tbuckley/cabot-search huggingface dataset:
Metabolic heterogeneity and plasticity of glioma stem cells in a mouse glioblastoma model
Authors: Shunsuke Shibao, Noriaki Minami, Naoyoshi Koike, Nobuyuki Fukui, Kazunari Yoshida, Hideyuki Saya, Oltea Sampetrean
Journal: Neuro-Oncology (2017)

Glioblastomas have been shown to rely on glycolysis as an energy source. However, recent evidence suggests that at least a subset of glioma cells with stem cell–like properties can thrive on oxidative phosphorylation. It remains unclear whether both metabolic phenotypes support tumor propagation, if they are independent, and how stable they are. The present study investigated these questions with the use of isogenic murine glioma stem cells (GSCs). GSCs were established from tumors formed by Ink4a/Arf–null, H-RasV12-expressing glioma-initiating cells that differed in extracellular acidification potential. Metabolic characteristics of GSCs were determined by measurement of glucose, oxygen, and glutamine uptake, ATP content, and lactate production. Effects of metabolic inhibitors and changes in oxygen or nutrient availability on lactate production and tumorsphere growth were also determined. GSCs were found either to consume more glucose and produce more lactate or to consume more oxygen and maintain a higher ATP content depending on the metabolic characteristics of the tumor cells of origin. The latter, mitochondrial-type GSCs increased lactate production after treatment with the oxidative phosphorylation inhibitor oligomycin or phenformin. Exposure to hypoxia also increased lactate production and expression of glycolysis-related enzymes and metabolites in mitochondrial-type GSCs in a reversible manner. Both glycolytic and mitochondrial-type energy production can sustain tumor propagation by isogenic GSCs. Whereas both phenotypes can be independent and stable, cells that rely on oxidative phosphorylation can also switch to a more glycolytic phenotype in response to metabolic stress, suggesting that plasticity is a further characteristic of GSC metabolism.
Clonal Hematopoiesis Increases Risk of Therapy-Related Myeloid Neoplasms
Authors: Koichi Takahashi, Feng Wang, Hagop M. Kantarjian, Doss Denaha, Kanhav Khann, Keyur P. Patel, Sattva S. Neelapu, Curtis Gumbs, Carlos E Bueso-Ramos, Courtney D. DiNardo, Simona Colla, Farhad Ravandi, Jianhua Zhang, Xifeng Wu, Felipe Samaniego, Guillermo Garcia-Manero, Andrew Futreal
Journal: Blood (2016)
Evaluation of respiratory function monitoring during the resuscitation of prematurely born infants
Authors: Antonia Milner, Vadivelam Murthy, Anthony Milner, Anne Greenough
Journal: European Respiratory Journal (2013)

Background : It is recommended that observation of chest wall expansion should be used during resuscitation to assess the appropriateness of the magnitude of the inflations, but even the most experienced neonatal staff can find it difficult to determine whether chest wall expansion is adequate. There are now commercially available on line monitoring systems which may help guide the resuscitation process.

Aim: To determine whether neonatal trainees found a respiratory function monitor helpful during the resuscitation of prematurely born infants.

Methods: The monitor displayed inflation and positive end expiratory pressures, tidal flow and volume and end tidal carbon dioxide (CO2). Heart rate and transcutaneous oxygen saturation were displayed separately. Trainees were asked to complete a survey questionnaire.

Results : Fifty one trainees had used the monitor, the majority on > 5 occasions. Eighty-three percent found the tidal volume display useful; 59% altered the inflation pressure based on the tidal volume; 52% considered 5mls/kg adequate; 33% 5mls/kg; 13% 6ml/kg and 2% 7ml/kg. If there was no CO2: 30 said they would reintubate. If there was no chest wall expansion but there was expired CO2: 32 trainees said they would not reintubate but would increase the pressure; a third of the most junior trainees said they would reintubate. If the oxygen saturation was <85% at one minute, 50% of the most junior trainees said they would increase the inspired oxygen, no senior trainee said they would increase it.

Conclusions: The usefulness of respiratory function monitoring during the resuscitation of prematurely born infants is dependent on the level of experience of the trainee.
Tumors in Mice Injected With Colloidal Thorium Dioxide
Authors: H. B. Andervont, M. B. Shimkin
Journal: JNCI Journal of the National Cancer Institute (1940)

Tumors in Mice Injected With Colloidal Thorium Dioxide Get access H. B. Andervont, H. B. Andervont senior biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar M. B. Shimkin M. B. Shimkin assistant surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 3, December 1940, Pages 349–353, https://doi.org/10.1093/jnci/1.3.349 Published: 01 December 1940
Role of reactive oxygen species in immune suppression in cancer
Authors: Cesar Corzo, Srinivas Nagaraj, Dmitry Gabrilovich
Journal: Cancer Research (2008)

245  The inability of the host immune system to develop and maintain an effective anti-tumor immune response is one of the main mechanisms of tumor progression. Multiple laboratories have demonstrated that myeloid-derived suppressive cells (MDSC) are active participants in suppression of T lymphocytes during tumor development; however, the mechanisms regulating this suppression are still unclear. MDSC from tumor-bearing animals, isolated from either spleen or from the tumor-microenvironment, were capable of inhibiting antigen-specific T lymphocytes. Interestingly, however, only tumor-derived MDSC were capable of suppressing T cell functions in a non-specific manner. Based on these findings, we set out to investigate the basis for these discrepancies. Our data indicate that MDSC from peripheral lymphoid organs produce high levels of reactive oxygen species (ROS), which are responsible for the observed T cell malfunctions. The hyper-production of ROS by MDSC is a consequence of STAT3 hyper-activation. Splenic MDSC had a significant increase in expression of two critical components of NADPH oxidase: gp91phoxand p47phox. The NADPH oxidase has long been considered a strong source of ROS in myeloid cells and we show that STAT3 may be partially responsible for this up-regulation. MDSC from tumor-microenvironment, in the other hand, generated low levels of ROS and showed decreased expression of NADPH oxidase components. However, mRNA levels of Inducible Nitric Oxide Synthase (iNOS) and Arginase I were dramatically upregulated in tumor-derived MDSC; the upregulation of these two factors was responsible for the non-specific suppression observed in tumor vicinity. We hope that these findings will help to clarify the mechanism of T cell suppression in cancer and to possibly develop new effective cancer treatment.
SP0011 SjÖgren's criteria revisited!
Authors: SJ Bowman
Journal: Annals of the Rheumatic Diseases (2017)

In clinical practice it is up to the clinician to use their judgement in making a diagnosis of pSS. In research it is essential to have agreed classification criteria so that there is confidence that participants in a study have the specified condition. During the 19809s a number of classification criteria were proposed with a major debate as to the advantages and disadvantages of each of these criteria. In 1988 a working group of 29 experts from 12 European countries initiated a study to develop consensus criteria. They published their initial findings in 1993 and in 2002 Vitali et al published the American European Consensus Group Criteria (AECG). The AECG criteria have been the most widely used "gold-standard" criteria for the classification of pSS in research studies. Criteria are never fixed in perpetuity, however, and as new technology such as ultrasound becomes more widely used or new data becomes available further revision is likely. In 2013, an International Collaboration, the Sjögren9s International Clinical Collaborative Alliance (SICCA) funded by the National Institutes for Health in the USA collected data from 1618 participants to devise the American College of Rheumatology (ACR) preliminary criteria for SS and in 2016 following a further international consensus group exercise the American College of Rheumatology – European League against Rheumatism (EULAR) consensus criteria for Sjögren9s syndrome have been published. In this presentation I will go through the development of these criteria, the underlying rationale and by the end of the talk attendees should have a better understanding of how these criteria can be used in research and to support clinical practice. <h3>Disclosure of Interest</h3> None declared
Risk stratification of Asian patients with heart failure and reduced ejection fraction: the effectiveness of the Echo Heart Failure Score
Authors: Lena Bosch, Erberto Carluccio, Stefano Coiro, Lingli Gong, David Sim, Daniel Yeo, Fazlur Jaufeerally, Kui T.G. Leong, Hean Y. Ong, Ng T. Pin, Arthur M. Richards, Fatih Arslan, Lieng H. Ling, Carolyn S.P. Lam, Giuseppe Ambrosio
Journal: European Journal of Heart Failure (2017)
Perioperative tobacco use treatments: putting them into practice
Authors: Margaret B Nolan, David O Warner
Journal: BMJ (2017)

Treatment for tobacco use is efficacious and beneficial to health. Although guidelines recommend that all patients who use tobacco are offered treatment as a part of their clinical care, implementing treatment has proven challenging. In the case of surgical patients, this lack of treatment is particularly unfortunate, as the benefits of abstinence from tobacco are immediate in terms of reducing the risk of surgical complications, including cardiovascular, respiratory, and wound related complications. Surgery also presents an opportunity for patients to quit for good and reduce the long term health risk. This review examines the principles of tobacco use treatment, the rationale for tobacco use treatment in the perioperative period, and how treatment can be incorporated into the routine care of surgical patients. The discipline of implementation science helps to frame these efforts by seeking to better understand how changes in clinical practice occur, and it has the potential to guide an evidence based approach to embedding tobacco treatment into the routine clinical care of surgical patients. This review uses the consolidated framework for implementation research, which includes five major domains, as a representative conceptual framework. A basic understanding of factors potentially important to successful implementation can help to guide clinicians who accept the challenge of implementing tobacco use treatment in surgical care.
Child and Adolescent Psychiatry
Authors: J. Goldin
Journal: BMJ (1999)

Understanding modulation of the host immune system by pathogens offers rich therapeutic potential. Parasitic filarial nematodes are often tolerated in human hosts for decades with little evidence of pathology and this appears to reflect parasite-induced suppression of host proinflammatory immune responses. Consistent with this, we have previously described a filarial nematode-derived, secreted phosphorylcholine-containing glycoprotein, ES-62, with immunomodulatory activities that are broadly anti-inflammatory in nature. We sought to evaluate the therapeutic potential of ES-62 in vitro and in vivo in an autoimmune disease model, namely, collagen-induced arthritis in DBA/1 mice. ES-62 given during collagen priming significantly reduced initiation of inflammatory arthritis. Crucially, ES-62 was also found to suppress collagen-induced arthritis severity and progression when administration was delayed until after clinically evident disease onset. Ex vivo analyses revealed that in both cases, the effects were associated with inhibition of collagen-specific pro-inflammatory/Th1 cytokine (TNF-α, IL-6, and IFN-γ) release. In parallel in vitro human tissue studies, ES-62 was found to significantly suppress macrophage activation via cognate interaction with activated T cells. Finally, ES-62 suppressed LPS-induced rheumatoid arthritis synovial TNF-α and IL-6 production. Evolutionary pressure has promoted the generation by pathogens of diverse mechanisms enabling host immune system evasion and induction of “tolerance.” ES-62 represents one such mechanism. We now provide proof of concept that parasite-derived immunomodulatory strategies offer a novel therapeutic opportunity in inflammatory arthritis.
Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies
Authors: Geoffrey Chupp, Michel Laviolette, Lauren Cohn, Charlene McEvoy, Sandeep Bansal, Adrian Shifren, Sumita Khatri, G. Mark Grubb, Edmund McMullen, Racho Strauven, Joel N. Kline
Journal: European Respiratory Journal (2017)

Bronchial thermoplasty is an endoscopic therapy for severe asthma. The previously reported, randomised sham-controlled AIR2 (Asthma Intervention Research 2) trial showed a significant reduction in severe asthma exacerbations, emergency department visits and hospitalisations after bronchial thermoplasty. More “real-world” clinical outcome data is needed. This article compares outcomes in bronchial thermoplasty subjects with 3 years of follow-up from the ongoing, post-market PAS2 (Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma) study with those from the AIR2 trial. 279 subjects were treated with bronchial thermoplasty in the PAS2 study. We compared the first 190 PAS2 subjects with the 190 bronchial thermoplasty-treated subjects in the AIR2 trial at 3 years of follow-up. The PAS2 subjects were older (mean age 45.9 versus 40.7 years) and more obese (mean body mass index 32.5 versus 29.3 kg·m −2 ) and took higher doses of inhaled corticosteroids (mean dose 2301 versus 1961 μg·day −1 ). More PAS2 subjects had experienced severe exacerbations (74% versus 52%) and hospitalisations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty. At year 3 after bronchial thermoplasty, the percentage of PAS2 subjects with severe exacerbations, emergency department visits and hospitalisations significantly decreased by 45%, 55% and 40%, respectively, echoing the AIR2 results. The PAS2 study demonstrates similar improvements in asthma control after bronchial thermoplasty compared with the AIR2 trial despite enrolling subjects who may have had poorer asthma control.
H3 K27M/I mutations promote context-dependent transformation in acute myeloid leukemia with RUNX1 alterations
Authors: Bernhard Lehnertz, Yu Wei Zhang, Isabel Boivin, Nadine Mayotte, Elisa Tomellini, Jalila Chagraoui, Vincent-Philippe Lavallée, Josée Hébert, Guy Sauvageau
Journal: Blood (2017)
Care Patterns and Outcomes in Atrial Fibrillation Patients With and Without Diabetes
Authors: Justin B. Echouffo-Tcheugui, Peter Shrader, Laine Thomas, Bernard J. Gersh, Peter R. Kowey, Kenneth W. Mahaffey, Daniel E. Singer, Elaine M. Hylek, Alan S. Go, Eric D. Peterson, Jonathan P. Piccini, Gregg C. Fonarow
Journal: Journal of the American College of Cardiology (2017)
超音波とマイクロバブルによる増強された脳由来神経栄養因子送達は,脳卒中後の白質修復を促進する【Powered by NICT】
Authors: Rodriguez-Frutos Berta, Otero-Ortega Laura, Ramos-Cejudo Jaime, Martinez-Sanchez Patricia, Barahona-Sanz Ines, Navarro-Hernanz Teresa, Gomez-de Frutos Maria del Carmen, Diez-Tejedor Exuperio, Gutierrez-Fernandez Maria
Journal: Biomaterials (2016)
Tracheal Foreign Body Removal Using Flexible Bronchoscope in a Pediatric Patient. A Novel Approach
Authors: Ashok Kumar Jayaraj, Praveen Kumar Jayaraj, Mallaiyappan Murugesh, Sivakumar Aruchamy, Amir Yousefzadeh, Naveed T. Siddiqui
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial
Authors: Joel Gallant, Adriano Lazzarin, Anthony Mills, Chloe Orkin, Daniel Podzamczer, Pablo Tebas, Pierre-Marie Girard, Indira Brar, Eric S Daar, David Wohl, Jürgen Rockstroh, Xuelian Wei, Joseph Custodio, Kirsten White, Hal Martin, Andrew Cheng, Erin Quirk
Journal: The Lancet (2017)
Global Initiative for Chronic Obstructive Lung Disease 2017 Classification and Lung Function Decline in Chronic Obstructive Pulmonary Disease
Authors: Wan C. Tan, Jean Bourbeau, Shawn D. Aaron, Guohai Zhou, Francois Maltais, Paul Hernandez, J. Mark Fitzgerald, Darcy D. Marciniuk, Brandie L. Walker, Don D. Sin
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Abstract 158: What’s the Nrf Got To Do With Alcoholic Cardiomyopathy?
Authors: Georges E Haddad, Robin K Walker, Miara Jeffress, Mustafa AlRubaiee, Nsini Umoh, Tiorra Ross, Stephanie Douglas
Journal: Circulation Research (2013)

The beneficial cardiovascular effects of low alcohol consumption are becoming more clinically evident. This is in sharp contrast with the detrimental ones associated with heavy alcohol drinking. We have previously shown that cardiac inotropy is closely related to the activation of the survival PI3K/Akt pathway. The objective of this study was to assess the role of the PI3K/Akt pathway in mediating the inotropic effects of chronic alcohol consumption. Littermate adult rats were put on a 3-months isocaloric Lieber-Decarli liquid diet with either low alcohol (LA: 5mM) or high alcohol (HA: 100mM) levels. The measured final blood alcohol concentrations were 0.02% and 0.46% respectively. In vivo intra-ventricular catheterization (Scisense/iWorks) of the left ventricle (LV) showed that an improved LV contractility (ESPVR and PRSW) of the LA group while the opposite occurred with the HA group. The alterations in contractility were independent of the afterload as in vitro cellular and sarcomeric inotropic measurements (Ionoptix) showed similar profile to the LV in vivo data. These functional LA effects were correlated with reduced H 2 O 2 levels (as well as SOD-3 activity) and enhanced Akt, NFκB, FOXO-1 and NRF1/2 gene expressions which translated into higher NRF2 protein levels and cardiocyte survival. On the contrary, HA increased H 2 O 2 level (as well as SOD-3 activity) and reduced the Akt, NFκB, FOXO-1 and NRF1/2 gene expressions which translated into lower NRF2 protein levels and cardiocyte survival. In addition, we observed dampening of caspase-3/7 activity with HA which was not affected with LA. We conclude that the improved low alcohol-induced cardiac inotropic function may be mediated through reduction of oxidative stress via Akt/NRF2 activation, which showed opposite expressions with the detrimental high alcohol effects. We also note that cell death occurrences may turn to necrotic pathways as alcohol exposure increases beyond LA levels.
History of breast feeding and risk of incident endometriosis: prospective cohort study
Authors: Leslie V Farland, A Heather Eliassen, Rulla M Tamimi, Donna Spiegelman, Karin B Michels, Stacey A Missmer
Journal: BMJ (2017)

Objective To investigate the association between lifetime breast feeding, exclusive breast feeding, postpartum amenorrhea, and incidence of endometriosis among parous women.Design Prospective cohort study.Setting Nurses' Health Study II, 1989-2011.Participants 72 394women who reported having one or more pregnancies that lasted at least six months, 3296 of whom had laparoscopically confirmed endometriosis. For each pregnancy, women reported duration of total breast feeding, exclusive breast feeding, and postpartum amenorrhea. Main outcome measures Incident self reported laparoscopically confirmed endometriosis (96% concordance with medical record) in parous women. Multivariable Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for diagnosis of endometriosis.Results Duration of total and exclusive breast feeding was significantly associated with decreased risk of endometriosis. Among women who reported a lifetime total length of breast feeding of less than one month, there were 453 endometriosis cases/100 000 person years compared with 184 cases/100 000 person years in women who reported a lifetime total of ≥36 months of breast feeding. For every additional three months of total breast feeding per pregnancy, women experienced an 8% lower risk of endometriosis (hazard ratio 0.92, 95% confidence interval 0.90 to 0.94; P<0.001 for trend) and a 14% lower risk for every additional three months of exclusive breast feeding per pregnancy (0.86, 0.81 to 0.90; P<0.001 for trend). Women who breastfed for ≥36 months in total across their reproductive lifetime had a 40% reduced risk of endometriosis compared with women who never breast fed (0.60, 0.50 to 0.72). The protective association with breast feeding was strongest among women who gave birth within the past five years (P=0.04 for interaction). The association with total breast feeding and exclusive breast feeding on endometriosis was partially influenced by postpartum amenorrhea (% mediated was 34% (95% confidence interval 15% to 59%) for total breast feeding and 57% (27% to 82%) for exclusive breast feeding).Conclusion Among women who experienced at least one pregnancy that lasted at least six months, breast feeding was inversely associated with risk of incident endometriosis. This association was partially, but not fully, influenced by postpartum amenorrhea, suggesting that breast feeding could influence the risk of endometriosis both through amenorrhea and other mechanisms. Given the chronic and incurable nature of endometriosis, breast feeding should be further investigated as an important modifiable behavior to mitigate risk for pregnant women.