of presentation.358 patients with EPTB (189 females; 169 males) were recruited over 45 months, with an age range of 18-83 years (females median 30 years; males median 38 years). 350 (98%) out of 358 patients (183 female, 167 male) had positive scans. 118 (33.7%) out of 350 had a single extrapulmonary site and 232 (66.3%) out of 350 had more than one site (organ) affected. Lymph nodes, skeleton, pleura and brain were common sites. 100 (28%) out of 358 EPTB patients had 18F-FDG PET/CT-positive sites in the lung. 110 patients were 18F-FDG PET/CT-positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites.18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies.
Evidence for preventive treatments in young patients at clinical high risk of psychosis: the need for context
Authors: Barnaby Nelson, Günter P Amminger, Andreas Bechdolf, Paul French, Ashok Malla, Anthony P Morrison, Stefanie J Schmidt, Jai L Shah, Andrew Thompson, Mark Van der Gaag, Stephen J Wood, Scott W Woods, Alison R Yung, Patrick D McGorry
Journal: The Lancet Psychiatry (2019)
Chimeric Antigen Receptor T-Cell Therapy for Cancer and Heart
Authors: Sarju Ganatra, Joseph R Carver, Salim S Hayek, Bonnie Ky, Monika J Leja, Daniel J Lenihan, Carrie Lenneman, Negaresh Mousavi, Jae H Park, Miguel Angel Perales, Thomas D Ryan, Marielle Scherrer-Crosbie, Richard M Steingart, Eric H Yang, Vlad Zaha, Ana Barac, Jennifer E Liu
Journal: Journal of the American College of Cardiology (2019)
A critical role of EphA2 receptor tyrosine kinase in tumor angiogenesis and metastasis
Authors: Dana Brantley-Sieders, Jin Chen
Journal: Cancer Research (2005)

6133  EphA2 receptor belongs to a unique family of tyrosine kinases (RTK) that mediate cell-cell adhesion/repulsion, cell-matrix adhesion, and cell migration. EphA2 is overexpressed in both breast tumor cells and blood vessel endothelial cells in the host environment in more than 70% of clinical breast cancer specimens. In addition, a high level of EphA2 expression consistently correlates with a high degree of tumor malignancy. To determine the role of EphA2 receptor in tumor neovascular growth, we initially blocked A-class Eph receptor tyrosine kinase activation by soluble EphA2-Fc or EphA3-Fc receptors. These soluble receptors inhibited 4T1 mammary tumor progression in vivo, providing the first functional evidence of EphA receptor involvement in breast tumor angiogenesis. To determine the specific role of EphA2 receptor in tumor angiogenesis, we characterized EphA2-deficient mice. EphA2-null endothelial cells (ECs) fail to undergo vascular assembly and migration in vitro and angiogenesis in vivo, and are defective in PI3K-dependent Rac1 GTPase activation in response to ligand stimulation. Loss of EphA2 receptor in the host significantly inhibited tumor volume, neovascularization and metastasis of orthotopically grafted 4T1 mammary tumors. In addition, EphA2-deficient ECs fail to migrate, coalesce, and incorporate into tumor blood vessels when co-transplanted with 4T1 tumor cells, indicating an EC-specific defect in tumor neovascularization. Taken together, these data suggest that host EphA2 receptor function is required in the tumor microenvironment for tumor angiogenesis and metastatic progression. Our findings are novel and significant in several respects. First, our data presented here, together with studies from other laboratories, indicate that EphA2 plays a key role in breast tumor progression through both tumor and host-dependent mechanisms. Because this single factor influences tumor progression in both tumor cells and tumor blood vessels, EphA2 receptor is an attractive target for the development of new treatments for breast cancer. Second, EphA2 receptor appears not to be required for embryonic development, but is critical in adult angiogenesis and cancer and thus targeted inhibition of EphA2 receptor should have limited side effects to normal tissue. Finally, the new mouse model of EphA2 deficient mice provides a novel tool to dissect the function of EphA2 in tumor cells and tumor endothelium in vivo in clinically relevant breast cancer models.
Thromboembolic risk assessment in patients receiving combination of anti-angiogenic plus anti-PD1 or anti-PD-L1: A descriptive study
Authors: P. Bravo, B. Vss, C. Baldini, P. Martin Romano, A. Hollebecque, A. Varga, P. Vuagnat, S. Champiat, A. Marabelle, B. Escudier, L. Albiges, Y. Loriot, C. Massard, A. Cataldi, S. Babai, A.-L. Voisin, O. Lambotte, M. Annereau, J.-M. Michot
Journal: Annals of Oncology (2019)
Activated PI3Kδ breaches multiple B cell tolerance checkpoints and causes autoantibody production
Authors: Anthony Lau, Danielle T. Avery, Katherine Jackson, Helen Lenthall, Stefano Volpi, Henry Brigden, Amanda J. Russell, Julia Bier, Joanne H. Reed, Joanne M. Smart, Theresa Cole, Sharon Choo, Paul E. Gray, Lucinda J. Berglund, Peter Hsu, Melanie Wong, Michael O’Sullivan, Kaan Boztug, Isabelle Meyts, Gulbu Uzel, Luigi D. Notarangelo, Robert Brink, Christopher C. Goodnow, Stuart G. Tangye, Elissa K. Deenick
Journal: The Journal of Experimental Medicine (2019)

Antibody-mediated autoimmune diseases are a major health burden. However, our understanding of how self-reactive B cells escape self-tolerance checkpoints to secrete pathogenic autoantibodies remains incomplete. Here, we demonstrate that patients with monogenic immune dysregulation caused by gain-of-function mutations in PIK3CD, encoding the p110δ catalytic subunit of phosphoinositide 3-kinase (PI3K), have highly penetrant secretion of autoreactive IgM antibodies. In mice with the corresponding heterozygous Pik3cd activating mutation, self-reactive B cells exhibit a cell-autonomous subversion of their response to self-antigen: instead of becoming tolerized and repressed from secreting autoantibody, Pik3cd gain-of-function B cells are activated by self-antigen to form plasmablasts that secrete high titers of germline-encoded IgM autoantibody and hypermutating germinal center B cells. However, within the germinal center, peripheral tolerance was still enforced, and there was selection against B cells with high affinity for self-antigen. These data show that the strength of PI3K signaling is a key regulator of pregerminal center B cell self-tolerance and thus represents a druggable pathway to treat antibody-mediated autoimmunity.
Impact of Open-Label Design on Patient-Reported Outcomes (PROs) Data in Randomized Clinical Trials of Immuno-Oncology (IO) Agents in Patients with Advanced or Metastatic Cancer: A 10-year systematic literature review (SLR)
Authors: A. Anota, A. Pozet, C. Lefevre, H. Lemasson, F.-E. Cotte, S. Guerzider, G. Mouillet, G. Eberst, E. Charton, V. Westeel
Journal: Annals of Oncology (2019)
<i>EGFR</i>Amplification Induces Increased DNA Damage Response and Renders Selective Sensitivity to Talazoparib (PARP Inhibitor) in Glioblastoma
Authors: Shaofang Wu, Feng Gao, Siyuan Zheng, Chen Zhang, Emmanuel Martinez-Ledesma, Ravesanker Ezhilarasan, Jie Ding, Xiaolong Li, Ningping Feng, Asha Multani, Erik P. Sulman, Roel G. Verhaak, John F. de Groot, Tim P. Heffernan, W.K. Alfred Yung, Dimpy Koul
Journal: Clinical Cancer Research (2019)

Exploration of novel strategies to extend the benefit of PARP inhibitors beyond BRCA-mutant cancers is of great interest in personalized medicine. Here, we identified EGFR amplification as a potential biomarker to predict sensitivity to PARP inhibition, providing selection for the glioblastoma (GBM) patient population who will benefit from PARP inhibition therapy.Selective sensitivity to the PARP inhibitor talazoparib was screened and validated in two sets [test set (n = 14) and validation set (n = 13)] of well-characterized patient-derived glioma sphere-forming cells (GSC). FISH was used to detect EGFR copy number. DNA damage response following talazoparib treatment was evaluated by γH2AX and 53BP1 staining and neutral comet assay. PARP-DNA trapping was analyzed by subcellular fractionation. The selective monotherapy of talazoparib was confirmed using in vivo glioma models.EGFR-amplified GSCs showed remarkable sensitivity to talazoparib treatment. EGFR amplification was associated with increased reactive oxygen species (ROS) and subsequent increased basal expression of DNA-repair pathways to counterelevated oxidative stress, and thus rendered vulnerability to PARP inhibition. Following talazoparib treatment, EGFR-amplified GSCs showed enhanced DNA damage and increased PARP-DNA trapping, which augmented the cytotoxicity. EGFR amplification-associated selective sensitivity was further supported by the in vivo experimental results showing that talazoparib significantly suppressed tumor growth in EGFR-amplified subcutaneous models but not in nonamplified models.EGFR-amplified cells are highly sensitive to talazoparib. Our data provide insight into the potential of using EGFR amplification as a selection biomarker for the development of personalized therapy.
Intravenous immunoglobulin for refractory eosinophilic fasciitis: A retrospective analysis from 3 tertiary care centers
Authors: Elizabeth Tkachenko, Alexa B. Steuer, Kelly Lo, Gabriela Cobos, Kristen Lo Sicco, Ruth Ann Vleugels, Alisa N. Femia
Journal: Journal of the American Academy of Dermatology (2019)
Income and Other Contributors to Poor Outcomes in U.S. Patients with Sarcoidosis
Authors: Logan J. Harper, Alicia K. Gerke, Xiao-Feng Wang, Manuel L. Ribeiro Neto, Robert P. Baughman, Kelli Beyer, Marjolein Drent, Marc A. Judson, Lisa A. Maier, Leslie Serchuck, Noopur Singh, Daniel A. Culver
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Socioeconomic factors are associated with worse disease severity at presentation in sarcoidosis, but the relative importance of socioeconomic variables on morbidity and disease burden has not been fully elucidated.
Severe Viral Myopericarditis With Autoantibodies Directed Against RNA Polymerase III
Authors: Marc Pineton de Chambrun, Jean-Luc Charuel, Guillaume Hékimian, François Lifermann, Alexis Mathian, Fleur Cohen-Aubart, Isabelle Melki, Charles-Edouard Luyt, Alain Combes, Zahir Amoura
Journal: Annals of Internal Medicine (2019)