tbuckley/cabot-search huggingface dataset:
The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies
Authors: Changbin Zhu, Johan M Kros, Caroline Cheng, Dana Mustafa
Journal: Neuro-Oncology (2017)

"Tumor-associated macrophages" (TAMs) form a significant cell population in malignant tumors and contribute to tumor growth, metastasis, and neovascularization. Gliomas are characterized by extensive neo-angiogenesis, and knowledge of the role of TAMs in neovascularization is important for future anti-angiogenic therapies. The phenotypes and functions of TAMs are heterogeneous and more complex than a classification into M1 and M2 inflammation response types would suggest. In this review, we provide an update on the current knowledge of the ontogeny of TAMs, focusing on diffuse gliomas. The role of TAMs in the regulation of the different processes in tumor angiogenesis is highlighted and the most recently discovered mechanisms by which TAMs mediate resistance against current antivascular therapies are mentioned. Novel compounds tested in clinical trials are discussed and brought in relation to different TAM-related angiogenesis pathways. In addition, potential therapeutic targets used to intervene in TAM-regulated tumor angiogenesis are summarized.
Hospitalization for Acute Pain in Sickle Cell Disease: Changes in Clinical Parameters and Factors Predicting Hospital Discharge and Re-Admission
Authors: Mehdi Nouraie, Debra L Weiner, Mariana Hildesheim, Ward Hagar, Oswaldo L Castro, Sophie Lanzkron, Victor R. Gordeuk, James F. Casella, Mark T. Gladwin, Gregory J. Kato
Journal: Blood (2016)
Prevalence of food allergies and intolerances documented in electronic health records
Authors: Warren W. Acker, Joseph M. Plasek, Kimberly G. Blumenthal, Kenneth H. Lai, Maxim Topaz, Diane L. Seger, Foster R. Goss, Sarah P. Slight, David W. Bates, Li Zhou
Journal: Journal of Allergy and Clinical Immunology (2017)
The influence of communication mode on written language processing and beyond
Authors: Laura Barca, Giovanni Pezzulo
Journal: Behavioral and Brain Sciences (2017)

Abstract Empirical evidence suggests a broad impact of communication mode on cognition at large, beyond language processing. Using a sign language since infancy might shape the representation of words and other linguistic stimuli – for example, incorporating in it the movements and signs used to express them. Once integrated into linguistic representations, this visuo-motor content can affect deaf signers’ linguistic and cognitive processing.
Near point convergence and other measures of vestibulo-ocular dysfunction are associated with protracted neurological recovery after sports concussion
Authors: Andrew Russman, Susan Linder, Bob Grey, Rick Figler, Jason Cruickshank, Maureen Lally, Jay Alberts, Tanujit Day
Journal: British Journal of Sports Medicine (2017)

Objective To characterise specific measures of neurologic dysfunction and recovery associated with concussion in student-athletes using the clinical examination and Cleveland Clinic Concussion application (C3 app). Design Retrospective observational study Setting Tertiary sports concussion clinic Participants 181 student-athletes aged 14-20 diagnosed with concussion by a Cleveland Clinic physician were included. Interventions C3 data were collected pre-season, and at least once post-injury, along with a physician clinical examination. Individuals were stratified into two groups based on recovery time: typical &lt;21 days (n=97) or protracted 21+ days (n=84). Outcome measures Near point convergence (NPC) and the following modules of the C3 app were administered: 1) Graded symptom checklist (GSC); 2) Standardised Assessment of Concussion (SAC); 3) Trail Making Test (TMT); 4) Simple and Choice Reaction Time; 5) Processing Speed Test (PST); 6) Biomechanical quantification of balance during the BESS. Main results At baseline, both groups performed similarly on all C3 modules. Significant differences in NPC were seen among the typical versus protracted group (mean 7.62 cm versus 13.57 cm, p=0.0002). Also, significantly worse performance among the protracted group was seen in GSC (p=0.0001), and measures affected by vestibulo-ocular dysfunction including biomechanical quantification of BESS (p&lt;0.05), simple and choice reaction time (p&lt;0.001), and TMT-B (p=0.01). No difference between groups was noted in BESS errors, SAC, or PST. Conclusions Abnormal NPC or convergence insufficiency is associated with protracted recovery and should be included in the assessment of student-athletes at baseline and post-injury. Identification of vestibulo-ocular dysfunction helps guide post-concussion assessment, treatment, and return-to-play decision-making. Competing interests Bob Gray, Rick Figler, Jason Cruickshank, Maureen Lally, Tanujit Day: None. Susan Linder and Jay Alberts have authored intellectual property associated with the mobile application presented in this study.
Lancet Commission: Stem cells and regenerative medicine
Authors: Giulio Cossu, Martin Birchall, Tracey Brown, Paolo De Coppi, Emily Culme-Seymour, Sahra Gibbon, Julian Hitchcock, Chris Mason, Jonathan Montgomery, Steve Morris, Francesco Muntoni, David Napier, Nazanin Owji, Aarathi Prasad, Jeff Round, Prince Saprai, Jack Stilgoe, Adrian Thrasher, James Wilson
Journal: The Lancet (2017)
Volume d’activité et effets indésirables dans les suites de dissection sous-muqueuse oesophagienne au japon
Journal: Endoscopy (2017)

La dissection sous muqueuse s’est imposée comme traitement endoscopique des tumeurs superficielles du tube digestif inaccessibles à une résection monobloc par mucosectomie. Les premières séries de publications émanaient exclusivement de centres experts et rapportaient de faibles taux de complications.
Hospital-Level Variation in Postpartum Readmissions
Authors: Mark A. Clapp, Sarah E. Little, Jie Zheng, Anjali J. Kaimal, Julian N. Robinson
Journal: JAMA (2017)

This study uses obstetric readmission rates from the 2013 National Readmission Database to describe hospital variance in postpartum readmissions and the percentage of variance attributed to hospital factors.
ATRT-09. CHROMATIN SEGMENTATION ANALYSES IN ATYPICAL TERATOID/RHABDOID TUMORS REVEAL H3K27ME3-MEDIATED EPIGENETIC SILENCING OF TUMOR SUPPRESSOR GENES AND IDENTIFY A NOVEL ROLE OF EZH2, ASSOCIATED WITH ACTIVE CHROMATIN
Authors: Pascal D. Johann, Serap Erkek, Lukas Chavez, Martina Finetti, Kornelius Kerl, Marc Zapatka, Amar Gajjar, Martin Hasselblatt, Stefan M. Pfister, Marcel Kool
Journal: Neuro-Oncology (2017)

Although SMARCB1 mutations represent the only genetic aberrations in atypical teratoid / rhabdoid tumors (ATRT), a comprehensive assessment of the epigenetic effect of SMARCB1 loss has not been achieved so far. We performed ChIP-sequencing for six active and repressive histone marks (H3K4me1, H3K4me3, H3K27me3, H3K27Ac, H3K9me3, H3K36me3) and EZH2 in 11 primary ATRTs, encompassing all three molecular subgroups of ATRT. Chromatin segmentation analyses revealed that across all three subgroups a high percentage of ATRT genomes resides in a quiescent state and active enhancer states are significantly underrepresented as compared to non-neoplastic brain tissues. These data show that loss of SMARCB1 generally results in a subgroup independent repression of genes In addition, we observed gain of the repressive mark H3K27me3 in ATRTs at genes bound by SMARCB1 in normal brain, in line with the known antagonistic role between SMARCB1 and EZH2. Tumor suppressor genes and neuronal transcription factors (such as NEUROD2) were particularly affected by this mechanism of epigenetic silencing. Interestingly, by comparing the genome wide distribution of EZH2 and H3K27me3, we also identified classes of ATRT-specific active genes bound by EZH2, but lackingH3K27me3, pointing at a non-canonical role of EZH2 in gene activation. In subgroup ATRT-TYR, which displayed the most striking pattern of EZH2 associated gene activation, this pattern could for instance explain the overexpression of previously identified subgroup specific signature genes such as BMP4. The comprehensive study of histone marks in this genomically simple but epigenetically heterogeneous disease enabled us to not only shed light on the chromatin landscape of these tumors but also on the potentially tumorigenic consequences of SMARCB1 loss. In addition, the dual role of EZH2 in these tumors further enhances the importance of this molecule as a therapeutic target.
Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease
Authors: Frederick E. Dewey, Viktoria Gusarova, Richard L. Dunbar, Colm O’Dushlaine, Claudia Schurmann, Omri Gottesman, Shane McCarthy, Cristopher V. Van Hout, Shannon Bruse, Hayes M. Dansky, Joseph B. Leader, Michael F. Murray, Marylyn D. Ritchie, H. Lester Kirchner, Lukas Habegger, Alex Lopez, John Penn, An Zhao, Weiping Shao, Neil Stahl, Andrew J. Murphy, Sara Hamon, Aurelie Bouzelmat, Rick Zhang, Brad Shumel, Robert Pordy, Daniel Gipe, Gary A. Herman, Wayne H.H. Sheu, I-Te Lee, Kae-Woei Liang, Xiuqing Guo, Jerome I. Rotter, Yii-Der I. Chen, William E. Kraus, Svati H. Shah, Scott Damrauer, Aeron Small, Daniel J. Rader, Anders Berg Wulff, Børge G. Nordestgaard, Anne Tybjærg-Hansen, Anita M. van den Hoek, Hans M.G. Princen, David H. Ledbetter, David J. Carey, John D. Overton, Jeffrey G. Reid, William J. Sasiela, Poulabi Banerjee, Alan R. Shuldiner, Ingrid B. Borecki, Tanya M. Teslovich, George D. Yancopoulos, Scott J. Mellis, Jesper Gromada, Aris Baras
Journal: New England Journal of Medicine (2017)

Loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease.
Video analysis of the evidence of concussive signs in national rugby league (nrl) match play
Authors: Andrew J Gardner, Christopher R Levi, Grant L Iverson
Journal: British Journal of Sports Medicine (2017)

Objective A video analysis of 201 National Rugby League (NRL) matches to document all signs of possible concussion during the 2014 season. Setting All match play from the 2014 NRL season. Participants All professional players participating in the 2014 season Outcome measures The total frequency of six concussion signs (unresponsiveness/loss of consciousness, slow to get up, clutching head, unsteadiness of gait, vacant stare, and seizure). Main results The concussion interchange rule was used 156 times, with 60 medically diagnosed concussions. The incidence rate for concussion was 17.26 (95% CI=13.44–22.16) per 1,000 player match hours, or approximately one concussion every 3.35 games. There were 127,062 tackles reviewed in the 201 matches, for an average of 632.1 tackles per match. Being slow to get up was observed 2,240 times, clutching the head 361 times, unsteadiness of gait 102 times, vacant stare 98 times, possible loss of consciousness (LOC) 52 times, and a seizure 4 times. Of the 2,240 instances of being slow to get up following a tackle, only 2.7% of those cases involved a medically diagnosed concussion. Of the 52 instances in which a player appeared to have brief LOC, 50 players were removed under the concussion interchange rule (96.2%). Of those 50, 24 were medically diagnosed as having sustained a concussion (48%). Conclusions Reviewing match video footage can be a useful addition to the sideline assessment of concussion. Competing interests Andrew Gardner has a clinical practice in neuropsychology involving individuals who have sustained sport-related concussion (including current and former athletes). He serves, in a voluntary capacity, as a member of the Australia Rugby Union (ARU) concussion advisory group. He has received travel funding from the Australian Football League (AFL) to present at the Concussion in Football Conference in 2013. Previous grant funding includes the NSW Sporting Injuries Committee, the Brain Foundation and the Hunter Medical Research Institute (HMRI), supported by Jennie Thomas. He is currently funded through the HMRI, supported by Anne Greaves. Grant Iverson has been reimbursed by the government, professional scientific bodies, and commercial organisations for discussing or presenting research relating to mild TBI and sport-related concussion at meetings, scientific conferences, and symposiums. He has a clinical and consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs (including professional athletes). Christopher Levi none.
Abstract 20459: Calcium/Calmodulin-Dependent Protein Kinase II Regulates KCNQ1 to Reduce the Slow Component of the Delayed Rectifier Potassium Current, IKs
Authors: Tyler Shugg, Minghai Shao, Aarti Chawla, Michael Rubart-von der Lohe, Andy Hudmon, Brian R Overholser
Journal: Circulation (2016)

Introduction: Sustained β-adrenergic receptor (β-AR) activation during heart failure has pathologic consequences including enhanced calcium/calmodulin-dependent protein kinase II (CaMKII) activity,...
MEDU-28. INVESTIGATING THE ROLE OF THE RNA BINDING PROTEIN, MUSASHI, IN GROUP 3 MEDULLOBLASTOMA
Authors: Michelle Kameda-Smith, Chitra Venugopal
Journal: Neuro-Oncology (2017)

Pediatric brain tumours are the leading cause of solid cancer mortality with medulloblastoma (MB) representing the most frequent malignant solid central nervous system (CNS) tumour. To date, most experimental efforts to understand the biological mechanism of solid cancers have been directed towards transcriptional regulatory mechanisms that modulate fate determination in stem and progenitor cells. However, little is known regarding post-transcriptional pathways that contribute to mRNA stability, translation into protein, and functional effects on cell fate. The mRNA binding protein, Musashi (Msi) has been observed to play a crucial role in promoting stem cell self–renewal and is implicated in CNS tumours including glioma and MB with associated poor clinical prognosis. Since the initial description of the “medulloblast” as the putative MB cell of origin, a crucial association between neural stem cells and MB tumorigenesis has long been postulated. Contemporary experimental frameworks recognize this paradigm as the cancer stem cell hypothesis. Since increasing brain tumour stem cell or brain tumour-initiating cell (BTIC) frequency is associated with tumor aggressiveness and poor patient outcome, we probed for Msi1 within 251 primary human MBs from four transcriptional databases and 74 NanoString-subgrouped MBs, and found it was enriched in aggressive MB subgroups. Applying gene knockdown and overexpression of Msi1 and 2 in Group 3 MB, we have performed in vitro assays elucidating how these RNA-binding proteins help to maintain the BTIC state. In parallel, cross-linking and immunoprecipitation experimentation have shed some light on the mechanism of Msi’s influence on RNA fate. Though transcriptional manipulation has uncovered novel druggable targets to treat MB, bench-to-bedside clinical translation of these targets has yet to yield significant patient benefit. For the first time, Msi analysis in MB provides a novel paradigm for treatment of MB through targeting post-transcriptional pathways and regulators.
Abstract 177: Interleukin 17 and Coronary Stenosis in Patients With Stable Coronary Artery Disease
Authors: Dinaldo Oliveira, Elaine Heide, Maira Pita, Danielle A Oliveira, Ricardo Pontes, Ivan Pitta
Journal: Circulation Research (2015)

Introduction: The role of the immune and inflammatory pathways in patients with coronary artery disease (CAD) is important but not complete understood. The aim of this study was to evaluate concentrations of the interleukins 17 (IL 17) according to severity of coronary stenosis in patients with stable CAD Hypothesis: There is no association between severity of coronary stenosis and IL 17 in patients with stable CAD. Methods: This is a cross-sectional, prospective, analytical study, conducted from january to september, 2013. We included 40 patients (P) with stable CAD, CCS III or IV, ischemic myocardial scintigraphy, who had not been subjected to any kind of myocardial revascularization and with coronary stenosis ≥ 50% according to current coronary angiography. There were 20 healthy volunteers (C), to take up comparison of concentrations of IL 17. Interleukins were evaluated in serum of patients and after 48 hours of cells in culture with and without stimulus. IL 17 A concentrations were expressed in pg / ml. Coronary stenosis were classified as severe (&gt; 70%) [SS] and intermediate (50 - 69%) [MS] according to coronary angiography. Results: Stenosis ≥ 50% were found in the anterior descending artery in 31 patients, in the left circumflex artery in 19 patients, and in the right coronary artery in 24 patients. No cases of stenosis were observed in the left main. Eighteen patients (45%) had single-artery disease, 8 patients (20%) had two-artery disease, and 14 patients (35%) had multiarterial disease. The comparison between the groups showed: IL 17: Serum: P with SS = 3.91 (3.91 -- 72.27) vs P with MS = 3.91 (3.91 -- 3.91) vs C = 3.91 (3.91 -- 28.8), p = 0.53; culture 48 hours without stimulus: P with SS = 3.91 (3.91 -- 3.91) vs P with MS = 3.91 (3.91 -- 86.8) vs C = 3.91 (3.91 -- 53.3), p = 0.55; culture 48 hours with stimulus: P with SS = 241.8 (3.91 -- 2200) vs P with MS = 217.5 (3.91 -- 1346) vs C = 154.3 (3.91 -- 1353), p = 0.7. Conclusions: There were no differences in concentrations of IL 17 according to severity of coronary stenosis, does not matter in serum or cell in culture. In conclusion, there was no association between severity of coronary stenosis and IL 17 in patients with stable CAD
Improved prediction of subconcussive neurophysiological changes by kinematic impulse
Authors: Thomas M Talavage, Katherine M Breedlove, Evan L Breedlove, Kausar Abbas, Trey Shenk, Thomas G Bowman, Eric A Nauman, Larry J Leverenz
Journal: British Journal of Sports Medicine (2017)

Objective For both subconcussive impacts and traditionally-defined concussion, neither the number of head impacts nor the magnitude has had a strong correlation to the incidence or severity of injury. Recent modelling work has suggested that impulse may be an important biomechanical factor, and therefore it is hypothesised that it may be a good predictor of subconcussive neurophysiological changes. Design Observational study. Setting American high school football team. Participants Nine male high school football athletes (mean age=16.4, range=15–17) volunteered. All participants were enrolled with parental consent. Assessment of risk factors Head impacts were monitored at all practices and games with the Head Impact Telemetry System. Baseline neurophysiology was measured prior to contact activity using a functional magnetic resonance imaging (fMRI) visual n-back task protocol. Subjects returned throughout the season and were re-evaluated according to the same protocol. Outcome measures Kinematic impulse was computed from head impact telemetry. Changes in neurophysiology were determined as the difference in the 2 vs. 1-back contrast. This contrast was determined for 116 anatomically defined regions of interest (ROI). Main results Stepwise regressions (P=0.05) relating kinematic impulse to ROI-specific changes in neurophysiology yielded significant correlations for 57/116 ROIs. 22/116 ROIs had an R2 value greater than 0.70. Correlations were found bilaterally for 16 anatomical ROIs, including the executive pre-frontal regions, basal ganglia, and thalamus. Conclusions The relationship between kinematic impulse and fMRI changes reported here are the strongest correlations to subconcussive changes reported to date. Correlations were observed bilaterally in regions associated with concussion symptoms. Competing interests None.
Increasing proportion of carbapenemase-producing Enterobacteriaceae and emergence of a MCR-1 producer through a multicentric study among hospital-based and private laboratories in Belgium from September to November 2015
Authors: Te Din Huang, Pierre Bogaerts, Catherine Berhin, Martin Hoebeke, Caroline Bauraing, Youri Glupczynski
Journal: Eurosurveillance (2017)

Carbapenemase-producing Enterobacteriaceae (CPE) strains have been increasingly reported in Belgium. We aimed to determine the proportion of CPE among Enterobacteriaceae isolated from hospitalised patients and community outpatients in Belgium in 2015. For the hospitalised patients, the results were compared to a previous similar survey performed in the same hospitals in 2012. Twenty-four hospital-based and 10 private laboratories collected prospectively 200 non-duplicated Enterobacteriaceae isolates from clinical specimens. All isolates were screened locally by carbapenem disk diffusion using European Committee on Antimicrobial Susceptibility Testing methodology. Putative CPE strains with inhibition zone diameters below the screening breakpoints were referred centrally for confirmation of carbapenemase production. From September to November 2015, we found a proportion of clinical CPE of 0.55% (26/4,705) and of 0.60% (12/1,991) among hospitalised patients and among ambulatory outpatients respectively. Klebsiella pneumoniae (26/38) and OXA-48-like carbapenemase (28/38) were the predominant species and enzyme among CPE. One OXA-48-producing Escherichia coli isolated from a hospital was found carrying plasmid-mediated MCR-1 colistin resistance. Compared with the 2012 survey, we found a significant increased proportion of clinical CPE (0.55% in 2015 vs 0.25% in 2012; p = 0.02) and an increased proportion of hospitals (13/24 in 2015 vs 8/24 in 2012) with at least one CPE detected. The study results confirmed the concerning spread of CPE including a colistin-resistant MCR-1 producer in hospitals and the establishment of CPE in the community in Belgium.
DIPG-06. REDEFINING THE CELLULAR ARCHITECTURE OF DIFFUSE MIDLINE GLIOMAS WITH H3 K27M MUTATIONS THROUGH LARGE-SCALE SINGLE-CELL ANALYSES
Authors: Mariella G. Filbin, Volker Hovestadt, Itay Tirosh, McKenzie Shaw, David N. Louis, Irene Slavc, Thomas Czech, Kristine Pelton, Liliana Goumnerova, Pratiti Bandopadhayay, Mark W. Kieran, Keith Ligon, Todd Golub, Brad Bernstein, Aviv Regev, Mario Suva
Journal: Neuro-Oncology (2017)

While human tumors are shaped by the genetic evolution of cancer cells, evidence also suggests that they display superimposed hierarchies reminiscent of normal development. Yet, relating the genetic and hierarchical models of cancer organization has been limited by technical challenges. Here, studying H3 K27M-mutant diffuse midline gliomas we profiled thousands of single cells from fresh tumors by RNA-seq and reconstructed the genetic and epigenetic cellular architecture of tumors in patients. We identified a subset of cancer cells that are differentiated along specialized glial programs while a distinct subset expresses neural stem/progenitor expression programs. By identifying distinct genetic clones, we show that these cellular architectures evolve during the progression of the tumors, suggesting that developmental programs and genetic influences coordinately determine tumor architecture. These results provide unprecedented insight into the cellular composition of midline brain tumors at single-cell resolution and may help harmonize the cancer stem cell and the genetic models of cancer, with critical implications for disease management.
Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models
Authors: Zhen Lu, Bingfeng Zuo, Renwei Jing, Xianjun Gao, Quan Rao, Zhili Liu, Han Qi, Hongxing Guo, HaiFang Yin
Journal: Journal of Hepatology (2017)