tbuckley/cabot-search huggingface dataset:
P3.02b-094 Rebiopsy Post Progression in EGFR Mutated Lung Cancer
Authors: Arun Chandrasekharan, Vijay Patil, Vanita Norohna, Amit Joshi, Anuradha Choughale, Kumar Rajeev, Abhishek Mahajan, Amit Janu, Supriya Goud, Sucheta More, Ashay Karpe, Anant Ramaswamy, Nikhil Pande, Alok Goel, Vikas Talreja, Kumar Prabhash
Journal: Journal of Thoracic Oncology (2017)
P3.02a-009 TPX-0005: A Multi-Faceted Approach to Overcoming Clinical Resistances from Current ALK or ROS1 Inhibitor Treatment in Lung Cancer
Authors: J. Jean Cui, Dayong Zhai, Wei Deng, Zhongdong Huang, Evan Rogers, Jane Ung, Jeffrey Whitten, Yishan Li
Journal: Journal of Thoracic Oncology (2017)
P3.01-055 In vitro Construction of Lung Cancer Organoids from Induced Lung Cancer Stem Like Cells
Authors: Hiroyuki Ogawa, Takashi Aoi, Nahoko Shimizu, Daisuke Hokka, Yugo Tanaka, Michiyo Koyanagi-Aoi, Yoshimasa Maniwa
Journal: Journal of Thoracic Oncology (2017)
Response to Lenalidomide, Doxorubicin and Dexamethasone (RAD) in Newly Diagnosed Multiple Myeloma Is Independent of Cytogenetic Risk and Retained after Double Stem Cell Transplant
Authors: Stefan Knop, Christian Langer, Monika Engelhardt, Lars-Olof Mügge, Albrecht Reichle, Wolf Rösler, Florian Bassermann, Bernd Hertenstein, Isrid Sturm, Christoph Röllig, Helmut Ostermann, Kerstin Schäfer-Eckart, Mark Ringhoffer, Andreas Günther, Christian Junghanss, Harald Biersack, Susanne Strifler, Andreas Bachinger, Hermann Einsele, Ralf C. Bargou
Journal: Blood (2014)
A working model of the deep relationships of diverse modern human genetic lineages outside of Africa
Authors: Mark Lipson, David Reich
Journal: Molecular Biology and Evolution (2016)

A major topic of interest in human prehistory is how the large-scale genetic structure of modern populations outside of Africa was established. Demographic models have been developed that capture the relationships among small numbers of populations or within particular geographical regions, but constructing a phylogenetic tree with gene flow events for a wide diversity of non-Africans remains a difficult problem. Here, we report a model that provides a good statistical fit to allele-frequency correlation patterns among East Asians, Australasians, Native Americans, and ancient western and northern Eurasians, together with archaic human groups. The model features a primary eastern/western bifurcation dating to at least 45,000 years ago, with Australasians nested inside the eastern clade, and a parsimonious set of admixture events. While our results still represent a simplified picture, they provide a useful summary of deep Eurasian population history that can serve as a null model for future studies and a baseline for further discoveries.
P1.06-043 A Study to Select Rational Therapeutics in Subjects with Advanced Malignancies (WINTHER) - The Sheba Experience in Lung Cancer Patients
Authors: Amir Onn, Jair Bar, Tal Sela, Aliza Ackerstein, Sharon Halperin, Goni Hout-Siloni, Sivan Lieberman, Hovav Nechushatan, Raanan Berger
Journal: Journal of Thoracic Oncology (2017)
Colony-Forming Unit Cell (CFU-C) Assays in Myelodysplastic Syndrome
Authors: Bing Li, Jinqin Liu, Shiqiang Qu, Robert Peter Gale, Ruixian Xing, Tiejun Qin, Yue Zhang, Zefeng Xu, Liwei Fang, Hongli Zhang, Lijuan Pan, Naibo Hu, Gang Huang, Zhijian Xiao
Journal: Blood (2015)
Identification and Characterization of an ALK Inhibitor That Attenuates the Proliferation and Survival of Anaplastic Large Cell Lymphoma-Derived Cell Lines and ALK Dependent Cell Lines.
Authors: Mangeng Cheng, Weihua Wan, Mark Albom, Linda Weinberg, Thelma Angeles, Matthew Quail, Lihui Lu, Ted Underiner, Robert Hudkins, Mark Ator, Bruce Ruggeri
Journal: Blood (2004)
S58 The use of remote monitoring to assess ventilator adherence and outcomes within a regional home mechanical ventilation service
Authors: YM Gn, R Moses, A Vyas
Journal: Thorax (2016)

<h3>Introduction</h3> Home mechanical ventilation (HMV) is a recognised evidence-based intervention for patients in chronic respiratory failure (CRF). However there is a paucity of evidence on the adherence to this treatment. This study examined the adherence of HMV and evaluated the clinical outcomes associated with adherence in a variety of patient populations – namely neuromuscular disease, chest wall disease, obesity hypoventilation syndrome and chronic obstructive pulmonary disease (COPD). <h3>Methods</h3> A retrospective study was carried out between May to June 2016. Adherence data was downloaded through remote monitoring. Primary outcomes included changes in blood gases at 3 and 6 months, and hospital admissions 12 months pre- and post-ventilation. Qualitative outcomes were obtained through a questionnaire conducted via telephone interviews. <h3>Results</h3> 62 patients were included in this study. Patients undertaking remote monitoring of HMV demonstrated an adherence rate of 90.3%, defined as more than 4 hours of ventilator use/night (mean [SD] = 7h 17min [2h 53min]). No significant difference in adherence was found between patients of different aetiologies. The blood gases improved significantly at 3 months compared to baseline (p &lt; 0.05). However, there was a universal trend for these parameters to return to baseline at 6 months regardless of the underlying disease. HMV reduced hospital admissions by 1.07 (1.27) per individual per annum (p &lt; 0.0001) and was most significant in the COPD group (p = 0.005). All patient groups indicated that HMV improved their quality of life. <h3>Conclusion</h3> This study has demonstrated that contrary to existing evidence, the adherence to HMV was extremely good across all diseases. Remote monitoring may play a role in this increased adherence. Although HMV contributed to improvements in blood gases at 3 months, there was a universal trend for these parameters to return to baseline at 6 months in all disease states despite good adherence. Our data therefore suggests that early follow-up is essential to detect deterioration and support the need for palliation. Nevertheless HMV remains an effective treatment to reduce hospital admissions and improve quality of life, if patients are adherent to the intervention.
S99 Efficacy of nintedanib on acute exacerbations reported as serious adverse events in the inpulsis® trials in idiopathic pulmonary fibrosis (IPF)
Authors: L Richeldi, H Koegler, M Trampisch, S Geier, M Kreuter
Journal: Thorax (2016)

<h3>Introduction</h3> The INPULSIS® trials assessed the effects of nintedanib versus placebo in patients with IPF. Time to first investigator-reported acute exacerbation over 52 weeks was a key secondary endpoint. Adverse events that were considered by an investigator to fulfil pre-defined criteria for an acute exacerbation were categorised by an adjudication committee as a confirmed acute exacerbation, suspected acute exacerbation, or not an acute exacerbation. We assessed the effect of nintedanib on acute exacerbations reported as serious adverse events and non-serious adverse events and the impact of these events on survival. <h3>Methods</h3> A <i>post-hoc</i> analysis of patients with acute exacerbations reported as serious adverse events or non-serious adverse events over 52 weeks was undertaken using pooled data from the INPULSIS® trials. <h3>Results</h3> Of the 63 patients who had ≥1 investigator-reported acute exacerbation, 49 (77.8%) had an acute exacerbation reported as a serious adverse event. Of these 49 patients, 31 (63.3%) had an adjudicated confirmed or suspected acute exacerbation reported as a serious adverse event. A higher proportion of patients with investigator-reported acute exacerbations reported as serious adverse events died than patients with acute exacerbations reported as non-serious adverse events (30 of 49 patients [61.2%] versus 1 of 15 patients [6.7%]) (Figure). Nintedanib significantly reduced the risk of a first investigator-reported acute exacerbation reported as a serious adverse event versus placebo (HR 0.57 [95% CI: 0.32, 0.99]; p = 0.0476). Investigator-reported acute exacerbations reported as serious adverse events occurred in 3.6% of patients in the nintedanib group and 6.1% in the placebo group. Nintedanib significantly reduced the risk of having a first adjudicated confirmed or suspected acute exacerbation reported as a serious adverse event versus placebo (HR 0.30 [95% CI: 0.14, 0.64]; p = 0.0019). Adjudicated confirmed or suspected acute exacerbations reported as serious adverse events occurred in 1.6% in the nintedanib group and 5.0% in the placebo group. <h3>Conclusion</h3> In pooled data from the INPULSIS® trials, nintedanib significantly reduced the risk of acute exacerbations reported as serious adverse events. Acute exacerbations reported as serious adverse events were associated with a much higher risk of death than acute exacerbations reported as non-serious adverse events.
Structural and functional alterations in the colonic microbiome of the rat in a model of stress induced irritable bowel syndrome
Authors: Nicolaas H. Fourie, Dan Wang, Sarah K. Abey, Amy L. Creekmore, Shuangsong Hong, Christiana G. Martin, John W. Wiley, Wendy A. Henderson
Journal: Gut Microbes (2017)

Stress is known to perturb the microbiome and exacerbate irritable bowel syndrome (IBS) associated symptoms. Characterizing structural and functional changes in the microbiome is necessary to understand how alterations affect the biomolecular environment of the gut in IBS. Repeated water avoidance (WA) stress was used to induce IBS-like symptoms in rats. The colon-mucosa associated microbiome was characterized in 13 stressed and control animals by 16S sequencing. In silico analysis of the functional domains of microbial communities was done by inferring metagenomic profiles from 16S data. Microbial communities and functional profiles were compared between conditions. WA animals exhibited higher α-diversity and moderate divergence in community structure (β-diversity) compared with controls. Specific clades and taxa were consistently and significantly modified in the WA animals. The WA microbiome was particularly enriched in Proteobacteria and depleted in several beneficial taxa. A decreased capacity in metabolic domains, including energy- and lipid-metabolism, and an increased capacity for fatty acid and sulfur metabolism was inferred for the WA microbiome. The stressed condition favored the proliferation of a greater diversity of microbes that appear to be functionally similar, resulting in a functionally poorer microbiome with implications for epithelial health. Taxa, with known beneficial effects, were found to be depleted, which supports their relevance as therapeutic agents to restore microbial health. Microbial sulfur metabolism may form a key component of visceral nerve sensitization pathways and is therefore of interest as a target metabolic domain in microbial ecological restoration.
P167 Does antifibrotic treatment outcomes differ in usual interstitial pneumonia based on HRCT criteria established by ATS/ERS/JRS/ALAT in 2011?
Authors: C Ng, J Hornsby, D Anderson
Journal: Thorax (2016)

<h3>Background</h3> Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and irreversible lung disease.<sup>1</sup> The diagnosis of IPF is made using clinical history, pulmonary function testing (PFT), and radiological appearances of Usual Interstitial Pneumonia (UIP) on High Resolution CT (HRCT) Scanning provided other appearances have been excluded. The diagnosis is frequently made at MDT where the images are categorised into Definite UIP, Possible UIP, or Inconsistent with UIP using HRCT criteria.<sup>2</sup> In the west of Scotland, patients demonstrating definite or possible UIP patterns on HRCT with a FVC &lt; 80% are considered for antifibrotic therapy. The aim of this study was to assess whether response to antifibrotic therapy in IPF is correlated with the aforementioned categories. The presence of pleural plaques was also considered. <h3>Methods</h3> We retrospectively divided 170 patients into three categories: definite UIP pattern, possible UIP pattern, and UIP with pleural plaques. Serial pulmonary function test results were obtained and the change in FVC calculated. Treatment failure was defined as a change in FVC% predicted of &gt;10% per year. The rate of treatment failure, overall mortality, 6-month and 12-month survival was compared between the three groups. <h3>Results</h3> 116 patients out of 170 were started on antifibrotic therapy. The average duration of therapy was 256 days. There was a trend towards higher treatment failure in possible (n = 3 of 12 25%) versus definite UIP patterns (n = 6 of 55 11%), this was not statistically significant. Overall mortality rates were similar between possible and definite UIP patterns at 6- and 12-months (Figure 1). 5 patients with UIP and pleural plaques were started on therapy. <h3>Conclusions</h3> Mortality at 12 months was similar in possible UIP and UIP groups; there was a trend towards higher levels of treatment failure in patients with possible UIP. A different disease process may exist in some patients with possible UIP which is non-responsive to antifibrotic treatment. Numbers are relatively small and further observation is warranted. <h3>References</h3> King TE, <i>et al</i>. Idiopathic pulmonary fibrosis. <i>Lancet Elsevier</i> 2011;<b>378</b>(9807):1949–61. Raghu G, <i>et al</i>. An official ATS/ERS/JRS/ALAT statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. <i>AJRCCM</i> 2011;<b>183</b>(6):788–824.
Abstract B10: Synthetic lethal screen to identify novel therapies targeting TP53-mutant colon cancer cells
Authors: Charles C. Weige, Erin L. Anderson, Joseph Richardson, Carlo Contreras, Phillip J. Buckhaults
Journal: Clinical Cancer Research (2017)

Abstract We have performed a genome-wide synthetic lethal screen for pathways that are essential for the survival of colon cancer cells with TP53 mutations. RKO colon cancer cells are wild-type for TP53, and display robust p53-dependent growth arrest and apoptosis. We have utilized an isogenic pair of RKO cells differing only in TP53 gene status (Wild Type vs homozygous null derivative) to screen a genome-wide GeCKO CRISPR library and identified pathways that are novel therapeutic targets for TP53-mutant colon cancers. After infection of these cells with the GeCKO CRISPR library and one week of culturing in vitro, we performed deep GeCKO CRIPSR amplicon sequencing to enumerate and identify all CRISPRs that were underrepresented in TP53 mutant compared to wild type cells. We identified multiple CRISPRs targeting the CHEK1 and the SHH genes which were underrepresented in TP53 knockout cells. We then tested small molecule inhibitors of CHEK1 (UCN01) and the SHH receptor SMO (Cyclopamine) against isogenic pairs of RKO, HCT116, and DLD1 cells and confirmed that each molecule is significantly more toxic to cells with mutant TP53 than to those with wild-type TP53. Future studies will focus on testing these and additional targets alone and in combination against primary colon tumor and normal avatars, and preclinical models of TP53-mutant colon cancer. Citation Format: Charles C. Weige, Erin L. Anderson, Joseph Richardson, Carlo Contreras, Phillip J. Buckhaults. Synthetic lethal screen to identify novel therapies targeting TP53-mutant colon cancer cells. [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 B10.
P95 Exploring the timing of Hypertonic Saline (HTS) and Airways Clearance Techniques (ACT) in Cystic Fibrosis (CF): a cross over study
Authors: K O’Neill, F Moran, I Bradbury, DG Downey, J Rendall, MM Tunney, JS Elborn, JM Bradley
Journal: Thorax (2016)

<h3>Background</h3> Streamlining the timing of treatments in CF is important to optimise adherence whilst ensuring efficacy. The optimal timing of HTS and ACTs is unknown. <h3>Objectives</h3> This study hypothesised that ACTs after HTS would be more effective than ACTs during HTS as measured by lung clearance index (LCI). FEV1, sputum weight and patient perceptions were also compared. <h3>Methods</h3> Adults with CF providing written informed consent were randomised (between days 10–14 of intravenous antibiotic course during a pulmonary exacerbation) to a crossover trial of ACTs after HTS inhalation or ACTs during HTS inhalation on alternate days. ACT treatment consisted of 10 cycles of active cycle of breathing technique using an Acapella®. The physiotherapist collecting the outcome measures was blinded. Patients completed a Multiple Breath Washout (MBW) test to obtain LCI and spirometry at baseline and 90 mins post treatment. Sputum collection during 90 mins, ease of clearance and satisfaction with treatment was also recorded. Wilcoxon test was used and p &lt; 0.05 was considered significant. <h3>Results</h3> Fourteen subjects were recruited and 13 completed the study (mean [SD] age 33 [12], FEV1% predicted 51 [22], LCI (no. turnovers) 14 [4]). Comparing the 2 treatments (ACT after HTS vs ACT during HTS), the change from baseline to 90 mins post treatment in LCI (p = 0.71) and FEV1% predicted (p = 0.97) was not significant. There was also no difference in sputum weight expectorated (p = 0.17), patient perceived ease of clearance (p = 0.33) or satisfaction (p = 0.28). The time taken for ACT during HTS was significantly shorter (p = 0.001). <h3>Conclusions</h3> In this small study, ACTs after HTS was no more effective than ACTs during HTS.
Abstract A11: Therapeutic targeting of GCB- and ABC-DLBCLS by rationally designed BCL6 inhibitors
Authors: Mariano Gonzalo Cardenas, Wenbo Yu, Wendy Beguelin, Teater R. Matthew, Huimin Geng, Rebecca Goldstein, Erin Oswald, Katerina Hatzi, Shao-Ning Yang, Joanna Cohen, Rita Shaknovich, Kenno Vanommeslaeghe, Huimin Cheng, Dongdong Liang, Hyoje Cho, Joshua Abbott, Wayne Tam, John P. Leonard, Leandro Cerchietti, Tomasz Cierpicki, Fengtian Xue, Alexander D. MacKerell, Ari Melnick
Journal: Clinical Cancer Research (2017)

Abstract Rationale: The BCL6 oncogene is constitutively activated by chromosomal translocations and amplification in ABC-DLBCLs, a class of DLBCLs that respond poorly to current therapies. Yet the role of BCL6 in maintaining these lymphomas has not been investigated. BCL6 mediates its effects by recruiting corepressors to an extended groove motif. Development of effective BCL6 inhibitors requires compounds exceeding the binding affinity of these corepressors. Objectives: To design small molecule inhibitors with superior potency vs. endogenous BCL6 ligands for unmet putative therapeutic needs such as targeting ABC-DLBCL. Findings: We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor with 10-fold greater potency than endogenous corepressors. The compound, called FX1, binds in such a way as to occupy an essential region of the BCL6 lateral groove. FX1 disrupts BCL6 repression complex formation, reactivates BCL6 target genes, and mimics the phenotype of mice engineered to express BCL6 with lateral groove mutations. This compound eradicated established DLBCLs xenografts at low doses. Most strikingly, FX1 suppressed ABC-DLBCL cells as well as primary human ABC-DLBCL specimens ex vivo. Conclusions: ABC-DLBCL is a BCL6 dependent disease that can be targeted by novel inhibitors able to exceed the binding affinity of natural BCL6 ligands. Citation Format: Mariano Gonzalo Cardenas, Wenbo Yu, Wendy Beguelin, Teater R. Matthew, Huimin Geng, Rebecca Goldstein, Erin Oswald, Katerina Hatzi, Shao-Ning Yang, Joanna Cohen, Rita Shaknovich, Kenno Vanommeslaeghe, Huimin Cheng, Dongdong Liang, Hyoje Cho, Joshua Abbott, Wayne Tam, John P. Leonard, Leandro Cerchietti, Tomasz Cierpicki, Fengtian Xue, Alexander D. MacKerell, Jr., Ari Melnick. Therapeutic targeting of GCB- and ABC-DLBCLS by rationally designed BCL6 inhibitors. [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 A11.
P1.07-010 Influence of Creatinine Clearance on Survival Parameters in Small Cell Lung Cancer Treated with Cisplatin-Based Chemotherapy Regimen
Authors: Sedat Gözel, Ahmet Sumbul, Ali Murat Sedef, Ayberk Besen, Huseyin Mertsoylu, Celal Batmaci, Fatih Kose
Journal: Journal of Thoracic Oncology (2017)
Iinsulin Levels and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) May Explain a Possible Important Role of the Pancreas In Sickle Cell Disease Patients Outcome
Authors: Magda Seixas, Valma Lopes, Rodrigo Cezar, Gildasio Carvalho, Larissa Rocha, Isa Lyra, Mitermayer Reis, Marilda Goncalves
Journal: Blood (2010)
P272 Epidemiology of idiopathic pulmonary fibrosis in the uk: findings from the british lung foundation’s ‘respiratory health of the nation’ project
Authors: N Snell, D Strachan, R Hubbard, J Gibson, T Maher, I Jarrold
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> The last comprehensive survey of UK respiratory disease epidemiology was the British Thoracic Society's 2006 Burden of Lung Disease report. We performed an analysis covering 2004–2012. Findings pertaining to IPF are presented here. <h3>Methods</h3> Prevalence and incidence rates were estimated from a primary care database (the Health Intelligence Network) representing ∼5 per cent of the population, using a broad range of primary care codes considered to encompass the IPF definition. Mortality figures were derived from official government statistics. For international mortality comparisons and numbers of hospital admissions/inpatient bed-days we used WHO data. <h3>Results</h3> An estimated 32,500 people in the UK live with IPF, a prevalence rate of about 50/100,000. This is more than double NICE's 2015 estimate of 15–25 per 100,000. There are around 6,000 new cases diagnosed/year, greater than previous estimates of around 5,000. Overall, 5,300 people/year die from IPF, slightly more than the previous commonly accepted estimate of 5,000. There are nearly 9,000 admissions/year for IPF, accounting for around 1.3% of all admissions due to lung disease and 1.4% of all hospital bed days, despite IPF affecting less than 0.25% of people who have had a lung disease diagnosis. IPF is 50% more common in men, and killed 60% more men than women from 2008–2012. In this period 13,974 men and 8,624 women died from IPF, broadly in line with previous estimates. Incidence increases with age, around 85% of diagnoses being made in people aged over 70. Prevalence is highest in Northern Ireland, north-west England, Scotland and Wales. IPF is least common in London. Incidence is not influenced by measures of deprivation. <h3>Conclusions</h3> Although rare, IPF is considerably more common than previously recognised and represents a small but significant burden on NHS hospital services.
Living near major roads is associated with increased dementia risk, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

People living close to a major traffic road have a slightly higher risk of developing dementia than those living further away but show no higher incidence of Parkinson’s disease or multiple sclerosis, a large, population based cohort study has found.1

Dementia, Parkinson’s disease, and multiple sclerosis are the most common neurodegenerative diseases and are increasing as people live longer. The factors causing these conditions remain largely unknown, but studies have shown that exposure to air pollution and noise may …
P1.05-029 SABRTOOTH-A Feasibility Study of SABR Compared to Surgery in Patients with Peripheral Stage I NSCLC Considered to Be at Higher Risk from Surgery
Authors: Kevin Franks, Michael Snee, Babu Naidu, David Sebag-Monterfiore, Matthew Callister, Jonathan Ferguson, Richard Booton, Martyn Kennedy, Catherine Lowe, Fiona Collinson, Lucy Mcparland, Rachel Naylor, Jo Webster, Walter Gregory, Janine Bestall, Jenny Hewison, David Baldwin
Journal: Journal of Thoracic Oncology (2017)