tbuckley/cabot-search huggingface dataset:
S20 Kbild scores have similar power to predict survival as pulmonary physiology in interstitial lung disease
Authors: C Sharp, C Baggott, SS Birring, HI Adamali
Journal: Thorax (2016)

<h3>Background</h3> The KBILD questionnaire is an ILD health related quality of life (HRQL) tool. Its relationship with survival has not been assessed. <h3>Aims</h3> Assess impact of KBILD scores on survival in a heterogeneous population with interstitial lung disease (ILD). <h3>Methods</h3> Patients attending the Bristol ILD service with fibrotic ILDs completed KBILD questionnaires, full lung function and exercise testing. Survival analysis using univariable and multivariable Weibull regression with an accelerated time-failure form was used to assess the significance of KBILD scores to predict all cause mortality. Comparison was made with lung function from the same clinic visit. Results are reported as hazard ratio and time ratio. Area under receiver operator characteristics (AUROC) curve analysis was used to assess sensitivity of KBILD for predicting 12-month mortality. <h3>Results</h3> 175 patients, 58% IPF, 67.4% male, completed a KBILD questionnaire. Mean values were; age 71yrs, KBILD 61, FVC 84%, DLCO 50%, walk distance 292m. 48% had oxygen desaturation on 6-minute walk. 47 patients (26.9%) died. Mean follow-up was 19.8 months, median 14.4 months. 156 patients had &gt;12 months follow-up and these were included in the prognostic evaluation. Univariable survival analysis showed age, KBILD, FVC, DLCO, walk distance and exertional desaturation to have prognostic significance for all cause mortality. Univariable analysis of the sub-categories of the KBILD score showed the psychological (p = 0.003) and breathlessness (p = 0.002) domains to be significant, while the chest symptoms domain was not (p = 0.269). After backwards stepwise selection the multivariable model contained age, KBILD, FVC and desaturation (Table 1). All included variables had prognostic significance. AUROC analysis showed KBILD had equivalent sensitivity for 12-month mortality to FVC, DLCO and better sensitivity than walk distance (c-statistic in Table 1). A KBILD score of 34 had 75% sensitivity for 12-month mortality, but only 10.5% specificity. Estimated median survival with KBILD of &lt;34 was 9.7 months, compared to 36.4 months for KBILD &gt; 34 (p = 0.02). <h3>Conclusions</h3> In this cohort, the KBILD has equivalent prognostic power in ILD to pulmonary physiology and exercise testing at a single point in time. It is important to assess HRQL to give ILD patients optimal prognostic information.
P2.06-019 A Phase II Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Patients (pts) with Resectable Non-Small Cell Lung Cancer (NSCLC)
Authors: Dwight Owen, Paul Bunn, Bruce Johnson, David Kwiatkowski, Mark Kris, Ignacio Wistuba, Mayank Gandhi, See Phan, David Shames, Katja Schulze, Coen Bernaards, Dara Aisner, Jamie Chaft, Justin Gainor, Jay Lee, John Minna, Mari Mino-Kenudson, Celia Garcia-Prieto, Valerie Rusch, Anita Sabichi, Liza Villaruz, Antoinette Wozniak, David Carbone
Journal: Journal of Thoracic Oncology (2017)
P2.01-088 Prenylation Inhibitors in Lung Adenocarcinoma: Comparison of Zoledronic Acid and a Novel Lipophilic Bisphosphonate
Authors: Eszter Molnar, Tamas Garay, Dominika Rittler, Marcell Baranyi, Clemens Aigner, Zoltan Lohinai, Balazs Dome, József Tímár, Balazs Hegedus
Journal: Journal of Thoracic Oncology (2017)
P2.02-044 Impact of N2 Extent and Nodal Response on Survival after Trimodal Treatment for Stage IIIA-N2 Non-Small Cell Lung Cancer
Authors: Hong Kwan Kim, Jong Ho Cho, Yong Soo Choi, Jae Ill Zo, Young Mog Shim, Keunchil Park, Myung-Ju Ahn, Jin Seok Ahn, Yong Chan Ahn, Hong Ryull Pyo, Joungho Han, Hojoong Kim, Jhingook Kim
Journal: Journal of Thoracic Oncology (2017)
Phase II Clinical Trial of Denileukin Diftitox In Combination with Rituximab In Previously Untreated Follicular B-Cell Non-Hodgkin's Lymphoma
Authors: Stephen M Ansell, Hui Tang, Grzegorz S. Nowakowski, Daniel Nikcevich, Garth D Nelson, Charles Erlichman, Thomas E Witzig
Journal: Blood (2010)
MA13.02 First-In-Human Clinical Experience with Real-Time Tumor Targeting via MLC Tracking for Stereotactic Radiotherapy of Lung Cancer
Authors: Jeremy Booth, Vincent Caillet, Nicholas Hardcastle, Carol Haddad, Kathryn Szymura, Ricky O'Brien, Benjamin Harris, Thomas Eade, Paul Keall
Journal: Journal of Thoracic Oncology (2017)
P1.08-076 Recurrence Patterns in Lung Cancer Patients Treated with Protocol Based Multimodality Treatment at a Tertiary Care Cancer Center in India
Authors: Ashish Jakhetiya, Vinay Kumar, Surayanarayana Deo, Nootan Shukla, Durgatosh Pandey, Prabhat Malik, Deepali Jain, Sunil Kumar
Journal: Journal of Thoracic Oncology (2017)
Abstract A33: Discovery of novel anti-cancer therapeutic agents for Notch activation complex kinase (NACK) targeting the Notch pathway
Authors: Xiaoxia Zhu, Zhiqiang Wang, Ke Jin, Luisana Astudillo, Wen Zhou, Jinshui Chen, Peter Buchwald, Stephan C. Schürer, Anthony J. Capobianco
Journal: Clinical Cancer Research (2017)

Abstract The Notch signaling pathway has been found to play an important role in multiple human cancers by regulating transcriptional programs. However, the mechanism by which Notch drives target gene transcription is still elusive. In our previous study, we have identified and characterized a novel Notch activation complex kinase, NACK, which acts as a Notch transcriptional co-activator and an essential regulator of Notch-mediated tumorigenesis and development. In this regard, NACK could become a putative drug target in anti-cancer therapies. The lack of three-dimensional (3D) structure of NACK hinders the designing of potential drug inhibitors. Therefore, computational methods are adopted to elucidate the structural and functional features of NACK, which further aid in designing new NACK inhibitors. Molecule docking (Glide) is utilized to obtain potential hit inhibitors for NACK, which will be validated using in-vitro and in-vivo assays. This will open avenues for the development of new therapies for Notch-dependent cancers. Citation Format: Xiaoxia Zhu, Zhiqiang Wang, Ke Jin, Luisana Astudillo, Wen Zhou, Jinshui Chen, Peter Buchwald, Stephan C. Schürer, Anthony J. Capobianco. Discovery of novel anti-cancer therapeutic agents for Notch activation complex kinase (NACK) targeting the Notch pathway. [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 A33.
Meat intake and risk of diverticulitis among men
Authors: Yin Cao, Lisa L Strate, Brieze R Keeley, Idy Tam, Kana Wu, Edward L Giovannucci, Andrew T Chan
Journal: Gut (2017)

Objective Diverticulitis is a common disease with a substantial clinical and economic burden. Besides dietary fibre, the role of other foods in the prevention of diverticulitis is underexplored. Design We prospectively examined the association between consumption of meat (total red meat, red unprocessed meat, red processed meat, poultry and fish) with risk of incident diverticulitis among 46 461 men enrolled in the Health Professionals Follow-Up Study (1986–2012). Cox proportional hazards models were used to compute relative risks (RRs) and 95% CIs. Results During 651 970 person-years of follow-up, we documented 764 cases of incident diverticulitis. Compared with men in the lowest quintile (Q1) of total red meat consumption, men in the highest quintile (Q5) had a multivariable RR of 1.58 (95% CI 1.19 to 2.11; p for trend=0.01). The increase in risk was non-linear, plateauing after six servings per week (p for non-linearity=0.002). The association was stronger for unprocessed red meat (RR for Q5 vs Q1: 1.51; 95% CI 1.12 to 2.03; p for trend=0.03) than for processed red meat (RR for Q5 vs Q1: 1.03; 95% CI 0.78 to 1.35; p for trend=0.26). Higher consumption of poultry or fish was not associated with risk of diverticulitis. However, the substitution of poultry or fish for one serving of unprocessed red meat per day was associated with a decrease in risk of diverticulitis (multivariable RR 0.80; 95% CI 0.63 to 0.99). Conclusions Red meat intake, particularly unprocessed red meat, was associated with an increased risk of diverticulitis. The findings provide practical dietary guidance for patients at risk of diverticulitis.
Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding
Authors: Pancras C. Wong, Dietmar Seiffert, J. Eileen Bird, Carol A. Watson, Jeffrey S. Bostwick, Mary Giancarli, Nick Allegretto, Ji Hua, David Harden, Jocelyne Guay, Mario Callejo, Michael M. Miller, R. Michael Lawrence, Jacques Banville, Julia Guy, Brad D. Maxwell, E. Scott Priestley, Anne Marinier, Ruth R. Wexler, Michel Bouvier, David A. Gordon, William A. Schumacher, Jing Yang
Journal: Science Translational Medicine (2017)

Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4. A PAR1 antagonist is approved for clinical use, but its use is limited by a substantial bleeding risk. Conversely, the potential of PAR4 as an antiplatelet target has not been well characterized. Using anti-PAR4 antibodies, we demonstrated a low bleeding risk and an effective antithrombotic profile with PAR4 inhibition in guinea pigs. Subsequently, high-throughput screening and an extensive medicinal chemistry effort resulted in the discovery of BMS-986120, an orally active, selective, and reversible PAR4 antagonist. In a cynomolgus monkey arterial thrombosis model, BMS-986120 demonstrated potent and highly efficacious antithrombotic activity. BMS-986120 also exhibited a low bleeding liability and a markedly wider therapeutic window compared to the standard antiplatelet agent clopidogrel tested in the same nonhuman primate model. These preclinical findings define the biological role of PAR4 in mediating platelet aggregation. In addition, they indicate that targeting PAR4 is an attractive antiplatelet strategy with the potential to treat patients at a high risk of atherothrombosis with superior safety compared with the current standard of care.
A Multi-Center and Multi-National Program To Assess the Clinical Accuracy of the Molecular Subclassification of Leukemia by Gene Expression Profiling.
Authors: Torsten Haferlach, Alexander Kohlmann, Guiseppe Basso, Marie-Christine Bene, James R. Downing, Jesus M. Hernandez, Wolf-Karsten Hofmann, Thomas J. Kipps, Truus te Kronnie, Wei-Min Liu, Sunhee Ro, Elisabeth MacIntyre, Ken I. Mills, Claude Preudhomme, Laura Z. Rassenti, John de Vos, Mickey Williams, Lothar Wieczorek, Robin Foa
Journal: Blood (2005)
Expression of CD56 in Acute Myeloid Leukemia (AML) Is Associated with Poor Outcome When Patients Treated with Stem Cell Transplant in Second Remission but Not in the First Remission
Authors: Naeem A. Chaudhri, Fahed Almhareb, Claudia Ulrike Walter, Randa Nounou, Salem Khalil, Nasir Bakshi, Tarek Owaidah, Hazzaa Al Zahrani, Said Mohamed, Walid Rasheed, Fahad Alsharif, Mahmoud Aljurf, Maher Albitar
Journal: Blood (2011)
Quantitative Significance of Minimal Residual Disease Before Myeloablative Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First and Second Complete Remission
Authors: Roland B. Walter, Sarah A. Buckley, John M. Pagel, Brent L. Wood, Ted A. Gooley, Brenda M. Sandmaier, Min Fang, Elihu H. Estey, Jerald P. Radich, Gary Schoch, Frederick R. Appelbaum
Journal: Blood (2012)
P2.05-058 Blood Biomarkers of Inflammation, Tumor Burden and Proliferation Predict Radiotherapy Response and Toxicity in Lung Cancer
Authors: Ahmed Salem, Hitesh Mistry, Alison Becken, Clare Hodgson, Pek Koh, Emma Dean, Lynsey Priest, Caroline Dive, Andrew Renehan, Corinne Faivre-Finn, Fiona Blackhall
Journal: Journal of Thoracic Oncology (2017)
P251 Does fractional exhale nitric oxide and methacholine challenge test help in the diagnosis of airways disease?
Authors: IJ Cliff, M Hepple, MB Allen
Journal: Thorax (2016)

<h3>Introduction</h3> With proposed NICE changes to the diagnosis of asthma,<sup>1</sup> which recommend the use of fractional exhale nitric oxide (FeNO) at a positive value of ≥35 ppb and a change in direct challenge test (Methacholine) from 16 to 8 mg/ml as a cut off for positive responses, we have reviewed our data to assess the impact of these changes. <h3>Methods</h3> A retrospective review of results from 2009 to 2016 where methacholine challenge tests<b> (</b>MCT) and FeNO were performed simultaneously in patients with normal spirometry in the assessment of airways disease. <h3>Results</h3> Results were available on 145 patients and are tabulated below for both the cut off for MCH of 16 mg/ml (current)<sup>2</sup> and the new cut off value of 8 mg/ml. <h3>Conclusions</h3> Altering the threshold for MCT produces 10 less positive results (7%) reducing the clinical assumption of airways disease. Likewise, 17 had a positive FeNO and a negative challenge test irrespective of the MCT threshold. However, adopting this change reduced the number of negative FeNO and positive MCT from 32 to 22. In our population, patients referred for a diagnosis of airways disease with normal spirometry showed a large number of patients were both negative for FeNO and MCT and changing the MCT threshold does not significantly impact our group. <h3>References</h3> NICE. Asthma: <i>diagnosis and monitoring of asthma in adults, children and young people. Draft for Consultation</i>. https://www.nice.org.uk/guidance/gid-cgwave0640/resources/asthma-diagnosis-and-monitoring-draft-guideline2 2015 (accessed 30 June 2016). Crapo R, <i>et al</i>. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. <i>AJRCCM</i> 2000;<b>161</b>(1):309.
Thrombin Generation Assessment in Platelet Rich Plasma Offers Additional Criteria for Low Molecular Weight Heparin Antithrombotic Fingerprint Characterization.
Authors: Grigorios T. Gerotziafas, Galea Vasso, Jeanine M. Walenga, Evi Kalodiki, Mourad Chaari, Hatmi Mohamed, Jawed Fareed, Elalamy Ismail
Journal: Blood (2009)
A Phase 2 Consortium (P2C) Trial of R115777 (Tipifarnib) in Myelofibrosis with Myeloid Metaplasia.
Authors: Ruben A. Mesa, John K. Camoriano, Susan M. Geyer, Scott H. Kaufmann, Candido E. Rivera, Charles Erlichman, Ayalew Tefferi
Journal: Blood (2004)
P2.03b-077 EGFR/ALK+ Patient-Derived Xenografts from Advanced NSCLC for TKI Drug Selection &amp; Resistance Development: The REAL-PDX Study
Authors: Michael Cabanero, Nhu-An Pham, Erin Stewart, Devalben Patel, Judy Mcconnell, Alexandria Grindlay, Frances Allison, Yuhui Wang, Ming Li, Frances Shepherd, Ming Tsao, Kazuhiro Yasufuku, Geoffrey Liu
Journal: Journal of Thoracic Oncology (2017)
Evidence that supports the prescription of low-carbohydrate high-fat diets: a narrative review
Authors: Timothy David Noakes, Johann Windt
Journal: British Journal of Sports Medicine (2017)

Low-carbohydrate high-fat (LCHF) diets are a highly contentious current topic in nutrition. This narrative review aims to provide clinicians with a broad overview of the effects of LCHF diets on body weight, glycaemic control and cardiovascular risk factors while addressing some common concerns and misconceptions. Blood total cholesterol and LDL-cholesterol concentrations show a variable, highly individual response to LCHF diets, and should be monitored in patients adhering to this diet. In contrast, available evidence from clinical and preclinical studies indicates that LCHF diets consistently improve all other markers of cardiovascular risk—lowering elevated blood glucose, insulin, triglyceride, ApoB and saturated fat (especially palmitoleic acid) concentrations, reducing small dense LDL particle numbers, glycated haemoglobin (HbA 1c ) levels, blood pressure and body weight while increasing low HDL-cholesterol concentrations and reversing non-alcoholic fatty liver disease (NAFLD). This particular combination of favourable modifications to all these risk factors is a benefit unique to LCHF diets. These effects are likely due in part to reduced hunger and decreased ad libitum calorie intake common to low-carbohydrate diets, allied to a reduction in hyperinsulinaemia, and reversal of NAFLD. Although LCHF diets may not be suitable for everyone, available evidence shows this eating plan to be a safe and efficacious dietary option to be considered. LCHF diets may also be particularly beneficial in patients with atherogenic dyslipidaemia, insulin resistance, and the frequently associated NAFLD.
Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology
Authors: Robert J. Morgan, Deborah K. Armstrong, Ronald D. Alvarez, Jamie N. Bakkum-Gamez, Kian Behbakht, Lee-may Chen, Larry Copeland, Marta Ann Crispens, Maria DeRosa, Oliver Dorigo, David M. Gershenson, Heidi J. Gray, Ardeshir Hakam, Laura J. Havrilesky, Carolyn Johnston, Shashikant Lele, Lainie Martin, Ursula A. Matulonis, David M. O'Malley, Richard T. Penson, Sanja Percac-Lima, Mario Pineda, Steven C. Plaxe, Matthew A. Powell, Elena Ratner, Steven W. Remmenga, Peter G. Rose, Paul Sabbatini, Joseph T. Santoso, Theresa L. Werner, Jennifer Burns, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2016)

This selection from the NCCN Guidelines for Ovarian Cancer focuses on the less common ovarian histopathologies (LCOHs), because new algorithms were added for LCOHs and current algorithms were revised for the 2016 update. The new LCOHs algorithms include clear cell carcinomas, mucinous carcinomas, and grade 1 (low-grade) serous carcinomas/endometrioid epithelial carcinomas. The LCOHs also include carcinosarcomas (malignant mixed Müllerian tumors of the ovary), borderline epithelial tumors (also known as low malignant potential tumors), malignant sex cord-stromal tumors, and malignant germ cell tumors.
P2.03b-064 Genomic Profiling in Non-Small Cell Lung Cancer: New Hope for Personalized Medicine
Authors: Satheesh Thungappa, Shekar Patil, H. Shashidhara, Mithua Ghosh, Sheela L, Siddesh Southekal, Upasana Mukherjee, Vidya Veldore
Journal: Journal of Thoracic Oncology (2017)
Impact d’un système automatisé pour le diagnostic de petites lésions colorectales par endocystoscopie: étude internationale “online”
Authors: E. Bories
Journal: Endoscopy (2016)

Le diagnostic optique des polypes colorectaux inférieur à 10 mm est un outil prometteur pour réduire les coûts et la morbidité de la coloscopie. En effet, les stratégies “laisser en place” et “réséquer et détruire” seraient acceptables si la VPN pour éliminer un adénome (AD) était supérieure à 90 % avec un haut niveau de confiance et si la précision diagnostique pour un AD ≤ 5 mm était supérieure à 90 %. Néanmoins certaines études évaluant cette stratégie auprès d’endoscopistes non experts ont été décevantes. L’endocystoscopie (EC) est une technique de microscopie in vivo en temps réel (magnification 380 ×, profondeur 50 µm, champs 700 × 600 µm) permettant de visualiser les noyaux et la lumière des glandes, après coloration par crystal violet et bleu de méthylène, permettant d’identifier un AD avec une exactitude comprise entre 94 et 100 %. Un système d’interprétation automatisée des images d’endocystoscopie en temps réel (EC-CAD) a été développé pour réduire la variabilité inter-observateur et améliorer la précision diagnostique.
Reduced-Intensity Conditioning Followed by Allogeneic Stem Cell Transplantation (allo-SCT) Is an Effective Salvage Treatment for Peripheral T-Cell Non-Hodgkin’s Lymphoma (PTCL).
Authors: Paolo Corradini, Anna Dodero, Marco Bregni, Francesco Zallio, Lucia Farina, Alessandro Rambaldi, Francesca Patriarca, Attilio Olivieri, Francesca Bonifazi, Alessandro Massimo Gianni, Corrado Tarella
Journal: Blood (2005)
P2.01-080 Mitosis Count of Lung Adenocarcinomas: Correlation between the Phosphorylated Histone 3, Number of Cancer Cells, Nuclear Grade, and Prognosis
Authors: Takashi Inoue, Yoshimasa Nakazato, Masayuki Chida, Yoshiyuki Ito, Morimichi Nishihira, Osamu Araki, Yoko Karube, Sumiko Maeda, Satoru Kobayashi
Journal: Journal of Thoracic Oncology (2017)
A Synthetic Mammalian Therapeutic Gene Circuit for Sensing and Suppressing Inflammation
Authors: Anže Smole, Duško Lainšček, Urban Bezeljak, Simon Horvat, Roman Jerala
Journal: Molecular Therapy (2017)

Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a "thresholder" to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device. This genetic circuit was autonomously activated by inflammatory signals, including endogenous cecal ligation and puncture (CLP)-induced inflammation in mice and serum from a systemic juvenile idiopathic arthritis (sIJA) patient, and could be reset externally by a chemical signal. The microencapsulated anti-inflammatory device significantly reduced the pathology in dextran sodium sulfate (DSS)-induced acute murine colitis, demonstrating a synthetic immunological approach for autonomous anti-inflammatory therapy. Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a "thresholder" to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device. This genetic circuit was autonomously activated by inflammatory signals, including endogenous cecal ligation and puncture (CLP)-induced inflammation in mice and serum from a systemic juvenile idiopathic arthritis (sIJA) patient, and could be reset externally by a chemical signal. The microencapsulated anti-inflammatory device significantly reduced the pathology in dextran sodium sulfate (DSS)-induced acute murine colitis, demonstrating a synthetic immunological approach for autonomous anti-inflammatory therapy.