tbuckley/cabot-search huggingface dataset:
IL-13Rα2 signals via MAPK pathways in intestinal epithelial cells and modulates IL-13Rα1 signaling through STAT6
Authors: Debasmita Mandal, Alan Levine
Journal: Cancer Research (2008)

5095   Patients with colonic inflammatory bowel disease (IBD), most particularly ulcerative colitis (UC), are at increased risk for developing colorectal cancer (CRC), which multiplies with disease duration: there is a 2% incidence of CRC after 10, a 9% after 20, and 19% after 30 years. The initiating trigger of a UC-associated tumor is unknown. Our research is focused on immunological mediators that may promote epithelial cell oncogenesis in IBD-associated cancer.  We previously reported low-grade dysplasia in colitic mice manifests after increased mucosal expression of IL-13 is detected. Inhibition of IL-13 activity late in colitis partially reverses inflammation and prevents dysplasia. In addition IL-13 expression by intestinal lamina propria NK T cells from elderly UC, but not control, patients is elevated. We therefore hypothesize that continual exposure to IL-13 in the inflamed colon may advance the onset of colitis-associated CRC.  As demonstrated by both flow cytometric and immunoblotting techniques expression of IL-13 receptor chains (IL-13Rα1 and IL-13Rα2) is increased in the epithelium from UC patients and CRC lesions consistent with a possible role for IL-13 in UC-associated CRC in the former situation and in CRC in general for the latter. In addition, we discovered using phospho-specific immunoblotting, epithelial cells from control tissue and non-UC inflammatory lesions expressing lower levels of IL-13Rα2 respond to IL-13 through a signaling pathway that involves ERK 1/2 JNK and p38 along with the canonical STAT6 pathway. However, in epithelial cells from UC lesions and colonic tumors IL-13 does not activate the STAT6 pathway. As these cells express higher levels of IL-13Rα2, we hypothesized that high IL-13Rα2 expression inhibits IL-13 signaling. To test this, signaling through IL-13Rα1 in a colonic epithelial cell line expressing low amounts of IL-13Rα2 was inhibited with a neutralizing antibody. IL-13 induced phosphorylation of ERK 1/2, JNK and p38 but not STAT6, indicating that IL-13Rα2 (considered as non-signaling chain) plays a role in signaling through the former but not the latter pathways. Consistent with our findings in patient’s samples, when IL-13Rα2 expression is increased in this same cell line, IL-13 signaling through STAT6 is inhibited and through MAPK enhanced. Contrary to current belief we conclude that IL-13Rα2 is not a decoy receptor, but instead increased expression of this chain in UC and CRC lesions biases the epithelial cell’s response toward enhanced MAPK signaling, which support increased cell cycle progression among other cellular processes, potentially contributing to unregulated cell growth. Our findings lead to a hypothesis that lower amount of IL-13Rα2 might heterodimerize with another unknown chain to signal through MAPK and higher density of IL-13Rα2 homodimerizes to block its own signaling and also signaling through IL-13Rα1.
Abstract 2865: Short Term Results of the Convergent Endo-Epicardial Ablation Procedure for the Treatment of Long Standing Persistent Atrial Fibrillation
Authors: Shane Bailey, Luigi Di Biase, Andy Kiser, Rodney Horton, Borut Gersak, Mark Landers, Andrew Hume, Majaz Sinkovec, Andrej Pernat, Andrea Natale
Journal: Circulation (2009)
Prognostic Model for Stratification of Radioresistant Nasopharynx Carcinoma to Curative Salvage Radiotherapy
Authors: You Quan Li, Yun Ming Tian, Sze Huey Tan, Ming Zhu Liu, Grace Kusumawidjaja, Enya H.W. Ong, Chong Zhao, Terence W.K. Tan, Kam Weng Fong, Kiattisa Sommat, Yoke Lim Soong, Joseph T.S. Wee, Fei Han, Melvin L.K. Chua
Journal: Journal of Clinical Oncology (2018)

Purpose To investigate for a prognostic index (PI) to personalize recommendations for salvage intensity-modulated radiotherapy (IMRT) in patients with locally recurrent nasopharyngeal carcinoma (lrNPC). Methods Patients with lrNPC from two academic institutions (Sun Yat-Sen University Cancer Center [SYSUCC-A; n = 251 (training cohort)] and National Cancer Centre Singapore [NCCS; n = 114] and SYSUCC-B [n = 193 (validation cohorts)]) underwent salvage treatment with IMRT from 2001 to 2015. Primary and secondary clinical end points were overall survival (OS) and grade 5 toxicity-free rate (G5-TFR), respectively. Covariate inclusion to the PIs was qualified by a multivariable two-sided P < .05. Discrimination and calibration of the PIs were assessed. Results The primary PI comprised covariates that were adversely associated with OS in the training cohort (gross tumor volumerecurrence hazard ratio [HR], 1.01/mL increase [ P < .001], agerecurrence HR, 1.02/year increase [ P = .008]; repeat IMRT equivalent dose in 2-Gy fractions [EQD2] ≥ 68 Gy HR, 1.42 [ P = .03]; prior radiotherapy-induced grade ≥ 3 toxicities HR, 1.90 [ P = .001]; recurrent tumor [rT]-category 3 to 4 HR, 1.96 [ P = .005]), in ascending order of weight. Discrimination of the PI for OS was comparable between training and both validation cohorts (Harrell's C = 0.71 [SYSUCC-A], 0.72 [NCCS], and 0.69 [SYSUCC-B]); discretization by using a fixed PI score cutoff of 252 determined from the training data set yielded low- and high-risk subgroups with disparate OS in the validation cohorts (NCCS HR, 3.09 [95% CI, 1.95 to 4.89]; SYSUCC-B HR, 3.80 [95% CI, 2.55 to 5.66]). Our five-factor PI predicted OS and G5-TFR (predicted v observed 36-month OS and G5-TFR, 22% v 15% and 38% v 44% for high-risk NCCS and 26% v 31% and 45% v 46% for high-risk SYSUCC-B). Conclusion We present a validated PI for robust clinical stratification of radioresistant NPC. Low-risk patients represent ideal candidates for curative repeat IMRT, whereas novel clinical trials are needed in the unfavorable high-risk subgroup.
α-Actinin Anchors PSD-95 at Postsynaptic Sites
Authors: Lucas Matt, Karam Kim, Anne C. Hergarden, Tommaso Patriarchi, Zulfiqar A. Malik, Deborah K. Park, Dhrubajyoti Chowdhury, Olivia R. Buonarati, Peter B. Henderson, Çiğdem Gökçek Saraç, Yonghong Zhang, Durga Mohapatra, Mary C. Horne, James B. Ames, Johannes W. Hell
Journal: Neuron (2018)
Natural language processing (NLP) software use in the discovery of incidental lung cancers.
Authors: Melissa Lynne Johnson, Brook E. Blakemore, Tammy M. Baxter, Javed Ashiq, Sharon P. Moore, Priscilla G. Smith, Dawn Michelle Stults, Howard A. Burris, David R. Spigel
Journal: Journal of Clinical Oncology (2016)

1559 Background: Low-dose computer tomography (LDCT) screening for individuals at high risk for developing lung cancer has led to earlier detection of suspicious nodules, rapid diagnosis, and a reduction in deaths due to lung cancer. Unfortunately, the majority of lung cancers are diagnosed at advanced stages where most patients will still die from their disease. We conducted a pilot study to evaluate whether chest CT scans performed routinely during emergency room (ER) visits for general medical conditions could be used to identify patients with incidental lung cancers. Methods: NLP software was used to review all CT scans obtained in 3 community-based hospital ERs in Nashville, TN and Dallas, TX from October, 2014 through December, 2015. All CT radiology reports containing key words such as: ‘nodule’, ‘opacity’, or ‘mass’ were identified by NLP software and collected by nurse navigators. Corresponding images were then reviewed by cancer center multi-disciplinary tumor boards (MDTB). Repeat imaging or biopsy was recommended based on National Comprehensive Cancer Network (NCCN) guidelines. Results: NLP software identified 1212 CT scans for MDTB review, which led to 64 biopsies (5% of NLP-identified cases). There were 37 cancer diagnoses (3% of NLP-identified cases) -26 (70%) lung cancers and 11 (30%) other cancers (including: head and neck, lymphoma, sarcoma, hepatic, breast, pancreatic, and gynecologic). Among the diagnosed lung cancers, 7 (27%) were early stage (TNM I or II) and were surgically treated for potential cure. Conclusions: The use of NLP software to review CT scans performed during routine ER encounters led to early diagnosis and successful treatment of patients whose cancers might otherwise have gone undetected until potentially much later. This pilot study is expanding to include multiple community hospitals across additional markets.
Psychological interventions used to reduce sports injuries: a systematic review of real-world effectiveness
Authors: Adam Gledhill, Dale Forsdyke, Eliot Murray
Journal: British Journal of Sports Medicine (2018)

Objective To systematically review studies examining the role of psychological interventions in injury prevention. The primary research question was: What is the real-world effectiveness of psychological intervention in preventing sports injuries? Design Mixed methods systematic review with best evidence synthesis. Data sources CINAHL, MEDLINE, PsycARTICLES, PsycINFO, SPORTDiscus, Science Direct and PubMed. Eligibility criteria for selecting studies Randomised controlled trials (RCT), non-RCTs that included a comparison group, before and after study designs and qualitative methods. Studies were required to outline specific unimodal or multimodal psychological interventions used in relation to injury prevention in the real-world setting. Outcome measure Studies were independently appraised with the Mixed Methods Appraisal Tool. Results Thirteen papers (incorporating 14 studies) met the eligibility criteria, of which 93% (13/14) reported a decrease in injury rates (effect size range=0.2–1.21). There was an overall moderate risk of bias in reporting (52%). There is a dominance of stress management-based interventions in literature due to the prominence of the model of stress and athletic injury within the area. Summary/conclusions Psychological interventions demonstrate small (0.2) to large (1.21) effects on sports injury rates. The research area demonstrates a cumulative moderate risk in reporting bias (52%). PROSPERO registration number CRD42016035879.
Who Is a Better Donor for Recipients of Allogeneic Hematopoietic Cell Transplantation: A Young HLA- Haploidenitcal Relative or an Older Fully HLA-Matched Sibling or Unrelated Volunteer?
Authors: Melhem M Solh, Xu Zhang, Scott R Solomon, Lawrence E Morris, H. Kent Holland, Asad Bashey
Journal: Blood (2017)
Abstract 12022: LinkCPR Improves the Quality of Hands-only CPR Performed by Laypersons Following the 2015 AHA Guidelines
Authors: Zhengfei Yang, Jinwu Chen, Tao Yu, Mary Ann Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2016)

Introduction: The AHA 2015 Resuscitation Guidelines changed the guidelines for chest compression (CC) rate and depth. Manikin studies have demonstrated that feedback/prompt systems improve the quality of CPR. On the other hand, LinkCPR (SunLife, China) is a newly designed feedback/promt device that can provide the real-time CC depth, rate, chest recoil feedback and data review. In this study, we investigated the effects of LinkCPR on the quality of CCs during hands-only CPR performed by laypersons based on the 2015 AHA guidelines. Hypothesis: LinkCPR improves the quality of CCs performed by laypersons. Methods: Eighty laypersons were assigned randomly to perform CPR on manikins with (Link group) or without (C group) LinkCPR. Participants underwent manual CPR training and took a written basic life support examination; they were then required to perform two min of hands-only CPR. The quality of CPR was quantified as the percentage of correct CCs (appropriate depth, rate, and complete recoil) each minute. Results: Thirty-nine participants in the Link group and 37 participants in the C group completed the study. There were no significant differences in gender and body mass index between groups. Reductions in the mean depth of CCs and proportion of correct CCs after the first minute of CPR were observed in both groups. However, significantly better performance was achieved by rescuers in the Link group when compared with those in C group during each of the 2 minute CPR periods (Table). Conclusion: LinkCPR improves the quality of hands-only CPR performed by laypersons following the standards of the 2015 AHA guidelines.
INSaFLU: an automated open web-based bioinformatics suite “from-reads” for influenza whole-genome-sequencing-based surveillance
Authors: Vítor Borges, Miguel Pinheiro, Pedro Pechirra, Raquel Guiomar, João Paulo Gomes
Journal: Genome Medicine (2018)

A new era of flu surveillance has already started based on the genetic characterization and exploration of influenza virus evolution at whole-genome scale. Although this has been prioritized by national and international health authorities, the demanded technological transition to whole-genome sequencing (WGS)-based flu surveillance has been particularly delayed by the lack of bioinformatics infrastructures and/or expertise to deal with primary next-generation sequencing (NGS) data. We developed and implemented INSaFLU (“INSide the FLU”), which is the first influenza-oriented bioinformatics free web-based suite that deals with primary NGS data (reads) towards the automatic generation of the output data that are actually the core first-line “genetic requests” for effective and timely influenza laboratory surveillance (e.g., type and sub-type, gene and whole-genome consensus sequences, variants’ annotation, alignments and phylogenetic trees). By handling NGS data collected from any amplicon-based schema, the implemented pipeline enables any laboratory to perform multi-step software intensive analyses in a user-friendly manner without previous advanced training in bioinformatics. INSaFLU gives access to user-restricted sample databases and projects management, being a transparent and flexible tool specifically designed to automatically update project outputs as more samples are uploaded. Data integration is thus cumulative and scalable, fitting the need for a continuous epidemiological surveillance during the flu epidemics. Multiple outputs are provided in nomenclature-stable and standardized formats that can be explored in situ or through multiple compatible downstream applications for fine-tuned data analysis. This platform additionally flags samples as “putative mixed infections” if the population admixture enrolls influenza viruses with clearly distinct genetic backgrounds, and enriches the traditional “consensus-based” influenza genetic characterization with relevant data on influenza sub-population diversification through a depth analysis of intra-patient minor variants. This dual approach is expected to strengthen our ability not only to detect the emergence of antigenic and drug resistance variants but also to decode alternative pathways of influenza evolution and to unveil intricate routes of transmission. In summary, INSaFLU supplies public health laboratories and influenza researchers with an open “one size fits all” framework, potentiating the operationalization of a harmonized multi-country WGS-based surveillance for influenza virus. INSaFLU can be accessed through https://insaflu.insa.pt .
Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study
Authors: Christina Orasch, Dominik Mertz, Jorge Garbino, Christian van Delden, Stephane Emonet, Jacques Schrenzel, Stefan Zimmerli, Lauro Damonti, Konrad Mühlethaler, Alexander Imhof, Christian Ruef, Jan Fehr, Reinhard Zbinden, Katia Boggian, Thomas Bruderer, Ursula Flückiger, Anna Conen, Nina Khanna, Reno Frei, Thomas Bregenzer, Frédéric Lamoth, Véronique Erard, Pierre-Yves Bochud, Thierry Calandra, Jacques Bille, Oscar Marchetti, Thomas Bregenzer, Anna Conen, Ursula Flückiger, Nina Khanna, Christina Orasch, Ulrich Heininger, Mario Franciolli, Lauro Damonti, Stefan Zimmerli, Madeleine Rothen, Claudine Zellweger, Madeleine Rothen, Philipp Tarr, Felix Fleisch, Christian Chuard, Véronique Erard, Stéphane Emonet, Jorge Garbino, Christian van Delden, Daniel Genne, Pierre-Yves Bochud, Thierry Calandra, Lauro Damonti, Véronique Erard, Frédéric Lamoth, Oscar Marchetti, Christina Orasch, Jean-Philippe Chave, Peter Graber, Rita Monotti, Enos Bernasconi, Marco Rossi, Martin Krause, Rein-Jan Piso, Frank Bally, Nicolas Troillet, Katia Boggian, Gerhard Eich, Jacques Gubler, Jan Fehr, Alexander Imhof, Christian Ruef, Gerhard Eich, Jacques Gubler, Christoph Berger, Hans Fankhauser, Ivo Heinzer, Reno Frei, Roland Hertel, Marisa Dolina, Orlando Petrini, Olivier Dubuis, Konrad Mühlethaler, Suzanne Graf, Martin Risch, Eva Ritzler, Dominique Fracheboud, Peter Rohner, Jacques Schrenzel, Reto Lienhardt, Jacques Bille, Frédéric Lamoth, Corinne Andreutti-Zaugg, Alberto Gallusser, Suzanne Graf, Gaby Pfyffer, Karin Herzog, Urs Schibli, Lysiane Tissière, Thomas Bruderer, Detlev Schultze, Reinhard Zbinden
Journal: Journal of Infection (2018)
Passive immunotherapy of viral infections: 'super-antibodies' enter the fray
Authors: Laura M. Walker, Dennis R. Burton
Journal: Nature reviews. Immunology (2018)

Antibodies have been used for more than 100 years in the therapy of infectious diseases, but a new generation of highly potent and/or broadly cross-reactive human monoclonal antibodies (sometimes referred to as 'super-antibodies') offers new opportunities for intervention. The isolation of these antibodies, most of which are rarely induced in human infections, has primarily been achieved by large-scale screening for suitable donors and new single B cell approaches to human monoclonal antibody generation. Engineering the antibodies to improve half-life and effector functions has further augmented their in vivo activity in some cases. Super-antibodies offer promise for the prophylaxis and therapy of infections with a range of viruses, including those that are highly antigenically variable and those that are newly emerging or that have pandemic potential. The next few years will be decisive in the realization of the promise of super-antibodies.
Mechanisms of <i>NT5C2</i> mutations Driving Thiopurine Resistance in Acute Lymphoblastic Leukemia
Authors: Chelsea Dieck, Gannie Tzoneva, Farhad Forouhar, Zachary Carpenter, Alberto Ambesi-Impiombato, Marta Sanchez-Martin, Liang Tong, Adolfo A. Ferrando
Journal: Blood (2017)
Harnessing genomics to improve outcomes for women with cancer in India: key priorities for research
Authors: Sudha Sundar, Poonam Khetrapal-Singh, Jon Frampton, Edward Trimble, Preetha Rajaraman, Ravi Mehrotra, Roopa Hariprasad, Arindam Maitra, Paramjit Gill, Vanita Suri, Radhika Srinivasan, Gurpreet Singh, J S Thakur, Preet Dhillon, Jean-Baptiste Cazier
Journal: The Lancet Oncology (2018)
High erythrocyte levels of the n-6 polyunsaturated fatty acid linoleic acid are associated with lower risk of subsequent rheumatoid arthritis in a southern European nested case–control study
Authors: Paola de Pablo, Dora Romaguera, Helena L Fisk, Philip C Calder, Anne-Marie Quirke, Alison J Cartwright, Salvatore Panico, Amalia Mattiello, Diana Gavrila, Carman Navarro, Carlotta Sacerdote, Paolo Vineis, Rosario Tumino, William E Ollier, Dominique S Michaud, Elio Riboli, Patrick J Venables, Benjamin A Fisher
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Findings relating to dietary intake of n-3 polyunsaturated fatty acids (PUFA) and risk of rheumatoid arthritis (RA) are mixed. Erythrocyte membrane PUFA is an accurate objective biomarker of PUFA status; however, there are little data on erythrocyte membrane PUFA and risk of RA. The objective was therefore to compare erythrocyte membrane PUFA between pre-RA individuals and matched controls from a population-based sample, and specifically to test the hypothesis that higher levels of longer chain n-3 PUFA are associated with lower risk of RA. Methods The European Prospective Investigation into Cancer and Nutrition (EPIC) is a large European prospective cohort study of apparently healthy populations. We undertook a nested case–control study by identifying RA cases with onset after enrolment (pre-RA) in four EPIC cohorts in Italy and Spain. Confirmed pre-RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. Conditional logistic regression analysis was used to estimate associations of PUFA with the development of RA, adjusting for potential confounders including body mass index, waist circumference, education level, physical activity, smoking status and alcohol intake. Results The study analysed samples from 96 pre-RA subjects and 258 matched controls. In this analysis, the median time to diagnosis (defined as time between date of blood sample and date of diagnosis) was 6.71 years (range 0.8–15). A significant inverse association was observed with n-6 PUFA linoleic acid (LA) levels and pre-RA in the fully adjusted model (highest tertile: OR 0.29; 95% CI 0.12 to 0.75; P for trend 0.01). No association was observed with any individual n-3 PUFA, total n-3 PUFA or total n-3:n-6 ratio. Conclusions Erythrocyte levels of the n-6 PUFA LA were inversely associated with risk of RA, whereas no associations were observed for other n-6 or n-3 PUFA. Further work is warranted to replicate these findings and to investigate if lower LA levels are a bystander or contributor to the process of RA development.
Meeting the Challenge: The National Cancer Institute’s Central Institutional Review Board for Multi-Site Research
Authors: Holly A. Massett, Sharon L. Hampp, Jacquelyn L. Goldberg, Margaret Mooney, Linda K. Parreco, Lori Minasian, Mike Montello, Grace E. Mishkin, Catasha Davis, Jeffrey S. Abrams
Journal: Journal of Clinical Oncology (2018)

The National Institutes of Health (NIH) issued a new policy that requires a single institutional review board (IRB) of record be used for all protocols funded by the NIH that are carried out at more than one site in the United States, effective January 2018. This policy affects several hundred clinical trials opened annually across the NIH. Limited data exist to compare the use of a single IRB to that of multiple local IRBs, so some institutions are resistant to or distrustful of single IRBs. Since 2001, the National Cancer Institute (NCI) has funded a central IRB (CIRB) that provides human patient reviews for its extensive national cancer clinical trials program. This paper presents data to show the adoption, efficiencies gained, and satisfaction of the CIRB among NCI trial networks and reviews key lessons gleaned from 16 years of experience that may be informative for others charged with implementation of the new NIH single-IRB policy.