tbuckley/cabot-search huggingface dataset:
Secreted ectodomain of SIGLEC-9 and MCP-1 ameliorate acute liver failure in rats by altering bone marrow macrophage polarity
Authors: T. Ito, M. Ishigami, A. Yamamoto, Y. Ishizu, T. Kazuya, T. Honda, K. Hayashi, T. Ishikawa, Y. Hirooka, H. Goto
Journal: Journal of Hepatology (2018)
Patient‐reported health‐related quality of life from the phase III TOURMALINE‐MM1 study of ixazomib‐lenalidomide‐dexamethasone versus placebo‐lenalidomide‐dexamethasone in relapsed/refractory multiple myeloma
Authors: Xavier Leleu, Tamas Masszi, Nizar J. Bahlis, Luisa Viterbo, Bartrum Baker, Peter Gimsing, Vladimir Maisnar, Olga Samoilova, Laura Rosiñol, Christian Langer, Kevin Song, Tohru Izumi, Charles Cleeland, Deborah Berg, Huamao Mark Lin, Yanyan Zhu, Tomas Skacel, Philippe Moreau, Paul G. Richardson
Journal: American Journal of Hematology (2018)

Abstract TOURMALINE‐MM1 is a phase III, randomized, double‐blind, placebo‐controlled study of ixazomib plus lenalidomide and dexamethasone (IRd) versus placebo‐Rd in patients with relapsed/refractory multiple myeloma following 1–3 prior lines of therapy. The study met its primary endpoint, demonstrating significantly longer progression‐free survival (PFS) in the IRd arm versus placebo‐Rd arm (median 20.6 vs 14.7 months, hazard ratio 0.74, P = .01), with limited additional toxicity. Patient‐reported health‐related quality of life (HRQoL) was a secondary endpoint of TOURMALINE‐MM1. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core‐30 (QLQ‐C30) and Multiple Myeloma Module 20 (QLQ‐MY20) were completed at screening, the start of cycles 1 and 2, every other cycle, the end of treatment, and every 4 weeks until progression. Over median follow‐up of 23.3 and 22.9 months in the IRd and placebo‐Rd arms, mean QLQ‐C30 global health status (GHS)/QoL scores were maintained from baseline over the course of treatment in both groups, with no statistically significant differences between groups. EORTC QLQ‐C30 function domain scores were also generally maintained from baseline; similarly, physical, emotional, and social function domains were maintained with IRd versus placebo‐Rd, with slightly higher mean change from baseline scores at earlier time points with IRd. Findings from this double‐blind study demonstrate that addition of ixazomib to Rd significantly improved efficacy while HRQoL was maintained, reflecting the limited additional toxicity seen with IRd versus placebo‐Rd, and support the feasibility of long‐term IRd administration.
Abstract 15819: Immune Regulatory T Cells Improve Vascular Function Through the Inhibition of Autophagy in Established Hypertension
Authors: Eman Radwan, Vishal Mali, Mohamed Trebak, Khalid Matrougui
Journal: Circulation (2016)

Introduction:  Growing studies report the involvement of immune T regulatory cells (Treg) in vascular complications in hypertension. We recently demonstrated that transfer of Treg cells before the development of hypertension prevents the development of hypertension and impaired vascular endothelium-dependent relaxation (EDR) in mice infused with angiotensin II (Ang II).   Hypothesis:  In this study, we determined whether we could rescue vascular function in an animal model with established hypertension by one single injection of Treg cells and whether Treg cells improve vascular function through the inhibition of autophagy and oxidative stress.   Methods:  Hypertension (HT) was induced by angiotensin II (Ang II, 400 ng/kg/min) for 4 weeks. Treg cells were isolated from control mice and then injected as a single bolus at the end of the second week for 2 weeks in the presence of Ang II. In another group, mice were injected daily with chloroquine (autophagy inhibitor, 10 mg/Kg) starting at the end of the second week for 2 weeks in the presence of Ang II. Blood pressure was measured once a week. At the end of experiment, EDR in mesenteric resistance artery (MRA) was assessed using wire myography, autophagy markers (Atg7, Atg5 and Beclin-1) were determined with Western blot analysis, and oxidative stress was assessed with NADPH oxidase activity.   Results:  The EDR was significantly reduced associated with an increase in autophagy markers (Atg7, Atg5 and Beclin-1), and oxidative stress in MRA from HT compared to control mice. The one single transfer of Treg cells to the hypertensive mice did not change the blood pressure but significantly improved the EDR through the inhibition of the autophagy markers and oxidative stress. The daily inhibition of autophagy reduced blood pressure, improved the EDR, and markedly decreased the autophagy markers as well as the oxidative stress.   Conclusions:  Our data demonstrate that one single injection of Treg cells can rescue the EDR in a mouse with established hypertension through the inhibition of autophagy and oxidative stress-dependent mechanism.
SunSmart schools: a New Zealand skin cancer primary prevention intervention blueprint for primary school settings
Authors: B.M. McNoe, A.I. Reeder, M.P. de Lange
Journal: British Journal of Dermatology (2018)

Funding sources: Cancer Society of New Zealand and University of Otago. Conflicts of interest: B.M.M. and A.I.R. received grants from the Cancer Society of New Zealand Inc during the study period. Dear Editor, Skin cancer is an important public health issue. Internationally, 2 to 3 million keratinocyte cancers and 132 000 melanoma skin cancers are diagnosed annually.1 Yet the risk of developing skin cancer can be mitigated by reducing exposure to ultraviolet radiation (UVR).2 Although exposure to excessive UVR throughout life is important for increasing melanoma risk, it may be particularly crucial during childhood.3 Children spend a considerable time at school and the school day encompasses the main period of high UVR. Pupils can spend at least part of that time outdoors and receive a substantial proportion of their total UVR exposure while at school.4 In addition, students take part in outdoor school events, such as sports days that can result in extended periods of exposure to high UVR levels.
Rigor in Quality Improvement Studies and the Role of Time-Series Methodologies
Authors: Arif H. Kamal, Shantanu Agrawal
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
KRAS-dependent AKT signaling drives hepatocyte proliferation to promote tumor development in a genetic model of liver cancer
Authors: T. Rösner, C. Lechler, K.-E. Birgit, K. Steiger, C. Mogler, D. Saur, J. Sage, R.M. Schmid, U. Ehmer
Journal: Journal of Hepatology (2018)
Promoting Risk Identification and Reduction of Cardiovascular Disease in Women Through Collaboration With Obstetricians and Gynecologists: A Presidential Advisory From the American Heart Association and the American College of Obstetricians and Gynecologists
Authors: Haywood L. Brown, John J. Warner, Eugenia Gianos, Martha Gulati, Alexandria J. Hill, Lisa M. Hollier, Stacey E. Rosen, Mary L. Rosser, Nanette K. Wenger
Journal: Circulation (2018)
A NEW FLANGED BILIARY COVERED STENT TO PREVENT PROSTHESIS MIGRATION. A PRELIMINARY REPORT
Authors: D Fregonese, P Zecchin, G Diamantis, T Slongo, A Mariniello
Journal: Endoscopy (2018)

Evaluation of migration rate, and efficacy of a new type of biliary covered stent, with large flange on distal end to prevent prosthesis migration [Niti-S Biliary Covered Stent (Flare Type)] The stents have 4, 6, 8 or 10 cm in length, a diameter of 10 mm, with proximal flange dilated up to 12 mm, and the distal one dilated up to 16 mm.
Safety and efficacy of ravidasvir plus sofosbuvir 12 weeks in noncirrhotic and 24 weeks in cirrhotic patients with hepatitis C virus genotypes 1, 2, 3 and 6: The STORM-C-1 phase II/III trial
Authors: I. Andrieux-Meyer, S.-S. Tan, N. Salvadori, F. Simon, T.R. Cressey, H.R.H.M. Said, M.R.A. Hassan, H. Omar, H.P. Tee, W.-K. Chan, K.L. Goh, S.F.S. Omar, A. Kamarulzaman, S. Kumar, S. Thongsawat, K. Thetket, A. Avihingsanon, S. Khemnark, S. Thanprasertsuk, J.-M. Piedagne, J. Brenner, S. Siva, N. Asimah, N. Da Silva, B. Pecoul, M. Lallemant, S. Murad
Journal: Journal of Hepatology (2018)
RNA-sequencing analysis of biopsies from chronic liver disease patients identifies gene signatures associated with progressive liver disease
Authors: D. Ramnath, K. Irvine, S. Lukowski, L. Horsfall, K. Loh, A. Clouston, P. Patel, A. Iyer, G. Lampe, J. Stow, K. Schroder, D. Fairlie, J. Powell, E. Powell, M. Sweet
Journal: Journal of Hepatology (2018)
Deaths from Falls Among Persons Aged ≥65 Years — United States, 2007–2016
Authors: Elizabeth Burns, Ramakrishna Kakara
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Deaths from unintentional injuries are the seventh leading cause of death among older adults (1), and falls account for the largest percentage of those deaths. Approximately one in four U.S. residents aged ≥65 years (older adults) report falling each year (2), and fall-related emergency department visits are estimated at approximately 3 million per year.* In 2016, a total of 29,668 U.S. residents aged ≥65 years died as the result of a fall (age-adjusted rate† = 61.6 per 100,000), compared with 18,334 deaths (47.0) in 2007. To evaluate this increase, CDC produced age-adjusted rates and trends for deaths from falls among persons aged ≥65 years, by selected characteristics (sex, age group, race/ethnicity, and urban/rural status) and state from 2007 to 2016. The rate of deaths from falls increased in the United States by an average of 3.0% per year during 2007-2016, and the rate increased in 30 states and the District of Columbia (DC) during that period. In eight states, the rate of deaths from falls increased for a portion of the study period. The rate increased in almost every demographic category included in the analysis, with the largest increase per year among persons aged ≥85 years. Health care providers should be aware that deaths from falls are increasing nationally among older adults but that falls are preventable. Falls and fall prevention should be discussed during annual wellness visits, when health care providers can assess fall risk, educate patients about falls, and select appropriate interventions.
Drug metabolism in drug discovery and development
Authors: Zhoupeng Zhang, Wei Tang
Journal: Acta Pharmaceutica Sinica B (2018)

Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics (PK), pharmacodynamics (PD), and safety should be carefully considered. This communication provides an overview of common strategies in the area of drug metabolism for improving PK/PD and safety profiles of drug candidates; these include, but are not limited to, collaboration with medicinal chemists on structure-activity relationships (SAR) to overcome high clearance, using deuterium replacement to further optimize a lead, prodrug approaches to circumvent formulation and delivery difficulties, and addressing issues such as species differences in metabolism, drug-drug interactions (DDI) and formation of reactive metabolites.
Algorithm to identify patients with an activity grade &gt; 2 in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD)-development in a large prospective multicenter UK study
Authors: P. Eddowes, M. Allison, E. Tsochatzis, Q. Anstee, D. Sheridan, I.N. Guha, J. Cobbold, Valérie Paradis, P. Bedossa, P. Newsome
Journal: Journal of Hepatology (2018)
In vitro and in vivo antiviral characterization of RO7049389, a novel small molecule capsid assembly modulator for the treatment of chronic hepatitis B
Authors: X. Zhou, Y. Zhou, X. Tian, F. Shen, G. Yang, W. Zhu, G. Ottaviani, J. Xie, H. Shen, J. Young, L. Gao
Journal: Journal of Hepatology (2018)
Abstract MP45: Effects of an mHealth Adaptive Intervention on Vascular Health and Cardiorespiratory Fitness
Authors: Catherine L Jarrett, Wesley J Tucker, Jane C Hurley, Michael Todd, Nishat Bhuiyan, Jacqueline A Fernandez, Marc A Adams, Siddhartha S Angadi
Journal: Circulation (2016)

Introduction: Behavioral economics-based interventions for increasing steps/day may improve cardiorespiratory fitness (CRF; Peak O2 uptake - VO2peak), central/aortic blood pressure, and vascular stiffness. The purpose of this study was to examine the effects of adaptive (Ad) physical activity (PA) goals (daily step goals based on prior 10-day window and a percentile algorithm) vs. static (St) PA goals (10,000 steps/day) combined with either immediate (Im) financial micro-incentives or delayed (De) incentives (Groups: Ad+Im; Ad+De; St+Im; St+De) on VO2peak, blood pressure and vascular stiffness. We hypothesized that participants randomized to adaptive goals with immediate reinforcement (Ad+Im) would have greater improvements in cardiovascular health measures than participants assigned to static goals and/or delayed reinforcement conditions (active controls). Methods: Inactive adults (Age = 41.8 ± 6.7yrs; BMI = 34.5 ± 6 kg/m2) were randomized to an adaptive/static goal intervention with either immediate micro-incentives or delayed incentives in a 4-month factorial RCT to improve steps/day. Additionally, all four groups received daily text-message prompts-to-action and Fitbit ZipTM activity monitors. Pre and post VO2peak (n=81) were estimated using a modified, sub-maximal Balke treadmill protocol while central blood pressures, augmentation index (Aix@75) (n=70) and carotid-femoral pulse wave velocity (cf-PWV) (n=64) were assessed with the Sphygmocor XCELTM device. Between- and within-group differences were examined using linear mixed models, adjusted for sex, age, race/ethnicity, and smoking history. Alpha was set at 0.05, and data are presented as estimated marginal means ± standard errors (SE). Results: All groups improved from pre to post, but we found no significant between-group differences in the degree of improvement. Across all groups, we found the following: VO2peak and all vascular markers improved significantly pre to post intervention (p&lt;0.05). VO2peak improved by ~5% (pre = 24.9 ± 0.65 vs. post = 26.3 ± 0.66 ml/kg/min). Central systolic blood pressures (cSBP) decreased (cSBP pre = 117.5 ± 2.1 vs. post = 113.1 ± 2.2 mmHg). Cf-PWV (pre = 7.5 ± 0.18 vs. post = 7.3 ± 0.18 m/sec) and AIX@75 (pre =14.1 ± 2.2 vs. post = 11.4 ± 2.2) decreased. Conclusion: Cardiorespiratory fitness and markers of vascular health improved when participants were simply provided a Fitbit and prompted daily to be more physically active, regardless of incentive or goal-setting approach. Implications for designing behavioral interventions for cardiovascular risk reduction will be discussed.
A high alpha-fetoprotein slope prior to therapy correlates with poor prognosis of patients with hepatocellular carcinomas
Authors: C. Czauderna, S. Koch, L. Pilz, S. Franck, H. Lang, R. Klöckner, M.-A. Wörns, P. Galle, J. Marquardt, A. Weinmann
Journal: Journal of Hepatology (2018)
P320Contribution of oxidized low density lipoproteins to arrhythmogenic cardiomyopathy adipogenesis
Authors: E Sommariva, I Stadiotti, L Arnaboldi, A Scopece, S Demetrio, M Casella, G Milano, C Tondo, A Corsini, G Pompilio
Journal: Cardiovascular Research (2018)

Background: Anthracyclines, like doxorubicin (DOX), are among the most potent antitumor drugs.However, their clinical use is hampered by severe cardiotoxicity.We previously demonstrated that inhibition of phosphoinositide 3-kinase c (PI3Kc) protects against anthracyclineinduced cardiomyopathy (manuscript under revision), but the underlying molecular mechanisms are still unexplored.Purpose: Here, we further test the hypothesis that anthracycline-damaged mitochondria activate Toll-like receptor 9 (TLR9)/PI3Kc signaling, which in turn inhibits protective autophagy, thus exacerbating anthracycline cardiotoxicity.Methods: Neonatal cardiomyocytes (NCMs) were isolated from mice expressing a kinase inactive PI3Kc (PI3Kc kinase-dead; KD) and wild-type (WT) controls, and treated with DOX (1 mM) or TLR9 agonist ODN1826 (1 mg/ml) 6 PI3Kc inhibitor AS605240 (500 nM) or TLR9 antagonist ODN2088 (1 mg/ml), for 1 hour before analyzing Akt/mTOR/Ulk-1 signaling.For in vivo studies, WT and KD mice were treated with 4 mg/kg DOX weekly for 3 weeks.Cardiac function was analyzed with echocardiography 6 weeks after the first injection.Electron microscopy (EM) study of morphology and signaling transduction were studied 3 days after the treatment.To investigate the role of protective autophagy in KD hearts, mice were treated with hydroxychloroquine (HCQ) or AAV9-shATG7, which silences the autophagy regulator ATG7 specifically in cardiomyocytes, together with DOX, as described above.Results: In NCMs, DOX significantly increased the phosphorylation of PI3K downstream targets and autophagy inhibitors, Akt, mTOR and Ulk-1.These effects were completely prevented by the TLR9 antagonist ODN2088, the PI3Kc selective inhibitor AS605240 and genetic PI3Kg inactivation (KD NCMs).Notably, the TLR9 agonist ODN1826, mimicking mitochondrial DNA (mitoDNA), similarly upregulated Akt/mTOR/Ulk-1 signaling in WT but not in KD NCMs.These results suggest that DOX activates PI3Kc through mitoDNA/TLR9.In vivo, EM studies showed more abundance of autolysosomes containing injured mitochondria in KD than WT hearts, highlighting the efficient autophagydependent disposal of DOX-damaged mitochondria in KD mice.Enhanced activation of PI3Kgdependent pathway correlated with a significant blunt of autophagy in DOX-treated hearts, whereas inhibition of PI3Kc promoted autophagy and decreased DOX-induced contractile dysfunction.Finally, inhibition of autophagy by HCQ or AAV9-shATG7 erased the protection in KD mice.Conclusion: Overall, this study demonstrates that PI3Kc prevents autophagic disposal of DOXdamaged mitochondria, resulting in cardiomyopathy.We propose PI3Kc inhibition as a novel strategy to reactivate targeted autophagy and limit cancer therapy-related heart disease.
Role of prostanoids in gastrointestinal cancer
Authors: Dingzhi Wang, Raymond N. DuBois
Journal: Journal of Clinical Investigation (2018)

Chronic inflammation is a risk factor for gastrointestinal cancer and other diseases. Most studies have focused on cytokines and chemokines as mediators connecting chronic inflammation to cancer, whereas the involvement of lipid mediators, including prostanoids, has not been extensively investigated. Prostanoids are among the earliest signaling molecules released in response to inflammation. Multiple lines of evidence suggest that prostanoids are involved in gastrointestinal cancer. In this Review, we discuss how prostanoids impact gastrointestinal cancer development. In particular, we highlight recent advances in our understanding of how prostaglandin E2 induces the immunosuppressive microenvironment in gastrointestinal cancers.
Effect of hepatitis C sustained virological response on the endothelial dysfunction and the cardiovascular risk. HepCAR study
Authors: R.M. Hernandez, R. Millan, Y. Sánchez, J. Ampuero, H.C. Macher, C. Jimeno, Ángela Rojas, I. Carmona, A. Gil-Gomez, S. Rodrigo, M.R. Gomez
Journal: Journal of Hepatology (2018)
Hepatitis C virus leaves epigenetic signature post cure by direct-acting antivirals that is linked to distinct mutation signature
Authors: M. Gal-Tanamy, S. Perez, A. Lavi-Itzkovitz, A. Kaspi, A. Davidovich, A. Tobar, A. Livoff, A. Nimer, E. Solomonov, A. El-Osta, G. Yaari, S.M. Stemmer, I. Haviv, M. Gal-Tanamy
Journal: Journal of Hepatology (2018)
Potential Clinical Targets in Hepatopulmonary Syndrome: Lessons From Experimental Models
Authors: Sarah Raevens, Michael B. Fallon
Journal: Hepatology (2018)

Hepatopulmonary syndrome (HPS) is a relatively common and potentially severe pulmonary complication of cirrhosis with increased risk of mortality. In experimental models, a complex interaction between pulmonary endothelial cells, monocytes, and the respiratory epithelium, which produces chemokines, cytokines, and angiogenic growth factors, causes alterations in the alveolar microvasculature, resulting in impaired oxygenation. Model systems are critical for evaluating mechanisms and for preclinical testing in HPS, due to the challenges of evaluating the lung in the setting of advanced liver disease in humans. This review provides an overview of current knowledge and recent findings in the rodent common bile duct ligation model of HPS, which recapitulates many features of human disease. We focus on the concepts of endothelial derangement, monocyte infiltration, angiogenesis, and alveolar type II cell dysfunction as main contributors and potential targets for therapy.
Validation study of graded prognostic assessment (GPA) of non-small cell lung cancer (NSCLC) patients with brain metastasis (BM).
Authors: Eberechi Sandra Agwa, Samuel T. Chao, Lingling Du, Vyshak Alva Venur, Paul Elson, Gene H. Barnett, Lilyana Angelov, John H. Suh, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2014)

8116 Background: NSCLC is the most common cause of BM and GPA is used as a prognostic index (PI) for BM. We evaluated its validity in a contemporary large cohort treated at a single tertiary care institution. Preliminary data was presented at ASCO 2013. Methods: IRB approved. NSCLC BM treated between 2000 and 2012 was identified from the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database. OS from the diagnosis of NSCLC BM was the primary end point.Cox proportional hazards models were used for data analysis. Results: 958 (54% male) patients were included for final analysis. Median age at BM diagnosis was 62 years (29-92). Karnofsky performance scale (KPS) was 90-100 in 345 (39%), 70-80 in 415 (47%) and <70 in 116 (13%) patients. Single BM was noted in 448 (47%), 2 BM in 169 (18%), 3 BM in 92 (10%), 4 BM in 49 (5%), 5 BM in 56 (6%) and >5 in 136 (14%) patients. Initial therapy included stereotactic radiosurgery (SRS) in 186 (20%) patients, whole brain radiation (WBRT) in 420 (44%), surgery (S) + WBRT in 132 (14%), WBRT + SRS in 138 (15%) and S + SRS in 23 (2%) patients, while 20 patients underwent only S, 11 patients received medical therapy alone, 17 were observed, 1 patient had S, WBRT + SRS. Median OS from diagnosis of BM was 7.8 months (95% C.I. 7.1-8.9).GPA for lung cancer is derived from KPS, number of BM, the presence/absence of extracranial metastases and age. GPA was prognostic for survival with very good separation between each of the groups (p<.0001). Conclusions: Even in the modern era GPA is still a valid PI for OS in NSCLC patients with BM. Factor N (%) Median survival (months) P* KPS 90-100 345 (39%) 12.0 <0.001 70-80 415 (47%) 7.5 < 70 116 (13%) 2.8 Number of brain metastases 1 448 (46%) 10.0 <0.001 2-3 261 (27%) 7.4 >3 241 (25%) 6.3 Extracranial metastases No 434 (46%) 12.1 <0.001 Yes 502 (54%) 5.6 Age (years) <50 122 (13%) 11.9 <0.001 50-60 291 (30%) 9.8 >60 544 (57%) 6.4 GPA 0 - 1.0 209 (24%) 3.4 <0.001 1.5 - 2.0 312 (36%) 7.0 2.5 - 3.0 275 (32%) 13.0 3.5 - 4.0 62 (7%) 23.2 *Proportional hazards model stratified by when brain metastases were diagnosed.