tbuckley/cabot-search huggingface dataset:
Abstract 17214: Differential Relationships Between Serum Cholesterol Efflux Capacities Measured From Three Cell Models and Coronary Artery Disease Status in the Montreal Heart Institute Biobank
Authors: David Rhainds, Low-Kam Cecile, Boulé Marie, Alem Sonia, Mongrain Ian, Dubé Marie-Pierre, Lettre Guillaume, Tardif Jean-Claude
Journal: Circulation (2015)

Recent clinical trials and Mendelian randomization studies suggest that raising HDL-cholesterol (HDL-C) concentration by itself is insufficient to lower cardiovascular (CV) risk, despite the established inverse relationship between HDL-C and cardiovascular risk. CV protection may derive from other characteristics of HDL. Such characteristics include the cholesterol efflux capacity of serum, the process by which HDL particles accept cholesterol from macrophages and other cell types. Recently, higher cholesterol efflux capacity was inversely associated with incident CV events over a &gt;9 year period of follow-up, with a 67% risk reduction in the highest quartile of efflux. In our study, cholesterol efflux capacity was measured for 2000 patients from the Montreal Heart Institute Biobank as the ratio of pooled control serum. When comparing unadjusted cholesterol efflux values between 1000 controls and 1000 cases with previous myocardial infarction (MI), we observed significant decreases of efflux capacity in cases with J774 macrophages in basal and cAMP-stimulated conditions, with human HepG2 hepatocytes and with BHK cells expressing human ABCA1. In regression models of MI status against efflux variables, also adjusted for age, sex, HDL-C, triglycerides and statin use, the reduction in cholesterol efflux capacity in cases vs. controls remained highly significant for J774 cells in basal (p value = 5.8x10-11) and cAMP-stimulated conditions (p = 5.3x10-8), while the difference was lost with HepG2 cells (p=0.16) and was reversed for ABCA1-dependent efflux using BHK-ABCA1 cells (p=5.9x10-4). Thus, the relationship of cholesterol efflux capacity of serum HDL and cardiovascular status is heterogeneous, which suggest that the repertoire of cholesterol transporters expressed in cells and samples characteristics, such as the HDL proteome and lipidome, interact in a unique manner for each cell type. Future work will consist in identifying sources of such differences at the molecular level.
The Variety of Cardiovascular Presentations of COVID-19
Authors: Justin A. Fried, Kumudha Ramasubbu, Reema Bhatt, Veli K. Topkara, Kevin J. Clerkin, Evelyn Horn, LeRoy Rabbani, Daniel Brodie, Sneha S. Jain, Ajay J. Kirtane, Amirali Masoumi, Koji Takeda, Deepa Kumaraiah, Daniel Burkhoff, Martin Leon, Allan Schwartz, Nir Uriel, Gabriel Sayer
Journal: Circulation (2020)

Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs Uriel and Sayer), who respond to the information and share their reasoning with the reader (regular type
Cardiac Resynchronization Therapy for Chemotherapy-Induced Cardiomyopathy
Authors: Arielle M. Schwartz, Stacy Westerman, Anant Mandawat
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Database Inaccuracies and Disparities in Care Among Homeless Adults Hospitalized for Cardiovascular Conditions
Authors: Utibe R. Essien, Dereck W. Paul, Margot Kushel
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Leveraging biological and statistical covariates improves the detection power in epigenome-wide association testing
Authors: Jinyan Huang, Ling Bai, Bowen Cui, Liang Wu, Liwen Wang, Zhiyin An, Shulin Ruan, Yue Yu, Xianyang Zhang, Jun Chen
Journal: Genome biology (2020)

Abstract Background Epigenome-wide association studies (EWAS), which seek the association between epigenetic marks and an outcome or exposure, involve multiple hypothesis testing. False discovery rate (FDR) control has been widely used for multiple testing correction. However, traditional FDR control methods do not use auxiliary covariates, and they could be less powerful if the covariates could inform the likelihood of the null hypothesis. Recently, many covariate-adaptive FDR control methods have been developed, but application of these methods to EWAS data has not yet been explored. It is not clear whether these methods can significantly improve detection power, and if so, which covariates are more relevant for EWAS data. Results In this study, we evaluate the performance of five covariate-adaptive FDR control methods with EWAS-related covariates using simulated as well as real EWAS datasets. We develop an omnibus test to assess the informativeness of the covariates. We find that statistical covariates are generally more informative than biological covariates, and the covariates of methylation mean and variance are almost universally informative. In contrast, the informativeness of biological covariates depends on specific datasets. We show that the independent hypothesis weighting (IHW) and covariate adaptive multiple testing (CAMT) method are overall more powerful, especially for sparse signals, and could improve the detection power by a median of 25% and 68% on real datasets, compared to the ST procedure. We further validate the findings in various biological contexts. Conclusions Covariate-adaptive FDR control methods with informative covariates can significantly increase the detection power for EWAS. For sparse signals, IHW and CAMT are recommended.
Which features of thin melanomas make them more likely to cause death
Authors: M. Claeson, P. Baade, S. Brown, H.P. Soyer, B.M. Smithers, A.C. Green, D.C. Whiteman, K. Khosrotehrani
Journal: British Journal of Dermatology (2020)

Skin cancer is the most common cancer in Western populations. Melanoma is the most dangerous form of the disease. Melanoma tends to grow in ‘thickness’ (depth of invasion into the skin) if left untreated, and thicker tumours are considered more advanced and harder to treat than thinner tumours. However, around one quarter of all deaths from melanoma in Queensland, Australia are caused by thin tumours, invading the skin's surface to a thickness of 1mm or less (≤1.00 mm). This study aimed to find factors that, at diagnosis, can identify patients who will eventually die from thin melanoma. Data from the Queensland Cancer Registry were analysed to compare the characteristics of 424 thin melanomas that caused the patient to die to 1,189 thin melanomas that did not lead to death. Thin melanomas located on the scalp were six times more likely to cause the patient's death, when they were compared to thin melanomas on the back. Also, the thicker of the thin melanomas, which penetrated the skin to 0.80‐1.00 mm thickness, were six times as likely to cause death, when compared to minimally invasive (thinner) tumours with a thickness of less than 0.30mm. This study showed that where on the body the tumour occurs, and increasing thickness, could identify the more dangerous tumours among the thin melanomas, at diagnosis. Patients with melanomas with these characteristics may need closer follow‐up after diagnosis and treatment. This is a summary of the study: Clinicopathological factors associated with death from thin (≤ 1.00 mm) melanoma
Vascular permeability in the fibrotic lung
Authors: Clemens K. Probst, Sydney B. Montesi, Benjamin D. Medoff, Barry S. Shea, Rachel S. Knipe
Journal: European Respiratory Journal (2020)

Idiopathic pulmonary fibrosis (IPF) is thought to result from aberrant tissue repair processes in response to chronic or repetitive lung injury. The origin and nature of the injury, as well as its cellular and molecular targets, are likely heterogeneous, which complicates accurate pre-clinical modelling of the disease and makes therapeutic targeting a challenge. Efforts are underway to identify central pathways in fibrogenesis which may allow targeting of aberrant repair processes regardless of the initial injury stimulus. Dysregulated endothelial permeability and vascular leak have long been studied for their role in acute lung injury and repair. Evidence that these processes are of importance to the pathogenesis of fibrotic lung disease is growing. Endothelial permeability is increased in non-fibrosing lung diseases, but it resolves in a self-limited fashion in conditions such as bacterial pneumonia and acute respiratory distress syndrome. In progressive fibrosing diseases such as IPF, permeability appears to persist, however, and may also predict mortality. In this hypothesis-generating review, we summarise available data on the role of endothelial permeability in IPF and focus on the deleterious consequences of sustained endothelial hyperpermeability in response to and during pulmonary inflammation and fibrosis. We propose that persistent permeability and vascular leak in the lung have the potential to establish and amplify the pro-fibrotic environment. Therapeutic interventions aimed at recognising and "plugging" the leak may therefore be of significant benefit for preventing the transition from lung injury to fibrosis and should be areas for future research.
Abstract 10472: Metabolomic Correlates of Longevity in the Community
Authors: Susan Cheng, Martin Larson, Elizabeth McCabe, Joanne Murabito, Eugene Rhee, Jennifer Ho, Paul Jacques, Anahita Ghorbani, Martin Magnusson, Amanda Souza, Amy Deik, Kerry Pierce, Kevin Bullock, Christopher O’Donnell, Olle Melander, Clary Clish, Ramachandran Vasan, Robert Gerszten, Thomas Wang
Journal: Circulation (2013)

BACKGROUND: Alterations in metabolism are hypothesized to influence lifespan as well as cardiovascular health, but data in humans are scant. METHODS: We used liquid chromatography/mass spectrometry...
Current status of liver transplantation in Latin America
Authors: Alan G. Contreras, Lucas McCormack, Wellington Andraus, Eduardo de Souza M Fernandes, Alan G. Contreras, Lucas McCormack, Wellington Andraus, Eduardo de Souza M. Fernandes, Alejandro Serrablo Requejo, Nicolás Jarufe, Martin Dib, Felix Carrasco, Martin Harguindeguy, Jose Pablo Garbanzo, Frans Serpa, Alejandro Gimenez, Ricardo Villaroel, Alonso Vera
Journal: International Journal of Surgery (2020)
Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations
Authors: Jason Phua, Li Weng, Lowell Ling, Moritoki Egi, Chae-Man Lim, Jigeeshu Vasishtha Divatia, Babu Raja Shrestha, Yaseen M Arabi, Jensen Ng, Charles D Gomersall, Masaji Nishimura, Younsuck Koh, Bin Du
Journal: The Lancet Respiratory Medicine (2020)

As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.
Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy
Authors: Daniel R. Principe, Matthew Narbutis, Sandeep Kumar, Alex Park, Navin Viswakarma, Matthew J. Dorman, Suneel D. Kamath, Paul J. Grippo, Melissa L. Fishel, Rosa F. Hwang, Dinesh Thummuri, Patrick W. Underwood, Hidayatullah G. Munshi, Jose G. Trevino, Ajay Rana
Journal: Cancer Research (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death with a median survival time of 6–12 months. Most patients present with disseminated disease and the majority are offered palliative chemotherapy. With no approved treatment modalities for patients who progress on chemotherapy, we explored the effects of long-term gemcitabine administration on the tumor microenvironment to identify potential therapeutic options for chemorefractory PDAC. Using a combination of mouse models, primary cell line–derived xenografts, and established tumor cell lines, we first evaluated chemotherapy-induced alterations in the tumor secretome and immune surface proteins by high throughput proteomic arrays. In addition to enhancing antigen presentation and immune checkpoint expression, gemcitabine consistently increased the synthesis of CCL/CXCL chemokines and TGFβ-associated signals. These secreted factors altered the composition of the tumor stroma, conferring gemcitabine resistance to cancer-associated fibroblasts in vitro and further enhancing TGFβ1 biosynthesis. Combined gemcitabine and anti-PD-1 treatment in transgenic models of murine PDAC failed to alter disease course unless mice also underwent genetic or pharmacologic ablation of TGFβ signaling. In the setting of TGFβ signaling deficiency, gemcitabine and anti-PD-1 led to a robust CD8+ T-cell response and decrease in tumor burden, markedly enhancing overall survival. These results suggest that gemcitabine successfully primes PDAC tumors for immune checkpoint inhibition by enhancing antigen presentation only following disruption of the immunosuppressive cytokine barrier. Given the current lack of third-line treatment options, this approach warrants consideration in the clinical management of gemcitabine-refractory PDAC. Significance: These data suggest that long-term treatment with gemcitabine leads to extensive reprogramming of the pancreatic tumor microenvironment and that patients who progress on gemcitabine-based regimens may benefit from multidrug immunotherapy. See related commentary by Carpenter et al., p. 3070
DDB1 E3 ligase controls dietary fructose-induced ChREBPα stabilization and liver steatosis via CRY1
Authors: Xin Tong, Deqiang Zhang, Omar Shabandri, Joon Oh, Ethan Jin, Kenneth Stamper, Meichan Yang, Zifeng Zhao, Lei Yin
Journal: Metabolism (2020)

Fructose over-consumption contributes to the development of liver steatosis in part by stimulating ChREBPα-driven de novo lipogenesis. However, the mechanisms by which fructose activates ChREBP pathway remain largely undefined. Here we performed affinity purification of ChREBPα followed by mass spectrometry and identified DDB1 as a novel interaction protein of ChREBPα in the presence of fructose. Depletion and overexpression of Ddb1 showed opposite effects on the ChREBPα stability in hepatocytes. We next tested the impact of hepatic Ddb1 deficiency on the fructose-induced ChREBP pathway. After 3-week high-fructose diet feeding, both Ddb1 liver-specific knockout and AAV-TBG-Cre-injected Ddb1flox/flox mice showed significantly reduced ChREBPα, lipogenic enzymes, as well as triglycerides in the liver. Mechanistically, DDB1 stabilizes ChREBPα through CRY1, a known ubiquitination target of DDB1 E3 ligase. Finally, overexpression of a degradation-resistant CRY1 mutant (CRY1-585KA) reduces ChREBPα and its target genes in the mouse liver following high-fructose diet feeding. Our data revealed DDB1 as an intracellular sensor of fructose intake to promote hepatic de novo lipogenesis and liver steatosis by stabilizing ChREBPα in a CRY1-dependent manner.
Biosimilar Uptake in Academic and Veterans Health Administration Settings: Influence of Institutional Incentives
Authors: Joshua F. Baker, Charles E. Leonard, Vincent Lo Re, Michael H. Weisman, Michael D. George, Jonathan Kay
Journal: Arthritis & Rheumatology (2020)

To compare uptake in the ordering of biosimilars at a Veterans Affairs Medical Center (VAMC) to that at an academic medical center, where institutional incentives for infused medications differ.We performed a cross-sectional study of medical record data and estimated institutional financial incentives at 2 medical centers in Philadelphia: 1) the University of Pennsylvania Health System (UPHS), and 2) the local VAMC. All ordering events for filgrastim or infliximab products were quantified over time and stratified according to product (biosimilar versus reference product) and center. Financial incentives to the institutions over time were determined based on actual drug costs for the VAMC and average sales prices (ASPs) and Medicare Part B reimbursement rates for UPHS.There were 15,761 infusions of infliximab at UPHS, of which 99% were for the reference product. There was a sharper decline in the use of reference products at the VAMC; 62% of the 446 infliximab infusions ordered at the VAMC were for the reference product. ASPs were consistently lower for biosimilar infliximab products, but the estimated institutional financial incentives remained similar over time for biosimilar and reference infliximab at UPHS. At the VAMC, the costs for 100-mg vials of reference infliximab and infliximab-abda were $623.48 and $115.58, respectively: a $507.90 (81%) savings per vial.The uptake of infliximab biosimilars has been slow at an academic medical center compared to a nearby VAMC, where financial savings are realized by the institution from its use. Slow adoption of biosimilar medications may impact the rates of decline in costs.
Bacterial CagA protein compromises tumor suppressor mechanisms in gastric epithelial cells
Authors: Manikandan Palrasu, Elena Zaika, Wael El-Rifai, Monica Garcia-Buitrago, Maria Blanca Piazuelo, Keith T. Wilson, Richard M. Peek, Alexander I. Zaika
Journal: Journal of Clinical Investigation (2020)

Approximately half of the world’s population is infected with the stomach pathogen Helicobacter pylori. Infection with H. pylori is the main risk factor for distal gastric cancer. Bacterial virulence factors, such as the oncoprotein CagA, augment cancer risk. Yet despite high infection rates, only a fraction of H. pylori–infected individuals develop gastric cancer. This raises the question of defining the specific host and bacterial factors responsible for gastric tumorigenesis. To investigate the tumorigenic determinants, we analyzed gastric tissues from human subjects and animals infected with H. pylori bacteria harboring different CagA status. For laboratory studies, well-defined H. pylori strain B128 and its cancerogenic derivative strain 7.13, as well as various bacterial isogenic mutants were employed. We found that H. pylori compromises key tumor suppressor mechanisms: the host stress and apoptotic responses. Our studies showed that CagA induces phosphorylation of XIAP E3 ubiquitin ligase, which enhances ubiquitination and proteasomal degradation of the host proapoptotic factor Siva1. This process is mediated by the PI3K/Akt pathway. Inhibition of Siva1 by H. pylori increases survival of human cells with damaged DNA. It occurs in a strain-specific manner and is associated with the ability to induce gastric tumor.
Abstract 249: The Costs and Acute Outcomes Following Pulmonary Vein Isolation for Atrial Fibrillation in Elderly Patients a Comparison Between Cryoballoon and Radiofrequency Ablation
Authors: Chao-Feng Chen
Journal: Circulation (2019)

Backgroup: Limited comparative data exist regarding catheter ablation (CA) of atrial fibrillation (AF) using second-generation cryoballoon (CB-2) ablation versus radiofrequency (RF) ablation in elderly patients (&gt;75 years ). This study aims to compare the costs and periprocedural outcomes in elderly patients using these two strategies. Methods: Elderly patients (&gt;75years) with symptomatic drug-refractory AF were included in the study. Pulmonary vein isolation (PVI) was performed in all patients by CB or RF. The costs and periprocedural outcomes of the two strategies are compared using SPSS 22. Results: 324 elderly patients with symptomatic drug-refractory paroxysmal/short-lasting persistent AF received PVI using RF (n=176) and CB-2 (n=148) from September 2016 to April 2019. The CB-2 was associated with shorter procedure duration and left atrial dwell time (128.9±18.3 vs. 152.8±18.9 minutes, P&lt;0.001; 89.4±18.4 vs. 101.9± 22.2minutes, P &lt;0.001), but greater fluoroscopy utilization (24.3±10.9 vs. 19.2±7.5 minutes, P &lt;0.001). Periprocedural complications occurred in 3.4% (CB-2) and 9.1% (RF) of patients (P=0.037). There was no significant difference between 2 groups for AF/atrial tachycardia (AT) recurrence until discharge (16.2 vs. 18.7%, P = 0.552). The length of stay after ablation was shorter, but the costs were greater in the CB-2 group ( P &lt;0.001). Conclusions: Both CB-2 and RF ablation appear to be safe and effective for AF in elderly patients (&gt;75 years). In addition, CB-2 is associated with shorter procedure time, left atrial dwell time, and length of stay after ablation, as well as lower complication rates, but its costs and fluoroscopy time are greater than those of the RF group.