tbuckley/cabot-search huggingface dataset:
Efficacy of metarrestin against ovarian cancer.
Authors: Margaux Jenna Kanis, Wenan Qiang, John Robert Lurain, Sui Huang, J. Julie Kim
Journal: Journal of Clinical Oncology (2015)

e16573 Background: A novel drug metarrestin (ML 246) was identified through a screen of compounds that disrupted the perinucleolar compartment (PNC), which is a nuclear structure associated with the metastatic potential of cancer cells. Although the function of PNCs is not entirely clear, they are observed in metastatic solid tumors including breast, prostate, pancreatic and colorectal cancers, and a higher PNC prevalence in tumor tissues generally associates with poor patient survival. However, in vivo analyses show a significant inhibition of distant metastases and reduction in metasatic tumor volume when treated with metarrestin. In this study, the effect of metarrestin on ovarian cancer cells was tested. Methods: The PNC prevalence (the percentage of cells containing at least one PNC) in SKOV3 and OVCAR3 ovarian cancer cell lines treated with two doses of metarrestin was determined by immunofluorescence with SH54, a monoclonal antibody that specifically recognizes PTB, an RNA binding protein that is highly concentrated in the PNC. Cell viability using a WST assay and a Matrigel invasion assay using a transwell system were performed. Results: Both SKOV3 and OVCAR3 cells are high in PNC prevalence. When treated with metarrestin, PNC prevalence and the number of cells that contain multiple PNCs were significantly reduced in SKOV3 and OVCAR3 cells. Cell viability assays showed minimal cell toxicity, in which treatment up to 20 uM metarrestin did not induce growth inhibition. Significant decreased cell viability was only observed when treated with metarrestin at 50 uM. Furthermore, metarrestin significantly inhibited invasion of SKOV3 and OVCAR3 cells. Conclusions: Metarrestin effectively reduces PNC prevalence in ovarian cancer cell lines, and significantly attenuates invasion of ovarian cancer cells without significant growth inhibition. We are currently testing metarrestin on metastasis of ovarian tumors in mouse xenograft models.
Determinants of Bioprosthetic Aortic Valve Degeneration
Authors: Christian Nitsche, Andreas A. Kammerlander, Klaus Knechtelsdorfer, Jakob A. Kraiger, Georg Goliasch, Carolina Dona, Laurin Schachner, Begüm Öztürk, Christina Binder, Franz Duca, Stefan Aschauer, Daniel Zimpfer, Diana Bonderman, Christian Hengstenberg, Julia Mascherbauer
Journal: JACC. Cardiovascular imaging (2019)
Abstract 20570: Geographic Representation and Reported Success Rates of Studies of Catheter Ablation for Atrial Fibrillation: Findings From the SMASH-AF Meta-Analysis Study Cohort
Authors: George C Leef, Alexander C Perino, Fahd N Yunus, Andrew Cluckey, Mintu Turakhia
Journal: Circulation (2016)

Introduction: Systematic reviews of catheter ablation for atrial fibrillation (AF) have large unexplained study heterogeneity. Geographic differences in study population or procedure strategy may b...
Anticonvulsant prophylaxis and steroid use in adults with metastatic brain tumors: summary of SNO and ASCO endorsement of the Congress of Neurological Surgeons guidelines*
Authors: Susan M Chang, Hans Messersmith, Manmeet Ahluwalia, David Andrews, Priscilla K Brastianos, Laurie E Gaspar, Na Tosha N Gatson, Justin T Jordan, Mustafa Khasraw, Andrew B Lassman, Julia Maues, Maciej Mrugala, Jeffrey Raizer, David Schiff, Glen Stevens, Ashley Sumrall, Martin Van den Bent, Michael A Vogelbaum
Journal: Neuro-Oncology (2019)

The Congress of Neurological Surgeons (CNS) has developed a series of guidelines on the treatment of adults with metastatic brain tumors, including systemic therapy and supportive care topics. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations.Two CNS Guidelines were reviewed for developmental rigor by methodologists and an independent multi-disciplinary Expert Panel was formed to review the content and assess agreement with the recommendations. The expert panel voted to endorse the two guidelines and ASCO and SNO independently reviewed and approved the ASCO/SNO guideline endorsement.The ASCO/SNO Expert Panel determined that the recommendations from the CNS anticonvulsants and steroids guidelines, published January 9, 2019, are clear, thorough, and based upon the most relevant scientific evidence. ASCO/SNO endorsed these two CNS guidelines, with minor alterations.Key recommendations include: prophylactic anti-epileptic drugs were not recommended for routine use; corticosteroids (specifically dexamethasone) were recommended for temporary symptomatic relief in patients with neurologic symptoms and signs related to mass effect from brain metastases.
Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B
Authors: Teng-Yu Lee, Yao-Chun Hsu, Hsiao-Ching Tseng, Shi-Hang Yu, Jaw-Town Lin, Ming-Shiang Wu, Chun-Ying Wu
Journal: JAMA Internal Medicine (2019)

Antiviral therapy cannot erase hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B, and it is not indicated for most hepatitis B virus (HBV) carriers. Another effective way of reducing HCC risk needs to be developed. Aspirin may prevent cancer development, but clinical evidence in patients with HBV-related HCC remains limited.To investigate the association of daily aspirin therapy with HBV-related HCC risk.In this Taiwan nationwide cohort study, we screened 204 507 patients with chronic hepatitis B for the period January 1, 1997, to December 31, 2012. After excluding patients with confounding conditions, 2123 patients who continuously received daily aspirin for 90 or more days (treated group) were randomly matched 1:4 with 8492 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores, consisting of the follow-up index date, baseline characteristics, and potentially chemopreventive drug use during follow-up. Data were analyzed from August 1 to November 30, 2018.Daily aspirin therapy during the study period.Both cumulative incidence of and hazard ratios (HRs) for HCC development were analyzed after adjusting patient mortality as a competing risk event.Of the 10 615 patients included in the analysis, 7690 (72.4%) were men; mean (SD) age was 58.8 (11.8) years. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (5.20%; 95% CI, 4.11%-6.29% vs 7.87%; 95% CI, 7.15%-8.60%; P < .001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Sensitivity subgroup analyses also verified this association (all HRs <1.0). In addition, older age (HR, 1.01 per year; 95% CI, 1.00-1.02), male sex (HR, 1.75; 95% CI, 1.43-2.14), and cirrhosis (HR, 2.89; 95% CI, 2.45-3.40) were independently associated with an increased HCC risk, but nucleos(t)ide analogue (HR, 0.54; 95% CI, 0.41-0.71) or statin (HR, 0.62; 95% CI, 0.42-0.90) use was correlated with a decreased HCC risk.Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC.
Abstract P241: Snoring is Associated With Obesity Among Middle Aged Slum-Dwelling Women in Mysore India
Authors: Karl F Krupp, Arun Srinivas, Khurram Nasir, Vijaya Srinivas, Elena Bastida
Journal: Circulation (2019)

Background: Globally, rates of obesity have trebled in the past four decades. India has more than 9.8 million men and 20 million women classified as obese. While poor diet and sedentary lifestyles are major causes, growing evidence suggests other factors like sleep-disordered-breathing may also be contributors. Methods: A cross-sectional survey was carried out between October 2017 and May 2018 among a nonprobability sample of slum-dwelling women, 40 to 64 years of age, in government-designated slums in Mysore, India. In addition to socio-demographics, data were collected on tobacco and alcohol consumption, diet, physical activity, sleep, quality of life, and personal and family history of diagnosed cardiometabolic disorders. Body mass Index (BMI) was calculated using anthropometry. Serum was tested for HbA1c and lipids. Electrocardiography was carried out by a trained medical technician. Results: In this sample of slum dwelling women, snoring was associated with obesity. Habitual snorers had more than double the odds (Adjusted Odds Ratio [aOR] 2.05; 95% Confidence Interval [CI]1.26-3.33; p&lt;0.004) of obesity I, and seven times the odds (aOR 7.71; CI: 3.58-16.62; p&lt;0.001) of having obesity II compared to non-snorers after adjustment for age, diabetes, hypertension, hypercholesterolemia, and daytime sleepiness. There was no difference in obesity status among participants reporting abnormal sleep duration, napping, daytime sleepiness, sleep apnea, insomnia, or use of sleep medication. Conclusion: The relationship of snoring and obesity has not been well explored. This study among slum-dwelling Indian women, found a significant relationship between snoring and obesity. Future research should explore the underlying mechanisms connecting snoring to BMI.
A study of intense neoadjuvant testosterone lowering therapy with goserelin and enzalutamide (Enza) in high-risk prostate cancer (PC) with multiparametric MRI (mpMRI).
Authors: Fatima Karzai, Ravi Amrit Madan, David James VanderWeele, Guinevere Chun, Marijo Bilusic, Lisa M. Cordes, Nicole Carrabba, Scott Wilkinson, Huihui Ye, Stephanie Harmon, Adam G. Sowalsky, Baris Turkbey, Peter A. Pinto, Peter L. Choyke, James L. Gulley, William L. Dahut
Journal: Journal of Clinical Oncology (2019)

63 Background: Neoadjuvant therapy with novel androgen receptor inhibitors, like enza, offer an opportunity to improve cure rates in men with high risk PC but also emphasizes the need for improved imaging techniques and genomic studies to evaluate treatment (trt) responses. We conducted a feasibility study using mpMRI to evaluate tumor responses and resistance in newly diagnosed, high-risk PC. Methods: Patients (pts) were treated with androgen deprivation therapy (ADT) + enza 160 mg po qdaily for 6 months (mos). Pts underwent 2 mpMRI: baseline and post 6 mos of therapy. Post-trt mpMRI was followed by radical prostatectomy (RP). Primary endpoint was feasibility of mpMRI for localization and detection of PC before and after therapy with ADT + enza. Results: 31 out of 33 pts completed 6 mos of therapy and underwent RP. Median on-study PSA was 9.58 (1.18-984.72 ng/dL). Median PSA post 6 mos of ADT + enza was &lt;0.02 (0.02-0.35 ng/mL). No pt was taken off-trt for adverse events. Median residual cancer burden (RCB) defined as volume of tumor corrected by tumor cellularity was 0.1584 (0.0001-12.32 cc). Using RCB of &lt;0.05 cc, 12 patients had minimal residual disease of which 4 pts were pathologic complete responses. Post-trt mpMRI volume correlated with final pathology in all cases. Conclusions: Neoadjuvant enza + ADT is tolerable and shows activity in a newly-diagnosed, high-risk population. mpMRI can be utilized to assess responses to trt. Analysis of genomic characteristics and resistance mechanisms is on-going. Clinical trial information: NCT02430480.
A Normal Prothrombin Time, Activated Partial Thromboplastin Time and Fibrinogen Level Do Not Eliminate Disseminated Intravascular Coagulation (DIC) and Bleeding Risk in Patients with Acute Promyelocytic Leukemia
Authors: Kathryn Sarah Simon, Prachi Kharkhanis, Catherine R. Caprara, Stephanie Debragga, Sheldon Bolds, Saleh Alghsoon, Martha L. Arellano, Ravindra Kolhe, Anand Jillella, Vamsi Kota
Journal: Blood (2017)
Assessment of a Risk Index for Suicide Attempts Among US Army Soldiers With Suicide Ideation
Authors: Kelly L. Zuromski, Samantha L. Bernecker, Peter M. Gutierrez, Thomas E. Joiner, Andrew J. King, Howard Liu, James A. Naifeh, Matthew K. Nock, Nancy A. Sampson, Alan M. Zaslavsky, Murray B. Stein, Robert J. Ursano, Ronald C. Kessler
Journal: JAMA Network Open (2019)

The Department of Veterans Affairs recently began requiring annual suicide ideation (SI) screening of all patients and additional structured questions for patients reporting SI. Related changes are under consideration at the Department of Defense. These changes will presumably lead to higher SI detection, which will require hiring additional clinical staff and/or developing a clinical decision support system to focus in-depth suicide risk assessments on patients considered high risk.To carry out a proof-of-concept study for whether a brief structured question battery from a survey of US Army soldiers can help target in-depth suicide risk assessments by identifying soldiers with self-reported lifetime SI who are at highest risk of subsequent administratively recorded nonfatal suicide attempts (SAs).Cohort study with prospective observational design. Data were collected from May 2011 to February 2013. Participants were followed up through December 2014. Analyses were conducted from March to November 2018. A logistic regression model was used to assess risk for subsequent administratively recorded nonfatal SAs. A total of 3649 Regular Army soldiers in 3 Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) surveys who reported lifetime SI were followed up for 18 to 45 months from baseline to assess administratively reported nonfatal SAs.Outcome was administratively recorded nonfatal SAs between survey response and December 2014. Predictors were survey variables.The 3649 survey respondents were 80.5% male and had a median (interquartile range) age of 29 (25-36) years (range, 18-55 years); 69.4% were white non-Hispanic, 14.6% were black, 9.0% were Hispanic, 7.0% were another racial/ethnic group. Sixty-five respondents had administratively recorded nonfatal SAs between survey response and December 2014. One additional respondent died by suicide without making a nonfatal SA but was excluded from analysis based on previous evidence that predictors are different for suicide death and nonfatal SAs. Significant risk factors were SI recency (odds ratio [OR], 7.2; 95% CI, 2.9-18.0) and persistence (OR, 2.6; 95% CI, 1.0-6.8), positive screens for mental disorders (OR, 26.2; 95% CI, 6.1-112.0), and Army career characteristics (OR for junior enlisted rank, 30.0; 95% CI, 3.3-272.5 and OR for senior enlisted rank, 6.7; 95% CI, 0.8-54.9). Cross-validated area under the curve was 0.78. The 10% of respondents with highest estimated risk accounted for 39.2% of subsequent SAs.Results suggest the feasibility of developing a clinically useful risk index for SA among soldiers with SI using a small number of self-report questions. If implemented, a continuous quality improvement approach should be taken to refine the structured question series.
Arachidonic Acid Induces Ferroptosis-Mediated Cell-Death in Multiple Myeloma
Authors: Cristina Panaroni, Keertik Fulzele, Rosemary Soucy, Ka Tat Siu, Kenta Mukaihara, Cherrie Huang, Shrikanta Chattopadhyay, Noopur Raje
Journal: Blood (2018)
Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway
Authors: Xing Zhang, Sen Wang, Haixiao Wang, Jiacheng Cao, Xiaoxu Huang, Zheng Chen, Penghui Xu, Guangli Sun, Jianghao Xu, Jialun Lv, Zekuan Xu
Journal: Molecular Cancer (2019)

CircRNA has emerged as a new non-coding RNA that plays crucial roles in tumour initiation and development. 'MiRNA sponge' is the most reported role played by circRNAs in many tumours. The AKT/mTOR axis is a classic signalling pathway in cancers that sustains energy homeostasis through energy production activities, such as the Warburg effect, and blocks catabolic activities, such as autophagy. Additionally, the AKT/mTOR axis exerts a positive effect on EMT, which promotes tumour metastasis. We detected higher circNRIP1 expression in gastric cancer by performing RNA-seq analysis. We verified the tumour promotor role of circNRIP1 in gastric cancer cells through a series of biological function assays. We then used a pull-down assay and dual-luciferase reporter assay to identify the downstream miR-149-5p of circNRIP1. Western blot analysis and immunofluorescence assays were performed to demonstrate that the circNRIP1-miR-149-5p-AKT1/mTOR axis is responsible for the altered metabolism in GC cells and promotes GC development. We then adopted a co-culture system to trace circNRIP1 transmission via exosomal communication and RIP experiments to determine that quaking regulates circNRIP1 expression. Finally, we confirmed the tumour suppressor role of microRNA-133a-3p in vivo in PDX mouse models. We discovered that knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in GC cells. MiR-149-5p inhibition phenocopied the overexpression of circNRIP1 in GC cells, and overexpression of miR-149-5p blocked the malignant behaviours of circNRIP1. Moreover, it was proven that circNRIP1 can be transmitted by exosomal communication between GC cells, and exosomal circNRIP1 promoted tumour metastasis in vivo. We also demonstrated that quaking can promote circNRIP1 transcription. In the final step, the tumour promotor role of circNRIP1 was verified in PDX models. We proved that circNRIP1 sponges miR-149-5p to affect the expression level of AKT1 and eventually acts as a tumour promotor in GC.
Abstract 023: The Natural History of Cigarette Smoking From Childhood to Middle-Age: The International Childhood Cardiovascular Cohort (i3C) Consortium
Authors: Tian Hu, Seana L Gall, Rachel Widome, Lydia A Bazzano, Trudy L Burns, Stephen R Daniels, Terence Dwyer, Johanna Ikonen, Markus Juonala, Mika Kahonen, Ronald J Prineas, Olli T Raitakari, Alan R Sinaiko, Julia Steinberger, Elaine M Urbina, Alison Venn, Jorma Viikari, Jessica G Woo, David R Jacobs
Journal: Circulation (2019)

Background: Smoking is known to cause clinical cardiovascular disease. We report the natural history of smoking from childhood until average age 47 years in the large cohort followed in the International Childhood Cardiovascular Cohort (i3C) Consortium, which consists of seven long-standing cohorts in the US, Finland and Australia. Methods: Data on childhood smoking status were obtained from questionnaires answered during age 6-19 during the 1980s. Childhood smoking status was categorized as never smoker, tried smoking only a few times, tried more extensively (including quitters), and regular smoker. The i3C participants had follow-up visits until 2015-18 (Finland 2010-12), when they reported whether they were smokers during their 20s and/or 40s. Results: Of the 9977 participants, prevalence of regular smoking decreased from 35.5% in their 20s, to 20.5% in their 40s; cessation was unrelated to childhood smoking status. As shown in the Figure, among 1816 participants queried at age 18/19, prevalence of regular smoking in their 20s was 4.1% (36/886) in those who never smoked even during adolescence, 12% (22/183) in those who tried only a few times, 21.5% (40/186) in those who tried more extensively, and 76.5% (429/561) in those who were regular smokers during childhood. The pattern was similar among 860 whose last childhood smoking status was queried at age 16/17 (some probably experimented more during the remainder of childhood), but smoking in their 20s was more common for all smoking experimentation groups than in 18/19 year olds. Conclusions: These long-term follow-up data suggest that prevalence of adult smoking was significantly related to level of smoking experimentation during adolescence. However, cessation during adulthood does not depend on childhood smoking status. Policy change (such as taxes and restrictions on smoking indoors) has proven to be one of the most powerful tobacco control tools. These data support an emerging new policy strategy, namely raising the legal cigarette purchase age to 21 years
Adverse events of special interest assessed by review of safety data in enzalutamide castration-resistant prostate cancer (CRPC) trials.
Authors: Bertrand F. TOMBAL, Andrew J. Armstrong, Jeffrey Kent Barrus, Tomasz M. Beer, Simon Chowdhury, Christopher P. Evans, Axel Heidenreich, Celestia S. Higano, Tomomi Kamba, Ping Lin, Natalia Nikolayeva, Jennifer Sugg, Joyce Leta Steinberg, Mary Ellen Taplin, Fred Saad
Journal: Journal of Clinical Oncology (2019)

237 Background: Androgen receptor inhibitor enzalutamide improves survival in patients with metastatic CRPC (mCRPC) and reduces risk of metastasis or death versus placebo in patients with non-metastatic CRPC (nmCRPC). This post hoc analysis evaluated the incidence of adverse events (AEs) of special interest reported with enzalutamide versus placebo in CRPC trials. Methods: Safety data from four Phase 3, placebo-controlled enzalutamide trials in men with CRPC (PROSPER, nmCRPC, NCT02003924; PREVAIL, mCRPC, NCT01212991; AFFIRM, mCRPC, NCT00974311; and 9785-CL-0232, mCRPC, NCT02294461) were assessed for AEs of special interest, including ischemic heart disease (IHD) [defined by narrow Standardised MedDRA Queries “Myocardial Infarction”/“Other Ischemic Heart Disease”], falls, and fractures. Data were reported as overall incidence and adjusted for treatment exposure (per 100 patient-years), and summarized as follows: patients receiving enzalutamide (n = 2799) and placebo (n = 1898) in all four Phase 3 trials. Results: Median treatment duration was 13.73 months with enzalutamide and 4.80 months with placebo in the combined Phase 3 trials. Overall incidence of IHD was higher with enzalutamide versus placebo in the combined Phase 3 trials (Table), remaining higher once adjusted for treatment exposure (2.5 with enzalutamide vs. 2.2 with placebo). Similarly, exposure-adjusted rate of falls and fractures were also higher with enzalutamide versus placebo (Table). Clinical trial information: NCT02003924 (PROSPER); NCT01212991 (PREVAIL); NCT00974311 (AFFIRM); NCT02294461 (9785-CL-0232). Conclusions: In this combined analysis of CRPC trials, incidences of IHD, falls, and fractures were higher with enzalutamide versus placebo in all patients. Efforts to identify patients at high risk for these AEs and reduce their risk, e.g. via exercise and cardiovascular risk reduction, are important in these patients, particularly in elderly men and those with cardiovascular comorbidities.[Table: see text]