tbuckley/cabot-search huggingface dataset:
Abstract 18038: Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension, Insights From a Network Analysis
Authors: Myriam Amsallem, Andrew J Sweatt, Marie Aymami, Tatiana Kuznetsova, Olaf Mercier, Elie Fadel, Michael V McConnell, Marlene Rabinovitch, Roham Zamanian, Francois Haddad
Journal: Circulation (2016)

Introduction:  Indices of right heart end-systolic remodeling are emerging as prognostic markers in patients with pulmonary arterial hypertension (PAH). We hypothesized that right ventricular (RV) end-systolic remodeling indices would be incremental to well-validated scores in PAH.   Methods:  From 2005 to 2014, 228 patients with PAH were prospectively enrolled. RV end-systolic remodeling index (RVESRI) was defined by RV lateral wall to septal length ratio. Network analysis of right heart metrics was performed using partial correlation diagrams. The incremental values of RV free wall longitudinal strain (RVLS) and RVESRI to well-validated risk scores such as the REVEAL registry were determined. The primary endpoint was death, lung transplant or readmission for heart failure. Correlates of endpoint were determined using Cox regression.   Results:  Mean (±standard deviation) age was 49 ±14 years, 78% were female, 33% had connective tissue disease, 52% were in NYHA class III or IV, and mean resistance was 11±6 Wood units. RVESRI had strong and central connectivity with other metrics, including right atrial area index, strain and eccentricity index. The RVESRI to RV systolic pressure relationship enabled the discrimination of three groups of patients with either adapted, adversely-remodeled and severely adversely-remodeled right ventricles. Mean follow-up was 3.9 ±2.4 years. Event free survival (primary endpoint) was 90.6% at 1 year, 78.0% at 3 years and 64.8% at 5 years. Among previously validated clinical scores, the REVEAL score emerged as the strongest correlate of outcome at 3 years. In multivariate analysis, NYHA class III/IV, RVESRI, and log N-terminal-pro brain natriuretic peptide were retained (Chi-square 62.2, p   Conclusions:  RVESRI has a central connectivity among RV metrics and provides incremental prognostic value to validated risk scores.
Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial
Authors: Arina J ten Cate-Hoek, Elham E Amin, Annemieke C Bouman, Karina Meijer, Lidwine W Tick, Saskia Middeldorp, Guy J M Mostard, Marije ten Wolde, Simone M van den Heiligenberg, Sanne van Wissen, Marlène HW van de Poel, Sabina Villalta, Erik H Serné, Hans-Martin Otten, Edith H Klappe, Ingrid M Bistervels, Mandy N Lauw, Margriet Piersma-Wichers, Paolo Prandoni, Manuela A Joore, Martin H Prins, Hugo ten Cate, Arina J ten Cate-Hoek, Hugo ten Cate, Manuela A Joore, Martin H Prins, Elham E Amin, Annemieke C Bouman, Karina Meijer, Margriet Piersma-Wichers, Lidwine W Tick, Martin R Nijziel, Saskia Middeldorp, Mandy Lauw, Y Whitney Cheung, Guy J M Mostard, Marije ten Wolde, Ingrid M Bistervels, Simone M van den Heiligenberg, Sanne van Wissen, Marlène H W van de Poel, Hans-Martin Otten, Erik H Serné, Edith H Klappe, Paolo Prandoni, Valentina Vedovetto, Sabina Villalta
Journal: The Lancet Haematology (2017)
Menopausal Hormone Therapy for Primary Prevention of Chronic Disease
Authors: Cora E. Lewis, Melissa F. Wellons
Journal: JAMA (2017)

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Combination of 247 Genome-Wide Association Studies Reveals High Cancer Risk as a Result of Evolutionary Adaptation
Authors: Konstantinos Voskarides
Journal: Molecular Biology and Evolution (2017)

Analysis of GLOBOCAN-2012 data shows clearly here that cancer incidence worldwide is highly related with low average annual temperatures and extreme low temperatures. This applies for all cancers together or separately for many frequent or rare cancer types (all cancers P = 9.49×10−18). Supporting fact is that Inuit people, living at extreme low temperatures, have the highest cancer rates today. Hypothesizing an evolutionary explanation, 240 cancer genome-wide association studies, and seven genome-wide association studies for cold and high-altitude adaptation were combined. A list of 1,377 cancer-associated genes was created to initially investigate whether cold selected genes are enriched with cancer-associated genes. Among Native Americans, Inuit and Eskimos, the highest association was observed for Native Americans (P = 6.7×10−5). An overall or a meta-analysis approach confirmed further this result. Similar approach for three populations living at extreme high altitude, revealed high association for Andeans-Tibetans (P = 1.3×10−11). Overall analysis or a meta-analysis was also significant. A separate analysis showed special selection for tumor suppressor genes. These results can be viewed along with those of previous functional studies that showed that reduced apoptosis potential due to specific p53 variants (the most important tumor suppressor gene) is beneficial in high-altitude and cold environments. In conclusion, this study shows that genetic variants selected for adaptation at extreme environmental conditions can increase cancer risk later on age. This is in accordance with antagonistic pleiotropy hypothesis.
Abstract 14668: Prospective, Randomized Comparison of 500 mg and 250 mg Acetylsalicylic Acid I.v. and 300 mg p.o. in Patients With Acute Coronary Syndrome (ACUTE Trial)
Authors: Uwe Zeymer, Juergen Vom Dahl, Raimund Erbel, Thomas Muenzel, Dietmar Trenk, Ralf Zahn, Irmgard Gebert, Alexander Roitenberg, Thomas Hohlfeld
Journal: Circulation (2015)

Background: Current national and international guidelines recommend the use of oral and/or intravenous (IV) acetylsalicylic acid as an alternative mode of application in patients with acute coronary syndrome (ACS) who are unable to swallow. However, acetylsalicylic acid IV has not been investigated in clinical trials and is not available everywhere. Aim: The primary objective of the present open-label, randomized, verum-controlled, parallel-group, phase III study was to demonstrate superiority of 250 or 500 mg acetylsalicylic acid IV treatment over oral treatment with 300 mg acetylsalicylic acid tablet to inhibit thromboxane A2 release at 5 minutes after a single dose of study drug in subjects with ACS with and without ST elevation. Methods: Acetylsalicylic acid naive patients with ACS were randomized into three groups to receive a single dose of acetylsalicylic acid either 300 mg orally, 250 or 500 mg intravenously. ThromboxaneA2 release (measured as the stable serum metabolite thromboxane B2), platelet aggregation and prostacyclin levels were measured 5 and 20 minutes after study drug administration. Patients were followed for 30 days for clinical events. Results: A total of 270 patients were randomized. The results of the primary and secondary endpoints are given in the table. Conclusion: The administration of 250 or 500 mg acetylsalicylic acid intravenously compared to 300 mg orally is associated with a faster and more effective inhibition with respect to thromboxane generation and inhibition of platelet aggregation, without any increase in bleeding complications. Therefore, i.v. administration of acetylsalicylic acid should be preferred in the acute management of patients with ACS.
Abstract 11447: Interaction Between Alcohol Habits and Gene Polymorphism of Ghrelin on the Risk of Essential Hypertension in Japanese Population
Authors: Masahiko Eto, Masanobu Okayama, Taro Takeshima, Maki Kumada, Takanori Aonuma, Yoshikazu Nakamura, Eiji Kajii
Journal: Circulation (2016)

Objectives: To evaluate the interactions between SNP of ghrelin gene( GHRL ) and alcohol habits on the risk of hypertension (HT:BP≥140/90) in Japanese. Methods: We analyzed 19036 Japanese subjects enrolled in the genome banking project at Jichi Medical University, including 8607 HT cases and 10429 non-HT controls.We divided the subjects into four groups according to gender and age (≤49 or ≥50).Alcohol habits were categorized to never, sometimes, and daily drinker for frequency of drinking. SNP rs696217(GG/GT/TT) of GHRL was genotyped by TaqMan method. Because the incidence of TT was low(&lt;5%), GT and TT were combined together. The frequencies of genotypes, alcohol habits, and the combinations of both were compared between cases and controls by chi-squared test. The strength of the associations was estimated by logistic regression analysis. For the interaction, we assessed the joint ORs, which were calculated for each of six combined categories created by cross-classification. Non-risk genotypes as reference were different in M≤49(GG) and others(GT/TT). Results: (1)Genotype distributions significantly differed in F≤49. The frequencies of alcohol habits and combined categories significantly differed in all groups. (2) Compared to GG, the ORs (95%CI) of GT/TT were 1.25(1.0-1.55)* in M≤49. Compared to GT/TT, the ORs (95%CI) of GG were 1.57(1.20-2.06)* in F≤49, 1.01(0.90-1.13) in M≥50, and 1.04(0.93-1.16) in F≥50.(3) Compared to never drinkers, the ORs (95%CI) of daily drinkers were 1.77(1.32-2.37)* in M≤49, 1.26 (0.88-1.80) in F≤49, 1.64(1.44-1.87)* in M≥50, and 1.13(0.90-1.43) in F≥50. (4) Compared to never drinker with GG, the joint ORs (95%CI) of daily drinker with GG or GT/TT was 2.04(1.39-2.99)* and 2.34(1.55-3.54)* in M≤49. Compared to never drinker with GT/TT, the joint ORs (95%CI) of daily drinker with GT/TT or GG was 1.02(0.47-2.21) and 2.01(1.24-3.24)* in F≤49, 1.64(1.32-2.03)* and 1.70(1.40-2.08)* in M≥50, and 1.05(0.69-1.58) and 1.21(0.90-1.62) in F≥50 *(p&lt;0.05). Conclusions: The interaction between GHRL rs696217 and alcohol habits had significant effects on HT risk in Japanese females≤49 years. The interactions between GHRL genotypes and alcohol habits may contribute to young-onset hypertension in Japanese females.
Abstract 11420: Racial Differences in Heart Failure Presentation and Outcome: A Get-With-The-Guidelines Heart Failure Study
Authors: Eben Eno, Karim Nathan, Ali Mithani, Mitra Daneshvar, Matthew Ortman, John Andriulli, Andrea M Russo
Journal: Circulation (2016)

Background: Millions of Americans are living with heart failure (HF), and minorities represent a large proportion of these patients. Racial differences in outcomes of patients with HF have been previously described. Examining racial differences in presentation and factors precipitating admission with HF in minorities may help to reduce gaps in care and improve outcomes. Methods: We examined 3763 all-cause admissions for HF at our center (2005-2012) using the GWTG-HF study. Minorities represented 33% of the overall cohort (1216 blacks and 39 other races). Baseline characteristics and outcomes were compared between minorities and Caucasians using independent T Test, Pearson Chi Square and Fisher Exact Test during index admissions. Results: Racial differences in baseline characteristics and comorbidities were identified. (Table) Compared to Caucasians, minorities were younger, had a higher BMI, and were more likely to have nonischemic cardiomyopathy, HTN, diabetes, and renal insufficiency. Minorities were also more likely to be uninsured and were less likely to have CAD, prior MI and atrial fibrillation. Minorities had a 1.3 times greater odds than Caucasians to be readmitted (95% CI 1.1 -1.5). When examining factors contributing to HF admission, minorities were more likely to have medical (34% vs. 17%) or dietary (63% vs. 51%) noncompliance, worsening renal failure (28% vs. 21%), or worsening hypertension (46% vs. 28%) than Caucasians. (p &lt;0.001 for all). Conclusion: Minorities with HF demonstrated significant differences in comorbidities, insurance status, and triggers for HF exacerbations than Caucasians, leading to a greater risk for re-hospitalization. A focus on racial differences in factors precipitating HF exacerbations or potential differences related to access to care that vary by race may provide a more targeted approach to improving outcomes and reducing readmissions, helping to reduce racial gaps.
A reversible thermoresponsive sealant for temporary closure of ocular trauma
Authors: Niki Bayat, Yi Zhang, Paulo Falabella, Roby Menefee, John J. Whalen, Mark S. Humayun, Mark E. Thompson
Journal: Science Translational Medicine (2017)

Open globe injuries are full-thickness injuries sustained to the eye wall (cornea or sclera), which cause immediate drops in intraocular pressure that may lead to retinal detachment and permanent vision loss if not treated rapidly after injury. The current standard of care for open globe injuries consists of suturing the margins closed, but the technique can be time-consuming, requires specialized training and equipment, and can lead to patient discomfort, abrasion, and infection from eye rubbing. We engineered an injectable, thermoresponsive sealant (TRS) and a custom tool to occlude open globe injuries. The smart hydrogel sealant consists of physically cross-linked N-isopropylacrylamide copolymerized with butylacrylate. At low temperatures, it can be injected as a liquid, and when raised to body temperature, a heat-induced gelation converts the hydrogel into a solidified occlusion. The sealant can be repositioned or removed without causing additional trauma via exposure to cold water. In vitro and ex vivo assessments of mechanical adhesion to eye tissue revealed maintenance of intraocular pressure that is five times greater than the physiological range with reversible seal strength comparable to cyanoacrylate (super glue). In vivo assessment in a rabbit model of ocular trauma demonstrated ease of use for TRS deployment, statistically significant improvement in wound sealing, and no evidence of neurotoxicity, retinal tissue degradation, or significant chronic inflammatory response after 30 days of exposure. Given the advantages of body heat-induced gelation, rapid reversible occlusion, and in vivo safety and efficacy, shape-adaptable TRSs have translational potential as smart wound sealants for temporary occlusion of surgical incisions or traumatic injuries.
Abstract 20072: Incremental Prognostic Value of Left Ventricular Global Longitudinal Strain and Late Gadolinium Enhancement in Patients with Dilated Cardiomyopathy
Authors: Misato Chimura, Tetsuari Onishi, Hiroya Kawai, Shinishiro Yamada, Yoshinori Yasaka
Journal: Circulation (2014)

Introduction: Reduced left ventricular (LV) global longitudinal strain (GLS) by two-dimensional speckle-tracking (2DST) echocardiography and late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) have been reported to be associated with unfavorable outcome in patient with heart failure (HF). We investigated to assess these 2 markers as prognostic parameters over conventional HF markers in patients with dilated cardiomyopathy (DCM). METHODS: We studied consecutive 179 DCM patients (Age 61±15 years, 121 males, LV ejection fraction (LVEF) 33±9%, NYHA class I: n= 0; II: n=71; III: n=107; IV: n=1) who underwent CMR and echocardiography with conventional assessment including LV end-diastolic and end-systolic volume (LVEDV, LVESV), LVEF and mitral regurgitation grade (MR), and with 2DST analysis of GLS. Brain natriuretic peptide (BNP) was measured. Outcome was assessed according to death and hospitalization with heart failure in the follow-up period for 3.8±2.5 years. RESULTS: There were 7 cardiac deaths and 40 HF hospitalizations in the follow-up period. Univariate Cox proportional hazard regression analysis showed NYHA class, systolic blood pressure, diastolic blood pressure, BNP, LVEDV, LVESV, LVEF, MR, GLS and positive LGE were significantly associated with outcome. Multivariate Cox proportional hazards regression analysis revealed GLS and positive LGE (p&lt;0.05 for both) were independent predictors of outcome. Dividing all 179 patients into 4 groups with the median of GLS (-8.3%) and the presence or absence of LGE, Kaplan-Meier analysis showed worse GLS predicted adverse events in patients with and without LGE (p&lt;0.05 for both). GLS and LGE provide additional benefit over conventional parameters (Age, NYHA class, LVEF and BNP). CONCLUSIONS: Risk stratification with LGE and GLS is useful to predict long-term outcome in DCM patients. These 2 markers provide incremental prognostic value to conventional HF markers.
Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience
Authors: Aisha Elsharkawy, Maissa El-Raziky, Wafaa El-Akel, Kadry El-Saeed, Rasha Eletreby, Mohamed Hassany, Manal Hamdy El-Sayed, Khaled Kabil, Sohier A. Ismail, Magdy El-Serafy, Ashraf Omar Abdelaziz, Mohamed Kamal Shaker, Ayman Yosry, Wahid Doss, Yehia El-Shazly, Gamal Esmat, Imam Waked
Journal: Journal of Hepatology (2017)
18F-FDG PET/CT Findings of Mesenchymal Chondrosarcoma of the Orbit
Authors: Mitsuteru Tsuchiya, Takayuki Masui, Yoshiro Otsuki, Harumi Sakahara
Journal: Clinical Nuclear Medicine (2017)

Mesenchymal chondrosarcoma of the orbit is an extremely rare and aggressive tumor. We report image findings of F-fluorodeoxyglucose (FDG) positron emission/computed tomography (PET/CT) in 2 cases, one primary case and one recurrent case. The F-FDG PET/CT images revealed high uptake with an SUVmax of 6.7 and 11.7, respectively. In both cases, the HEY1-CoA2 gene fusion was positive. The high uptake of F-FDG in mesenchymal chondrosarcoma of the orbit well suggests the malignancy of this tumor.
Abstract 19810: Oxidized LDL Exposure Enhances Baseline Platelet Activation and Amplifies Shear-mediated Activation
Authors: Shirzad Shir, Ahmed A Harhash, Marvin Slepian
Journal: Circulation (2017)

Introduction:  Atherosclerotic heart disease is the leading cause of advanced cardiac failure. For end-stage patients, mechanical circulatory support is essential. While live-saving, it is often limited by device-related thrombosis. Blood is exposed to abnormal flow and high levels of shear stress within these devices, and shear has been associated with platelet activation. These patients exhibit hypercholesterolemia, and the deposition of oxidized low density lipoprotein (oxLDL) along arteries foreshadows cardiac failure. It remains unknown if there is a mechanistic link between atherogenic lipids and shear-mediated platelet activation.   Hypothesis:  We hypothesize that oxLDL and shear exhibit synergistic effects on platelet activation, creating an environment susceptible to thrombosis.   Methods:  Human gel filtered platelets (GFP) isolated from 8 donors were incubated with 0.5 u g oxLDL or non-oxidized LDL (nLDL) for 15 minutes, and then exposed to uniform shear flow in a hemodynamic shearing device (HSD) at 37 °C. Samples were collected at 0 (no shear exposure), 2, and 5 minute time points during shear exposure of 70 dynes/cm 2 . Platelet activity was measured using a prothrombinase based platelet activation assay.   Results:  GFP incubated with oxLDL had a twofold increase in platelet activation levels compared to baseline controls (p    Conclusions:  Exposure of platelets to oxLDL significantly increased their susceptibility to shear-mediated activation - with a net higher level of activation as well as an acceleration of activation. Our findings suggest that persistent hyperlipidemia in mechanical circulatory support patients may be a further risk factor amplifying device-related thrombosis. Further studies are warranted as to the mechanisms operative in oxLDL amplified platelet activation and their contribution to thrombotic risk.
Differentiation between Oppositely Oriented Microtubules Controls Polarized Neuronal Transport
Authors: Roderick P. Tas, Anaël Chazeau, Bas M.C. Cloin, Maaike L.A. Lambers, Casper C. Hoogenraad, Lukas C. Kapitein
Journal: Neuron (2017)

Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely. In addition, microtubules with similar orientations and modifications form bundles that bias transport. Importantly, because the plus-end-directed Kinesin-1 selectively interacts with acetylated microtubules, this organization guides this motor out of dendrites and into axons. In contrast, Kinesin-3 prefers tyrosinated microtubules and can enter both axons and dendrites. This separation of distinct microtubule subsets into oppositely oriented bundles constitutes a key architectural principle of the neuronal microtubule cytoskeleton that enables polarized sorting by different motor proteins.