tbuckley/cabot-search huggingface dataset:
Abstract 14419: Effect of Nebivolol or Atenolol versus Placebo on Cardiovascular Health in Subjects With Borderline Blood Pressure: The EVIDENCE Study
Authors: Daniel Duprez, Natalia Florea, Catherine Koukol, Sue Duval, Jay N Cohn
Journal: Circulation (2016)

Introduction:  Identifying individuals with early markers for cardiovascular disease (CVD) raises the possibility for pharmacotherapy to slow progression of CVD. Among betablockers nebivolol (NEB) in contrast to atenolol (ATE) has claimed to have beneficial effects on endothelial function.   Hypothesis:  NEB slows progression of early CVD more than ATE in subjects free of overt CVD with borderline BP.   Methods:  60 asymptomatic subjects (age range, 18-80 years) with borderline BP and abnormal small artery elasticity underwent a panel of 10 tests measuring large and small artery elasticity, resting and treadmill exercise BP, carotid IMT, retinal vascular photography, micro-albuminuria, ECG, echocardiogram and plasma NT-proBNP. Each test was scored as normal (0), borderline (1) or abnormal (2) and the total disease score (DS) was calculated by adding the test scores. Subjects were randomized double-blind in parallel to receive placebo (PLAC, n=22), NEB 5/10 mg/d (n=20), ATE 25/50 mg/d (N=18) once daily for 9 months. A panel of these 10 tests was performed at baseline and after 9 months of treatment. The DS was compared at baseline and after 9 months PLAC, NEB and ATE in each group and between the 3 groups.   Results:  After 9 months the mean (standard deviation) DS decreased from baseline DS 4.3 (2.6) in the NEB group to 2.8 (2.4) (P    Conclusions:  Nebivolol is more effective than atenolol in improving small artery elasticity, a measure of endothelial dysfunction. These data suggest that nebivolol, by virtue of its favorable effects on endothelial function, may slow progression of cardiovascular disease in asymptomatic subjects with borderline blood pressure more effectively than atenolol, despite their equal blood pressure lowering effect.
Abstract 17348: Clinical Outcomes in Acute Coronary Syndrome Patients Following Coronary Artery Bypass Grafting in Relation to Timing of Ticagrelor Discontinuation: Insights From the CAPITAL Registry
Authors: Juan J Russo, Tyler E James, Nikita Malhotra, Daniel Goubran, Fraser D Rubens, Michael Bourke, Jean-Yves Dupuis, Vincent Chan, Kuljit Singh, Marc T Ruel, Derek Y So
Journal: Circulation (2015)

Background: We sought to assess in-hospital clinical outcomes in ACS patients undergoing CABG in relation to the duration of ticagrelor discontinuation prior to surgery. Methods: We identified consecutive ACS patients who underwent CABG after having received ticagrelor. Patients were divided into 3 groups based on the timing of surgery after discontinuation of ticagrelor (&lt;48 hours, 48 hours to &lt;5 days, 5 days or more). We then compared clinical outcomes following CABG in relation to the duration of ticagrelor discontinuation prior to surgery. Clinical variables evaluated included postoperative bleeding, need for surgical reopening or blood transfusions, and length of stay in the intensive care unit (ICU). Results: Of 664 ACS patients undergoing CABG between January 2012 and March 2015, 53 received ticagrelor prior to CABG. Ticagrelor had been discontinued &lt;48 hours prior to CABG in 22 patients (41%); 48 hours to &lt;5 days in 19 (36%); and 5 days or more in 12 (23%). Patients who underwent CABG &lt;48 hours after ticagrelor discontinuation were more likely to require blood transfusions and a prolonged ICU stay (defined as &gt;3 days). In addition, they had numerically higher, but non-statistically significant, rates of postoperative bleeding. Patients who underwent CABG 48 hours to &lt;5 days after ticagrelor discontinuation had similar rates of postoperative bleeding and duration of ICU stay compared to patients who waited at least 5 days. Conclusions: A significant proportion of ACS patients (77%) who require CABG undergo surgery before the guideline recommended ticagrelor discontinuation period of 5 days. Patients who undergo CABG &lt;48 hours after ticagrelor discontinuation are more likely to require postoperative blood transfusions and a prolonged ICU stay. Notably, patients who undergo CABG 48 hours to &lt;5 days after ticagrelor discontinuation have similar postoperative outcomes compared to patients who undergo CABG after 5 days of ticagrelor discontinuation.
Abstract 16010: Reduced Expression of miR-130a-3p Contributes to Endothelial Cell Senescence and Age-dependent Impairment of Neovascularization
Authors: Wahiba Dhahri, Sylvie Dussault, Michel Desjarlais, Raphaël Mathieu, Alain Rivard
Journal: Circulation (2016)

Background:  Aging, a major cardiovascular risk factor, is also associated with impaired neovascularization in response to ischemia. Micro RNAs (miRNAs) are small noncoding RNAs emerging as key regulators of several physiological and pathological processes. Here we investigated the potential role of miRNAs in endothelial cell senescence and age-dependent impairment of neovascularization.   Methods/Results:  Mouse aortic endothelial cells (MAECs) were isolated from young (2 months old) and old (15 months old) C57Bl/6 mice. In other experiments, low passage (young) human umbilical vein endothelial cells (HUVECs) were compared to high passage (old) HUVECs. Next generation sequencing and qRT-PCR analyses identified miR-130a-3p as a pro-angiogenic miRNA which expression is significantly reduced in old  vs  young endothelial cells (ECs). Transfection of young ECs with a miR-130a-3p inhibitor led to accelerated senescence (β-Galactosidase assay) and impaired EC angiogenic functions including migration, proliferation and tube formation. Conversely, forced expression of miR-130a-3p in old ECs reduced senescence and improved EC angiogenic functions. In a mouse model of hindlimb ischemia, intramuscular injection of a miR-130a-3p mimic in older mice restored blood flow recovery (Laser Doppler imaging) and vascular densities in ischemic muscles (CD31 immunostaining), improved functional mobility and reduced tissue damages. Interestingly, forced expression of miR-130a-3p in older mice was also associated with a significant increase in the number of bone marrow-derived pro-angiogenic cells (PACs) after ischemia. Moreover, the functional activities of PACs (migration, adhesion to an endothelial monolayer and integration into tubular networks) were all improved in older mice treated with miR-130a-3p mimic compared to those treated with a miR mimic control.   Conclusions:  Decreased expression of miR-130a-3p contributes to endothelial cell senescence and age-dependent impairment of neovascularization. Forced expression of miR-130a-3p using a miRNA mimic could constitute a novel therapeutic strategy to improve blood flow recovery and reduce tissue ischemia in older patients with severe ischemic vascular diseases.
Creating a graft-friendly environment for stem cells in diseased brains
Authors: Robert Y.L. Tsai
Journal: Journal of Clinical Investigation (2017)

Most of the adult CNS lacks regenerative activity in terms of both neuron birth and neurite outgrowth. While this regeneration-unfriendly environment of the adult CNS may preserve the existing neuronal circuitry that takes years to develop in higher organisms, it also poses a major obstacle for CNS repair later in life. In this issue of the JCI, Song et al. report on their development of a strategy that uses region-specific and molecularly engineered astrocytes to turn an unfavorable brain environment into a favorable one for engrafted neural stem/progenitor cells (NSC/NPCs). In a rat model of Parkinson's disease (PD), cografting NPCs with midbrain-derived astrocytes engineered to overexpress the transcription factors Nurr1 and Foxa2 promotes maturation and survival of the graft, resulting in therapeutic improvement. The results of this study raise the prospect of using modified astrocytes to improve the survival, maturation, and integration of engrafted NSC/NPCs as a restorative treatment for PD.
Factors associated with four atypical cases of congenital syphilis in England, 2016 to 2017: an ecological analysis
Authors: Martina Furegato, Helen Fifer, Hamish Mohammed, Ian Simms, Paul Vanta, Sharon Webb, Kirsty Foster, Margaret Kingston, André Charlett, Bhavita Vishram, Claire Reynolds, Noel Gill, Gwenda Hughes
Journal: Eurosurveillance (2017)

Four isolated cases of congenital syphilis born to mothers who screened syphilis negative in the first trimester were identified between March 2016 and January 2017 compared with three cases between 2010 and 2015. The mothers were United Kingdom-born and had no syphilis risk factors. Cases occurred in areas with recent increases in sexually-transmitted syphilis among women and men who have sex with men, some behaviourally bisexual, which may have facilitated bridging between sexual networks.
Abstract 20698: Renal Denervation Lowers the Slope of the Pressure-Diuresis Relation and Blunts the Diuretic Response to Acute Volume Load in Heart Failure
Authors: Kiyokazu Abe, Takafumi Sakamoto, Yasuhiro Oga, Keita Saku, Sumio Hoka, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Circulation (2016)

Background: Previous animal studies have shown that renal denervation (RDN) was beneficial in chronic heart failure (CHF) by increasing the sodium excretion and inhibiting the renin release. Howeve...
Immunogenetic factors driving formation of ultralong VH CDR3 in Bos taurus antibodies
Authors: Thaddeus C Deiss, Melissa Vadnais, Feng Wang, Patricia L Chen, Ali Torkamani, Waithaka Mwangi, Marie-Paule Lefranc, Michael F Criscitiello, Vaughn V Smider
Journal: Cellular and Molecular Immunology (2017)
NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017
Authors: Samir Gupta, Dawn Provenzale, Scott E. Regenbogen, Heather Hampel, Thomas P. Slavin, Michael J. Hall, Xavier Llor, Daniel C. Chung, Dennis J. Ahnen, Travis Bray, Gregory Cooper, Dayna S. Early, James M. Ford, Francis M. Giardiello, William Grady, Amy L. Halverson, Stanley R. Hamilton, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Patrick M. Lynch, Arnold J. Markowitz, Robert J. Mayer, Reid M. Ness, Niloy Jewel Samadder, Moshe Shike, Shajanpeter Sugandha, Jennifer M. Weiss, Mary A. Dwyer, Ndiya Ogba
Journal: Journal of the National Comprehensive Cancer Network (2017)

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the management of patients with high-risk syndromes associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to assess comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on genes newly associated with CRC risk on multigene panels, the associated evidence, and currently recommended management strategies.
Abstract 12443: Incident Heart Failure Risk After Acute Myocardial Infarction is Stratified by the Intermountain Major Adverse Cardiovascular Events (IMACE) Risk Scores
Authors: Benjamin D Horne, Joseph B Muhlestein, Durgesh Bhandary, Abdallah G Kfoury, Greta L Hoetzer, Tami L Bair, Naeem D Khan, Donald L Lappé
Journal: Circulation (2016)

Introduction: Previously, the Intermountain Mortality Risk Scores (IMRS) were created to predict all-cause mortality, but also predicted incident heart failure (HF) in unselected catheterization laboratory patients. The Intermountain Major Adverse Cardiovascular Events (IMACE) risk scores were created using IMRS principles to predict MACE (CV mortality, recurrent myocardial infarction [MI], stroke) for acute MI patients. Hypothesis: IMACE stratifies the risk of HF in acute MI patients free of HF at baseline. Methods: Acute MI patients (females: 1,846; males: 4,720) hospitalized at the Intermountain Heart Institute (9/1993-4/2015) were included if they were free from a clinical HF diagnosis and (if available) had LVEF &gt;40%. Incident HF was monitored electronically in Intermountain’s 22 hospitals. A composite of HF and all-cause mortality was also examined. IMACE was computed from previously-derived weightings for age, complete blood count and comprehensive metabolic panel factors, and B-type natriuretic peptide. Results: Mean age at MI was 65.1±13.6 years in females and 59.8±12.3 in males. Cumulative HF-free survival was 90.2% during follow-up of 8.8±5.9 years (max: 21.6 years). Median time to HF diagnosis was 6.0 years, with a stable annual hazard (median 0.4%/year; interquartile range: 0.4%-0.6%). IMACE risk scores (high- vs. low-risk) predicted HF (Figure) in females (HR=3.72, CI=1.68, 8.27) and males (HR=6.90, CI=3.82, 12.48). IMACE predicted mortality/HF for females (HR=6.39, CI=4.83, 8.42) and males (HR=6.34, CI=5.12, 7.85). Other HF predictors were 16 of 53 clinical and treatment variables. Conclusions: IMACE effectively stratified HF incidence after acute MI in patients initially free from HF. Data suggested high-risk females died prior to HF diagnosis. IMACE is a clinically feasible tool for efficiently identifying MI patients for whom additional evaluation and more aggressive therapeutic management may improve long-term prognosis.
Abstract 17237: Synergistic Reduction of Myocardial Ischemia Reperfusion Injury by Ischemic Preconditioning and Myocardial SOCS3 Deficiency in Mice
Authors: Shoichiro Nohara, Takanobu Nagata, Hideo Yasukawa, Yusuke Sugi, Kazutoshi Mawatari, Daisuke Fukui, Sachiko Kyogoku, Hideki Ohshima, Tomoko Minami, Jinya Takahashi, Koutatsu Shimozono, Tatsuhiro Shibata, Yoshihiro Fukumoto
Journal: Circulation (2016)

Introduction:  Ischemic preconditioning (IPC) has cardiac protective effects. However, the effect is not certain in clinical trials and the inhibitory mechanism underlying the cardioprotection by IPC remains unknown. Suppressor of cytokine signaling-3 (SOCS3) is a cytokine-inducible negative regulator of JAK-STAT signaling pathway. In this study, we investigated the role of myocardial SOCS3 against the ischemia reperfusion injury (IRI) during IPC.   Hypothesis:  We hypothesized that IPC combination with myocardial SOCS3 deficiency would have synergistic effects in the reduction of myocardial injury after IRI.   Methods:  Myocardial IPC was elicited by three cycles of 5 min left ascending coronary artery occlusion and 5 min reperfusion, and after the IPC, the coronary artery was reoccluded to induce ischemia reperfusion injury. The infarct size was estimated by evans blue dye and triphenyltetrazolium chloride staining. We precisely evaluated the phosphorylation of STAT3 and the expression of SOCS3 after IPC in wild-type (WT) and cardiac-specific SOCS3 knockout mice (SOCS3-CKO).   Results:  STAT3 phosphorylation was faint immediately after IPC, marked at 1 h after IPC, and suppressed at 3 h after IPC; this transient activation of STAT3 was closely correlated with the induction of SOCS3 expression in WT. In contrast, STAT3 phosphorylation after IPC was significantly greater and sustained in SOCS3-CKO than in WT ( p   Western blot analysis revealed that anti-apoptotic Bcl-xL and myeloid cell leukemia-1 (Mcl-1) expression after myocardial ischemia reperfusion injury were significantly increased in SOCS3-CKO/IPC (+) compared with WT/IPC(+) ( p    Conclusions:  Thus, myocardial SOCS3 deficiency and IPC have synergistic effects in the reduction of myocardial injury after IRI. Our results suggest that IPC combination with myocardial SOCS3 inhibition may be a novel strategy for the reduction of myocardial injury after IRI.
Abstract 45: Development of a molecular diagnostic tool for more precise diagnosis of oral squamous cell carcinoma
Authors: Martha Rolland Jacobsen, Harsh Dongre, Israa Ahmed, Vidisha Tuljaurkar, Prathamesh S. Pai, Asawari Patil, Dipak Sapkota, Anne Christine Johannessen, Nenad Filipovic, Milind Vaidya, Sharda Sawant, Daniela Elena Costea
Journal: Clinical Cancer Research (2017)

Abstract Expression of cancer-associated biomarkers represents a great potential for a more precise diagnosis for patient stratification and more personalized treatment of oral squamous cell carcinoma (OSCC). The aim of this study was to develop an immunohistochemistry-based malignancy index diagnostic system (IHC-MIDS) based on the expression of a panel of several molecules expressed by different tumor components and involved in different oncogenic pathways. IHC was performed on paraffin embedded formalin fixed tissue samples from 102 patients for the following biomarkers: p16, p53, ki67, p75NTR, LoxL4, aSMA, Foxp3, CD68, CD 163, CD80, FVIII and D2-40. The stained tissues were scanned and quantified using Immage J open source software. An IHC-MIDS score was developed using correlation-based feature selection algorithm. IHC-MIDS was able to stratify OSCC lesions for several clinical pathological features, including the risk of recurrence. This study shows that a scoring system based on expression of a panel of biomarkers is more precise than the use of a single biomarker and that it can be used for risk stratification of OSCC lesions in order to guide further management. Citation Format: Martha Rolland Jacobsen, Harsh Dongre, Israa Ahmed, Vidisha Tuljaurkar, Prathamesh S. Pai, Asawari Patil, Dipak Sapkota, Anne Christine Johannessen, Nenad Filipovic, Milind Vaidya, Sharda Sawant, Daniela Elena Costea. Development of a molecular diagnostic tool for more precise diagnosis of oral squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 45.
Abstract 11401: Exercise and Cardiac Function by Tissue Doppler Imaging. The Copenhagen City Heart Study
Authors: Gowsini Joseph, Peter Sogaard, Gitte Nielsen, Tor Biering-Sorensen, Peter Schnohr, Jan Skov Jensen, Rasmus Mogelvang
Journal: Circulation (2016)

Introduction: TDI (Tissue Doppler Imaging) is a sensitive marker of myocardial dysfunction and mortality in heart disease and in the general population. Regular physical activity is associated with risk reduction in coronary heart disease and mortality. There is a need for studies to clarify whether exercise has beneficial effects on cardiac function. Hypothesis: Regular physical exercise is associated with better cardiac function measured by TDI in the general population Methods: 2,162 persons from the general population were examined by echocardiography and TDI. Peak systolic (s′), early diastolic (e′) and late diastolic (a′) velocities were measured by color TDI. Longitudinal displacement (LD) was calculated from the velocity curve during ejection. Statistical tests were performed by linear univariate and multivariable regression analyses, in relation to age groups (&lt;50years, 50-65 years, &gt;65 years) and physical activity level: I (inactivity), II (light activity), III (moderate activity) and IV (high-level activity). These levels were graded from the physical activity questionnaire, which contained information about activity level at work and in leisure time. Results: Participants aged&lt;50 years had a significantly higher level of e′ and LD in the most active group: e′=11.0 (± standard deviation, SD=2.0), p&lt;0.001; LD=12.8 (SD=2.1), p&lt;0.003. This pattern remained significant after adjusting for sex, hypertension, diabetes, and ischaemic heart disease and after Bonferroni correction. For e′, there was significant interaction between age and activity level (p&lt;0.001), which supports the findings of better cardiac function with increasing activity among the young age group. Conclusion: In the general population, the association between increasing level of exercise and better cardiac function was found only in the youngest age group ( &lt;50 years old). Among the elder age groups higher level of activity was not correlated to better cardiac function.
Turning the tide: A plea for cognitively lean interpretations of infant behaviour
Authors: Miriam Beisert, Norbert Zmyj, Moritz M Daum
Journal: Behavioral and Brain Sciences (2017)

Abstract Keven &amp; Akins (K&amp;A) revisit the controversial subject of neonatal imitation through analysing the physiological foundations of neonatal spontaneous behaviour. Consequently, they regard imitative capacities in neonates as unlikely. We welcome this approach as an overdue encouragement to refuse cognitively rich interpretations as far as cognitively lean interpretations are conceivable, and apply this rationale to other phenomena in early childhood development.
Interleukin-25 is involved in cutaneous T-cell lymphoma progression by establishing a T helper 2-dominant microenvironment
Authors: R. Nakajima, T. Miyagaki, M. Hirakawa, T. Oka, N. Takahashi, H. Suga, A. Yoshizaki, H. Fujita, Y. Asano, M. Sugaya, S. Sato
Journal: British Journal of Dermatology (2017)

Interleukin (IL)‐25 is a member of the IL‐17 family, which can promote and augment T‐helper (Th) type 2 responses. The expression of IL‐25 and its cognate receptor, IL‐25 receptor (IL‐25R), is upregulated and correlated with disease activity in Th2‐associated diseases. To examine the expression and function of IL‐25 in cutaneous T‐cell lymphoma (CTCL). Expression and location of IL‐25 in lesional skin was investigated with immunohistochemistry. The effect of various cytokines on IL‐25 production from normal human epidermal keratinocytes was assessed by quantitative reverse‐transcription real‐time polymerase chain reaction. Serum IL‐25 levels were measured by enzyme‐linked immunosorbent assay. The direct effect of IL‐25 on tumour cells was also examined using CTCL cell lines and peripheral blood mononuclear cells in patients with Sézary syndrome. IL‐25 expression was increased in epidermal keratinocytes in lesional skin of CTCL. Th2 cytokines, IL‐4 and IL‐13, and periostin induced IL‐25 expression by normal human epidermal keratinocytes. Serum IL‐25 levels were increased in patients with advanced CTCL and correlated with serum lactate dehydrogenase levels. MyLa cells expressed IL‐25R and its expression was augmented by stimulation with IL‐25. IL‐25 enhanced IL‐13 production from MyLa cells via phosphorylation of signal transducer and activator of transcription 6. Peripheral blood mononuclear cells from one patient with Sézary syndrome expressed IL‐25R and showed increase of IL‐13 production by IL‐25. Th2 cytokines highly expressed in CTCL lesional skin induce IL‐25 production by epidermal keratinocytes, which may, in turn, lead to formation of a Th2‐dominant microenvironment through the direct induction of IL‐13 by tumour cells.