tbuckley/cabot-search huggingface dataset:
Abstract 14977: Association of Childhood Psychosocial Environment With Incident Cardiovascular Disease in Middle Adulthood: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Jacob B Pierce, Kiarri N Kershaw, Catarina I Kiefe, David R Jacobs, Stephen Sidney, Sharon S Merkin, Joe Feinglass
Journal: Circulation (2018)

Introduction: Individuals who report higher degrees of adverse psychosocial environments in childhood have higher rates of cardiovascular disease (CVD) in adulthood. However, previous studies on th...
A phase II study of novel three peptides combination with gemcitabine as a first-line therapy for advanced pancreatic cancer (VENUS-PC study).
Authors: Hiroaki Tanaka, Nobuaki Suzuki, Haruo Iguchi, Kazuhiro Uesugi, Kosei Hirakawa, Ryosuke Amano, Atsushi Aruga, Takashi Hatori, Ishizaki Hidenobu, Yuzo Umeda, Mitsuo Shimada, Kazuhiko Yoshimatsu, Ryoichi Shimizu, Hiroaki Ozasa, Hiroto Hayashi, Koichiro Sakata, Tomio Ueno, Hiroyuki Furukawa, Shoichi Hazama, Masaaki Oka
Journal: Journal of Clinical Oncology (2015)

3045 Background: The novel HLA-A*2402-binding peptides derived from KIF20A (RAB6KIFL) belong to the kinesin superfamily of motor proteins, which play critical roles in the trafficking of molecules and organelles during the growth of pancreatic cancer. A phase I cancer vaccination trial using KIF20A determined its safety and immunogenicity in advanced pancreatic cancer (PC) patients (J Immunother 2014;37:36-42). We further performed a phase II trial using not only KIF20A but also an antiangiogenic cancer vaccine targeting VEGFR1 (vascular endothelial growth factor receptor 1) and VEGFR2. This revealed the safety and immunogenicity in advanced colorectal cancer as presented at the 2011 ASCO Oral Abstract Session (J Transl Med. 2014; 12:63). We try to evaluate the benefit of the cancer vaccination in combination with gemcitabine (GEM) as first-line therapy in advanced PC patients. Methods: Sixty-eight chemotherapy naïve PC patients were enrolled to evaluate primarily the one year survival rate, and secondarily overall survival. Each of the three peptides was mixed with 1ml of Incomplete Freund’s adjuvant and subcutaneously administered weekly. GEM was administered at a dose of 1000 mg/m2 on days 1, 8, and 15 in a 28-day cycle. All enrolled patients received the therapy without knowing the HLA-A status, and the HLA genotypes were revealed at analysis point and then, the endpoints were evaluated between the HLA-A*2402 positive and HLA-A*2402 negative group. Results: Between June 2012 and May 2013, a total of 68 patients were enrolled in this study. No severe adverse effects of grade 3 or higher related to these three peptides were observed. The one year survival rate was 30.3%. Median survival time was 9.2months. Response rate was 11.8% and disease control rate was 73.5%, respectively. The HLA genotype will be revealed in March 2015 and the endpoints compared between HLA-A*2402 positive and negative group will be presented at this meeting. Conclusions: These results suggest that this combination therapy will be feasible and promising for the treatment of advanced pancreatic cancer. Clinical trial information: UMIN000008082.
A comparison of public reimbursement for oncology versus non-oncology drugs in Canada.
Authors: Nevzeta Bosnic, Krishna Donepudi, Jason Goodfield, Yvonne Zhang
Journal: Journal of Clinical Oncology (2015)

e17509 Background: In Canada, oncology drugs are reviewed by the pan-Canadian Oncology Drug Review (pCODR) while non-oncology drugs are reviewed by the Common Drug Review (CDR). pCODR began accepting submissions for oncology drugs in July 2011. Both pCODR and CDR evaluate drugs for clinical effectiveness and cost-effectiveness to provide formulary listing recommendations to the publicly funded drug plans for all provinces excluding Quebec. The decision to list and under what criteria is under the authority of the provinces. There is limited published research that compares oncology and non-oncology drug reimbursement rates (RR) and time to listing (TTL) in publicly funded formularies in Canada. The objective of this study was to identify and report on differences in public RR and TTL between oncology and non-oncology drugs in Canada. Methods: This analysis studied all pCODR and CDR recommendations from July 2011 to December 2014. IMS Brogan iMAM Database was used to gather provincial listing data for all drugs selected in this study. Public sources were used to determine submission dates, recommendation dates and recommendation decisions. TTL was calculated from CDR/pCODR recommendation date to the date of public formulary listing. Results: 81% (30 of 37) of drugs received a positive recommendation from pCODR and 63% (64 of 102) of drugs received a positive recommendation from CDR. 78% (29 of 37) of submissions to pCODR received at least one provincial listing versus only 38% (39 of 102) of drugs reviewed by CDR. The average time to receive first provincial listing for oncology and non-oncology drugs was 127 and 151 days, respectively. Across all provinces, average TTL was similar between oncology and non-oncology drugs. Conclusions: Oncology drugs in Canada had a higher reimbursement rate and similar time to listing on provincial formularies compared to non-oncology drugs.
Long-Term Azithromycin Reduces <i>Haemophilus influenzae</i> and Increases Antibiotic Resistance in Severe Asthma
Authors: Steven L. Taylor, Lex E. X. Leong, Fredrick M. Mobegi, Jocelyn M. Choo, Steve Wesselingh, Ian A. Yang, John W. Upham, Paul N. Reynolds, Sandra Hodge, Alan L. James, Christine Jenkins, Matthew J. Peters, Melissa Baraket, Guy B. Marks, Peter G. Gibson, Geraint B. Rogers, Jodie L. Simpson
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: The macrolide antibiotic azithromycin reduces exacerbations in adults with persistent symptomatic asthma. However, owing to the pleotropic properties of macrolides, unintended bacteriological consequences such as augmented pathogen colonization or dissemination of antibiotic-resistant organisms can occur, calling into question the long-term safety of azithromycin maintenance therapy.Objectives: To assess the effects of azithromycin on the airway microbiota, pathogen abundance, and carriage of antibiotic resistance genes.Methods: 16S rRNA sequencing and quantitative PCR were performed to assess the effect of azithromycin on sputum microbiology from participants of the AMAZES (Asthma and Macrolides: The Azithromycin Efficacy and Safety) trial: a 48-week, double-blind, placebo-controlled trial of thrice-weekly 500 mg oral azithromycin in adults with persistent uncontrolled asthma. Pooled-template shotgun metagenomic sequencing, quantitative PCR, and isolate whole-genome sequencing were performed to assess antibiotic resistance.Measurements and Main Results: Paired sputum samples were available from 61 patients (n = 34 placebo, n = 27 azithromycin). Azithromycin did not affect bacterial load (P = 0.37) but did significantly decrease Faith's phylogenetic diversity (P = 0.026) and Haemophilus influenzae load (P < 0.0001). Azithromycin did not significantly affect levels of Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, or Moraxella catarrhalis. Of the 89 antibiotic resistance genes detected, five macrolide resistance genes and two tetracycline resistance genes were increased significantly.Conclusions: In patients with persistent uncontrolled asthma, azithromycin reduced airway H. influenzae load compared with placebo but did not change total bacterial load. Macrolide resistance increased, reflecting previous studies. These results highlight the need for studies assessing the efficacy of nonantibiotic macrolides as a long-term therapy for patients with persistent uncontrolled asthma.
The association of rising serum uric acid levels with survival in renal cell carcinoma.
Authors: Kendrick Yim, Ahmet Bindayi, Rana R. McKay, Reza Mehrazin, Omer Raheem, Charles Field, Aaron Bloch, Robert Wake, Stephen Ryan, Anthony Patterson, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2019)

608 Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative and postoperative SUA levels between 8/2005-8/2014. Increased SUA was defined as &gt; 7mg/dL for males and &gt; 5.7 mg/dL for females. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. Results: 905 patients were analyzed. Decreased/stable SUA levels were noted in 675(74.6%) and increased SUA levels were noted in 230(25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs 18.3%, p = 0.004). Increased SUA had significantly greater de novo CKD (38.7% vs. 18.4%, p &lt; 0.001) and proteinuria (30.9% vs. 20.7%, p = 0.002). KMA demonstrated improved 5-year OS for patients with decreased/stable SUA compared to increased SUA for stage I, (93% vs. 60%), stage II (87% vs. 50%), and stage III (88% vs. 62%) RCC (all p &lt; 0.001). MVA revealed that increasing BMI (OR 1.05, p = 0.009), statin use (OR 0.11, p &lt; 0.001), dyslipidemia (OR 2.66, p = 0.004), stage III/IV cancer (OR 1.89, p = 0.015 and OR = 10.78, p &lt; 0.001), and postoperative de novo CKD stage 3 (OR 5.95, p &lt; 0.001) were predictors for increased postoperative SUA levels. MVA revealed increasing BMI (OR 1.09, p = 0.002), increasing SUA (OR = 4.70, p &lt; 0.001), stage IV RCC (OR = 7.7, p &lt; 0.001, and de novo CKD stage 3 (OR 7.07, p &lt; 0.001) to be independent risk factors for worsened all-cause mortality. Conclusions: Increasing SUA post operatively was associated with worsened outcomes in RCC patients. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.
Abstract P180: Combined Effect of Income and Medication Adherence on Mortality in Newly Treated Hypertension: a Nationwide Study of 16 Million Person-years
Authors: Hokyou Lee, Jong Heon Park, Sungha Park, Hyeon Chang Kim
Journal: Circulation (2019)

Introduction: Low socioeconomic status and poor medication adherence are known to increase mortality among patients with hypertension, but their combined effects have not been well studied. Hypothesis: We hypothesized that excess risks for all-cause and cardiovascular deaths by medication adherence are greater in lower income individuals with hypertension. Methods: We followed 1,679,527 persons, aged 30 to 80 years, with newly treated hypertension and no prior cardiovascular disease (CVD), for 10 years using the Korean National Health Insurance database. Exposure variables were household income in quintiles and medication adherence estimated by medication possession ratio: good (≥0.8), moderate (0.5 to &lt;0.8), or poor (&lt;0.5). Outcomes were all-cause and CVD-related deaths. We used Cox proportional hazards model to calculate hazard ratios (HR) adjusted for age, sex, comorbidity, and other covariates. Results: Both low income and poor adherence were independently associated with higher mortality (HR=1.51, 95% CI=1.49-1.54, lowest vs. highest income; HR=1.65, 95% CI=1.64-1.67, poor vs. good adherence). However, when stratified by combination of income and adherence (figure), excess risk by non-adherence gradually increased towards lower household income, especially in men. Excess risk for death by poor medication adherence was 117% (HR, 2.78 vs. 1.61, poor vs. good adherence) in lowest-income men and 59% in highest-income men. In women, risk difference by income was also present, but was not as prominent as in men. Excess risk for death by poor adherence was 75% (HR, 2.07 vs. 1.32, poor vs. good adherence) in lowest-income women and 54% in highest-income women. Similar findings were observed for CVD-related death also. Conclusion: Poor medication adherence is associated with higher mortality, but patients with low income are subject to greater excess risk by non-adherence. This highlights the potential importance of promoting adherence for risk reduction especially in low-income patients with hypertension.
Harnessing the Power of Machine Learning in Dementia Informatics Research: Issues, Opportunities, and Challenges
Authors: Gavin Tsang, Xianghua Xie, Shang-Ming Zhou
Journal: IEEE Reviews in Biomedical Engineering (2019)

Dementia is a chronic and degenerative condition affecting millions globally. The care of patients with dementia presents an ever-continuing challenge to healthcare systems in the 21st century. Medical and health sciences have generated unprecedented volumes of data related to health and wellbeing for patients with dementia due to advances in information technology, such as genetics, neuroimaging, cognitive assessment, free texts, routine electronic health records, etc. Making the best use of these diverse and strategic resources will lead to high-quality care of patients with dementia. As such, machine learning becomes a crucial factor in achieving this objective. The aim of this paper is to provide a state-of-the-art review of machine learning methods applied to health informatics for dementia care. We collate and review the existing scientific methodologies and identify the relevant issues and challenges when faced with big health data. Machine learning has demonstrated promising applications to neuroimaging data analysis for dementia care, while relatively less effort has been made to make use of integrated heterogeneous data via advanced machine learning approaches. We further indicate future potential and research directions in applying advanced machine learning, such as deep learning, to dementia informatics.
Glioblastoma cancer stem cell biology: Potential theranostic targets
Authors: Farzaneh Sharifzad, Saeid Ghavami, Javad Verdi, Soura Mardpour, Mahsa Mollapour Sisakht, Zahra Azizi, Adeleh Taghikhani, Marek J. Łos, Esmail Fakharian, Marzieh Ebrahimi, Amir Ali Hamidieh
Journal: Drug Resistance Updates (2019)
Influence of geographic mobility on lung cancer survival.
Authors: Daniel Jacob Becker, David S Fink, Benjamin Philip Levy
Journal: Journal of Clinical Oncology (2015)

e17628 Background: An expanding body of research attests to the importance of social determinants of cancer outcomes. The fundamental paradigm of social epidemiology is that health outcomes are worse for the powerless than for the empowered in social hierarchies. We used geographic mobility as a novel marker of social capital in an examination of lung cancer mortality. Methods: We used the Surveillance Epidemiology and End Results 9 (SEER) database to conduct a cross sectional analysis of patients with stage I- IV lung cancer, diagnosed between 2000 and 2010. We examined the association of geographic mobility, defined as different birth state and diagnosis state, with lung cancer specific survival (LCSS). We used multivariable Cox Proportional Hazards to model the association between geographic mobility and LCSS, controlling for age, sex, race, stage, and location of diagnosis. Results: We included 47,619 (46.3%) patients born and diagnosed with stage I-IV lung cancer in the same state (SS), and 55,235 (53.7%) patients born and diagnosed with lung cancer in different states (DS). The DS group was slightly older and had more African Americans than the SS group (16.7% versus 8.0% p < 0.001). In the overall adjusted model, SS patients were more likely to die from lung cancer (HR 1.03 [95% CI 1.01-1.04]), as were males (HR 1.14 [CI 1.12-1.15], African Americans (HR 1.05 [1.02-1.08]), and elderly patients ( > 80) (HR 1.83 [1.77-1.90). The effect of geographic mobility differed by race (p for interaction 0.005). Among African Americans lack of geographic mobility was associated with a 10% increase in death from lung cancer (HR 1.10 CI 1.05-1.15). White lung cancer patients showed a smaller effect of geographic mobility (HR 1.02 CI 1.00-1.03). Conclusions: African Americans with lung cancer have more geographic mobility than whites. African American lung cancer patients born and diagnosed in the same state, however, are more likely to die from lung cancer. The combination of race and geographic mobility can be used to identify disadvantaged patients at high risk of poor lung cancer outcomes. Future studies should consider geographic mobility as a covariate when social determinants of health are pertinent.
Abstract 14244: Gender-Specific Association Between Serum Markers of Systemic Inflammation and Interstitial Cardiac Fibrosis: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Victor Nauffal, Bharath Ambale Venkatesh, Colin Wu, Hossein Bahrami, Russell Tracy, Mary Cushman, David A Bleumke, Joao A Lima
Journal: Circulation (2015)

Introduction: Inflammation contributes to pathogenic ventricular remodeling. Recently, T1 mapping has been used to non-invasively measure interstitial myocardial fibrosis. We examined the association between baseline markers of systemic inflammation and interstitial fibrosis measured using T1 mapping at 10 years follow-up in MESA. Methods and Results: 1,156 participants underwent cardiac magnetic resonance imaging with T1 mapping. All analyses were stratified by gender. Three hierarchical multivariable linear regression models were constructed to assess the risk-adjusted association of baseline C-reactive protein (CRP), interleukin 6 (IL-6) and fibrinogen with 25 minutes post-contrast myocardial T1 time (T1Myo25). Shorter T1Myo25 reflect increasing levels of interstitial fibrosis. We found a non-linear relationship between IL-6 and T1Myo25 in males (Figure 1A). A significant negative association between T1Myo25 and increasing levels of IL-6 was found in males that reversed at IL-6 levels ≥2.7pg/ml. Moreover in males, increasing levels of fibrinogen were significantly negatively associated with T1Myo25, while a similar but non-significant trend was found for CRP (Figure 1B). In women, there was a similar inverse association between T1Myo25 and increasing levels of all three markers of systemic inflammation prior to adjusting for body mass index that became statistically non-significant following adjustment (Figure 1B). Similar associations with markers of inflammation were found using extracellular volume fraction and T1Myo12 as measures of interstitial fibrosis. Conclusions: Markers of systemic inflammation in males, particularly IL-6 and fibrinogen, are independently associated with increased interstitial fibrosis. In females, this association may be mediated by the obesity-induced inflammatory-state. These findings highlight the early role of inflammation in the pathogenesis of heart failure.
Dietary Restrictions and Nutrition in the Prevention and Treatment of Cardiovascular Disease
Authors: Sebastian Brandhorst, Valter D. Longo
Journal: Circulation Research (2019)

Cardiovascular disease (CVD) is the leading cause of death in many developed countries and remains one of the major diseases strongly affected by the diet. Nutrition can affect CVD directly by contributing to the accumulation of vascular plaques and also indirectly by regulating the rate of aging. This review summarizes research on nutrition and CVD incidence based on a multipillar system that includes basic research focused on aging, epidemiological studies, clinical studies, and studies of centenarians. The relevant research linking nutrition and CVD with focus on macronutrients and aging will be highlighted. We will review some of the most relevant studies on nutrition and CVD treatment, also focusing on interventions known to delay aging. We will discuss both everyday dietary compositions, as well as intermittent and periodic fasting interventions with the potential to prevent and treat CVD.
Abstract P293: Effects of Diets That Vary in Fatty Acid Composition on Fecal Short-chain Fatty Acid Levels and Their Relationship With Circulating Lipids and Lipoproteins
Authors: Kate J Bowen, Penny M Kris-Etherton, Peter J Jones, Lavanya Reddivari
Journal: Circulation (2019)

Introduction: The short-chain fatty acids (SCFA) acetic acid, propionic acid, and butyric acid are microbial-produced metabolites that can influence host physiology through regulation of hepatic cholesterol metabolism. These biologically relevant gut metabolites may play a role in the hypocholesterolemic effects of select dietary components. The objective of this exploratory study was to determine the effects of diets that differ only in fatty acid composition on fecal SCFA levels and to assess their correlations with circulating lipids, lipoproteins, and apolipoproteins. Hypothesis: We assessed the hypothesis that dietary fat quality will differentially affect fecal SCFA and there will be significant associations between fecal SCFA levels and those of circulating total cholesterol, low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and apolipoprotein (apo) B. Methods: In a double-blind, randomized, three period crossover, controlled feeding clinical trial, participants with ≥2 metabolic syndrome criteria (n=20) were provided with a weight maintenance, controlled feeding base diet plus conventional canola oil, high-oleic acid canola oil (HOCO), or a control oil (control diet formulated to represent a Western diet fatty acid profile) for 6 weeks followed by washout periods of ≥4 weeks. The macronutrient profiles of the diets were: canola diet [17.5% monounsaturated fatty acid (MUFA), 9.2% polyunsaturated fatty acid (PUFA), 6.6% saturated fatty acid (SFA)], HOCO diet (19.1% MUFA, 7.0% PUFA, 6.4% SFA), and control diet (10.5% MUFA, 10.0% PUFA, 12.3% SFA). Fecal and blood samples were collected at study enrollment and at the end of each diet. Results: After 6 weeks, a trend toward a treatment effect on endpoint fecal propionic acid was observed ( P =0.09), with a trend toward a higher concentration following the control compared to the canola diet ( P =0.09). Acetic acid was increased from baseline following the control diet ( P =0.04). After the control diet only, fecal levels of propionic acid were positively correlated with blood levels of LDL-C, non-HDL-C, and apo B (r=0.52 to 0.64, P =0.003 to 0.02), with a trend for total cholesterol (r=0.39, P =0.10), and acetic acid was positively correlated with LDL-C and apo B levels (r=0.48 to 0.49, P =0.03 to 0.04), with a trend for non-HDL-C (r=0.44, P =0.06). No significant correlations between fecal SCFA and lipids and lipoproteins were observed after the two canola oil-based diets. Conclusions: In conclusion, these data suggest that the adverse effects of a contemporary Western diet fatty acid profile on circulating lipid and lipoprotein parameters compared to diets higher in unsaturated fat and lower in SFA may be mediated by gut-derived SCFA.