tbuckley/cabot-search huggingface dataset:
Association of a DNA damage response deficiency (DDRD) assay with prognosis in resected esophageal and gastric adenocarcinoma.
Authors: Richard C. Turkington, Laura A Knight, Rosalie V. Douglas, Jaine K. Blayney, Leanne Stevenson, Damian McManus, Andrena McCavigan, Steven M. Walker, Jan Bornschein, Shona MacRae, Fergus Noble, Timothy J Underwood, Robert O'Neill, Stephen McQuaid, Ken Arthur, Jacqueline James, Martin McKinlay Eatock, Paul D Harkin, Rebecca C. Fitzgerald, Richard D. Kennedy
Journal: Journal of Clinical Oncology (2017)

4026 Background: Current strategies to guide the selection of neo-adjuvant or adjuvant therapy in esophageal and gastric adenocarcinomas (EAC/GAC) are inadequate. We assessed a clinically validated 44 gene DNA Damage Response Deficiency (DDRD) assay to predict prognosis following neo-adjuvant DNA damaging chemotherapy (CT) in EAC and adjuvant CT or chemo-radiotherapy (CRT) in GAC. Methods: Transcriptional profiling of 273 formalin fixed paraffin embedded pre-treatment endoscopic EAC biopsies was performed using the Almac Diagnostics Xcel array. All EAC patients were treated with cisplatin-based neo-adjuvant chemotherapy followed by surgical resection between 2003 and 2014 at four UK centers in the OCCAMS consortium. Further validation was performed using a publically available dataset of 270 resected gastric cancers treated with adjuvant platinum-based CT, CRT or surgery alone at the Samsung Medical Centre, Seoul, Korea. The association between the DDRD score and prognosis was assessed by Kaplan-Meier analysis and Cox Proportional Hazards regression. Results: A total of 66 EAC samples (24%) were characterized as DDRD positive with the remaining 207 samples (76%) being DDRD negative. DDRD assay positivity was associated with improved DFS (HR 0.58; 95% CI 0.36-0.93; p = 0.024) and OS (HR 0.56; 95% CI 0.34-0.92; p = 0.023) following multivariate analysis. DDRD positive patients had a higher pathological response rate (p = 0.033) and a higher rate of loco-regional versus distant relapse (30% vs 20%; p = 0.013). For GAC, 132 samples (49%) were characterized as DDRD positive with the remaining 138 (51%) being DDRD negative. DDRD positivity was associated with improved DFS (HR 0.48; 95% CI 0.25-0.96; p = 0.037) following D2 gastrectomy and adjuvant CT or CRT. DDRD status was not associated with DFS in the surgery alone cohort (HR 0.87; 95% CI 0.55-1.38; p = 0.562). Conclusions: The DDRD assay is strongly predictive of benefit from DNA damaging neo-adjuvant CT and esophagectomy in EAC and gastrectomy and CT/CRT in GAC and can be applied to routine diagnostic material.
Ankyrin repeat domain 1 regulates innate immune responses against herpes simplex virus 1: A potential role in eczema herpeticum
Authors: Lianghua Bin, Xiaozhao Li, Brittany Richers, Joanne E. Streib, Jack W. Hu, Patricia Taylor, Donald Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2018)
Validation of multidisciplinary diagnosis in IPF
Authors: Diego Castillo, Simon Walsh, David M Hansell, Martina Vasakova, Vincent Cottin, Goksel Altinisik, Stefano Palmucci, Martina Sterclova, Sergio Harari, Luca Richeldi, Carlo Vancheri, Athol U Wells
Journal: The Lancet Respiratory Medicine (2018)
Post-Transplant Cyclophosphamide Contributes to Impaired Graft-Versus-Leukemia Effects and Regulates Graft-Versus-Host Disease in the Murine Stem Cell Transplant Model
Authors: Yosuke Makuuchi, Yasuhiro Nakashima, Hideo Koh, Takahiko Nakane, Hirohisa Nakamae, Masayuki Hino
Journal: Blood (2017)
Mitochondrial Oxidative Stress Is Associated With Age-Related Glandular Remodeling And Nasal Polyp Formation
Authors: Ara Jo, Thomas B. Casale, Lydia A. Suh, Roderick G. Carter, David B. Conley, Robert C. Kern, Bruce K. Tan, Anju T. Peters, Leslie C. Grammer, Robert P. Schleimer, Seong Ho Cho
Journal: Journal of Allergy and Clinical Immunology (2018)
Prognostic Impact of NPM1/FLT3-ITD genotypes from Randomized Patients with Acute Myeloid Leukemia (AML) Treated within the International Ratify Study
Authors: Konstanze Döhner, Christian Thiede, Richard A. Larson, Thomas W Prior, Guido Marcucci, Dan Jones, Jürgen Krauter, Michael Heuser, Francesco Lo Coco, Tiziana Ottone, Josep Nomdedeu, Sumithra J Mandrekar, Ben L. Sanford, Kristine Laumann, Susan M. Geyer, Rebecca B. Klisovic, Andrew Wei, Jorge Sierra, Miguel A. Sanz, Joseph M. Brandwein, T. M. M de Witte, Joop H. Jansen, Dietger Niederwieser, Frederick R. Appelbaum, Bruno C Medeiros, Martin S. Tallman, Richard F. Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Yuan Cheng, Celine Pallaud, Richard M. Stone, Hartmut Döhner, Clara D. Bloomfield
Journal: Blood (2017)
Redefining Hypertension — Assessing the New Blood-Pressure Guidelines
Authors: George Bakris, Matthew Sorrentino
Journal: New England Journal of Medicine (2018)

Interview with Dr. George Bakris on new blood-pressure guidelines from the American College of Cardiology and the American Heart Association. (07:58)Download Shifting the threshold for hypertension to 130/80 mm Hg, as the new guidelines do, will overburden our primary care physician workforce, and many people will receive pharmacologic therapy that will carry more risk than benefit.
Safety and Efficacy of the Combination of Ibrutinib and Nivolumab in Patients with Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia
Authors: Anas Younes, Joshua Brody, Cecilia Carpio, Armando Lopez-Guillermo, Dina Ben-Yehuda, A. Burhan Ferhanoglu, Arnon Nagler, Muhit Ozcan, Irit Avivi, Francesc Bosch Albareda, María Dolores Caballero Barrigón, Aisha Masood, Michael Streit, John Alvarez, Rob Ceulemans, Behzad Kharabi Masouleh, Sriram Balasubramanian, Michael Schaffer, Shean-Sheng Wang, Nele Fourneau, Wojciech Jurczak
Journal: Blood (2017)
Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients
Authors: Jorine de Haan, Magali Verheecke, Kristel Van Calsteren, Ben Van Calster, Roman G Shmakov, Mina Mhallem Gziri, Michael J Halaska, Robert Fruscio, Christianne A R Lok, Ingrid A Boere, Paolo Zola, Petronella B Ottevanger, Christianne J M de Groot, Fedro A Peccatori, Karina Dahl Steffensen, Elyce H Cardonick, Evgeniya Polushkina, Lukas Rob, Lorenzo Ceppi, Gennady T Sukhikh, Sileny N Han, Frédéric Amant
Journal: The Lancet Oncology (2018)
Abstract 16374: The Vancouver General Hospital Pericardial Effusion Risk Index
Authors: Calvin Ka Wing Tong, Ken Gin, John Jue, Pui Kee Lee, Parvathy Nair, Elena Szefer, Darby Thompson, Michael Tsang, Teresa Tsang
Journal: Circulation (2016)

Background: Management of hemodynamically stable patients with at least moderate sized pericardial effusion is often at the discretion of attending cardiologists. Objective scoring index to guide p...
Impact of Bone Marrow Biopsy on Risk Stratification of Low-Risk IgG MGUS Patients
Authors: Mark Bustoros, Eftathios Kastritis, Chia-Jen Liu, Nikolaos Kanellias, David Liu, Maria Gavriatopoulou, Adriana Perilla Glen, Maria Roussou, Patrick Henrick, Magdalini Migkou, Alexandra Savell, Kimberly Noonan, Kaitlen Reyes, Bradley Rivotto, Houry Leblebjian, Claudia Paba-Prada, Dimitrios C. Ziogas, Jacob Laubach, Robert L. Schlossman, Kenneth C Anderson, Paul G Richardson, Irene M Ghobrial, Meletios A. Dimopoulos
Journal: Blood (2017)
Abstract 16255: Left Persistent Superior Vena Cava as an Arrhythmogenic Source in Atrial Fibrillation, A Large Multicenter Observational Study
Authors: Moustapha Atoui, Donita Atkins, Madhav Lavu, Rizwan Afzal, Sandia Iskandar, Sudharani Bommana, Luigi DiBiase, Kalyanam Shivkumar., Jared Bunch, Sanghamitra Mohanty, Carola Gianni, Andrea Natale, Raghuveer Dendi, Madhu Reddy, Dhanunjaya Lakkireddy
Journal: Circulation (2016)

Introduction: the left persistent superior vena cava (LPSVC) is one of the most frequent congenital anomalies. It has been described in few reported cases to be implicated in the initiation and mai...
Role Of Parenchymal Interdependence In The Short-Term Dynamics Of Recruitment/derecruitment In Injured Lung: A Modelling Study
Authors: L. Broche, A. Tannoia, Mariangela Pellegrini, S. Derosa, A. Sindaco, João Batista Borges, L. Porra, Anders Larsson, Göran Hedenstierna, A. Bravin, G. Perchiazzi, A. S. Wexler, S. Verbanck, J. H. T. Bates, S. Bayat
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Role Of Parenchymal Interdependence In The Short-Term Dynamics Of Recruitment/derecruitment In Injured Lung : A Modelling Study
The impact of dual inhibition on the androgen receptor and mTOR pathway cross talk in vitro and in vivo in prostate cancer models
Authors: Adam Schayowitz, Gauri Sabnis, Vincent Njar, Olga Goloubeva, Angela Brodie
Journal: Cancer Research (2008)

1212  Androgen ablation is the standard treatment for advanced disease. Despite initial success, approximately 70% of patients eventually progress to hormone refractory prostate cancer (HRPC). To investigate the mechanisms of this resistance we utilized human prostate cancer cells (LNCaP). Our studies suggest a compensatory signaling mechanism and cross-talk pathway between AR and PI3K/Akt/mTOR pathway occurs with androgen ablation treatment in-vitro. We also demonstrated that dual inhibition of AR and mTOR synergistically inhibited cell proliferation. The current investigation analyzed the interaction of the AR and mTOR pathways in-vitro and in-vivo. Using co-immunoprecipitation of Akt and AR, it was found that the interaction between the pathways increases 7-fold as cells progressed from a hormone sensitive to hormone resistant model. The interaction was reduced 36% with bicalutamide and 54% with our novel anti-androgen/androgen synthesis inhibitor, VN/124-1. Everolimus, an mTOR inhibitor, also reduced the interaction modestly (37%). However, bicalutamide plus everolimus reduced the interaction by 71% while VN/124-1 plus verolimus reduced the interaction by nearly 100%. An in vivo hormone dependent LNCaP xenograft investigation demonstrated that the addition of everolimus to bicalutamide resistant tumors significantly decreased growth rate and tumor volume compared to single agent bicalutamide (p=0.0001) or everolimus (p=0.04). Additional in vivo experiments investigated tumors progression following anti-androgen therapy. PSA increased in control mice from 2.9±0.2ng/nl at week 2 to 4.3±0.568ng/ml at week 3 and to 7.4±0.783ng/ml at week 4 confirming disease progression. Both bicalutamide and VN/124-1 increased IGFR, p-Akt, p-70S6K and p-P6S6 protein expression compared to control xenografts. A third xenograft investigation with hormone resistant prostate cancer cells (HP-LNCaP) demonstrated that dual inhibition with everolimus (5mg/kg/QW-PO) and VN/124-1 (100mg/kg/QD-SC) significantly (p=0.03) reduced tumor volume and growth rate compared to single agent everolimus. Furthermore, growth trends indicate that VN/124-1 plus everolimus was more effective than bicalutamide plus everolimus. In summary, the interaction between the AR and Akt pathways is decreased by dual inhibition of AR and mTOR. As tumors progress on anti-androgen therapy, there is a more rapid increase in signal transduction pathway activation compared to controls. As such, the combination of anti-androgen, such as VN/124-1, and mTOR inhibitors from the beginning significantly reduced tumor volume compared to everolimus or bicalutamide alone in HRPC xenografts. Improved understanding of the interaction between the AR and mTOR pathways reveals a better strategy for treating disease progression that may delay, re-sensitize or prevent HRPC.
Abstract 15019: Relation Between Fibrous Cap Thickness and No Reflow Phenomenon in Patients with Acute Myocardial Infarction
Authors: Yohei Goto, Syoji Iwaya, Eisuke Miura, Yuko Matsui, Hironori Kaneko, Yuichi Ujiie, Keiji Sakamoto, Yoshitane Seino, Mikihiro Kijima, Yukio Maruyama
Journal: Circulation (2011)

Background:  No reflow phenomenon after percutaneous coronary intervention (PCI) has been shown to lead to poorer outcome in patients with acute myocardial infarction (AMI). Recent studies have reported about possible causes of this phenomenon, such as distal embolization of thrombus and plaque contents. Little is known about the surface morphologies of culprit coronary artery in AMI and it is still difficult to predict no reflow phenomenon. We assessed the hypothesis that released substances from easily ruptured plaque due to PCI might play a role for no reflow phenomenon in AMI.   Objectives:  The aim of this study is to investigate the predictor of no reflow phenomenon using optical coherence tomography (OCT) as well as intravascular ultrasound (IVUS).   Methods:  45 patients with AMI, who underwent OCT and IVUS before primary PCI were included. No reflow phenomenon was defined using coronary angiography as decrease in TIMI flow grade without mechanical coronary obstruction. Fibrous cap thickness was measured by OCT, and plaque characteristics were determined using previously validated criteria. Arterial remodeling and attenuated plaque were assessed by IVUS.   Results:  No reflow phenomenon occurred in 7 cases (group 1), and was not found in 38 cases (group 2). Fibrous cap thickness of group 1 was smaller (45.7±19.5 micrometer in group 1, 69.0±55.4 micrometer in group 2, p=0.0076), positive remodeling was more frequent (85.7% in group 1, 39.3% in group 2, p=0.028). Frequency of attenuated plaque, plasma C-reactive protein level, lipid profile, number of diseased vessels and stent size were not different significantly between two groups. Multiple logistic regression analysis indicated that thin-cap fibroatheroma was the strongest predictor of no reflow phenomenon (odds ratio 2.76, 95% confidence interval; 1.56 to 160.51; p=0.0196), and that neither attenuated plaque (p=0.7208) nor positive remodeling (p=0.1202) was significant predictors.   Conclusions:  No reflow phenomenon increased in cases presenting thin-cap fibroatheroma. OCT highly predicted no reflow phenomenon, suggesting that OCT is useful for predicting no reflow phenomenon in primary PCI in AMI.
Invasive Aspergillosis in Chronic Lymphocytic Leukemia: Therapy and Outcomes
Authors: Narjust Duma, Jonas Paludo, Brian Kabat, Aaron Tande, Kari G Chaffee, Timothy G. Call, Saad Sirop Kenderian, Wei Ding, Jose F. Leis, Melissa C. Larson, Asher A. Chanan-Khan, Michael Conte, Susan Marie Schwager, Susan L Slager, Neil E. Kay, Tait D. Shanafelt, Sameer A. Parikh
Journal: Blood (2017)
Primary Analysis of Juliet: A Global, Pivotal, Phase 2 Trial of CTL019 in Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Stephen J. Schuster, Michael R. Bishop, Constantine S. Tam, Edmund K. Waller, Peter Borchmann, Joseph P. McGuirk, Ulrich Jaeger, Samantha Jaglowski, Charalambos Andreadis, Jason R. Westin, Isabelle Fleury, Veronika Bachanova, Stephen Ronan Foley, P. Joy Ho, Stephan Mielke, John M. Magenau, Harald Holte, Koen Van Besien, Marie Jose Kersten, Takanori Teshima, Kensei Tobinai, Paolo Corradini, Oezlem Anak, Lida Bubuteishvili Pacaud, Christopher del Corral, Rakesh Awasthi, Feng Tai, Gilles Salles, Richard Thomas Maziarz
Journal: Blood (2017)
Erlotinib as neoadjuvant treatment in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation (NCT01217619, ESTERN).
Authors: Baohui Han, Liwen Xiong, Jiayuan Sun, Rong Li, Yuqing Lou, Yanwei Zhang
Journal: Journal of Clinical Oncology (2012)

e17551 Background: Patients with stage IIIA N2 NSCLC have poor outcomes with 5-year survival rate. Tyrosine kinase inhibitor monotherapy have been demonstrated a significant improvement in OR rate and PFS as first-line treatment for metastatic NSCLC patients with EGFR mutation. The objective of trial is to explore the efficacy and safety profile of erlotinib as neoadjuvant treatment in patients of stage IIIA-N2 NSCLC with EGFR mutation. The purpose of this neoadjuvant regime is to down-stage and increase complete resection rate in this patients setting. Methods: This is a single arm, one center, phase II study of erlotinib as neoadjuvant treatment in patients with Endobronchial Ultrasound (EBUS) confirmed stage IIIA-N2 NSCLC with activating EGFR mutation in exon 19 or 21. The primary endpoint is to evaluate radical resection rate. The secondary endpoint is pathological complete resection rate (pCR), objective response rate (ORR), disease free survival (DFS), overall survival (OS), quality of life (QoL) and safety profile. A total of 44 patients will be enrolled. Patients with IIIA-N2 NSCLC with pathologically confirmed ipsilateral mediastinal metastasis by EBUS. The biopsy specimen shows EGFR mutation in exon 19 or 21. All patients will be treated by erlotinib 150mg orally per day for 56 days. Patients will be assessed by Chest CT for the efficacy evaluation in day 29 and right after day 56. Patients get benefit from neoadjuvant treatment and evaluated as technically resectable will receive surgery. All the post-operative patients will receive standard adjuvant treatment. The adjuvant regime is decided by the investigator for the patients’ benefits. After adjuvant treatment patients will enter nomal follow-up including regular chest CT and ultrasound examination Results: Current enrollment: The study has enrolled 5 patients. One male patient, aged 47, with stable disease after neoadjuvant treatment, got right upper lobe resection on 17 Jan 2012. Conclusions: Erlotinib as neoadjuvant treatment in patients of stage IIIA-N2 NSCLC with activating EGFR mutation is feasible.
Mitochondrial Carrier Homolog 2 (MTCH2) Regulates the Differentiation of AML Cells By Controlling Pyruvate Entry into the Mitochondria, Nuclear Localization of Pyruvate Dehydrogenase Complex and H3 and H4 Histone Acetylation
Authors: Dilshad H. Khan, Michael Mullokandov, Yan Wu, Marcela Gronda, Rose Hurren, Xiaoming Wang, Neil MacLean, Danny V. Jeyaraju, G. Wei Xu, Rob C. Laister, Zachary Blatman, Troy Ketela, Mark D. Minden, Atan Gross, Aaron D. Schimmer
Journal: Blood (2017)
Have the 10-year outcomes of patients with early inflammatory arthritis improved in the new millennium compared with the decade before? Results from the Norfolk Arthritis Register
Authors: James M Gwinnutt, Deborah P M Symmons, Alexander J MacGregor, Jacqueline R Chipping, Tarnya Marshall, Mark Lunt, Suzanne M M Verstappen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objective</h3> To compare the 10-year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart. <h3>Methods</h3> Patients with IP were recruited to the Norfolk Arthritis Register from 1990 to 1994 (cohort 1 (C1)) and from 2000 to 2004 (cohort 2 (C2)). Demographic and clinical data were collected at baseline and at years 1, 2, 3, 5, 7 and 10. Longitudinal disease activity (swollen/tender 51 joint counts (SJC51/TJC51)) and disability (Health Assessment Questionnaire (HAQ)) were compared between the cohorts using population-average negative binomial regression and generalised estimating equation analysis, respectively. Risk of 10-year mortality was compared between cohorts using Cox models. Risk of cardiovascular disease (CVD) mortality was compared between cohorts using competing risks analysis. Mortality rate ratios (MRR), adjusted for changes in mortality risk of the general population, were calculated using Poisson regression. <h3>Results</h3> In total 1653 patients were recruited (C1=1022, C2=631). Patients in C2 had 17% lower SJC51 than C1 over 10 years (95% CI −23% to −10%), whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared with C1 (all-cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: subhazard ratio 0.58, 95% CI 0.37 to 0.93). After accounting for changes in mortality risk in the general population, the difference in mortality was non-significant (all-cause: MRR 0.78, 95% CI 0.56 to 1.10; CVD: MRR 0.77, 95% CI 0.48 to 1.24). <h3>Conclusion</h3> Disease activity significantly improved in the new millennium, whereas disability and mortality were unchanged.
Association of Treatment for Hodgkin Lymphoma With Estrogen Receptor Status of Subsequent Breast Cancers
Authors: Diana R. Withrow, Lindsay M. Morton, Rochelle E. Curtis, Sara J. Schonfeld, Amy Berrington de González
Journal: JAMA Oncology (2018)

This population-based cohort study examines the association of radiotherapy for Hodgkin lymphoma with risk of ER-positive and ER-negative breast cancers using data from the US National Cancer Institute Surveillance, Epidemiology, and End Results database.
Statin wars: have we been misled about the evidence? A narrative review
Authors: Maryanne Demasi
Journal: British Journal of Sports Medicine (2018)

Statins are the most widely prescribed, cholesterol-lowering drugs in the world. Despite the expiration of their patents, revenue for statins is expected to rise, with total sales on track to reach an estimated US$1 trillion by 2020. A bitter dispute has erupted among doctors over suggestions that statins should be prescribed to millions of healthy people at low risk of heart disease. There are concerns that the benefits have been exaggerated and the risks have been underplayed. Also, the raw data on the efficacy and safety of statins are being kept secret and have not been subjected to scrutiny by other scientists. This lack of transparency has led to an erosion of public confidence. Doctors and patients are being misled about the true benefits and harms of statins, and it is now a matter of urgency that the raw data from the clinical trials are released.
Morgan's canon is not evidence
Authors: Steven Samuel, Nicola Clayton
Journal: Behavioral and Brain Sciences (2018)

Abstract Mahr &amp; Csibra's (M&amp;C's) account of the communicative function of episodic memory relies more heavily on the case against episodic memory in nonhumans than their description suggests. Although the communicative function of episodic memory may be accurate as it pertains to human behaviour, we question whether Morgan's canon is a suitable foundation on which to build theories of supposedly human-specific traits.
Preemptive Daratumumab Therapy for Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma: Rationale and Design of the Polish Myeloma Consortium Predator Study
Authors: Krzysztof Jamroziak, Krzysztof Giannopoulos, Tomasz Wrobel, Adam Nowicki, Bartosz Pula, Norbert Grząśko, Justyna Rybka, Paweł J. Robak, Agnieszka Druzd-Sitek, Adam Walter-Croneck, Katarzyna Brzeźniakiewicz-Janus, Jarosław Czyż, Krzysztof Warzocha, Dominik Dytfeld
Journal: Blood (2017)