tbuckley/cabot-search huggingface dataset:
Abstract 19229: IL-18 a Powerful Activator of B-cells is Associated With Mortality in Acute Decompensated Heart Failure
Authors: Andrea M Cordero-Reyes, Keith A Youker, Ahmed Soliman, Mohamed El-Beheary, Arvind Bhimaraj, Barry H Trachtenberg, Guha Ashrith, Vijay Nambi, Guillermo Torre-Amione, Jerry D Estep
Journal: Circulation (2014)

Background:  Pre-clinical studies have demonstrated that in acute heart failure B-cell cytokines are elevated and these are associated with worsening of the heart failure state. The association of cytokines with markers of cardiac injury is not well established. Therefore we aim to determine if specific cytokines are present during an ADHF episode and its association with cardiac biomarkers and mortality.   Methods:  We studied 27 sequential patients admitted with ADHF. Serum samples within 24 hours of admission were analyzed. Using a Procarta multiplex cytokine panel assay (Affymetrix/eBioscience) we measured the following cytokines: INF-γ, IL-12, IL-13, IL-1β, IL-2, TNF- α, IL-4, IL-5, IL-6, GM-CSF and IL-18. Data was retrieved from patient charts and the primary endpoint was mortality within 1 year. We constructed AUC curves to determine optimal cut-off values and p-values ≤ 0.05 were considered significant.   Results:  Mean age was 79 ± 9, 19 were Caucasian, 21 male, and 15 had heart failure with reduced ejection fraction. We obtained measurable levels for the following cytokines IL-18, INF-γ, IL-6, IL-1β and IL-4 while IL-12, IL-13 TNF- α, IL-5, and GM-CSF had undetectable levels. We found increased levels of IL-18, and INF-γ in patients who died (p=0.05 and 0.09 respectively). There was a significant correlation between IL-18 and INF- γ (r=0.818, p-value= 0.0001) and IL-18 and BNP levels (r=0.392, p-value= 0.04).There was significantly increased mortality in patients with IL-18 >120 pg/ml. (figure)   Conclusion:  Both IL-18 and INF- γ are cytokines related to B-cell differentiation, activation and plasma cell production and they are associated with increased mortality in patients with ADHF. Additionally, there was a positive correlation between IL-18 and BNP levels and may add prognostic value in HF patients. These findings suggest a potential role of B-cells in outcomes of acute decompensated heart failure.
Détection précoce de la grippe en Europe et fuite du SRAS de laboratoires de haute sécurité
Authors: J C Desenclos
Journal: Eurosurveillance (2003)

Dans ce numero, Radun et al decrivent une investigation retrospective d'un cas de SRAS chez 21 ressortissants allemands ayant sejourne a l'hotel 'M' de Hong-Kong entre le 21 fevrier et le 3 mars 2003 (1). Les auteurs ont ainsi pu detecter
TCT-175 Diagnostic performance of Fractional Flow Reserve derived from Computed Tomography compared to Invasive Coronary Angiography derived Fractional Flow Reserve
Authors: Jai Parekh, Saurabh Aggarwal, Rohit Loomba, Gaurav Aggarwal, Ram Belbase, Hemantha Koduri, Brent Wilson, Rohit Arora, Venkata M. Alla
Journal: Journal of the American College of Cardiology (2017)
TCT-293 Is it possible to predict fractional flow reserve in side branch after main vessel stenting in coronary bifurcation lesions by means of intracoronary electrocardiogram? A proof of concept FFRvs.icECG
Authors: Dobrin Vassilev, Liubomir Dosev, Kiril Karamfiloff
Journal: Journal of the American College of Cardiology (2017)
Abstract 18190: Association Between Coronary CT Angiography and Reduced Admissions Rate in Emergency Department Chest Pain in Diabetics
Authors: Zain Kassam, Kevin Lazo, Pamela Noack, Jennifer Conroy, Michael Poon
Journal: Circulation (2016)

Introduction:  Coronary CT Angiography (CCTA) has been shown to safely triage, rule out acute coronary syndrome (ACS), and reduce inpatient resource use in low risk patients presenting to the ED with chest pain. The impact of CCTA as the standard of care (SOC) on resource utilization in diabetics, a high risk ACS population, has not been studied.   Hypothesis:  Routine use of CCTA in the ED to evaluate chest pain in diabetics safely reduces in-hospital resource utilization.   Methods:  We conducted a retrospective, risk matched, multivariate analysis of two diabetic ED patient cohorts (n=370), who presented with Chest Pain and received CCTA as SOC or our former standard evaluation (SE); measuring hospital admissions, cardiac interventions, recidivism rates, and downstream utilization.   Results:  SE patients were 9 times more likely to be admitted or observed (p   Conclusion:  CCTA reduced the need for inpatient stay, ICA, and stress testing in diabetics. CCTA’s anatomical information may have reduced the use of PCI in the initial workup for ACS. MACE numbers for CCTA were at least as good as for SE. Improved discharge planning and appropriate outpatient referrals to address medical concerns in these high risk patients may be needed to prevent recurrent ED visits resulting in unnecessary resource utilization.
Self-monitoring of blood glucose did not improve HbA<sub>1c</sub> or QoL at 1 year in non–insulin-treated type 2 diabetes
Authors: Harvey J. Murff
Journal: Annals of Internal Medicine (2017)

Source Citation Young LA, Buse JB, Weaver MA, et al; Monitor Trial Group. Glucose self-monitoring in non-insulin-treated patients with type 2 diabetes in primary care settings: a randomized trial. JAMA Intern Med. 2017;177:920-9. 28600913
Dual targeting of RAF-MEK-ERK and PI3K-AKT-mTOR pathways in RAS-mutant cancers: Preclinical insights and institutional experience from a clinical trial of binimetinib (MEK162) plus BYL719.
Authors: Udai Banerji, Alan David Smith, Andrea Zivi, David Lorente, Karim Rihawi, Nina Tunariu, Adam Stewart, Parames Thavasu, Audrey Kaag, Rajkumar Radhakrishnan, Heiko Maacke, L Rhoda Molife, Stanley B. Kaye, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2014)

e13559 Background: Current development is focused on agents targeting the RAF-MEK-ERK and PI3K-AKT-mTOR pathways. Combinations of these agents may address causes of de novo resistance. Identifying patients (pts) most likely to benefit from these combinations is important. Methods: A panel of 20 cell lines (5 BRAFM, 5 KRASM, 5 PIK3CAM and 5 BRAF/PIK3CA/KRASWT) were exposed to MEK and/or AKT inhibitors and evaluated for inhibition of pathway signaling and cell growth. Inhibition of signaling output of the RAF-MEK-ERK (p-ERK) and PI3K-AKT-mTOR (p-S6) pathways was quantified by ELISA. Growth inhibition was determined using sulforhodamine B assay. Based on the results of preclinical experiments, at our center we prioritized enrolling pts with RAS mutant tumors (including ovarian cancer and non-small cell lung cancer [NSCLC]) into an ongoing phase 1b clinical trial (CMEK162X2109) evaluating the combination of MEK inhibitor binimetinib (MEK162) and the PI3K-α inhibitor BYL719 in pts with RAS and RAF mutant tumors. Results: Significantly greater growth inhibition was seen in BRAFM and PIK3CAM cells at maximal MEK inhibition (P = 0.004) and AKT inhibition (P = 0.038) respectively, however KRASMcells lines were sensitive to either MEK or AKT inhibition. Among pts treated at our center, durable (> 10 months) partial responses (PR) were seen in 3/4 pts with RAS mutant ovarian cancer, previously pre-treated with chemotherapy in the dose escalation phase. Three of these patients had low grade ovarian cancer with KRAS mutations and one patient had a clear cell ovarian cancer with a dual PIK3CA + KRAS mutation. In the expansion phase, a PR was observed in a pt with KRAS mutant NSCLC who had received 2 lines of chemotherapy. Conclusions: Signaling output in RAS mutant cancers occurs through both the PI3K-AKT-mTOR and RAF-MEK-ERK pathways and thus those cancers are more likely to benefit from dual blockade. Pts with RAS mutant tumors, particularly low-grade serous ovarian cancer, may benefit from combined treatment as evidenced by preliminary clinical activity in an ongoing clinical trial of binimetinib plus BYL719. Clinical trial information: NCT01449058.
CD31 Expression Determines Redox Status and Chemoresistance in Human Angiosarcomas
Authors: Vivek Venkataramani, Stefan Küffer, Kenneth C.P. Cheung, Xuejun Jiang, Lorenz Trümper, Gerald G. Wulf, Philipp Ströbel
Journal: Clinical Cancer Research (2017)

Purpose: Angiosarcomas are soft tissue sarcomas with endothelial differentiation and vasoformative capacity. Most angiosarcomas show strong constitutive expression of the endothelial adhesion receptor CD31/PECAM-1 pointing to an important role of this molecule. However, the biological function of CD31 in angiosarcomas is unknown.Experimental Design: The expression levels of CD31 in angiosarcoma cells and its effects on cell viability, colony formation, and chemoresistance were evaluated in human angiosarcoma clinical samples and in cell lines through isolation of CD31high and CD31low cell subsets. The redox-regulatory CD31 function linked to YAP signaling was determined using a CD31-blocking antibody and siRNA approach and was further validated in CD31-knockout endothelial cells.Results: We found that most angiosarcomas contain a small CD31low cell population. CD31low cells had lost part of their endothelial properties and were more tumorigenic and chemoresistant than CD31high cells due to more efficient reactive oxygen species (ROS) detoxification. Active downregulation of CD31 resulted in loss of endothelial tube formation, nuclear accumulation of YAP, and YAP-dependent induction of antioxidative enzymes. Addition of pazopanib, a known enhancer of proteasomal YAP degradation resensitized CD31low cells for doxorubicin resulting in growth suppression and induction of apoptosis.Conclusions: Human angiosarcomas contain a small aggressive CD31low population that have lost part of their endothelial differentiation programs and are more resistant against oxidative stress and DNA damage due to intensified YAP signaling. Our finding that the addition of YAP inhibitors can resensitize CD31low cells toward doxorubicin may aid in the rational development of novel combination therapies to treat angiosarcomas. Clin Cancer Res; 24(2); 460-73. ©2017 AACR.
Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic <i>BRAF</i> V600–Mutant Anaplastic Thyroid Cancer
Authors: Vivek Subbiah, Robert J. Kreitman, Zev A. Wainberg, Jae Yong Cho, Jan H.M. Schellens, Jean Charles Soria, Patrick Y. Wen, Christoph Zielinski, Maria E. Cabanillas, Gladys Urbanowitz, Bijoyesh Mookerjee, Dazhe Wang, Fatima Rangwala, Bhumsuk Keam
Journal: Journal of Clinical Oncology (2017)

Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.
Challenges in Communicating and Understanding Predictive Biomarker Imaging for Alzheimer Disease
Authors: Winston Chiong
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
TCT-547 Comparison of Clinical Outcomes Between Ticagrelor and Prasugrel in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Jumin Won, Min Chul Kim, Myung Ho Jeong, Young Joon Hong, Doo Sun Sim, Youngkeun Ahn, Tae Hoon Ahn, Seung Ki-Bae, Dong Joo Oh, Hyo-Soo Kim, Hyeon Cheol Gwon, In Whan Seong, Young Jo Kim, Seok-Kyu Oh, Jei Keon Chae
Journal: Journal of the American College of Cardiology (2017)
Uncoupling the Oncogenic Engine
Authors: Axel Schambach, Juliane W. Schott, Michael A. Morgan
Journal: Cancer Research (2017)

Inhibition of oncogenic signaling and correction of aberrant metabolic processes may be key paradigms to eliminate cancer cells. The high incidence of activating RAS mutations and hyperactivated ERK1/2 signaling observed in many human tumors and the lack of effective targeted therapies to elicit long-term inhibition of the RAS-ERK1/2 signaling pathway add to the importance of discovering novel strategies to treat malignancies characterized by elevated RAS-ERK1/2 signaling. In this review, we describe connections between oncogenic signaling and cancer cell metabolism and how these links may be exploited for novel modern molecular medicine approaches. Cancer Res; 77(22); 6060-4. ©2017 AACR.
Altering histone modifications in the RARΒ2 promoter can reverse ATRA-resistance in colon cancer by restoring expression despite dense promoter DNA methylation
Authors: Emile M. Youssef, Jean-Pierre J. Issa
Journal: Cancer Research (2004)

4166  All-trans retinoic acid (ATRA) has differentiation and apoptotic effects on a variety of cancer cells. However, a high percentage of colon cancer cells are ATRA-resistant, and this has been attributes to DNA hypermethylation and silencing of RARΒ2 gene. In the present study, we investigated ways to render ATRA-resistant cells sensitive to ATRA. Five colon cancer cell lines (RKO, LoVo, SW48, HCT116, and SW480) were studied for epigenetic RARΒ2 promoter alteration using Methylation Specific PCR (MSP), sequencing of bisulfite-treated DNA, and Chromatin Imunoprecipitation (ChIP) assay. All cancer cell lines examined showed loss of RARΒ2 expression by promoter hypermethylation. Three cell lines showed relative growth inhibition after 10 days of treatment with 1 uM ATRA but the cell lines SW480 and RKO showed complete resistance with 0% growth inhibition. The two resistant cells (SW480 and RKO) also showed no induction of RARΒ2 expression after treatment with 1 uM ATRA. However, when the cells were pretreated with a 200 nM trichostatine A (TSA), a histone deacetylation inhibitor, followed by 1 uM ATRA for 24 h, strong restoration of RARΒ2 expression was seen. There was no restoration of expression of RARΒ1 and TIG1, two other silenced retinoid-induced genes with the same treatment. The restored expression of RARΒ2 by combined TSA-ATRA treatment, but not with each agent separately was associated with significant growth inhibition after 5 days (> 90%, P
Cisplatin-resistant U87-MG/Pt glioblastoma cell line shows higher sensitivity to STI-571 compared to its parental cell line
Authors: Tiziana Servidei, Daniela Meco, Roberta Morosetti, Anna Riccardi, Angela M. Di Francesco, Riccardo Riccardi, Carlo Dominici
Journal: Cancer Research (2004)

3876  STI-571 (Gleevec, imatinib mesylate) is a kinase inhibitor that specifically targets the activated Abl oncoprotein and several membrane tyrosine kinase receptors, including PDGF-R. Both PDGF ligands and receptors are often overexpressed in gliomas, suggesting the existence of an autocrine stimulatory loop. It is known that PDGF-R signals mainly through PI3K/Akt and Ras/MAPK pathways. PI3K/Akt is a major cell survival pathway and constitutively active AKT2 has been demonstrated to confer cisplatin resistance. In a previous study, it has been shown that STI-571 inhibits the growth of the human glioblastoma cell line U87-MG in nude mice. In the present study we compared STI-571 antiproliferative activity on U87-MG and on its cisplatin-resistant variant U87-MG/Pt. U87-MG/Pt was selected in our laboratory by culturing cells in stepwise increasing concentrations of cisplatin (resistance index ∼ 10) and displays a lower level of PDGF-R protein expression than U87-MG. Unexpectedly, U87-MG/Pt cells were significantly more sensitive to STI-571 than U87-MG (IC50 values = 18.6 ± 3.9 μM vs. 32.6 ± 3.9 μM, respectively; P
TCT-453 Quantification of Disturbed Coronary Blood Flow: Disturbed Vorticity Index and its Relation With Fractional Flow Reserve
Authors: Miao Chu, Clemens von Birgelen, Yingguang Li, Jelmer Westra, Junqing Yang, Niels Holm, William Wijns, Shengxian Tu
Journal: Journal of the American College of Cardiology (2017)
Efficient therapy for refractory Pompe disease by mannose 6-phosphate analogue grafting on acid α-glucosidase
Authors: Ilaria Basile, Afitz Da Silva, Khaled El Cheikh, Anastasia Godefroy, Morgane Daurat, Alice Harmois, Marc Perez, Catherine Caillaud, Henry-Vincent Charbonné, Bernard Pau, Magali Gary-Bobo, Alain Morère, Marcel Garcia, Marie Maynadier
Journal: Journal of Controlled Release (2017)
Health and Wealth in the United States and England—Two Very Different Countries With Similar Findings
Authors: Martin McKee, David Stuckler
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Dezassete anos de formação em epidemiologia de intervenção em Veyrier-du-Lac, 1984-2000
Authors: P Malfait, B Helynck
Journal: Eurosurveillance (2001)

No inicio da decada de 80, as entidades envolvidas na area da saude publica realizaram seminarios para avaliar a formacao dos epidemiologistas em Franca; estes demonstraram a inadequacao no ensino da epidemiologia de campo. Ate esta altura, a epidemiologia em Franca tinha estado largamente confinada a investigacao. A evolucao da pratica da saude publica, que exigia uma necessidade crescente de tomar decisoes com base em dados epidemiologicos, tornou necessario o desenvolvimento de uma rede de epidemiologistas de intervencao com formacao em metodos de trabalho normalizados.
In Vivo Imaging of Glutamine Metabolism to the Oncometabolite 2-Hydroxyglutarate in IDH1/2 Mutant Tumors
Authors: Lucia Salamanca-Cardona, Hardik Shah, Alex J. Poot, Fabian M. Correa, Valentina Di Gialleonardo, Hui Lui, Vesselin Z. Miloushev, Kristin L. Granlund, Sui S. Tee, Justin R. Cross, Craig B. Thompson, Kayvan R. Keshari
Journal: Cell Metabolism (2017)
Rewriting the transcriptome: adenosine-to-inosine RNA editing by ADARs
Authors: Carl R. Walkley, Jin Billy Li
Journal: Genome biology (2017)

One of the most prevalent forms of post-transcritpional RNA modification is the conversion of adenosine nucleosides to inosine (A-to-I), mediated by the ADAR family of enzymes. The functional requirement and regulatory landscape for the majority of A-to-I editing events are, at present, uncertain. Recent studies have identified key in vivo functions of ADAR enzymes, informing our understanding of the biological importance of A-to-I editing. Large-scale studies have revealed how editing is regulated both in cis and in trans. This review will explore these recent studies and how they broaden our understanding of the functions and regulation of ADAR-mediated RNA editing.
Availability, cost, and prescription patterns of antihypertensive medications in primary health care in China: a nationwide cross-sectional survey
Authors: Meng Su, Qiuli Zhang, Xueke Bai, Chaoqun Wu, Yetong Li, Elias Mossialos, George A Mensah, Frederick A Masoudi, Jiapeng Lu, Xi Li, Sebastian Salas-Vega, Anwen Zhang, Yuan Lu, Khurram Nasir, Harlan M Krumholz, Lixin Jiang
Journal: The Lancet (2017)