tbuckley/cabot-search huggingface dataset:
Serum Alanine Aminotransferase Elevations in Survivors of Childhood Cancer: A Report From the St. Jude Lifetime Cohort Study
Authors: Daniel M. Green, Mingjuan Wang, Matthew J. Krasin, DeoKumar Srivastava, Mary V. Relling, Carrie R. Howell, Kirsten K. Ness, Sue C. Kaste, William Greene, Dennis W. Jay, Israel Fernandez‐Pineda, Ching‐Hon Pui, Sima Jeha, Michael W. Bishop, Wayne L. Furman, Leslie L. Robison, Melissa M. Hudson
Journal: Hepatology (2018)

The purpose of this study was to define the prevalence of and risk factors for elevated serum alanine aminotransferase (ALT) level among adult childhood cancer survivors (CCS). The study cohort comprised 2,751 CCS from the St. Jude Lifetime Cohort Study (>10 years postdiagnosis, age ≥18 years). Serum ALT level was graded using the Common Terminology Criteria for Adverse Events v. 4.03. Modified Poisson regression models were used to estimate relative risks and 95% confidence intervals for the association between demographic and clinical factors and grades 1-4 ALT on the selected models. A total of 1,339 (48.7%) CCS were female; 2,271 (82.6%) were non-Hispanic white. Median age at evaluation was 31.4 years (interquartile range [IQR] = 25.8-37.8); median elapsed time from diagnosis to evaluation was 23.2 years (IQR = 17.6-29.7). A total of 1,137 (41.3%) CSS had ALT > upper limit of normal (Common Terminology Criteria for Adverse Events v. 4.03 grade 1-1,058 (38.5%); grade 2-56 (2.0%); grade 3-23 (0.8%); grade 4-none). Multivariable models demonstrated non-Hispanic white race/ethnicity, age at evaluation in years, being overweight or obese, presence of the metabolic syndrome, current treatment with atorvastatin or rosuvastatin or simvastatin, hepatitis C virus infection, prior treatment with busulfan or thioguanine, history of hepatic surgery, and the percentage of liver treated with ≥10 Gray, ≥15 Gray, or ≥20 Gray were associated with elevated ALT. Conclusion: Grade 3 or 4 hepatic injury is infrequent in CCS. Mild hepatic injury in this group may be amenable to lifestyle modifications.
Antioxidants for preventing and reducing muscle soreness after exercise: a Cochrane systematic review
Authors: Mayur K Ranchordas, David Rogerson, Hora Soltani, Joseph T Costello
Journal: British Journal of Sports Medicine (2018)

Objective To determine whether antioxidant supplements and antioxidant-enriched foods can prevent or reduce delayed-onset muscle soreness after exercise. Methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, SPORTDiscus, trial registers, reference lists of articles and conference proceedings up to February 2017. Results In total, 50 studies were included in this review which included a total of 1089 participants (961 were male and 128 were female) with an age range of 16–55 years. All studies used an antioxidant dosage higher than the recommended daily amount. The majority of trials (47) had design features that carried a high risk of bias due to selective reporting and poorly described allocation concealment, potentially limiting the reliability of their findings. We rescaled to a 0–10 cm scale in order to quantify the actual difference between groups and we found that the 95% CIs for all five follow-up times were all well below the minimal important difference of 1.4 cm: up to 6 hours (MD −0.52, 95% CI −0.95 to −0.08); at 24 hours (MD −0.17, 95% CI −0.42 to 0.07); at 48 hours (mean difference (MD) −0.41, 95% CI −0.69 to −0.12); at 72 hours (MD −0.29, 95% CI −0.59 to 0.02); and at 96 hours (MD −0.03, 95% CI −0.43 to 0.37). Thus, the effect sizes suggesting less muscle soreness with antioxidant supplementation were very unlikely to equate to meaningful or important differences in practice. Conclusions There is moderate to low-quality evidence that high-dose antioxidant supplementation does not result in a clinically relevant reduction of muscle soreness after exercise of up to 6 hours or at 24, 48, 72 and 96 hours after exercise. There is no evidence available on subjective recovery and only limited evidence on the adverse effects of taking antioxidant supplements.
Heart Rate and Cardiac Rhythm Relationships With Bisoprolol Benefit in Chronic Heart Failure in CIBIS II Trial
Authors: PhilippeLechat, Jean-SébastienHulot, SylvieEscolano, AlainMallet, AlainLeizorovicz, MarieWerhlen-Grandjean, GilbertPochmalicki, HenryDargie
Journal: Circulation (2001)

Background—β-Blockade–induced benefit in heart failure (HF) could be related to baseline heart rate and treatment-induced heart rate reduction, but no such relationships have been demonstrated. Methods and Results—In CIBIS II, we studied the relationships between baseline heart rate (BHR), heart rate changes at 2 months (HRC), nature of cardiac rhythm (sinus rhythm or atrial fibrillation), and outcomes (mortality and hospitalization for HF). Multivariate analysis of CIBIS II showed that in addition to β-blocker treatment, BHR and HRC were both significantly related to survival and hospitalization for worsening HF, the lowest BHR and the greatest HRC being associated with best survival and reduction of hospital admissions. No interaction between the 3 variables was observed, meaning that on one hand, HRC-related improvement in survival was similar at all levels of BHR, and on the other hand, bisoprolol-induced benefit over placebo for survival was observed to a similar extent at any level of both BHR and H...
Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study
Authors: Elliot B Tapper, Neehar D Parikh
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To describe liver disease related mortality in the United States during 1999-2016 by age group, sex, race, cause of liver disease, and geographic region. <h3>Design</h3> Observational cohort study. <h3>Setting</h3> Death certificate data from the Vital Statistics Cooperative, and population data from the US Census Bureau compiled by the Center for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (1999-2016). <h3>Participants</h3> US residents. <h3>Main outcome measure</h3> Deaths from cirrhosis and hepatocellular carcinoma, with trends evaluated using joinpoint regression. <h3>Results</h3> From 1999 to 2016 in the US annual deaths from cirrhosis increased by 65%, to 34 174, while annual deaths from hepatocellular carcinoma doubled to 11 073. Only one subgroup—Asians and Pacific Islanders—experienced an improvement in mortality from hepatocellular carcinoma: the death rate decreased by 2.7% (95% confidence interval 2.2% to 3.3%, P&lt;0.001) per year. Annual increases in cirrhosis related mortality were most pronounced for Native Americans (designated as "American Indians" in the census database) (4.0%, 2.2% to 5.7%, P=0.002). The age adjusted death rate due to hepatocellular carcinoma increased annually by 2.1% (1.9% to 2.3%, P&lt;0.001); deaths due to cirrhosis began increasing in 2009 through 2016 by 3.4% (3.1% to 3.8%, P&lt;0.001). During 2009-16 people aged 25-34 years experienced the highest average annual increase in cirrhosis related mortality (10.5%, 8.9% to 12.2%, P&lt;0.001), driven entirely by alcohol related liver disease. During this period, mortality due to peritonitis and sepsis in the setting of cirrhosis increased substantially, with respective annual increases of 6.1% (3.9% to 8.2%) and 7.1% (6.1% to 8.4%). Only one state, Maryland, showed improvements in mortality (−1.2%, −1.7% to −0.7% per year), while many, concentrated in the south and west, observed disproportionate annual increases: Kentucky 6.8% (5.1% to 8.5%), New Mexico 6.0% (4.1% to 7.9%), Arkansas 5.7% (3.9% to 7.6%), Indiana 5.0% (3.8% to 6.1%), and Alabama 5.0% (3.2% to 6.8%). No state showed improvements in hepatocellular carcinoma related mortality, while Arizona (5.1%, 3.7% to 6.5%) and Kansas (4.3%, 2.8% to 5.8%) experienced the most severe annual increases. <h3>Conclusions</h3> Mortality due to cirrhosis has been increasing in the US since 2009. Driven by deaths due to alcoholic cirrhosis, people aged 25-34 have experienced the greatest relative increase in mortality. White Americans, Native Americans, and Hispanic Americans experienced the greatest increase in deaths from cirrhosis. Mortality due to cirrhosis is improving in Maryland but worst in Kentucky, New Mexico, and Arkansas. The rapid increase in death rates among young people due to alcohol highlight new challenges for optimal care of patients with preventable liver disease.
Adverse Bioenergetic Consequences of Na+-Ca2+ Exchanger–Mediated Ca2+ Influx in Cardiac Myocytes
Authors: MichaelKohlhaas, ChristophMaack
Journal: Circulation (2010)

Background—In heart failure, the Na+-Ca2+ exchanger (NCX) is upregulated and mediates Ca2+ influx (instead of efflux) during the cardiac action potential. Although this partly compensates for impaired sarcoplasmic reticulum Ca2+ release and supports inotropy, the energetic consequences have never been considered. Because NCX-mediated Ca2+ influx is rather slow and mitochondrial Ca2+ uptake (which stimulates NADH production by the Krebs cycle) is thought to be facilitated by high Ca2+ gradients in a “mitochondrial Ca2+ microdomain,” we speculated that NCX-mediated Ca2+ influx negatively affects the bioenergetic feedback response. Methods and Results—With the use of a patch-clamp–based approach in guinea-pig myocytes, cytosolic and mitochondrial Ca2+ ([Ca2+]c and [Ca2+]m, respectively) was determined within the same cell after varying Ca2+ influx via L-type Ca2+ channels (ICa,L) or the NCX. The efficiency of mitochondrial Ca2+ uptake, indexed by the slope of plotting [Ca2+]m against [Ca2+]c during each Ca2+...
Preoperative Predictors of Death and Sustained Ventricular Tachycardia After Pulmonary Valve Replacement in Patients With Repaired Tetralogy of Fallot Enrolled in the INDICATOR Cohort
Authors: Tal Geva, Barbara Mulder, Kimberlee Gauvreau, Sonya V. Babu-Narayan, Rachel M. Wald, Kelsey Hickey, Andrew J. Powell, Michael A. Gatzoulis, Anne Marie Valente
Journal: Circulation (2018)

Risk factors for adverse clinical outcomes have been identified in patients with repaired tetralogy of Fallot before pulmonary valve replacement (PVR). However, pre-PVR predictors for post-PVR sustained ventricular tachycardia and death have not been identified.Patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort (International Multicenter TOF Registry), a 4-center international cohort study, who had a comprehensive preoperative evaluation and subsequently underwent PVR were included. Preprocedural clinical, ECG, cardiovascular magnetic resonance, and postoperative outcome data were analyzed. Cox proportional hazards multivariable regression analysis was used to evaluate factors associated with time from pre-PVR cardiovascular magnetic resonance until the primary outcome: death, aborted sudden cardiac death, or sustained ventricular tachycardia.Of the 452 eligible patients (median age at PVR, 25.8 years), 36 (8%) reached the primary outcome (27 deaths, 2 resuscitated death, and 7 sustained ventricular tachycardia) at a median time after PVR of 6.5 years. Cox proportional hazards regression identified pre-PVR right ventricular ejection fraction <40% (hazard ratio, 2.39; 95% CI, 1.18-4.85; P=0.02), right ventricular mass-to-volume ratio ≥0.45 g/mL (hazard ratio, 4.08; 95% CI, 1.57-10.6; P=0.004), and age at PVR ≥28 years (hazard ratio, 3.10; 95% CI, 1.42-6.78; P=0.005) as outcome predictors. In a subgroup analysis of 230 patients with Doppler data, predicted right ventricular systolic pressure ≥40 mm Hg was associated with the primary outcome (hazard ratio, 3.42; 95% CI, 1.09-10.7; P=0.04). Preoperative predictors of a composite secondary outcome, postoperative arrhythmias and heart failure, included older age at PVR, pre-PVR atrial tachyarrhythmias, and a higher left ventricular end-systolic volume index.In this observational investigation of patients with repaired tetralogy of Fallot, an older age at PVR and pre-PVR right ventricular hypertrophy and dysfunction were predictive of a shorter time to postoperative death and sustained ventricular tachycardia. These findings may inform the timing of PVR if confirmed by prospective clinical trials.
Carbon pricing, co-pollutants, and climate policy: Evidence from California
Authors: James K. Boyce, Michael Ash
Journal: PLoS Medicine (2018)

Carbon pricing policies, a critical instrument to manage the costs of greenhouse gas (GHG) pollution, now cover roughly 20% of the world's carbon emissions from fossil fuel combustion [1].By increasing the price of fossil fuels via a carbon tax or a cap-and-permit system, these policies reduce their use and provide incentives for investments in alternative energy sources and energy efficiency.Carbon pricing can also yield public health co-benefits by reducing emissions of hazardous air co-pollutants along with carbon dioxide and can, in principle, improve environmental equity by reducing disproportionate pollution burdens in socioeconomically disadvantaged communities.In this issue of PLOS Medicine, Rachel Morello-Frosch and colleagues report the first evidence-based assessment of air pollution equity outcomes of California's carbon pricing policy implemented in 2013.They found that, over the 2011-2015 study period, emissions from industrial facilities of GHGs and co-pollutants-particulate matter (PM 2.5 ), sulfur oxides, nitrogen oxides, volatile organic compounds (VOCs), and air toxics (roughly 600 chemicals subject to Toxics Release Inventory reporting)-were almost as likely to increase as to decrease and that neighborhoods with emission increases tended to have higher percentages of racial and ethnic minority, poor, less educated, and linguistically isolated residents [2].These findings suggest that climate policy can best fulfill its potential if designed explicitly to achieve widely shared health co-benefits and improved environmental equity.
Dressings and securements for the prevention of peripheral intravenous catheter failure in adults (SAVE): a pragmatic, randomised controlled, superiority trial
Authors: Claire M Rickard, Nicole Marsh, Joan Webster, Naomi Runnegar, Emily Larsen, Matthew R McGrail, Fiona Fullerton, Emilie Bettington, Jennifer A Whitty, Md Abu Choudhury, Haitham Tuffaha, Amanda Corley, David J McMillan, John F Fraser, Andrea P Marshall, E Geoffrey Playford
Journal: The Lancet (2018)
Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
Authors: Quanbo Ji, Yuxuan Zheng, Guoqiang Zhang, Yuqiong Hu, Xiaoying Fan, Yu Hou, Lu Wen, Li Li, Yameng Xu, Yan Wang, Fuchou Tang
Journal: Annals of the Rheumatic Diseases (2018)

Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq).We performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index and correspondence analysis.We identified seven molecularly defined populations of chondrocytes in the human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA.Our results provide new insights into chondrocyte taxonomy and present potential clues for effective and functional manipulation of human OA cartilage regeneration that could lead to improved health.
LRRK2 activation in idiopathic Parkinson’s disease
Authors: Roberto Di Maio, Eric K. Hoffman, Emily M. Rocha, Matthew T. Keeney, Laurie H. Sanders, Briana R. De Miranda, Alevtina Zharikov, Amber Van Laar, Antonia F. Stepan, Thomas A. Lanz, Julia K. Kofler, Edward A. Burton, Dario R. Alessi, Teresa G. Hastings, J. Timothy Greenamyre
Journal: Science Translational Medicine (2018)

Wild-type LRRK2 is activated in nigrostriatal dopamine neurons in idiopathic Parkinson’s disease and plays a pathogenic role in this neurodegenerative disorder.
Do DPP-4 Inhibitors Cause Heart Failure Events by Promoting Adrenergically Mediated Cardiotoxicity?
Authors: Milton Packer
Journal: Circulation Research (2018)

Rationale: DPP-4 (dipeptidyl peptidase-4) inhibitors have increased the risk of heart failure events in both randomized clinical trials and observational studies, but the mechanisms that underlie their deleterious effect remain to be elucidated. Previous work has implicated a role of these drugs to promote cardiac fibrosis. Objective: This article postulates that DPP-4 inhibitors increase the risk of heart failure events by activating the sympathetic nervous system to stimulate cardiomyocyte cell death, and it crystallizes the findings from both experimental studies and clinical trials that support the hypothesis. Methods and Results: Inhibition of DPP-4 not only potentiates the actions of GLP-1 (glucagon-like peptide-1; which can increase myocardial cAMP) but also potentiates the actions of SDF-1 (stromal cell-derived factor 1), NPY (neuropeptide Y), and substance P to activate the sympathetic nervous system and stimulate β-adrenergic receptors to cause cardiomyocyte apoptosis, presumably through a CaMKII (Ca++/calmodulin-dependent protein kinase II) pathway. An action of SDF-1 to interfere with cAMP and protein kinase A signaling may account for the absence of a clinically overt positive chronotropic effect. This conceptual framework is supported by the apparent ability of β-blocking drugs to attenuate the increased risk of DPP-4 inhibitors in a large-scale clinical trial. Conclusions: Sympathetic activation may explain the increased risk of heart failure produced by DPP-4 inhibitors. The proposed mechanism has major implications for clinical care because in the treatment of patients with type 2 diabetes mellitus, DPP-4 inhibitors are widely prescribed, but β-blockers are underutilized because of fears that they might mask hypoglycemia.
Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool
Authors: Paul W Sperduto, Brian J Deegan, Jing Li, Krishan R Jethwa, Paul D Brown, Natalie Lockney, Kathryn Beal, Nitesh G Rana, Albert Attia, Chia-Lin Tseng, Arjun Sahgal, Ryan Shanley, William A Sperduto, Emil Lou, Amir Zahra, John M Buatti, James B Yu, Veronica Chiang, Jason K Molitoris, Laura Masucci, David Roberge, Diana D Shi, Helen A Shih, Adam Olson, John P Kirkpatrick, Steve Braunstein, Penny Sneed, Minesh P Mehta
Journal: Neuro-Oncology (2018)

Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985-2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors.A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively.The 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0-1.0, 1.5-2.0, 2.5-3, and 3.5-4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively.The updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com.
Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: 24-month outcomes from a randomised controlled study
Authors: Geoffrey D Coughlin, John W Yaxley, Suzanne K Chambers, Stefano Occhipinti, Hema Samaratunga, Leah Zajdlewicz, Patrick Teloken, Nigel Dunglison, Scott Williams, Martin F Lavin, Robert A Gardiner
Journal: The Lancet Oncology (2018)
Association of preoperative glucose concentration with myocardial injury and death after non-cardiac surgery (GlucoVISION): a prospective cohort study
Authors: Zubin Punthakee, Pilar Paniagua Iglesias, Pablo Alonso-Coello, Ignasi Gich, Inmaculada India, Germán Malaga, Ruben Diaz Jover, Hertzel C Gerstein, P J Devereaux
Journal: The Lancet Diabetes & Endocrinology (2018)
Burden of disease in Brazil, 1990–2016: a systematic subnational analysis for the Global Burden of Disease Study 2016
Authors: Fatima Marinho, Valéria Maria de Azeredo Passos, Deborah Carvalho Malta, Elizabeth Barboza França, Daisy M X Abreu, Valdelaine E M Araújo, Maria Teresa Bustamante-Teixeira, Paulo A M Camargos, Carolina Cândida da Cunha, Bruce Bartholow Duncan, Mariana Santos Felisbino-Mendes, Maximiliano Ribeiro Guerra, Mark D C Guimaraes, Paulo A Lotufo, Wagner Marcenes, Patricia Pereira Vasconcelos Oliveira, Marcel de Moares Pedroso, Antonio L Ribeiro, Maria Inês Schmidt, Renato Azeredo Teixeira, Ana Maria Nogales Vasconcelos, Mauricio L Barreto, Isabela M Bensenor, Luisa C C Brant, Rafael M Claro, Alexandre Costa Pereira, Ewerton Cousin, Maria Paula Curado, Kadine Priscila Bender dos Santos, André Faro, Cleusa P Ferri, João M Furtado, Julia Gall, Scott D Glenn, Alessandra Carvalho Goulart, Lenice Harumi Ishitani, Christian Kieling, Roberto Marini Ladeira, Isis Eloah Machado, Sheila Cristina Ouriques Martins, Francisco Rogerlândio Martins-Melo, Ana Paula Souto Melo, Molly K Miller-Petrie, Meghan D Mooney, Bruno P Nunes, Marcos Roberto Tovani Palone, Claudia C Pereira, Davide Rasella, Sarah E Ray, Leonardo Roever, Raphael de Freitas Saldanha, Itamar S Santos, Ione J C Schneider, Diego Augusto Santos Silva, Dayane Gabriele Alves Silveira, Adauto Martins Soares Filho, Tatiane Cristina Moraes Sousa, Celia L Szwarcwald, Jefferson Traebert, Gustavo Velasquez-Melendez, Yuan-Pang Wang, Rafael Lozano, Christopher J L Murray, Mohsen Naghavi
Journal: The Lancet (2018)

Political, economic, and epidemiological changes in Brazil have affected health and the health system. We used the Global Burden of Disease Study 2016 (GBD 2016) results to understand changing health patterns and inform policy responses.
Construction of a bilayered vascular graft with smooth internal surface for improved hemocompatibility and endothelial cell monolayer formation
Authors: Xianhao Dong, Xingyu Yuan, Lina Wang, Jinlong Liu, Adam C. Midgley, Zhihong Wang, Kai Wang, Jianfeng Liu, Meifeng Zhu, Deling Kong
Journal: Biomaterials (2018)