tbuckley/cabot-search huggingface dataset:
Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial
Authors: Hagop M Kantarjian, Pierre Fenaux, Mikkael A Sekeres, Jeffrey Szer, Uwe Platzbecker, Andrea Kuendgen, Gianluca Gaidano, Wieslaw Wiktor-Jedrzejczak, Nancy Carpenter, Bhakti Mehta, Janet Franklin, Aristoteles Giagounidis
Journal: The Lancet Haematology (2018)
Adjunctive Glucocorticoid Therapy in Patients with Septic Shock
Authors: Balasubramanian Venkatesh, Simon Finfer, Jeremy Cohen, Dorrilyn Rajbhandari, Yaseen Arabi, Rinaldo Bellomo, Laurent Billot, Maryam Correa, Parisa Glass, Meg Harward, Christopher Joyce, Qiang Li, Colin McArthur, Anders Perner, Andrew Rhodes, Kelly Thompson, Steve Webb, John Myburgh
Journal: New England Journal of Medicine (2018)

We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days.
Systemic therapy with tumor suppressor FUS1-nanoparticles for stage IV lung cancer
Authors: Charles Lu, Carmen Sepulveda, Lin Ji, Rajagopal Ramesh, Sean O'Connor, Gitanjali Jayachandran, Marshall Hicks, Reginald Munden, J. Lee, Nancy Templeton, John McMannis, Jack Roth
Journal: Cancer Research (2007)

LB-348   The tumor suppressor gene FUS1 is frequently inactivated early in the development of lung cancer. FUS1 mediates apoptosis in cancer cells but not normal cells through its interaction with Apaf1. We developed a DOTAP:cholesterol nanoparticle encapsulating a FUS1 expression plasmid that showed selective uptake by cancer cells compared to normal cells. In this clinical trial a DOTAP:cholesterol FUS1 nanoparticle was injected intravenously in stage IV lung cancer patients who had progressive disease after cisplatin combination chemotherapy based on preclinical data showing successful treatment of metastatic lung cancer in mouse xenograft models. Nanoparticle-DNA complexes were manufactured in GMP facilities to meet specifications of OD400, size, appearance, and transfection efficiency. Patients received doses ranging from 0.01-0.03mg/kg at 3 week intervals for a maximum of 6 doses. Dexamethasone and diphenhydramine premedications were added and eliminated the only clinically significant toxicity of fever. To date 13 patients have been entered on the study at three different doses (0.1, 0.02, 0.03mg/kg). All patients could be evaluated for the primary endpoint of toxicity, and with pretreatment, there was no significant drug related toxicity. Four patients received only one dose because of rapidly progressing disease at a site requiring local treatment. Eight patients received two or more doses and can be evaluated for response with 3 patients achieving stable disease (3 - 7 months) and 5 patients progressing. Median survival time for all patients is 14.6 months which compares favorably to the published 7 months median survival for second line chemotherapy and 4 months for best supportive care for non-small cell lung cancer. Actuarial survival at 12 months was 55%. A maximum tolerated dose (MTD) has not been reached. Pre and 24 hour posttreatment tumor biopsies were obtained from 3 patients. A quantitative real time reverse transcriptase PCR (RT-PCR) analysis using a plasmid FUS1 sequence-specific probe was performed on samples blinded to time of biopsy. A high level of plasmid FUS1 expression was detected in all 3 posttreatment samples but not in three pretreatment samples and negative controls by RT-PCR. DOTAP:cholesterol FUS1 nanoparticles can be safely administered intravenously in patients with stage IV lung cancer. Gene expression is detected in tumors, and there is an indication of anti-tumor activity.
Mutational landscape of a chemically-induced mouse model of liver cancer
Authors: Frances Connor, Tim F. Rayner, Sarah J. Aitken, Christine Feig, Margus Lukk, Javier Santoyo-Lopez, Duncan T. Odom
Journal: Journal of Hepatology (2018)

Highlights•High burden of stochastic point mutations in carcinogen-induced murine tumours.•Distinct mutational imprint in tumours arising after diethylnitrosamine exposure.•Mutations in Ras/MAPK pathway genes drive DEN-initiated liver tumorigenesis.•Apc mutations associated with progression of DEN-initiated tumours to carcinoma.Graphical abstractAbstractBackground & AimsCarcinogen-induced mouse models of liver cancer are used extensively to study the pathogenesis of the disease and are critical for validating candidate therapeutics. These models can recapitulate molecular and histological features of human disease. However, it is not known if the genomic alterations driving these mouse tumour genomes are comparable to those found in human tumours. Herein, we provide a detailed genomic characterisation of tumours from a commonly used mouse model of hepatocellular carcinoma (HCC).MethodsWe analysed whole exome sequences of liver tumours arising in mice exposed to diethylnitrosamine (DEN). Mutational signatures were compared between liver tumours from DEN-treated and untreated mice, and human HCCs.ResultsDEN-initiated tumours had a high, uniform number of somatic single nucleotide variants (SNVs), with few insertions, deletions or copy number alterations, consistent with the known genotoxic action of DEN. Exposure of hepatocytes to DEN left a reproducible mutational imprint in resulting tumour exomes which we could computationally reconstruct using six known COSMIC mutational signatures. The tumours carried a high diversity of low-incidence, non-synonymous point mutations in many oncogenes and tumour suppressors, reflecting the stochastic introduction of SNVs into the hepatocyte genome by the carcinogen. We identified four recurrently mutated genes that were putative oncogenic drivers of HCC in this model. Every neoplasm carried activating hotspot mutations either in codon 61 of Hras, in codon 584 of Braf or in codon 254 of Egfr. Truncating mutations of Apc occurred in 21% of neoplasms, which were exclusively carcinomas supporting a role for deregulation of Wnt/β-catenin signalling in cancer progression.ConclusionsOur study provides detailed insight into the mutational landscape of tumours arising in a commonly used carcinogen model of HCC, facilitating the future use of this model to better understand the human disease.Lay summaryMouse models are widely used to study the biology of cancer and to test potential therapies. Herein, we have described the mutational landscape of tumours arising in a carcinogen-induced mouse model of liver cancer. Since cancer is a disease caused by genomic alterations, information about the patterns and types of mutations in the tumours in this mouse model should facilitate its use to study human liver cancer.
Myeloma Lytic Bone Lesions Characterization with WB-LDCT and 18f-FDG PET/MRI
Authors: Albana Lico, Gregorio Barilà, Filippo Crimì, Lucia Checuz, Tamara Berno, Stefania Vio, Antonio Branca, Lucia Ammirati, Matteo Leoncin, Pietro Zucchetta, Carmelo Lacognata, Francesco Piazza, Gianpietro Semenzato, Renato Zambello
Journal: Blood (2017)
No Effect of Benralizumab Treatment on Antibody Response to Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Moderate to Severe Asthma: Results From the Phase IIIb ALIZE Trial
Authors: Pamela L. Zeitlin, Mila Leong, Jeremy Cole, Raburn M. Mallory, Vivian H. Shih, Richard F. Olsson, Mitchell Goldman
Journal: Journal of Allergy and Clinical Immunology (2018)
Tourmaline US-MM6, an Open-Label, Single-Arm, Multicenter Study Evaluating the Effectiveness and Safety of Ixazomib in Combination with Lenalidomide and Dexamethasone (IRd) in Patients (pts) with Newly Diagnosed Multiple Myeloma (NDMM) Switching from a Bortezomib-Based Triplet Induction Regimen
Authors: Robert M Rifkin, Ralph V. Boccia, Suman Kambhampati, Joshua R Richter, Saad Z Usmani, Jack Aiello, Brittany Sickler, Magdalena Schoeneich, Bingxia Wang, Susan Zelt, Presley Whidden, Lawrence E Dollar, Liviu Niculescu, Stephen J Noga
Journal: Blood (2017)
Phenotypic analysis of human CD4+ T cells specific for immediate early 63 protein of varicella-zoster virus
Authors: L Jones, A P Black, G N Malavige, G S Ogg
Journal: British Journal of Dermatology (2008)

Open reading frame 63 of varicella-zoster Virus (VZV) encodes an immediate early (IE) phosphoprotein (IE63) that is believed to be important for viral infectivity and establishing latency. Evidence suggests that VZV-specific T cells are crucial in the control of viral replication; however, data addressing the existence of IE63 protein-specific CD4+ T cells are limited. Using IFN-gamma immunosorbent assays, we identified high frequencies of responses to overlapping peptides spanning the IE63 protein both ex vivo and after in vitro restimulation in healthy VZV-seropositive individuals. We identified a commonly recognised epitope, restricted by HLA-DRB1*1501, which was naturally processed and presented by keratinocytes. We proceeded to investigate the frequency and phenotype of the epitope-specific CD4+ T cells using HLA class II tetrameric complexes. Epitope-specific CD4+ T cells were detectable ex vivo and showed a mixed central and effector-memory differentiation phenotype, with a significant proportion showing evidence of recent activation and rapid effector function. In summary these data implicate persistent low-level or recurrent VZV antigen exposure in healthy immune donors and are compatible with a role for IE63-specific CD4+ T cells in the control of viral reactivation.
Tumor necrosis factor alpha, a neurotoxic proinflammatory cytokine for oxaliplatin-induced peripheral neuropathy.
Authors: Zohreh Ghoreishi, Ali Esfahani, Mohammad Asghari Jafarabadi, Hormoz Ayromlou
Journal: Journal of Clinical Oncology (2016)

e15095 Background: Colorectal cancer (CRC) has a progressive incidence throughout the world and peripheral neuropathy is the major dose-limiting side effect of oxaliplatin, a chemotherapeutic agent for CRC. Proinflammatory cytokines are involved in neuropathy and inflammatory pain. The association between pre-chemotherapy serum levels of proinflammatory cytokines and oxaliplatin induced peripheral neuropathy (OXIPN) was assessed in this study. Methods: Eligible patients with colon cancer who were candidate for chemotherapy with oxaliplatin were recruited in the study. Serum levels of interleukin-1 beta (IL-1 β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and hs-CRP were measured before the onset of chemotherapy and their associations with incidence and severity of OXIPN were evaluated. “reduced Total Neuropathy Score/ rTNS” was used for measurement the OXIPN. rTNS included clinical and electrophysiological assessments. Analysis was performed on data of trial IRCT201112158397N2. Results: Fifty-nineeligible patients with colon cancer completed the study. After adjusting for intervention effect, age, and body mass index, prechemotherapy serum levels of TNF-α had a significant positive association with incidence (OR = 2.70, .95% CI = (1.28- 5.70), p = 0.009) and severity of OXIPN (B = .34, .95% CI = (.03 - .65), p = 0.030). There was no statistically significant association between serum levels of IL-1 β, IL-6, hs-CRP and OXIPN. Conclusions: TNF-α was presented for the first time as a neurotoxic proinflammatory cytokine in developing OXIPN, and a possible target for prophylaxis or treatment of OXIPN. Clinical trial information: IRCT201112158397N2.
Improved survival using specialized multidisciplinary board in sarcoma patients
Authors: J.-Y. Blay, P. Soibinet, N. Penel, E. Bompas, F. Duffaud, E. Stoeckle, O. Mir, J. Adam, C. Chevreau, S. Bonvalot, M. Rios, P. Kerbrat, D. Cupissol, P. Anract, F. Gouin, J. -E. Kurtz, C. Lebbe, N. Isambert, F. Bertucci, M. Toumonde, A. Thyss, S. Piperno-Neumann, P. Dubray-Longeras, P. Meeus, F. Ducimetière, A. Giraud, J. -M. Coindre, I. Ray-Coquard, A. Italiano, A. Le Cesne
Journal: Annals of Oncology (2017)
Global access of patients with kidney disease to health technologies and medications: findings from the Global Kidney Health Atlas project
Authors: Htay Htay, Mona Alrukhaimi, Gloria E. Ashuntantang, Aminu K. Bello, Ezequiel Bellorin-Font, Mohammed Benghanem Gharbi, Branko Braam, John Feehally, David C. Harris, Vivekanand Jha, Kailash Jindal, Kamyar Kalantar-Zadeh, Rumeyza Kazancioglu, Peter G. Kerr, Adeera Levin, Meaghan Lunney, Ikechi G. Okpechi, Michelle E. Olah, Timothy Olusegun Olanrewaju, Mohamed A. Osman, Yasin Parpia, Jeffrey Perl, Bilal Qarni, Harun Ur Rashid, Ahmed Rateb, Eric Rondeau, Babatunde Lawal Salako, Laura Sola, Irma Tchokhonelidze, Marcello Tonelli, Natasha Wiebe, Isaac Wirzba, Chih-Wei Yang, Feng Ye, Alexander Zemchenkov, Ming-hui Zhao, David W. Johnson
Journal: Kidney International Supplements (2018)
Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study
Authors: R Scott McClelland, Jairam R Lingappa, Sujatha Srinivasan, John Kinuthia, Grace C John-Stewart, Walter Jaoko, Barbra A Richardson, Krista Yuhas, Tina L Fiedler, Kishorchandra N Mandaliya, Matthew M Munch, Nelly R Mugo, Craig R Cohen, Jared M Baeten, Connie Celum, Julie Overbaugh, David N Fredricks
Journal: The Lancet Infectious Diseases (2018)
Population-Based Surveillance of Birth Defects Potentially Related to Zika Virus Infection — 15 States and U.S. Territories, 2016
Authors: Augustina Delaney, Cara Mai, Ashley Smoots, Janet Cragan, Sascha Ellington, Peter Langlois, Rebecca Breidenbach, Jane Fornoff, Julie Dunn, Mahsa Yazdy, Nancy Scotto-Rosato, Joseph Sweatlock, Deborah Fox, Jessica Palacios, Nina Forestieri, Vinita Leedom, Mary Smiley, Amy Nance, Heather Lake-Burger, Paul Romitti, Carrie Fall, Miguel Valencia Prado, Jerusha Barton, J. Michael Bryan, William Arias, Samara Viner Brown, Jonathan Kimura, Sylvia Mann, Brennan Martin, Lucia Orantes, Amber Taylor, John Nahabedian, Amanda Akosa, Ziwei Song, Stacey Martin, Roshan Ramlal, Carrie Shapiro-Mendoza, Jennifer Isenburg, Cynthia A. Moore, Suzanne Gilboa, Margaret A. Honein
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Zika virus infection during pregnancy can cause serious birth defects, including microcephaly and brain abnormalities (1). Population-based birth defects surveillance systems are critical to monitor all infants and fetuses with birth defects potentially related to Zika virus infection, regardless of known exposure or laboratory evidence of Zika virus infection during pregnancy. CDC analyzed data from 15 U.S. jurisdictions conducting population-based surveillance for birth defects potentially related to Zika virus infection.* Jurisdictions were stratified into the following three groups: those with 1) documented local transmission of Zika virus during 2016; 2) one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents; and 3) less than one case of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents. A total of 2,962 infants and fetuses (3.0 per 1,000 live births; 95% confidence interval [CI] = 2.9-3.2) (2) met the case definition.† In areas with local transmission there was a non-statistically significant increase in total birth defects potentially related to Zika virus infection from 2.8 cases per 1,000 live births in the first half of 2016 to 3.0 cases in the second half (p = 0.10). However, when neural tube defects and other early brain malformations (NTDs)§ were excluded, the prevalence of birth defects strongly linked to congenital Zika virus infection increased significantly, from 2.0 cases per 1,000 live births in the first half of 2016 to 2.4 cases in the second half, an increase of 29 more cases than expected (p = 0.009). These findings underscore the importance of surveillance for birth defects potentially related to Zika virus infection and the need for continued monitoring in areas at risk for Zika.
Response to: ‘Depression and anxiety associate with less remission after 1 year in rheumatoid arthritis’ by Boer<i>et al</i>
Authors: Brigitte Michelsen, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2018)

We thank Boer et al for their interesting report1 validating our findings of depression and anxiety as strong negative predictors of remission in rheumatoid arthritis (RA).2

Depression and anxiety are frequent disorders among patients with inflammatory arthritides,3 4 and emphasis on these conditions may be important in a treat-to-target strategy, not only in the shared decision-making …
Myelofibrosis (MF) Leukemic Transformation (LT) in the Era of Ruxolitinib and Genomics: Characteristics and Outcomes
Authors: Lorenzo Falchi, Dai Chihara, Prithviraj Bose, Zeev Estrov, Hagop M. Kantarjian, Farhad Ravandi, Srdan Verstovsek
Journal: Blood (2017)
Programme frequency, type, time and duration do not explain the effects of balance exercise in older adults: a systematic review with a meta-regression analysis
Authors: Melanie K Farlie, Lauren Robins, Romi Haas, Jennifer L Keating, Elizabeth Molloy, Terry P Haines
Journal: British Journal of Sports Medicine (2018)

Objective The objective of this systematic review was to examine the effects of different balance exercise interventions compared with non-balance exercise controls on balance task performance in older adults. Design Systematic review. Data sources Medline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Scopus and Cochrane Database of Systematic Reviews were searched until July 2017. Eligibility criteria for selecting studies Systematic reviews and meta-analyses of randomised trials of balance exercise interventions for older adults were identified for extraction of eligible randomised trials. Eligibility criteria for inclusion of randomised trials in meta-analyses were comparison of a balance exercise intervention with a control group that did not perform balance exercises, report of at least one end-intervention balance outcome measurement that was consistent with the five subgroups of balance exercise identified, and full-text article available in English. Results Ninety-five trials were included in meta-analyses and 80 in meta-regressions. For four balance exercise types (control centre of mass, multidimensional, mobility and reaching), significant effects for balance exercise interventions were found in meta-analyses (standardised mean difference (SMD) 0.31–0.50), however with considerable heterogeneity in observed effects (I 2 : 50.4%–80.6%). Risk of bias assessments (Physiotherapy Evidence Database score and funnel plots) did not explain heterogeneity. One significant relationship identified in the meta-regressions of SMD and balance exercise frequency, time and duration explained 2.1% of variance for the control centre of mass subgroup. Conclusion Limitations to this study included the variability in design of balance interventions, incomplete reporting of data and statistical heterogeneity. The design of balance exercise programmes provides inadequate explanation of the observed benefits of these interventions.
Characterization Of Hereditary Angioedema Attacks Requiring Reinjection Of Icatibant: Findings From The Icatibant Outcome Survey
Authors: Irmgard Andresen, Hilary J. Longhurst, Laurence Bouillet, Teresa Caballero, Andrea Zanichelli, Marcus Maurer, Anete S. Grumach, Anette Bygum, Jaco Botha, Werner Aberer
Journal: Journal of Allergy and Clinical Immunology (2018)
Characteristics and Management of IgA Vasculitis (Henoch‐Schönlein) in Adults: Data From 260 Patients Included in a French Multicenter Retrospective Survey
Authors: Alexandra Audemard-Verger, Benjamin Terrier, Agnès Dechartres, Johan Chanal, Zahir Amoura, Noémie Le Gouellec, Patrice Cacoub, Noémie Jourde-Chiche, Geoffrey Urbanski, Jean-François Augusto, Guillaume Moulis, Loic Raffray, Alban Deroux, Aurélie Hummel, Bertrand Lioger, Mélanie Catroux, Stanislas Faguer, Julie Goutte, Nihal Martis, François Maurier, Etienne Rivière, Sébastien Sanges, Aurélie Baldolli, Nathalie Costedoat-Chalumeau, Mélanie Roriz, Xavier Puéchal, Marc André, Christian Lavigne, Boris Bienvenu, Arsène Mekinian, Elie Zagdoun, Charlotte Girard, Alice Bérezné, Loïc Guillevin, Eric Thervet, Evangéline Pillebout
Journal: Arthritis & Rheumatology (2017)

Objective Data on adult IgA vasculitis (Henoch‐Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population. Methods Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models. Results The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine ( P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10–12.33 ( P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28–10.99 ( P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29–2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00–3.20; P = 0.049). Conclusion This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first‐line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.