tbuckley/cabot-search huggingface dataset:
Abstract 12607: Renin Angiotensin Aldosterone System Inhibition Prevents the Arterial Stiffness Elevation Resulting in the Amelioration of Inappropriate Cardiovascular Response During Exercise in Patients With Hypertension
Authors: Kanae Yabu, Takashi Masuda, Misao Ogura, Ryosuke Shimizu, Daisuke Kamekawa, Ayako Akiyama, Yumi Kamada, Shinya Tanaka, Nobuaki Hamazaki, Akihiro Aoyama, Takeshi Nakamura, Emi Maekawa, Minako Tojo, Junya Ako
Journal: Circulation (2015)

Introduction: Patients with hypertension (HT) are known to show an increased activity of renin-angiotensin-aldosterone system (RAAS) secondary to sympathetic hyperactivity. The RAAS hyperactivity was reported to induce vascular endothelial dysfunction and elevated functional arterial stiffness resulting in an inappropriate cardiovascular response during exercise such as an excessive blood pressure (BP) elevation. This study investigated whether a long-term RAAS inhibition ameliorated the inappropriate cardiovascular response during exercise in HT patients. Methods: Eighty HT patients (64±14 years, 48 males) were divided into two groups based on antihypertensives: angiotensin II receptor blocker (ARB) group and L-type calcium channel blocker (CCB) group. Patients were followed up for one year, after their BP was controlled below 140/90 mmHg. Patients received a cycle ergometer test, and blood examination before and after the follow-up period. We determined systolic blood pressure (SBP) elevation during the exercise test as the change from baseline SBP to peak SBP (ΔSBP). We assessed the changes in plasma renin, aldosterone, noradrenaline (NORA) and adrenaline (ADRN), and brachial-ankle pulse wave velocity (PWV) before and after the exercise test (ΔNORA and ΔADRN as sympathetic activity parameters and ΔPWV as a functional arterial stiffness). Results: ΔSBP after the follow-up period was significantly lower in the ARB group than in the CCB group (P&lt;0.001). ΔADRN and ΔPWV increased significantly after the follow-up period in the CCB group as compared with baseline assessment (P&lt;0.05, respectively) despite no significant changes in the ARB group. Those after the follow-up period were significantly lower in the ARB group than in CCB group (P&lt;0.05, P&lt;0.001). Conclusions: RAAS inhibition prevented the arterial stiffness elevation resulting in the amelioration of inappropriate cardiovascular response during exercise in HT patients.
From Puppy to Patient
Authors: Justine V. Cohen
Journal: JAMA Internal Medicine (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 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
ERK activation results in sustained TGF-beta signaling by preventing ligand-induced type II receptor degradation in a human B cell lymphoma cell line
Authors: Gang Chen, Paritosh Ghosh, Dan Longo
Journal: Cancer Research (2008)

5112   Transforming growth factor-β (TGF-β) inhibits cell proliferation by arresting cells in the G1 phase of cell cycle in a variety of cell types. The critical regulators in this process include p15INK4b, p21CIP/WAF1, p27, and c-Myc. Activation of the TGF-β signaling occurs via ligand-induced heteromeric complex formation of type II (TβRII) and type I (TβRI) serine/threonine kinase receptors, which in turn propagates the TGF-β signal by phosphorylating and activating receptor-regulated Smad proteins, Smad2 and Smad3. With the formation of complex with Smad4, the activated Smads complex then translocates to the nucleus where, in association with transcriptional co-activators or repressors, it binds to the promoters of TGF-β-responsive genes, p15INK4b, p21CIP/WAF1, p27, and c-Myc. There is growing evidence that the deficiency in TGF-β signaling correlates with increased cancer risk. Here we describe a B cell lymphoma cell line, RL, which is resistant to TGF-β-induced growth arrest, and has transient TGF-β-induced nuclear translocation of Smad2 and Smad3. Analysis of TβRII reveals ligand-induced receptor down-regulation in a time-dependent manner. With a low dose of PMA, RL cells restore the sensitivity to TGF-β by up-regulating TβRII and sustained TGF-β signaling. Consistent with up-regulation of TβRII, there is ERK activation after PMA treatment. A P-ERK inhibitor U0126 blocks PMA-induced up-regulation of TβRII indicating a role for P-ERK activity in stabilizing TβRII. In HaCaT cells, a TGF-β responsive cell line, U0126 can induce down-regulation of TβRII and attenuate TGF-β signaling. Collectively, our data suggest that ERK activation sustains TGF-β signaling by preventing TβRII degradation.
Development of self-assembled multi-arm polyrotaxanes nanocarriers for systemic plasmid delivery in vivo
Authors: Ying Ji, Xiangsheng Liu, Max Huang, Jinhong Jiang, Yu-Pei Liao, Qi Liu, Chong Hyun Chang, Han Liao, Jianqin Lu, Xiang Wang, Melissa J. Spencer, Huan Meng
Journal: Biomaterials (2018)
Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts
Authors: Ryan C Ungaro, Berkeley N Limketkai, Camilla Bjørn Jensen, Kristine Højgaard Allin, Manasi Agrawal, Thomas Ullman, Jean-Frederic Colombel, Tine Jess
Journal: Gut (2018)

Objective The benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA. Design Our primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA. Results A total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF. Conclusion In two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.
Integrated automated particle tracking microfluidic enables high‐throughput cell deformability cytometry for red cell disorders
Authors: Puneeth Guruprasad, Robert G. Mannino, Christina Caruso, Hanqing Zhang, Cassandra D. Josephson, John D. Roback, Wilbur A. Lam
Journal: American Journal of Hematology (2018)

Investigating individual red blood cells (RBCs) is critical to understanding hematologic diseases, as pathology often originates at the single-cell level. Many RBC disorders manifest in altered biophysical properties, such as deformability of RBCs. Due to limitations in current biophysical assays, there exists a need for high-throughput analysis of RBC deformability with single-cell resolution. To that end, we present a method that pairs a simple in vitro artificial microvasculature network system with an innovative MATLAB-based automated particle tracking program, allowing for high-throughput, single-cell deformability index (sDI) measurements of entire RBC populations. We apply our technology to quantify the sDI of RBCs from healthy volunteers, Sickle cell disease (SCD) patients, a transfusion-dependent beta thalassemia major patient, and in stored packed RBCs (pRBCs) that undergo storage lesion over 4 weeks. Moreover, our system can also measure cell size for each RBC, thereby enabling 2D analysis of cell deformability vs cell size with single cell resolution akin to flow cytometry. Our results demonstrate the clear existence of distinct biophysical RBC subpopulations with high interpatient variability in SCD as indicated by large magnitude skewness and kurtosis values of distribution, the "shifting" of sDI vs RBC size curves over transfusion cycles in beta thalassemia, and the appearance of low sDI RBC subpopulations within 4 days of pRBC storage. Overall, our system offers an inexpensive, convenient, and high-throughput method to gauge single RBC deformability and size for any RBC population and has the potential to aid in disease monitoring and transfusion guidelines for various RBC disorders.
Cytonuclear Coevolution following Homoploid Hybrid Speciation in<i>Aegilops tauschii</i>
Authors: Changping Li, Xuhan Sun, Justin L Conover, Zhibin Zhang, Jinbin Wang, Xiaofei Wang, Xin Deng, Hongyan Wang, Bao Liu, Jonathan F Wendel, Lei Gong
Journal: Molecular Biology and Evolution (2018)

The diploid D-genome lineage of the Triticum/Aegilops complex has an evolutionary history involving genomic contributions from ancient A- and B/S-genome species. We explored here the possible cytonuclear evolutionary responses to this history of hybridization. Phylogenetic analysis of chloroplast DNAs indicates that the D-genome lineage has a maternal origin of the A-genome or some other closely allied lineage. Analyses of the nuclear genome in the D-genome species Aegilops tauschii indicate that accompanying and/or following this ancient hybridization, there has been biased maintenance of maternal A-genome ancestry in nuclear genes encoding cytonuclear enzyme complexes (CECs). Our study provides insights into mechanisms of cytonuclear coevolution accompanying the evolution and eventual stabilization of homoploid hybrid species. We suggest that this coevolutionary process includes likely rapid fixation of A-genome CEC orthologs as well as biased retention of A-genome nucleotides in CEC homologs following population level recombination during the initial generations.
Differentiating Fat Embolism Syndrome Due to Bone Marrow Necrosis in Patients with Sickle Hemoglobinopathies from Thrombotic Thrombocytopenic Purpura (TTP)
Authors: Radhika Gangaraju, Jori May, Paul MacLennan, Vishnu V.B. Reddy, Marisa B. Marques
Journal: Blood (2018)
Inconsistent Reporting of Potential Conflicts of Interest in <i>JAMA Cardiology</i>
Authors: Mark B. McClellan
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
A More Balanced Approach to Dietary Supplement Data—Reply
Authors: Dima Mazen Qato, G. Caleb Alexander, Stacy Tessler Lindau
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
Abstract 23084: Marked Global Variability in Cost Effectiveness of Lipid-Lowering and Combination Antihypertensive Therapies in Primary Prevention: Analyses of the HOPE-3 Trial
Authors: Andre Lamy, Wesley Tong, Eva Lonn, Balakumar Swaminathan, Hyejung Jung, Jackie Bosch, Salim Yusuf
Journal: Circulation (2017)

Background: The Heart Outcomes Prevention Evaluation (HOPE) - 3 trial demonstrated that low dose lipid-lowering medication alone or with an angiotensin receptor blocker (ARB)+ thiazide resulted in a significantly lower risk of cardiovascular events compared to placebo in intermediate risk persons without cardiovascular disease. Since use of these medications in primary prevention could have significant cost implication, we report the cost analysis of the HOPE-3 trial. Methods: Hospitalization events, procedures, medications and study drugs were extracted for each patient. We applied country-specific costs to healthcare resources consumed for each patient. We calculated average cost per patient for the length of the study (median follow-up 5.6 years). Costs are reported in US dollars and discounted at 3% per year. The costs of the study drugs vary considerably between countries and we use the most locally affordable (generic) lipid-lowering medication and ARB + diuretic combination. Results: In most regions, use of lipid-lowering medication in combination with antihypertensive drugs in HOPE-3 was cost-neutral or cost-saving as the cost of these medications was offset by savings in other costs (events, procedures, and usual medications). Surprisingly, in India and China, the cost of these medications is the main component of overall health expenditures, being more expensive than all other costs. Conclusions: The use of lipid-lowering medication alone or with antihypertensives agents is cost-saving in most regions by providing significant clinical benefit to intermediate risk persons without cardiovascular disease. Prices for these generic drugs in India and particularly in China are high relative to other costs and policies to reduce the prices of these are needed to ensure that generics are more affordable. Primary prevention using lipid-lowering medication and antihypertensive agents would be cost-neutral or cost-saving worldwide.
Fasiglifam-Induced Liver Injury in Patients With Type 2 Diabetes: Results of a Randomized Controlled Cardiovascular Outcomes Safety Trial
Authors: Venu Menon, A. Michael Lincoff, Stephen J. Nicholls, Susan Jasper, Kathy Wolski, Darren K. McGuire, Cyrus R. Mehta, Julio Rosenstock, Claudia Lopez, John Marcinak, Charlie Cao, Steven E. Nissen
Journal: Diabetes Care (2018)

OBJECTIVE To evaluate the cardiovascular (CV) safety of fasiglifam, a first-in-man G-protein–coupled receptor 40 (GPR40) agonist, in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A phase 3 multicenter randomized double-blind placebo-controlled two-arm trial was intended to randomize 5,000 participants with type 2 diabetes at high CV risk to fasiglifam or placebo. The primary objective of the trial was to rule out an upper noninferiority bound &amp;gt;1.3 for a one-sided 97.5% confidence limit of the hazard ratio (HR) for CV composite events during treatment with fasiglifam compared with placebo. The primary outcome was the time to first occurrence of any component of the major adverse CV event composite of CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina. RESULTS The study enrolled 3,207 participants but was terminated because of liver safety concerns. Increased rates of liver enzyme elevation (AST/ALT ≥3–5 × upper limit of normal [ULN]) with fasiglifam were observed. The incidence of ALT or AST ≥3 × ULN with fasiglifam compared with placebo was 2.1% vs. 0.5%, P &amp;lt; 0.001, and the incidence for ≥10 × ULN was 0.31% vs. 0.06%, P &amp;lt; 0.001. A primary CV composite outcome occurred in 40 participants, 2.5% each in the fasiglifam and placebo arms at 12 months (HR 1.05; 95% CI 0.67, 1.63). CONCLUSIONS Development of fasiglifam was terminated due to concerns of drug-induced liver injury. Performance of a U.S. Food and Drug Administration–mandated CV outcomes trial supported the termination of the fasiglifam clinical program.
AB0465 Safety and duration of biologic treatment in elderly patients with rheumatoid arthritis
Authors: S. Garrote Corral, A. Garcia Fernandez, P. Moran Alvarez, F.J. Bachiller Corral
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Several differences may be expected between young and elderly patients with rheumatoid arthritis (RA), safety and efficacy results are variable in the different previous studies.<sup>1,2</sup> <h3>Objectives</h3> To compare the duration and safety of biological treatment in patients with RA depending on the age of onset of therapy, in a Spanish tertiary centre. <h3>Methods</h3> We conducted a retrospective observational study of patients with a diagnosis of RA who were receiving biologic treatment. They were diagnosed between February 1980 and February 2017, on the basis of criteria ACR/EULAR 2010 or 1987 ACR criteria. The information was obtained from review of medical records. We divided the patients in two groups according to age of the onset of treatment: elderly group (≥65 years) and young group (&lt;65 years). <h3>Results</h3> 140 patients were included. At the beginning of the treatment 89 were under 65 years and 51 older (65–74 years: 28 patients,&gt;75 years: 23). The average duration of the disease from diagnosis until the beginning of the biological treatment was 103±91 months in young patients and 142,86±109,5 months in elderly patients (p: 0,023). We detected no differences between both groups at baseline characteristics, except for comorbidities and sex. DAS28PCR prior to biologic therapy was 5.20±1.44 in young patients and 5.14±0813 in elderly (p: 0,37). Duration of the treatment was similar in both groups. Suspension of biologic treatment occurred in 50 young patients (56%) and 30 elderly patients (58%) (table 1). The causes are detailed in table 2. Adverse effects were more frequent in the elderly but without statistical significance. There were 9 cases of cancer in elderly patients (17.3%) and 4 cases in young patients (4.6%) p: 0013. The average diagnosis of cancer prior to the introduction of biologic treatment was 5.8±7.1 years. <h3>Conclusions</h3> Our study corroborate that biologic treatment has similar duration and safety in elderly and young patient.<sup>1,2</sup> <h3>References</h3> [1] Ishchenko A, Lories RJ. Safetyand Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance; Drugs Aging2016;33:387–398. [2] Lahaye C, et al. Overview of biologic treatments in the elderly. Joint Bone Spine2015;82(2015):154–160. <h3>Disclosure of Interest</h3> None declared
Tralokinumab did not demonstrate oral corticosteroid-sparing effects in severe asthma
Authors: William W. Busse, Guy G. Brusselle, Stephanie Korn, Piotr Kuna, Antoine Magnan, David Cohen, Karin Bowen, Teresa Piechowiak, Millie M. Wang, Gene Colice
Journal: European Respiratory Journal (2018)

Long-term oral corticosteroid (OCS) use in patients with severe asthma is associated with significant adverse effects. This 40-week, randomised, double-blind trial evaluated the OCS-sparing potential of tralokinumab in patients with severe, uncontrolled asthma requiring maintenance OCS treatment plus inhaled corticosteroids/long-acting β 2 -agonists. Overall, 140 patients were randomised to tralokinumab 300 mg or placebo (n=70 in each group) administered subcutaneously every 2 weeks. The primary end-point was percentage change from baseline in average OCS dose at week 40, while maintaining asthma control. Secondary end-points included proportion of patients with a prescribed maintenance OCS dose of ≤5 mg, those with a ≥50% reduction in prescribed maintenance OCS dose and asthma exacerbation rate. Safety was also assessed. At week 40, the percentage reduction from baseline in the final daily average OCS dose was not significantly different between tralokinumab and placebo (37.62% versus 29.85%; p=0.271). There were no significant between-treatment differences for any secondary end-point. Overall, reporting of adverse events and serious adverse events were similar for the tralokinumab and placebo groups. Although a greater proportion of tralokinumab-treated patients reported upper respiratory tract infections (35.7% versus 14.3%), there were no reported cases of pneumonia. Overall, tralokinumab did not demonstrate an OCS-sparing effect in patients with severe asthma.