tbuckley/cabot-search huggingface dataset:
PDTM-23. DELTA-24-RGD ONCOLYTIC ADENOVIRUS MEDIATES ANTI-TUMOR EFFECT IN LOCALIZED AND DISSEMINATED AT/RT MURINE MODELS
Authors: Marc Garcia-Moure, Marisol González Huarriz, Virginia Laspidea, Lucía Marrodán, Candelaria Gomez-Manzano, Juan Fueyo, Ana Patiño-García, Marta M Alonso
Journal: Neuro-Oncology (2019)

Abstract Atypical teratoid/rhabdoid tumors (AT/RTs) are rare pediatric brain tumors affecting mainly infants and young children. However, AT/RTs encompass almost 10% of death caused by pediatric brain tumors, and the 2-year overall survival for these children remains below 20%. For this reason, AT/RT ranks among the deadliest pediatric brain tumors. Therefore, it is clear we need to find out new therapeutic options for these children. Delta-24-RGD oncolytic adenovirus has already demonstrated its efficacy in Phase I/II clinical trials in adult patients affected by high grade gliomas with no evidence of severe side effects. Of interest for pediatric brain tumors, the safety of Delta-24-RGD is has been demonstrated in an ongoing Phase I clinical trial for the treatment of DIPGs (NCT03178032). For these reasons, we propose to evaluate the anti-tumor effect of Delta-24-RGD in preclinical models of AT/RT. In vitro, the virus was able to infect and replicate in three different cell culture models of AT/RT, inducing a dose-dependent cytotoxic effect that results in IC50 values below 1 PFU/cell. In vivo, intratumor administration of the virus in mice bearing orthotopic localized AT/RT (supratentorial and infratentorial) extended significantly the survival the animals, leading to up to 20% of long-term survivors. We have also generated models of disseminated disease through intraventricular injection of the tumor cells, thus mimicking the lesions found in patients. AT/RT cell lines were transduced with a luc-expressing lentivirus in order to facilitate the follow up of these tumors. In disseminated AT/RT models, light emission reveals reduction of tumor growth in Delta-24-RGD treated animals in comparison to those mock treated, thus obtaining an increased overall survival. In conclusion, these results demonstrate that Delta-24-RGD could be a feasible therapeutic choice for patients affected by AT/RT.
Why does oxygen supplementation during exercise training in COPD patients with exercise-induced desaturation not consistently improve exercise capacity?
Authors: Daniel Langer, Rik Gosselink
Journal: European Respiratory Journal (2019)

<b>Additional improvements in functional capacity are only likely to occur when adjunct interventions applied during pulmonary rehabilitation enable patients to train at higher intensities during their general exercise-training programme</b>http://bit.ly/2TMxEel
A Retrospective Study on Inotuzumab Ozogamicin in Infants and Young Children with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Authors: Erica Brivio, Raoull Hoogendijk, Christophe Chantrain, Fanny Rialland, Audrey Contet, Sarah Elitzur, Luciano Dalla-Pozza, Krisztian Kallay, Chi Kong Li, Motohiro Kato, Inna V Markova, Kjeld Schmiegelow, Nicole Bodmer, Rob Pieters, Christian Michel Zwaan
Journal: Blood (2019)
Allogeneic Anti-Bcma CAR-T Cells Show Tumour Specific Killing Against Primary Multiple Myeloma Cells from Different Genomic Sub-Groups
Authors: Ana M Metelo, Ieuan Walker, Agnieszka Jozwik, Charlotte Graham, Charlotte Attwood, Katy Sanchez, Alan Dunlop, Kirsty Cuthill, Carmel Rice, Matthew Streetly, Trevor Bentley, Bijan Boldajipour, Cesar Sommer, Barbra Sasu, Reuben Benjamin
Journal: Blood (2019)
A Population-Based Analysis of Predictors of Survival and Trends in Outcomes of Elderly Patients with Multiple Myeloma (MM)
Authors: Vivek Kumar, Meghna Ailawadhi, Mays F Abdulazeez, Suman Biswas, Sri Lekha Bodepudi, Leyla Bojanini, Vivek Roy, Taimur Sher, Victoria R. Alegria, Rami Manochakian, Aneel Paulus, Asher A. Chanan-Khan, Sikander Ailawadhi
Journal: Blood (2019)
MNGI-11. HIGH-GRADE AND LOW-GRADE MENINGIOMAS HARBOR DIFFERING METABOLOMIC PROFILES
Authors: Garrett Fitzpatrick, Maryam Rahman, Timothy Garrett, Jesse Kresak
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Meningiomas are the most common primary brain tumor in adults. While the majority of meningiomas are low-grade and effectively treated by resection alone, there is a subset of tumors that have a high incidence of recurrence, metastatic potential, and morbidity. Radiation has been employed with variable success for high-grade meningiomas. No chemotherapeutic approaches have proven effective against these tumors to date. There is a need for a better understanding of this tumor type in order to provide our patients with better treatment options. OBJECTIVE The purpose of this study is to investigate the metabolomic profile of meningiomas with a focus on comparing low- and high-grade tumors and identifying biologically significant metabolites which could correlate with overall and disease-free survival. METHODS Ten tumor samples of each meningioma grade (WHO grades I-III) were collected from the Florida Center for Brain Tumor Research. Global metabolomic profiling by liquid chromatography mass spectrometry was performed on the frozen tumor samples. Statistical analyses were performed using the Southeast Center for Integrated Metabolomics Galaxy interface. Select metabolites which significantly differed between low-grade (WHO Grade I) and high-grade (WHO grade II-III) were identified using the Human Metabolome Database. RESULTS Differing metabolomic profiles between low-grade and high-grade meningiomas were confirmed by multivariate analysis and demonstrated by unsupervised hierarchical clustering. Notably, lysophospholipid and sphingolipid metabolism was increased in the high-grade tumors, while FAPy-adenine, an oxidized nucleoside which may serve as a tumor marker, was decreased. Guanine was found to be consistently decreased in patients with negative outcomes. CONCLUSIONS High-grade and low-grade meningiomas harbor different metabolomic profiles. The significance of these specific differences requires further investigation.
Assessment of Jugular Venous Blood Flow Stasis and Thrombosis During Spaceflight
Authors: Karina Marshall-Goebel, Steven S. Laurie, Irina V. Alferova, Philippe Arbeille, Serena M. Auñón-Chancellor, Douglas J. Ebert, Stuart M. C. Lee, Brandon R. Macias, David S. Martin, James M. Pattarini, Robert Ploutz-Snyder, L. Christine Ribeiro, William J. Tarver, Scott A. Dulchavsky, Alan R. Hargens, Michael B. Stenger
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Exposure to a weightless environment during spaceflight results in a chronic headward blood and tissue fluid shift compared with the upright posture on Earth, with unknown consequences to cerebral venous outflow. <h3>Objectives</h3> To assess internal jugular vein (IJV) flow and morphology during spaceflight and to investigate if lower body negative pressure is associated with reversing the headward fluid shift experienced during spaceflight. <h3>Design, Setting, and Participants</h3> This prospective cohort study included 11 International Space Station crew members participating in long-duration spaceflight missions . Internal jugular vein measurements from before launch and approximately 40 days after landing were acquired in 3 positions: seated, supine, and 15° head-down tilt. In-flight IJV measurements were acquired at approximately 50 days and 150 days into spaceflight during normal spaceflight conditions as well as during use of lower body negative pressure. Data were analyzed in June 2019. <h3>Exposures</h3> Posture changes on Earth, spaceflight, and lower body negative pressure. <h3>Main Outcomes and Measures</h3> Ultrasonographic assessments of IJV cross-sectional area, pressure, blood flow, and thrombus formation. <h3>Results</h3> The 11 healthy crew members included in the study (mean [SD] age, 46.9 [6.3] years, 9 [82%] men) spent a mean (SD) of 210 (76) days in space. Mean IJV area increased from 9.8 (95% CI, −1.2 to 20.7) mm<sup>2</sup>in the preflight seated position to 70.3 (95% CI, 59.3-81.2) mm<sup>2</sup>during spaceflight (<i>P</i> &lt; .001). Mean IJV pressure increased from the preflight seated position measurement of 5.1 (95% CI, 2.5-7.8) mm Hg to 21.1 (95% CI, 18.5-23.7) mm Hg during spaceflight (<i>P</i> &lt; .001). Furthermore, stagnant or reverse flow in the IJV was observed in 6 crew members (55%) on approximate flight day 50. Notably, 1 crew member was found to have an occlusive IJV thrombus, and a potential partial IJV thrombus was identified in another crew member retrospectively. Lower body negative pressure was associated with improved blood flow in 10 of 17 sessions (59%) during spaceflight. <h3>Conclusions and Relevance</h3> This cohort study found stagnant and retrograde blood flow associated with spaceflight in the IJVs of astronauts and IJV thrombosis in at least 1 astronaut, a newly discovered risk associated with spaceflight. Lower body negative pressure may be a promising countermeasure to enhance venous blood flow in the upper body during spaceflight.
DDIS-03. DEVELOPMENT OF A NOVEL CLASS OF cGAS AGONISTS TO TRIGGER STING PATHWAY-DEPENDENT INNATE IMMUNE RESPONSES AGAINST GLIOBLASTOMA
Authors: Alexander Stegh
Journal: Neuro-Oncology (2019)

Abstract The Stimulator of Interferon Genes (STING) pathway represents a major innate immune sensing mechanism for tumor-derived DNA. Modified cyclic dinucleotides (CDNs) that mimic the endogenous STING ligand cGAMP are currently being explored in patients with solid tumors that amenable to intratumoral delivery. Inadequate bioavailability and insufficient lipophilicity are limiting factors for clinical CDN development, in particular when consideration is given to systemic administration approaches. We have shown that the formulation of oligonucleotides into Spherical Nucleic Acid (SNA) nanostructures, i.e., the presentation of oligonucleotides at high density on the surface of nanoparticle cores, lead to biochemical and biological properties that are radically different from those of linear oligonucleotides. First-generation SNAs conjugated with TLR9-agonsitic DNA oligonculeotides (NCT03086278; solid cancers) and intravenously administered, brain-penetrant siRNA-based SNAs (NCT03020017, recurrent GBM) have recently entered clinical trials. Here, we report the development of a STING-agonistic immunotherapy by targeting cGAS, the sensor of cytosolic dsDNA upstream of STING, with SNAs presenting dsDNA at high surface density. The strategy of using SNAs exploits the ability of cGAS to raise STING responses by delivering dsDNA and inducing the catalytic production of endogenous CDNs. SNA nanostructures carrying a 45bp IFN-simulating dsDNA oligonucleotide, the most commonly used and widely characterized cGAS activator, potently activated the cGAS-STING pathway, as evidenced by increased IRF responses, elevated protein marker expression indicative of the activated M1 macrophage state, and enhanced expression of pro-inflammatory cytokines in macrophage cultures in vitro, and in intracranial isogenic GBM explants in vivo. Our use of SNAs addresses the challenges of nucleic acid delivery to intracranial tumor sites, exploits the binding of closely-spaced, neighboring dsDNA molecules on the SNA surface to enhance the formation of a dimeric cGAS:DNA complex, and establishes cGAS-agonistic SNAs as a novel class of immune-stimulatory modalities for triggering innate immune responses against tumor.
Excessive Weight Gain Before and During Gestational Diabetes Mellitus Management: What Is the Impact?
Authors: Robyn A. Barnes, Tang Wong, Glynis P. Ross, Michelle M. Griffiths, Carmel E. Smart, Clare E. Collins, Lesley MacDonald-Wicks, Jeff R. Flack
Journal: Diabetes Care (2019)

OBJECTIVE Conventional gestational diabetes mellitus (GDM) management focuses on managing blood glucose in order to prevent adverse outcomes. We hypothesized that excessive weight gain at first presentation with GDM (excessive gestational weight gain [EGWG]) and continued EGWG (cEGWG) after commencing GDM management would increase the risk of adverse outcomes, despite treatment to optimize glycemia. RESEARCH DESIGN AND METHODS Data collected prospectively from pregnant women with GDM at a single institution were analyzed. GDM was diagnosed on the basis of Australasian Diabetes in Pregnancy Society 1998 guidelines (1992–2015). EGWG means having exceeded the upper limit of the Institute of Medicine–recommended target ranges for the entire pregnancy, by GDM presentation. The relationship between EGWG and antenatal 75-g oral glucose tolerance test (oGTT) values and adverse outcomes was evaluated. Relationships were examined between cEGWG, insulin requirements, and large-for-gestational-age (LGA) infants. RESULTS Of 3,281 pregnant women, 776 (23.6%) had EGWG. Women with EGWG had higher mean fasting plasma glucose (FPG) on oGTT (5.2 mmol/L [95% CI 5.1–5.3] vs. 5.0 mmol/L [95% CI 4.9–5.0]; P &amp;lt; 0.01), after adjusting for confounders, and more often received insulin therapy (47.0% vs. 33.6%; P &amp;lt; 0.0001), with an adjusted odds ratio (aOR) of 1.4 (95% CI 1.1–1.7; P &amp;lt; 0.01). aORs for each 2-kg increment of cEGWG were a 1.3-fold higher use of insulin therapy (95% CI 1.1–1.5; P &amp;lt; 0.001), an 8-unit increase in final daily insulin dose (95% CI 5.4–11.0; P &amp;lt; 0.0001), and a 1.4-fold increase in the rate of delivery of LGA infants (95% CI 1.2–1.7; P &amp;lt; 0.0001). CONCLUSIONS The absence of EGWG and restricting cEGWG in GDM have a mitigating effect on oGTT-based FPG, the risk of having an LGA infant, and insulin requirements.
Fractional analysis of bronchoalveolar lavage fluid cytology in cystic fibrosis patients with normal lung function
Authors: F. Ratjen, E Rietschel, M Griese, M. Ballmann, I Kleinau, G Döring, D Reinhardt, K Paul, None for the bronchoalveolar lavage for the evaluation of anti-inflammatory treatment (beat) study group
Journal: European Respiratory Journal (2000)

Cystic fibrosis (CF) is associated with a neutrophil dominated airway inflammation. So far bronchoalveolar lavage (BAL) studies in CF have used pooled BAL samples which may be more representative of the alveolar compartment rather than the airways. To assess whether the first sample of a BAL is more sensitive in the evaluation of airway inflammation, the authors have studied 105 stable CF patients aged 5-37 yrs with a mean forced expiratory volume in one second (FEV1) of 96+/-15% (mean+/-SD). BAL cytology of the first and pooled samples were compared to reference values obtained in children without respiratory disease. Absolute cell counts and the percentage of neutrophils were significantly increased in CF patients. If the 95% confidence interval was used as a cut-off point, 17/105 CF patients had a normal percentage of neutrophils in pooled BAL samples, but only three also had a normal percentage of neutrophils in the first BAL aliquot. Therefore, neutrophil dominated airway inflammation is more pronounced in the first, mainly bronchial, bronchoalveolar lavage sample suggesting that sequential analysis of bronchoalveolar lavage fluid may have a higher sensitivity to detect early inflammatory changes in CF patients.
Experience of online peer support for alopecia
Authors: L.L. Iliffe, A.R. Thompson
Journal: British Journal of Dermatology (2019)

Patients and their family members can find it helpful to share their stories with fellow sufferers. Online groups are particularly useful for those who are shy or self‐conscious about how they look. Alopecia UK is a support group for people experiencing hair loss. Their website links to a monitored Facebook group restricted to members. There is not much research into the benefits of online support for skin conditions, so these psychologists from Sheffield in the UK interviewed 12 people who had been helped by the Alopecia UK Facebook group. The usual method for this type of research is “content analysis” in which patient interviews are analysed to identify themes. These researchers used “interpretative phenomenological analysis”. First, they asked participants for a screenshot of a post they had found particularly helpful. Then they asked a set of questions about their experience with the website and with the screenshot. Finally, they analysed the interviews to look for themes expressed both by individuals and by the group. The participants, all women, described how the online forum enabled them to let go of feelings of misery and unattractiveness, to share practical tips about dealing with their appearance, to feel less alone and more normal and to become more accepting of their appearance and more confident socially. A few reported unhelpful comments and inaccurate advice. The study suggests that online peer support can encourage sufferers to adjust to chronic (long‐term) conditions by connecting them within a safe and private community. Platforms like this could be used in combination with other therapies.
Phase 1/2 Study of Tirabrutinib (ONO/GS-4059), a Next-Generation Bruton's Tyrosine Kinase (BTK) Inhibitor, Monotherapy in Patients with Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL)
Authors: Motoo Nagane, Yoshitaka Narita, Kazuhiko Mishima, Yasuhito Terui, Yoshiki Arakawa, Hajime Yonezawa, Katsunori Asai, Noriko Fukuhara, Kazuhiko Sugiyama, Naoki Shinojima, Junsaku Kitagawa, Arata Aoi, Ryo Nishikawa
Journal: Blood (2019)
Broad Efficacy of the Translation Inhibitor Omacetaxine in Relapsed/Refractory Multiple Myeloma Samples
Authors: Zachary J Walker, Beau M Idler, Michael J VanWyngarden, Brett M. Stevens, Shelby C Bearrows, Lorraine N Davis, Andrew Hammes, Clayton Smith, Craig T Jordan, Tomer M Mark, Peter A Forsberg, Daniel W Sherbenou
Journal: Blood (2019)
Risk of Relapse after Anti-PD1 Discontinuation and Efficacy of Anti-PD1 Re-Treatment in Patients with Hodgkin Lymphoma
Authors: Guillaume Manson, Pauline Brice, Charles Herbaux, Maria Silva, Krimo Bouabdallah, Bénédicte Deau-Fisher, Juliette Bouteloup, Jean Marc Schiano de Collela, Emmanuelle Nicolas-Virelizier, Marie Maerevoet, Herve Ghesquieres, Aspasia Stamatoulas Bastard, Chloe Antier, Florence Poizeau, Laurent Dercle, Roch Houot
Journal: Blood (2019)
Personal Use of Drug Samples by Physicians and Office Staff
Authors: Fred Rosner
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Dr Westfall and colleagues<sup>1</sup>consider the personal use of drug samples by physicians and office staff to constitute "a substantial gift from pharmaceutical companies" and that "the ethical implications... warrant further debate." Gifts to physicians from the pharmaceutical industry constitute a long-accepted tradition in the complex relationships between drug companies and the medical profession. Medical students are offered free books, free reflex hammers, free tuning forks, and a variety of other gifts. At medical conventions, physicians strolling through the exhibition halls are able to obtain gratis dozens of different items from pens to key chains, from calculators to watches, from tennis balls to floppy disks, from fresh juices to espresso coffee, and on and on.<sup>2</sup> Should these gifts be considered to constitute a bribe? Are these gifts given freely by the pharmaceutical industry with no ulterior motives? Although drug companies and biotechnology firms consider these gifts to be
Interim Analysis of a Prospective Multicentre Study Using Next Generation Sequencing for Kinase Domain Mutational Analysis in CML Patients on First or Subsequent TKI Therapy
Authors: Hugues De Lavallade, Sophie Jackson, Heather Oakervee, Sebastian Francis, Edward Belsham, Paul Cahalin, Joanne Ewing, Jenny Byrne, Kate Rothwell, Sandra Hassan, Srinivas Pillai, Priyanka Mehta, Anshu Garg, Mhairi Copland, Oliver Ottmann, Deepti Radia, Patrick Harrington, Rachel Greig, Nicholas Lea, Michael Thompson, Aytug Kizilors
Journal: Blood (2019)
A Cross-Sectional Study Examining the Effects of Patient Information Level on Healthcare Experience in 2 Patient Populations: Extranodal Natural Killer T-Cell Lymphoma (ENKTL) and Waldenstrom Macroglobulinemia (WM)
Authors: Natalie M Dren, Lorna E Warwick, Olufunmilayo A Bamigbola
Journal: Blood (2019)
The Efficacy and Safety Profile of Ixazomib-Based Regimens in Patients with Relapsed/Refractory Multiple Myeloma in Routine Clinical Practice: Real World Data from a Multi-Center Study in China
Authors: Jing Li, Li Bao, Zhong-jun Xia, Kaiyang Ding, Bingzong Li, Bing Chen, Zhengzheng Fu, Sili Wang, Wenhao Zhang, Xin Zhou, Luoming Hua, Wei Yang, Luo Jun, Liang Wang, Tianhong Xu, Yang Yang, Weida Wang, Guolin Wu, Yun Huang, Peng Liu
Journal: Blood (2019)
Safety Profile for Lenalidomide-Based and Non-Lenalidomide-Based First-Line Therapy for Multiple Myeloma in Transplant Ineligible Patients: Real-World Evidence from a European Post-Authorization Safety Study
Authors: Michele Cavo, Valerio De Stefano, Angel Ramirez Payer, Martin Wiesholzer, Yvonne Tromp, Gaëtan Vanstraelen, Baerbel Schaedlich, Richez Valentine, Sujith Dhanasiri, Elisabeth Kueenburg, Barbara Rosettani, Claire Martin, Stefano Pozzi, Pamela Bacon, Barbara Gamberi
Journal: Blood (2019)
Longitudinal profiling of plasma cytokines in melioidosis and their association with mortality: a prospective cohort study
Authors: T. Kaewarpai, P. Ekchariyawat, R. Phunpang, S.W. Wright, A. Dulsuk, B. Moonmueangsan, C. Morakot, E. Thiansukhon, N.P.J. Day, G. Lertmemongkolchai, T.E. West, N. Chantratita
Journal: Clinical Microbiology and Infection (2019)

ObjectivesTo characterize plasma cytokine responses in melioidosis and analyse their association with mortality.MethodsA prospective longitudinal study was conducted in two hospitals in Northeast Thailand to enrol 161 individuals with melioidosis, plus 13 uninfected healthy individuals and 11 uninfected individuals with diabetes to act as controls. Blood was obtained from all individuals at enrolment (day 0), and at days 5, 12 and 28 from surviving melioidosis patients. Interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, and tumour necrosis factor-α (TNF-α) were assayed in plasma. The association of each cytokine and its dynamics with 28-day mortality was determined.ResultsOf the individuals with melioidosis, 131/161 (81%) were bacteraemic, and 68/161 (42%) died. On enrolment, median levels of IFN-γ, IL-6, IL-8, IL-10, IL-23 and TNF-α were higher in individuals with melioidosis compared with uninfected healthy individuals and all but IFN-γ were positively associated with 28-day mortality. Interleukin-8 provided the best discrimination of mortality (area under the receiver operating characteristic curve 0.78, 95% CI 0.71–0.85). Over time, non-survivors had increasing IL-6, IL-8 and IL-17A levels, in contrast to survivors. In joint modelling, temporal trajectories of IFN-γ, IL-6, IL-8, IL-10 and TNF-α predicted survival.ConclusionsIn a severely ill cohort of individuals with melioidosis, specific pro- and anti-inflammatory and T helper type 17 cytokines were associated with survival from melioidosis, at enrolment and over time. Persistent inflammation preceded death. These findings support further evaluation of these mediators as prognostic biomarkers and to guide targeted immunotherapeutic development for severe melioidosis.
Azacitidine in Pediatric Hematologic Myeloid Malignancies: A Retrospective Study
Authors: Emilie Saucier, Florence Rabian, Hélène Boutroux, Marion Strullu, Karine Morand, Florian Chevillon, Benoit Brethon, Nicolas Boissel, Guy Leverger, André Baruchel
Journal: Blood (2019)
A Novel Chemical Compound Inhibiting Hematopoietic Cell Kinase (iHCK) Has a Synergic Effect with Azacytidine (Aza) or Cytarabine (Ara-C) for Acute Myeloid Leukemia Treatment
Authors: Fernanda Marconi Roversi, Maura Lima Pereira Bueno, Cristiane Okuda Torello, Fernanda I Della Via, Renata Giardini Rosa, Juares Ednaldo Romero Bianco, Adriana Silva Santos Duarte, Eduardo M Rego, Alessio Molinari, Maurizio Botta, Sara T Olalla Saad
Journal: Blood (2019)