tbuckley/cabot-search huggingface dataset:
S115 Hot-hmv uk trial secondary outcome analysis: early readmission is reduced by the addition of home mechanical ventilation to home oxygen therapy in copd patients with chronic respiratory failure following a life-threatening exacerbation
Authors: PB Murphy, G Arbane, S Bourke, P Calverley, A Crooks, L Dowson, N Duffy, GJ Gibson, P Hughes, JR Hurst, K Lewis, R Mukherjee, A Nickol, N Oscroft, J Pepperell, S Rehal, I Smith, J Stradling, W Wedizcha, MI Polkey, M Elliott, N Hart
Journal: Thorax (2016)

<h3>Introduction</h3> Hospital readmission following treatment for a life-threatening exacerbation of COPD with acute NIV is frequent and associated with an adverse impact in terms of lung function and health related quality of life. They have been identified as a priority area in the NHS with financial penalties for any patient readmitted within 28 days following discharge. <h3>Method</h3> A multicentre open labelled randomised controlled trial recruited patients with persistent hypercapnia (PaCO<sup>2</sup> &gt; 7 kPa) 2–4 weeks following resolution of acute acidosis. Patients were randomised to either home oxygen therapy (HOT) or HOT and home mechanical ventilation (HOT-HMV). HMV was titrated overnight to control nocturnal hypercapnia. Follow up was for 12 months. The primary outcome, 12-month admission free survival, has been reported previously demonstrating a significant treatment effect (ERS 2016). Secondary outcome analysis included 28-day all-cause hospital readmission and 12 month exacerbation rate. <h3>Results</h3> 116 patients were randomised (HOT = 59, HOT-HMV = 57), age 67 ± 10 years, FEV1 0.6 ± 0.2 L, PaCO<sup>2</sup> 7.9 ± 0.9 kPa. 28-day readmission was 22 (37%) in the HOT and 7 (12%) in the HOT-HMV arm (unadjusted HR 0.27, 0.12 to 0.63, p = 0.003; adjusted HR 0.26, 0.11 to 0.61, p = 0.002) (Figure 1). 12 month exacerbation rate was reduced from median 5 (1 to 9) per year in the HOT arm to 4 (2to 6) in the HOT-HMV arm (unadjusted HR 0.64 (0.44 to 0.94); p = 0.022; adjusted HR 0.66, 0.46 to 0.95, p = 0.026). <h3>Conclusion</h3> The addition of HMV to HOT in patients with persistent hypercapnia following an acute life-threatening exacerbation of COPD reduces both 28-day readmission and 12 month exacerbation frequency. These data strongly support a change in clinical practice in the management of patients with severe COPD and persistent hypercapnia.
P2.04-003 Chemotherapy in Advanced Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort
Authors: Claire Merveilleux Du Vignaux, Maria Bluthgen, Laurent Mhanna, Eric Dansin, Laurent Greillier, Eric Pichon, Hervé Léna, Christelle Clément-Duchêne, Gilbert Massard, Virginie Westeel, Marie Robert, Xavier Quantin, Gérard Zalcman, Luc Thiberville, Thierry Molina, Julien Mazieres, Benjamin Besse, Nicolas Girard
Journal: Journal of Thoracic Oncology (2017)
LR11 Is a Potential Serum and Histological Biomarker for Intravascular Large B-Cell Lymphoma
Authors: Chikako Ohwada, Takeharu Kawaguchi, Naomi Shimizu, Masahiro Takeuchi, Emiko Sakaida, Yusuke Takeda, Kazuhisa Fujikawa, Kosei Matsue, Morihiro Higashi, Jun-Ichi Tamaru, Kotaro Yokote, Hideaki Bujo, Chiaki Nakaseko
Journal: Blood (2012)
Cooperative Calcium Signaling Mediated by Glycoprotein (GP) Ib-IX-V, GPVI and Integrin α2β1 during Platelet Adhesion to Collagen under Flow.
Authors: Luigi De Marco, Maria Rita Cozzi, Mario Mazzucato, Monica Battiston, Martine Jandrot Perrus, Zaverio M. Ruggeri
Journal: Blood (2007)
Circulating tumor cells and detection of EGFR mutation in cell-free tumor DNA in blood plasma in metastatic non-small cell lung cancer with <i>EGFR</i> mutation.
Authors: K. Isobe, Y. Hata, S. Sakaguchi, K. Sato, K. Sugino, G. Sano, S. Sakamoto, Y. Takai, K. Shibuya, K. Takagi, S. Homma
Journal: Journal of Clinical Oncology (2011)

7595 Background: The purpose of this study was to assess the correlation between the numbers of circulating tumor cells (CTCs), prognosis and the positivity of blood plasma EGFR mutation in cell-free tumor DNA in metastatic non-small cell lung cancer with positive epidermal growth factor receptor (EGFR) gene mutation in the primary site. Methods: Of the 20 patients with primary lung cancer who showed EGFR mutaion in the primary site, CTCs were counted using CellSearch system (Veridex) after the appearance of EGFR TKI resistance. Furthermore, cell-free tumor DNA was extracted from blood plasma samples of the 20 patients by QIAamp Circulating Nucleic Acid Kit (Qiagen), and was analyzed for EGFR mutation using cycleave real-time PCR assay. Results: Patient characteristics included 5 males and 15 females with a mean age of 64.1 yrs (43 to 82), performance status of 0 in 5, 1 in 11, and 2 in 4, respectively. Pathological classification of lung cancer were adenocarcinoma in 19, squamous cell carcinoma in 1, clinical stage were stage IV in 15 and recurrence after surgical resection in 5 with distant metastases, respectively. The localization of EGFR mutation in the primary site were exon 18 G719C in 1, exon 18 G725A + exon 19 deletion in 2, exon 19 deletion in 7, exon21 L858R in 9, exon 18 G791S + exon 21 L858R in 1→ exon 18 G719S + exon 21 L858R in 1, respectively. CTCs were detected in 7 out of 20 cases (35%). Numbers of CTCs ( per 7.5 ml) were 1 in 3 cases, 3 in 1 case, 8 in 1 case, 14 in 1 case, and 24 in 1 case, respectively. Negative CTCs group showed a significant longer survival than that of positive CTCs group (³a1 / 7.5 ml) from the times of detecting CTCs (MST: not reached vs. 3.8 months, p < 0.05). EGFR mutation in tumor cell-free DNA in blood plasma were detected in 6 out of 20 cases (30%). The lacalization of detected EGFR mutation were same as their primary site, without any new resistance mutation. Positive detective rates of EGFR mutation in blood plasma were 71.1% (5 out of 7 cases) in positive CTCs group and 7.7% (1 out of 13 cases) in negative CTCs group (p < 0.05). Conclusions: The numbers of CTCs were correlated not only prognosis but also the positivity of EGFR mutation in cell-free tumor DNA in blood plasma.
Quantitative PET Reporter Gene Imaging with [11C]Trimethoprim
Authors: Mark A. Sellmyer, Iljung Lee, Catherine Hou, Brian P. Lieberman, Chenbo Zeng, David A. Mankoff, Robert H. Mach
Journal: Molecular Therapy (2017)

There is a need for improved methods to image genetically engineered cells, including immune cells used for cell-based therapy. Given the genetic manipulation inherent to gene therapy, the use of a reporter protein is a logical solution and positron emission tomography (PET) can provide the desired sensitivity and spatial localization. We developed a broadly applicable PET imaging strategy based on the small bacterial protein E. coli dihydrofolate reductase (Ec dhfr) and its highly specific small molecule inhibitor, trimethoprim (TMP). The difference in TMP affinity for bacterial compared to mammalian DHFR suggests that a TMP radioligand would have a low background in unmodified mammalian tissues and high retention in Ec dhfr engineered cells, providing high contrast imaging. Here, we describe the in vitro properties of [11C]TMP and show over 10-fold increased signal in transgenic Ec dhfr cells compared to control. In a mouse xenograft model, [11C]TMP rapidly accumulated in Ec dhfr carrying cells within minutes of intravenous administration. Moreover, [11C]TMP can identify less than a million xenografted cells in a small volume in tissues other than the abdominal compartment. This limit of detection is a clinically relevant number and bodes well for clinical translation especially given that [11C]TMP is an isotopologue of clinically approved antibiotic. There is a need for improved methods to image genetically engineered cells, including immune cells used for cell-based therapy. Given the genetic manipulation inherent to gene therapy, the use of a reporter protein is a logical solution and positron emission tomography (PET) can provide the desired sensitivity and spatial localization. We developed a broadly applicable PET imaging strategy based on the small bacterial protein E. coli dihydrofolate reductase (Ec dhfr) and its highly specific small molecule inhibitor, trimethoprim (TMP). The difference in TMP affinity for bacterial compared to mammalian DHFR suggests that a TMP radioligand would have a low background in unmodified mammalian tissues and high retention in Ec dhfr engineered cells, providing high contrast imaging. Here, we describe the in vitro properties of [11C]TMP and show over 10-fold increased signal in transgenic Ec dhfr cells compared to control. In a mouse xenograft model, [11C]TMP rapidly accumulated in Ec dhfr carrying cells within minutes of intravenous administration. Moreover, [11C]TMP can identify less than a million xenografted cells in a small volume in tissues other than the abdominal compartment. This limit of detection is a clinically relevant number and bodes well for clinical translation especially given that [11C]TMP is an isotopologue of clinically approved antibiotic.
Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice
Authors: Xiaoguang Li, Zhihao Wang, Lu Tan, Yali Wang, Chengbiao Lu, Rongxiang Chen, Shujuan Zhang, Yuan Gao, Yanchao Liu, Yaling Yin, Xinghua Liu, Enjie Liu, Ying Yang, Yu Hu, Zhipeng Xu, Fuqiang Xu, Jie Wang, Gong-Ping Liu, Jian-Zhi Wang
Journal: Molecular Therapy (2017)

Patients with Alzheimer's disease (AD) commonly show anxiety behaviors, but the molecular mechanisms are not clear and no efficient intervention exists. Here, we found that overexpression of human wild-type, full-length tau (termed htau) in hippocampus significantly decreased the extracellular γ-aminobutyric acid (GABA) level with inhibition of γ oscillation and the evoked inhibitory postsynaptic potential (eIPSP). With tau accumulation, the mice show age-dependent anxiety behaviors. Among the factors responsible for GABA synthesis, release, uptake, and transport, we found that accumulation of htau selectively suppressed expression of the intracellular vesicular GABA transporter (vGAT). Tau accumulation increased miR92a, which targeted vGAT mRNA 3' UTR and inhibited vGAT translation. Importantly, we found that upregulating GABA tones by intraperitoneal injection of midazolam (a GABA agonist), ChR2-mediated photostimulating and overexpressing vGAT, or blocking miR92a by using specific antagomir or inhibitor efficiently rescued the htau-induced GABAergic dysfunctions with attenuation of anxiety. Finally, we also demonstrated that vGAT level decreased while the miR92a increased in the AD brains. These findings demonstrate that the AD-like tau accumulation induces anxiety through disrupting miR92a-vGAT-GABA signaling, which reveals molecular mechanisms underlying the anxiety behavior in AD patients and potentially leads to the development of new therapeutics for tauopathies.
Association of MDM2 Gene Polymorphisms SNP285 and 309 with Myelodysplastic Syndromes (MDS) Susceptibility and Outcome.
Authors: Kathy L. McGraw, Lan Min Zhang, William Fulp, Hui-Yi Lin, Andres Jerez, Ashley A. Basiorka, Gisela Caceres, Dana E Rollison, Debbie Billingsley, Sandra E. Kurtin, Lubomir Sokol, P.K. Epling-Burnette, Mar Mallo, Francesc Sole, Maria Jose Calasanz, Jose Cervera, Esperanza Such, Teresa Gonzalez, Jaroslaw P. Maciejewski, Alan F. List
Journal: Blood (2012)
Complex Immunosuppressive Action of Farnesyltransferase Inhibitor (FTI) R115777 (Tipifarnib, Zarnestra®) with Induction of Apoptosis in T Cells from Patients with Large Granular Lymphocyte (LGL) Leukemia.
Authors: Fanqi Bai, JianXiang Zou, Jun Yang, Edna Ku, Sheng Wei, Thomas P. Loughran, P.K. Epling-Burnette
Journal: Blood (2006)
P188 Nasal high flow (NHF) – is it appropriately prescribed? a retrospective case review of 93 adult patients requiring nasal high flow oxygen within a district general hospital
Authors: A Leadbetter, K Heron, J Robinson, R Mason
Journal: Thorax (2016)

<h3>Background</h3> Nasal high flow (NHF) delivers warmed humidified oxygen up to 65L/min and is commonly used in intensive care units (ICU). In a non-critical care settings it can provide a bridge to ICU for hypoxic patients, and symptom palliation for those unsuitable for escalation. Evidence to support NHF use in a non-critical care setting is limited. We aimed to review patient selection and clinical outcomes for individuals commenced on NHF over two winter periods, in order to highlight prognostic indicators and develop a clinical guideline. <h3>Method</h3> We performed a retrospective review of 93 cases managed with NHF September-December in 2014 and 2015 in a medium sized DGH. Patients were included regardless of diagnosis and treatment escalation plan. Data was collected on patient demographics, diagnosis, management and clinical outcome. Results described as %(n). <h3>Results</h3> 93 patients (mean age 71.2 yrs, SD 14.8). Presenting complaint: Pneumonia 57.0% (53), Aspiration pneumonia 4.3% (4), Pulmonary embolism 4.3% (4), Pulmonary oedema 3.2% (3), Interstitial Lung Disease 3.2% (3), other diagnoses 28.0% (26). Clinical indication: Hypoxia 64.5% (60), hypoxia and work of breathing 14.0% (13), work of breathing alone 7.5% (7) and palliation 14.0% (13). 42 patients (45%) were assessed by ICU, of which 21 patients were deemed appropriate [mean age 65 yrs (40–84)]. 62% (13) were intubated. 81% (17) survived to discharge; 5.9% (1) required LTOT. No significant correlation was present between flow rates and mortality (p = 0.7). 72 patients (77.4%) were managed in non-critical care settings [mean age 72.7 yrs (28–99)]. 48.6% (35) survived to discharge, 14.3% (5) required LTOT and 5.7% (2) died within 30 days of discharge. Flow rates ranged 20–65 L/min. In non-ICU patients, survival was negatively correlated with increasing flow rates (r = −0.86). Patients requiring ≥60 L/min had an 86% mortality rate (p = 0.0001). <h3>Conclusion</h3> Mortality rates were higher in patients managed on NHF in a non-critical care setting. A negative correlation was present between flow rates and survival outside of ICU. This may be explained by an older patient cohort, associated comorbidities and premorbid performance status. However this information could help guide clinical decision making in acutely unwell patients with limited escalation options.
THE USE OF CYCLOSPORINE (C) ONLY IN CADAVERIC RENAL-TRANSPLANT RECIPIENTS (CRTR) - CONVERSION TO PREDNISOLONE (P) AND AZATHIOPRINE (A) AFTER 4 MONTHS
Authors: Adam Tegzess, A Donker, Sytze Meijer, van Willem Son, F van der Woude, Mjh Slooff, L van der Slikke
Journal: Kidney International (1984)
T(8;9)(p22;p24)/PCM1-JAK2 Activates SOCS2 and SOCS3 Via STAT5
Authors: Stefan Ehrentraut, Stefan Nagel, Michaela Scherr, Bjoern Schneider, Hilmar Quentmeier, Robert Geffers, Monika Prochorec-Sobieszek, Rhett P Ketterling, Ryan A Knudson, Andrew L. Feldman, Marshall Kadin, Hans G. Drexler, Roderick AF MacLeod
Journal: Blood (2012)
OA01.07 Alternative Follow-Up Methods Based on Recurrence Patterns after Surgery for Non-Small Cell Lung Cancer
Authors: Katsuya Watanabe, Kentaro Sakamaki, Teppei Nishii, Atsuo Gorai, Taketsugu Yamamoto, Takuya Nagashima, Kohei Ando, Yoshihiro Ishikawa, Tetsukan Woo, Hiroyuki Adachi, Yutaka Kumakiri, Takamitsu Maehara, Haruhiko Nakayama, Munetaka Masuda
Journal: Journal of Thoracic Oncology (2017)
A Highly Efficient, Clinically Applicable Transfection Method to Redirect the Specificity of Immune Cells and Enhance Their Anti-Tumor Capacity
Authors: Linhong Li, Lawrence Wolfraim, Cornell Allen, Angelia Viley, Hiroyuki Fujisaki, Dario Campana, Joseph C. Fratantoni, Madhusudan V Peshwa
Journal: Blood (2008)
MA08.02 Clinical Research Platform into Molecular Testing, Treatment, Outcome (CRISP): A Prospective German Registry in Stage IV NSCLC AIO-TRK-0315
Authors: Frank Griesinger, Wilfried Eberhardt, Norbert Marschner, Martina Jänicke, Annette Hipper, Aysun Karatas, Martin Sebastian, Michael Thomas, Peter Schirmacher
Journal: Journal of Thoracic Oncology (2017)
The Rev II Trial: Lenalidomide and Dexamethasone As Second Line Treatment in Myeloma Followed By Extended Lenalidomid Vs Len/Dex
Authors: Johan Lund, Sigrid Karstorp, Evren Alici, Astrid Gruber, Birgitta Lauri, Cecilie Blimark, Agneta Swedin, Markus Hansson, Karin Forsberg, Lucia Ahlberg, Carlsson Conny, Anders Waage, Peter Gimsing, Annette Juul Vangsted, Ulf Christian Frølund, Mats Hardling, Ulf-Henrik Mellqvist, Hareth Nahi
Journal: Blood (2015)
Next Generation Sequencing and Functional Analysis of Mirna Expression in Acute Myeloid Leukemia Patients with Different FLT3 Mutations: Block of MiR-155 in FLT3-ITD Driven AML Leads to Downregulation of Myeloid Blasts in Vivo
Authors: Dennis Gerloff, Alexander Arthur Wurm, Jens-Uwe Hartmann, Nadja Hilger, Anne-Marie Müller, Christiane Katzerke, Daniela Bräuer-Hartmann, Carolina Yaeko Namasu, Michael Cross, Sebastian Schwind, Knut Krohn, Stephan Fricke, Dietger Niederwieser, Gerhard Behre
Journal: Blood (2015)
P3.02b-109 Molecular Profiling of EGFR-Positive NSCLC with Secondary T790M Resistance Mutation and Tertiary Transformation into Small-Cell Lung Cancer
Authors: Martin Faehling, Anna-Lena Volckmar, Albrecht Stenzinger, Birgit Schwenk, Sebastian Kramberg, Jörn Sträter
Journal: Journal of Thoracic Oncology (2017)
P2.06-039 Searching for Standards: Multicenter Ring Trials to Evaluate Technologies for the Enrichment of Circulating Tumor Cells
Authors: Sebastian Bender, Merlin Luetke-Eversloh, Rui Neves, Nikolas Stoecklein, Leon Terstappen, Barbara Baggiani, Thomas Krahn, Klaus Pantel, Thomas Schlange
Journal: Journal of Thoracic Oncology (2017)
Follow-Up of Clinical Manifestations and Platelet Function Test in Patients with Essential Thrombocythemia on Anagrelide Treatment.
Authors: Patricia S. Vassallu, Nora P. Goette, Ana C. Glembotsky, Paula G. Heller, Laura I. Kornblihtt, Paola R. Lev, Daniel C. Chazarreta, Juan P. Salim, Maria S. Laguna, Rosana F. Marta, Felisa C. Molinas
Journal: Blood (2005)
P1.06-021 Treatment Patterns and Healthcare Resource Use from a Retrospective Cohort of Japanese Patients with Advanced Non-Small Cell Lung Cancer
Authors: Terufumi Kato, Kiyoshi Mori, Koichi Minato, Hideki Katsura, Kazuko Taniguchi, Ashwini Arunachalam, Smita Kothari, Xiting Cao, Hiroshi Isobe
Journal: Journal of Thoracic Oncology (2017)
A Perspective on Out-of-Pocket Spending
Authors: Amanda Frost, Eric Barrette
Journal: JAMA Internal Medicine (2017)

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Blocking Tumor-Educated MSC Paracrine Activity Halts Osteosarcoma Progression
Authors: S. Rubina Baglio, Tonny Lagerweij, Maria Pérez-Lanzón, Xuan Dung Ho, Nicolas Léveillé, Sonia A. Melo, Anne-Marie Cleton-Jansen, Ekaterina S. Jordanova, Laura Roncuzzi, Michelina Greco, Monique A.J. van Eijndhoven, Giulia Grisendi, Massimo Dominici, Roberta Bonafede, Sinead M. Lougheed, Tanja D. de Gruijl, Nicoletta Zini, Silvia Cervo, Agostino Steffan, Vincenzo Canzonieri, Aare Martson, Katre Maasalu, Sulev Köks, Tom Wurdinger, Nicola Baldini, D. Michiel Pegtel
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets. Experimental Design: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma, we evaluated the effect of tumor extracellular vesicle (EV)–educated mesenchymal stem cells (TEMSC) on osteosarcoma progression. Characterization and functional studies were designed to assess the mechanisms underlying MSC education. Independent series of tissue specimens were analyzed to corroborate the preclinical findings, and the composition of patient serum EVs was analyzed after isolation with size-exclusion chromatography. Results: We show that EVs secreted by highly malignant osteosarcoma cells selectively incorporate a membrane-associated form of TGFβ, which induces proinflammatory IL6 production by MSCs. TEMSCs promote tumor growth, accompanied with intratumor STAT3 activation and lung metastasis formation, which was not observed with control MSCs. Importantly, intravenous administration of the anti-IL6 receptor antibody tocilizumab abrogated the tumor-promoting effects of TEMSCs. RNA-seq analysis of human osteosarcoma tissues revealed a distinct TGFβ-induced prometastatic gene signature. Tissue microarray immunostaining indicated active STAT3 signaling in human osteosarcoma, consistent with the observations in TEMSC-treated mice. Finally, we isolated pure populations of EVs from serum and demonstrated that circulating levels of EV-associated TGFβ are increased in osteosarcoma patients. Conclusions: Collectively, our findings suggest that TEMSCs promote osteosarcoma progression and provide the basis for testing IL6- and TGFβ-blocking agents as new therapeutic options for osteosarcoma patients. Clin Cancer Res; 23(14); 3721–33. ©2017 AACR.
MA17.01 Microarray Identification of Genetic Drivers of Brain Metastasis in Lung Adenocarcinoma
Authors: Gavitt Woodard, Vivianne Ding, Matthew Rosenblum, Fleur Leguay, Clara Zoon-Besselink, Kirk Jones, Tasha Lea, Michael Mcdermott, Il-Jin Kim, David Jablons
Journal: Journal of Thoracic Oncology (2017)
OA24.01 Radiotherapy Quality Assurance of Concurrent Chemoradiotherapy in PROCLAIM Phase III Trial
Authors: Anthony Brade, Frederik Wenz, Friederike Koppe, Yolande Lievens, Belen San Antonio, Neill Iscoe, Anwar Hossain, Nadia Chouaki, Suresh Senan
Journal: Journal of Thoracic Oncology (2017)
P3.01-033 Changes in the Tumor Microenvironment during Lymphatic Metastasis of Lung Squamous Cell Carcinoma
Authors: Shinnosuke Ikemura, Nao Aramaki, Satoshi Fujii, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Takeshi Kuwata, Motohiro Kuwata, Atsushi Ochiai, Tomoko Betsuyaku, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii
Journal: Journal of Thoracic Oncology (2017)