tbuckley/cabot-search huggingface dataset:
Knowledge of risk factors and modes of gene transmission among women at risk for hereditary breast and ovarian cancer syndrome.
Authors: M. C. Katapodi, S. L. DeFlon, K. J. Milliron, L. L. Northouse, S. Merajver
Journal: Journal of Clinical Oncology (2011)

e12017 Background: Hereditary Breast and Ovarian Cancer (HBOC) is a collective term used to describe genetic susceptibility to breast and/or ovarian cancer. Most HBOC cases are attributed to BRCA1 and BRCA2 genes (BRCA1/2). Once a case of HBOC is identified, the risk of carrying a BRCA1/2 mutation and its implications extends to family members. This study examined whether female relatives from HBOC families can identify risk factors associated with HBOC and modes of BRCA1/2 gene transmission. Methods: This quantitative, descriptive, cross-sectional study assessed frequencies of correct responses to 19 items assessing knowledge of HBOC risk factors and 17 items assessing knowledge of modes of gene inheritance. All items have been previously validated. The sample consisted of 172 women, who based on pedigree analysis had >10% of carrying an-HBOC predisposing genetic mutation, but had NOT pursued genetic testing. Results: The majority of items assissing risk factors associated with HBOC were correcty identified by more than 50% of respondents. Sporadic occurence of breast cancer was correctly identified by 95% of the sample. Of the 17 items assessing knowledge of gene mutation transmission, 2 items were correctly identified by 87% of participants: that inherited and non-inherited mutations can cause cancer, and that genetic testing cannot predict risk of developing cancer. Approximately 50% knew that men can pass on a BRCA1/2 mutation to their children, and correctly identified all family history signs indicative of a mutation-harboring family. Fewer women (<35%) correctly identified the numeric probabilities of developing HBOC and of passing on a BRCA1/2 mutation to offspring. Conclusions: Educational interventions are needed to educate women at risk for HBOC. Identifying appropriate information dissemination information strategies to target these women should be a priority for healthcare providers. These strategies should also focus on encouraging communication among women at high risk for HBOC and their family members.
P2.03b-050 Prognostic Value of HLA-A2 Status in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients
Authors: Laura Mezquita, Melinda Charrier, Laura Faivre, Jordi Remon, David Planchard, Maria Bluthgen, Louise Dupraz, Francesco Facchinetti, Jihene Lahmar, Annas Gazzah, Jean-Charles Soria, Jean Pierre Pignon, Nathalie Chaput, Benjamin Besse
Journal: Journal of Thoracic Oncology (2017)
Philadelphia Chromosome-Positive Leukemia Patients Who Harbor Imatinib-Resistant Mutations Have a Higher Likelihood of Developing Additional Mutations Associated with Resistance to Novel Tyrosine Kinase Inhibitors.
Authors: Simona Soverini, Alessandra Gnani, Sabrina Colarossi, Fausto Castagnetti, Francesca Palandri, Panagiota Giannoulia, Stefania Paolini, Elisabetta Abruzzese, Serena Merante, Michela Rondoni, Ilaria Iacobucci, Angela Poerio, Gianantonio Rosti, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2007)
The clinicopathologic characteristics of kidney diseases related to monotypic IgA deposits
Authors: Marguerite Vignon, Camille Cohen, Stanislas Faguer, Laure-Hélène Noel, Celine Guilbeau, Marion Rabant, Sarah Higgins, Aurélie Hummel, Alexandre Hertig, Hélène Francois, Moglie Lequintrec, Eve Vilaine, Bertrand Knebelmann, Jacques Pourrat, Dominique Chauveau, Jean-Michel Goujon, Vincent Javaugue, Guy Touchard, Khalil El Karoui, Frank Bridoux
Journal: Kidney International (2017)
P148 Making sense of patient-reported currently treated asthma using routinely collected data
Authors: MA Al Sallakh, SE Rodgers, RA Lyons, A Sheikh, GA Davies
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Currently treated asthma (CTA) is commonly assessed in epidemiological studies and is typically self-reported. We investigated how patient understanding of this label compared with objective measures extracted from routinely collected data. <h3>Methods</h3> We used the Welsh Health Survey 2014 results for individuals aged 16+. Self-reported CTA was measured with the question: “Are you currently being treated for asthma?” We included those who had valid responses, are record-linked to the Secure Anonymised Information Linkage databank, and had complete GP practice registrations between 2009 and 2014. From the GP dataset, we queried their most recent prescriptions, if any, and whether they had ever recorded asthma diagnosis, and cross-tabulated these variables with self-reported CTA. We examined the concordance between self-reported CTA and each of ‘ever prescriptions’, ‘ever diagnosis’, and ‘having prescriptions in varying backward intervals from mid-2014’, with the latter repeated by adding ‘ever diagnosis’. <h3>Results</h3> Of 4,291 eligible people, 10.2% self-reported CTA but, of these, 11.2% had no prescriptions in the past 12 months and 22.4% had no recorded asthma diagnosis ever. Figure 1A shows full intersections between the variables. For concordance between self-reported CTA and each of ‘ever prescriptions’ and ‘ever diagnosis’, Cohen’s kappa was 0.42 and 0.68, respectively. For concordance between self-reported CTA and ‘prescriptions in backward intervals’, kappa was 0.76 for the 12-month interval but peaked to 0.77 at 9-months. After adding ‘ever diagnosis’, the kappa became 0.78 for the 12-month measure (which represents the treated asthma criteria of the Quality of Outcomes Framework, QOF), and peaked to 0.79 at 18-months (Figure 1B). <h3>Conclusion</h3> In Wales, self-reported currently treated asthma showed good concordance with the QOF treated asthma criteria but a slightly better concordance with ‘any prescriptions in the last 18 months and ever diagnosis’ measured from routine GP data. However, the concordance remains suboptimal, demonstrating that self-reported CTA should be used with caution, and objective measures from routinely collected health data are preferred.
How Low Should We Go With Blood Pressure?
Authors: Paolo Verdecchia, Fabio Angeli, Gianpaolo Reboldi
Journal: Circulation Research (2017)

ViewpointsT raditional blood pressure (BP) measurement has made its time.We should familiarize ourselves with automated unattended BP measurements.This method will virtually eliminate the BP rise associated with the presence of doctors or even nurses.Using such a protocol in patients who meet the SPRINT (Systolic Blood Pressure Intervention Trial) inclusion/exclusion criteria, a blood pressure target of ≤120 mm Hg will lead to an important reduction in the risk of stroke and heart attack.The SPRINT (Systolic Blood Pressure Intervention Trial), ClinicalTrials.govnumber, NCT01206062, funded by the National Institutes of Health, is a landmark trial that, for the reasons outlined below, is expected to change our clinical approach to the management of hypertensive patient. 1 The authors of this article believe that SPRINT significantly contributed to the progress of cardiovascular medicine although some implications of the study need to be assessed judiciously.To substantiate our opinion that BP goals should be reassessed lower after SPRINT, we will try to briefly summarize what SPRINT shows, what it confirms, and what it adds to existing knowledge. How Low Should We Go With Blood Pressure?
Cost Effectiveness of Treatments after Failure of a First-Line Hypomethylating Agent in Myelodysplastic Syndromes (MDS)
Authors: Christopher R. Cogle, Sudipto Mukherjee, Moira E. Lawrence, Thomas J. McKearn, Rita Percy, Michael E. Petrone, Scott Megaffin, Ayanna M Anene, Jesse Ortendahl, Dorothy Romanus, Tanya GK Bentley
Journal: Blood (2014)
Studies on the Transport Mechanism of Sulfonamide Compounds in Renal Tubules : Stopflow Analysis Applied to the Excretion of Sulfonamide Compounds
Authors: Minoru Sugita, Ko Sugita, Toshiyuki Furukawa, Hiroshi Abe
Journal: Circulation (1967)

1) Tubular transport of sulfonamide compound occurs in a bidirectional manner; that is, both unconjugated and acetylated sulfonamide compound are secreted in the proximal segment and reabsorbed in the distal segment of the kidneys. The site of sulfonamide compound secretion is approximately identical with that of PSP or PAH secretion and the site of reabsorption lies between the sites of Na reabsorption and K secretion. 2) It is suggested that sulfonamide compounds are actively secreted in the proximal segment, and that for distal reabsorption an active transport and a partly diffusion mechanism are involved.
The Importance of Molecular Phenotype in Predicting Overall Survival in Patients with Relapsed or Primary Refractory DLBCL Treated with Second-Line Chemotherapy and ASCT.
Authors: Craig H. Moskowitz, Tarun Kewalramani, Paul Hamlin, Stephen D. Nimer, Andrew D. Zelenetz, Julie Teruya-Feldstein
Journal: Blood (2004)
OA16.05 Socioeconomic Determinants of Late Diagnosis of Lung Cancer in France: A Nationwide Study (the TERRITOIRE Study)
Authors: Pierre Jean Souquet, Isabelle Durand-Zaleski, Christos Chouaid, Didier Debieuvre, Arnaud Scherpereel, Jérôme Fernandes, Virginie Westeel, Cécile Blein, Anne-Françoise Gaudin, Soline Leblanc, Hervé Lemasson, Nicolas Ozan, François-Emery Cotté, Pierre Chauvin
Journal: Journal of Thoracic Oncology (2017)
OA10.03 YAP-NOTCH and STAT3 Signaling Rebound as a Compensatory Response to Gefitinib or Osimertinib Treatment in EGFR Mutant Lung Cancer
Authors: Rafael Rosell, Imane Chaib, Niki Karachaliou, Peng Cao, Miguel Angel Molina Vila, Xueting Cai, Ana Drozdowskyj, Jie Yang, Chunping Hu, Andrés Cardona, Alex Frías, Chiara Lazzari, Alberto Verlicchi, Jordi Codony Servat, Carles Codony Servat, José Luis Ramírez Serrano, Alain Vergnenegre, Patrick Ma, Trever Bivona
Journal: Journal of Thoracic Oncology (2017)
Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells
Authors: Ahmed Katsha, Lihong Wang, Janet Arras, Omar M. Omar, Jeffrey Ecsedy, Abbes Belkhiri, Wael El-Rifai
Journal: Clinical Cancer Research (2017)

Purpose: Aurora kinase A (AURKA) is overexpressed in several cancer types, making it an attractive druggable target in clinical trials. In this study, we investigated the role of AURKA in regulating EIF4E, cap-dependent translation, and resistance to mTOR inhibitor, RAD001 (everolimus).Experimental Design: Tumor xenografts and in vitro cell models of upper gastrointestinal adenocarcinomas (UGC) were used to determine the role of AURKA in the activation of EIF4E and cap-dependent translation. Overexpression, knockdown, and pharmacologic inhibition of AURKA were used in vitro and in vivoResults: Using in vitro cell models, we found that high protein levels of AURKA mediate phosphorylation of EIF4E and upregulation of c-MYC. Notably, we detected overexpression of endogenous AURKA in everolimus-resistant UGC cell models. AURKA mediated phosphorylation of EIF4E, activation of cap-dependent translation, and an increase in c-MYC protein levels. Targeting AURKA using genetic knockdown or a small-molecule inhibitor, alisertib, reversed these molecular events, leading to a decrease in cancer cell survival in acquired and intrinsic resistant cell models. Mechanistic studies demonstrated that AURKA binds to and inactivates protein phosphatase 2A, a negative regulator of EIF4E, leading to phosphorylation and activation of EIF4E in an AKT-, ERK1/2-, and mTOR-independent manner. Data from tumor xenograft mouse models confirmed that everolimus-resistant cancer cells are sensitive to alisertib.Conclusions: Our results indicate that AURKA plays an important role in the activation of EIF4E and cap-dependent translation. Targeting the AURKA-EIF4E-c-MYC axis using alisertib is a novel therapeutic strategy that can be applicable for everolimus-resistant tumors and/or subgroups of cancers that show overexpression of AURKA and activation of EIF4E and c-MYC. Clin Cancer Res; 23(14); 3756-68. ©2017 AACR.
P171 Health inequality exists in pirfenidone prescription for idiopathic pulmonary fibrosis in the english midlands according to patient location
Authors: FA Woodhead, S Townsend, D Desai
Journal: Thorax (2016)

<h3>Background</h3> Pirfenidone is approved in England by NICE for the treatment of Idiopathic Pulmonary Fibrosis (IPF) but its prescription is limited to certain specialised centres. We hypothesised that this may lead to health inequality in the access to the drug per head of population in an area of the Midlands <h3>Methods</h3> 2 prescribing centres (PC), and 4 non-prescribing centres(NPC) referring into them were studied. They were the George Eliot Hospital (GEH) in Nuneaton and South Warwick FT (SWFT) in Warwick (both NPCs) referring to University Hospitals of Coventry &amp; Warwickshire (UHCW) in Coventry, and Kettering General Hospital (KGH) and Northampton General Hospital (NGH), (both NPCs) referring to Glenfield Hospital, University Hospitals of Leicester (UHL). The number of patients prescribed pirfenidone up to January 2016 was collected, and corrected per 100,000 head of population according to the patient postcode from 2011 census data. All patients were from the CV,LE or NN postcode areas. As data were not normally distributed, analysis was performed with non-parametric statistics using ‘R’, a statistics package. We collected the time and distance of travel to patients’ local hospital, and to their PC. <h3>Results</h3> There were a total of 64 postcode areas (PCAs) in the region. Travel times to local hospitals (either a PC or NPC according to area) were normally distibuted with a median of 19 minutes (range 5–40). Travel time to relevant PC was bimodally distributed, with a median of 26 ½ minutes (range 5–64). This was significantly different (p,1*10^−7). There were no pirfenidone patients in 20 PCAs. Where patients’ local hospital was a NPS there were significantly more pirfenidone-free PCAs (15/32) than where the local hospital was a PC (5/32), p = 0.015. Median number of pirfenidone patients per 100,000 population was significantly less (2.18) where the local hospital was a NPC than where the local hospital was a PC (4.76), p = 0.019. There were also significant differences across all 6 hospitals in the median prevalence of pirfenidone prescriptions (p = 0.003). <h3>Conclusions</h3> Our data suggest there are significant health inequality in access to pirfenidone according to patients’ location and whether their local hospital is a PC or not.
Proposal of Progressive Adult Onset EBV-Associated Lymphoproliferative Disorder (PAEBV) as a Rapid-Onset Neoplastic Disease.
Authors: Rie Hyo, Yasunobu Abe, Kisato Nosaka, Kyoko Taniguchi, Rika Sakai, Nobuhiko Noda, Michihide Shimono, Kazutaka Sunami, Noriko Usui, Koichi Ohshima, Ritsuro Suzuki
Journal: Blood (2009)
P186 Incidence and outcome of congenital lung agenesis in the north of england
Authors: N Robertson, N Miller, J Rankin, M McKean, M Brodlie, M Thomas
Journal: Thorax (2016)

<h3>Introduction</h3> Congenital lung agenesis is a rare abnormality which has been reported to have an estimated incidence of 1 in 15,000 pregnancies and to carry a poor prognosis, especially when associated with congenital heart anomalies. (1) However, precise incidence data has previously been unavailable and clinical management has improved in recent years with an unknown impact on outcomes. <h3>Methods</h3> We used the North of England register of congenital anomalies (NorCAS) cross-referenced with clinical data from our regional paediatric respiratory centre to calculate the first known accurate incidence estimate for this condition. Detailed clinical and outcome data were then collected with informed consent from the families of affected infants. <h3>Results</h3> The incidence of lung agenesis was 0.12 per 100,000 live births (95% confidence interval 0.03–0.31). Four cases were identified with a median age at follow-up of 5 years. Lung agenesis was associated with complex congenital heart disease (complete atrioventricular septal defect with left atrial isomerism) in one case, and with aortic coarctation and atrial septal defect in another. Both these patients had their heart defects successfully repaired. The third patient had a normal heart but musculoskeletal problems, while lung agenesis was the only anomaly in the fourth patient. All four patients are well and not on home oxygen. <h3>Conclusions</h3> We reviewed the course of the four patients with lung agenesis born in the region between 2004 and 2013, and report that medium term outcomes have been good, even when associated with congenital heart disease and other anomalies. This information will provide a useful starting point when counselling parents whose unborn baby has an antenatal diagnosis of lung agenesis. We aim to follow-up these patients to report long-term outcomes as these remain unknown and there is concern about the potential for the development of late onset pulmonary hypertension.<sup>1</sup> <h3>Reference</h3> Muensterer O, Abellar R, Otterburn D, <i>et al</i>. Pulmonary agenesis and associated pulmonary hypertension: A case report and review on variability, therapy, and outcome. <i>Eur J Pediatr Surg Rep</i> 2015;<b>3</b>:33–9.
PTBP1 Interacts with PKM2 in an NPM-ALK-Dependent Manner and Contributes to the Pathogenesis of Anaplastic Large Cell Lymphoma (ALCL)
Authors: Johnvesly Basappa, Steven R Hwang, Scott RP McDonnell, Venkatesh Basrur, Carlos Murga-Zamalloa, Kojo S.J. Elenitoba-Johnson, Megan S Lim
Journal: Blood (2014)
Elevated Endothelial Progenitor Cells during Painful Sickle Cell Crisis
Authors: Erfan Nur, Rachel T. van Beem, Jaap Jan Zwaginga, Precious Landburg, Eduard J. van Beers, Ashley Duits, John-John Schnog, Ingrid Lommerse, C. Ellen Van der Schoot, Hetty C. de Boer, Dees P.M. Brandjes, Bart J. Biemond
Journal: Blood (2008)
Platelet and Red Blood Cell (RBC) Transfusion Requirements of Nonmyeloablative (NM) HLA-Matched Related and Unrelated Donor Hematopoietic Cell Transplantation (HCT): Influence of Genetic Disparity and ABO-Incompatibility.
Authors: Zejing Wang, Gary Schoch, Wendy M. Leisenring, Brenda M. Sandmaier, David G. Maloney, Rainer F. Storb
Journal: Blood (2006)
P190 Characteristics and outcome of patients with active tuberculosis requiring intensive care admission, 2010–2015
Authors: NM Shah, S Patel, K Myall, H Milburn, RA Breen
Journal: Thorax (2016)

<h3>Introduction</h3> Severe tuberculosis (TB) infection requiring admission to the intensive care unit (ICU) has been reported to be associated with a poor prognosis; however, no data on this cohort of patients from the UK is available. We sought to characterise and report the outcome of this patient group, looking to identify prognostic markers of a poor outcome. <h3>Methods</h3> All patients admitted to the ICU at our London tertiary referral centre between 01/01/10 and 31/12/15 and coded as having TB were identified and cross-referenced against the London TB register. <h3>Results</h3> 29 patients were identified which represents 4% (29/790) of all TB notified at our centre in the study period. Median age was 41 years (22–86); 72% were male. 69% had pulmonary TB; 24% were HIV-infected, with a median CD4 count on admission of 134/uL (17–277). 14% were AFB smear-positive; 79% had culture-positive TB and 86% grew fully-sensitive organisms. The most frequent indications for ICU admission were hypoxic respiratory failure (38%), haemodynamic compromise (24%) and hypercapnic respiratory failure (21%). Median A-a gradient was 12.9 kPa, median PaO<sub>2</sub>/FiO<sub>2</sub> ratio was 29.9 kPa. 72% required mechanical ventilation (median ventilation days 8.4). Two patients received extracorporeal membrane oxygenation therapy for severe respiratory failure. Median APACHE II score was 16 and median SOFA score was 4. Median length of stay in ICU was 7 days and in hospital was 24. At 30 days, 35% remained in-patients (of which 14% remained in ICU), 59% had been discharged home and 21% had died. Table 1 summarises the differences between survivors and those who died. <h3>Conclusion</h3> In our TB population, the requirement for ICU care was infrequent, with respiratory failure being the most common indication. ICU and overall hospital length of stay was prolonged, but with a majority of patients surviving to discharge. Possible markers of a poor outcome include age, and a requirement for cardiovascular/renal support. These markers and TB-related factors now need to be explored in a larger cohort.
Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of Transgenes in Differentiated Cells of All Germ Layers
Authors: So Gun Hong, Ravi Chandra Yada, Kyujoo Choi, Arnaud Carpentier, T. Jake Liang, Randall K. Merling, Colin L. Sweeney, Harry L. Malech, Moonjung Jung, Marcus A.F. Corat, Aisha A. AlJanahi, Yongshun Lin, Huimin Liu, Ilker Tunc, Xujing Wang, Maryknoll Palisoc, Stefania Pittaluga, Manfred Boehm, Thomas Winkler, Jizhong Zou, Cynthia E. Dunbar
Journal: Molecular Therapy (2017)

Nonhuman primate (NHP) induced pluripotent stem cells (iPSCs) offer the opportunity to investigate the safety, feasibility, and efficacy of proposed iPSC-derived cellular delivery in clinically relevant in vivo models. However, there is need for stable, robust, and safe labeling methods for NHP iPSCs and their differentiated lineages to study survival, proliferation, tissue integration, and biodistribution following transplantation. Here we investigate the utility of the adeno-associated virus integration site 1 (AAVS1) as a safe harbor for the addition of transgenes in our rhesus macaque iPSC (RhiPSC) model. A clinically relevant marker gene, human truncated CD19 (hΔCD19), or GFP was inserted into the AAVS1 site in RhiPSCs using the CRISPR/Cas9 system. Genetically modified RhiPSCs maintained normal karyotype and pluripotency, and these clones were able to further differentiate into all three germ layers in vitro and in vivo. In contrast to transgene delivery using randomly integrating viral vectors, AAVS1 targeting allowed stable transgene expression following differentiation. Off-target mutations were observed in some edited clones, highlighting the importance of careful characterization of these cells prior to downstream applications. Genetically marked RhiPSCs will be useful to further advance clinically relevant models for iPSC-based cell therapies.Graphical abstract
P3.02c-046 Safety, Clinical Activity and Biomarker Results from a Phase Ib Study of Erlotinib plus Atezolizumab in Advanced NSCLC
Authors: Charles Rudin, Andrés Cervantes, Afshin Dowlati, Benjamin Besse, Brigette Ma, Daniel Costa, Peter Schmid, Rebecca Heist, Victoria Villaflor, Indrani Sarkar, Mahrukh Huseni, Paul Foster, Carol O'Hear, Scott Gettinger
Journal: Journal of Thoracic Oncology (2017)
IGF Signaling Is Critical for Growth and Survival of T-Cell Acute Lymphoblastic Leukemia Cells and Is Potentiated by Notch Upregulation of IGF1R
Authors: Hind Medyouf, Samuel Gusscott, Carol Wai, Marcus Leung, Florence Armstrong, Francoise Pflumio, Michael Pollak, Andrew P. Weng
Journal: Blood (2008)
Prevalence and Prognostic Impact of RUNX1 Mutations In Patients with Acute Myeloid Leukemia (AML): A Study In 1649 Patients Registered In the AML96 Protocol of the DSIL/SAL
Authors: Katharina Gerstenberger, Christoph Röllig, Markus Schaich, Thomas Illmer, Uwe Platzbecker, Martin Bornhäuser, Gerhard Ehninger, Christian Thiede
Journal: Blood (2010)
OA13.06 Autologous Dendritic Cells Loaded with Allogeneic Tumor Cell Lysate (Pheralys®) in Patients with Mesothelioma: Final Results of a Phase I Study
Authors: Joachim Aerts, Robin Cornelissen, Cor Van Der Leest, Joost Hegmans, Koen Bezemer, Margaretha Kaijen-Lambers, Ferry Eskens, Eric Braakman, Bronno Van Der Holt, Rudi Hendriks, Henk Hoogsteden
Journal: Journal of Thoracic Oncology (2017)
Single Nucleotide Polymorphisms Influence the Phenotype of Mutations P618A and R1336W found in the ADAMTS13 Gene of Congenital TTP Patients.
Authors: Barbara Plaimauer, Gabriele Mohr, Waltraud Wernhart, Katharina Bruno, Gerhard Antoine, Manfred Rieger, Friedrich Scheiflinger
Journal: Blood (2004)