tbuckley/cabot-search huggingface dataset:
Abstract 13096: Mechanisms Underlying Associations Between Optimism, Hostility, and Cardiovascular Risk
Authors: Elena Salmoirago-Blotcher, Kathleen Hovey, Christopher Andrews, Matthew Allison, Robert L Brunner, Natalie L Denburg, Charles Eaton, Lorena Garcia, Shawnita Sealy-Jefferson, Oleg Zaslavsky, Joseph Kang, Stephen G Post, Hilary A Tindle, Sylvia Wassertheil-Smoller
Journal: Circulation (2016)

Introduction: Optimism has been associated with reduced cardiovascular (CV) risk, while cynical hostility has been linked with worse CV risk. The pathophysiological mechanism(s) underlying these associations are largely unexplored. We sought to examine associations between optimism, hostility, and heart rate variability (HRV). Hypothesis: Greater optimism will be associated with higher HRV, while greater hostility will be associated with lower HRV. Methods: Participants (n=3,372) enrolled in the Myocardial Ischemia and Migraine Study, a Women’s Health Initiative (WHI) ancillary study, underwent a 24-hour ambulatory ECG monitoring (AECG) 3 years after WHI enrollment. Optimism (Life Orientation Test-Revised), cynical hostility (Cook-Medley questionnaire), demographics, and CV risk factors were assessed at baseline. HRV measures included standard deviation of all analyzed N-N intervals (SDNN); standard deviation of average N-N interval over 5 min (SDANN); and average heart rate (HR). Multivariable linear regression models examined the relationship between optimism, hostility and HRV indices adjusted for demographics and coronary risk factors. Results: After excluding women with previous CV disease, missing data, and AECG &lt;12 hours, 2655 were included in the analysis. At baseline, more optimistic women were more likely to be younger, white, educated, non-smokers, physically active, and to have lower systolic blood pressure (SBP). More hostile women were more likely to be older, Hispanic or African American, less educated, diabetic, obese, smokers, and to have high cholesterol and high SBP. We found a significant inverse association between hostility and HRV (SDANN: adjusted β= -0.54; 95% CI -0.97, -0.11; SDNN: -0.49; 95% CI -0.93, -0.05). Optimism was not associated with HRV indices (SDANN: adjusted β= 0.10; 95% CI -0.25, 0.44; SDNN: 0.03; 95% CI -0.32, 0.39). Average HR was not associated with optimism or hostility. Conclusions: A worse autonomic balance may play a role in the physiopathology of unfavorable CV outcomes observed among women with higher cynical hostility. The lack of association between HRV and optimism suggests that other (behavioral?) factors may play a role in the protective association between optimism and CV outcomes.
Abstract 12201: Infants With 22q11.2 Deletion Syndrome Undergoing Repair of Tetralogy of Fallot, Interrupted Aortic Arch, and Truncus Arteriosus have Longer Hospitalizations and Increased Rates of Infection
Authors: Mary K Olive, Carlos M Mery, Amelia S Wallace, Kevin D Hill, Jeffrey P Jacobs, Erle H Austin, Sara K Pasquali, Marshall L Jacobs, Jeffrey S Heinle, Daniel J Penny
Journal: Circulation (2016)

Introduction: 22q11.2 deletion syndrome (22q11del) is common in patients with certain types of congenital heart disease. The prevalence of 22q11del and its impact on clinical outcomes remains unclear as only small single center studies are available and have shown conflicting data. Methods: All infants with tetralogy of Fallot (TOF), truncus arteriosus (TA), interrupted aortic arch (IAA), or IAA+TA included in the STS Congenital Heart Surgery Database from 1/10 to 6/15 were included. Infants with single ventricle lesions, pulmonary atresia with MAPCAs, and trisomies were excluded. Perioperative mortality and STS-defined major morbidities were compared between patients with and without 22q11del. Analyses were performed using Wilcoxon rank sum or chi-square tests. Results: A total of 5,179 patients were included. 22q11del was present in 255 (6.3%) patients with TOF, 160 (28.8%) with TA, 206 (38.4%) with IAA, and 19 (28.8%) with IAA+TA undergoing repair. For all procedural cohorts, there was no significant difference in perioperative mortality between the two groups. Infants with 22q11del had a longer hospitalization and a higher incidence of postoperative infections (Table). Within the TOF cohort only, infants with 22q11del had a higher incidence of the STS-defined composite major morbidity measure (12.5% vs. 6.1%, p&lt;0.01), largely driven by an increased incidence of unplanned re-interventions (9.9% vs. 4.3%, p&lt;0.01) and phrenic nerve injuries (2.5% vs. 0.8%, p=0.01). Conclusions: 22q11del is common in infants undergoing repair of TOF, TA, IAA, and IAA+TA. While operative mortality for the diagnostic groups was not impacted by 22q11del, patients with 22q11del did have longer hospitalizations and a higher incidence of infectious complications. Families should be counseled appropriately and further strategies should be developed to limit the morbidity in patients with 22q11del undergoing congenital heart surgery.
Will This Hospitalized Patient Develop Severe Alcohol Withdrawal Syndrome?
Authors: Evan Wood, Loai Albarqouni, Stacey Tkachuk, Carolyn J. Green, Keith Ahamad, Seonaid Nolan, Mark McLean, Jan Klimas
Journal: JAMA (2018)

<h3>Importance</h3> Although severe alcohol withdrawal syndrome (SAWS) is associated with substantial morbidity and mortality, most at-risk patients will not develop this syndrome. Predicting its occurrence is important because the mortality rate is high when untreated. <h3>Objective</h3> To assess the accuracy and predictive value of symptoms and signs for identifying hospitalized patients at risk of SAWS, defined as delirium tremens, withdrawal seizure, or clinically diagnosed severe withdrawal. <h3>Data Sources</h3> MEDLINE and EMBASE (1946-January 2018) were searched for articles investigating symptoms and signs predictive of SAWS in adults. Reference lists of retrieved articles were also searched. <h3>Study Selection</h3> Original studies that were included compared symptoms, signs, and risk assessment tools among patients who developed SAWS and patients who did not. <h3>Data Extraction and Synthesis</h3> Data were extracted and used to calculate likelihood ratios (LRs), sensitivity, and specificity. A meta-analysis was performed to calculate summary LR. <h3>Results</h3> Of 530 identified studies, 14 high-quality studies that included 71 295 patients and 1355 relevant cases of SAWS (1051 cases), seizure (53 cases), or delirium tremens (251 cases) were analyzed. A history of delirium tremens (LR, 2.9 [95% CI 1.7-5.2]) and baseline systolic blood pressure 140 mm Hg or higher (LR, 1.7 [95% CI, 1.3-2.3) were associated with an increased likelihood of SAWS. No single symptom or sign was associated with exclusion of SAWS. Six high-quality studies evaluated combinations of clinical findings and were useful for identifying patients in acute care facilities at high risk of developing SAWS. Of these combinations, the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was most useful, with an LR of 174 (95% CI, 43-696; specificity, 0.93) when patients had 4 or more individual findings and an LR of 0.07 (95% CI, 0.02-0.26; sensitivity, 0.99) when there were 3 or fewer findings. <h3>Conclusions and Relevance</h3> Assessment tools that use a combination of symptoms and signs are useful for identifying patients at risk of developing severe alcohol withdrawal syndrome. Most studies of these tools were not fully validated, limiting their generalizability.
The Risk of Gout Among Patients With Sleep Apnea: A Matched Cohort Study
Authors: Milica Blagojevic‐Bucknall, Christian Mallen, Sara Muller, Richard Hayward, Sophie West, Hyon Choi, Edward Roddy
Journal: Arthritis & Rheumatology (2018)

Obstructive sleep apnea (OSA) is associated with a range of serious comorbidities. This study was undertaken to investigate whether people with OSA are more likely to develop gout, in the short and long term, compared to those without OSA.A matched retrospective cohort study was undertaken using the UK Clinical Practice Research Datalink. Individuals age ≥18 years who received a diagnosis of OSA between 1990 and 2010 were identified and matched on age, sex, and practice with up to 4 individuals without OSA; follow-up was until the end of 2015. Hazard ratios (HRs) were estimated using Cox regression adjusted for general health, lifestyle, and comorbidity characteristics. The risk of developing gout was assessed at different time points, and the body mass index (BMI) category-specific results were presented.The study sample included 15,879 patients with OSA and 63,296 without. The median follow-up was 5.8 years. We found that 4.9% of patients with OSA and 2.6% of patients without the disorder developed gout. The incidence rate per 1,000 person-years was 7.83 (95% confidence interval [95% CI] 7.29-8.40) and 4.03 (95% CI 3.84-4.23) among those with and without OSA, respectively. The adjusted HR was 1.42 (95% CI 1.29-1.56). The risk of developing gout among OSA patients compared to those without was highest 1-2 years after the index date (HR 1.64 [95% CI 1.30-2.06]). This finding persisted among those who were overweight and obese. For those with normal BMI, the highest significant HR (2.02 [95% CI 1.13-3.62]) was observed at 2-5 years after the index date.In this study, patients with OSA continued to be at higher risk of developing gout beyond the first year following the diagnosis. Our results further indicate that peak incidences of gout vary according to BMI.
Long-Term Cardiovascular Risk Associated With Stage 1 Hypertension Defined by the 2017 ACC/AHA Hypertension Guideline
Authors: Yue Qi, Xueyu Han, Dong Zhao, Wei Wang, Miao Wang, Jiayi Sun, Jun Liu, Yan Li, Shen Gao, Yongchen Hao, Qiuju Deng, Jing Liu
Journal: Journal of the American College of Cardiology (2018)
Abstract 19894: Lifetime Predictions of Coronary Heart Disease, Congestive Heart Failure, and Stroke to Enable Preventive Treatment Decisions in Type 2 Diabetes Patients
Authors: Bart S Ferket, Girish N Nadkarni, Steven G Coca
Journal: Circulation (2016)

Introduction: Lifetime CVD predictions are increasingly recommended to support shared decision making on preventive interventions. We sought to predict lifetime CVD outcomes in T2D patients accordi...
Abstract 17303: High Plasma Levels of Presepsin, a Marker of Bacterial Infection, Reflect Global Fontan Pathophysiology
Authors: Yuka Toyoshima, Hideo Ohuchi, Yohsuke Hayama, Mitsuhiro Fujino, Midori Fukuyama, Jun Negishi, Tohru Iwasa, Kenichi Kurosaki
Journal: Circulation (2017)

Background: Presepsin is a soluble fragment of CD14 which is released in the process of phagocytosis of bacteria. High plasma levels of presepsin (PL-PSEP) are reported in patients with liver cirrh...
Neurofilaments as biomarkers in neurological disorders
Authors: Michael Khalil, Charlotte E. Teunissen, Markus Otto, Fredrik Piehl, Maria Pia Sormani, Thomas Gattringer, Christian Barro, Ludwig Kappos, Manuel Comabella, Franz Fazekas, Axel Petzold, Kaj Blennow, Henrik Zetterberg, Jens Kuhle
Journal: Nature Reviews Neurology (2018)
The two-pore domain potassium channel TREK-1 mediates cardiac fibrosis and diastolic dysfunction
Authors: Dennis M. Abraham, Teresa E. Lee, Lewis J. Watson, Lan Mao, Gurangad Chandok, Hong-Gang Wang, Stephan Frangakis, Geoffrey S. Pitt, Svati H. Shah, Matthew J. Wolf, Howard A. Rockman
Journal: Journal of Clinical Investigation (2018)

Cardiac two-pore domain potassium channels (K2P) exist in organisms from Drosophila to humans; however, their role in cardiac function is not known. We identified a K2P gene, CG8713 (sandman), in a Drosophila genetic screen and show that sandman is critical to cardiac function. Mice lacking an ortholog of sandman, TWIK-related potassium channel (TREK-1, also known Kcnk2), exhibit exaggerated pressure overload–induced concentric hypertrophy and alterations in fetal gene expression, yet retain preserved systolic and diastolic cardiac function. While cardiomyocyte-specific deletion of TREK-1 in response to in vivo pressure overload resulted in cardiac dysfunction, TREK-1 deletion in fibroblasts prevented deterioration in cardiac function. The absence of pressure overload–induced dysfunction in TREK-1–KO mice was associated with diminished cardiac fibrosis and reduced activation of JNK in cardiomyocytes and fibroblasts. These findings indicate a central role for cardiac fibroblast TREK-1 in the pathogenesis of pressure overload–induced cardiac dysfunction and serve as a conceptual basis for its inhibition as a potential therapy.
Abstract 614: ERK Signaling: the Pivotal Regulator of Arterial Differentiation
Authors: Bin Ren, Anthony A Lanahan, Julie Paye, Karen L Moodie, Zhen W Zhuang, Randall T Peterson, Michael Simons
Journal: Circulation (2007)

Background: We have previously observed defective arterial morphogenesis characterized by reduced size and branch number of smaller arteries and ongoing low-level ischemia in mice with homozygous disruption of synectin gene expression (Chittenden et al Dev Cell 2006). Endothelial cells derived from synectin knock out (KO) mice demonstrate reduced responsiveness to VEGF, especially in terms of activation of Erk-1/2. Since Erk activation has been previously linked to arterial morphogenesis, we evaluated whether activation of Erk signaling in synectin KO mice and endothelial cells (ECs) would restore arterial formation. Hypothesis: Erk-1/2 activation is required for arteriogenesis Methods: In vitro studies were conducted with primary arterial ECs isolated from synectin KO mice. In vivo studies were carried out in 5–6 week old synectin KO mice. Results: Since partial inhibition of PI3K activity has previously been shown to activate Erk-1/2 by inhibiting a direct negative feedback loop, we treated synectin−/−a...
Zero-sum thinking and economic policy
Authors: Paul H. Rubin
Journal: Behavioral and Brain Sciences (2018)

Abstract A main tenet of folk economics is the assumption that the world is zero-sum. Many implications stem from this assumption. These include: beliefs regarding taxation; beliefs regarding economic regulation; beliefs regarding inequality; and the core of Marxist economics. Zero-sum folk economic thinking is short-term and deals with distribution; standard economic thinking deals with the size of the pie and is longer-term.
再狭窄除去(DESIRE)試験での減量およびステントグラフティングの血管内超音波分析の結果
Authors: Tamai H, Aizawa T, Asakura Y, Tsuchikane E, Tanaka S, Uchiyama T, Matsubara T, Kato J, Fujii K, Fitzgerald Pj
Journal: Circulation (2001)
Comparison of fractionated and single session radiosurgery for radiation resistant brain metastases.
Authors: Eric Karl Oermann, Jing Wu, Brian Timothy Collins, David E. Morris, Matthew G. Ewend
Journal: Journal of Clinical Oncology (2012)

2091 Background: Melanoma and renal cell carcinoma are commonly called radiation resistant tumors due to the decreased response rate to traditional radiation (1.8-2 Gy /Fraction). Large brain metastases from radioresistant primaries are clinical challenges. This study examines the impact of fractionation on the treatment of intracranial metastases from radiation resistant tumors. Methods: Patients with a primary diagnosis of melanoma or renal cell carcinoma and intracranial metastases who completed treatment at The University of North Carolina with frameless robotic radiosurgery between 2007-2011 were retrospectively analyzed. Patients were treated with either single or 3-5 fractions depending on volume. The study’s primary endpoints were overall survival (OS) and local control (LC), and its secondary endpoint was patient steroid requirements. Outcomes data and pre-treatment variables were analyzed for significance using appropriate non-parametric tests. Results: 25 patients were included in the single fraction arm and 13 patients in the multi-fraction arm, and both had equivalent pre-treatment characteristics with the exception of tumor volume which was larger in the multi-fraction arm (p=0.01). At a median follow-up of 4.7 months (range, 1.8-11.6), the median OS for all patients was 6.2 months. One year survival was 35.1% and 5 patients (13%) had local failures at a median time to local failure of 5.5 months. Patients in the multi-fraction arm failed at a higher rate (10.5%) than patients in the single fraction arm (2.6%) (p=0.04), but there was no difference in OS (p=0.34). There was no difference between pre-treatment and post-treatment steroid requirements between the two arms (p=0.351). Conclusions: Fractionation is intended to facilitate radiosurgery in large tumors by limiting high doses of radiation to a large portion of normal brain. In our study of radioresistant intracranial metastases, large tumors receiving multi-fraction radiosurgery had decreased local control with no difference in toxicity or OS. These results suggest a need for either dose escalation, or combination therapy designed to reduce tumor size (resection or aspiration) in order to facilitate single fraction treatment.
Presynaptic Biogenesis Requires Axonal Transport of Lysosome-Related Vesicles
Authors: Anela Vukoja, Ulises Rey, Astrid G. Petzoldt, Christoph Ott, Dennis Vollweiter, Christine Quentin, Dymtro Puchkov, Eric Reynolds, Martin Lehmann, Svea Hohensee, Stefanie Rosa, Reinhard Lipowsky, Stephan J. Sigrist, Volker Haucke
Journal: Neuron (2018)

Nervous system function relies on the polarized architecture of neurons, established by directional transport of pre- and postsynaptic cargoes. While delivery of postsynaptic components depends on the secretory pathway, the identity of the membrane compartment(s) supplying presynaptic active zone (AZ) and synaptic vesicle (SV) proteins is unclear. Live imaging in Drosophila larvae and mouse hippocampal neurons provides evidence that presynaptic biogenesis depends on axonal co-transport of SV and AZ proteins in presynaptic lysosome-related vesicles (PLVs). Loss of the lysosomal kinesin adaptor Arl8 results in the accumulation of SV- and AZ-protein-containing vesicles in neuronal cell bodies and a corresponding depletion of SV and AZ components from presynaptic sites, leading to impaired neurotransmission. Conversely, presynaptic function is facilitated upon overexpression of Arl8. Our data reveal an unexpected function for a lysosome-related organelle as an important building block for presynaptic biogenesis.
TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma
Authors: Manuel António Campos, Sofia Macedo, Margarida Fernandes, Ana Pestana, Joana Pardal, Rui Batista, João Vinagre, Agostinho Sanches, Armando Baptista, José Manuel Lopes, Paula Soares
Journal: Journal of the American Academy of Dermatology (2018)
Endothelial Shear Stress and Plaque Erosion
Authors: Erika Yamamoto, Vikas Thondapu, Eric Poon, Tomoyo Sugiyama, Francesco Fracassi, Jouke Dijkstra, Hang Lee, Andrew Ooi, Peter Barlis, Ik-Kyung Jang
Journal: JACC. Cardiovascular imaging (2018)
Industry-funded versus non-profit-funded critical care research: a meta-epidemiological overview
Authors: Perrine Janiaud, Ioana-Alinea Cristea, John P. A. Ioannidis
Journal: Intensive Care Medicine (2018)

To study the landscape of funding in intensive care research and assess whether the reported outcomes of industry-funded randomized controlled trials (RCTs) are more favorable. We systematically assembled meta-analyses evaluating any type of intervention in the critical care setting and reporting the source of funding for each included RCT. Furthermore, when the intervention was a drug or biologic, we searched also the original RCT articles, when their funding information was unavailable in the meta-analysis. We then qualitatively summarized the sources of funding. For binary outcomes, separate summary odds ratios were calculated for trials with and without industry funding. We then calculated the ratio of odds ratios (RORs) and the summary ROR (sROR) across topics. ROR < 1 implies that the experimental intervention is relatively more favorable in trials with industry funding compared with trials without industry funding. For RCTs included in the ROR analysis, we also examined the conclusions of their abstract. Across 67 topics with 568 RCTs, 88 were funded by industry and another 73 had both industry and non-profit funding. Across 33 topics with binary outcomes, the sROR was 1.10 [95% CI (0.96–1.26), I2 = 1%]. Conclusions were not significantly more commonly unfavorable for the experimental arm interventions in industry-funded trials (21.3%) compared with trials without industry funding (18.2%). Industry-funded RCTs are the minority in intensive care. We found no evidence that industry-funded trials in intensive care yield more favorable results or are less likely to reach unfavorable conclusions.
Abstract 10198: Endothelin B Receptor Agonist, IRL-1620 is an Effective Neurovascular Remodeling Agent in Diabetic Rats With Cerebral Ischemia
Authors: Monica Husby, Mary G Leonard, Anil Gulati
Journal: Circulation (2015)

Endothelin B (ETB) receptor agonist, IRL-1620 administered at 2, 4, 6 hr post-cerebral ischemia, has been shown to significantly aid in neuroprotection and neurovascular remodeling in normal rats. The incidence of type 2 diabetes mellitus (diabetes) is on the rise and it can be expected that there will be an upsurge of associated diseases, such as ischemic stroke in patients with diabetes. The present study was conducted to determine the efficacy and neurovascular remodeling effect of IRL-1620 in normal (non-diabetic) and diabetic rats following cerebral ischemia induced by right middle cerebral artery (MCAO). The induction of diabetes was achieved through a high-fat diet and single low dose (45 mg/kg) of streptozotocin. IRL-1620 (5 μg/kg) was administered intravenously at 4, 6, and 8 hr after MCAO on day 0, 3 and 6 (total of 15 μg/kg in three divided doses on day 0, 3 and 6). A mortality of 46% was observed by day 7 in normal rats with MCAO when treated with vehicle, while it was 17% when treated with IRL-1620. In diabetic rats 90% mortality was observed by day 7 post-MCAO when treated with vehicle, while it was 45% when treated with IRL-1620. Functional outcome for the IRL-1620 group was significantly better in both non-diabetic and diabetic rats compared to the vehicle group. In both non-diabetic (80.81%; p=0.02) and diabetic (69.58%; p=0.04) rats a significant reduction in infarct volume was seen in the IRL-1620 group compared to the vehicle group. Significantly more blood vessels/30μm brain slice were observed in the IRL-1620 versus vehicle group. Immunofluorescence staining revealed a significant increase in ETB receptor expression for rats treated with IRL-1620, compared to vehicle. Co-localization of VEGF+ve and endothelial cells in diabetic rats was higher (p=0.0009) in the IRL-1620 group (15.5±1.1%) compared to the vehicle group (10.2±0.81%). In diabetic rats, the IRL-1620 group had significantly (p=0.0012) more neurons in the cortex compared to the vehicle group as well as the highest levels of neuronal replication. Administration of BQ-788, a specific ETB receptor antagonist, attenuated the effects of IRL-1620. It is concluded that IRL-1620 is an effective neurovascular remodeling agent and may be useful in the treatment of cerebral ischemia.