tbuckley/cabot-search huggingface dataset:
Abstract P1-05-14: Copy number aberration-induced gene breakage analysis identifies recurrent <i>FOXP1</i> fusions in breast cancer
Authors: A Mohd Noor, S Maguire, J Watkins, J Quist, H Mirza, A Tutt, C Gillett, R Natrajan, A Grigoriadis
Journal: Cancer Research (2017)

Abstract Background: Genomic instability is a critical feature of breast cancers, which manifests in genome-wide copy number aberrations (CNA), often causing “gene breakage” and the generation of fusion genes. We aimed to identify aborted transcripts with underlying CNAs and to investigate the molecular landscape of breast cancers harbouring such events. Methods: A walking student's t-test algorithm was applied to Affymetrix Exon 1.0ST array data of 123 breast cancers to identify regions of aborted transcription and overlaid with DNA breakpoints derived from matched Affymetrix SNP6 ASCAT-segmented copy number. Aborted transcripts were investigated as potential fusion gene partners through RNA-seq analysis of 151 breast cancer samples (TCGA) and 51 breast cancer cell lines (BCCL) using ChimeraScan. Clinical correlates were established for clinicopathological features, genomic instability measures, and gene expression-based molecular classifiers including PAM50, TNBCtype, IntClust subtypes and immune signatures. Results: One hundred and six genes with recurrent CNA-induced aborted transcription were identified. Aborted transcription showed hormone receptor subtype-specificity for 7 genes (nTNBC=1, nNon-TNBC=6) and was less prevalent in samples of IntClust 2 and IntClust 4 subtypes (p: 0.0043, 0.0011). Aborted transcripts were more frequently observed in samples with greater copy-neutral loss of heterozygosity (p=0.012), while aborted transcription of 54/106 genes significantly affected enrichment of 27 tumor-infiltrating lymphocyte subpopulations.14 aborted transcripts were found as a fusion gene with one partner in RNA-seq of TCGA and BCCL, while 19 were involved in multiple fusion events (range=1-6, median=2). Nine of 106 genes displayed gene breakage and fusion events exclusively in samples with an enriched tandem duplication phenotype. Notably, FOXP1, localised to a tumour suppressor locus at 3p14.1, reported the highest number of fusion configurations (n=6) with concurrent aborted transcription across all RNA-seq datasets (nPRADA=9, nTCGA=38, nBCCL=6). Conclusion: CNA-induced gene breakage affects the molecular landscape of breast cancers and is linked with many genomic configurations of interest including copy-neutral loss of heterozygosity and tandem duplications. In particular, the role of recurrent gene fusions of the tumour suppressor, FOXP1, in tumourigenesis warrants further investigation. Citation Format: Mohd Noor A, Maguire S, Watkins J, Quist J, Mirza H, Tutt A, Gillett C, Natrajan R, Grigoriadis A. Copy number aberration-induced gene breakage analysis identifies recurrent FOXP1 fusions in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-14.
Obesity in pregnancy is related to higher rates of cerebral palsy, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Women who are overweight or obese in early pregnancy are more likely to have a child with cerebral palsy than women of normal weight, a large Swedish cohort study published in JAMA has shown.

Despite advances in obstetric and neonatal care in recent years, the prevalence of cerebral palsy in children born at full term has risen. Although preterm delivery is a risk factor, most children with cerebral palsy are born at full term, and the …
A CD47xCD19 Bispecific Antibody That Remodels the Tumor Microenvironment for Improved Killing and Provokes a Memory Immune Response to Cancer B Cells
Authors: Walter G. Ferlin, Xavier Chauchet, Vanessa Buatois, Susana Salgado-Pires, Limin Shang, Elie Dheilly, Krzysztof Masternak, Zoë Johnson, John F DiPersio, Julie Ritchey, Linda Eissenberg, Marie H. Kosco-Vilbois, Nicolas Fischer
Journal: Blood (2016)
Retraction Note: Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu
Authors: Vasundhara Varthakavi, Ellen Heimann-Nichols, Rita M Smith, Yuehui Sun, Richard J Bram, Showkat Ali, Jeremy Rose, Lingmei Ding, Paul Spearman
Journal: Nature Medicine (2010)
Enforced Expression of Pax-5 Results in Developmental Arrest, Immortalisation and Aberrant Expression of B Lineage Genes in Committed Myeloid Progenitors.
Authors: Kristina Anderson, Corinne Rusterholz, Robert Mansson, Christina Jensen, Karl Bacos, Yutaka Sasaki, Mikael Sigvardsson, Sten Eirik W. Jacobsen
Journal: Blood (2004)
Ditching the Itch with Anti–Type 2 Cytokine Therapies for Atopic Dermatitis
Authors: Lynda C. Schneider
Journal: New England Journal of Medicine (2017)

Atopic dermatitis is a chronic inflammatory disease characterized by intense pruritus and dry, inflamed skin. An impaired skin barrier and a dysregulated immune response to a variety of triggers are key factors in the complex pathophysiological mechanism of this disease. The predominant early immunologic response in atopic dermatitis includes type 2 helper T (Th2) cells, innate lymphoid cells, and keratinocytes that produce the type 2 cytokines, such as thymic stromal lymphopoietin (TSLP, a major promoter of atopy) and interleukins 4, 13, and 31.1 Interleukins 4 and 13 and TSLP inhibit the differentiation of keratinocytes and thereby reduce the production of . . .
Adherence to capecitabine in preoperative treatment of stage II and III rectal cancer: do we need to worry?
Authors: R. Font, J.A. Espinas, L. Layos, M. Martinez Villacampa, J. Capdevila, M. Tobeña, A. Pisa, C. Pericay, C. Lezcano, E. Fort, I. Cardona, N. Berga, J. Solà, J.M. Borras
Journal: Annals of Oncology (2017)
Vav1, a Rho GTPase Guanine Exchange Factor (GEF) Is Required to Integrate gp130 Cytokine Signaling for Successful Engraftment of Murine Hematopoietic Stem Cells Following Irradiation
Authors: Serena De Vita, Yanhua Li, Chad Everett Harris, Meaghan McGuinness, David A. Williams
Journal: Blood (2016)
Imatinib Discontinuation Following a Major Molecular Response: Impact of Interferon Alpha and Leukemia Stem Cell Burden (The STOP Study).
Authors: Perttu Koskenvesa, Satu Mustjoki, Anu Räsänen, Mirja Vapaatalo, Kari Remes, Tuija Lundán, Jukka Vakkila, Bengt Simonsson, Kimmo Porkka
Journal: Blood (2008)
Breast Cancer Risk Reduction Clinical Practice Guidelines in Oncology
Journal: Journal of the National Comprehensive Cancer Network (2003)

Breast cancer risk factor analysis allows the identification of women at very high risk for the future development of breast cancer. Many of the known risk factors are either not modifiable or are not reasonably modifiable because of social implications or other potential health benefits (eg, those associated with hormone replacement therapy). Thus, effective strategies to decrease the risk of breast cancer are needed. The recent demonstration that the use of tamoxifen for 5 years decreases the future risk of breast cancer by approximately 49% provides the opportunity for a risk-reduction intervention. Women taking tamoxifen must be monitored for the occurrence of well-defined toxicities, including hot flashes and, more rarely, endometrial carcinoma, thromboembolic disease, and cataract formation. Strategies are available for the management of tamoxifen toxicity. In special circumstances, such as in carriers of BRCA1 or BRCA2 mutations, the risk of future breast cancer is very high, and the performance of a bilateral prophylactic mastectomy may be considered. Women considering bilateral prophylactic mastectomy should undergo multidisciplinary consultation so that they may make a fully informed decision. The panel strongly encourages patients and health care providers to participate in clinical trials to test new strategies for decreasing the risk of breast cancer. Only through the accumulated experience gained from well-designed, prospective clinical trials will additional advances in the reduction of breast cancer risk be realized.
Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery
Authors: Süleyman Bilecen, Joris A. H. de Groot, Cor J. Kalkman, Alexander J. Spanjersberg, George J. Brandon Bravo Bruinsma, Karel G. M. Moons, Arno P. Nierich
Journal: JAMA (2017)

<h3>Importance</h3> Fibrinogen concentrate might partly restore coagulation defects and reduce intraoperative bleeding. <h3>Objective</h3> To determine whether fibrinogen concentrate infusion dosed to achieve a plasma fibrinogen level of 2.5 g/L in high-risk cardiac surgery patients with intraoperative bleeding reduces intraoperative blood loss. <h3>Design, Setting, and Participants</h3> A randomized, placebo-controlled, double-blind clinical trial conducted in Isala Zwolle, the Netherlands (February 2011-January 2015), involving patients undergoing elective, high-risk cardiac surgery (ie, combined coronary artery bypass graft [CABG] surgery and valve repair or replacement surgery, the replacement of multiple valves, aortic root reconstruction, or reconstruction of the ascending aorta or aortic arch) with intraoperative bleeding (blood volume between 60 and 250 mL suctioned from the thoracic cavity in a period of 5 minutes) were randomized to receive either fibrinogen concentrate or placebo. <h3>Interventions</h3> Intravenous, single-dose administration of fibrinogen concentrate (n = 60) or placebo (n = 60), targeted to achieve a postinfusion plasma fibrinogen level of 2.5 g/L. <h3>Main Outcomes and Measures</h3> The primary outcome was blood loss in milliliters between intervention (ie, after removal of cardiopulmonary bypass) and closure of chest. Safety variables (within 30 days) included: in-hospital mortality, myocardial infarction, cerebrovascular accident or transient ischemic attack, renal insufficiency or failure, venous thromboembolism, pulmonary embolism, and operative complications. <h3>Results</h3> Among 120 patients (mean age; 71 [SD, 10] years, 37 women [31%]) included in the study, combined CABG and valve repair or replacement surgery comprised 72% of procedures and had a mean (SD) cardiopulmonary bypass time of 200 minutes (83) minutes. For the primary outcome, median blood loss in the fibrinogen group was 50 mL (interquartile range [IQR], 29-100 mL) compared with 70 mL (IQR, 33-145 mL) in the control group (<i>P</i> = .19), the absolute difference 20 mL (95% CI, −13 to 35 mL). There were 6 cases of stroke or transient ischemic attack (4 in the fibrinogen group); 4 myocardial infarctions (3 in the fibrinogen group); 2 deaths (both in the fibrinogen group); 5 cases with renal insufficiency or failure (3 in the fibrinogen group); and 9 cases with reoperative thoracotomy (4 in the fibrinogen group). <h3>Conclusions and Relevance</h3> Among patients with intraoperative bleeding during high-risk cardiac surgery, administration of fibrinogen concentrate, compared with placebo, resulted in no significant difference in the amount of intraoperative blood loss. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01124981and EudraCT No:2009-018086-12
R.I.S.C.L: A Holistic Molecular Diagnostic Tool for Myeloid Malignancies
Authors: Thomas D McKerrell, Ignacio Varela, Nicolo Bolli, Postingl Hannes, Zemin Ning, German Tischler, Anthony Bench, Bridget Manasse, Joanna Baxter, Jorge Sierra, Dora Foukaneli, Allan Warren, Vincenza Colona, Chris Tyler-Smith, Brian Huntly, Josep F. Nomdedeu, Mike Scott, George Vassiliou
Journal: Blood (2014)
Anti-Tumor Phagocytic Cell Activation in Multiple Myeloma By the IAP Antagonist LCL161: Results of a Phase II Clinical Trial
Authors: P. Leif Bergsagel, Martha Q. Lacy, David Dingli, Shaji K. Kumar, Sikander Ailawadhi, Angela Dispenzieri, Francis Buadi, Morie A. Gertz, A. Keith Stewart, Craig B. Reeder, Heidi E. Kosiorek, Amylou C. Dueck, Yi Lin, Asher Alban Chanan-Khan, Marta Chesi
Journal: Blood (2015)
Small-Molecule Stabilization of 14-3-3 Protein-Protein Interactions Stimulates Axon Regeneration
Authors: Andrew Kaplan, Barbara Morquette, Antje Kroner, SooYuen Leong, Carolin Madwar, Ricardo Sanz, Sara L. Banerjee, Jack Antel, Nicolas Bisson, Samuel David, Alyson E. Fournier
Journal: Neuron (2017)
Spk-9001: Adeno-Associated Virus Mediated Gene Transfer for Hemophilia B Achieves Sustained Mean Factor IX Activity Levels of &gt;30% without Immunosuppression
Authors: Lindsey A. George, Spencer K. Sullivan, Adam Giermasz, Jonathan M. Ducore, Jerome M. Teitel, Adam Cuker, Lisa M. Sullivan, Suvankar Majumdar, Catherine E. McGuinn, Aline M. Galvao, Alvin Y. Luk, J. Fraser Wright, Yifeng Chen, Daniel J. Hui, Katie Wachtel, Teresa Urich, Daniel Takefman, Linda B. Couto, Marcus E. Carr, Xavier M. Anguela, Katherine A. High
Journal: Blood (2016)
Pharmacokinetic and Safety of CT-P10, a Biosimilar Candidate to the Rituximab Reference Product, in Patients with Newly Diagnosed Advanced Stage Follicular Lymphoma (AFL)
Authors: Bertrand Coiffier, Juan-Manuel Sancho, Wojciech Jurczak, Jin Seok Kim, Raj V Nagarkar, Edvard Zhavrid, Jose Angel Hernandez Rivas, Aliaksandr Prokharau, Mamia Zodelava, Dzhelil Osmanov, Michinori Ogura, Christian Buske, Larry Kwak, Sang Joon Lee, Sung Young Lee, Yun Ju Bae, Won Seog Kim
Journal: Blood (2016)
Default of cancer treatment association with psychological distress and desire for psychological support.
Authors: Caryn Mei-Hsien Chan, Wan Azman Wan Ahmad, Mastura Md Yusof, Gwo Fuang Ho, Edward Krupat
Journal: Journal of Clinical Oncology (2014)

9567 Background: Default of treatment is highly prevalent among cancer patients, with delayed or incomplete treatment shown to result in worse clinical outcomes such as treatment resistance, disease progression as well as poorer survival. Our objective was to identify psychosocial variables and characteristics associated with cancer default. We hypothesized that cancer patients who are psychologically distressed are more likely to: (a) refuse, delay or discontinue cancer treatment and routine patient follow up, and (b) decline offers for psychological support. Methods: This study is part of a larger prospective study assessing the psychosocial needs of patients with cancer. A total of 467 consecutive adult cancer patients attending scheduled oncology follow-ups at a single academic medical centre completed the Hospital Anxiety and Depression Scale and reported their preference for psychological support at baseline, 4-6 weeks and 12-18 months follow-up. Default was defined as refusal, delay or discontinuation of treatment or visit, despite the ability to do so. Results: A total of 159 of 467 (34.0%) cancer patients were defaulters. Of these 159 defaulters, 89 (55.9%) desired psychological support, compared to only 13 (4.22%) of 308 non-defaulters. Although not associated with each other, desire for psychological support and psychological distress were the only variables found to be significantly associated with default of appointment or cancer treatment using a chi-square and a repeated-measures ANCOVA at p = 0.001 and p = 0.015 respectively. No other remarkable differences between defaulters and non-defaulters were discerned. Conclusions: To date there are few published studies on rates of default among adult oncology patients. Our results show that defaulters had higher psychological distress but greater desire for support compared to non-defaulters. Patients who refuse cancer treatment initially should be offered psychological support, with their desire for treatment re-evaluated later on. Patients may be more willing to accept cancer treatment if desirous of and given psychological support. This in turn could potentially increase treatment acceptance rates and improve survival.
Detection of early subclinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarised gas MRI
Authors: Helen Marshall, Alex Horsley, Chris J Taylor, Laurie Smith, David Hughes, Felix C Horn, Andrew J Swift, Juan Parra-Robles, Paul J Hughes, Graham Norquay, Neil J Stewart, Guilhem J Collier, Dawn Teare, Steve Cunningham, Ina Aldag, Jim M Wild
Journal: Thorax (2017)

Hyperpolarised <sup>3</sup>He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6–16 years) with clinically stable mild cystic fibrosis (CF) (FEV<sub>1</sub>&gt;−1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure–function relationships.
Education and coronary heart disease: mendelian randomisation study
Authors: Taavi Tillmann, Julien Vaucher, Aysu Okbay, Hynek Pikhart, Anne Peasey, Ruzena Kubinova, Andrzej Pajak, Abdonas Tamosiunas, Sofia Malyutina, Fernando Pires Hartwig, Krista Fischer, Giovanni Veronesi, Tom Palmer, Jack Bowden, George Davey Smith, Martin Bobak, Michael V Holmes
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To determine whether educational attainment is a causal risk factor in the development of coronary heart disease. <b>Design</b>&nbsp;Mendelian randomisation study, using genetic data as proxies for education to minimise confounding. <b>Setting</b>&nbsp;The main analysis used genetic data from two large consortia (CARDIoGRAMplusC4D and SSGAC), comprising 112 studies from predominantly high income countries. Findings from mendelian randomisation analyses were then compared against results from traditional observational studies (164 170 participants). Finally, genetic data from six additional consortia were analysed to investigate whether longer education can causally alter the common cardiovascular risk factors. <b>Participants</b>&nbsp;The main analysis was of 543 733 men and women (from CARDIoGRAMplusC4D and SSGAC), predominantly of European origin. <b>Exposure</b>&nbsp;A one standard deviation increase in the genetic predisposition towards higher education (3.6 years of additional schooling), measured by 162 genetic variants that have been previously associated with education. <b>Main outcome measure</b>&nbsp;Combined fatal and non-fatal coronary heart disease (63 746 events in CARDIoGRAMplusC4D). <b>Results</b>&nbsp;Genetic predisposition towards 3.6 years of additional education was associated with a one third lower risk of coronary heart disease (odds ratio 0.67, 95% confidence interval 0.59 to 0.77; P=3×10<sup>−8</sup>). This was comparable to findings from traditional observational studies (prevalence odds ratio 0.73, 0.68 to 0.78; incidence odds ratio 0.80, 0.76 to 0.83). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely, although this remains an untestable possibility. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index, and a favourable blood lipid profile. <b>Conclusions</b>&nbsp;This mendelian randomisation study found support for the hypothesis that low education is a causal risk factor in the development of coronary heart disease. Potential mechanisms could include smoking, body mass index, and blood lipids. In conjunction with the results from studies with other designs, these findings suggest that increasing education may result in substantial health benefits.
Erratum: Functionally defined therapeutic targets in diffuse intrinsic pontine glioma
Authors: Catherine S Grasso, Yujie Tang, Nathalene Truffaux, Noah E Berlow, Lining Liu, Marie-Anne Debily, Michael J Quist, Lara E Davis, Elaine C Huang, Pamelyn J Woo, Anitha Ponnuswami, Spenser Chen, Tessa B Johung, Wenchao Sun, Mari Kogiso, Yuchen Du, Lin Qi, Yulun Huang, Marianne Hütt-Cabezas, Katherine E Warren, Ludivine Le Dret, Paul S Meltzer, Hua Mao, Martha Quezado, Dannis G van Vuurden, Jinu Abraham, Maryam Fouladi, Matthew N Svalina, Nicholas Wang, Cynthia Hawkins, Javad Nazarian, Marta M Alonso, Eric H Raabe, Esther Hulleman, Paul T Spellman, Xiao-Nan Li, Charles Keller, Ranadip Pal, Jacques Grill, Michelle Monje
Journal: Nature Medicine (2015)
Epstein Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes (CTL) Expressing an Anti-CD30 Chimeric T Cell Receptor (CTCR) for the Treatment of Hodgkin’s Disease (HD).
Authors: B. Savoldo, C. M. Rooney, H. E. Heslop, H. Abken, A. Hombach, L. Zhang, M. Pule, G. Dotti, M. K. Brenner
Journal: Blood (2004)
Hydroxychloroquine Diminishes Lymphoproliferation in the Fas Deficient MRL/lpr−/− Murine Model of Autoimmune Lymphoproliferative Syndrome (ALPS).
Authors: Kennichi C. Dowdell, Lesley Pesnicak, Lilia Bi, Victoria Hoffmann, V. Koneti Rao, Stephen E. Straus
Journal: Blood (2007)
Physical examination of the elbow, what is the evidence? A systematic literature review
Authors: Elisa L Zwerus, Matthijs P Somford, François Maissan, Jelle Heisen, Denise Eygendaal, Michel PJ van den Bekerom
Journal: British Journal of Sports Medicine (2017)

Primary to provide an overview of diagnostic accuracy for clinical tests for common elbow (sport) injuries, secondary accompanied by reproducible instructions to perform these tests.A systematic literature review according to the PRISMA statement.A comprehensive literature search was performed in MEDLINE via PubMed and EMBASE.We included studies reporting diagnostic accuracy and a description on the performance for elbow tests, targeting the following conditions: distal biceps rupture, triceps rupture, posteromedial impingement, medial collateral ligament (MCL) insufficiency, posterolateral rotatory instability (PLRI), lateral epicondylitis and medial epicondylitis. After identifying the articles, the methodological quality was assessed using the QUADAS-2 checklist.Our primary literature search yielded 1144 hits. After assessment 10 articles were included: six for distal biceps rupture, one for MCL insufficiency, two for PLRI and one for lateral epicondylitis. No articles were selected for triceps rupture, posteromedial impingement and medial epicondylitis. Quality assessment showed high or unclear risk of bias in nine studies. We described 24 test procedures of which 14 tests contained data on diagnostic accuracy.Numerous clinical tests for the elbow were described in literature, seldom accompanied with data on diagnostic accuracy. None of the described tests can provide adequate certainty to rule in or rule out a disease based on sufficient diagnostic accuracy.
Tyrosine Kinase Inhibitor Imatinib Mesylate Induces Generalized Skin Hypopigmentation In Chinese Patients with Chronic Myelogenous Leukemia.
Authors: Yingjia Wang, Yanmin Zhao, Lizhen Liu, Weijie Cao, Kangni Wu, Longyan Chen, Xiaohong Yu, He Huang
Journal: Blood (2010)
Comparison of Prognostic Factors and Outcomes of Patients with Secondary Acute Myeloid Leukemia (AML) Following Myelodysplastic Syndromes (MDS), Myeloproliferative Disorders (MPD), or Therapy-Related AML (t-AML).
Authors: Sanjay Mohan, Paul Elson, Cristina Rodriguez, Rachid Baz, Matt Kalaycio, Ronald Sobecks, Anjali Advani, Jaroslaw P. Maciejewski, Edward Copelan, Mikkael A. Sekeres
Journal: Blood (2007)
Abstract P6-12-16: Delivery and anti-tumor activity of nanoliposomal irinotecan (Nal-IRI, MM-398) in metastatic xenograft models of triple negative breast cancer
Authors: H Lee, M Ventura, N Bernards, AS Mohammad, W Foltz, J Fitzgerald, DA Jaffray, PR Lockman, J Zheng, BS Hendriks
Journal: Cancer Research (2017)

Abstract This abstract was not presented at the symposium.