tbuckley/cabot-search huggingface dataset:
P2.03b-042 MET exon 14 Mutations Encode a Hyperactive Kinase and Therapeutic Target in Lung Adenocarcinoma
Authors: Nir Peled, Xinyuan Lu, John Greer, Wei Wu, Peter Choi, Alice Berger, Byron Hann, Matthew Meyerson, Eric Collisson
Journal: Journal of Thoracic Oncology (2017)
Son speaks out on behalf of Indian doctors charged over death of patient
Authors: Anne Gulland
Journal: BMJ (2017)

The son of two doctors arrested in India after the death of a patient has condemned increasing violence against healthcare staff.

Kusum Tamhane, a consultant obstetrician and gynaecologist, and her husband Uttam Tamhane, a consultant general surgeon, alongside another doctor, Sanjay Ladkat, and a nurse, Manisha Mandlik, who work in Pune, India, were arrested on 4 January, five months after the death of a female patient from anaphylaxis.

The patient, whose usual doctor was not available, presented with stomach ache to Sanjeevani Hospital, owned by the Tamhanes, on 4 August last year. After …
Long-Term Safety and Efficacy of rFVIIIFc in Adults and Adolescents with Severe Hemophilia A: A Longitudinal Analysis of A-LONG and ASPIRE
Authors: K John Pasi, David J Perry, Johnny Mahlangu, Barbara A Konkle, Savita Rangarajan, Simon Brown, Hideji Hanabusa, Shannon Jackson, Ingrid Pabinger, Lynda M Cristiano, Yingwen Dong, Elisa Tsao, Glenn F Pierce, Geoffrey Allen
Journal: Blood (2015)
OA02.05 Expression of miR-223 in Mesothelioma Xenografts Originates from Stromal Cells in the Tumor Microenvironment
Authors: Kadir Sarun, Yuen Yee Cheng, Michaela Kirschner, Nico Van Zandwijk, Ruby Lin, Glen Reid
Journal: Journal of Thoracic Oncology (2017)
P2.03a-055 Predicting Risk of Chemotherapy-Induced Severe Neutropenia in Lung Patients: A Pooled Analysis of US Cooperative Group Trials
Authors: Xiaofei Wang, Xiaowen Cao, Thomas Stinchcombe, Jeffrey Bradley, Alex Adjei, David R. Gandara, Suresh Ramalingam, Herbert Pang, Everett Vokes, Jeffrey Crawford
Journal: Journal of Thoracic Oncology (2017)
Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial
Authors: Jemma O'Connor, Michael J Vjecha, Andrew N Phillips, Brian Angus, David Cooper, Beatriz Grinsztejn, Gustavo Lopardo, Satyajit Das, Robin Wood, Aimee Wilkin, Hartwig Klinker, Pacharee Kantipong, Karin L Klingman, David Jilich, Elbushra Herieka, Eileen Denning, Ibrahim Abubakar, Fred Gordin, Jens D Lundgren
Journal: The Lancet HIV (2017)

The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.
OA03.07 KEYNOTE-010: Durable Clinical Benefit in Patients with Previously Treated, PD-L1-Expressing NSCLC Who Completed Pembrolizumab
Authors: Roy Herbst, Edward Garon, Dong-Wan Kim, Byoung Chul Cho, Shirish Gadgeel, Hervé Léna, Alfonso Gúrpide, Ji-Youn Han, Catherine Dubos Arvis, Margarita Majem, Martin Forster, Isabelle Monnet, Silvia Novello, Hideo Saka, Zsuzsanna Szalai, Matthew Gubens, Wu-Chou Su, Gregory Lubiniecki, Yue Shentu, Geri Ferraro, Paul Baas
Journal: Journal of Thoracic Oncology (2017)
P93 In- vitro activity of seven hospital biocides against mycobacterium abscessus
Authors: S Caskey, JE Moore, JC Rendall
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> <i>Mycobacterium abscessus</i> pulmonary infection in patients with cystic fibrosis (CF) is associated with significant morbidity, and the prevalence is increasing. The cause of the apparent increase is unknown. Contributing factors may include the ageing CF population, and the potential for patient-to-patient transmission. To date, there is a paucity of data describing the activity of common hospital biocides against this organism. <h3>Methods</h3> <i>M. abscessus </i>isolates (<i>n </i>=13) were recovered from CF and non CF respiratory specimens. Seven commonly employed hospital biocides (Steri-7<sup>TM</sup>, Difficile-S<sup>TM</sup>, Hydrex<sup>TM</sup>, Cutan<sup>TM</sup>, Stellisept<sup>TM</sup>, Rely<sup>+</sup>On<sup>TM</sup> PeraSafe<sup>TM</sup>, Distaclor<sup>TM</sup>) were assayed for their biocidal activity against <i>M. abscessus</i>. Fresh cultures of NTM were exposed to biocide in liquid medium as per manufacturers instruction and were immediately plated following the completion of the contact period. The mean concentration of NTM plated was 9.82 × 10<sup>6 </sup>colony forming units (CFU) (range: 1.63 × 10<sup>5</sup> – 1.12 × 10<sup>8</sup>). Additionally, the remaining bacteria/biocide solution was enriched non-selectively in Mueller Hinton broth (37<sup>o</sup>C/1 week). Following this, growth of surviving bacteria was assessed with broth turbidity. <h3>Results</h3> After appropriate exposure of NTM to biocide, all NTM isolates survived in Steri-7<sup>TM</sup>, Hydrex<sup>TM</sup>, Stellisept<sup>TM</sup> and Rely<sup>+</sup>On<sup>TM</sup> PeraSafe<sup>TM</sup>. One out of 13 NTM cultures was killed by Difficile-S <sup>TM</sup> and 1 by Distaclor<sup>TM</sup>, representing a 5 log kill. Two isolates were killed by Cutan<sup>TM </sup>again representing a 5 log kill. Following enrichment, Stellisept<sup>TM</sup> showed the greatest biocidal activity with 11/13 isolates, whereas 2/13 cultures were killed by Distaclor<sup>TM</sup>. All other biocide/culture combinations yielded growth. <h3>Conclusions</h3> These data indicate that <i>M. abscessus</i> may persist after exposure to several commonly employed hospital biocides. Given the importance of effective infection prevention and control, further work is urgently needed to define unequivocal biocide contact treatments to ensure successful eradication. <h3>Acknowledgements</h3> SC is a CF Trust funded Clinical Fellow
Efficacy of Lenalidomide-Based Regimens in Multiple Myeloma Complicated by Extramedullary Plasmacytomas at Relapse or Progression.
Authors: Jose Manuel Calvo-Villas, Adrian Alegre, Ricarda García-Sánchez, Miguel T Hernández, Pilar Giraldo, Maite Zudaire, Bremo Gusmao, Juan N Rodríguez, Carmen Calle, Gemma Ramirez, Belen Iñigo, Joaquin Martinez, Albert Oriol
Journal: Blood (2009)
Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate
Authors: Tracy S. Zimmermann, Verena Karsten, Amy Chan, Joseph Chiesa, Malcolm Boyce, Brian R. Bettencourt, Renta Hutabarat, Saraswathy Nochur, Akshay Vaishnaw, Jared Gollob
Journal: Molecular Therapy (2017)

Advancement of RNAi-based therapeutics depends on effective delivery to the site of protein synthesis. Although intravenously administered, multi-component delivery vehicles have enabled small interfering RNA (siRNA) delivery and progression into clinical development, advances of single-component, systemic siRNA delivery have been challenging. In pre-clinical models, attachment of a triantennary N-acetylgalactosamine (GalNAc) ligand to an siRNA mediates hepatocyte uptake via the asialoglycoprotein receptor enabling RNAi-mediated gene silencing. In this phase 1 study, we assessed translation of this delivery approach by evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of a GalNAc-siRNA conjugate, revusiran, targeting transthyretin (TTR). Subjects received a placebo or ascending doses of revusiran subcutaneously ranging from 1.25–10 mg/kg in the single and 2.5–10 mg/kg in the multiple ascending dose phases. Revusiran was generally well tolerated, with transient, mild to moderate injection site reactions the most common treatment-emergent adverse events. Doses of 2.5–10 mg/kg revusiran elicited a significant reduction of serum TTR versus the placebo (p < 0.01), with mean TTR reductions of approximately 90% observed with multiple dosing. These results demonstrate translation of this novel delivery platform, enabling clinical development of subcutaneously administered GalNAc-siRNAs for liver-based diseases. Advancement of RNAi-based therapeutics depends on effective delivery to the site of protein synthesis. Although intravenously administered, multi-component delivery vehicles have enabled small interfering RNA (siRNA) delivery and progression into clinical development, advances of single-component, systemic siRNA delivery have been challenging. In pre-clinical models, attachment of a triantennary N-acetylgalactosamine (GalNAc) ligand to an siRNA mediates hepatocyte uptake via the asialoglycoprotein receptor enabling RNAi-mediated gene silencing. In this phase 1 study, we assessed translation of this delivery approach by evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of a GalNAc-siRNA conjugate, revusiran, targeting transthyretin (TTR). Subjects received a placebo or ascending doses of revusiran subcutaneously ranging from 1.25–10 mg/kg in the single and 2.5–10 mg/kg in the multiple ascending dose phases. Revusiran was generally well tolerated, with transient, mild to moderate injection site reactions the most common treatment-emergent adverse events. Doses of 2.5–10 mg/kg revusiran elicited a significant reduction of serum TTR versus the placebo (p < 0.01), with mean TTR reductions of approximately 90% observed with multiple dosing. These results demonstrate translation of this novel delivery platform, enabling clinical development of subcutaneously administered GalNAc-siRNAs for liver-based diseases.
High-Dose Methotrexate, Ifosfamide, Etoposide and Dexamethasone (MIED) Is an Active Salvage Regimen for Children with Recurrent or Refractory Malignant Lymphoma.
Authors: John T. Sandlund, Ching-Hon Pui, Yinmei Zhou, Eric J. Lowe, Sue C. Kaste, Larry E. Kun, Matthew J. Krasin, Mihaela Onciu, Raul C. Ribeiro, Scott C. Howard, Monika L. Metzger, Mary V. Relling, Gregory A. Hale, Renee Rencher, Kim Darnell, Melissa M. Hudson
Journal: Blood (2007)
Chronic Graft-Versus-Host (cGVHD) after Non-Myeloablative Stem Cell Transplantation (NST) with Rituximab-Containing Conditioning Regimens for Non-Hodgkin’s Lymphoma.
Authors: Rima M. Saliba, Issa F. Khouri, Marcos de Lima, Chitra Hosing, Grace Okoroji, Sandra Acholonou, Farzaneh Maadani, Jorge De Jesus, Yvonne Hsu, Richard E. Champlin, Daniel R. Couriel
Journal: Blood (2006)
Long Term Follow-Up of 4-Hydroperoxycyclophosphamide Purged Autologous Bone Marrow Transplantation in Non-Hodgkin’s Lymphoma Patients with High Risk of Bone Marrow Involvement.
Authors: Elise A. Chong, Charalambos Andreadis, Stephen J. Schuster, Selina M. Luger, David L. Porter, Sunita Nasta, Rebecca Elstrom, Steven Goldstein, Robert Sachs, Lisa Downs, Joel Green, Patricia A. Mangan, Kimberly A. Hummel, Edward A. Stadtmauer
Journal: Blood (2004)
Proenkephalin, Renal Dysfunction, and Prognosis in Patients With Acute Heart Failure
Authors: Leong L. Ng, Iain B. Squire, Donald J.L. Jones, Thong Huy Cao, Daniel C.S. Chan, Jatinderpal K. Sandhu, Paulene A. Quinn, Joan E. Davies, Joachim Struck, Oliver Hartmann, Andreas Bergmann, Alexandre Mebazaa, Etienne Gayat, Mattia Arrigo, Eiichi Akiyama, Zaid Sabti, Jens Lohrmann, Raphael Twerenbold, Thomas Herrmann, Carmela Schumacher, Nikola Kozhuharov, Christian Mueller
Journal: Journal of the American College of Cardiology (2017)
P153 Does asthma control, mood disturbance or health status influence daily physical activity levels in patients with severe asthma?
Authors: T Pandya, S Majd, S Hewitt, T Harvey-Dunston, PH Bradding, RH Green, SJ Singh, RA Evans
Journal: Thorax (2016)

<h3>Introduction</h3> We aimed to assess the level of daily physical activity and investigate the relationship with asthma control, mood disturbance and health status in patients with severe asthma. <h3>Methods</h3> Patients with severe asthma (step 4–5 of the British Thoracic Society guidelines), MRC dyspnoea grade ≥2, were recruited from specialists in difficult-to-treat asthma. All patients were asked to wear SensewareTM activity monitor for seven days during waking hours with a minimum data requirement of eight hours per day for four days.<sup>1</sup> Participants completed the Asthma Control Questionnaire (ACQ), Hospital Anxiety and Depression Scale (HADS), Chronic Respiratory Questionnaire (CRQ) and Asthma Quality of Life Questionnaire (AQLQ). Pearson’s correlation coefficient was used to assess the relationship between physical activity, asthma control, mood disturbance and health status. <h3>Results</h3> 45 participants (24 female, mean [SD] age 54 [13] yr, BMI 32 [7] kg/m<sup>2</sup>) provided written consent and physical activity data was available for 41 patients. The mean (SD) number of days of physical activity data available was 6.1 [1.9] days. The mean (SD) number of steps per day was 5258 [3030] with only 84 [82] active minutes. Only 16 patients achieved any moderate physical activity (3–4.5 metabolic equivalents [METS]) and for less than six minutes per day. The mean [SD] ACQ was 13.6 [6.1], HADS anxiety and depression domains 6.5 [4.9] and 4.5 [2.8], respectively, CRQ Dyspnoea domain 3.4 [1.5], AQLQ environmental, symptoms, activity and emotional domains of 4.9 [1.4], 5.0 [1.4], 5.0 [1.2] and 4.9 [1.5], respectively. Table 1 shows the correlations between steps per day, and measures of asthma control, mood disturbance, and health status. <h3>Conclusions</h3> Patients with severe asthma demonstrated low levels of physical activity but there were no relationships with asthma control, mood disturbance or health status. <h3>Reference</h3> Demeyers H, <i>et al</i>. <i>Chest</i> 2014;<b>146</b>(2):318–27.
P2.03a-020 Metronomic Oral Vinorelbine Monotherapy in Elderly Patients with Advanced NCSLC
Authors: Kostas Tzimopoulos, Emilia Tsaroucha, Erini Bourgani, Charalabos Kerasiotis, Anastasios Kalianos, Christina Kolokytha, Angeliki Rapti
Journal: Journal of Thoracic Oncology (2017)
S21 Identification of clinical prognostic parameters in patients with idiopathic pulmonary fibrosis
Authors: K Rogers, C Hadinnapola, K Sylvester, M Toshner, H Parfrey
Journal: Thorax (2016)

Idiopathic Pulmonary Fibrosis (IPF) is a progressive, scarring lung disease with a poor prognosis and median survival of 3 years. It is a heterogeneous disorder with varying rates of progression which presents a challenge for accurate prognostic prediction. The composite physiologic index (CPI) and the Gender, Age and Physiology (GAP) score are validated scoring systems for prognostic determination in IPF. Our data suggest these scoring systems have limited usefulness and we have undertaken a modelling approach to evaluate clinical prognostic parameters. <h3>Methods</h3> Gender, age, smoking history, presence of emphysema on HRCT thorax and echocardiogram confirmed pulmonary hypertension were collected retrospectively from 253 IPF patients (in accordance with ATS/ERS criteria and MDT consensus) from a single centre in the UK between 19<sup>th</sup> April 2007 and 13<sup>th</sup> November 2014. Lung function including FEV<sub>1</sub>, FVC, DLco and 6 minute walk test (distance, resting and minimum oxygen saturation and maximum heart rate) were collected at baseline, 6 and 12 months of follow up. Survival data were censored at 1<sup>st</sup> January 2016. The relationship between GAP or CPI and survival was analysed by Spearman’s correlation, ROC area under the curve and Chi<sup>2</sup> analysis. Multivariate analysis and linear regression were used for the modelling. <h3>Results</h3> Of the 253 patients included 188 were male (74%) with age 71.4 ± 8.3 years (mean ± SD). There were 164 (64.8%) ex-smokers and 12 (4.7%) current smokers. At presentation 19 patients had pulmonary hypertension and 35 had evidence of emphysema on HRCT thorax. Baseline lung function FEV<sub>1</sub> 79 ± 22% predicted, FVC 82 ± 19% predicted, DLco 45 ± 15% predicted (mean ± SD). Median survival was 1169 days (3.2 years). The association between survival and CPI (r<sup>2</sup> 0.59, p &lt; 0.01) or GAP (r<sup>2</sup> 0.45, p &lt; 0.01) was modest. However ROC curve analysis demonstrated that GAP and CPI were poor predictors of survival. Chi<sup>2</sup> analysis shows there is no significant difference between these scoring systems. Multivariate analysis demonstrated that baseline% predicted DLco (r<sup>2</sup> = 0.32, p = 6×10<sup>–20</sup>) (Figure 1) had the strongest association with survival. <h3>Conclusion</h3> Our data suggest that baseline percent predicted DLco may be a better predictor of outcome in patients with IPF. These results required validation by an independent cohort.
S133 Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd
Authors: RL Clifford, N Fishbane, P Rajasekar, AJ Fisher, MS Kobor, AJ Knox, TL Hackett
Journal: Thorax (2016)

<h3>Rationale</h3> Lung fibroblasts are implicated in respiratory disease pathology including chronic obstructive pulmonary disease (COPD). Phenotypic differences between fibroblasts isolated from the airway versus the parenchyma have been described but no studies have compared the cell types on a genome wide scale. DNA methylation is a reversible modification of the DNA structure with the ability to affect cell function via the alteration of gene expression. Here we compared genome wide DNA methylation profiles from airway and parenchymal fibroblasts and assessed modification to these profiles in cells isolated from individuals with COPD. <h3>Methods</h3> DNA was isolated from parenchymal and airway fibroblasts at passage 4, and bisulphite treated. Site specific, quantitative genome wide methylation was determined using the Illumina 450K Infinium Methylation BeadChip array. Linear modelling and DMRcate functions identified differentially methylated sites and regions respectively between airway and parenchymal fibroblasts isolated from individuals with normal lung function versus those with COPD. <h3>Results</h3> 3980 CpG (methylation) sites significantly differed after Bonferroni correction between airway and parenchymal fibroblasts isolated from healthy individuals. These sites had a broad distribution of effect size, with 240 CpG sites displaying a difference in methylation of &gt;50%. 78 of these sites validated in a second cohort of 7 sets of paired airway and parenchymal fibroblasts isolated from the same individual. There was genomic proximity to these sites and DMRcate was used to refine the individual CpG sites to 5 regions of interest associated with 5 genes; HLX, TWIST1, CREB5, SKAP2 and PRDM16. Differences in methylation were less pronounced when comparing cells isolated from healthy individuals to those with COPD. In airway fibroblasts 47 DMRcate regions were identified with a maximum difference in methylation of at least 20%. In parenchymal fibroblasts 3 DMRcate regions were identified with a maximum difference in methylation of at least 20%. <h3>Conclusions</h3> DNA methylation profiles are significantly different between airway and parenchymal fibroblasts but only small modifications are associated with COPD. Future work will focus on validating a methylation based markers of parenchymal versus airway fibroblasts and associating our differential observations with gene/protein expression.
Health care service barriers to breast cancer screening among Egyptian females.
Authors: H. M. E. El-Mansy, H. M. Ismail, I. F. Kharboush, M. M. Tawfik, O. G. El Sharkawy, H. Mamdouh, H. Sallam
Journal: Journal of Clinical Oncology (2011)

1585 Background: Egyptian women did not utilize breast cancer screening service. The potential causes for this problem include economical, social and healthcare service barriers. No studies addressing barriers to breast cancer screening among Egyptian women could be traced. Methods: To determine possible health care service barriers to breast cancer screening among Egyptian females.Descriptive, cross-sectional study was conducted. A structured interview questionnaires was used, Six hundredfemales aged 40 years or above, who never sought breast cancer screening service before and never been diagnosed with breast cancer were interviewed in the Family Health Centers in Alexandria governorate, Egypt. Results: Multiple health care service barriers were reported. Lack of privacy in the screening place was the most frequently identified potential barrier(71.4%), followed by the absence of female Doctor/Nurse to perform the screening (42.9%), Difficulty to take an appointment (38.5%), the far distance to the screening facility was anticipated as a barrier in (38.1%), also (37.5%) reported they do not know where to find the service. (90.8%) of the women reported that a structured program for breast cancer screening will encourage them to undergo the screening periodically, among which (70.7%) think the service should be offered by primary health centers, (19.1%) see it should be offered by health insurance, only (9.7%) think that this service should be provided by the private sector. Conclusions: Lack of privacy, lack of female healthcare providers and lack of information about the service place, were the most frequent potential health care service barriers to screening among Egyptian women. Structured breast cancer screening program seems to be important in order to increase the utilization of the service. Recognizing these barriers and addressing culturally specific issues may improve utilization of breast cancer screening among Egyptian women.
Expression of P73 Splice Variants Correlates to Resistance to DNA Damaging Drugs in Childhood T-Lineage Acute Lymphoblastic Leukemia.
Authors: Marrit Meier, Monique L. Den Boer, Jules P.P. Meijerink, Monique Passier, Elisabeth R. Van Wering, Gritta E. Janka-Schaub, Rob Pieters
Journal: Blood (2004)
Myocardial Tissue Engineering With Cells Derived From Human-Induced Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold
Authors: Ling Gao, Molly E. Kupfer, Jangwook P. Jung, Libang Yang, Patrick Zhang, Yong Da Sie, Quyen Tran, Visar Ajeti, Brian T. Freeman, Vladimir G. Fast, Paul J. Campagnola, Brenda M. Ogle, Jianyi Zhang
Journal: Circulation Research (2017)

Conventional 3-dimensional (3D) printing techniques cannot produce structures of the size at which individual cells interact.Here, we used multiphoton-excited 3D printing to generate a native-like extracellular matrix scaffold with submicron resolution and then seeded the scaffold with cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human-induced pluripotent stem cells to generate a human-induced pluripotent stem cell-derived cardiac muscle patch (hCMP), which was subsequently evaluated in a murine model of myocardial infarction.The scaffold was seeded with ≈50 000 human-induced pluripotent stem cell-derived cardiomyocytes, smooth muscle cells, and endothelial cells (in a 2:1:1 ratio) to generate the hCMP, which began generating calcium transients and beating synchronously within 1 day of seeding; the speeds of contraction and relaxation and the peak amplitudes of the calcium transients increased significantly over the next 7 days. When tested in mice with surgically induced myocardial infarction, measurements of cardiac function, infarct size, apoptosis, both vascular and arteriole density, and cell proliferation at week 4 after treatment were significantly better in animals treated with the hCMPs than in animals treated with cell-free scaffolds, and the rate of cell engraftment in hCMP-treated animals was 24.5% at week 1 and 11.2% at week 4.Thus, the novel multiphoton-excited 3D printing technique produces extracellular matrix-based scaffolds with exceptional resolution and fidelity, and hCMPs fabricated with these scaffolds may significantly improve recovery from ischemic myocardial injury.
Chemo-Mobilization Provides Superior Mobilization and Collection in Autologous Stem Cell Transplants but with Less Predictability and At a Higher Cost,
Authors: Nelson J. Chao, Daniel T Grima, George Carrum, Leona Holmberg, Henry C. Fung, Stephen Brown, Mitchell E. Horwitz, Lisa M Bernard, Junya Kanda, Jane L. Liesveld, Brian McClune, Paul Shaughnessy, Guido J. Tricot
Journal: Blood (2011)