tbuckley/cabot-search huggingface dataset:
Abstract 13490: Cardiac Progenitor Cell Therapy in Right Heart Failure With Preserved Ejection Fraction
Authors: Daiki Ousaka, Takuya Goto, Shuta Ishigami, Toshikazu Sano, Kenta Hirai, Shinichi Ohtsuki, Shingo Kasahara, Shunji Sano, Hidemasa Oh
Journal: Circulation (2016)

Background: Hear failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by normal EF with abnormal relaxation. Although the significance of HFpEF in right ventricle (RV) remains elusive as well as cell therapy responses in HFpEF patients with single ventricular heart diseases (SHD) have not yet clarified. Purpose: We investigated the underlying mechanisms and potential benefits of cardiosphere-derived cell (CDC) therapy in HFpEF includes rat models and human SHD. Methods: Pulmonary artery banding (PAB) was created in rats for 4 weeks as RV failure models. In human study, 40 patients, aged 2.2±1.4 years, 91% diagnosed as RV type SHD, were analyzed. Both rat and human studies were defined as follows (HFpEF; EF≧40%, HFrEF; EF&lt;40%), and intracoronary CDC infusion responses were assessed. Results: Rats received PAB showed RV dysfunction with significant cardiac fibrosis those were addressed by increased expression of heart failure or fibrosis related genes in both HFpEF and HFrEF rats rather than controls. CDC infusion led to marked increase in EF in rats with HFrEF but not HFpEF. Although CDC infusion did not augment EF in HFpEF, this treatment significantly decreased interstitial fibrosis and improved myocardial elastance in both HFpEF and HFrEF compared with baseline. Furthermore, CDC treatment markedly reduced Col1, Col3, NPPA and MMP2 expressions in both groups, whereas inflammatory cytokine such as Ccl2 and IL6 decreased only in HFrEF. Notably, CDC infusion did not affect the expression of MMP9, TIMP1 and TIMP2 in both groups. In human study, there was no difference in the incidence of late gadolinium enhancement detected by cMRI in two groups (20% in HFrEF and 15% in HFpEF); however, HFrEF but not HFpEF patients demonstrated a marked improvement in EF and reduced ventricular volumes and mass one year after CDC infusion. In contrast, the beneficial effects of CDC therapy could be observed by improved myocardial strain, elastance, and diastolic function in both groups. Conclusions: Our translational and clinical research of HFpEF in RV suggests that CDC infusion may have significant impact on diastolic relaxation and myocardial stiffening improvements to reverse ventricular fibrosis and remodeling leading to RV failure.
Inhibition of Casein Kinase 2 Disrupts Differentiation of Myeloid Cells in Cancer and Enhances the Efficacy of Immunotherapy in Mice
Authors: Ayumi Hashimoto, Chan Gao, Jerome Mastio, Andrew Kossenkov, Scott I. Abrams, Ashok V. Purandare, Heshani Desilva, Susan Wee, John Hunt, Maria Jure-Kunkel, Dmitry I. Gabrilovich
Journal: Cancer Research (2018)

The role of myeloid cells as regulators of tumor progression that significantly impact the efficacy of cancer immunotherapies makes them an attractive target for inhibition. Here we explore the effect of a novel, potent, and selective inhibitor of serine/threonine protein kinase casein kinase 2 (CK2) on modulating myeloid cells in the tumor microenvironment. Although inhibition of CK2 caused only a modest effect on dendritic cells in tumor-bearing mice, it substantially reduced the amount of polymorphonuclear myeloid-derived suppressor cells and tumor-associated macrophages. This effect was not caused by the induction of apoptosis, but rather by a block of differentiation. Our results implicated downregulation of CCAAT-enhancer binding protein-α in this effect. Although CK2 inhibition did not directly affect tumor cells, it dramatically enhanced the antitumor activity of immune checkpoint receptor blockade using anti-CTLA-4 antibody. These results suggest a potential role of CK2 inhibitors in combination therapies against cancer.Significance: These findings demonstrate the modulatory effects of casein kinase 2 inhibitors on myeloid cell differentiation in the tumor microenvironment, which subsequently synergize with the antitumor effects of checkpoint inhibitor CTLA4. Cancer Res; 78(19); 5644-55. ©2018 AACR.
Comment on Bril et al. Clinical and Histologic Characterization of Nonalcoholic Steatohepatitis in African American Patients. Diabetes Care 2018;41:187–192
Authors: Brian L. Pearlman, Andrew Hinds, Alexandra-Elise Zakaud Dakaud
Journal: Diabetes Care (2018)

We read with interest the article by Bril et al. (1). We commend the authors for undertaking this comparative study between Caucasians and African Americans using histologic analysis in an attempt to elucidate racial differences in nonalcoholic fatty liver disease (NAFLD). However, we are not convinced that the authors’ conclusion that nonalcoholic steatohepatitis (NASH) “occurs as frequently, and as severe[ly]” in African Americans as it does in non-Hispanic whites is definitive.

We agree …
The role of HLA-A*33:01 in patients with cholestatic hepatitis attributed to terbinafine
Authors: Robert John Fontana, Elizabeth Theresa Cirulli, Jiezhun Gu, David Kleiner, David Ostrov, Elizabeth Phillips, Ryan Schutte, Huiman Barnhart, Naga Chalasani, Paul Brent Watkins, Jay H. Hoofnagle
Journal: Journal of Hepatology (2018)
Abstract 12498: Antihypertensive Medication Use and Blood Pressure Control Among 384000 Chinese Adults: Pilot Results From the China PEACE Million Persons Project
Authors: Yuan Lu, Jiapeng Lu, Xiuyuan Cheng, Lin Mu, Xiaochen Wang, Xinyue Li, George Linderman, Haibo Zhang, Hongyu Zhao, Erica Spatz, Chaoqun Wu, Meng Su, Jiamin Liu, John Spertus, Frederick Masoudi, Harlan Krumholz, Lixin Jiang
Journal: Circulation (2016)

Introduction: While high blood pressure (BP) is a leading risk factor for cardiovascular diseases, little is known about the current status of treatment and BP control in China. This study aims to characterize the patterns of antihypertensive medication use and BP control in a recent Chinese national screening project. Methods: During the pilot phase of the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project, 384,234 adults aged 40-75 years were enrolled from the general population in four provinces in China between 2014-2015. We describe the prevalence, awareness, treatment, and control of hypertension in the study population, assess antihypertensive medication use, and characterize patients with uncontrolled hypertension using multivariate regression models. Hypertension was defined as BP ≥140/90mmHg, current antihypertensive medication use, or prior hypertension diagnosis. Awareness and control were defined as self-reported prior diagnosis and BP&lt;140/90 mmHg, respectively, among those with hypertension. Results: The prevalence of hypertension in middle-aged Chinese adults was 43.7%; the awareness, treatment, and control of hypertension were 38.6%, 28.2%, and 8.2% (Figure). Among patients receiving antihypertensive medication, 85.5% used one medication and 13.5% used two. Calcium channel blockers (CCB) were most commonly used (56.1%), followed by angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) (19.6%); CCB plus ACEI/ARB was the most commonly used combination therapy regimen (7.6%). Men, lower income, less education, and obesity were associated with uncontrolled hypertension (all p values&lt;0.05). Conclusions: Awareness, treatment, and control of hypertension were low in middle-aged Chinese adults, far lower than those in the United States. Improving BP control in China will likely require improving diagnosis and more aggressive treatment.
Human Autoantibodies against the AMPA Receptor Subunit GluA2 Induce Receptor Reorganization and Memory Dysfunction
Authors: Holger Haselmann, Francesco Mannara, Christian Werner, Jesús Planagumà, Federico Miguez-Cabello, Lars Schmidl, Benedikt Grünewald, Mar Petit-Pedrol, Knut Kirmse, Joseph Classen, Fatih Demir, Nikolaj Klöcker, David Soto, Sören Doose, Josep Dalmau, Stefan Hallermann, Christian Geis
Journal: Neuron (2018)
Mechanisms Underlying Muscle Protein Imbalance Induced by Alcohol
Authors: Scot R. Kimball, Charles H. Lang
Journal: Annual Review of Nutrition (2018)

Both acute intoxication and longer-term cumulative ingestion of alcohol negatively impact the metabolic phenotype of both skeletal and cardiac muscle, independent of overt protein calorie malnutrition, resulting in loss of skeletal muscle strength and cardiac contractility. In large part, these alcohol-induced changes are mediated by a decrease in protein synthesis that in turn is governed by impaired activity of a protein kinase, the mechanistic target of rapamycin (mTOR). Herein, we summarize recent advances in understanding mTOR signal transduction, similarities and differences between the effects of alcohol on this central metabolic controller in skeletal muscle and in the heart, and the effects of acute versus chronic alcohol intake. While alcohol-induced alterations in global proteolysis via activation of the ubiquitin-proteasome pathway are equivocal, emerging data suggest alcohol increases autophagy in muscle. Further studies are necessary to define the relative contributions of these bidirectional changes in protein synthesis and autophagy in the etiology of alcoholic myopathy in skeletal muscle and the heart.
Agreed: The Harm Principle Cannot Replace the Best Interest Standard … but the Best Interest Standard Cannot Replace The Harm Principle Either
Authors: D. Micah Hester, Kellie R. Lang, Nanibaa' A Garrison, Douglas S. Diekema
Journal: The American Journal of Bioethics (2018)

In Bester’s article (2018) challenging the use of the harm principle and advocating sole reliance on the use of a best interest standard (BIS) in pediatric decision-making, we believe that the auth...
Structuring Research to Address Discrimination as a Factor in Child and Adolescent Health
Authors: Nia Heard-Garris, David R. Williams, Matthew Davis
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Prognostic Significance of Hypoalbuminemia in Patients with Relapsed/Refractory Hodgkin’s Lymphoma (R/R-HL) Undergoing Salvage Autologous Bone Marrow/Peripheral Stem Cell Transplantation (auto-BM/PSCT).
Authors: Kiarash Kojouri, Christian El-Khoury, Shubham Pant, Nancy Kohrt, George B. Selby, Howard Ozer, Rammurti Kamble, Mohamed A. Kharfan-Dabaja
Journal: Blood (2004)
Case 26-2018: A 48-Year-Old Man with Fever, Chills, Myalgias, and Rash
Authors: Sarah E. Turbett, William G. Tsiaras, Shaunagh McDermott, George Eng
Journal: New England Journal of Medicine (2018)

A 48-year-old man presented with fever, chills, myalgias, and diarrhea. On evaluation, he had generalized lymphadenopathy, hepatosplenomegaly, diffuse rash, and moderate eosinophilia. Diagnostic test results were received.
Abstract 19554: Lipoprotein(a) and Risk of Ischemic Stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Kristine S Alexander, Neil A Zakai, Fred Unverzagt, Virginia Wadley, Brett M Kissela, Suzanne E Judd, Stephen Glasser, Mary Cushman
Journal: Circulation (2015)

Background: Increased lipoprotein (a) (Lp(a)) is associated with coronary risk, but links with stroke have been less consistent. Blacks have 2-4-fold higher Lp(a) levels than whites, and have higher stroke incidence than whites, but have been under-represented in studies of Lp(a) and stroke to date. Hypothesis: Lp(a) is a risk factor for ischemic stroke, and this risk differs by race. Methods: REGARDS recruited 30,239 black and white U.S. men and women in 2003-7 to study regional and racial differences in stroke mortality. We measured Lp(a) by immunonepholometric assay in 572 cases of incident ischemic stroke and a 1,104-person cohort random sample. The hazard ratio of stroke by baseline Lp(a) was calculated using Cox proportional hazards models, stratified by race. Lp(a) was modeled both as a continuous variable (per sex- and race-specific SD) and in sex- and race-specific quartiles, given known differences in distributions by race and sex. Results: As shown in the Figure, being in the 4 th vs 1 st Lp(a) quartile was associated with ischemic stroke in black but not white participants, adjusted for age and sex (Model 1). The HRs were essentially unchanged with added adjustment for stroke risk factors (Model 2). There was no significant association between Lp(a) as a continuous variable and stroke, though race-specific patterns were similar. There remained no association between Lp(a) and stroke in whites when we used the sex- and race-specific 90 th percentile as a cut-off (HR: 0.91 95% CI: 0.52, 1.60). Discussion: Lp(a) was associated with ischemic stroke risk in black but not white REGARDS participants, this might partly explain the black/white disparity in stroke. Further studies in racially diverse groups are necessary to confirm these findings. Figure 1. Hazard ratios for Lp(a) and stroke in blacks and whites, per quartile (compared with first quartile) and SD.
Comparing Adjuvant vs Early-Salvage Radiotherapy After Radical Prostatectomy
Authors: Firas Abdollah, Deepansh Dalela, Mani Menon
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Abstract 11735: Periprocedural Cerebral Ischemic Events With TAVI Performed Without Prior Balloon Dilatation of the Aortic Valve: A Randomized Prospective Study
Authors: Florence Leclercq, Jessica Labour, Nicolas Menjot de Champfleur, Jean Christophe Macia, Benoit Lattuca, Laurent Schmutz, Richard Gervasoni, Audrey Agullo, Helene Vernhet, Guillaume Cayla
Journal: Circulation (2015)

Introduction: Balloon aortic valvuloplasty (BAV) is considered as an essential part of Transcatheter Aortic Valve Implantation (TAVI) procedure, but cerebral embolization may occur during this step. Hypothesis: We assessed the hypothesis that TAVI performed without prior BAV may be associated with decrease of risk of periprocedural cerebral ischemia assessed using diffusion-weighted (DW) magnetic resonance imaging (MRI). Methods: In this prospective monocentric study we randomized consecutive patients who underwent TAVI with the new generation balloon expandable SAPIEN 3 prosthesis. Group 1 (n=14) included patients with BAV performed prior implantation of the prosthesis and group 2 (n=14) patients with direct implantation of the valve. Periprocedural cerebral ischemia was assessed blindly by neurological testing and serial cerebral DW MRI at baseline and within 3 days after TAVI. Results: On the 28 patients included, mean age was 83 years (78-86),18 were of female gender (64.3%) and mean logistic Euroscore II was 8.4 (6.3-10.6) without significant differences between the 2 groups. Implantation of the valve was successful in all patients. Considering the total population, preexisting silent ischemic brain abnormalities were observed in 11 patients (39.3%) and microbleeds in 14 patients (50 %). New foci of restricted diffusion, mainly lacunar, and new microbleeds were found on cerebral DW MRI in respectively 13 (46.4%) and 6 (21%) patients after the procedure without significant difference between the 2 groups (table 1). There were neither apparent impairments of neurocognitive function or neurological events during the in-hospital stay in the 2 groups. In conclusion: Direct implantation of new generation balloon expandable prosthesis appears feasible but is not associated with reduction of periprocedural ischemic cerebral events . These results argue for embolization occurring during positioning of the valve rather than during balloon valvuloplasty.
Abstract 12633: Echocardiographic Evaluation of Cardiac Function and Hemodynamic During LVAD-based Resuscitation in Pigs
Authors: Rashad Zayat, Nima Hatam, Andreas Ebeling, Christoph Nix, Gernot Marx, Rüdiger Autschbach, Michael Fries, Matthias Derwall
Journal: Circulation (2016)

Introduction: We have previously shown that primary survival after cardiac arrest (CA) can be improved by optimizing circulation during CPR using a minimal invasive left ventricular assist device (Impella 2.5, iCPR). Whether calculated flow values derived from the Impella Controller during CA are reliable is unknown. Hypothesis: iCPR provides a preservation of right (RV) and left ventricular (LV) function following CA. The transpulmonary flow (TPF) inferred by pulsed-wave Doppler (PWD) during iCPR correlates well with the calculated blood-flow derived from the LVAD controller Methods: Ventricular fibrillation (VF) was electrically induced in 5 anesthetized pigs. Animals were left untreated for 10 minutes before iCPR was attempted. In addition to invasive hemodynamic monitoring, all animals received transesophageal echocardiography at baseline, during untreated cardiac arrest, at the initiation of iCPR, 30 minutes, and 5 hours following ROSC. Results: Preservation of systolic biventricular function within the first 5 hours following ROSC was observed in all individuals. All functional parameters almost returned to baseline values: baseline vs. 5hrs after ROSC: global longitudinal strain (GLS): -25±4.3% vs. -20±2.7%; p =0.388; ejection fraction: 64±8.8% vs. 61.32±10.3%, p =0.971;Stroke volume index: 28.32±8.9 vs. 24.71±12.86 mL/m 2 , p =0.545. The unloading of the LV volume was sufficient (LV-end-diastolic volume (mL): baseline, cardiac arrest, 30min after iCPR, 5hrs. after ROSC: 55.38±2.8, 64.7±9.9, 45.69±7.4, 49.46±13.9). PWD derived TPF during VF correlated well with the calculated flow (TPF: 1.8±0.39 L/min, Impella-Flow: 1.7±0.28 L/min., r =0.868, CI: -0.05842 to 0.9912, p =0.056). RV systolic function did not recover within the same time frame as compared to LV: baseline vs. 5 hrs after ROSC: Tricuspid annular systolic velocity: 11.6±1 vs. 8.5±1 cm/s, p =0.005, RV-fractional area shortening: 42±6.2 vs. 33±6.9 %, p =0.006. Conclusion: iCPR during cardiac arrest provided sufficient unloading of the LV as well as protection and preservation of the LV systolic function. The calculated Impella flow during iCPR correlated well with PWD derived TPF. Further studies are required to quantify effects of iCPR on changes in RV function.
Amyloid-Beta (1-40) Peptide and Subclinical Cardiovascular Disease
Authors: Kimon Stamatelopoulos, Christine J. Pol, Colby Ayers, Georgios Georgiopoulos, Aikaterini Gatsiou, Emmanouil S. Brilakis, Amit Khera, Konstantinos Drosatos, James A. de Lemos, Konstantinos Stellos
Journal: Journal of the American College of Cardiology (2018)
O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis
Authors: Kekoa Taparra, Hailun Wang, Reem Malek, Audrey Lafargue, Mustafa A. Barbhuiya, Xing Wang, Brian W. Simons, Matthew Ballew, Katriana Nugent, Jennifer Groves, Russell D. Williams, Takumi Shiraishi, James Verdone, Gokben Yildirir, Roger Henry, Bin Zhang, John Wong, Ken Kang-Hsin Wang, Barry D. Nelkin, Kenneth J. Pienta, Dean Felsher, Natasha E. Zachara, Phuoc T. Tran
Journal: Journal of Clinical Investigation (2018)

Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation. Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP). HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis. However, its function during tumorigenesis is poorly understood. One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT). Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway. We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis. To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins. O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis. Conversely, loss of O-GlcNAcylation delayed lung tumorigenesis. O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis. Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.
Exosomal double-stranded DNA as a biomarker for the diagnosis and preoperative assessment of pheochromocytoma and paraganglioma
Authors: Liang Wang, Ying Li, Xin Guan, Jingyuan Zhao, Liming Shen, Jing Liu
Journal: Molecular Cancer (2018)

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are the most heritable endocrine tumors. Genetic testing for 12 driver susceptibility genes is recommended in all PCC and PGL cases. However, detection of somatic mutations in PCC and PGL remains unrealizable for genetic diagnosis and preoperative assessment. We compared the serum exosomal DNA and tumor tissue DNA from patients or mice with PCC or PGL and found double-stranded DNA (dsDNA) fragments in the circulating exosomes of patients with PCC or PGL. Exosomal dsDNA shared the same mutations in the susceptibility genes with that of the parent tumor cells. Moreover, our research showed that serum-derived exosomal dsDNA in PCC and PGL was highly consistent with the paired tumor genome. Our findings provide the first definitive evidence of the presence of exosomal dsDNA that can be used as a noninvasive genetic marker in one of the most effective somatic mutation screens for the diagnosis and preoperative assessment of PCCs and PGLs.