tbuckley/cabot-search huggingface dataset:
Endogenous retroviral signatures predict immunotherapy response in clear cell renal cell carcinoma
Authors: Christof C. Smith, Kathryn E. Beckermann, Dante S. Bortone, Aguirre A. De Cubas, Lisa M. Bixby, Samuel J. Lee, Anshuman Panda, Shridar Ganesan, Gyan Bhanot, Eric M. Wallen, Matthew I. Milowsky, William Y. Kim, W. Kimryn Rathmell, Ronald Swanstrom, Joel S. Parker, Jonathan S. Serody, Sara R. Selitsky, Benjamin G. Vincent
Journal: Journal of Clinical Investigation (2018)

Human endogenous retroviruses (hERVs) are remnants of exogenous retroviruses that have integrated into the genome throughout evolution. We developed a computational workflow, hervQuant, which identified more than 3,000 transcriptionally active hERVs within The Cancer Genome Atlas (TCGA) pan-cancer RNA-Seq database. hERV expression was associated with clinical prognosis in several tumor types, most significantly clear cell renal cell carcinoma (ccRCC). We explored two mechanisms by which hERV expression may influence the tumor immune microenvironment in ccRCC: (i) RIG-I–like signaling and (ii) retroviral antigen activation of adaptive immunity. We demonstrated the ability of hERV signatures associated with these immune mechanisms to predict patient survival in ccRCC, independent of clinical staging and molecular subtyping. We identified potential tumor-specific hERV epitopes with evidence of translational activity through the use of a ccRCC ribosome profiling (Ribo-Seq) dataset, validated their ability to bind HLA in vitro, and identified the presence of MHC tetramer–positive T cells against predicted epitopes. hERV sequences identified through this screening approach were significantly more highly expressed in ccRCC tumors responsive to treatment with programmed death receptor 1 (PD-1) inhibition. hervQuant provides insights into the role of hERVs within the tumor immune microenvironment, as well as evidence that hERV expression could serve as a biomarker for patient prognosis and response to immunotherapy.
A Case of Severe Intractable Contamination-Based Obsessive-Compulsive Disorder
Authors: Brian P. Brennan, Ryan J. Jacoby, Alik S. Widge
Journal: JAMA Psychiatry (2018)

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 Psychiatry 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 Psychiatry journal
Emerging roles of long non-coding RNAs in tumor metabolism
Authors: Hui Sun, Zhaohui Huang, Weiqi Sheng, Mi-die Xu
Journal: Journal of Hematology & Oncology (2018)

Compared with normal cells, tumor cells display distinct metabolic characteristics. Long non-coding RNAs (lncRNAs), a large class of regulatory RNA molecules with limited or no protein-coding capacity, play key roles in tumorigenesis and progression. Recent advances have revealed that lncRNAs play a vital role in cell metabolism by regulating the reprogramming of the metabolic pathways in cancer cells. LncRNAs could regulate various metabolic enzymes that integrate cell malignant transformation and metabolic reprogramming. In addition to the known functions of lncRNAs in regulating glycolysis and glucose homeostasis, recent studies also implicate lncRNAs in amino acid and lipid metabolism. These observations reveal the high complexity of the malignant metabolism. Elucidating the metabolic-related functions of lncRNAs will provide a better understanding of the regulatory mechanisms of metabolism and thus may provide insights for the clinical development of cancer diagnostics, prognostics and therapeutics.
Antithrombotic Therapy After Percutaneous Coronary Intervention in Atrial Fibrillation: The Triple Trouble
Authors: Massimo Leggio, Augusto Fusco, Paolo Severi, Mario Lombardi, Elisa Caldarone, Stefania D’Emidio, Massimo Armeni, Daniela Mereu, Maria Grazia Bendini, Andrea Mazza
Journal: Drugs (2018)
Abstract 17935: AL Cardiac Amyloidosis is Associated With Increased Heart Transplant Waitlist Mortality That Should Be Considered When Allocating Donor Hearts
Authors: Laura C Kobashigawa, Karla C Verkouw, Jerry D Estep, Mathew S Maurer, Mazen Hanna, Jignesh Patel, Ronald M Witteles, Mark Zucker, Teresa De Marco, Marc J Semigran, Van N Selby
Journal: Circulation (2016)

Introduction: A new United Network for Organ Sharing (UNOS) donor heart allocation scheme is being proposed. Previous studies found patients (pts) with cardiac amyloidosis (all amyloid types) do not have increased orthotopic heart transplant (OHT) waitlist mortality compared to pts listed for other cardiomyopathies. We assessed if waitlist mortality is higher in light-chain (AL) amyloid compared to transthyretin (TTR) amyloid and non-amyloid cardiomyopathies (N-ACM), as this may suggest an allocation priority for AL amyloid pts. Methods: Using the International Consortium for Cardiac Amyloid Transplantation (ICCAT) Registry, we analyzed cardiac amyloidosis pts listed for OHT from 1997 to 2015. The Fine-Gray model was used to compare waitlist mortality between AL and TTR pts, accounting for the competing risk of transplantation. To account for the introduction of proteasome inhibitors, the analysis was repeated with the cohort restricted to pts listed in 2008 or later. AL and TTR waitlist mortality was the...
Abstract 18343: B-type Natriuretic Peptide (BNP) Levels Correlate With Indices of Left Ventricular Function and Predict Outcomes Following Transcatheter Aortic Valve Implantation (TAVI): A Cardiovascular Magnetic Resonance Imaging Study
Authors: Alistair C Lindsay, Ritesh Kanyal, Paramvir Sawhney, Helen Broadhurst, Katie Harron, Raad Mohiaddin, Alison Duncan, Carlo Di Mario, Simon W Davies, Neil Moat
Journal: Circulation (2015)

Background: High levels of B-type natriuretic peptide (BNP) have been shown to predict outcomes following transcatheter aortic valve implantation (TAVI). However, the relationship between pre-procedural BNP levels and magnetic resonance imaging (MRI) parameters of cardiac function has not previously been described in patients with severe aortic stenosis undergoing TAVI. Methods: 108 patients underwent cardiac MRI and had measurements of BNP taken prior to TAVI. MRI was performed using a 1.5T scanner; steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Gadolinium enhancement was assessed after injection of 0.1 mmol/kg of gadolinium contrast agent. Semi-automated image analysis was performed by two specialist reviewers blinded to patient treatment. Results: The mean age of the population studied was 79 years (IQR 74-85); mean follow-up was 805 days (IQR 368-1025). The mean BNP level was 698 ng/l (range 14-6048); univariate linear regression showed significant relationships between BNP and left ventricular (LV) ejection fraction (p&lt;0.0001), end diastolic volume (p=0.001), end systolic volume (p&lt;0.0001), and indexed mass (p=0.012). Median BNP levels were lower in patients who survived than in those who died (287ng/l vs. 560ng/l; p=0.099); ROC curve analysis found a BNP level of &gt;170ng/l to be the optimal cutoff for the prediction of all-cause mortality. Survival curve analysis showed a significantly increased risk of all-cause mortality in patients with BNP&gt;170ng/l and MRI LV ejection fraction &lt;50% (Hazard ratio 5.72, p=0.015; Figure). Conclusions: In patients with severe aortic stenosis undergoing TAVI, BNP levels are closely correlated with LV function, indexed LV mass, and both end-systolic and end-diastolic volumes, as measured by MRI. Patients with BNP&gt;170ng/l and MRI LV ejection fraction&lt;50% are at significantly higher risk of death following TAVI.
Abstract 13483: Pathological Decline in Incretin Hormone Glucagon-like Peptide-1 Causes Cardiac Apoptosis and Dysfunction in Pressure-overloaded Heart Failure Through Cyclic AMP-dependent Mechanisms. -Distinct Role of Protein Kinase a and EPAC
Authors: Morihiko Aoyama, Yasuko K Bando, Haruya Kawase, Akio Monji, Toko Mitsui, Atsuya Shimizu, Toyoaki Murohara
Journal: Circulation (2014)

Introduction: Ample evidence demonstrates cardiovascular protection by incretin hormone glucagon-like peptide-1 (GLP-1) through the cyclic AMP axis. GLP-1 is known for its inotropic effect on heart, however, the role of GLP-1 in heart failure remains uncertain. Hypothesis: To explore the pathophysiological role of GLP-1 in heart failure Methods: Pressure overload-induced heart failure model was generated by transverse aortic constriction in mice (TAC). Results: At 4 week after the operation, TAC exhibited systolic left-ventricular dysfunction, myocardial hypertrophy and augmented apoptosis. Unexpectedly, circulating GLP-1 concentration was markedly decreased in TAC (in pM; 0.86±0.10 for TAC versus 2.13±0.54 for sham) with concomitant reduction of myocardial cyclic AMP concentration (in pmole/mg protein; 33.0±1.4 for TAC versus 42.2±1.5). TAC exhibited pathological changes in signaling molecules of myocardial contractility [SERCA, phospho-phospholamban(Serine16; pPL), β-myosin heavy chain (MYH7)], remodeling (Akt/mTOR/S6K), and cell death markers (procaspase-3/Bcl2 for apoptosis and PINK/PARKIN complex for mitophagy detecting damaged mitochondria). All of these changes observed in TAC heart were reversed selectively by treatment with GLP-1 analog exendin-4 (Ex4; 24nmole/kg/day for 4 weeks) and indirect supplement of GLP-1 by a DPP4 inhibitor alogliptin (ALO; 10mg/kg/day for 4 weeks). In vitro TUNEL assay using cultured cardiomyocytes revealed that Ex-4 reduced myocardial apoptosis in a cAMP/EPAC1-dependent but PKA-independent manner (Figure). Conclusions: Pressure-overloaded heart failure exhibits decline in GLP-1, leading to cAMP/EPAC1-dependent impairment in myocardial apoptosis, and cAMP/PKA/pPL/SERCA-dependent myocardial contractile dysfunction. Our data suggest the distinct role of PKA and EPAC in pathophysiology underlying heart failure.
Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non–Small-Cell Lung Cancer
Authors: Kathryn C. Arbour, Laura Mezquita, Niamh Long, Hira Rizvi, Edouard Auclin, Andy Ni, Gala Martínez-Bernal, Roberto Ferrara, W. Victoria Lai, Lizza E.L. Hendriks, Joshua K. Sabari, Caroline Caramella, Andrew J. Plodkowski, Darragh Halpenny, Jamie E. Chaft, David Planchard, Gregory J. Riely, Benjamin Besse, Matthew D. Hellmann
Journal: Journal of Clinical Oncology (2018)

Treatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroids may reduce efficacy of PD-(L)1 blockade. On-treatment corticosteroids for treatment of immune-related adverse events do not seem to affect efficacy, but the potential impact of baseline corticosteroids at the time of treatment initiation is unknown. Clinical trials typically excluded patients who received baseline corticosteroids, which led us to use real-world data to examine the effect of corticosteroids at treatment initiation.
Abstract 16042: Plasminogen Activator Inhibitor-1 Predicts the Risk of Hypertension in American Indians: Findings From the Strong Heart Study
Authors: Hao Peng, Fawn Yeh, Ying Zhang, Giovanni de Simone, Lyle G. Best, Elisa T. Lee, Barbara V. Howard, Jinying Zhao
Journal: Circulation (2016)

Background: Plasminogen activator inhibitor 1 (PAI-1) deficiency prevents hypertension and vascular fibrosis in animal models. A higher level of plasma PAI-1 was associated with hypertension in cro...
Raising NAD in Heart Failure
Authors: Matthew A. Walker, Rong Tian
Journal: Circulation (2018)

It has long been known that cellular NAD levels are a critical regulator of metabolism and bioenergetics.The intracellular NAD pool consists of both oxidized (NAD + ) and reduced forms (NADH).NAD + is the main hydride acceptor in intermediary metabolism.Electrons derived from substrate catabolism are carried by NADH and used for oxidative phosphorylation and biosynthetic reactions.These reduction-oxidation reactions are not only essential for mitochondrial function and cell metabolism but also serve as important modulators of cell signaling. 1,2NAD + functions as a cosubstrate for sirtuin deacylases, ADP-ribose transferases, and cyclic ADP-ribose synthases that govern posttranslational modification of proteins, DNA repair, and inflammatory responses. 2he cellular NAD + level is determined by the NAD(H) pool size (total NAD + and NADH concentration) as well as its reduction-oxidation state.The former is dependent on cellular NAD + consumption and regeneration, whereas the latter is regulated by cell metabolism and mitochondrial function (Figure).Emerging evidence suggests that derangements in the myocardial NAD pool are causally linked to metabolic remodeling and mitochondrial dysfunction in the failing heart.Stabilizing the intracellular NAD + level represents a promising therapeutic strategy to improve myocardial bioenergetics and cardiac function. 1,3,4In this issue of Circulation, Diguet et al 5 report exciting data suggesting that supplementation with a NAD + precursor, nicotinamide riboside (NR), reduces cardiac dysfunction in preclinical models of heart failure.In a genetic mouse model of dilated cardiomyopathy, induced by the deletion of serum response factor in the heart (SRF HKO ), Diguet et al 5 found that supplementation of NR in the diet significantly reduced left ventricular contractile dysfunction and chamber dilation.A similar, albeit moderate, effect was also observed in mice with pressure overload-induced hypertrophy and dysfunction.These observations are consistent with prior work demonstrating the beneficial effects of increasing NAD levels on cardiac hypertrophy and function in models of agonist-induced pathological hypertrophy, 6 chronic pressure overload, 7 and mitochondrial cardiomyopathy associated with Friedreich's ataxia. 7Therefore, this study adds support to the emerging concept of increasing NAD levels as a therapeutic strategy for heart failure.Despite the compelling evidence that expanding the intracellular NAD pool benefits the failing heart, the question of how it works remains not fully answered.8][9] Those studies suggested that protein hyperacetylation was attributable to impaired NAD + -dependent protein deacetylation by sirtuins, especially Sirt3, the mitochondria-localized sirtuin. 7,8The benefit
Heterogeneity of Epigenetic and Epithelial Mesenchymal Transition Marks in Hepatocellular Carcinoma with Keratin 19 Proficiency
Authors: Naosuke Yokomichi, Naoshi Nishida, Yuzo Umeda, Fumitaka Taniguchi, Kazuya Yasui, Toshiaki Toshima, Yoshiko Mori, Akihiro Nyuya, Takehiro Tanaka, Takeshi Yamada, Takahito Yagi, Toshiyoshi Fujiwara, Yoshiyuki Yamaguchi, Ajay Goel, Masatoshi Kudo, Takeshi Nagasaka
Journal: Liver Cancer (2018)

Keratin 19 (K19) expression is a potential predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). To clarify the feature of K19-proficient HCC, we traced epigenetic footprints in cultured cells and clinical materials.In vitro, KRT19 promoter methylation was analyzed and 5-aza-2'-deoxycytidine with trichostatin A (TSA) treatment was performed. Among 564 surgically resected HCCs, the clinicopathological relevance of K19-proficent HCCs was performed in comparison with hepatocytic (HepPar-1 and arginase-1), epithelial-mesenchymal transition (E-cadherin and vimentin), biliary differentiation-associated (K7 and NOTCH-1) markers, and epigenetic markers (KRT19 promoter/long interspersed nucleotide element-1 [LINE-1] methylation status).KRT19 promoter methylation was clearly associated with K19 deficiency and 5-aza-2'-deoxycytidine with TSA treatment-stimulated K19 re-expression, implicating DNA methylation as a potential epigenetic process for K19 expression. After excluding HCCs with recurrence, TNM stage as IIIB or greater, preoperative therapy, transplantation, and combined hepatocellular cholangiocarcinoma, we assessed 125 of 564 HCC cases. In this cohort, K19 expression was found in 29 HCCs (23.2%) and corresponded with poor survival following surgery (p = 0.025) and extrahepatic recurrence-free survival (p = 0.017). Compared with K19-deficient HCCs, lower KRT19 promoter methylation level was observed in K19-proficient HCCs (p < 0.0001). Conversely, HCC with genome-wide LINE-1 hypermethylation was frequently observed in K19-proficient HCCs (p = 0.0079). Additionally, K19 proficiency was associated with K7 proficiency (p = 0.043), and reduced E-cadherin and HepPar-1 expression (p = 0.043 and p < 0.0001, respectively).K19-proficient HCC exhibited poor prognosis owing to extrahepatic recurrence, with molecular signatures differing from those in conventional cancer stem cells, providing novel insights of the heterogeneity underlying tumor development.
Long-Term Mortality and Early Valve Dysfunction According to Anticoagulation Use
Authors: Pavel Overtchouk, Paul Guedeney, Stéphanie Rouanet, Jean Philippe Verhoye, Thierry Lefevre, Eric Van Belle, Helene Eltchaninoff, Martine Gilard, Pascal Leprince, Bernard Iung, Olivier Barthelemy, Hervé Le Breton, Géraud Souteyrand, Eric Vicaut, Gilles Montalescot, Jean-Philippe Collet
Journal: Journal of the American College of Cardiology (2018)
Hepatitis B virus genome recycling and de novo secondary infection events maintain stable cccDNA levels
Authors: Chunkyu Ko, Anindita Chakraborty, Wen-Min Chou, Julia Hasreiter, Jochen M. Wettengel, Daniela Stadler, Romina Bester, Theresa Asen, Ke Zhang, Karin Wisskirchen, Jane A. McKeating, Wang-Shick Ryu, Ulrike Protzer
Journal: Journal of Hepatology (2018)
Abstract 12837: Nondipper Pulse Rate Pattern is Associated With Cardiovascular Events, but Night Pulse Rate is Not: Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Yukako Ogoyama, Tomoyuki Kabutoya, Satoshi Hoshide, Keita Negishi, Kazuomi Kario
Journal: Circulation (2015)

Introduction: Nondipper patterns of pulse rate (PR) as well as blood pressure (BP) have been associated with cardiovascular events. High night PR is also associated cardiovascular events. Hypothesis: We assessed the hypothesis that a nondipper PR pattern was independently associated with cardiovascular events in patients with cardiovascular risk factors, adjusting for night pulse rate. Methods: Ambulatory BP monitoring was conducted at baseline in 1443 patients who had one or more cardiovascular risk factors. PR nondipping status was defined as (awake PR - sleep PR)/awake PR &lt; 0.1. Results: The nondipper PR patients (N=339) were older (66.8±10.6 vs. 63.9±11.8, p&lt;0.001) and had a higher night PR (65.5±9.6 vs. 58.9±7.3/min, p&lt;0.001) than the dipper PR patients (N=1104). The mean follow-up period was 60±30 months; in that time 50 patients (4.5%) in the dipper PR group and 34 patients (10.0%) in the nondipper PR group suffered primary endpoints (log rank 22.2, p&lt;0.001). On the Cox proportional hazards model including age, gender and night systolic blood pressure, nondipper PR was an independent predictor of cardiovascular event (hazard ratio 2.38, 95% confidence interval 1.51-3.74, p&lt;0.001), but night PR was not (p=0.50). We analyzed four groups according to BP and PR dipping status, the combination of nondipper BP and nondipper PR constituted a higher risk of cardiovascular events and stroke than the sum of the other three combination risks (Log rank= 39.2, p&lt;0.001, figure). When we added the nondipper BP pattern in the model, nondipper PR remained an independent predictor of cardiovascular events (hazard ratio 2.29, 95% confidence interval 1.50-3.51, p&lt;0.001). After excluding patients who took beta blockers (N=1003), nondipper PR was an independent predictor of cardiovascular events (hazard ratio 2.16, 95% confidence interval 1.22-3.82, p=0.008). Conclusions: The nondipper PR pattern was associated with cardiovascular events, but night pulse rate was not.
Abstract 12651: Medication Adherence Mediates the Relationship Between Heart Failure Symptoms and Cardiac Event-Free Survival in Patients With Heart Failure
Authors: Jia-rong Wu, Debra K Moser
Journal: Circulation (2015)

Background: Heart failure (HF) symptoms such as dyspnea and ankle swelling are common and may precipitate hospitalization. Poor medication adherence is presumed to be associated with symptom exacerbations and hospitalization, yet how HF symptoms, medication adherence, and hospitalization are related remain unclear. Objective: The purpose of this study was to explore the relationships among HF symptoms, medication adherence, and cardiac event-free survival in patients with HF. Methods: We enrolled 219 patients with HF (male 65%, age 60±12). Patients’ demographic and clinical data were collected at baseline. Medication adherence was monitored using the Medication Event Monitoring System. HF symptoms were assessed using the Self-Care of Heart Failure Index. Patients were followed for up to 3 1/2 years to collect outcome data. Cardiac events (cardiac rehospitalization and mortality) were obtained by patient/family interview and hospital database review. Linear regression and survival analyses were used for data analyses. Results: HF patients who reported dyspnea or ankle swelling were more likely to have poor medication adherence (p = .05). Poor medication adherence was associated with worse cardiac event-free survival (p =.006). In Cox regression, patients with HF symptoms had 2 times greater risk for a cardiac event than patients without HF symptoms (p = .042). HF symptom was not a significant predictor of cardiac event-free survival after entering medication adherence in the model (p = .091), indicating mediation of the relationship between HF symptoms and outcomes by medication adherence (Figure). Conclusion: Medication adherence mediated the relationship between HF symptoms and cardiac event-free survival in this sample. It is important to develop interventions to improve medication adherence to reduce HF symptoms and high hospitalization and mortality rates in patients with HF.