tbuckley/cabot-search huggingface dataset:
Abstract 3: Interaction Between NFκB and NFAT Coordinates Cardiac Hypertrophy and Pathological Remodeling
Authors: Qinghang Liu, Jeffery Molkentin
Journal: Circulation Research (2011)

Both NFAT and NFkB are Rel homology domain-containing family members of transcription factors whose independent activities are critically involved in regulating cardiac hypertrophy and failure. Here we identified a novel transcriptional regulatory mechanism whereby NFkB and NFAT directly interact and synergistically promote transcriptional activation of one another in cardiomyoctes. We showed that NFkB-p65 co-immunoprecipitates with NFAT isoforms in cardiomyocytes, and this interaction is mapped to the Rel homology domain (RHD) within p65. Intriguingly, overexpression of p65-RHD disrupts the association between endogenous p65 and NFATc1, leading to reduced NFAT luciferase activity. Overexpression of p65-RHD or IKKβ leads to significant nuclear translocation of NFATc1, and expression of a constitutively nuclear NFATc1-SA similarly facilitated p65 nuclear translocation, further suggesting a physical interaction between p65 and NFATc1. Indeed, we observed that combined overexpression of p65 and NFAT leads to synergistic activation of NFAT transcriptional activity in cardiomyocytes. Conversely, NFAT transcriptional activity in cardiomyocytes is significantly reduced by inhibition of NFkB with IkBαM or dominant negative IKKβ. Importantly, hypertrophic agonist-induced NFAT activity is also significantly reduced in NFkB-p65 null MEFs compared to wild-type MEFs, while adenoviral-mediated expression of p65 restored NFAT luciferase activity in p65 null MEFs. In vivo, cardiac-specific deletion of NFkB-p65 using a Cre-LoxP system caused a ∼ 50% reduction in NFAT activity in NFAT-luciferase reporter mice. Moreover, ablation of p65 in the mouse heart decreased the hypertrophic response following pressure overload stimulation, reduced the degree of pathological remodeling, and preserved contractile function. Taken together, our results suggest a direct interaction between NFAT and NFkB pathways that may serve as a novel signaling mechanism in cardiac hypertrophy and failure.
TCTAP C-205 Triple Threat: Anomalous Origin of the Right Coronary Artery Associated with Coronary-cameral Fistula and Apical Hypertrophic Cardiomyopathy
Authors: Jeffrey Sibulo Delos Santos, Noemi Serion Pestano, Rogelio Ventura Tangco
Journal: Journal of the American College of Cardiology (2017)
The Lung Microbiome: Key to Respiratory Ills?
Authors: Jeff Lyon
Journal: JAMA (2017)

The word microbiome has become a catch term only in the past decade, but it refers to something as old as humanity itself: the diverse and unimaginably vast population of microorganisms that share our bodies. These microbiota compose an ecosystem whose constituent cells and genes actually outnumber our own, and without which we would be unable to carry out many functions necessary for life. Medicine has succeeded in mapping much of the gut microbiome, but only recently has advanced technology enabled researchers to identify and study the inhabitants of the human respiratory system and possibly use this information to diagnose and treat respiratory disease.
Skin fibroblasts are potent suppressors of inflammation in experimental arthritis
Authors: C. Bouffi, C. Bony, C. Jorgensen, D. Noel
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Fibroblasts possess in vitro immunomodulatory properties that are similar to those of multipotent mesenchymal stromal cells (MSC) but their role has been poorly investigated in vivo. Here, we compared the effect of MSC or skin fibroblast injection on the host immune response in the collagen-induced arthritis model. <h3>Materials and methods</h3> Fibroblasts were isolated from the skin of DBA1 mice and immunophenotyped by flow cytometry. Their capacity to differentiate into chondrocytes, adipocytes and osteoblasts was evaluated after culture in specific inducing conditions. Immunosuppresssion was evaluated in concanavalin A-induced proliferative assay. In the CIA model, 10<sup>6</sup> fibroblasts were intravenously injected at day 18 and 24 after collagen II immunisation. Arthritis was evaluated by the measure of clinical signs (paw swelling and inflammation) and immunological parameters (dosage of collagen II-specific immunoglobulins, inflammatory cytokines and proliferation of T lymphocytes). <h3>Results</h3> We first confirm that skin fibroblasts isolated from DBA1 mice lack the capacity to differentiate into osteoblasts or chondrocytes but possess the capacity to differentiate into adipocytes. We also report that fibroblasts inhibit the proliferation of T lymphocytes in a concanavalin A-induced proliferative assay and secrete modulatory molecules, in particular PGE2 and NO. To assess their role in vivo, 10<sup>6</sup> fibroblasts were intravenously injected at day 18 and 24 after collagen II immunisation of DBA1 mice. We show that similar to MSCs, the intravenous injection of fibroblasts efficiently suppress the clinical signs of arthritis and delay the disease onset. This effect is associated with a reduced inflammation and notably, increased levels of interleukin (IL) -5, IL-10 and IL-13 in the spleens of treated mice. To further characterise the mechanism of immunosuppression, we performed phenotypic analyses and could not detect any induction of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells whereas a population of CD4<sup>+</sup>IL-10<sup>+</sup> T cells is slightly increased after fibroblast injection and significantly upregulated after MSC administration. <h3>Conclusion</h3> Our study shows the therapeutic efficacy of systemic injection of syngeneic fibroblasts to reduce the clinical signs of arthritis and strongly suggests that fibroblasts induce a Th2 immune profile although we cannot exclude that IL-10 secreting Treg cells may be generated.
Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways
Authors: Khadijah Edueng, Denny Mahlin, Per Larsson, Christel A.S. Bergström
Journal: Journal of Controlled Release (2017)

We developed a step-by-step experimental protocol using differential scanning calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy (PLM) and a small-scale dissolution apparatus (μDISS Profiler) to investigate the mechanism (solid-to-solid or solution-mediated) by which crystallization of amorphous drugs occurs upon dissolution. This protocol then guided how to stabilize the amorphous formulation. Indapamide, metolazone, glibenclamide and glipizide were selected as model drugs and HPMC (Pharmacoat 606) and PVP (K30) as stabilizing polymers. Spray-dried amorphous indapamide, metolazone and glibenclamide crystallized via solution-mediated nucleation while glipizide suffered from solid-to-solid crystallization. The addition of 0.001%–0.01% (w/v) HPMC into the dissolution medium successfully prevented the crystallization of supersaturated solutions of indapamide and metolazone whereas it only reduced the crystallization rate for glibenclamide. Amorphous solid dispersion (ASD) formulation of glipizide and PVP K30, at a ratio of 50:50% (w/w) reduced but did not completely eliminate the solid-to-solid crystallization of glipizide even though the overall dissolution rate was enhanced both in the absence and presence of HPMC. Raman spectroscopy indicated the formation of a glipizide polymorph in the dissolution medium with higher solubility than the stable polymorph. As a complementary technique, molecular dynamics (MD) simulations of indapamide and glibenclamide with HPMC was performed. It was revealed that hydrogen bonding patterns of the two drugs with HPMC differed significantly, suggesting that hydrogen bonding may play a role in the greater stabilizing effect on supersaturation of indapamide, compared to glibenclamide.
Comprehensive transcriptome analysis of neocortical layers in humans, chimpanzees and macaques
Authors: Zhisong He, Dingding Han, Olga Efimova, Patricia Guijarro, Qianhui Yu, Anna Oleksiak, Shasha Jiang, Konstantin Anokhin, Boris Velichkovsky, Stefan Grünewald, Philipp Khaitovich
Journal: Nature Neuroscience (2017)
Trimodality therapy for stage II-III carcinoma of the esophagus: A dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy.
Authors: Matthew D. Wood, Bassem I. Zaki, Stuart R. Gordon, John E. Sutton, Mikhail Lisovsky, Jiang Gui, Konstantin H. Dragnev, Jeffrey Alan Bubis, James R. Rigas
Journal: Journal of Clinical Oncology (2012)

e14514 Background: This dose escalation study was performed to determine the recommended phase II dose of capecitabine to be delivered concurrently with thoracic radiation therapy and weekly docetaxel in patients with locally advanced esophageal carcinoma. Methods: Patients with operable stage II or III esophageal carcinoma were staged by endoscopic ultrasonography and CT. Two cycles of docetaxel (80 mg/m 2 ) and carboplatin (target AUC of 6) were delivered over 6 weeks, followed by concurrent weekly docetaxel (15 mg/m 2 ), thoracic radiotherapy (50.4 Gy in 28 fractions), and increasing doses of capecitabine (500-3500 mg) given prior to each fraction of radiotherapy. After re-staging, responding patients continued to esophagectomy. Results: Forty-four patients were enrolled and 40 were evaluable for the dose-ranging component of chemoradiotherapy. The median age was 63 (range 47-87), 32 patients (80%) were male, and 36 (90%) had adenocarcinoma while 4 (10%) had squamous cell carcinoma. EUS stages at enrollment were T3N1 (29), T3N0 (4), T2N1 (6), and T4N0 (1). The maximum tolerated dose of capecitabine was 3500 mg. Common non-hematologic grade 3 or 4 toxicities were dysphagia (n=6, 15%) and nausea/vomiting (n=3, 8%). Common grade 3 or 4 hematologic toxicities were ANC and WBC abnormalities (n=10, 25% and n=9, 23% respectively). Overall, 58% of patients had no stage 3 or 4 toxicity. Thirty-six patients had surgery; 83% had R0 (curative) resection and 14% had complete pathological response (pCR). With a median follow-up time of 18.9 months, the median overall survival was 23.5 months, with 34% and 27% alive at three and five years, respectively. The three- and five-year relapse-free survival was 37%. In patients who had pCR or microscopically residual disease, 5-year survival was 74% (n=8). Conclusions: The recommended phase II dose of capecitabine is 3500 mg when given concurrently with 50.4 Gy in 28 fractions of thoracic radiotherapy with weekly docetaxel. This trimodality therapy for locally advanced esophageal carcinoma was well-tolerated and remarkably active. This regimen holds promise for treatment of esophageal carcinoma and warrants further investigation.
The Activated B-Cell Subtype of Diffuse Large B-Cell Lymphoma As Determined By Whole Genome Expression Profiling on Paraffin Embedded Tissue Is Independently Associated with Reduced Overall and Progression Free Survival in the Rituximab Era: Results from the UK NCRI R-CHOP 14 v 21 Phase III Trial
Authors: Mary Gleeson, Andrew Jack, David Cunningham, Nicholas Counsell, Nichola McWhirter, Rebecca Chalkley, Eliza A Hawkes, Nick Chadwick, Anthony Laurie, Paul Smith, Christopher Pocock, Kirit M Ardeshna, John A. Radford, Andrew McMillan, John Davies, Deborah Turner, Anton Kruger, Peter Johnson, Cathy H Burton, David C Linch, Sharon L Barrans
Journal: Blood (2016)
TCTAP C-286 Successful Valve-in-Valve Implantation for Symptomatic Severe Paravalvular Aortic Regurgitation at Follow-up after Transcatheter Aortic Valve Replacement
Authors: Ungjeong Do, Minsoo Kim, Hanbit Park, Yong-Hoon Yoon, Sang-Cheol Cho, Osung Kwon, Kyusup Lee, Jung Ae Hong, Do-Yoon Kang, Cheol Hyun Lee, Pil Hyung Lee, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2017)
TCTAP A-100 To Reduce In-hospital Cardiac Arrest Using Innovative Early Warning Information System
Authors: WangTing Hung, Wei-Chun Huang, Cheng-Hung Chiang, Chin-Chang Cheng, Wang-Chuan Juan, Shu-Hung Kuo, Kun Chang Lin, Po Hsiang Lin, Guang-Yuan Mar, Shue-Ren Wann, Yao-shen Chen, Chun-Peng Liu
Journal: Journal of the American College of Cardiology (2017)
Project management: importance for diagnostic laboratories
Authors: A. Croxatto, G. Greub
Journal: Clinical Microbiology and Infection (2017)

BackgroundThe need for diagnostic laboratories to improve both quality and productivity alongside personnel shortages incite laboratory managers to constantly optimize laboratory workflows, organization, and technology. These continuous modifications of the laboratories should be conducted using efficient project and change management approaches to maximize the opportunities for successful completion of the project.AimThis review aims at presenting a general overview of project management with an emphasis on selected critical aspects.SourcesConventional project management tools and models, such as HERMES, described in the literature, associated personal experience, and educational courses on management have been used to illustrate this review.ContentThis review presents general guidelines of project management and highlights their importance for microbiology diagnostic laboratories. As an example, some critical aspects of project management will be illustrated with a project of automation, as experienced at the laboratories of bacteriology and hygiene of the University Hospital of Lausanne. It is important to define clearly beforehand the objective of a project, its perimeter, its costs, and its time frame including precise duration estimates of each step. Then, a project management plan including explanations and descriptions on how to manage, execute, and control the project is necessary to continuously monitor the progression of a project to achieve its defined goals. Moreover, a thorough risk analysis with contingency and mitigation measures should be performed at each phase of a project to minimize the impact of project failures.ImplicationsThe increasing complexities of modern laboratories mean clinical microbiologists must use several management tools including project and change management to improve the outcome of major projects and activities.
Former journal editor is found guilty of data fabrication
Authors: Clare Dyer
Journal: BMJ (2017)

A former journal editor fabricated data in a research paper when he was working as a registrar at King’s College Hospital in London, a medical practitioners tribunal has concluded.1

Paul Grant, now a consultant diabetologist in Brighton, edited the British Journal of Diabetes from 2014 to 2016. In 2016 he was appointed editor in chief of Clinical Medicine , the journal of …
Studies of the Epidemiology of Staphylococcal Infection
Authors: Lawrence S. Cohen, F. Robert Fekety, Leighton E. Cluff
Journal: New England Journal of Medicine (1962)

STAPHYLOCOCCUS aureus belonging to bacteriophage Type 80/81 has been the single commonest strain responsible for infection in hospitalized patients during the past several years.1 2 3 4 5 6 The frequent use of antibiotics in hospitals may be partly responsible for the presence of infections in the hospital with Type 80/81 and other antibiotic-resistant staphylococci.7 , 8 The introduction of new antibiotics and the varying use of those presently available could result in the emergence of strains differing in antibiotic sensitivity from that of the bacteriophage Type 80/81 organism. Recently, neomycin-resistant staphylococci were reported as the cause of infection in patients receiving this drug for preoperative preparation . . .
Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade
Authors: Martina Schmittnaegel, Nicolò Rigamonti, Ece Kadioglu, Antonino Cassará, Céline Wyser Rmili, Anna Kiialainen, Yvonne Kienast, Hans-Joachim Mueller, Chia-Huey Ooi, Damya Laoui, Michele De Palma
Journal: Science Translational Medicine (2017)

Combination of antiangiogenic treatment and immune checkpoint inhibition improves antitumor immunity.
The PARP Inhibitor Olaparib Antagonizes Leukemic Growth Induced By TET1 Overexpression in AML1-ETO Positive Acute Myeloid Leukemia
Authors: Shiva Bamezai, Jing He, Deniz Sahin, Fabian Mohr, Fabio Ciccarone, Naidu M Vegi, Alex Pulikkottil Jose, Medhanie A. Mulaw, Paola Caiafa, Konstanze Döhner, Hartmut Döhner, Michaela Feuring-Buske, Christian Buske, Vijay P.S. Rawat
Journal: Blood (2016)
Efficacy and tolerance of ruxolitinib in refractory sclerodermatous chronic graft‐versus‐host disease
Authors: C. Hurabielle, F. Sicre de Fontbrune, H. Moins‐Teisserenc, M. Robin, M. Jachiet, T. Coman, N. Dhedin, C. Cassius, F. Chasset, A. Masson, D. Michonneau, M. Bagot, A. Bergeron, G. Socié, R. Peffault de Latour, J.‐D. Bouaziz
Journal: British Journal of Dermatology (2017)
THE EFFECT OF BODY CHECKING POLICY CHANGE ON OFFENSIVE GAME SKILL PERFORMANCE IN 13–14 YEAR OLD ICE HOCKEY PLAYERS
Authors: Ash Kolstad, Luc Nadeau, Paul Eliason, Luz Palacios-Derflingher, Claude Goulet, Carolyn A. Emery
Journal: British Journal of Sports Medicine (2017)

Background Policy allowing body checking (BC) increases injury and concussion risk in youth ice hockey players. Hockey Calgary introduced BC policy change in 2015 that disallows BC at the Bantam (ages 13–14) non-elite level (lowest 60% by division of play). Objective To compare game offensive performance (OP) between non-elite Bantam players playing in a league allowing BC and players in a league not allowing BC. Design Prospective cohort. Setting Arenas in Calgary, Alberta. Participants Non-elite Bantam games were videotaped in Calgary, Alberta during the 2014–15 (n=348 players) and 2015–16 (n=309 players) playing seasons. Assessment of Risk Factors Players from the 2014–15 season played in a league allowing BC, while players from 2015–16 season played in a league where BC was not allowed. Main Outcome Measurements Using Dartfish video analysis software, games were analyzed for OP metrics for the puck carrier using the ice hockey adapted Team Sport Assessment Procedure. These metrics included puck possession (conquered puck from an opponent and received pass from a teammate) and puck outcome (successful shot on goal, lost puck to an opponent, and offensive pass to a teammate). Unadjusted incidence rate-ratios (IRRs), clustered by game, were calculated for each puck action per team game between players in Calgary, Alberta 2014–15 (BC allowed) and 2015–16 (BC not allowed). Results No differences were found in puck possession metrics [conquered puck IRR=1.07 (95% CI: 1.00,1.16), received pass IRR=1.05 (95% CI: 0.93,1.18)] or puck outcome [successful shot IRR=0.97 (95% CI: 0.86,1.10), lost puck IRR=1.07 (95% CI: 0.98,1.18), offensive pass IRR=0.98 (95% CI: 0.86,1.12)]. Conclusions There were no differences found across all OP metrics between a non-elite Bantam league allowing BC and a league not allowing BC. There is no evidence to conclude that offensive performance was negatively nor positively affected by Hockey Calgary's decision to disallow BC at Bantam non-elite levels.
Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part IV. Special resuscitation situations
Journal: JAMA (1992)

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Factors associated with participation in resistance training: a systematic review
Authors: Ryan E Rhodes, David R Lubans, Nandini Karunamuni, Sarah Kennedy, Ronald Plotnikoff
Journal: British Journal of Sports Medicine (2017)

Objective Regular participation in resistance training (RT) is critical to health and recommended in most international physical activity guidelines. Few people, however, participate in RT. The purpose of this review was to assess the demographic, behavioural, intrapersonal, interpersonal and environmental factors associated with participating in RT. Data sources Eligible studies were from English peer-reviewed published articles that examined correlates or determinants of RT in adult samples. Searches were performed from August 2015 to April 2016 in six databases. Results We identified 51 independent data sets, from nine countries, primarily of moderate to high quality, and 23 factors related to participating in RT. Education, perceived health status, quality of life, affective judgements, self-efficacy, intention, self-regulation behaviours, subjective norm and programme leadership were associated with RT. Conclusion Low education levels and poor health status were associated with low participation rates in RT. Intrapersonal factors including affective judgements, self-efficacy, and self-regulation behaviours, and interpersonal factors including subjective norms and programme leadership may be important for promoting RT behaviours.