tbuckley/cabot-search huggingface dataset:
Dissecting inherent intratumor heterogeneity in patient-derived glioblastoma culture models
Authors: Jian Teng, Cintia Carla da Hora, Rami S. Kantar, Ichiro Nakano, Hiroaki Wakimoto, Tracy T. Batchelor, E. Antonio Chiocca, Christian E. Badr, Bakhos A. Tannous
Journal: Neuro-Oncology (2016)

Molecular profile of glioblastoma multiforme (GBM) revealed 4 subtypes, 2 of which, proneural and mesenchymal, have been predominantly observed, with the latter displaying a more aggressive phenotype and increased therapeutic resistance. Single-cell RNA sequencing revealed that multiple subtypes actually reside within the same tumor, suggesting cellular heterogeneity in GBM. Further, plasticity between these 2 subtypes is observed during tumor recurrence and in response to radiation therapy. Patient-derived GBM stemlike cells were cultured as neurospheres. These cells were differentiated in serum by attaching to the culture dishes. The "floating" cells that were not attached/differentiated were harvested from the conditioned medium. The characteristics of these cells were studied with limiting dilution assays and immunofluorescence staining. Cell growth and nuclear factor-kappaB (NFkB) activation were monitored using bioluminescent assays as well as quantitative polymerase chain reaction and western blotting. In vivo tumorigenesis was evaluated in orthotopic xenograft models using bioluminescence imaging. Patient-derived GBM stemlike cells undergo differentiation by attaching to the culture dish in serum-containing medium. We observed that a small subset of these cells escape this adhesion/differentiation and grow as floating cells. These cells displayed enhanced cancer stem cell properties with a molecular and phenotypic mesenchymal signature, including resistance to radiation and targeted therapies, a more aggressive tumor formation, and NFkB activation. Our results endorse inherent intratumor molecular subtype heterogeneity in glioblastoma and provide a valuable approach to study phenotypic plasticity, which could be applied to find novel therapeutic strategies to eradicate this aggressive tumor and can be extended to other cancer types.
MA01.11 Implementation of LDCT Lung Cancer Screening into Practice. Results of Regional Early Detection Program
Authors: Maciej Bryl, Beata Nikisch, Wojciech Dyszkiewicz, Cezary Piwkowski, Mariusz Kasprzyk, Wojciech Kasprzak, Aleksander Barinow-Wojewodzki
Journal: Journal of Thoracic Oncology (2017)
Exercising as “weekend warrior” still yields mortality benefit, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

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A Prospective Study of Bortezomib in Combination with Melphalan and Prednisone for Patients with Previously Untreated Multiple Myeloma.
Authors: Cristina Gasparetto, George P. Keogh, Jon P. Gockerman, Mitchell Horwitz, Joseph O. Moore, Carlos DeCastro, Louis Diehl, Patty Davis, Nelson Chao, David A. Rizzieri
Journal: Blood (2005)
Artificially Sweetened Beverages and the Response to the Global Obesity Crisis
Authors: Maria Carolina Borges, Maria Laura Louzada, Thiago Hérick de Sá, Anthony A. Laverty, Diana C. Parra, Josefa Maria Fellegger Garzillo, Carlos Augusto Monteiro, Christopher Millett
Journal: PLoS Medicine (2017)

Christopher Millett and colleagues argue that artificially sweetened beverages should not be promoted as part of a healthy diet.
MA17.02 Genome-Wide Copy Number and Mutational Analysis in Longitudinal Biopsies of Matched Primary and Metastatic Pulmonary Adenocarcinomas
Authors: Thomas Lorber, Noemi Andor, Tanja Dietsche, Valeria Perrina, Darius Juskevicius, Arthur Krause, David Müller, Didier Lardinois, Michael Barrett, Christian Ruiz, Lukas Bubendorf
Journal: Journal of Thoracic Oncology (2017)
DNA Copy Number Changes Have Gene Dosage Effects with Consequent Impact On Disease Biology and Prognosis in Multiple Myeloma
Authors: Mehmet Kemal Samur, Parantu K Shah, Xujun Wang, Norman Huang, Stephane Minvielle, Magrangeas Florence, Herve Avet-Loiseau, Nikhil C. Munshi, Cheng Li
Journal: Blood (2012)
P2.06-003 A Phase Ib Study of the Combination of Afatinib and Ruxolitinib in EGFR Mutant Non-Small Cell Lung Cancer (NSCLC) Progressed on EGFR-TKI
Authors: Ji Soo Park, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho
Journal: Journal of Thoracic Oncology (2017)
Fertility concerns in young women with breast cancer: Results from a prospective cohort study.
Authors: K. J. Ruddy, S. Gelber, R. M. Tamimi, E. S. Ginsburg, L. Schapira, S. E. Come, M. E. Meyer, E. P. Winer, A. H. Partridge
Journal: Journal of Clinical Oncology (2011)

6025 Background: Prior research on fertility concerns in young women with breast cancer has been cross-sectional, and evaluated experiences of survivors rather than newly diagnosed patients. Little is known about how fertility concerns influence treatment decisions or steps taken to preserve fertility at diagnosis. We sought to evaluate fertility issues in the setting of an ongoing multicenter cohort study of young women with newly diagnosed breast cancer. Methods: Women <age 40 with new breast cancer were identified prospectively by pathology record review at participating centers. Consenting participants received a baseline mailed survey, which included sociodemographic, medical, and psychosocial items, plus a modified version of our Fertility Issues Survey (FIS). Results: The first 478 respondents were included in this analysis. Median age was 37 (range 17-40 years); 160 (33%) were nulliparous; 174 (36%) wished to have biologic children in the future prior to their cancer diagnoses, and 113 (24%) wished that at the time of the survey; 308 (64%) recalled discussing fertility with a doctor at diagnosis. Fertility concerns led 4 women (1%) to choose not to receive chemo, 8 (2%) to choose one chemo over another, 6 (1%) to consider not taking hormone therapy, 15 (3%) to forgo hormone therapy, and 45 (9%) to consider taking hormone therapy for <5 yrs. Fifty-three women (11%) took special steps to lessen the chance of infertility: embryo cryopreservation in 30 (6%), oocyte cryopreservation in 6 (1%), and GnRH agonist in 16 (3%). Conclusions: Many young women with newly diagnosed breast cancer harbor concerns about fertility. For some, these impact their treatment decisions and prompt interventions to preserve fertility. Research to address how concerns change over time, as well as how to optimally preserve fertility and fertility outcomes in young survivors, is warranted. Not at all A little Somewhat Very/a lot Level of concern about infertility after treatment 50% 14% 13% 23% Treatment decisions affected 75% 8% 9% 8%
P2.02-016 Real World Experience with Chemoradiotherapy in Locally Advanced NSCLC
Authors: Joaquín Gimeno, Irene Torres, Jorge Hernando, Ana Comin, Isabel Pajares, Mar Puertas, Pilar Felices, Ana Nuño, Juan Lao, Angel Artal Cortes
Journal: Journal of Thoracic Oncology (2017)
P2.01-062 Impact of the Tissue Distribution of Subpopulations of TILs and PD-L1 Expression on the Clinical Outcome of NSCLC
Authors: Giovanni Bocchialini, Giulia Mazzaschi, Denise Madeddu, Angela Falco, Caterina Frati, Andrea Gervasi, Bruno Lorusso, Costanza Lagrasta, Paolo Carbognani, Luca Ampollini, Marcello Tiseo, Federico Quaini
Journal: Journal of Thoracic Oncology (2017)
Risk Adapted Dose Intensive DICEP Salvage Chemotherapy Prior to Autologous Stem Cell Transplantation Yields Successful Outcomes in Chemotherapy Refractory Lymphoma.
Authors: Stuart L. Goldberg, Natalya Selina, Manzurul A. Sikder, Jack W. Hsu, David S. Siegel, Andrew A. Jennis, Richard J. Rosenbluth, Robert A. Preti, Andrew L. Pecora, Scott D. Rowley
Journal: Blood (2004)
Infarct Size and Left Ventricular Ejection Fraction in Acute Myocardial Infarction
Authors: Masatsugu Hori, Michitoshi Inoue, Masayoshi Mishima, Takashi Shimazu, Hiroshi Abe, Sugao Fukui, Nobuhisa Ohgitani, Takazo Minamino
Journal: Circulation (1977)
P3.02a-002 Pulmonary Sarcomatoid Carcinoma with ALK Rearrangement: Frequency, Clinical-Pathologic Characteristics, and Response to ALK Inhibitor
Authors: Xinru Chen, Yu Zhang, Jiabin Lu, Chunwei Xu, Jianzhong Liang, Fang Wang, Wenyong Sun, Jingping Yuan, Sangao Fang, Huijuan Wang, Hui Wang, Xuewen Liu, Likun Chen
Journal: Journal of Thoracic Oncology (2017)
P73 Acute Non Invasive Ventilation (NIV)–related nasal bridge pressure ulceration: effect of a proactive prevention approach
Authors: G Stygall, K Morley, L Pickup, A Oakes, P Antoine-Pitterson, B Chakraborty, R Mukherjee
Journal: Thorax (2016)

<h3>Introduction</h3> NIV applied via full face masks is increasingly becoming the standard of care in the treatment of acute hypercapnic respiratory failure. Most guidelines suggest good skin care: strategies include regular pressure relief, use of masks with softer cushions/pressure-avoidance masks and application of pressure-relieving dressing to the skin to redistribute pressure and reduce friction. We set out to examine the effect of a systematic proactive prevention approach to prevent Grade 2 Pressure ulcers in a Ward Based Physiotherapy-led acute NIV service in a general hospital serving a population of about 400000. This included (a) prophylactic protective dressing and (b) reactive change to a pressure-avoidance mask for identified Grade 1 pressure sore. <h3>Methods</h3> Data was collected from 01/05/2014 and 31/08/2015 which included an 8-month period before (period1) and an 8-month period after (period2) introduction of the proactive prevention approach. Five main sets of data were collected; the NIV mask used (model and size), whether the mask was changed, the total number of days using NIV, pressure ulcer grading and the outcome of the NIV admission. A pressure ulcer was defined as Grade 2 or above. <h3>Results</h3> Grade 2 Pressure ulcer rates showed a trend in reduction by over 50% following the change in practice (but fell short of statistical significance: chi-squared test p-value = 0.3). In period1 there were 11 Grade 2 pressure ulcers from 109 admissions; in period2 there were 5 pressure ulcers from 105 admissions. Benefits of using total face masks for NIV delivery were also noted with those patients who were poorly complaint with the standard NIV full face mask to prevent treatment failure. <h3>Conclusions</h3> An early prophylactic pressure-relieving dressing and a reactive change to a pressure-avoidance mask for identified Grade 1 pressure sore, can reduce the chance of developing Grade 2 pressure ulcers for patients using NIV acutely. Further studies including longitudinal data on a proactive prevention approach adjusted for acute NIV duration for NIV-related nasal bridge pressure ulceration are needed to confirm the utility of this approach.
Active Estrogen Receptor-alpha Signaling in Ovarian Cancer Models and Clinical Specimens
Authors: Courtney L. Andersen, Matthew J. Sikora, Michelle M. Boisen, Tianzhou Ma, Alec Christie, George Tseng, Yongseok Park, Soumya Luthra, Uma Chandran, Paul Haluska, Gina M. Mantia-Smaldone, Kunle Odunsi, Karen McLean, Adrian V. Lee, Esther Elishaev, Robert P. Edwards, Steffi Oesterreich
Journal: Clinical Cancer Research (2017)

Abstract Purpose: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha (ERα) in approximately 80% of HGSOC and some small but promising clinical trials of endocrine therapy, ERα has been understudied as a target in this disease. We sought to identify hormone-responsive, ERα-dependent HGSOC. Experimental Design: We characterized endocrine response in HGSOC cells across culture conditions [ two-dimensional (2D), three-dimensional (3D), forced suspension] and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression. Estrogen-regulated transcriptome data were overlapped with public datasets to develop a comprehensive panel of ERα target genes. Expression of this panel and ERα H-score were assessed in HGSOC samples from patients who received endocrine therapy. Time on endocrine therapy was used as a surrogate for clinical response. Results: Proliferation is ERα-regulated in HGSOC cells in vitro and in vivo, and is partly dependent on 3D context. Transcriptomic studies identified genes shared by cell lines and PDX explants as ERα targets. The selective ERα downregulator (SERD) fulvestrant is more effective than tamoxifen in blocking ERα action. ERα H-score is predictive of efficacy of endocrine therapy, and this prediction is further improved by inclusion of target gene expression, particularly IGFBP3. Conclusions: Laboratory models corroborate intertumor heterogeneity of endocrine response in HGSOC but identify features associated with functional ERα and endocrine responsiveness. Assessing ERα function (e.g., IGFBP3 expression) in conjunction with H-score may help select patients who would benefit from endocrine therapy. Preclinical data suggest that SERDs might be more effective than tamoxifen. Clin Cancer Res; 23(14); 3802–12. ©2017 AACR.
P2.01-064 Molecular Context of Immune Microenvironment in Early-Stage Lung Squamous Cell Carcinoma
Authors: Esther Conde, Alejandra Caminoa, Carolina Dominguez, Stefan Walter, Marta Alonso, Susana Hernandez, Luis Jimenez, Luis Madrigal, Antonio Calles, Javier De Castro, Fernando Lopez-Rios
Journal: Journal of Thoracic Oncology (2017)
P44 Comparison of structural brain abnormalities and cognitive function in COPD patients after hospitalisation, stable COPD patients and healthy age-matched controls
Authors: MK Bajaj, CA Spilling, JW Dodd, PW Jones, FA Howe, EH Baker, TR Barrick
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Cognitive impairment is a common co-morbidity in chronic obstructive pulmonary disease (COPD) and is associated with poor disease management, greater disability and mortality [Chang <i>et al.,</i> J Am Geriatr Soc, 2012;60:1839–46]. We have previously shown that cognitive impairment is worse in COPD patients during and after hospitalisation for exacerbations, than in those with stable disease [Dodd <i>et al.</i> Chest, 2013;144:119–27]. Our aim was to use multimodal brain magnetic resonance imaging (MRI) to compare structural brain abnormalities between hospitalised and stable COPD patients and healthy controls. <h3>Methods</h3> 23 COPD patients hospitalised for exacerbations within the last year (hospitalised), 17 COPD patients not hospitalised within the last year (stable) and 23 healthy age-matched controls, were recruited. Exclusion criteria included neurological or psychiatric disorders, cerebrovascular disease or hypertension. Cognition was measured using the Montreal Cognitive Assessment. T1-weighted (T1W), diffusion tensor (DTI) and Fluid Attenuated Inversion Recovery (FLAIR) were acquired using a Philips 3T scanner. The following brain indicators were calculated: normalised whole brain and ventricular volumes (scan: T1W, software: SIENAX), white matter microstructural fractional anisotropy and mean diffusivity – compared voxelwise using tract–based spatial statistics (DTI, FSL), and white matter lesion volume (FLAIR, <i>dispunc</i>). Ethical approval was obtained (15/LO/0425). <h3>Results</h3> Cognition was clinically impaired in hospitalised COPD (median (IQR); 23.0 (5)) but not in stable patients (27.0 (2)) or controls (28.5 (3)), with a significant difference only between hospitalised patients and controls (<i>p</i> &lt; 0.0001). No significant differences were found in normalised whole brain volume, however, normalised brain ventricular volume was significantly greater in hospitalised COPD, compared to stable COPD (<i>p</i> = 0.046) and controls (<i>p</i> = 0.028). Hospitalised and stable COPD patients had widespread significant reductions in fractional anisotropy and increased mean diffusivity throughout the white matter skeleton, compared to controls (<i>p</i> &lt; 0.001). Hospitalised patients had the highest white matter lesion volume, however this was not significantly different between groups. <h3>Conclusions</h3> Hospitalised COPD patients have greater cognitive impairment compared to stable COPD and controls with evidence of greater ventricular and white matter lesion volumes and damaged white matter microstructure. Mechanisms behind these neuropathological processes and possible links to observed cognitive dysfunction remain unclear, but may involve ischaemic small-vessel disease.
S125 Smoking cessation knowledge, beliefs and current practices among uk child health professionals
Authors: MJP Robertson, A Gupta, J Arumugam
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Two million children in the UK are regularly exposed to second-hand smoke (SHS) in the home and many more are exposed in other settings. The consequences of this are well recognised and include higher incidences of: numerous acute illnesses; hospital admissions; school absences and increased smoking rates in later life. Together these result in significant costs to the NHS and wider economy. Barriers to improved practice have been reported in other professional groups in the UK and in Child Health Doctors and Nurses in other countries. We could find no previously published data from the UK on this topic with which to inform and improve our own staff training and support. <h3>Methods</h3> An electronic questionnaire was developed, covering beliefs, knowledge and current practice. The survey was distributed through professional groups, training and healthcare delivery organisations. <h3>Results</h3> 140 responses were received, from Consultants (22%), trainee Paediatricians (32%), Nurses (34%) and others (11%), including Physiotherapists, Pharmacists, Healthcare Assistants and Play Therapists. Respondents came from 19/21 UK regions. Respondents believe it is important to support smoking cessation for the parents of their patients but are likely to perceive the barriers to this as arising from the smokers more than from deficiencies in their own knowledge and skills (see Table 1). However, we identified significant knowledge gaps. When asked if 7 facts about SHS and cessation were true or false, incorrect answers ranged from 2–41% and ‘don’t know’ from 10–46%. Only 41% knew how to make a referral to their local cessation service. 63% of respondents last had training about smoking cessation more than 5 years ago. <h3>Conclusions</h3> Our findings show that Child Health Professionals’ beliefs about the impact of smoking and the importance of smoking cessation are not borne out in their practice. This is likely to be due to a lack of knowledge and training, despite the existence of high quality and easily accessible national resources.<sup>1</sup> We believe that every Child Health organisation should appoint smoking cessation champions who can build links with local specialist services in order to promote training and good practice among their colleagues. <h3>Reference</h3> National Centre for Smoking Cessation and Training (NCSCT). http://www.ncsct.co.uk
Predicting Survival in Amyotrophic Lateral Sclerosis: Should We Move Forward from Vital Capacity?
Authors: Giuseppe Francesco Sferrazza Papa, Giulia Michela Pellegrino, Fabiano Di Marco, Massimo Corbo, Stefano Centanni
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

hemorrhage, neoplasm, and others.Additional sonographic signs are needed for further differentiation (3).Even the presence of air bronchogram inside the consolidation on lung ultrasound has been reported in patients with pulmonary neoplasm, not pneumonia (4).In summary, the presence of air bronchogram inside the consolidation is not specific for pneumonia, and further sonographic signs such as dynamic air bronchogram are needed to support the diagnosis.In this case, resorptive atelectasis rather than pneumonia is more likely to be the cause of the rapid relief of pulmonary consolidation on lung ultrasound.
P270 Stenotrophomonas maltophilia infection in a bronchiectasis cohort
Authors: E Pigott, S Cowman, R Wilson, MR Loebinger
Journal: Thorax (2016)

<h3></h3> <i>Stenotrophomonas maltophilia</i> has uncertain clinical significance in bronchiectasis patients. This retrospective study describes the characteristics and outcomes of this patient group. Bronchiectasis patients with <i>S. maltophilia</i> were identified from microbiology records and demographic data was recorded from electronic patient information. Comparisons were made to a previously prospectively collected dataset of bronchiectasis patients without <i>S. maltophilia</i> growth. There were 174 patients with <i>S. maltophilia</i> and bronchiectasis. Intravenous and oral antibiotics were taken by 38.7% and 48.1% of the cohort respectively in the 2 months prior to the first <i>S. maltophilia</i> culture. Patients were followed up for a median of 6 (2–11) years and the mortality was 28.7%. Infection resolved (3 negative sputa) in 119/174 patients with recurrence of infection in 32/119. Specific treatment for the <i>S. maltophilia </i>was given in 91/174 patients, however treatment did not significantly affect resolution. Failure of resolution was however significantly associated with mortality (p &lt; 0.001) (Figure 1). In the year prior to <i>S. maltophilia</i> culture, 12.7% grew non-tuberculosis mycobacterium (NTM). In comparison with a separate bronchiectasis cohort, those with <i>S. maltophilia</i> had a lower FEV1 (59.2% vs 68.4%) and there was more immunodeficiency as the underlying aetiology (10.3% vs 2.38%). Persistent <i>S. maltophilia</i> has a poor outcome in bronchiectasis. It may act as a marker of disease severity and the requirement for antibiotics, and acquisition frequently follows antibiotic use. It was also associated with the isolation of NTM. The resolution of infection is common but is not related to treatment directed against the organism, however persistent infection is associated with increased mortality.
Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity
Authors: Hugo A. Tejeda, Jocelyn Wu, Alana R. Kornspun, Marco Pignatelli, Vadim Kashtelyan, Michael J. Krashes, Brad B. Lowell, William A. Carlezon, Antonello Bonci
Journal: Neuron (2017)
P3.02c-032 Interstitial Pneumonitis Associated with Immune Checkpoint Inhibitors Treatment in Cancer Patients
Authors: Myriam Delaunay, Amelie Lusque, Nicolas Meyer, Jean-Marie Michot, Judith Raimbourg, Jacques Cadranel, Gérard Zalcman, Valerie Gounant, Denis Moro-Sibilot, Nicolas Girard, Luc Thiberville, David Planchard, Anne Cecile Metivier, Fabrice Barlesi, Eric Dansin, Maurice Pérol, Eric Pichon, Oliver Gautschi, Früh Martin, Samia Collot, Marion Jaffro, Gregoire Prevot, Julie Milia-Baron, Julien Mazieres
Journal: Journal of Thoracic Oncology (2017)