tbuckley/cabot-search huggingface dataset:
Abstract P227: Metformin Inhibits Glucose-Induced mTOR Activation and ER Stress in Rodent Heart
Authors: Shiraj Sen, Patrick Guthrie, Heinrich Taegtmeyer
Journal: Circulation Research (2011)

Background: When subjected to increased workload, the heart remodels both metabolically and structurally by increasing glucose metabolism and activating the mTOR signaling pathway. Specifically, glucose activates mTOR in a TSC2-dependent manner. We now examined whether metformin regulation of AMPK, a major upstream regulator of TSC2, modulates mTOR activation and endoplasmic reticulum (ER) stress when hearts are subjected to increased workload. Methods: Working hearts from 12 week old male Sprague Dawley rats were perfused ex vivo (5 mM glucose) at physiologic pre- and afterload. At 30 minutes, the workload was doubled. Hearts were freeze-clamped at 60 minutes. Hearts received either the AMPK activator metformin (10 mM) or the ER stress relieving agent sodium 4-phenylbutyrate (10 mM) directly in the perfusate. Rates of glucose uptake and oxidation were measured with radiolabeled substrate (3H, 14C). Cardiac power, the mTOR signaling pathway, and markers of ER stress were assessed. Results: With increased workload rates of glucose uptake and oxidation doubled, with rates of glucose uptake exceeding those of glucose oxidation. Neither metformin nor sodium 4-phenylbutyrate significantly changed those rates. In control hearts, there was a downregulation of AMPK, an activation of mTOR, an induction of ER stress, and a decline in contractile function. Perfusion with media containing metformin activated AMPK, prevented glucose-mediated mTOR activation, alleviated ER stress and improved cardiac function (25% increase in cardiac power). In a separate group of animals nearly identical findings were obtained when metformin (300 mg/kg/day) was administered in vivo for one week. The functional improvement was also observed when ER stress was directly relieved with sodium 4-phenylbutyrate, as well. Conclusion: Our results implicate a critical role for glucose metabolism and AMPK in load-induced mTOR activation. Metformin improves contractile function in rat hearts subjected to increased workload by relieving ER stress. The relief of ER stress by metformin suggests previously unrecognized beneficial effects of AMPK activation in the hemodynamically stressed heart.
First-Episode Schizophrenia and Diabetes Risk
Authors: Xilong Cui, Jianbo Liu, Xuerong Luo
Journal: JAMA Psychiatry (2017)

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TRTH-29. CONTEXT-SPECIFIC TUMOR SUPPRESSIVE FUNCTION OF THE CANONICAL WNT PATHWAY IN PEDIATRIC MEDULLOBLASTOMA HIGHLIGHTS A THERAPEUTIC STRATEGY FOR TREATMENT-REFRACTORY SUBGROUPS
Authors: Branavan Manoranjan, Chitra Venugopal, Michelle Kameda-Smith, David Bakhshinyan, Minomi Subapanditha, Bradley Doble, Sheila Singh
Journal: Neuro-Oncology (2017)

Current molecular subgroups of childhood medulloblastoma (MB) recognize distinct disease entities of which activated Wnt signaling is associated with a distinct subgroup and the best overall outcome. In contrast, non-Wnt MBs are characterized by metastatic disease, increased rate of recurrence, and poor overall survivorship. Given the excellent clinical outcome in Wnt-driven MB, we aimed to convert treatment-resistant MB subgroups 3 and 4 into an ostensibly benign tumor. Activated Wnt signaling by way of Wnt agonists decreased in vitro self-renewal of primary MB cells. Comparative RNA-sequencing of control and transgenic lines containing a stabilized beta-catenin mutant demonstrated a reduction in self-renewal genes following beta-catenin overexpression, including Sox2 and Bmi1. In order to validate the therapy-sensitive nature of Wnt-activated cells, we developed stable human Group 3 and 4 patient-derived lines containing a 7XTOPFlash reporter to determine the presence of endogenous Wnt signaling. Rare subclonal Wnt-active cells demonstrated a reduced self-renewal and tumor-initiating capacity through in vivo limiting dilution assays when compared to bulk Wnt-inactive cells from Group 3 and 4 MBs. The therapeutic relevance of these findings were demonstrated with an in vivo survival advantage in mice with orthotopic injections of cells containing stabilized beta-catenin overexpression or endogenous Wnt-active cells. Resulting xenograft tumors were smaller in size, maintained a lower rate of proliferation, and reduction in MB self-renewal genes. To develop a rationale clinical therapeutic, we used a novel substrate-competitive peptide inhibitor for GSK. Treatment with our peptide inhibitor showed a significant reduction in tumor burden and metastatic disease with a corresponding increase in survival of patient-derived Group 3 and 4 tumors that were otherwise treatment-resistant. Our work establishes activated Wnt signaling as a novel treatment paradigm in childhood MB, identifies a rationale therapeutic approach for recurrent MB, and provides evidence for the context-specific tumor suppressive function of the canonical Wnt pathway.
Graphene Oxide/Ag Nanoparticles Cooperated with Simvastatin as a High Sensitive X‐Ray Computed Tomography Imaging Agent for Diagnosis of Renal Dysfunctions
Authors: Zhan Li, Longlong Tian, Jianli Liu, Wei Qi, Qiang Wu, Haijing Wang, Mohammad Chand Ali, Wangsuo Wu, Hongdeng Qiu
Journal: Advanced Healthcare Materials (2017)

Graphene oxides (GO) are attracting much attention in the diagnosis and therapy of the subcutaneous tumor as a novel biomaterial, but its diagnosis to tissue dysfunction is yet to be found. Here, a novel application of GO for diagnosis of renal dysfunction via contrast‐enhanced computed tomography (CT) is proposed. In order to serve as contrast‐enhanced agent, Ag nanoparticles (AgNPs) are composited on the surface of GO to promote its X‐ray absorption, and then simvastatin is coinjected for eliminating in vivo toxicity induced by AgNPs. It is found that GO/AgNPs can enhance the imaging of CT into the lung, liver, and kidney of mice for a long circulation time (≈24 h) and a safety profile in vivo in the presence of simvastatin. Interestingly, the lower dose of GO/AgNPs (≈0.5 mg per kg bw) shows an excellent performance for CT imaging of renal perfusion, and visually exhibits the right renal dysfunction in model mice. Hence, this work suggests that graphene nanoparticles will play a vital role for the future medical translational development including drug carrier, biosensing, and disease therapy.
La combinaison de la technique du tunnel et de la contre-traction par clip: la solution technique pour – les dissections oesophagiennes?
Authors: J Jacques, R Legros, J Rivory, L Mesturoux, D Sautereau, T Ponchon, M Pioche
Journal: Endoscopy (2016)

L'œsophage est un des sites les plus difficiles pour la réalisation de dissections sous-muqueuse. En effet l'étroitesse de la lumière rend les manœuvres de l'endoscope difficile et la finesse de la paroi et l'absence de séreuse augmentent le risque de perforation. Toutefois, malgré ces difficultés techniques, l'épidémiologie des tumeurs superficielles œsophagiennes (Carcinome épidermoide et Adénocarcinome sur œsophage de Barrett) combinée à la morbi-mortalité importante de la chirurgie œsophagienne en font un site essentiel pour les endoscopistes pratiquant la dissection sous-muqueuse. Techniquement le point le plus important est d'assurer une bonne exposition de la couche sous muqueuse après l'incision muqueuse. Pour cela, deux techniques ont été décrites: la technique du tunnel et la contre-traction par clip attaché à un fil qui améliorent l'exposition de la sous-muqueuse mais présentant chacune des limites techniques propres.
A Higher Proportion of the EGFR T790M Mutation May Contribute to the Better Survival of Patients with Exon 19 Deletions Compared with Those with L858R
Authors: E-E Ke, Qing Zhou, Qiu-Yi Zhang, Jian Su, Zhi-Hong Chen, Xu-Chao Zhang, Chong-Rui Xu, Jin-Ji Yang, Hai-Yan Tu, Hong-Hong Yan, Yi-Chen Zhang, Fei-Yu Niu, Yi-Long Wu
Journal: Journal of Thoracic Oncology (2017)
Editorial pour Endoscopy 2016
Authors: P Bulois
Journal: Endoscopy (2016)

Ce numéro d'endoscopy contient l'ensemble des résumés des travaux relatifs à l'endoscopie retenus pour présentation aux Journées Francophones d'Hépato-gastro-entérologie et d'Oncologie Digestive (JFHOD) 2016. Cette sélection témoigne une nouvelle fois du dynamisme de la recherche francophone en endoscopie digestive.
Elevated levels of interleukin-1 beta (IL-1 beta) and IL-6 in serum and increased production of IL-1 beta mRNA in lymph nodes of patients with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome
Authors: RK Gherardi, L Belec, G Fromont, M Divine, D Malapert, P Gaulard, JD Degos
Journal: Blood (1994)
Virologic Monitoring of Poliovirus Type 2 after Oral Poliovirus Vaccine Type 2 Withdrawal in April 2016 — Worldwide, 2016–2017
Authors: Ousmane M. Diop, Humayun Asghar, Evgeniy Gavrilin, Nicksy Gumede Moeletsi, Gloria Rey Benito, Fem Paladin, Sirima Pattamadilok, Yan Zhang, Ajay Goel, Arshad Quddus
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The Global Polio Eradication Initiative (GPEI) has made substantial progress since its launch in 1988; only 37 wild poliovirus type 1 (WPV1) cases were detected in 2016, the lowest annual count ever. Wild poliovirus type 3 has not been detected since November 2012, and wild poliovirus type 2 was officially declared eradicated in September 2015. This success is attributable to the wide use of live oral poliovirus vaccines (OPVs). Since 2001, numerous outbreaks were caused by the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (1). In 2015, circulating VDPV type 2 (cVDPV2) outbreaks were detected in five countries worldwide (Nigeria, Pakistan, Guinea, Burma, and South Sudan), and VDPV2 single events were reported in 22 countries. These events prompted the GPEI to withdraw the type 2 component (Sabin2) of trivalent OPV (tOPV) in a globally coordinated, synchronized manner in April 2016 (2,3), at which time all OPV-using countries switched to using bivalent OPV (bOPV), containing Sabin types 1 and 3. This report details for the first time the virologic tracking of elimination of a live vaccine that has been withdrawn from routine and mass immunization systems worldwide (3). To secure elimination, further monitoring is warranted to detect any use of tOPV or monovalent OPV type 2 (mOPV2).
Assessment of Mobilization Cost for Multiple Myeloma Using 2 Different Mobilization Strategies: High-Dose Cyclophosphamide Versus Plerixafor. on Behalf of IFM
Authors: Zoe van de Wyngaert, Nabih Azar, Pascal Lenain, Margaret Macro, Jean-Henri Bourhis, Laurent Garderet, Arnaud Jaccard, Lionel Karlin, Christine Giraud, Stéphanie Guidez, Benjamin Hebraud, Muriel Roussel, Gerald Marit, Cyrille Hulin, Eric Deconinck, Michel Attal, Philippe Moreau, Denis Caillot, Samuel Limat, Xavier Leleu, Marie-Lorraine Chretien
Journal: Blood (2016)
Abstract P107: Interactions of the BDNF Val66Met Polymorphism, Gender, and High-Carbohydrate Diets on Risk Factors for Cardiovascular Diseases
Authors: Minshan Hu, Ronghui Li, Zhen Zhang, Yongyan Song, Yuanhao Li, Ding Zhi Fang
Journal: Circulation Research (2011)

Background_ Brain-derived neurotrophic factor (BDNF) is a member of the “neurotrophin” family of growth factors, it was lately found involved in cardiovascular diseases(CVDs), somehow whether BDNF has any effect on dyslipidemia has not been detected. We hypothesized that Val (Valine) 66Met (Methionine ) polymorphism of BDNF could change risk factors of CVDs including serum lipids profile difference, and interaction with a high-CHO diet could modified these factors. Methods and Results_ Fifty-six young and healthy Chinese subjects were recruited. A stabilization diet of 54% carbohydrate was first given to exclude these subjects’ own various diet background interferences, and then a high-CHO diet of 70% carbohydrate was followed to study its intervention effect. The serum lipid profiles were analyzed at baseline, after the stabilization diet and after the high-CHO diet. After the stabilization diet, significant difference among BDNF Val66Met polymorphism was found for the females’ body mass index (BMI) with the means appeared at Val/Val&gt;Val/Met&gt;Met/Met. After the high-CHO diet, most of the cardiovascular risk factors were changed to a more favorable direction and the effect has gender difference. But interestingly, both TAG and food intake notably increased in female Met carriers. Conclusions_ The above results indicate that although Met mutation could be protective to CVDs in females, after interacting with high-CHO diet, due to the rising triacylglycerol (TAG) and food intake, the risk for carbohydrate-induced hypertriacylglycerolemia happens in these female Met carriers was actually increased.
Innovative behaviourbehavior modification strategies to reduce concussion risk in high school american football athletes
Authors: Erin B Wasserman, Jason P Mihalik, Kody R Campbell, Patricia Combs, Melissa A Fraser, Erin Grand, Maryalice Nocera, Johna K Register-Mihalik, Kevin M Guskiewicz, Stephen W Marshall
Journal: British Journal of Sports Medicine (2017)

Objective To improve tackling and blocking techniques to reduce concussion in high school American football players, and to evaluate the program’s feasibility and acceptance. Design Clustered quasi-experimental study. Setting High schools. Participants Varsity American high school football players on three teams (two intervention; one control). Interventions All players wore in-helmet head impact accelerometers. “High-risk” intervention team players were selected and attended clinician-coach-player mentoring sessions designed to change playing technique. Accelerometer data were used for “high-risk” selection and during mentoring sessions to reinforce the technique-driven intervention. Outcome measures The change in top-of-head impacts and impacts with peak linear acceleration&gt;60 g was compared between intervention and control subjects using linear risk models. Coaches and players completed post-season exit surveys. Main results Ninety-seven players (70 intervention; 27 control) participated. Thirteen (19%) intervention players were identified as “high risk” and received mentoring. The mentored players’ high magnitude impacts (percent&gt;60 g) in practices dropped 1.9 percent from pre-intervention to post-intervention. There was no change in non-mentored players. In post-season surveys, mentored players “strongly agreed” (56%) or “agreed” (44%) that the study improved their playing behaviours. Among intervention team coaches, three (43%) thought the study was “very effective” in changing football player behaviours about safe play, and the remaining four (57%) thought it was “effective.” Conclusions There is growing concern head impact frequency and severity may result in neurological issues for some athletes later in life. If head impact frequency and severity can be reduced through behavioural intervention, this can have a great public health impact. Competing interests This study is funded by a grant from the National Centre for Injury Prevention and Control (Grant #R49CE002479).
Sex, breathing and statistics
Authors: Samy Suissa, Anne V. Gonzalez, Ian Shrier
Journal: European Respiratory Journal (2017)

Breathlessness is a complex symptom that results from the interplay of physiological, psychological, social and environmental factors [1]. Breathlessness is also common, and is associated with increased morbidity and mortality [2, 3]. A number of studies have shown that breathlessness is reported more frequently by women than men, both from population-based surveys and in patients with chronic obstructive pulmonary disease [4]. Women are more likely to report mMRC breathlessness and this appears to be related to smaller lung volume <http://ow.ly/hoDM30ayQWH>
Variation of Red Blood Cell Rheology and Adhesiveness during Vaso-Occlusive Crises in Sickle Cell Patients
Authors: Regine Hierso, Claudine Lapoumeroulie, Philippe Connes, Sara El Hoss, Catia Oliveira, Sylvie Cochet, Yves Colin Aronovicz, Caroline Le Van Kim, Marc Romana, Marie Dominique Hardy-Dessources
Journal: Blood (2016)
Association of Prescription Drug Price Rebates in Medicare Part D With Patient Out-of-Pocket and Federal Spending
Authors: Stacie B. Dusetzina, Rena M. Conti, Nancy L. Yu, Peter B. Bach
Journal: JAMA Internal Medicine (2017)

The increasing cost of prescription drugs is a burden for patients and threatens the financial stability of the US health care system. Rebates are a form of price concession paid by a pharmaceutical manufacturer to the health plan sponsor or the pharmacy benefit manager working on the plan's behalf. Proponents argue that rebates result from vigorous negotiations that help lower overall drug costs. Critics argue that rebates have perversely increased the costs patients pay out of pocket, as well as the costs for Medicare as a whole. This special communication discusses how the availability of rebates for drugs covered by the Medicare Part D program may raise costs for patients and Medicare while increasing the profits of Part D plan sponsors and pharmaceutical manufacturers. Two policy alternatives are herein proposed that would reconfigure cost sharing to lower patient out-of-pocket costs and reduce cost shifting to Medicare.
Role of miRNA in Micro-Environment Mediated Drug Resistance in Acute Promyelocytic Leukemia to Arsenic Trioxide
Authors: Saravanan Ganesan, Vairavan Lakshmanan, Hamenth Kumar Palani, Nithya Balasundaram, Ansu Abu Alex, Sachin David, Anu Korula, Biju George, Poonkuzhali Balasubramanian, Harsha Gowda, Neha Vyas, Dasaradhi Palakodeti, Vikram Mathews
Journal: Blood (2016)
CD8+CD25+Foxp3+ T cells with suppressive function accumulate at tumor site in cancer colorectal patients
Authors: Nathalie Chaput, Samy Louafi, Armelle Bardier, Eva Compera, Jean-Christophe Vaillant, Laurent Hannoun, Thierry Poynard, Michelle Rosenzwajg, David Klatzmann, Julien Taieb
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

256 

Tumors express antigens that should induce immune-mediated rejection, but spontaneous rejection of established tumors is rare. Recent work demonstrates that one reason for the lack of tumor rejection is that tumors actively defeat host immunity. Natural FOXP3+CD25+CD4+ regulatory T cells (T4reg) actively suppress pathological and physiological immune responses, contributing to the maintenance of immunological self-tolerance and immune homeostasis. T4reg, which are engaged in the maintenance of self-tolerance, might hamper effective immunosurveillance against emerging cancer cells and impede effective immune responses to established tumors. Indeed, it has been shown that T4reg infiltration in ovarian cancer is correlated with poor survival of patients. Elevated proportions of T4regs among tumor-infiltrating lymphocytes have been also described in many other types of cancers. In the present prospective study, we analyzed blood regulatory T cells and infiltrating the tumor tissue (CRC) compare with normal adjacent tissue (NT) in 32 colorectal cancer patients. Interestingly, next to the T4reg, we found a significant accumulation in the blood and in the cancer tissue of CD8+CD25+Foxp3+ T (T8reg) with a phenotype closely related to T4reg. T8reg infiltrating cancer tissue bore an activated phenotype as suggested by an increased expression of CTLA-4, GITR and TGF-β1 compared to normal adjacent tissue. Moreover T8reg could suppress CD4+CD25- T cells proliferation and TH1 cytokine production ex-vivo demonstrating that tumor infiltrating T8reg harbor suppressive capacities. Finally, T8reg ratio [T8regCRC/T8regNT] was correlated to the tumor stage suggesting accumulation and/or differentiation in situ during tumor growth. Altogether these data shows for the first time that T8reg are increase in colorectal cancer patients and may participate to the global immunosuppression during tumor growth.
Do NAA/CHO and NAA/CR ratios as measure by 1h MR spectroscopy differ between symptomatic and non-symptomatic concussed athletes in the early post injury period?
Authors: Antonio Belli, David Davies, Zhangjie Su, Connor Bentley, Douglas Hammond, Michael Grey, Valentina Di Pietro, Lisa Hill, Shaun Evans
Journal: British Journal of Sports Medicine (2017)

<h3>Objective</h3> Changes in cerebral N-acetylaspartate and choline (NAA/Cho) or creatine (NAA/Cr) following a mild traumatic brain injury (mTBI) in sport have been measured by 1H (Proton) magnetic resonance spectroscopy (1H-MRS). We intend to investigate the effect that presenting symptomatology has on these parameters. <h3>Design</h3> Observational cohort study. <h3>Setting</h3> UK Premiership and Championship Rugby. <h3>Participants</h3> Athletes aged 18-40 years. <h3>Interventions (or assessment of risk factors)</h3> Concussed athletes identified by members of their enhanced-care clinical team. Imaging undertaken on a Philips Achieva 3.0 T MR scanner (32 channel SENSE coil). A PRESS sequence (et 37 ms, rt 2000 ms) generated spectra in a 20 mm MRS cubic voxel in right-sided superior frontal white matter. Symptoms were assessed using the IMPACT and SCAT-3 concussion assessment tools. Recruits were divided into either ‘symptomatic’ or ‘non-symptomatic’ at presentation based on a minimum severity score from either of these assessments. <h3>Outcome measures</h3> Analysis of raw parameters was undertaken utilising the TARQUIN 1H-MRS analytical software package. A Mann-Whitney-U test was performed to compare results between the symptomatic and non-symptomatic groups. <h3>Main results</h3> 33 concussed professional athletes were recruited. Of these a total of 7 Symptomatic (6 male, mean age 24yrs, scoring a total symptom severity score of &lt;10 on either assessment measure) and 11 non-symptomatic (all male, mean age 25 yrs) athletes tested within the target window (2–4 days). Ratios between groups did not vary significantly (NAA/Cho mean 4.43 vs 4.53 and NAA/Cr 1.24 vs 1.26, p=0.84 and p=0.99 respectively). <h3>Conclusions</h3> Within this population of concussed professional athletes early 1H-MRS did not differentiate between athletes presenting with modest/no symptoms and those presenting with significant symptoms. <h3>Competing interests</h3> None.