tbuckley/cabot-search huggingface dataset:
Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease
Authors: Faiez Zannad, Stefan D. Anker, William M. Byra, John G.F. Cleland, Min Fu, Mihai Gheorghiade, Carolyn S.P. Lam, Mandeep R. Mehra, James D. Neaton, Christopher C. Nessel, Theodore E. Spiro, Dirk J. van Veldhuisen, Barry Greenberg
Journal: New England Journal of Medicine (2018)

Heart failure is associated with activation of thrombin-related pathways, which predicts a poor prognosis. We hypothesized that treatment with rivaroxaban, a factor Xa inhibitor, could reduce thrombin generation and improve outcomes for patients with worsening chronic heart failure and underlying coronary artery disease.
Cost Effectiveness of Transplanting HCV-Infected Livers Into Uninfected Recipients With Preemptive Antiviral Therapy
Authors: Emily D. Bethea, Sumeyye Samur, Fasiha Kanwal, Turgay Ayer, Chin Hur, Mark S. Roberts, Norah Terrault, Raymond T. Chung, Jagpreet Chhatwal
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract P271: Diet in Association with Weight Change and the Development of Overweight and Obesity - A Prospective Study of Men
Authors: Susanne Rautiainen, I-Min Lee, Howard D
Journal: Circulation (2016)

Background: Obesity has become an epidemic affecting all age and socioeconomic groups worldwide with tremendous health consequences. Research is needed to determine modifiable lifestyle factors, including dietary factors, to prevent adults from becoming overweight or obese. Hypothesis: Diet is associated with weight change and overweight and obesity development. Methods: The Harvard Alumni Health Study is a prospective cohort study of men who matriculated at Harvard University from 1916-1950, and who have been followed by periodic questionnaires since 1962. We studied 6614 men free of cancer, cardiovascular disease, and diabetes (mean age, 65.5 years) who were nonobese (body mass index (BMI) &lt;30 kg/m 2 ) based on a 1988 questionnaire that also inquired about lifestyle, clinical, and dietary factors (23-item food frequency questionnaire). We considered individual dietary factors and a derived Dietary Approaches to Stop Hypertension (DASH) score of 6 dietary components: high intake of fruits, vegetables, fish, and low-fat dairy products, and low intake of sweets and red/processed meats). Men reported body weight on follow-up questionnaires in 1993 and 1998; 5- and 10-year body weight changes were computed along with the odds ratios (ORs) (95% confidence intervals (CIs)) of becoming overweight or obese, adjusting for various lifestyle and clinical factors as well as baseline BMI. Results: Over a 10-year period, 631 of 3906 initially normal weight (BMI≤25 kg/m 2 ) men became overweight or obese, and 230 of 6614 men initially nonobese (BMI≤30 kg/m 2 ) became obese. The multivariable-adjusted 5-year mean changes in body weight (standard deviation) were 0.03 (0.12), -0.12 (0.07), and -0.36 (0.09) kg, among men consuming total dairy products ≤6 times/week, 1-2 times/day, and ≥3 times/day (P-trend: 0.009), respectively, primarily driven by high-fat dairy intake (P, trend = 0.02). These associations weakened for 10-year weight changes. Higher tea consumption was inversely associated with greater 10-year (P-trend = 0.04), but not 5-year, weight loss. Among initially normal weight men, alcohol intake was inversely associated with a lower odds of becoming overweight or obese (OR (95% CI) for ≥168 versus 0 grams/week, 0.69 (0.49, 0.98); P, trend = 0.08). Other individual dietary factors were not associated with the odds of becoming overweight or obese. When investigating a combination of 6 beneficial dietary factors derived from the DASH score, an inverse linear association was observed with a lower OR of becoming obese (P-trend = 0.048), but not for becoming overweight or obese. Conclusion: In this prospective study of older men, selected individual dietary factors as well as a broader score reflecting a beneficial diet was related to less weight gain and lower odds of becoming overweight or obese.
Supramolecular Nanotherapeutics: Turning Toxicants into Safe Therapeutic Drugs: Cytolytic Peptide−Photosensitizer Assemblies for Optimized In Vivo Delivery of Melittin (Adv. Healthcare Mater. 16/2018)
Authors: Hao‐Ran Jia, Ya‐Xuan Zhu, Ke‐Fei Xu, Fu‐Gen Wu
Journal: Advanced Healthcare Materials (2018)

In article number 1800380, Fu-Gen Wu and co-workers illustrate a novel supramolecular strategy that successfully turns cytolytic melittin, a peptide component in bee venom, into a safe and tumor-targeting therapeutic nanodrug. The nanostructure is assembled by melittin, photosensitizer chlorin e6 (Ce6), and hyaluronic acid, which exhibits reduced hemolytic activity, laser-enhanced tumor penetration, and efficient tumor ablation by chemo-photodynamic dual therapy.
Abstract 17570: Inducible Pluripotent Stem Cell-Derived Extracellular Vesicles Mitigates Aging-Associated Arterial Stiffness and Hypertension
Authors: Rui Feng, Mujib Ullah, Kai Chen, Quaisar Ali, Yi Lin, Han Lei, Zhongjie Sun
Journal: Circulation (2017)

Objective: Aging is a major risk factor for the development of hypertension and arterial stiffness. This study was designed to assess the effect of indicible pluripotent stem cells (iPSC)-derived e...
Erlotinib versus vinorelbine plus cisplatin as adjuvant therapy in Chinese patients with stage IIIA EGFR mutation-positive non-small-cell lung cancer (EVAN): a randomised, open-label, phase 2 trial
Authors: Dongsheng Yue, Shidong Xu, Qun Wang, Xiaofei Li, Yi Shen, Heng Zhao, Chun Chen, Weimin Mao, Wei Liu, Junfeng Liu, Lanjun Zhang, Haitao Ma, Qiang Li, Yue Yang, Yongyu Liu, Haiquan Chen, Changli Wang
Journal: The Lancet Respiratory Medicine (2018)
Bioavailability of Fat-Soluble Vitamins and Phytochemicals in Humans: Effects of Genetic Variation
Authors: Patrick Borel, Charles Desmarchelier
Journal: Annual Review of Nutrition (2018)

Recent data have shown that interindividual variability in the bioavailability of vitamins A (β-carotene), D, and E, and carotenoids (lutein and lycopene), as well as that of phytosterols, is modulated by single nucleotide polymorphisms (SNPs). The identified SNPs are in or near genes involved in intestinal uptake or efflux of these compounds, as well as in genes involved in their metabolism and transport. The phenotypic effect of each SNP is usually low, but combinations of SNPs can explain a significant part of the variability. Nevertheless, results from these studies should be considered preliminary since they have not been validated in other cohorts. Guidelines for future studies are provided to ensure that sound associations are elucidated that can be used to build consolidated genetic scores that may allow recommended dietary allowances to be tailored to individuals or groups by taking into account the multiloci genotypic signature of people of different ethnic origin or even of individuals.
Abstract 15969: Impact of a Comprehensive ST Elevation Myocardial Infarction Protocol on Outcomes of Patients Excluded From Door to Balloon Time Public Reporting
Authors: Chetan Huded, Kathleen Kravitz, Venu Menon, Travis Gullett, Samir Kapadia, Scott Hantz, Stephen Ellis, Mouin Abdallah, Damon Kralovic, Seth Podolsky, Steve Meldon, Deborah Brosovich, Elizabeth Smith, Umesh Khot
Journal: Circulation (2017)

Introduction: A subset of ST elevation myocardial infarction (STEMI) patients were excluded from door to balloon time (D2BT) public reporting based on criteria set by the Center for Medicare and Me...
Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain
Authors: Hussein A. Tawbi, Peter A. Forsyth, Alain Algazi, Omid Hamid, F. Stephen Hodi, Stergios J. Moschos, Nikhil I. Khushalani, Karl Lewis, Christopher D. Lao, Michael A. Postow, Michael B. Atkins, Marc S. Ernstoff, David A. Reardon, Igor Puzanov, Ragini R. Kudchadkar, Reena P. Thomas, Ahmad Tarhini, Anna C. Pavlick, Joel Jiang, Alexandre Avila, Sheena Demelo, Kim Margolin
Journal: New England Journal of Medicine (2018)

Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases.
Abstract 15202: Functional Mitral Regurgitation is a Quantitative Determinant of Mortality in Patients With Left Ventricular Dysfunction in Clinical Practice
Authors: Giovanni Benfari, Clemence Antoine, Wayne L Miller, Hector I Michelena, Vuyisile T Nkomo, Maurice Enriquez-Sarano
Journal: Circulation (2016)

Background: Functional mitral regurgitation (FMR) grading in left ventricular (LV) dysfunction is controversial. Pilot studies suggested mortality-risk at low effective regurgitant orifice (ERO) bu...
Abstract 14937: Protein Network of VASP in Lipid Raft of Platelets
Authors: Vahideh Rabani, Damien Montange, Nicolas F Meneveau, Siamak Davani
Journal: Circulation (2016)

Introduction: VAsodilator-Stimulated Phosphoprotein (VASP) represents a very sensitive marker of platelet responsiveness to ADP receptor (P2Y12) inhibitors. After platelet stimulation, VASP is colocalized with F-actin on Detergent Resistant Membrane (DRM) but the protein network involved is not well known. We aimed to investigate interactive proteins with VASP on DRM of platelets. Methods: Lipid rafts of human platelets were isolated using Triton X100 1% (w/v) and sucrose gradient. After ultracentrifugation, sucrose fractions were sampled. Lipidomics analysis was performed to identify fractions enriched in cholesterol and sphingomyelin (considered as DRM). These enriched fractions were selected for further proteomic analyses. Post analysis of proteomics results was performed to identify participating protein pathways around VASP. Results: Sucrose fractions containing platelet DRMs were identified (Fig., left). In these fractions, we identified potential proteins interacting with VASP (Fig, right). Some of...
Abstract 18862: Wall Shear Stress in Pulmonary Hypertension
Authors: Triston B Smith, Vitaly O Kheyfets, Theodore Schroeder, Jeffrey Mueller, David Lasorda, Jennifer Spotti, Ender A Finol, Srinivas Murali
Journal: Circulation (2013)

Pulmonary arterial hypertension (PAH) leads to morphometric remodeling of the pulmonary arteries. Computational fluid dynamics (CFD) modeling has the potential to reveal continuum metrics associated with the stress acting on the vascular endothelium in a non- invasive manner. We hypothesized that the PA endothelium of PAH patients will be subject to abnormal wall shear stress (WSS), and thus investigated the relationship of spatially averaged WSS (SAWSS) with invasive measurements of pulmonary vascular resistance (PVR) and compliance (C). Methods: Computed tomography angiography (CTA) and RHC were used to acquire images and hemodynamic data in 19 PH patients. Each patient’s pulmonary vascular tree was reconstructed from CT images up to 6 generations. The inlets and outlets were extended to 10 times their hydraulic diameters and a volumetric mesh created within element dimensions determined by a systematic mesh convergence study. Each CFD model was simulated using a structured tree outflow boundary condition. Constant flow rate simulations were performed using the numerical solver Fluent (ANSYS Inc., Lebanon, NH) after adjusting for patient-specific scaling parameters. Finally, SAWSS on the surface of the pulmonary arterial endothelium was obtained during post-processing. Correlations between SAWSS and hemodynamics were made. Results: Figure 1 shows a power-regression correlation between SAWSS and PVR, and linear-regression correlation between SAWSS and C. SAWSS decreases for increasing PVR and decreasing C. Conclusions: Pulmonary arterial WSS obtained by our CFD model can be used as a physiologically relevant quantitative metric of PAH severity, which likely precedes vascular and ventricular remodeling. Its application as a non-invasive surrogate for disease progression and evaluation of response to PH specific therapies needs further investigation.
Pulmonary function and bronchial reactivity 4 years after the first virus‐induced wheezing
Authors: Annamari Leino, Minna Lukkarinen, Riitta Turunen, Tytti Vuorinen, Maria Söderlund‐Venermo, Tero Vahlberg, Carlos A. Camargo, Yury A. Bochkov, James E. Gern, Tuomas Jartti
Journal: Allergy (2018)

Abstract Background Wheezing illnesses among young children are common and are a risk factor for asthma. However, determinants of childhood bronchial reactivity, a key feature of asthma, are largely unknown. The aim of this study was to determine how patient characteristics during the first severe virus‐induced wheezing episode are associated with pulmonary function at preschool age. Methods Study consisted of 76 children presenting with their first wheezing episode at the ages of 3 to 23 months. At study entry, viral etiology, rhinovirus genome load, atopic and clinical characteristics, and standardized questionnaire were analyzed. At 4‐year follow‐up visit, impulse oscillometry with exercise challenge was performed. Results At study entry, the mean age of the children was 12 months ( SD 6.0), 57 (75%) were rhinovirus positive, and 22 (30%) were sensitized. At follow‐up visit four years later, the mean age of the children was 60 months ( SD 7.9) and 37 (49%) were using asthma medication regularly (discontinued before testing in 25 [68%] children). Bronchial reactivity (≥35% change in mean crude values of resistance) after exercise challenge or bronchodilation was present in nine (12%) children. Children with atopic sensitization at the time of the first wheezing episode were more often likely to develop bronchial reactivity (odds ratio 8.8, P = 0.03) than the children without sensitization. No other significant associations were found. Conclusions Atopic sensitization at the time of the first severe wheezing episode is an important early risk factor for increased bronchial reactivity at preschool age.
Reducing the Rate of Minimally Invasive Hysterectomy for Fibroids in Favor of Abdominal Surgery—There Is Always Something Evil in Good Intentions—Reply
Authors: Francesco Multinu, Andrea Mariani, Shannon K. Laughlin-Tommaso
Journal: JAMA Surgery (2018)

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Abstract 11181: Angiotensin Type 1 Receptor Blocker Enhances H2O2-induced Coronary Collateral Vasodilatation and Improves Diabetes-induced Microvascular Endothelial Dysfunction and H2O2 Production during Acute Coronary Occlusion in Canine Coronary Native Collateral Microcirculation in vivo
Authors: Toyotaka Yada
Journal: Circulation (2012)

Background: We examined whether an angiotensin type 1 receptor blocker (ARB) enhances hydrogen peroxide (H2O2, endothelium-derived hyperpolarizing factor)-induced vasodilatation and production duri...
Abstract 14003: Refinement of the Heart Failure Somatic Perception Scale Dyspnea Subscale
Authors: Ruth M Masterson Creber, Corrine Y Jurgens, Christopher S Lee
Journal: Circulation (2017)

Background: Dyspnea is a hallmark symptom of heart failure (HF). The Heart Failure Somatic Perception Scale has a 6-item Dyspnea Subscale (HFSPSD) that is known to independently predict clinical ou...
Immunotherapy for Melanoma Metastatic to the Brain
Authors: Samra Turajlic, James Larkin
Journal: New England Journal of Medicine (2018)

Most practicing physicians will recall from their training that the average prognosis for patients with central nervous system (CNS) metastases from melanoma was death within a matter of weeks to months.1 This reflected the natural history of a disease on which systemic treatment had a negligible effect. Local therapies, such as surgery and radiotherapy, can palliate symptoms in selected patients, but the outcomes, particularly in patients with multiple metastases treated with whole-brain radiotherapy, are often poor. Moreover, CNS involvement often causes substantial functional impairment, and the use of high-dose glucocorticoids to alleviate edema adds further iatrogenic complications. Patients with CNS . . .
Systemic Therapy in Advanced Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort
Authors: Claire Merveilleux du Vignaux, Eric Dansin, Laurent Mhanna, Laurent Greillier, Eric Pichon, Mallorie Kerjouan, Christelle Clément-Duchêne, Bertrand Mennecier, Virginie Westeel, Marie Robert, Xavier Quantin, Gérard Zalcman, Luc Thiberville, Hervé Lena, Thierry Molina, Fabien Calcagno, Pierre Fournel, Julien Mazières, Benjamin Besse, Nicolas Girard
Journal: Journal of Thoracic Oncology (2018)
Caspase-11 auto-proteolysis is crucial for noncanonical inflammasome activation
Authors: Bettina L. Lee, Irma B. Stowe, Aaron Gupta, Opher S. Kornfeld, Merone Roose-Girma, Keith Anderson, Søren Warming, Juan Zhang, Wyne P. Lee, Nobuhiko Kayagaki
Journal: The Journal of Experimental Medicine (2018)

Intracellular LPS sensing by caspase-4/5/11 triggers proteolytic activation of pore-forming gasdermin D (GSDMD), leading to pyroptotic cell death in Gram-negative bacteria-infected cells. Involvement of caspase-4/5/11 and GSDMD in inflammatory responses, such as lethal sepsis, makes them highly desirable drug targets. Using knock-in (KI) mouse strains, we herein provide genetic evidence to show that caspase-11 auto-cleavage at the inter-subunit linker is essential for optimal catalytic activity and subsequent proteolytic cleavage of GSDMD. Macrophages from caspase-11–processing dead KI mice (Casp11Prc D285A/D285A) exhibit defective caspase-11 auto-processing and phenocopy Casp11−/− and caspase-11 enzymatically dead KI (Casp11Enz C254A/C254A) macrophages in attenuating responses to cytoplasmic LPS or Gram-negative bacteria infection. GsdmdD276A/D276A KI macrophages also fail to cleave GSDMD and are hypo-responsive to inflammasome stimuli, confirming that the GSDMD Asp276 residue is a nonredundant and indispensable site for proteolytic activation of GSDMD. Our data highlight the role of caspase-11 self-cleavage as a critical regulatory step for GSDMD processing and response against Gram-negative bacteria.
Alkylating histone deacetylase inhibitors may have therapeutic value in experimental myeloperoxidase-ANCA vasculitis
Authors: Dearbhaile Dooley, Mirjan M. van Timmeren, Vincent P. O’Reilly, Gareth Brady, Eóin C. O’Brien, Barbara Fazekas, Fionnuala B. Hickey, Emma Leacy, Charles D. Pusey, Frederick W.K. Tam, Thomas Mehrling, Peter Heeringa, Mark A. Little
Journal: Kidney International (2018)
Abstract 12966: Combination of Urine Sodium Concentration and Plasma Brain Natriuretic Peptide Level Best Predicted the Clinical and Hemodynamic Effects of Tolvaptan Therapy in Patients With Heart Failure
Authors: Yuichi Sato, Kaoru Dohi, Tetsushiro Takeuchi, Muneyoshi Tanimura, Emiyo Sugiura, Naoto Kumagai, Shiro Nakamori, Naoki Fujimoto, Norikazu Yamada, Masaaki Ito
Journal: Circulation (2015)

Purpose: We identified the best predictors of clinical response to simple add-on tolvaptan (TLV) therapy in patients with heart failure (HF). Methods: We retrospectively enrolled 60 HF patients with excess fluid retention despite receiving adequate medical therapy including oral diuretics. All patients received simple add-on TLV (median of 7.5mg/day). They underwent right heart catheterization at baseline and after 7-day treatment. Results: Although the majority of patients were successfully treated with simple add-on TLV therapy (Group 1), but 22% (Group 2) were defined as being unsuccessfully treated because 1) HF symptom score worsened or 2) HF symptom score &gt;6, and mean pulmonary capillary wedge pressure (PCWP) &gt;18 mmHg and mean right atrial pressure (RAP) &gt;10 mmHg after TLV therapy. Although the degrees of body weight reduction and increment of urine volume were similar between the two groups, HF symptom score and mean PCWP and RAP improved, and plasma BNP level decreased only in the group 1 after TLV therapy. The group 2 had lower urine sodium/creatinine ratio (UNa/UCr) and higher plasma BNP level than responders at baseline, and they were identified as the independent predictors of unsuccessful TLV therapy by multivariate logistic regression analysis. Receiver operating characteristic curve analysis showed that UNa/UCr was the strongest predictor of unsuccessful TLV therapy with cut-off point of 46.5 mEq/gCr (AUC 0.847, 95% CI; 0.718-0.976, sensitivity 77%, specificity 81%, P&lt;0.001). Furthermore, combination with UNa/UCr 778 pg/ml best predicted unsuccessful TLV therapy with sensitivity of 54%, specificity of 100%, positive predictive value of 100%, negative predictive value of 89%, and accuracy of 90%. Conclusion: Simple add-on tolvaptan therapy ameliorated HF symptoms and provided hemodynamic improvement in majority of patients with HF, and the measurements of UNa/UCr and BNP level can help clinicians tailor HF treatment.
MACSE v2: Toolkit for the Alignment of Coding Sequences Accounting for Frameshifts and Stop Codons
Authors: Vincent Ranwez, Emmanuel J P Douzery, Cédric Cambon, Nathalie Chantret, Frédéric Delsuc
Journal: Molecular Biology and Evolution (2018)

Multiple sequence alignment is a prerequisite for many evolutionary analyses. Multiple Alignment of Coding Sequences (MACSE) is a multiple sequence alignment program that explicitly accounts for the underlying codon structure of protein-coding nucleotide sequences. Its unique characteristic allows building reliable codon alignments even in the presence of frameshifts. This facilitates downstream analyses such as selection pressure estimation based on the ratio of nonsynonymous to synonymous substitutions. Here, we present MACSE v2, a major update with an improved version of the initial algorithm enriched with a complete toolkit to handle multiple alignments of protein-coding sequences. A graphical interface now provides user-friendly access to the different subprograms.