tbuckley/cabot-search huggingface dataset:
Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy
Authors: Stefan Schmidt, Annett Linge, Alex Zwanenburg, Stefan Leger, Fabian Lohaus, Constanze Krenn, Steffen Appold, Volker Gudziol, Alexander Nowak, Cläre von Neubeck, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Hatice Bunea, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, David Mönnich, Daniel Zips, Gustavo B. Baretton, Frank Buchholz, Michael Baumann, Mechthild Krause, Steffen Löck
Journal: Clinical Cancer Research (2018)

Abstract Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms. Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3, and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2, and ACTN1. The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation (P &amp;lt; 0.001). Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364–74. ©2018 AACR.
More women at risk of infertility from medical treatment should be offered preservation techniques
Authors: Ingrid Torjesen
Journal: BMJ (2018)

Only a fraction of women and girls who could benefit from fertility preservation because of their medical treatment are being offered it, a specialist has said.

Melanie Davies, a ‎consultant obstetrician and gynaecologist at University College London Hospitals and clinical director of the National Institute for Health and Care Excellence’s women’s health guideline programme, said that every year a few thousand women and prepubescent girls undergo medical treatment that destroys or substantially reduces the chances that they can have children. But even though NICE recommends that people with cancer be offered cryopreservation if radiotherapy or chemotherapy is likely to affect their fertility,1 only a few hundred women a year receive it.

Davies was …
Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the Breast
Authors: Mintsje de Boer, Flora E. van Leeuwen, Michael Hauptmann, Lucy I. H. Overbeek, Jan Paul de Boer, Nathalie J. Hijmering, Arthur Sernee, Caroline A. H. Klazen, Marc B. I. Lobbes, René R. W. J. van der Hulst, Hinne A. Rakhorst, Daphne de Jong
Journal: JAMA Oncology (2018)

Breast implants are among the most commonly used medical devices. Since 2008, the number of women with breast implants diagnosed with anaplastic large-cell lymphoma in the breast (breast-ALCL) has increased, and several reports have suggested an association between breast implants and risk of breast-ALCL. However, relative and absolute risks of breast-ALCL in women with implants are still unknown, precluding evidence-based counseling about implants.To determine relative and absolute risks of breast-ALCL in women with breast implants.Through the population-based nationwide Dutch pathology registry we identified all patients diagnosed with primary non-Hodgkin lymphoma in the breast between 1990 and 2016 and retrieved clinical data, including breast implant status, from the treating physicians. We estimated the odds ratio (OR) of ALCL associated with breast implants in a case-control design, comparing implant prevalence between women with breast-ALCL and women with other types of breast lymphoma. Cumulative risk of breast-ALCL was derived from the age-specific prevalence of breast implants in Dutch women, estimated from an examination of 3000 chest x-rays and time trends from implant sales.Relative and absolute risks of breast-ALCL in women with breast implants.Among 43 patients with breast-ALCL (median age, 59 years), 32 had ipsilateral breast implants, compared with 1 among 146 women with other primary breast lymphomas (OR, 421.8; 95% CI, 52.6-3385.2). Implants among breast-ALCL cases were more often macrotextured (23 macrotextured of 28 total implants of known type, 82%) than expected (49 193 sold macrotextured implants of total sold 109 449 between 2010 and 2015, 45%) based on sales data (P < .001). The estimated prevalence of breast implants in women aged 20 to 70 years was 3.3%. Cumulative risks of breast-ALCL in women with implants were 29 per million at 50 years and 82 per million at 70 years. The number of women with implants needed to cause 1 breast-ALCL case before age 75 years was 6920.Breast implants are associated with increased risk of breast-ALCL, but the absolute risk remains small. Our results emphasize the need for increased awareness among the public, medical professionals, and regulatory bodies, promotion of alternative cosmetic procedures, and alertness to signs and symptoms of breast-ALCL in women with implants.
Trivalent flu vaccine won’t protect against influenza B strain predominantly circulating
Authors: Jacqui Wise
Journal: BMJ (2018)

Public Health England has warned that the trivalent flu vaccine most commonly administered in general practice will not protect against the strain of influenza B that appears to be predominately circulating this year. The latest figures show influenza is circulating at higher than seasonally expected levels, with increases in GP consultations and emergency department attendance.1

In the last week of 2017 there were 24 influenza deaths reported across the UK with 48 confirmed in the past three months, according to the latest monitoring figures. The overall GP consultation rate for influenza-like illness increased to 21 per 100 000 population, up from 18.9 in the week to 24 December. This is above the normal of 13.1 per 100 000 for this season. There were also increases in out-of-hours calls for influenza-like illness with …
Abstract #3559: A quantitative survey of tyrosine phosphorylation changes with erlotinib treatment in EGFR mutant and wildtype NSCLC cell lines
Authors: Warren Shih, Jiefei Tong, Paul Taylor, Akira Sakurada, Kevin Brown, Michael Moran, Ming-Sound Tsao
Journal: Cancer Research (2009)

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor that is frequently expressed in carcinoma. Erlotinib is a small molecule inhibitor of EGFR preventing the receptor9s autophosphorylation and downstream signaling. Erlotinib has been approved for second line treatment of advanced stage non-small-cell lung cancer (NSCLC) patients. NSCLC patients with mutations in the kinase domain of EGFR (L858R and exon 19 deletion) and/or EGFR gene amplifications demonstrate greater response rates and improved survival when treated by erlotinib. However, not all molecular factors that influence the clinical response to this drug are as yet identified. Greater understanding on how erlotinib influences EGFR induced cellular signaling in wild type or EGFR mutant/amplified NSCLC cells lines may provide insights on potential novel biomarkers for predicting response to erlotinib treatment, and/or novel downstream targets that may be developed against lung cancer that are resistant to erlotinib. A general quantitative survey of tyrosine phosphorylation comparing EGFR mutant, EGFR amplified wild type and EGFR low copy number wild-type NSCLC cell lines using tandem mass spectrometry (LTQ Orbitrap) was generated following erlotinib treatment, to probe differences in the impact of erlotinib on cellular phosphotyrosine targets in erlotinib-sensitive and erlotinib-resistant cell lines. Preliminary downstream effectors of erlotinib have been identified and quantified by analysis of high resolution extracted ion currents. A subset of these will be subject to validation and quantification in xenograft tumor models by using Selected Reaction Monitoring (SRM) with a triple quadrupole instrument (TSQ Quantum Ultra). (Supported by the Ontario Institute of Cancer Research Grant 07NOV-78)   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3559.
Multicentre prospective evaluation of real-time optical diagnosis of T1 colorectal cancer in large non-pedunculated colorectal polyps using narrow band imaging (the OPTICAL study)
Authors: Yara Backes, Matthijs P Schwartz, Frank ter Borg, Frank H J Wolfhagen, John N Groen, Wouter H de Vos tot Nederveen Cappel, Jeroen van Bergeijk, Joost M J Geesing, Bernhard W M Spanier, Paul Didden, Frank P Vleggaar, Miangela M Lacle, Sjoerd G Elias, Leon M G Moons
Journal: Gut (2018)

Objective This study evaluated the preresection accuracy of optical diagnosis of T1 colorectal cancer (CRC) in large non-pedunculated colorectal polyps (LNPCPs). Design In this multicentre prospective study, endoscopists predicted the histology during colonoscopy in consecutive patients with LNPCPs using a standardised procedure for optical assessment. The presence of morphological features assessed with white light, and vascular and surface pattern with narrow-band imaging (NBI) were recorded, together with the optical diagnosis, the confidence level of prediction and the recommended treatment. A risk score chart was developed and validated using a multivariable mixed effects binary logistic least absolute shrinkage and selection (LASSO) model. Results Among 343 LNPCPs, 47 cancers were found (36 T1 CRCs and 11 ≥T2 CRCs), of which 11 T1 CRCs were superficial invasive T1 CRCs (23.4% of all malignant polyps). Sensitivity and specificity for optical diagnosis of T1 CRC were 78.7% (95% CI 64.3 to 89.3) and 94.2% (95% CI 90.9 to 96.6), and 63.3% (95% CI 43.9 to 80.1) and 99.0% (95% CI 97.1 to 100.0) for optical diagnosis of endoscopically unresectable lesions (ie, ≥T1 CRC with deep invasion), respectively. A LASSO-derived model using white light and NBI features discriminated T1 CRCs from non-invasive polyps with a cross-validation area under the curve (AUC) of 0.85 (95% CI 0.80 to 0.90). This model was validated in a temporal validation set of 100 LNPCPs (AUC of 0.81; 95% CI 0.66 to 0.96). Conclusion Our study provides insights in the preresection accuracy of optical diagnosis of T1 CRC. Sensitivity is still limited, so further studies will show how the risk score chart could be improved and finally used for clinical decision making with regard to the type of endoresection to be used and whether to proceed to surgery instead of endoscopy. Trial registration number NTR5561.
Tax processed food to subsidise healthier options and tackle obesity, says think tank
Authors: Z. Kmietowicz
Journal: BMJ (2015)

The tendency for common processed foods such as crisps and biscuits to become cheaper over the past 30 years, while fruit and vegetables have become more expensive, is driving the obesity epidemic, a think tank has said. It recommends that governments consider introducing taxes on unhealthy foods and use these to subsidise other food groups.

The Overseas Development Institute, an independent think tank on international development and humanitarian issues, studied food prices in four countries—Brazil, China, Korea, and Mexico—and compared what was happening there to food prices changes in the United States and United Kingdom.

It found that in the newly rich countries fruit and …
Splicing variant of <i>WDFY4</i> augments MDA5 signalling and the risk of clinically amyopathic dermatomyositis
Authors: Yuta Kochi, Yoichiro Kamatani, Yuya Kondo, Akari Suzuki, Eiryo Kawakami, Ryosuke Hiwa, Yukihide Momozawa, Manabu Fujimoto, Masatoshi Jinnin, Yoshiya Tanaka, Takashi Kanda, Robert G Cooper, Hector Chinoy, Simon Rothwell, Janine A Lamb, Jiří Vencovský, Heřman Mann, Koichiro Ohmura, Keiko Myouzen, Kazuyoshi Ishigaki, Ran Nakashima, Yuji Hosono, Hiroto Tsuboi, Hidenaga Kawasumi, Yukiko Iwasaki, Hiroshi Kajiyama, Tetsuya Horita, Mariko Ogawa-Momohara, Akito Takamura, Shinichiro Tsunoda, Jun Shimizu, Keishi Fujio, Hirofumi Amano, Akio Mimori, Atsushi Kawakami, Hisanori Umehara, Tsutomu Takeuchi, Hajime Sano, Yoshinao Muro, Tatsuya Atsumi, Toshihide Mimura, Yasushi Kawaguchi, Tsuneyo Mimori, Atsushi Takahashi, Michiaki Kubo, Hitoshi Kohsaka, Takayuki Sumida, Kazuhiko Yamamoto
Journal: Annals of the Rheumatic Diseases (2018)

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases in which both genetic and environmental factors play important roles. To identify genetic factors of IIM including polymyositis, dermatomyositis (DM) and clinically amyopathic DM (CADM), we performed the first genome-wide association study for IIM in an Asian population.We genotyped and tested 496 819 single nucleotide polymorphism for association using 576 patients with IIM and 6270 control subjects. We also examined the causal mechanism of disease-associated variants by in silico analyses using publicly available data sets as well as by in in vitro analyses using reporter assays and apoptosis assays.We identified a variant in WDFY4 that was significantly associated with CADM (rs7919656; OR=3.87; P=1.5×10-8). This variant had a cis-splicing quantitative trait locus (QTL) effect for a truncated WDFY4isoform (tr-WDFY4), with higher expression in the risk allele. Transexpression QTL analysis of this variant showed a positive correlation with the expression of NF-κB associated genes. Furthermore, we demonstrated that both WDFY4 and tr-WDFY4 interacted with pattern recognition receptors such as TLR3, TLR4, TLR9 and MDA5 and augmented the NF-κB activation by these receptors. WDFY4 isoforms also enhanced MDA5-induced apoptosis to a greater extent in the tr-WDFY4-transfected cells.As CADM is characterised by the appearance of anti-MDA5 autoantibodies and severe lung inflammation, the WDFY4 variant may play a critical role in the pathogenesis of CADM.
ASP7266, a novel antibody against human TSLPR, in the treatment of allergic disease
Authors: Mako Numazaki, Kaori Hanaoka, Emiko Imamura, Masashi Maeda, Kazunori Arai, Tetsu Saito, Fujiko Takamura, Hiroshi Suzuki, Satoshi Kubo, Shigetada Furukawa
Journal: Journal of Allergy and Clinical Immunology (2018)
Comparison of Five Major Guidelines for Statin Use in Primary Prevention in a Contemporary General Population
Authors: Martin Bødtker Mortensen, Børge Grønne Nordestgaard
Journal: Annals of Internal Medicine (2018)

Background: Five major organizations recently published guidelines for using statins to prevent atherosclerotic cardiovascular disease (ASCVD): in 2013, the American College of Cardiology/American Heart Association (ACC/AHA); in 2014, the United Kingdom's National Institute for Health and Care Excellence (NICE); and in 2016, the Canadian Cardiovascular Society (CCS), the U.S. Preventive Services Task Force (USPSTF), and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS). Objective: To compare the utility of these guidelines for primary prevention of ASCVD. Design: Observational study of actual ASCVD events during 10 years, followed by a modeling study to estimate the effectiveness of different guidelines. Setting: The Copenhagen General Population Study. Participants: 45 750 Danish persons aged 40 to 75 years who did not use statins and did not have ASCVD at baseline. Measurements: The number of participants eligible to use statins according to each guideline and the estimated number of ASCVD events that statins could have prevented. Results: The percentage of participants eligible for statins was 44% by the CCS guideline, 42% by ACC/AHA, 40% by NICE, 31% by USPSTF, and 15% by ESC/EAS. The estimated percentage of ASCVD events that could have been prevented by using statins for 10 years was 34% for CCS, 34% for ACC/AHA, 32% for NICE, 27% for USPSTF, and 13% for ESC/EAS. Limitation: This study was limited to primary prevention in white Europeans. Conclusion: Guidelines recommending that more persons use statins for primary prevention of ASCVD should prevent more events than guidelines recommending use by fewer persons. Primary Funding Source: Copenhagen University Hospital.
Remembering Patient Gender in Sexual Orientation–Based Research
Authors: John R. Blosnich, M. Reuel Friedman, Ken Ho
Journal: JAMA Internal Medicine (2018)

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Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans
Authors: Thomas Gstrein, Andrew Edwards, Anna Přistoupilová, Ines Leca, Martin Breuss, Sandra Pilat-Carotta, Andi H. Hansen, Ratna Tripathy, Anna K. Traunbauer, Tobias Hochstoeger, Gavril Rosoklija, Marco Repic, Lukas Landler, Viktor Stránecký, Gerhard Dürnberger, Thomas M. Keane, Johannes Zuber, David J. Adams, Jonathan Flint, Tomas Honzik, Marta Gut, Sergi Beltran, Karl Mechtler, Elliott Sherr, Stanislav Kmoch, Ivo Gut, David A. Keays
Journal: Nature Neuroscience (2018)
Unstable Housing and Diabetes-Related Emergency Department Visits and Hospitalization: A Nationally Representative Study of Safety-Net Clinic Patients
Authors: Seth A. Berkowitz, Sara Kalkhoran, Samuel T. Edwards, Utibe R. Essien, Travis P. Baggett
Journal: Diabetes Care (2018)

OBJECTIVE Homelessness is associated with worse diabetes outcomes, but the relationship between other forms of unstable housing and diabetes is not well studied. We assessed whether unstable housing was associated with increased risk for diabetes-related emergency department use or hospitalization. RESEARCH DESIGN AND METHODS We used data from the 2014 Health Center Patient Survey (HCPS), a cross-sectional, nationally representative survey of patients who receive care at federally funded safety-net health centers. We included nonhomeless adults (aged ≥18 years) with self-reported diabetes. Unstable housing was defined as not having enough money to pay rent or mortgage, moving two or more times in the past 12 months, or staying at a place one does not own or rent. The primary outcome was self-report of diabetes-related emergency department visit or inpatient hospitalization in the last 12 months. We also examined use of housing assistance. RESULTS Of 1,087 participants, representing 3,277,165 adults with diabetes, 37% were unstably housed. Overall, 13.7% of participants reported a diabetes-related emergency department visit or hospitalization in the past year. In logistic regression analyses adjusted for multiple potential confounders, unstable housing was associated with greater odds of diabetes-related emergency department use or hospitalization (adjusted odds ratio 5.17 [95% CI 2.08–12.87]). Only 0.9% of unstably housed individuals reported receiving help with housing through their clinic. CONCLUSIONS Unstable housing is common and associated with increased risk of diabetes-related emergency department and inpatient use. Addressing unstable housing in clinical settings may help improve health care utilization for vulnerable individuals with diabetes.
CTL019 Model-Based Cellular Kinetic Analysis of Chimeric Antigen Receptor (CAR) T Cells to Characterize the Impact of Tocilizumab on Expansion and to Identify Correlates of Cytokine Release Syndrome Severity
Authors: Andrew M Stein, Stephan A Grupp, John E Levine, Theodore W Laetsch, Michael A Pulsipher, Michael W Boyer, Keith J August, Bruce L Levine, Carl H June, Lori Tomassian, Sweta Shah, Mimi Leung, Pai-Hsi Huang, Sebastien Jolivet, Rakesh Awasthi, Karen Thudium Mueller, Patricia A Wood, Shannon L Maude
Journal: Blood (2017)
Genomic Correlates of Response to Everolimus in Aggressive Radioiodine-refractory Thyroid Cancer: A Phase II Study
Authors: Glenn J. Hanna, Naifa L. Busaidy, Nicole G. Chau, Lori J. Wirth, Justine A. Barletta, Antonio Calles, Robert I. Haddad, Stefan Kraft, Maria E. Cabanillas, Guilherme Rabinowits, Anne O'Neill, Sewanti A. Limaye, Erik K. Alexander, Francis D. Moore, Krystof Misiwkeiwicz, Tom Thomas, Matthew Nehs, Ellen Marqusee, Stephanie L. Lee, Pasi A. Jänne, Jochen H. Lorch
Journal: Clinical Cancer Research (2018)

Purpose: Targeting mutations leading to PI3K/mTOR/Akt activation are of interest in thyroid cancer. We evaluated the efficacy of everolimus in aggressive, radioactive iodine-refractory (RAIR) thyroid cancer and correlated tumor mutational profiling with response. Exploratory medullary and anaplastic thyroid cancer cohorts were included.Experimental Design: This single-arm, multi-institutional phase II study was conducted from 2009 to 2013 in patients with incurable RAIR thyroid cancer who had radiographic progression six months prior to enrollment. The primary endpoint was progression-free survival (PFS) with a median follow-up of 31.8 months. The study is closed to enrollment but treatment and follow-up are ongoing. A targeted next-generation sequencing platform was used for mutational analysis.Results: Thirty-three patients with differentiated thyroid cancer (DTC), 10 with medullary thyroid cancer (MTC), and 7 with anaplastic thyroid cancer (ATC) enrolled. For the DTC cohort, median PFS was 12.9 months (95% CI, 7.3-18.5) with a 2-year PFS of 23.6% (95% CI, 10.5-39.5). Median OS was not reached; 2-year OS was 73.5% (95% CI, 53.8-85.8). Among ATC patients, 1 had a partial response and was progression-free until 17.9 months after study entry and one had disease stability for 26 months, respectively. The genomically profiled cohort enriched for PI3K/mTOR/Akt alterations. PI3K/mTOR/Akt-mutated ATC subgroups appeared to benefit from everolimus. Treatment-related adverse events were as anticipated.Conclusions: Everolimus has significant antitumor activity in thyroid cancer. While genomic profiling does not currently guide therapeutic selection in thyroid cancer patients, these data have important implications when considering the use of an mTOR inhibitor in an era of precision medicine. Clin Cancer Res; 24(7); 1546-53. ©2018 AACR.