tbuckley/cabot-search huggingface dataset:
Transcranial doppler ultrasound measures of neurovascular coupling are maintained following acute sport-related concussion
Authors: Jonathan D Smirl, Alexander D Wright, Kevin Bouliane, Kelsey Bryk, Paul van Donkelaar
Journal: British Journal of Sports Medicine (2017)

Objective To determinethe extentto which an acute sport-related concussion disrupts elevations in cerebral blood velocity (CBV) in the posterior cerebral artery (PCA) during visual tasks. Design Prospective Cohort. Setting Laboratory. Participants 136 male contact-sport athletes (19.1±1.4 years) recruited, subset of 14 participants (19±1.4 years) sustained concussions. Intervention Transcranial Doppler ultrasound was used to index CBV in the PCA during a series of visual tasks. Participants closed their eyes (20 seconds), and when prompted, opened their eyes and completed a visual task (40 seconds). Testing was completed prior to the start of their athletic season (T0), and again (if concussed) at 72-hours (T1), 2-weeks (T2), and 1-month (T3) post-injury. The raw traces from each trial were averaged to enhance the signal-to-noise ratio of the outcome measurements. Independent variable tested was time (4 points). Outcome measures Eyes-closed CBV (cm/s), peak elevation in CBV (cm/s), relative change in CBV (%) and total activation during the first 30 seconds of the task (indexed via area under the curve-AUC) Main results RM-ANOVA indicated there were no time effects forany of the outcome metrics: Eyes-closed CBV (p=0.473), peak CBV (p=0.541),% CBV elevation (p=0.603) and AUC (p=0.972). Conclusions These negative findings are important, as they indicate the PCA is able to maintain nutrient delivery required for visual challenges. Thus, neurovascular coupling is maintained despite the reported impairments in indices of cerebral autoregulation in the same population. Competing interests None.
Abstract 294: Atrogin-1 Is Required for Atrophic Remodeling of the Heart
Authors: Kedryn K Baskin, Rebecca Salazar, Wenhao Chen, Heinrich Taegtmeyer
Journal: Circulation Research (2012)

The heart adapts to changes in load by remodeling both metabolically and structurally. During this process, cardiomyocytes break down unnecessary or damaged proteins and use the resulting amino acids for the synthesis of new proteins and/or energy provision. Protein degradation via the ubiquitin proteasome system is controlled by ubiquitin ligases, which determine the specific proteins to be degraded. Atrogin-1 is a muscle specific ubiquitin ligase required for skeletal muscle atrophy, and over-expressing Atrogin-1 inhibits the development of cardiac hypertrophy. We tested the hypothesis that Atrogin-1 is required for atrophic remodeling of the unloaded heart. Hearts from wild type (WT) and Atrogin-1 -/- mice were subjected to mechanical unloading by heterotopic transplantation. In WT hearts, seven days of unloading significantly reduced heart weight and myocyte cross-sectional area, while hearts lacking Atrogin-1 significantly hypertrophied. Conventional markers of atrophic remodeling, such as the reactivation of the fetal gene program were detected in both WT and Atrogin-1 -/-transplanted hearts. Proteasome activity and markers of autophagy were increased after unloading, although not significantly different between WT and Atrogin-1 -/- hearts. Pathways regulating protein synthesis were enhanced in the absence of Atrogin-1; there was an increase in activated Akt and its downstream pathway including mTOR, 4E-BP1, and p70 S6 kinase. Additionally, calcinuerin, a known target of Atrogin-1 involved in hypertrophy and protein synthesis, was upregulated in unloaded Atrogin-1 deficient hearts. Consequently, μunloaded” cardiomyocytes lacking Atrogin-1 in vitro exhibit increased basal rates of protein synthesis. While inhibition of calcineurin decreased rates of protein synthesis in unloaded cardiomyocytes in the absence of Atrogin-1, protein synthesis rates were still higher than in WT unloaded cardiomyocytes. These results suggest that more than one pathway regulating protein synthesis is controlled by Atrogin-1 in the heart. Furthermore, the data provide evidence that Atrogin-1 not only enhances protein degradation, but also keeps protein synthesis in check. Thus Atrogin-1 has a duel role in regulating cardiac mass.
Heart rate variability: exploring age, sex &amp; concussion symptoms in youth athletes
Authors: Melissa Paniccia, Verweel Lee, Tim Taha, Michelle Keightley, Scott Thomas, Nick Reed
Journal: British Journal of Sports Medicine (2017)

Objective (1) Explore the influence of age, sex on heart rate variability (HRV) in youth athletes; (2) Examine the relationship between baseline/pre-injury concussion symptom domains (physical, cognitive, emotional, fatigue) and HRV Design Cross-sectional. Setting Pre-injury/baseline data was obtained from youth athletes across various sports in the Greater Toronto Area. Participants Youth athletes between 13–18 years of age (N=294), in which females and males were equally represented across age groups. Inclusion criteria: between 13–18 years old, English speaking. Exclusion criteria: developmental and neurological diagnoses. Intervention Independent variables of interest included demographic factors such as age and sex as well as concussion symptoms. Concussion symptoms were measured using the Post Concussion Symptom Inventory and were stratified by physical, cognitive, fatigue and emotional domains. Outcome measures Heart rate variability, collected over 24 hours was the main outcome of interest and included time (e.g. SDNN, RMSSD) and frequency domain measures (e.g. HF, Total Power). Variables were logarithmically transformed to increase robustness of linear regression models. Main results Statistical threshold set at p ≤ 0.05. Significant age effects revealed that older participants displayed higher HRV compared to younger athletes. Significant interaction effect between concussion symptoms and sex on HRV. Cognitive and fatigue symptoms in healthy youth athletes had significant effect on HRV. Conclusions This study highlights the potential value of a novel neurophysiological indicator used in conjunction with the self-report of symptoms for clinical management. Prospective longitudinal research is needed to further explore the multi-faceted contextual influences of a youth athlete’s environment. Competing interests None.
Why would the discovery of gestures produced by signers jeopardize the experimental finding of gesture-speech mismatch?
Authors: Timothy Koschmann
Journal: Behavioral and Brain Sciences (2017)

Mismatch occurs when there is a discrepancy between produced gestures and co-occurring speech. In this commentary, I explore why research on mismatch might be called into question by changing views of what constitutes a gesture. I argue that the experimental procedure for producing mismatch, through its coding methods, is blind to the tight temporal coordination of gesture and affiliated talk.
Finding useful data across multiple biomedical data repositories using DataMed
Authors: Lucila Ohno-Machado, Susanna-Assunta Sansone, George Alter, Ian Fore, Jeffrey Grethe, Hua Xu, Alejandra Gonzalez-Beltran, Philippe Rocca-Serra, Anupama E Gururaj, Elizabeth Bell, Ergin Soysal, Nansu Zong, Hyeon-eui Kim
Journal: Nature Genetics (2017)
Pomalidomide + Low-Dose Dexamethasone Following Second-Line Lenalidomide-Based Therapy in Relapsed or Refractory Multiple Myeloma: A Phase 2 Study Investigating Efficacy and Safety
Authors: David S. Siegel, Gary J. Schiller, Kevin W. Song, Richy Agajanian, Keith Stockerl-Goldstein, Hakan Kaya, Michael Sebag, Fred J. Reu, Ehsan Malek, Jorge L Mouro, Weiyuan Chung, Shankar Srinivasan, Max Qian, Syed Rizvi, Anjan Thakurta, Nizar J. Bahlis
Journal: Blood (2016)
Intravital imaging of fluorescently labeled therapeutic monoclonal antibody on the surface of tumor cells in metastatic tumor xenografts using a multiphoton microscopy.
Authors: Koji Tanaka, Shozo Ide, Tadanobu Shimura, Masato Okigami, Yuji Toiyama, Takahito Kitajima, Satoru Kondo, Hiroki Imaoka, Mikio Kawamura, Susumu Saigusa, Yoshinaga Okugawa, Masaki Ohi, Yasuhiro Inoue, Keiichi Uchida, Toshimitsu Araki, Yasuhiko Mohri, Akira Mizoguchi, Masato Kusunoki
Journal: Journal of Clinical Oncology (2014)

e22062 Background: The optical imaging using a bioluminescent or fluorescent probe can visualize, characterize, and measure the biological process of anticancer drugs at the molecular and cellular levels in human and preclinical animal settings. We reported in vivo visualization and characterization of anticancer drug efficacy on human tumor xenografts at the metastatic sites by a MPM with an organ stabilizer (Japanese Patent No.5268282). In this study, we visualize and characterize the binding of fluorescently labeled monoclonal antibody (mAb) to its cell surface receptor of tumor cells in metastatic tumor xenografts of the living mice using a MPM in vivo real-time. Methods: A human gastric cancer (NUGC4), colorectal cancer cell line (HT29), and green fluorescent protein expressing nude mice were used to make gastric peritoneal metastasis or colorectal liver metastasis model. In vitro, the bindings of Zenon Alexa Fluor 594 labeled anti-c-MET mAb or anti-epidermal growth factor receptor antibody (cetuximab) to viable NUGC4 or HT29 cells were imaged using a fluorescence microscopy. In vivo, the binding of fluorescently labeled anti-c-MET mAb or cetuximab to each tumor cells of peritoneal or liver metastatic xenografts was imaged using a MPM. Results: The binding of fluorescently labeled anti-c-MET mAb or cetuximab (red) to the surface of each tumor cells was observed by a fluorescence microscopy. The metastatic tumors which consisted of label-free tumor cells (black) and murine stromal cells (green) were observed by a MPM. The fluorescently labeled mAbs were visualized within tumor vessels of the metastatic tumor immediately after an intravenous administration. Thereafter, fluorescently label-free tumor cells were identified by the binding of fluorescently labeled mAbs to c-MET or EGFR of tumor cells. Conclusions: Our preliminary results suggest that optical imaging (or optical pathology) using a MPM can visualize and characterize in vivo real-time biological process of a fluorescently labeled mAb at the cellular level on the metastatic site in preclinical animal settings.
Scottish GPs call for more BMA resources Smoking decline in England reversed GMSC will discuss prescription fraud
Authors: Linda Beecham
Journal: BMJ (1998)

Representatives of Scottish GPs have called for the BMA to put more resources into its Scottish Office in the form of staff and parliamentary and press advice to give greater strength to their negotiators.

At the General Medical Services Committee last week the chairman of the Scottish GMSC, Dr Brian Keighley, said that the revolutionary white paper on the health service in Scotland, Designed to Care , was “the first concrete example of devolution. We must make sure that it works for us and our patients, and that we are not divided and ruled.”

For the first time GPs' terms and conditions of service will differ in England and Scotland, but he hoped that this could be turned to GPs' advantage. As soon as one country negotiated an advantageous arrangement the appropriate GMSC chairman would demand changes to redress the balance. The government would find it difficult to counter such an argument.

Primary care trusts will be established almost immediately in Scotland, but the biggest difference is that Scottish GPs will have no direct say in how hospital …
SIRT3-Mediated Dimerization of IDH2 Directs Cancer Cell Metabolism and Tumor Growth
Authors: Xianghui Zou, Yueming Zhu, Seong-Hoon Park, Guoxiang Liu, Joseph O'Brien, Haiyan Jiang, David Gius
Journal: Cancer Research (2017)

The isocitrate dehydrogenase IDH2 produces α-ketoglutarate by oxidizing isocitrate, linking glucose metabolism to oxidative phosphorylation. In this study, we report that loss of SIRT3 increases acetylation of IDH2 at lysine 413 (IDH2-K413-Ac), thereby decreasing its enzymatic activity by reducing IDH2 dimer formation. Expressing a genetic acetylation mimetic IDH2 mutant (IDH2K413Q) in cancer cells decreased IDH2 dimerization and enzymatic activity and increased cellular reactive oxygen species and glycolysis, suggesting a shift in mitochondrial metabolism. Concurrently, overexpression of IDH2K413Q promoted cell transformation and tumorigenesis in nude mice, resulting in a tumor-permissive phenotype. IHC staining showed that IDH2 acetylation was elevated in high-risk luminal B patients relative to low-risk luminal A patients. Overall, these results suggest a potential relationship between SIRT3 enzymatic activity, IDH2-K413 acetylation-determined dimerization, and a cancer-permissive phenotype. Cancer Res; 77(15); 3990-9. ©2017 AACR.
La chirurgie endoscopique combinée laparoscopique et endoluminale peut être un traitement standard pour les tumeurs sous-muqueuses de l’estomac: une étude rétrospective
Journal: Endoscopy (2017)

Le standard de traitement des tumeurs sous-muqueuses gastrique (TSMg) à risque évolutif est la résection complète en marge saine. Des approches mini-invasives par laparoscopie ou endoscopie endoluminale sont de plus en plus utilisées dans cette indication. Toutefois, il peut être difficile d’identifier la ligne de résection appropriée en laparoscopie, surtout pour les lésions endoluminale et les tumeurs localisées à la jonction œsogastrique. De même, la résection endoluminale de tumeurs implantées profondément dans la muscularis propria pose le problème de la prise en charge du défect pariétal, notamment en cas de lésion supérieure à 30 mm. Cette étude évaluait donc les possibilités de combiner ces 2 approches. Après contrôle vasculaire par laparoscopie, une incision latérale péri-tumorale était réalisée par voie endoscopique. Puis la dissection était menée par voie endoscopique en utilisant un IT-knife2 jusqu’à la séreuse. Après perforation de la séreuse par voie endoluminale, la résection transmurale était achevée en combinant les 2 approches puis, après récupération de la pièce opératoire via les orifices de trocart, la paroi gastrique était suturée chirurgicalement.
Dietary tannic acid stimulates production of reactive oxygen intermediates and growth factor and inflammatory gene expression in human colon tumor cells
Authors: Joshua P. Gray, Vladimir Mishin, Diane E. Heck, Jeffrey D. Laskin
Journal: Cancer Research (2005)

5181  Tannic acid (penta-m-digalloyl glucose) is a polycyclic aromatic compound produced by a variety of plants. Humans ingest tannic acid in many foods, beverages, and medicinal products. Many studies have shown tannic acid to be anticarcinogenic and antimutagenic, particularly in the presence of other procarcinogenic insults. At low levels in the diet, tannic acid reduces spontaneous hepatomas in C3H mice, and has been proposed as a chemopreventative agent for colon cancer. However, tannic acid also has negative impacts on health. Betel nuts, routinely chewed in the cheek after dinner in some Asian countries, contain 11-26% tannins and are believed to contribute to the high levels of cheek and esophageal cancers in those countries. In animal studies, tannic acids decrease feed intake, growth rate, energy uptake, and protein digestability. Tannic acid applied to burns also causes tumors in experimental animals, suggesting that it may promote carcinogenesis. Our laboratory has been investigating the tumor promoting activity of tannic acid. We found that tannic acid (10-100 μM) is a prooxidant and can generate hydrogen peroxide and produce hydroxyl radicals in the presence of transition metals as measured using terephthalate, a free radical trapping agent, the product of which becomes highly fluorescent upon hydroxylation. Using plasmid DNA unwinding assays, tannic acid was also found to cause single and double stranded DNA breaks, a finding consistent with the formation of reactive oxygen intermediates. Using CX-1, a human carcinoma line, we found that tannic acid causes extensive lipid peroxidation. This reaction was time-dependent up to at least 5 h and was inhibited by the anti-oxidant dimethyl sulfoxide (0.1%). During this time we found that tannic acid was a potent inducer of growth factor and inflammatory gene expression. Tannic acid increased expression of IL-8, TGFβ, RANTES, and GM-CSF by 3-16 fold, and IL-8 by 220 fold. Other transcript markers of inflammation, including iNOS and COX-2, were induced 3-10 fold even at very low concentrations of tannic acid (1 μM). Taken together, our data suggest that dietary tannic acid has prooxidant activity that can damage lipids and DNA. Moreover, it has the ability to induce growth factors and inflammatory cytokines that may be important in regulating tumor cell growth. These studies suggest that tannic acid in the diet may contribute to the progression of colon cancer. Supported by NIH grants ES05022, ES007148, CA093798 and CA100994.
Dysphagia after Occipitocervical Fusion
Authors: Jaetaek Hong, Seonghoon Lim
Journal: New England Journal of Medicine (2017)

Dysphagia developed in a 64-year-old man after posterior occipitocervical fusion for atlantoaxial subluxation. Videofluoroscopic studies that revealed nasopharyngeal regurgitation and delayed aspiration are available at NEJM.org.
Predicting the future from the past: volatile markers for respiratory infections
Authors: Wojciech Filipiak, Clemens Ager, Jakob Troppmair
Journal: European Respiratory Journal (2017)

We read with great interest the editorial by Agusti [1] which reflected on past advances in technology in general, in respiratory medicine more specifically, and which tried to predict potential future advances. Among the latter, the use of exhaled biomarkers for detection of lung cancer caught our attention and we want to bring the editor's and readers' attention to a rapidly advancing related field of respiratory medicine, namely the analysis of volatile biomarkers of bacterial infections in exhaled breath. Like all living cells, bacteria produce numerous volatile organic compounds (VOCs), of which some may be species-specific and thus provide a biological fingerprint of pathogen presence. Detection of such bacteria-derived metabolites in exhaled breath is completely non-invasive and can be performed repeatedly without any burden to the patient. It is increasingly recognised as an innovative and promising diagnostic technique for early detection of emerging pulmonary infections [2]. Furthermore, breath analysis has high potential to advance precision diagnosis of pathogens as it reflects individual susceptibility to disease causing agents and also to therapeutic agents. Apart from this, the potential for non-invasive "real-time" analysis of exhaled biomarkers and the application of portable, point-of-care, sensor-based devices for personalised monitoring of disease state and therapy progress is a clear advancement beyond the current state-of-the-art in clinical practice. Ultimately such methodology could lead to more timely and hence more effective antibiotic use. Volatile organic compounds (VOCs) for the detection of respiratory infections <http://ow.ly/rdhy30aEGQt>
Should same day discharge general anaesthesia be a notifiable condition for being unfit to drive?
Authors: Emma L Simpson, Mark W Davies
Journal: BMJ (2017)

Sokol uses pathos very effectively to highlight the dangers of driving when unfit.1 As anaesthetists, we routinely advise patients that they will be unfit to drive while their reactions are impaired by the residual effects of their anaesthetic drugs—usually for 24-48 …
Abstract P172: Circulating Heat Shock Protein 70 and Antiheat Shock Protein 70 Antibodies in Atrial Fibrillation: Relation with Atrial Fibrillation Type and Response to Catheter Ablation
Authors: Jelena Kornej, Claudia Reinhardt, Jedrzej Kosiuk, Arash Arya, Gerhard Hindricks, Volker Adams, Daniela Husser, Andreas Bollmann
Journal: Circulation Research (2011)

Background: HSP and anti-HSP antibodies have been associated with AF development and progression. This study investigated the possible association between circulating heat shock protein 70 (HSP70) and anti-HSP70 antibodies as well their changes and rhythm outcome after atrial fibrillation (AF) catheter ablation. Methods: In 67 patients with AF (59±11 years, 66 % male, 66 % lone AF) undergoing catheter ablation, circulating HSP70 and anti-HSP70 antibodies levels were quantified before and 6 months after catheter ablation. Serial 7-day Holter ECGs were used to detect AF recurrences. Results: At baseline, HSP70 was detectable in 14 patients (21 %), but there was no correlation between clinical or echocardiographic variables and the presence or the level of HSP70. Patients with paroxysmal AF (n=39) showed lower anti-HSP70 antibodies (median 43, IQR 28 - 62 µg/ml) than patients with persistent AF (n=28; 53, 41 - 85 µg/ml, p=.035). Using multivariable regression analysis, AF type was the only variable associated with anti-HSP70 antibodies (Beta=.342, p=.008). At 6 months, HSP70 was present in 27 patients (41 %, p&lt;.001 vs. baseline) with an overall increase (median 0, IQR 0 - 0 vs. 0, 0 - 0.09 ng/ml, p=.029). Similarly, there was an increase of anti-HSP70 antibodies (48, 36 - 72 vs. 57, 43 - 87 µg/ml, p&lt;.001). AF recurrence rates were higher in patients with HSP70 increase &gt;0.025 ng/ml (32 vs. 11 %, p=.038) or anti-HSP70 antibodies increase &gt;2.5 µg/ml (26 vs. 4 %, p=.033). Conclusion: HSP70 and anti-HSP70 antibodies may be involved in the progression of AF and AF recurrence after catheter ablation.
DIPG-21. GENOMIC LANDSCAPE OF THE FIRST 100 TUMORS REGISTERED IN THE BIOLOGICAL MEDICINE FOR DIPG ERADICATION (BIOMEDE) TRIAL
Authors: David Castel, Emilie Barret, Stephanie Picot, Alexandre Plessier, Ludivine Le Dret, Karsten Nysom, Sophie Huybrechts, Perrine Capolino, Marie-Cecile Le Deley, Gilles Vassal, Stephanie Puget, Pascale Varlet, Jacques Grill, Marie-Anne Debily
Journal: Neuro-Oncology (2017)

BACKGROUND: Genomic analyses of DIPG have been so far mostly performed on autopsy samples or in retrospective studies. In the frame of the BIOMEDE randomized trial of three targeted therapies (erlotinib, everolimus, dasatinib) based on three biomarkers (EGFR, PTEN and PDGFRA respectively), a systematic whole exome and RNA sequencing of stereotactic biopsies was performed at diagnosis. These analyses were implemented to inform the results of the trial and define additional targets that could be used to guide therapies at relapse. PATIENTS AND METHODS: The results of the first 100 patients from France, Denmark and Belgium are presented. Seventy-five percent of the samples could be profiled for DNA &/or RNA, no frozen material was available for 6% of the tumors and only one sample was not contributive. RESULTS: Tumor samples from all but one patients included in the study on the basis of histology showed a loss of H3-K27 trimethylation. With respect to histone H3-K27M mutation, 75% of the samples were mutated in the H3F3A gene, 17% in the HIST1H3B gene and 8% were wild-type for all histone H3 genes. TP53 or PPM1D mutations were identified in 75% of H3F3A-K27M DIPG while never found in HIST1H3B-K27M tumours. ACVR1 mutations were almost exclusively found in HIST1H3B-K27M mutated samples, except for two histone H3 wild-type and one H3F3A-K27M mutated samples. Receptor Tyrosine-Kinases mutations or amplifications were restricted to H3F3A-K27M DIPG. Most tumors showed copy number variations. But gains of chromosome 1q and whole chromosome 2 were more frequent in the HIST1H3B-K27M mutated samples. On the opposite, chromothripsis-like structural copy number aberrations mostly affected TP53 or PPM1D mutated samples. Translocations were only rarely identified and none was recurrent. CONCLUSION: This study refines the description of the differences in the subtypes of DIPG and may support specific treatment adaptations with respect to potential biomarkers.