tbuckley/cabot-search huggingface dataset:
Prognostic Value of Quantitative Stress Perfusion Cardiac Magnetic Resonance
Authors: Eva C. Sammut, Adriana D.M. Villa, Gabriella Di Giovine, Luke Dancy, Filippo Bosio, Thomas Gibbs, Swarna Jeyabraba, Susanne Schwenke, Steven E. Williams, Michael Marber, Khaled Alfakih, Tevfik F. Ismail, Reza Razavi, Amedeo Chiribiri
Journal: JACC. Cardiovascular imaging (2017)

This study sought to evaluate the prognostic usefulness of visual and quantitative perfusion cardiac magnetic resonance (CMR) ischemic burden in an unselected group of patients and to assess the validity of consensus-based ischemic burden thresholds extrapolated from nuclear studies.There are limited data on the prognostic value of assessing myocardial ischemic burden by CMR, and there are none using quantitative perfusion analysis.Patients with suspected coronary artery disease referred for adenosine-stress perfusion CMR were included (n = 395; 70% male; age 58 ± 13 years). The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, aborted sudden death, and revascularization after 90 days. Perfusion scans were assessed visually and with quantitative analysis. Cross-validated Cox regression analysis and net reclassification improvement were used to assess the incremental prognostic value of visual or quantitative perfusion analysis over a baseline clinical model, initially as continuous covariates, then using accepted thresholds of ≥2 segments or ≥10% myocardium.After a median 460 days (interquartile range: 190 to 869 days) follow-up, 52 patients reached the primary endpoint. At 2 years, the addition of ischemic burden was found to increase prognostic value over a baseline model of age, sex, and late gadolinium enhancement (baseline model area under the curve [AUC]: 0.75; visual AUC: 0.84; quantitative AUC: 0.85). Dichotomized quantitative ischemic burden performed better than visual assessment (net reclassification improvement 0.043 vs. 0.003 against baseline model).This study was the first to address the prognostic benefit of quantitative analysis of perfusion CMR and to support the use of consensus-based ischemic burden thresholds by perfusion CMR for prognostic evaluation of patients with suspected coronary artery disease. Quantitative analysis provided incremental prognostic value to visual assessment and established risk factors, potentially representing an important step forward in the translation of quantitative CMR perfusion analysis to the clinical setting.
Adherence to quality indicators of Barrett’s esophagus surveillance: where do we stand?
Authors: Donevan Westerveld, Dennis Yang
Journal: Endoscopy (2017)

Barrett’s esophagus (BE) is a precursor for the development of esophageal adenocarcinoma (EAC). Recent data indicate that surveillance endoscopy is associated with improved outcomes of EAC in patients with BE [1]. Various gastrointestinal societies recommend adherence to the use of a validated classification system (Prague C & M) and systematic four-quadrant biopsy protocol (Seattle protocol) in order to standardize BE surveillance and promote high-quality care [2] [3]. Nonetheless, adherence to these standardized practices remains variable.
Clinical Sequencing for Patients with Pancreatic Cancer
Authors: Hideyuki Hayashi, Shigeki Tanishima, Ryo Mori, Yasunobu Okamura, Toraji Amano, Ichiro Kinoshita, Yoshito Komatsu, Hirotoshi Dosaka-akita, Hiroshi Nishihara
Journal: Annals of Oncology (2017)
L’objectif de l’élimination de la rougeole en 2010 : il faut cibler les groupes à risque spécifiques
Authors: J. S. Spika
Journal: Eurosurveillance (2006)

Des progres importants ont ete realises ces dernieres annees dans la region Europe de l’Organisation Mondiale de la Sante (OMS) pour atteindre l’objectif d’elimination de la rougeole et de la rubeole en 2010. Ces objectifs ont ete fixes en 2005 par le Bur
TCT-797 Ten years follow-up results of primary percutaneous coronary intervention in left main coronary artery disease
Authors: Jesus Piqueras-Flores, Ignacio Sanchez-Perez, Fernando Lozano, María Thiscal López Lluva, Natalia Pinilla-Echeverri, Ramón Maseda Uriza, Manuel Marina-Breysse, Alfonso Jurado-Román
Journal: Journal of the American College of Cardiology (2017)
Interleukin-1 Beta as a Target for Atherosclerosis Therapy
Authors: Peter Libby
Journal: Journal of the American College of Cardiology (2017)

Inflammatory pathways drive atherogenesis and link conventional risk factors to atherosclerosis and its complications. One inflammatory mediator has come to the fore as a therapeutic target in cardiovascular disease. The experimental and clinical evidence reviewed here support interleukin-1 beta (IL-1β) as both a local vascular and systemic contributor in this regard. Intrinsic vascular wall cells and lesional leukocytes alike can produce this cytokine. Local stimuli in the plaque favor the generation of active IL-1β through the action of a molecular assembly known as the inflammasome. Clinically applicable interventions that interfere with IL-1 action can improve cardiovascular outcomes, ushering in a new era of anti-inflammatory therapies for atherosclerosis. The translational path described here illustrates how advances in basic vascular biology may transform therapy. Biomarker-directed application of anti-inflammatory interventions promises to help us achieve a more precise and personalized allocation of therapy for our cardiovascular patients.
Functional interaction between BRCA1 and protein phosphatase 1α
Authors: Lih-Ching Hsu
Journal: Cancer Research (2007)

4533   The tumor suppressor BRCA1 plays an important role in regulating fundamental cellular functions, such as cell cycle checkpoint control and DNA repair. The phosphorylation status of BRCA1 is tightly associated with its function. Protein kinases involved in DNA damage checkpoint control, such as ATM, ATR, and hCds1/Chk2, phosphorylate and activate BRCA1 upon DNA damage and subsequently induce G2 arrest. We have reported previously that protein phosphatase 1α (PP1α) interacts with and dephosphorylates BRCA1 phosphorylated by hCds1/Chk2, and may serve as a regulator of BRCA1 function. PP1α is one of the major subtypes of serine/threonine protein phosphatase 1, which regulates cell metabolism and cell cycle progression. Proteins that interact with the catalytic subunit of PP1, such as regulatory subunits and substrates, usually contain a conserved PP1-binding motif, the RVxF motif, which binds to a hydrophobic groove on the surface of the catalytic subunit. The catalytic subunit of PP1α interacts with BRCA1 through binding to BRCA1 fragment 4 (BF4), which contains amino acids 759-1064. Sequence analysis has revealed the presence of a putative PP1-binding motif in the BF4 region of BRCA1. Expression vectors of GST-BF4 and BRCA1GFP carrying mutations in the putative PP1-binding motif were constructed by PCR-based mutagenesis. Both GST pull down assay and co-immunoprecipitation analysis indicated that mutation or deletion of critical residues in the putative PP1-binding motif substantially abolished the interaction between BRCA1 and PP1α. Furthermore, unlike the wild-type BRCA1, expression of PP1 non-binding mutant BRCA1 proteins failed to enhance cell survival after DNA damage in BRCA1-mutated cell line HCC1937. These results indicate that interaction with PP1α is critical for BRCA1 function.
Brote de gastroenteritis por Campylobacter jejuni en un colegio de Madrid, España
Authors: M Jiménez, P Soler, J D Venanzi, P Canté, C Varela, J. F. Martinez Navarro
Journal: Eurosurveillance (2005)

En mayo de 2003 se detecto un brote de gastroenteritis por Campylobacter en un colegio de Madrid, Espana. Se identificaron ochenta y un casos de un total de 253 personas estudiadas. Un estudio de cohorte retrospectiva mostro asociacion entre el consumo de unas natillas hechas con leche UHT (ultra high temperature) y la enfermedad (RR: 3.15; 95% CI: 1.25-7.93). Las natillas se contaminaron probablemente con Campylobacter jejuni proveniente de carne de pollo que se preparo el dia anterior en la misma cocina. Nuestras recomendaciones fueron recordar periodicamente a las autoridades escolares como actuar si sospechan un brote en su colegio; incluir en cada investigacion ambiental el seguimiento de una jornada completa de trabajo de los manipuladores de alimentos y su entorno con el fin de detectar comportamientos de riesgo; mejorar el estudio microbiologico de las superficies y utensilios de las cocinas colectivas y mejorar la educacion sanitaria de los manipuladores de alimentos.
<i>MECOM</i>,<i>HBS1L-MYB</i>,<i>THRB-RARB, JAK2</i>, and<i>TERT</i>polymorphisms defining the genetic predisposition to myeloproliferative neoplasms: A study on 939 patients
Authors: Adrian P. Trifa, Claudia Bănescu, Anca S. Bojan, Cristian M. Voina, Ștefana Popa, Simona Vișan, Alina D. Ciubean, Florin Tripon, Delia Dima, Viola M. Popov, Ștefan C. Vesa, Mihaela Andreescu, Tünde Török‐Vistai, Romeo G. Mihăilă, Nicoleta Berbec, Ioan Macarie, Andrei Coliţă, Maria Iordache, Alina C. Cătană, Marius F. Farcaș, Ciprian Tomuleasa, Kinga Vasile, Cristina Truică, Adriana Todincă, Lavinia Pop‐Muntean, Raluca Manolache, Horia Bumbea, Ana‐Maria Vlădăreanu, Mihaela Gaman, Cristina M. Ciufu, Radu A. Popp
Journal: American Journal of Hematology (2017)

Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical myeloproliferative neoplasms (MPN), characterized by specific somatic mutations in JAK2, CALR or MPL genes. JAK2 46/1 and TERT rs2736100 polymorphisms are known to significantly predispose to MPN. This study aimed to establish the additional contribution of the recently described MECOM rs2201862, HBS1L-MYB rs9376092 and THRB-RARB rs4858647 polymorphisms to the occurrence of MPN. These three polymorphisms, along with JAK2 46/1 and TERT rs2736100 were genotyped in 939 MPN patients (454 with ET, 337 with PV and 148 with PMF) and 483 controls. MECOM rs2201862 associated significantly with each MPN entity, except for ET, and with all major molecular sub-types, especially those CALR-mutated (OR = 1.4; 95% CI = 1.1-1.8; P-value = .005). HBS1L-MYB rs9376092 associated only with JAK2 V617F-mutated ET (OR = 1.4; 95% CI = 1.1-1.7; P-value = .003). THRB-RARB rs4858647 had a weak association with PMF only (OR = 1.5; 95% CI = 1-2.1; P-value = .04). Surprisingly, JAK2 46/1 haplotype was associated significantly not only with JAK2 V617F-mutated MPN, but also with CALR-mutated MPN (OR = 1.4; 95% CI = 1.1-1.8; P-value = .01). TERT rs2736100 was associated equally strong with all MPN, regardless of phenotype or molecular sub-type. In conclusion, JAK2 46/1, TERT rs2736100 and MECOM rs2201862 are the chief predisposing polymorphisms to MPN.
Virus respiratoires et syndromes grippaux : une enquête dans la région de Rome, hiver 2004-2005
Authors: G Rezza, C Valdarchi, S Puzelli, M Ciotti, F Farchi, C Fabiani, L Calzoletti, I Donatelli, C F Perno
Journal: Eurosurveillance (2006)

L’information disponible sur l’etiologie virale des syndromes grippaux (SG) dans les pays du sud de l’Europe est limitee. L’article suivant decrit les principaux resultats d’une enquete menee dans la region de Rome pendant l’hiver 2004-2005. 
La definition de cas du syndrome grippal etait une fievre superieure a 37.5°C accompagnee au moins d’un symptome constitutionnel et d’un symptome respiratoire, rapporte pendant la periode de l’enquete. Le virus de la grippe et les autres virus respiratoires etaient identifies par PCR a partir de prelevements pharynges. Les informations individuelles de base etaient recueillies sur un formulaire standard. 
Sur les 173 cas de syndromes grippaux de l’enquete, 74 ont eu des tests positifs pour un virus, et deux pour deux virus. Au total, 33,5% des cas etaient positifs pour les virus influenza, 5,2% pour les adenovirus, 3,5% pour les virus parainfluenza, 1,7% pour les coronavirus et 1,2% pour le virus respiratoire syncitial. La proportion de detections de virus grippaux etait plus elevee pendant la periode de « forte activite grippale ». La distribution des agents viraux variait selon les groupes d’âge, les virus influenza etant plus frequemment detectes chez les jeunes patients. 
Des pathogenes viraux etaient identifies chez moins de 50% de cas de SG pendant la saison grippale active. La detection de virus autres que les virus influenza etait sporadique, sans que de grandes epidemies dues a des agents specifiques n’aient pu etre mises en evidence.
miR-6883 Family miRNAs Target CDK4/6 to Induce G1 Phase Cell-Cycle Arrest in Colon Cancer Cells
Authors: Amriti R. Lulla, Michael J. Slifker, Yan Zhou, Avital Lev, Margret B. Einarson, David T. Dicker, Wafik S. El-Deiry
Journal: Cancer Research (2017)

CDK4/6 targeting is a promising therapeutic strategy under development for various tumor types. In this study, we used computational methods and The Cancer Genome Atlas dataset analysis to identify novel miRNAs that target CDK4/6 and exhibit potential for therapeutic development in colorectal cancer. The 3'UTR of CDK4/6 mRNAs are targeted by a family of miRNAs, which includes miR-6883-5p, miR-149*, miR-6785-5p, and miR-4728-5p. Ectopic expression of miR-6883-5p or miR-149* downregulated CDK4 and CDK6 levels in human colorectal cancer cells. RNA-seq analysis revealed an inverse relationship between the expression of CDK4/6 and miR-149* and intronic miRNA-6883-5p encoding the clock gene PER1 in colorectal cancer patient samples. Restoring expression of miR-6883-5p and miR-149* blocked cell growth leading to G0-G1 phase cell-cycle arrest and apoptosis in colorectal cancer cells. CDK4/6 targeting by miR-6883-5p and miR-149* could only partially explain the observed antiproliferative effects. Notably, both miRNAs synergized with the frontline colorectal cancer chemotherapy drug irinotecan. Further, they resensitized mutant p53-expressing cell lines resistant to 5-fluorouracil. Taken together, our results established the foundations of a candidate miRNA-based theranostic strategy to improve colorectal cancer management. Cancer Res; 77(24); 6902-13. ©2017 AACR.
Sistema Europeu de Vigilância da Resistência Antimicrobiana: objectivos e organização
Authors: S L A M Bronzwaer, W Goettsch, B Olsson-Liljequist, M C J Wale, A Vatopoulos, M. J.W Sprenger
Journal: Eurosurveillance (1999)

Numa conferencia da Uniao Europeia (UE), realizada em Setembro de 1998 na Dinamarca, sobre a necessidade de vigilância dos microorganismos resistentes (a ameaca microbiana), concluiu-se que ‘A vigilância Europeia eficaz deve ser alvo de um acordo e do envolvimento activo por parte de todos os participantes’ (1). Os padroes da resistencia aos antibioticos diferem bastante entre os estados membros da UE (2,3). Os estudos efectuados sugerem que as politicas e as linhas de orientacao sobre a utilizacao de antibioticos podem afectar a prevalencia da resistencia (4,5).
Abstract 105: Platelet-Neutrophil Aggregates play a crucial role in regulating vasculitis in Kawasaki Disease
Authors: Kentaro Ueno
Journal: Circulation (2015)

Objective: Circulating platelet-neutrophil aggregates play a crucial role in amplifying acute inflammation and could promote adverse effects involving vascular injury. The aim of this study was to clarify the role of platelet-neutrophil aggregates in patients with Kawasaki disease (KD). Methods: We analyzed 40 patients with KD (30 intravenous immunoglobulin [IVIG] responders and 10 IVIG non-responders), 7 febrile patients with bacterial infections, and 9 normal volunteers. Thirty-three patients with KD were treated with IVIG alone, and remaining seven were treated with IVIG plus prednisolone. We evaluated the rate of platelet-neutrophil aggregates and measured the platelet factor 4 (PF4) and β-thromboglobulin (β-TG) levels in patients with KD. Results: The rate of platelet-neutrophil aggregates was significantly higher in patients with KD than in both patients with bacterial infection and normal volunteers. There was a trend toward increased rate of platelet-neutrophil aggregates within 2 or 3 days after IVIG than before IVIG. The rate of platelet-neutrophil aggregates was significantly higher in patients who showed coronary artery abnormalities (CAA) than in those who showed without CAA and was correlated with PF4 and β-TG levels in patients with KD. Comparing time course analysis, the rate of platelet-neutrophil aggregates was significantly decreased in patients treated with IVIG plus prednisolone than in those treated with IVIG alone. Conclusions: Our findings demonstrate that platelet-neutrophil aggregates play a crucial role in regulating vasculitis, and are involved in the development of CAA. Additional prednisolone treatment in the acute phase of KD might have a potential role in inhibiting amplified reciprocal inflammatory activation by suppressing platelet-neutrophil aggregates.
TRPC5 Does Not Cause or Aggravate Glomerular Disease
Authors: Xuexiang Wang, Ranadheer R. Dande, Hao Yu, Beata Samelko, Rachel E. Miller, Mehmet M. Altintas, Jochen Reiser
Journal: Journal of the American Society of Nephrology (2017)

Transient receptor potential channel 5 (TRPC5) is highly expressed in brain and kidney and mediates calcium influx and promotes cell migration. In the kidney, loss of TRPC5 function has been reported to benefit kidney filter dynamics by balancing podocyte cytoskeletal remodeling. However, in vivo gain-in-function studies of TRPC5 with respect to kidney function have not been reported. To address this gap, we developed two transgenic mouse models on the C57BL/6 background by overexpressing either wild-type TRPC5 or a TRPC5 ion-pore mutant. Compared with nontransgenic controls, neither transgenic model exhibited an increase in proteinuria at 8 months of age or a difference in LPS-induced albuminuria. Moreover, activation of TRPC5 by Englerin A did not stimulate proteinuria, and inhibition of TRPC5 by ML204 did not significantly lower the level of LPS-induced proteinuria in any group. Collectively, these data suggest that the overexpression or activation of the TRPC5 ion channel does not cause kidney barrier injury or aggravate such injury under pathologic conditions.
Abstract 19342: The Impact of PCSK9 Inhibitors on Lipid Levels and Outcomes in Patients With Primary Hypercholesterolemia: A Network Meta-analysis
Authors: Michael J Lipinski, Ricardo O Escarcega, Thibault Lhermusier, Nevin C Baker, Rebecca Torguson, H. Bryan Brewer, Ron Waksman
Journal: Circulation (2015)

Introduction: We performed a network meta-analysis of randomized controlled trials (RCTs) in patients with primary hypercholesterolemia to compare the impact of PCSK9 inhibitors with placebo and ezetimibe on lipid levels and outcomes. Hypothesis: PCSK9 inhibitors will significantly lower LDL-C greater than ezetimibe and improve outcomes. Methods: MEDLINE/PubMed, Cochrane CENTRAL, and ClinicalTrials.gov were searched for RCTs assessing PCSK9 inhibitors versus other therapies in patients with primary hypercholesterolemia. Mixed treatment comparison model generation was performed to directly and indirectly compare PCSK9 inhibition on lipid levels with ezetimibe and placebo. Odds ratios with 95% confidence intervals (OR [95% CIs]) were generated with random-effect models to compare outcomes. Results: Our meta-analysis included 17 RCTs with 13,083 patients that were randomized to PCSK9 inhibitors (n=8,250), placebo (n=3,957), ezetimibe (n=846), or PCSK9 inhibitors and ezetimibe (n=30). The mean age was 59±10, 52% were male, 34% had coronary artery disease, 51% had hypertension, 19% had diabetes mellitus, baseline LDL of 122±36 mg/dL, total cholesterol of 199±39 mg/dL, and HDL of 51±14 mg/dL. PCSK9 inhibitors significantly reduced LDL cholesterol by 57% relative to placebo (p&lt;0.001) and 36.1% relative to ezetimibe (p&lt;0.001). PCSK9 inhibitors reduced the incidence of all-cause mortality (OR 0.43 [95% CI 0.22-0.82], p=0.01) with a trend for cardiovascular death (OR 0.50 [95% CI 0.22-1.13], p=0.10) and cardiovascular events (OR 0.67 [95% CI 0.43-1.04], p=0.07) when compared with placebo. Conclusions: PCSK9 inhibition significantly improved lipid profiles and reduced the incidence of all-cause mortality compared with placebo. Thus, PCSK9 inhibitor therapy, once approved, may serve as an excellent alternative for patients with statin intolerance and for those who do not respond to conventional lipid reduction therapy.
TCT-321 Transcatheter Aortic Valve Replacement with a Self-Expanding Bioprosthesis Augmented with a Porcine Pericardial Wrap
Authors: Daniel O'Hair, Renuka Jain, Amanda Kirby, Jayant Khitha, Bijoy Khandheria, Suhail Allaqaband, Tanvir Bajwa
Journal: Journal of the American College of Cardiology (2017)
Fundamentals of Laser‐Based Hydrogel Degradation and Applications in Cell and Tissue Engineering
Authors: Shantanu Pradhan, Keely A. Keller, John L. Sperduto, John H. Slater
Journal: Advanced Healthcare Materials (2017)

The cell and tissue engineering fields have profited immensely through the implementation of highly structured biomaterials. The development and implementation of advanced biofabrication techniques have established new avenues for generating biomimetic scaffolds for a multitude of cell and tissue engineering applications. Among these, laser-based degradation of biomaterials is implemented to achieve user-directed features and functionalities within biomimetic scaffolds. This review offers an overview of the physical mechanisms that govern laser-material interactions and specifically, laser-hydrogel interactions. The influences of both laser and material properties on efficient, high-resolution hydrogel degradation are discussed and the current application space in cell and tissue engineering is reviewed. This review aims to acquaint readers with the capability and uses of laser-based degradation of biomaterials, so that it may be easily and widely adopted.