tbuckley/cabot-search huggingface dataset:
Abstract A30: Kinome dynamics in triple negative breast cancer in response to chemotherapy
Authors: Sara H. Velarde, Jerry Usary, Chuck Perou, Gary L. Johnson
Journal: Clinical Cancer Research (2017)

Abstract Triple negative breast cancers (TNBC) have lower expression levels of the receptors (estrogen, progesterone, Her2) used in targeted therapy than other breast cancer subtypes. This makes chemotherapy the main option for treatment for TNBC patients. Only about 22% of TNBC patients respond to chemotherapy, so it is important to understand the tumor cell response involved in TNBC chemo-resistance in order to develop more effective therapies. We have studied the kinome response to paclitaxel and carboplatin in tumor samples derived from TNBC patients in both HIM PDXs (Human-In-Mouse Patient Derived Xenografts) and cell lines derived from HIM PDX lines. Integration of RNAseq and Multiplexed Inhibitor Bead/Mass Spectrometry (MIB/MS) analysis of kinome dynamics in HIM PDXs in response to carboplatin and paclitaxel treatment identified multiple pathways whose expression and/or MIB binding dynamics were changed or altered after chemotherapy. Multiple survival and apoptotic regulators, including NFkB, JNK, ErbB, Sonic Hedgehog and Hippo pathways, were altered over the course of chemotherapy treatment. We are interrogating these pathways in both the HIM PDXs and HIM cell lines to determine each pathway's role in chemosensitivity with the goal of developing pharmacological strategies to increase the efficacy of chemotherapy, as well as kinase inhibitors, in the clinic. Citation Format: Sara H. Velarde, Jerry Usary, Chuck Perou, Gary L. Johnson. Kinome dynamics in triple negative breast cancer in response to chemotherapy. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A30.
Myotomie par voie endoscopique: une méta-analyse
Authors: G. Rahmi
Journal: Endoscopy (2016)

La myotomie par voie endoscopique (POEM) est un nouveau traitement mini-invasif des troubles moteurs de l’oesophage et en particulier de l’achalasie du sphincter inférieur de l’œsophage (SIO). Le premier cas a été réalisé chez un humain en 2010. Elle correspond à la section des fibres de la musculeuse grâce à la réalisation d’un tunnel sous-muqueux.
P166 The emerging role of airway clearance techniques in the treatment of interstitial lung disease
Authors: L Skevington-Postles, S Akers, P George, G Housley, J Beadle, A Devaraj, F Chua
Journal: Thorax (2016)

<h3>Introduction</h3> Patients with interstitial lung disease (ILD) may develop airway abnormalities as part of their underlying condition, in response to fibrotic/tractional dilatation or as a result of repeated bronchiolar infection. While current practice guidelines recommend the provision of pulmonary rehabilitation for ILD patients, no other interventions have been endorsed. We assessed the symptomatic need of patients with ILD for airway clearance techniques (ACT’s) using a visual analogue scale, and whether, in those with fibrotic ILD, the presence of traction bronchiectasis was correlated with the need for ACT’s. <h3>Methods</h3> Over a 15-week period, data were prospectively collected on ILD patients who consented for detailed physiotherapy assessment and intervention. Those who reported a sensation of persistent secretion retention, frequent chest infections (&gt;2 in 6 months) or those with pre-existing airway disease had a full clearance assessment. The radiological presence or absence of traction bronchiectasis was noted, as was evidence of other airway pathology such as bronchiolitis. <h3>Results</h3> 30 ILD inpatients (16 females) were included in the study (Table 1). The commonest causes for admission were ILD staging (<i>n</i> = 10) and disease deterioration requiring intravenous treatment (<i>n</i> = 14). 27 patients (90%) required physiotherapy input and 11 patients (41%) required ACT’s. 9 patients had positive sputum microbiology; of these, 3 were first isolates. 7 of these 9 patients had traction bronchiectasis on CT acquired within 3 months of assessment. One patient did not undergo CT. The presence of traction bronchiectasis correlated with a higher sputum microbial yield (p &lt; 0.05) but not with a need for ACT (p &gt; 0.05). <h3>Conclusion</h3> Airway abnormalities are often not a principal therapeutic focus in ILD but symptoms related to mucostasis, recurrent infection and airflow limitation may be disabling. In this study, the majority of patients with positive microbiology had traction bronchiectasis. Although no firm conclusions can be drawn regarding the role of ACT’s in their management, this intervention improved the yield of specimens for microbial analysis and facilitated pathogen-directed antimicrobial therapy. These findings suggest that a systematic physiotherapy approach including optimisation of airway clearance can benefit patients with parenchymal lung disease.
Opioid Therapy for Chronic Pain
Authors: Jane C. Ballantyne, Jianren Mao
Journal: New England Journal of Medicine (2003)

A difficult decision for physicians who treat patients with chronic pain not associated with terminal disease is whether and how to prescribe opioid therapy, which can relieve pain and improve mood and level of functioning in many such patients. This review considers current guidelines for opioid therapy in patients with chronic pain unrelated to malignant conditions and outlines caveats, areas of uncertainty, and management strategies.
Abstract 16514: Screening for Outflow Cannula Malfunction of Left Ventricular Assist Devices Using Doppler Echocardiography: Establishing New Reference Values
Authors: Jonathan Grinstein, Eric Kruse, Gabriel Sayer, Savitri Fedson, Gene H Kim, Nitasha Sarswat, Sirtaz Adatya, Takeyoshi Ota, Valluvan Jeevanandam, Victor Mor-Avi, Nir Uriel, Roberto Lang
Journal: Circulation (2015)

Background: Echocardiographic assessment of left ventricular assist devices (LVAD) is used as a screening tool to evaluate the integrity and mechanics of the pump and circuit. We aimed to 1) establish the normal range and upper reference limit of peak velocity of the outflow cannula for the modern era of LVADs and 2) assess the performance of the current reference limit and our new reference limit in patients with continuous flow LVADs as a screening tool for cannula malfunction. Methods: LVAD outflow peak velocities were measured with Doppler echocardiography (TTE) in 57 patients with LVADs (HeartMate II (HMII) = 44, HeartWare (HW) = 13). The average velocity and the upper and lower normal reference limits (defined as +/- two standard deviations from the mean) for each LVAD type was then calculated. The upper reference limit was then used as a screening threshold for cannula malfunction. Results: The average outflow cannula peak velocity for the HMII cohort was 1.94 m/sec +/- 0.42 with an upper and lower reference limit of 2.78 m/sec and 1.10 m/sec, respectively. The average outflow cannula peak velocity for the HW cohort was 2.36 +/- 0.53 with an upper and lower reference limit of 3.42 m/sec and 1.3 m/sec, respectively, which was significantly higher than the HMII cohort (p=0.004). Velocities from both cohorts were dramatically higher than the commonly citied upper reference limit velocities of 2 m/sec. Use of the previously cited reference limit poorly discriminated between normal and malfunctioning LVAD cannulas whereas our new reference limit identified all four patients with outlet cannula malfunction (Figure1). Conclusions: In both HeartMate II and HeartWare LVADs, the average peak outflow velocity and reference limit for the normal population as measured by Doppler-TTE was markedly higher than currently cited LVAD reference limits. Patients with peak outflow velocities above our upper reference limit should be evaluated for LVAD outflow cannula malfunction.
P1.08-069 One Surgeon's 30-Year Experience of Surgical Treatment for Pancoast Tumor
Authors: Hiroshi Niwa, Masayuki Tanahashi, Haruhiro Yukiue, Eriko Suzuki, Naoko Yoshii, Masayuki Shitara, Toshio Fujino, Yasunori Kaminuma
Journal: Journal of Thoracic Oncology (2017)
The caecal mucus sign
Authors: Jason Behary, Jason Minco Hui
Journal: Gut (2017)

A 60-year-old man with a history of colonic adenoma underwent routine surveillance colonoscopy. He has been asymptomatic. At colonoscopy, there was adherent mucus identified at the base of the caecal pole (figure 1A). The adherent mucus covered the appendiceal orifice (figure 1B). A CT scan of the abdomen revealed no abnormality.



Figure 1 
(A) Endoscopic view of the caecal pole. (B) Close-up view of the adherent mucus.



What is the most likely diagnosis and management?

Adherent mucus at appendiceal orifice should alert the endoscopist to suspect appendiceal mucinous neoplasm (appendiceal …
Abstract A39: A small molecule inhibitor of the Notch transcriptional activation complex
Authors: Luisana Astudillo, Anthony J. Capobianco
Journal: Clinical Cancer Research (2017)

Abstract Deregulation of the Notch pathway underlies many aspects of cancer physiology depending on cell type and context. In many human cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of the neoplastic phenotype. Notch also plays a central role in cancer stem cells, which may underlie a role in metastasis and resistance to therapy. The important and diverse role played by Notch in cancer makes it an exceedingly attractive target for anti-neoplastic therapeutics. However, the full range of potential targets in the pathway have been under-explored. To date, there are no small molecule inhibitors that directly target the intracellular Notch pathway or the assembly of the transcriptional activation complex. We have developed an in vitro assay that quantitatively measures the assembly of the Notch transcriptional complex on DNA. Through computer-aided drug design we explored potential ligand binding sites and screened for compounds that could disrupt the assembly of the Notch transcriptional activation complex. Herein we report the identification and characterization of a small molecule inhibitor of the Notch transcriptional activation complex, termed Inhibitor of Mastermind Recruitment-1 (IMR-1). We demonstrate that IMR-1 disrupts the recruitment of Mastermind-like 1 (Maml1) to the Notch transcriptional activation complex on chromatin and thereby causes a decrease in Notch target gene transcription. Furthermore, IMR-1 inhibits the growth of Notch-dependent cell lines and significantly abrogates the growth of patient-derived tumor xenografts. Therefore, our data suggest that a novel class of Notch inhibitors targeting the transcriptional activation complex may represent a new paradigm for Notch-based anticancer therapeutics. Citation Format: Luisana Astudillo, Anthony J. Capobianco. A small molecule inhibitor of the Notch transcriptional activation complex. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A39.
P2.06-047 LRRK2-In-1 Inhibit Proliferation of Doublecortin and CaM Kinase-Like-1 (DCLK1)-Positive Lung Cancer Cells
Authors: Hiroyuki Tao, Yuka Mimura-Kimura, Yusuke Mimura, Akio Hara, Daigo Murakami, Masashi Furukawa, Masataro Hayashi, Kazunori Okabe
Journal: Journal of Thoracic Oncology (2017)
Polycomb Group Protein BMI1 In Leukemia Development and Progression:Blocking the Cell Differentiation
Authors: Hong-jie Shen, Xin Ding, Jian-nong Cen, Yuan-yuan Wang, Xiao-fei Qi, Jun He, Li Yao, Tian-tian Wang, Zi-Xing Chen
Journal: Blood (2010)
Upper Gastrointestinal Acute Graft-Versus-Host Disease Adds Minimal Prognostic Value When Present in Isolation or in Addition to Grade I or Other Grade II-Defining GvHD Manifestations
Authors: Sarah Nikiforow, Michael Hemmer, Stephen R. Spellman, Amin M. Alousi, Daniel R. Couriel, Joseph A Pidala, Mukta Arora, Corey S Cutler, Tao Wang
Journal: Blood (2015)
What will the next influenza season bring about: seasonal influenza or the new A(H1N1)v? An analysis of German influenza surveillance data
Authors: H Uphoff, S Geis, A Grüber, A M Hauri
Journal: Eurosurveillance (2009)

For the next influenza season (winter 2009-10) the relative contributions to virus circulation and influenza-associated morbidity of the seasonal influenza viruses A(H3N2), A(H1N1) and B, and the new influenza A(H1N1)v are still unknown. We estimated the chances of seasonal influenza to circulate during the upcoming season using data of the German influenza sentinel scheme from 1992 to 2009. We calculated type and subtype-specific indices for past exposure and the corresponding morbidity indices for each season. For the upcoming season 2009-10 our model suggests that it is unlikely that influenza A(H3N2) will circulate with more than a low intensity, seasonal A(H1N1) with more than a low to moderate intensity, and influenza B with more than a low to median intensity. The probability of a competitive circulation of seasonal influenza A with the new A(H1N1)v is low, increasing the chance for the latter to dominate the next influenza season in Germany.
Evidence That the MPL 515L and 515K Mutations Occur in a Lympho-Myeloid Progenitor in Idiopathic Myelofibrosis and Are Associated with TPO Hypersensitivity.
Authors: Ronan Chaligne, Jean-Pierre Le Couedic, Carole Tonetti, Rodolphe Besancenot, Orianne Wagner-Ballon, Najet Debili, William Vainchenker, Stephane Giraudier
Journal: Blood (2006)
Higher Parathyroid Hormone Level Is Associated With Increased Arterial Stiffness in Type 1 Diabetes
Authors: Emilie H. Zobel, Simone Theilade, Bernt Johan von Scholten, Frederik Persson, Lise Tarnow, Maria Lajer, Tine W. Hansen, Peter Rossing
Journal: Diabetes Care (2017)

Vascular calcification is a common consequence of aging, hypercholesterolemia, chronic renal insufficiency, and diabetes (1). Stiffening of the large arteries is a result of vascular calcification. Carotid–femoral pulse wave velocity (cfPWV) is considered the gold standard measure of arterial stiffness (2) and has been shown to be a strong predictor of mortality and cardiovascular outcome.

We evaluated the association between arterial stiffness (evaluated by cfPWV) and bone mass density (evaluated with dual-energy X-ray absorptiometry at the femoral neck), as well as a comprehensive panel of bone markers, in a well-characterized cohort of 347 persons with type 1 diabetes. We hypothesized that vascular calcification is linked to decalcification of the bones.

The participants were recruited from the outpatient clinic at Steno Diabetes Center, Gentofte, Denmark. Written informed patient consent and ethical approval of the study were obtained.

A total of 164 (47%) participants were women, mean ± SD age was 55.8 ± 9.6 years and cfPWV was 11.0 ± 3.4 m/s, and median …
Dynamics of Chimerism In Regulatory T Lymphocytes (Treg; CD4+/CD25+) After Allogeneic Stem Cell Transplantation
Authors: Víctor Noriega, Carolina Martinez-Laperche, David Serrano, Gabriela Rodriguez-Macias, Mi Kwon, Jorge Gayoso, Pascual Balsalobre, Jose Luis Diez-Martin, Ismael Buno
Journal: Blood (2010)
OA23.02 Efficacy and Safety of Necitumumab Continuation Monotherapy in Patients with EGFR-Expressing Tumors in SQUIRE, a Phase 3 Study
Authors: Tudor Ciuleanu, Mark Socinski, Coleman Obasaju, Alexander Luft, Aleksandra Szczęsna, Rodryg Ramlau, Beatrix Bálint, Olivier Molinier, Henrik Depenbrock, Shivani Nanda, Luis Paz-Ares, Nick Thatcher
Journal: Journal of Thoracic Oncology (2017)
P3.02b-047 Co-Activation of STAT3 and YAP1 Signaling Pathways Limits EGFR Inhibitor Response in Lung Cancer
Authors: Niki Karachaliou, Imane Chaib, Andrés Cardona, Guillermo López-Vivanco, Alain Vergnenegre, José Miguel Sánchez, Mariano Provencio, Filippo De Marinis, Antonio Passaro, Enric Carcereny, Noemi Reguart, Rosario García Campelo, Mariacarmela Santarpia, Santiago Viteri, Miguel Angel Molina Vila, Xuefei Li, Caicun Zhou, Teresa Morán, José Luis Ramírez Serrano, Trever Bivona, Patrick Ma, Ana Drozdowskyj, Peng Cao, Rafael Rosell
Journal: Journal of Thoracic Oncology (2017)
Alemtuzumab (Campath 1-H) in Patients with HTLV-1 Associated Adult T-Cell Leukemia/Lymphoma.
Authors: Kamal Sharma, John E. Janik, Deirdre O’Mahony, Donn Stewart, Stefania Pittaluga, Maryalice Stetler-Stevenson, Elaine S. Jaffe, Mark Raffeld, Thomas A. Fleisher, Cathryn C. Lee, Nicole Urquhart, Seth Steinberg, Thomas A. Waldmann, John C. Morris
Journal: Blood (2008)
Phase II Study of Enzastaurin in Patients with Follicular Lymphoma: Updated Final Clinical Results and Immunohistochemical Correlations
Authors: Lee Schwartzberg, Robert Hermann, Ian W. Flinn, Douglas Flora, Eric D. Hsi, Oday Hamid, Scott P. Myrand, Boris Lin, Donald Thornton, Peipei Shi, Tuan S Nguyen, Martin Dreyling
Journal: Blood (2012)
S30 Sensations associated with experimentally evoked cough: a comparison of chronic cough patients with healthy controls
Authors: J Mitchell, B Al-Sheklly, B Issa, T Collier, D Corfield, JA Smith
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Cough is generally considered a protective airway reflex, however emerging evidence suggests chronic coughing is provoked by noxious sensations from the airway and serves to relieve these sensations. We have found patients with unexplained chronic coughing identify sensations of irritation, tickle (throat) and the urge to cough (UTC) as important sensations provoking coughing. We hypothesised that inhaling low dose tussive agents would evoke similar sensations and could provide a model for investigating chronic cough. <h3>Methods</h3> Twelve chronic cough patients (mean age 61.4 yrs, 75% female, median cough duration 7 yrs) and 10 healthy volunteers (mean age 48.8 yrs, 40% female) inhaled increasing concentrations of citric acid from a dosimeter (0.01–4 M, 18 ascending concentrations). Following each inhalation subjects rated irritation, tickle, UTC and taste on 100 mm visual analogue scales (VAS; 0mm = none and 100 mm = worst). The experiment continued until subjects coughed at least twice on any concentration of citric acid (C2). Somatosensory amplification score (SSAS) and State Trait Anxiety Index (STAI) were also collected. For the analysis, VAS data were aligned by the C2 concentration and sensation VAS scores compared using Mann-Whitney U tests. STAI scores were also compared with Mann-Whitney U tests and SSAS with an independent T test. <h3>Results</h3> The chronic cough patients had a much lower C2 than healthy controls (median 0.094 vs. 0.5M, p = 0.009). The UTC VAS and coughs evoked were similar at C2 and for the preceding concentrations in both groups, Figure 1. However, tickle, irritation and taste were rated more highly in healthy volunteers compared with chronic cough patients at C2 and for several preceding concentrations. For example, at C2, irritation VAS was significantly higher in healthy controls (dp = 0.035) and tickle VAS was borderline significant (p = 0.052) compared with chronic cough patients, however taste differences were not significant (p = 0.29). SSAS, STAI state and trait were not significantly different between the groups (p = 0.23, p = 0.096 and p = 0.62 respectively). <h3>Conclusions</h3> These data suggest that as well as differences in cough threshold, chronic cough patients exhibit heightened urge-to-cough rather than other sensations in response to low level tussive agents.
P7 Clinicians’ perspectives of health related quality of life and priorities in deciding management for malignant pleural effusion
Authors: P Sivakumar, D Curley, NM Rahman, YCG Lee, D Feller-Kopman, A West, L Ahmed
Journal: Thorax (2016)

<h3>Introduction</h3> Malignant pleural effusion (MPE) management has dramatically changed in the last decade with the increasing use of indwelling pleural catheters (IPC) and thoracoscopy. Although treatment is aimed at improving health related quality of life (HRQOL), data on outcomes are limited, with management guided by clinician perspectives and experiences. <h3>Aims</h3> We sought clinician perspectives of HRQOL for patients with MPE and its impact on decision making worldwide. We present the UK data. <h3>Methods</h3> We invited all respiratory doctors in the UK to complete an online survey advertised in the British Thoracic Society newsletter and by e-mail. Responses to questions with ranked options were assigned consecutive integers with lower values indicating a more favoured or higher prioritised response. Responses to best answer questions are presented as frequencies and percentages. <h3>Results</h3> 121 UK-based doctors (104 consultants, 1 associate specialist, 16 respiratory registrars) completed the survey. Factors determining HRQOL (rank 1–9): shortness of breath and chest pain (mean rank 1.48) and functional status (mean rank 2.57) were ranked the most important. Social set up – mean rank 5.16, depression/anxiety – mean rank 5.22, tumour type and stage – mean rank 5.78, distance to travel for medical care – mean rank 5.86, age – mean rank 6.59, financial difficulties from treatment – mean rank 8.27. Factors in the decision to offer intervention for MPE (rank 1–6): breathlessness ranked highest (mean rank 1.83) followed by the risk of significant harm from procedure vs chance of benefit (mean rank 2.73). Perspectives on which interventions most improve HRQOL are presented in Figure 1. <h3>Conclusion</h3> Shortness of breath and chest pain ranked highly in the perspective of HRQOL with shortness of breath a key factor in offering intervention. There is a lack of consensus on the ideal treatment to maximise HRQOL, which may reflect the paucity of data. Robust clinical trial evidence on HRQOL outcomes is therefore required to guide management decisions of patients with MPE. This should be complemented by a patient survey to ascertain differences in clinician and patient perspectives of quality of life and care.