tbuckley/cabot-search huggingface dataset:
TMOD-07. ADVANCED ULTRA-HIGH FIELD MRI ON TUMOR HABITAT IN ORTHOTOPIC MOUSE MODELS FOR PEDIATRIC BRAIN TUMORS
Authors: Jenna Steiner, Angela Pierce, Andrea Griesinger, Bethany Veo, Aaron Knox, Nathan Dahl, Adam Green, Nicholas Foreman, Rajeev Vibhakar, Natalie Serkova
Journal: Neuro-Oncology (2019)

Brain tumors are the second most common malignancy in childhood. Magnetic resonance imaging (MRI) is the preferred clinical modality for the management of pediatric brain tumors due to its exquisite soft tissue contrast and non-ionizing radiation. Pediatric brain tumors have a diverse array of clinical manifestations, cellular and molecular phenotypes, and tumor habitats. There is an unmet need to develop human-faithful pediatric mouse models and fast high-resolution functional MRI to characterize biologically relevant structure-function relationships in vivo. Here, we report on non-gadolinium, Multiparametric Advanced Fast Imaging (MAFI) at a 9.4T MRI scanner, followed by radiomics analysis to detect, characterize and differentiate three distinct brain tumor subtypes of orthotopic patient-derived xenograft (PDX) mouse models. The total MAFI scan time (turboRARE T2-MRI, FLAIR, intrinsic susceptibility (IS)-MRI, and diffusion weighted imaging (DWI)) was 17 minutes. High-resolution T2-MRI detected lesions (> 0.2 mm3) in the posterior fossa for medulloblastomas, in the pons for DIPG, and in the cerebellum for ependymomas, with metastatic spread to cortex (medulloblastoma), spine (DIPG) and olfactory bulb (ependymoma), each n=12. IS-MRI revealed increased tumor blood volume (mostly in medulloblastomas) at the early stage of tumor engraftment. High cellularity (indicated by low ADC on DWI) was characteristic of medulloblastomas and ependymomas, along with high peritumoral edema on DWI and FLAIR. For radiomics analysis, each image was segmented into three regions (with 360 radiomics features each): well-defined tumor, peritumoral edema and tumor necrosis. A subset of twelve tumoral, six peritumoral and two necrotic MAFI radiomics features was found to be predictive of the tumor subtype (P<0.0002) independent of tumor anatomical location. In summary, the 9.4 Tesla MAFI MRI protocol discriminates among specific radiological features for three distinct orthotopic models: medulloblastomas exhibit higher levels of necrosis, cellularity and angiogenesis as compared to ependymomas (high peritumoral edema) and DIPG (low blood volume/vessel density).
Socioeconomic position and use of healthcare in the last year of life: A systematic review and meta-analysis
Authors: Joanna M. Davies, Katherine E. Sleeman, Javiera Leniz, Rebecca Wilson, Irene J. Higginson, Julia Verne, Matthew Maddocks, Fliss E. M. Murtagh
Journal: PLoS Medicine (2019)

Low socioeconomic position (SEP) is recognized as a risk factor for worse health outcomes. How socioeconomic factors influence end-of-life care, and the magnitude of their effect, is not understood. This review aimed to synthesise and quantify the associations between measures of SEP and use of healthcare in the last year of life.
MEDU-45. DEVELOPMENT OF A NEW ETOPOSIDE-BOUND MAGNETIC NANOPARTICLE DESIGNED TO TREAT MEDULLOBLASTOMA CELLS DISSEMINATED WITHIN CEREBROSPINAL FLUID PATHWAYS
Authors: Amanda Kwasnicki, Sajani Lakka, Alexander Willis, Bhargava Karumudi, George Lee, Bing Liu, Sangyeul Hwang, Darian Esfahani, Ying Liu, Herbert Engelhard
Journal: Neuro-Oncology (2019)

BACKGROUND: Medulloblastoma cells notoriously disseminate within CSF pathways. Magnetic nanoparticles (MNPs) have potential for enhancing delivery of chemotherapy to these cells. Successful clinical use of MNPs within CSF has been hampered due to limited capacity for targeting at human-sized distances, and choice of therapeutic component. Here, we present data related to the creation and in vitro use of an MNP system containing: 1) AuFe base particles having streptavidin binding sites, and 2) biotinylated etoposide. Etoposide was chosen due to its previous use in the spinal subarachnoid space, and ease of biotinylation. Aggregates of MNPs were moved by a rotating magnet, with “surface walking” even at 10-15cm. METHODS: Etoposide-MNPs were characterized by electron microscopy, UV-vis spectroscopy, and dynamic light scattering (DLS). The rotating magnet was provided by Pulse Therapeutics. Cultured D283 cells were seeded into standard multiwell plates, and custom-made trays designed to measure translational motion. Videography was used to determine particle velocity. Cellular responses to etoposide-MNPs (vs. controls) were studied by light microscopy and MTT assay. RESULTS: Etoposide was successfully bound to base particles through the streptavidin-biotin interaction. 1 - 100uM etoposide was used. DLS showed the diameter of etoposide-MNPs to be 218+/-72nm. Etoposide-MNPs could be moved remotely by the rotating magnet, which produced a tangential velocity of 0.12+/-0.002cm/sec at 8-7cm. With 2 hours of treatment, 5uM etoposide-MNPs caused morphologic changes, and decreased D283 viability to 0.76+/-0.01% of controls. CONCLUSIONS: These data demonstrate that the novel etoposide-MNPs have cytotoxic effect, and can be targeted at physiologic distances. While further studies are underway, etoposide-MNPs, may ultimately prove useful for magnetic targeting within CSF pathways, after introduction via lumbar puncture or Ommaya reservoir. An improved ability to eradicate malignant cells within CSF would be a major step forward in the treatment of patients with disseminated medulloblastoma.
EVALUATION OF THE INTEROBSERVER CONCORDANCE OF THE ENDOSCOPIC CLASSIFICATION OF INTRAPAPILLARY CAPILLARY LOOPS FOR ESOPHAGEAL SQUAMOUS CELLS CARCINOMA OF THE JAPAN ESOPHAGEAL SOCIETY
Authors: O Okazaki, L Meireles de Azeredo Coutinho, C Casamali, G Ferreira Ayala Farias, A Coutunho Madruga Neto, T Arantes de Carvalho Visconti, F Shiguehissa Kawaguti, B Da Costa Martins, L Henrique Lenz, A Vaz Safatle-Ribeiro, U Ribeiro, F Maluf-Filho
Journal: Endoscopy (2019)

Endoscopic evaluation of superficial esophageal squamous cancer (ESCC) is crucial to estimate the invasion depth and decide the most appropriate therapeutic strategy. Recently, the JES published a new magnifying endoscopic (ME) classification to predict the invasion depth of SESCC based on microvessel morphology, with a reported accuracy of up to 90%. The objective of this study was to evaluate the inter and intra-observer agreement of the JES classification in a Western oncological center.
The Correlation of Serum Mesothelin Level With Pleural Thickness in Malignant Pleural Mesothelioma Makes it a Valuable Tool for Monitoring Tumor Progression
Authors: Vincenzo Fontana, Antonella Vigani, Maria Pia Pistillo, Ugo Giannoni, Ilan Rosemberg, Pier Aldo Canessa, Giovanni Berisso, Paola Ferro, Maria Cristiana Franceschini, Marika Tonarelli, Silvio Roncella
Journal: Journal of Thoracic Oncology (2019)
Genetic Analysis of Uveal Melanoma in 658 Patients Using the Cancer Genome Atlas Classification of Uveal Melanoma as A, B, C, and D
Authors: Pornpattana Vichitvejpaisal, Lauren A. Dalvin, Mehdi Mazloumi, Kathryn G. Ewens, Arupa Ganguly, Carol L. Shields
Journal: Ophthalmology (2019)
The effect of gefapixant, a P2X3 antagonist, on cough reflex sensitivity: a randomised placebo-controlled study
Authors: Alyn H. Morice, Michael M. Kitt, Anthony P. Ford, Andrew M. Tershakovec, Wen-Chi Wu, Kayleigh Brindle, Rachel Thompson, Susannah Thackray-Nocera, Caroline Wright
Journal: European Respiratory Journal (2019)

We evaluated the effect of gefapixant on cough reflex sensitivity to evoked tussive challenge. In this phase 2, double-blind, two-period study, patients with chronic cough (CC) and healthy volunteers (HV) were randomised to single-dose gefapixant 100 mg or placebo in a crossover fashion. Sequential inhalational challenges with ATP, citric acid, capsaicin and distilled water were performed 1, 3 and 5 h after dosing. Mean concentrations evoking ≥2 coughs (C2) and ≥5 coughs (C5) post dose versus baseline were co-primary endpoints. Objective cough frequency (coughs·h −1 ) over 24 h and a cough severity visual analogue scale (VAS) were assessed in CC patients. Adverse events were monitored. 24 CC patients and 12 HV were randomised (mean age 61 and 38 years, respectively). The cough challenge threshold increased for ATP by 4.7-fold (C2, p≤0.001) and 3.7-fold (C5, p=0.007) for gefapixant versus placebo in CC patients; in HV, C2 and C5 increased 2.4-fold (C2, p=0.113; C5, p=0.003). The distilled water C2 and C5 thresholds increased significantly (p&lt;0.001) by a factor of 1.4 and 1.3, respectively, in CC patients. Gefapixant had no effect on capsaicin or citric acid challenge. Median cough frequency was reduced by 42% and the least squares mean cough severity VAS was 18.0 mm lower for gefapixant versus placebo in CC patients. Dysgeusia was the most frequent adverse event (75% of HV and 67% of CC patients). ATP-evoked cough was significantly inhibited by gefapixant 100 mg, demonstrating peripheral target engagement. Cough count and severity were reduced in CC patients. Distilled water may also evoke cough through a purinergic pathway.
Serum-based soluble markers differentiate psoriatic arthritis from osteoarthritis
Authors: Vinod Chandran, Fatima Abji, Anthony V Perruccio, Rajiv Gandhi, Suzanne Li, Richard J Cook, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2019)

Objectives We aimed to identify soluble biomarkers that differentiate psoriatic arthritis (PsA) from osteoarthritis (OA). Methods Markers of cartilage metabolism (cartilage oligomeric matrix protein [COMP], hyaluronan), metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor [HGF], insulin, leptin) and inflammation (C-reactive protein [CRP], interleukin-1β [IL-1β], IL-6, IL-8, tumour necrosis factor alpha [TNFα], monocyte chemoattractant protein-1 [MCP-1], nerve growth factor [NGF]) were compared in serum samples from 201 patients with OA, 77 patients with PsA and 76 controls. Levels across the groups were compared using the Kruskal-Wallis test. Pairwise comparisons were made with Wilcoxon rank-sum test. Multivariate logistic regression analyses were performed to identify markers that differentiate PsA from OA. Receiver operating characteristic (ROC) curves were constructed based on multivariate models. The final model was further validated in an independent set of 73 PsA and 75 OA samples using predicted probabilities calculated with coefficients of age, sex and biomarkers. Results Levels of the following markers were significantly different across the three groups (p&lt;0.001)—COMP, hyaluronan, resistin, HGF, insulin, leptin, CRP, IL-6, IL-8, TNFα, MCP-1, NGF. In multivariate analysis, COMP (OR 1.24, 95% CI 1.06 to 1.46), resistin (OR 1.26, 95% CI 1.07 to 1.48), MCP-1 (OR 1.10, 95% CI 0.07 to 1.48) and NGF (OR&lt;0.001, 95% CI &lt;0.001 to 0.25) were found to be independently associated with PsA versus OA. The area under the ROC curve (AUROC) for this model was 0.99 compared with model with only age and sex (AUROC 0.87, p&lt;0.001). Similar results were obtained using the validation sample. Conclusion A panel of four biomarkers may distinguish PsA from OA. These results need further validation in prospective studies.
Barbara Ansell: a person ahead of her time
Authors: Pat Woo, Nico M Wulffraat, Alan Tyndall
Journal: Annals of the Rheumatic Diseases (2019)

In 1951, Barbara Ansell, a young 28-year-old physician and aspiring cardiologist, was encouraged by Professor Eric Bywaters to join him in the Special Unit for Juvenile Rheumatism, recently created by the Medical Research Council (MRC) of UK, located at the Canadian Red Cross Memorial Hospital in Taplow, Buckinghamshire, UK. She had been advised that cardiology 'was a man's world'. Although initially aimed at research and treatment of rheumatic fever, this unit of pathologists and clinicians morphed into a unit for juvenile chronic arthritis as the incidence of rheumatic fever gradually waned. At that time, a child with chronic arthritis would mostly be confined to bed at home, perhaps with aspirin and/or cortisone medication and bore a grim prognosis regarding both function and survival. She began her pioneering work there with her MD thesis (1965) on the classification of children with chronic arthritis. Her clinical skill and experience were legendary. Her major clinical achievements are listed in box 1. She also was actively engaged with scientists in the search for the causes of the diseases she encountered. She was ideally placed in the shared environment of MRC facilities next to a general hospital. Box 2 is a short summary of the main milestones and breadth of her work. In 1988, the world-renowned paediatric rheumatologist, Barbara Ansell CBE, FRCP, FRCS, FRCPCH, retired as director of the MRC Division of Rheumatology at Northwick Park, Harrow, UK. She left as a legacy an army of former colleagues, protegées and friends from all areas of healthcare, dedicated to children and adolescents with rheumatic diseases. By then the outcome for such young patients had improved dramatically. Gratifyingly, Barbara did see the fulfilment of her long-held dream, expressed passionately at her retirement Festschrift: the beginning of truly effective therapies. Box 1 ### Barbara Ansell: Key achievements
MicroRNAs in COPD: small molecules with big potential
Authors: Brian D. Hobbs, Kelan G. Tantisira
Journal: European Respiratory Journal (2019)

<b>MicroRNA research in&nbsp;COPD can help explain the observed heterogeneity, not only in clinical presentation, but also in treatment response, particularly as it relates to inhaled corticosteroids</b>http://ow.ly/HbYo30o7lIt
Surgical outcomes of patients with diffuse-type tenosynovial giant-cell tumours: an international, retrospective, cohort study
Authors: Monique J L Mastboom, Emanuela Palmerini, Floortje G M Verspoor, Anja J Rueten-Budde, Silvia Stacchiotti, Eric L Staals, Gerard R Schaap, Paul C Jutte, Will Aston, Hans Gelderblom, Andreas Leithner, Dietmar Dammerer, Akihiko Takeuchi, Quirina Thio, Xiaohui Niu, Jay S Wunder, Michiel A J van de Sande, M. Fiocco, P.D.S. Dijkstra, R.J.P. Van der Wal, P.A. Daolio, P. Picci, A. Gronchi, S. Ferrari, H. Özger, R.G. Maki, H.W.B. Schreuder, I.C.M. Van der Geest, J.A.M. Bramer, W.J.B. Mastboom, M. Boffano, E. Goldenitsch, D. Campanacci, P. Cuomo, P.C. Ferguson, A.M. Griffin, Y. Sun, T. Schubert, K. Patel, M.S.J. Aranguren, A. Blancheton, F. Gouin, H.R. Dürr, C.F. Capellen, J. Schwab, S. Iwata, O. Vyrva, W. Weschenfelder, E.H.M. Wang, M. Wook Joo, Y.K. Kang, Y.G. Chung, W. Ebeid, J. Bruns, T. Ueda
Journal: The Lancet Oncology (2019)
Abstract 013: An Environment-wide Association Study Identifies Novel and Replicated Nutrients and Pollutants Associated with Serum Lipid Levels
Authors: Chirag J Patel, Mark R Cullen, John P Ioannidis, Atul J Butte
Journal: Circulation (2012)

Introduction: Both genetic and environmental factors contribute to triglyceride, LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) levels. While genome-wide association studies test the genetic factors systematically, testing and reporting a few factors may lead to fragmented literature for environmental correlates. Hypothesis: We hypothesize that one may systematically screen environmental factors to discover and replicate robust correlations with serum lipid levels. To address this hypothesis, we conduct an environment-wide association study (EWAS) to comprehensively and systematically associate multiple environmental factors with serum lipid levels. Methods: We utilized four independent surveys from the National Health and Nutrition Examination Survey (NHANES), collected between 1999 and 2006. 322 urine and blood markers of environmental factors were assayed in 500 to 7000 individuals. We used linear regression to associate each standardized environmental factor (mean subtracted and divided by the standard deviation) to triglycerides, LDL-C, and HDL-C adjusting for age, age-squared, sex, ethnicity, socioeconomic status (SES), and body mass index (BMI). Final estimates were additionally adjusted for waist circumference, diabetes status, blood pressure, and cohort. Multiple comparisons were controlled for the false discovery rate (the estimated ratio of false positives among statistically significant findings). Significant findings were tentatively validated across surveys. Finally, we conducted sensitivity analyses adjusting for 62 questionnaire-based variables in order to assess the degree of bias. Results: We identified and validated 22, 8, and 17 environmental factors correlated with triglycerides, LDL-C and HDL-C levels, respectively. Novel associations include markers of air pollution associated with lower HDL-C (p=0.006, 3% lower, N=2000) and vitamin E (-tocopherol) associated with unfavorable lipid levels (triglycerides: p=10 -17 , 17% higher, N=3000; LDL-C: p=3x10 -14 , 6% higher, N=3,000; HDL-C: p=6x10 -6 , 3% lower, N=7000). We also confirmed many known or previously speculated associations, such as lower levels in HDL-C with a marker of nicotine, cotinine, and higher triglycerides and lower HDL-C with levels of persistent fat-soluble contaminants, and lower triglycerides and higher HDL-C levels with nutrient markers such as iron, folate, vitamin C, and vitamin D, and enterolactone. Conclusions: EWAS is a way to create hypothesis regarding the association of environmental factors to serum lipids. Due to the cross-sectional nature of the surveys, findings may be biased by confounders or may be reverse causal. Nonetheless, we document a wide array of both known and novel associations, such as nutrients, vitamins, and persistent pollutants, with lipid levels that should be examined in depth in longitudinal studies.
Inherited <i> <scp>MC</scp> 1R </i> variants in patients with melanoma are associated with better survival in women
Authors: F.E. Lira, S. Podlipnik, M. Potrony, G. Tell‐Martí, N. Calbet‐Llopart, A. Barreiro, C. Carrera, J. Malvehy, S. Puig
Journal: British Journal of Dermatology (2019)

Women have a better melanoma prognosis, and fairer skin/hair colour. The presence of inherited MC1R variants has been associated with a better melanoma prognosis, but its interaction with sex is unknown.To evaluate the relationship between germline MC1R status and survival, and determine any association with sex.This was a cohort study including 1341 patients with melanoma from the Melanoma Unit of the Hospital Clinic of Barcelona, between January 1996 and April 2018. We examined known sex-related prognosis factors as they relate to features of melanoma and evaluated the sex-specific role of MC1R in overall and melanoma-specific survival. Hazard ratios (HRs) were calculated using univariate and multivariate Cox logistic regression.Men showed lower overall survival than women (P < 0·001) and the presence of inherited MC1R variants was not associated with better survival in our cohort. However, in women the presence of MC1R variants was associated with better overall survival in the multivariate analysis [HR 0·57, 95% confidence interval (CI) 0·38-0·85; P = 0·006] but not in men [HR 1·26, 95% CI 0·89-1·79; P = 0·185 (P-value for interaction 0·004)]. Analysis performed for melanoma-specific survival showed the same level of significance.Inherited MC1R variants are associated with improved overall survival in women with melanoma but not in men. Intrinsic sex-dependent features can modify the role of specific genes in melanoma prognosis. We believe that survival studies of patients with melanoma should include analysis by sex and MC1R genotype. What's already known about this topic? Inherited MC1R variants have been associated with a better melanoma prognosis, but their interaction with sex is unknown. What does this study add? MC1R variants are related to better overall survival and melanoma-specific survival in women but not in men. What is the translational message? These differences between the sexes could imply future changes in melanoma follow-up and treatment strategies. This provides a basis for understanding the interaction between sex-related genes and germline variants in cancer.
Establishing Mouse Models of B-Cell Non-Hodgkin's Lymphoma
Authors: Weili Xue, Weiming Li, Yanjie Zhang, Yue Song, Xuan Lan, Zhaoming Li, Xudong Zhang, Ken H. Young, Mingzhi Zhang, Xiaoyan Feng, Guannan Wang, Zhiyuan Zhou, Lisha Lu, Yingjun Wang, Mengyuan Jin
Journal: Blood (2017)
Adjuvant haploidentical virus-specific T lymphocytes for treatment of disseminated adenovirus infection in a premature infant
Authors: Jeffery J. Auletta, Pablo J. Sánchez, Erin K. Meyer, Lynn C. O'Donnell, Kevin A. Cassady, Christopher P. Ouellette, Shaina Hecht, Alejandro Diaz, Leeann R. Pavlek, Douglas P. Salamon, Christina L. Gallagher, Hillary Bradbury, Sarah L. Welfley, Jacqueline Magers, Debra L. Armbruster, Margaret G. Lamb, Robin J. Nakkula, Kevin Bosse, Dean A. Lee
Journal: Journal of Allergy and Clinical Immunology (2019)
CCSP counterbalances airway epithelial-driven neutrophilic chemotaxis
Authors: Lucie Knabe, Aurélie Petit, Charlotte Vernisse, Jérémy Charriot, Martine Pugnière, Corinne Henriquet, Souphatta Sasorith, Nicolas Molinari, Pascal Chanez, Jean-Philippe Berthet, Carey Suehs, Isabelle Vachier, Engi Ahmed, Arnaud Bourdin
Journal: European Respiratory Journal (2019)

Club cell secretory protein (CCSP) knockout mice exhibit increased airway neutrophilia, as found in chronic obstructive pulmonary disease (COPD). We therefore investigated whether treating COPD airway epithelia with recombinant human CCSP (rhCCSP) could dampen exaggerated airway neutrophilia.Control, smoker and COPD air-liquid interface (ALI) cultures exposed to cigarette smoke extract (CSE) were treated with and without rhCCSP. The chemotactic properties of the supernatants were assessed using Dunn chambers. Neutrophil chemotaxis along recombinant human interleukin 8 (rhIL8) gradients (with and without rhCCSP) was also determined. rhCCSP-rhIL8 interactions were tested through co-immunoprecipitation, Biacore surface plasmon resonance (SPR) and in silico modelling. The relationship between CCSP/IL8 concentration ratios in the supernatant of induced sputum from COPD patients versus neutrophilic airway infiltration assessed in lung biopsies was assessed.Increased neutrophilic chemotactic activity of CSE-treated ALI cultures followed IL8 concentrations and returned to normal when supplemented with rhCCSP. rhIL8-induced chemotaxis of neutrophils was reduced by rhCCSP. rhCCSP and rhIL8 co-immunoprecipitated. SPR confirmed this in vitro interaction (equilibrium dissociation constant=8 µM). In silico modelling indicated that this interaction was highly likely. CCSP/IL8 ratios in induced sputum correlated well with the level of small airway neutrophilic infiltration (r2=0.746, p<0.001).CCSP is a biologically relevant counter-balancer of neutrophil chemotactic activity. These different approaches used in this study suggest that, among the possible mechanisms involved, CCSP may directly neutralise IL8.
Exome sequencing and pathogenicity-network analysis of five French families implicate mTOR signalling and autophagy in familial sarcoidosis
Authors: Alain Calender, Clarice X. Lim, Thomas Weichhart, Adrien Buisson, Valérie Besnard, Pierre Antoine Rollat-Farnier, Claire Bardel, Pascal Roy, Vincent Cottin, Gilles Devouassoux, Amélie Finat, Stéphane Pinson, Serge Lebecque, Hilario Nunes, Dominique Israel-Biet, Abderazzaq Bentaher, Dominique Valeyre, Yves Pacheco
Journal: European Respiratory Journal (2019)

<b>Sarcoidosis is a multifactorial disease induced by environmental and genetic factors. Whole exome sequencing in 5 familial cases of the disease suggest that genetic defects in Rac1 and mTor functional hubs may be relevant to sarcoidosis pathogenesis</b>. http://bit.ly/2xooHx3