tbuckley/cabot-search huggingface dataset:
Abstract MP22: Association Of Intra-individual Daily Variability In Sleep With Metabolic Outcomes In Youth: Multidimensional Assessment Of Preschoolers Study (MAPS)
Authors: Mercedes R Carnethon, Mandy Wong, Charles Hansell, Kristen KNUTSON, Megan McCabe, Amy Krefman, Amanda M Perak, Wakschlag Lauren, Norrina B Allen
Journal: Circulation (2020)

Background: Average nightly sleep duration is associated with cardiometabolic health; both short- and long-sleep are associated with obesity, diabetes, hypertension and cardiovascular disease. An equally important measure of cardiometabolic health is an individual’s daily variability (DV) in sleep timing and duration. Greater intra-individual DV is associated with less favorable cardiometabolic health in adults, but less is known about the association of DV with cardiometabolic health in youth. We hypothesize that DV in sleep timing and duration is associated with less favorable body mass index (BMI), systolic blood pressure and waist girth among youth. Methods: Boys and girls aged 9-13 years old who wore the Actigraph GT-3X BT on their non-dominant wrist for a minimum of 4 days and had available measures of cardiometabolic health were included in the analysis (N=91). Validated algorithms from ActiLife software were used to determine daily total sleep time, sleep efficiency, sleep onset and time out of bed. We calculated DV in sleep onset, time out of bed and duration as the coefficient of variation (CV = standard deviation/overall mean). Average sleep measures were calculated across the days worn. We modeled the association of each sleep measure with metabolic outcomes using multivariable linear regression. Results: On average, participants slept for 7.23 (SD=1.4) hours per night, BMI percentile (BMI%) was 63.0 (SD=30.9), waist girth was 66.7 cm (SD=10.8) and systolic blood pressure percentile (SBP%) was 41.4 (SD= 21.4). Higher DV in sleep onset was associated with significantly higher BMI% and positively associated with SBP%. There was no association of average sleep measures with any outcomes. Findings were consistent by sex and age. Conclusions: Daily variability in time to sleep in youth was associated with higher BMI% and a modest association with SBP%. Future studies should test whether promoting consistent bedtimes can improve cardiometabolic health.
Abstract 15165: Paradoxical Association Between Epicardial Fat Volume and Lower Risk of Major Adverse Cardiac Events in Asymptomatic Patients With Very High Coronary Artery Calcium Score
Authors: Mohamad Karnib, Armando Ugo Cavallo, Sadeer G Al-Kindi, David A Zidar, Sanjay Rajagopalan, Farshad Forouzandeh
Journal: Circulation (2018)

Background: Epicardial adipose tissue has been linked to coronary artery disease. Whether epicardial fat volume (EFV) is associated with risk of cardiovascular disease in patients with extensive co...
The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression
Authors: Yuqing Wu, Siwei Zhang, Xiaoxiao Gong, Samantha Tam, Desheng Xiao, Shuang Liu, Yongguang Tao
Journal: Molecular Cancer (2020)

Abstract Ferroptosis, a novel form of regulated cell death, is different from other types of cell death in morphology, genetics and biochemistry. Increasing evidence indicates that ferroptosis has significant implications on cell death linked to cardiomyopathy, tumorigenesis, and cerebral hemorrhage to name a few. Here we summarize current literature on ferroptosis, including organelle dysfunction, signaling transduction pathways, metabolic reprogramming and epigenetic regulators in cancer progression. With regard to organelles, mitochondria-induced cysteine starvation, endoplasmic reticulum-related oxidative stress, lysosome dysfunction and golgi stress-related lipid peroxidation all contribute to induction of ferroptosis. Understanding the underlying mechanism in ferroptosis could provide insight into the treatment of various intractable diseases including cancers.
Abstract 392: Use of a Low Resource Model for Group Cardiopulmonary Resuscitation Training: Knowledge Gains and Attitude Changes
Authors: Matthias Goldstein, Benjamin Goldstein, Joel Novograd, Inayzha Wallace, Leah Goldstein, Kailah Carden
Journal: Circulation (2019)

Introduction: CPR training and regular skills practice is often limited by the availability of a high resource device such as a manikin torso. We investigated the knowledge gains and attitude changes in student participants of group hands-only CPR training (20-50 participants) using a low resource device, a bed pillow, to practice skills. Methods: Hands-only CPR trainings, utilizing a bed pillow for skills practice, were conducted for groups of college students. Using a one-group pre-test post-test design, participants (n=360) completed a questionnaire which included demographic information, prior history of CPR training, and multiple-choice questions to evaluate knowledge. Five-point Likert scale questions were used to assess attitudes specific to willingness to perform CPR, confidence in ability to perform CPR and likeliness to practice skills in the next year. The survey was completed prior to training. The participants then watched a demonstration followed by interactive skills practice on a pillow. A specially designed printed pillow case was used to show hand position landmarks and review information. The post training survey was then completed and each participant was provided a printed pillow case for future skills practice and review. Results: 129 participants (36%) had no prior CPR training, there were more females 273 (76%) than males, and the average age of participants was 20 years old. Correct knowledge regarding depth of compressions increased by 47% (47 to 94) while speed of compression knowledge increased by 52% (40 to 92). In a paired analysis, there were significant differences (p&lt;.0001) in all attitude measures from pre-to-post training. Willingness to perform CPR increased 31% (gain=0.94, pre test=3.01), confidence to perform CPR, 45% (gain=1.18, pre test=2.64) and likeliness to practice skills in the next year, 20% (gain=0.59, pre test=2.97). Conclusions: Participation in group hands-only CPR training using a low resource device for skills practice resulted in significant knowledge gains and improved attitudes in the areas of willingness to perform CPR, confidence to perform CPR and skills practice likeliness. This training method can provide an accessible and cost-effective means for providing group CPR training.
Abstract 15: Trends in Atrial Fibrillation-related Cardiovascular Mortality Rates in The United States: 1999-2017
Authors: Yoshihiro Tanaka, Nilay Shah, Rod Passman, Philip Greenland, Sadiya Khan
Journal: Circulation (2020)

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in adults and the prevalence is increasing due to the aging of the population and the growing burden of vascular risk factors. Although deaths due to cardiovascular disease (CVD) death have dramatically decreased in recent years, trends in AF-related CVD death has not been previously investigated. Purpose: We sought to quantify trends in AF-related CVD death rates in the United States. Methods: AF-related CVD death was ascertained using the CDC WONDER online database. AF-related CVD deaths were identified by listing CVD (I00-I78) as underlying cause of death and AF (I48) as contributing cause of death among persons aged 35 to 84 years. We calculated age-adjusted mortality rates (AAMR) per 100,000 population, and examined trends over time estimating average annual percent change (AAPC) using Joinpoint Regression Program (National Cancer Institute). Subgroup analyses were performed to compare AAMRs by sex-race (black and white men and women) and across two age groups (younger: 35-64 years, older 65-84 years). Results: A total of 522,104 AF-related CVD deaths were identified between 1999 and 2017. AAMR increased from 16.0 to 22.2 per 100,000 from 1999 to 2017 with an acceleration following an inflection point in 2009. AAPC before 2009 was significantly lower than that after 2009 [0.4% (95% CI, 0.0 - 0.7) vs 3.5% (95% CI, 3.1 - 3.9), p &lt; 0.001). The increase of AAMR was observed across black and white men and women overall and in both age groups (FIGURE), with a more pronounced increase in black men and white men. Black men had the highest AAMR among the younger decedents, whereas white men had the highest AAMR among the older decedents. Conclusion: This study revealed that death rate for AF-related CVD has increased over the last two decades and that there are greater black-white disparities in younger decedents (&lt;65 years). Targeting equitable risk factor reduction that predisposes to AF and CVD mortality is needed to reduce observed health inequities.
Phase I study of continuous oral dosing of an irreversible CYP17 inhibitor, abiraterone (A), in castration refractory prostate cancer (CRPC) patients (p) incorporating the evaluation of androgens and steroid metabolites in plasma and tumor
Authors: G. Attard, T. A. Yap, A. H. Reid, C. Parker, M. Barrett, F. Raynaud, M. Dowsett, D. Dearnaley, G. Lee, J. S. De Bono
Journal: Journal of Clinical Oncology (2007)

5063 Background: Despite androgen deprivation therapy, recent studies indicate high levels of intra-tumor androgens and continued androgen receptor (AR) signalling in CRPC. Methods: A phase I trial to evaluate the safety and tolerability of A administered once daily at 250, 500, 750, 1,000 and 2,000 mg to chemotherapy-naïve CRPC p. Extensive endocrine evaluation and CTC enumeration were undertaken. Tumor biopsies pre- and post-therapy were evaluated for androgen levels and TMPRSS2/ETS gene translocations. To investigate secondary resistance due to activation of a promiscuous AR by raised precursor steroids upstream of CYP17, all p who progressed were offered combination treatment of A with dexamethasone 0.5mg od (D). Results: 15 p were treated in 3-p cohorts with PSA declines &gt;70% in 9/16 p ( table ) and subsequent expansion of the maximum biologically available dose of 1,000mg (19 p treated to date). All p had progressed on LHRH agonists and antiandrogens, 7/15 on diethylstilboestrol and 7/15 on steroids. No dose limiting toxicities were observed and the only = grade 2 toxicity was reversible hypertension (5 pts) due to CYP17 inhibition. Pharmacokinetics were dose-proportional; mean drug clearance was 803L/hour; mean Vd was 11680L; mean elimination half-life was 10.6 hours. At all dose levels, treatment was associated with increased steroid precursor levels upstream of CYP17, including up to a 300-fold rise in corticosterone levels, as well as loss of detection of adrenal androgens. Circulating testosterone levels were in the castrate range (&lt;50 ng/dl) at baseline, rapidly becoming undetectable (&lt;1 ng/dl) in all p. Conclusion: A can be safely administered to CRPC pts with CYP17 suppression and important anti-tumor activity suggesting that at least 60% of CRPC are still hormone driven. Phase II evaluation of 1,000 mg is ongoing. [Table: see text] [Table: see text]
Abstract P203: Dietary Magnesium, C-reactive Protein and Interleukin-6: The Strong Heart Family Study
Authors: Nandana Rao, Rozenn Lemaitre, Colleen Sitlani, Jason G Umans, Lyle G BEST, Amanda M Fretts
Journal: Circulation (2020)

Background: Both experimental animal and human observational studies have suggested that magnesium (Mg) deficiency influences systemic inflammation. Whether this association is modified by genes associated with Mg metabolism and transport is unknown. Objective: To examine associations of reported Mg intake, and the interaction of reported Mg intake with a single nucleotide polymorphisms (SNP) related to Mg metabolism and transport, on serum markers of inflammation (i.e., C-reactive protein (CRP) and interleukin 6 (IL-6)). Methods: This cross-sectional study included 1,924 participants from the Strong Heart Family Study—a study of risk factors for cardiovascular diseases among American Indians (AIs) from 12 communities in the United States. Intake of Mg from foods and dietary supplements was ascertained using a 119-item Block food frequency questionnaire. Serum hsCRP and IL-6 were measured from blood collected after a 12-hour fast, and candidate SNP (rs3740393) was genotyped using MetaboChip. Generalized estimating equations, with clusters defined by family membership, were used to examine associations of Mg intake, and the interaction of rs3740393 with estimated dietary Mg, on CRP and IL-6. Results: FFQ-estimated Mg intake was not associated with CRP or IL-6. We observed no interaction of reported Mg intake with rs3740393 on CRP (p-interaction=0.70). However, we observed an interaction (p-interaction=0.018) of reported Mg intake with rs3740393 on IL-6. (Table). Conclusion: Reported Mg intake is inversely associated with serum IL-6 among carriers of the C allele at rs3740393. Future research is necessary to replicate this finding, and to examine other Mg-related genes that may influence associations of Mg intake or sufficiency with inflammation.
Randomized study comparing nab-paclitaxel with solvent-based paclitaxel in Chinese patients (pts) with metastatic breast cancer (MBC)
Authors: Z. Guan, F. Feng, Q. L. Li, Z. Jiang, Z. Shen, S. Yu, J. Feng, J. Huang, Z. Yao, M. J. Hawkins
Journal: Journal of Clinical Oncology (2007)

1038 Background: The results of a large clinical study comparing solvent-based paclitaxel 175 mg/m 2 with 130-nM albumin-bound paclitaxel (nab-paclitaxel) 260 mg/m 2 demonstrated that nab-paclitaxel had greater efficacy and a favorable safety profile in pts with MBC (Gradishar et al., JCO, 2005; 23:7794). The maximum tolerated dose of nab-paclitaxel was 300 mg/m 2 infused over 30 minutes without premedication in Chinese pts with solid tumors (Teng et al., Ai Zheng, 2004;23:1431). The aim of this randomized study is to compare the response rates and to evaluate the safety of nab-paclitaxel with those of solvent-based paclitaxel in Chinese pts with MBC. Methods: In this open-label, multicenter study, 210 pts with MBC were assigned to either solvent-based paclitaxel 175 mg/m 2 intravenously (IV) over 3 hours every 3 weeks (q3w) with standard premedication (steroids and antihistamines) or nab-paclitaxel 260 mg/m 2 IV over 30 minutes q3w with no premedication for 1–6 cycles. The primary endpoints were the overall response rate (ORR, complete or partial response) and toxicity. Stable disease (SD) at =16 weeks was measured. All pts who received at least 1 dose of study drug were evaluable for study endpoints. Results: 210 pts (median age, 50 years; 70% postmenopausal) were enrolled from 29 June 2005 - 1 August 2006. Efficacy results are summarized in the Table . The common toxicities occurring at =20% were alopecia (78%), peripheral neuropathy (75%, 7% gr 3), neutropenia (65%), leucopenia (60%), myalgia (39%), arthralgia (23%), and nausea (21%) and were similar between groups (P = NS). Gr 3/4 neutropenia, measured on days 1 and 8, were similar between groups (p = 0.202). Conclusions: Compared to solvent- based paclitaxel, treatment with nab-paclitaxel was associated with a higher response rate and longer time to progression without increased toxicity. These comparative data in Chinese pts are almost identical to results previously reported in Caucasian pts (Gradishar et al, JCO, 2005). [Table: see text] [Table: see text]
Abstract P493: Small Dense Low-density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression
Authors: Hiroaki Ikezaki, Yuya Yokota, Masumi Ai, Bela F Asztalos, Masayuki Murata, Jun Hayashi, Ernst J Schaefer
Journal: Circulation (2020)

Introduction: Carotid intimal medical thickness (cIMT) is associated with cardiovascular disease (CVD). The association between atherogenic lipoproteins including small dense low-density lipoprotein cholesterol (sdLDL-C) and carotid intimal medial thickness (cIMT) progression has not been fully evaluated in a prospective cohort study. Hypothesis: We assessed the hypothesis that sdLDL-C is the most atherogenic lipoproteins with regard to cIMT progression. Methods: Kyushu and Okinawa Population Study (KOPS) is a community-based, prospective, and observational study in Japan which has been underway since 2004 and a total of 18,762 participants have been enrolled. For this study, we included 2,030 male and female participants (median age 59 years at baseline) who were free of CVD and off cholesterol lowering medication, and had cIMT measured at both baseline and after 5 years follow-up survey. Using plasma samples obtained from those subjects after overnight fast, we measured total cholesterol, direct low-density lipoprotein cholesterol (LDL-C), sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), adiponectin and high sensitivity C reactive protein (hs CRP). Their cIMT levels were measured by B-mode ultrasonography with a 10 MHz probe at far walls of their both right and left common carotid arteries. Results: Median cIMT at baseline was 0.63 mm and median 5 year progression was 0.18 mm. After adjustment for standard CVD risk factor including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C &lt; 100 mg/dL, considered to be at low CVD risk, elevated sdLDL-C were associated with cIMT progression ( P for trend = 0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Conclusions: In conclusion, both sdLDL-C and direct LDL-C are significantly associated with cIMT progression. Moreover sdLDL-C has stronger relationship with cIMT progression than does LDL-C; therefore, measurement of sdLDL-C may allow for the formulation of optimal therapy to cIMT progression.
Radiographic evaluation of recurrent glioblastoma multiforme (GBM) in patients treated with bevacizumab and irinotecan
Authors: J. Andre, K. Spearman, S. Lu, S. Hwang, L. Dorsett, S. Raval
Journal: Journal of Clinical Oncology (2007)

12512 Background: Recurrent GBM carries a poor prognosis after first-line therapies have been exhausted, even in the setting of gross total resection. Bevacizumab and Irinotecan have shown promising results in patients with recurrent GBM (Stark-Vance, et al. Neuro- Oncol, 2005). We sought to retrospectively document the short-term effects of this chemotherapeutic regimen on recurrent GBM, as evidenced by comparative MRI brain scans obtained prior to, and one-month following initiation of treatment. Methods: We collected brain MRI data from August 2005 to December 2006, in which post-contrast spin-echo T1-weighted images demonstrated measurable enhancement and/or GBM tumor mass. Having failed temozolomide and radiation therapy, 14 consecutive patients’ MRI scans were available for review at this institution by a neuro-radiologist, in which both pre- and post-treatment hard and/or soft copy MR images were available for direct measurement. Each was treated with Bevacizumab 5 mg/kg IV and Irinotecan 125 mg/m2 IV infusion every 2 weeks until disease progression, or development of unacceptable toxicity. We measured pre- and post-treatment recurrent GBM bulk tumor in anteroposterior, transverse, and cranio-caudad dimensions, and calculated volumetric data, assuming an ellipsoid tumor configuration. Results: Pre-treatment MRI scans were performed 2 weeks prior to initiation of therapy (Mean: 13 days; Median: 10 days). Post-treatment scans were performed at approximately one month following initial treatment (Mean: 30 days; Median: 28 days). All patients witnessed significant decrease in tumor bulk volume ranging from 15.3 to 89.8%, having received an average of two cycles of chemotherapy. We observed a mean decrease in tumor volume of 46.6% (SD = 22.6%; SEM = 6.0%; 95% CI = 33.6 - 60.0 % decrease). Conclusions: We report 46.6% mean reduction in recurrent GBM tumor bulk at an average of 1-month post-treatment in patients treated with an average of two cycles of Bevacizumab and Irinotecan therapy. These promising initial results necessitate further long-term prospective evaluation of this chemotherapy. No significant financial relationships to disclose.
Abstract P357: Relative Validity and Reliability of a Diet Risk Screener (DRS) for Clinical Practice
Authors: Emily A Johnston, Kristina S Petersen, Linda VAN HORN, Diane C Mitchell, Jeannette M Beasley, Penny M Kris-etherton
Journal: Circulation (2020)

Poor diet quality contributes significantly to cardiometabolic mortality in the US. Diet assessment methodology is burdensome and non-standardized. Screeners for clinical use that rapidly assess dietary choices associated with cardiometabolic risk could enhance prevention. This study evaluated the relative validity and reliability of the Diet Risk Screener (DRS) in a sample of US adults with the hypothesis that the DRS would correlate with a validated measure of diet quality. The DRS includes nine questions related to foods/food groups strongly associated with cardiometabolic mortality based on previous evidence. Adults ages 35-75 were recruited through a national health volunteer registry (ResearchMatch.org). Participants completed the DRS and a validated food frequency questionnaire (FFQ) (Vioscreen.com) in random order on one occasion. To assess reliability, participants who completed the DRS were asked to repeat it within three months. The DRS was scored 0 (low risk) to 27 (high risk) and compared with the Healthy Eating Index (HEI)-2015 calculated from the FFQ (max. score 100). The DRS was moderately correlated with HEI-2015 [(n=126, 87% female; mean HEI-2015: 63.3 (95% CI: 61.1, 65.4); mean DRS: 11.8 (95% CI: 10.8, 12.8); r=-0.6, p&lt;0.001; R 2 =0.36]. Furthermore, the DRS ranked 37% (n=47) of subjects in the same quintile and 41% (n=52) within ± 1 quintile of the HEI-2015 (weighted kappa=0.27). The DRS had high reliability (n=102, ICC: 0.83). Mean completion time was two minutes. The DRS may be useful in clinical or other time-limited settings to quickly identify individuals at high risk of diet-related preventable cardiometabolic mortality.
Pharmacoeconomic analysis of a combination of capecitabine (X) with docetaxel (D) and trastuzumab (H) first-line in HER2- positive advanced or metastatic breast cancer
Authors: A. Bonetti, A. Santoro, A. Cirrincione, G. Giuliani, R. Bell
Journal: Journal of Clinical Oncology (2007)

17036 Background: A recently published (Wardley et al ESMO 2006) randomized phase II trial (CHAT) compared XDH with DH. The primary endpoint, overall response rate, was similar with XDH (71%) and DH (73%), while XDH showed superior time to progression (TTP) (hazard ratio [HR] 0.70, p=0.045, median 18.2 vs 13.8 months, respectively) and a trend toward superior progression-free survival (HR 0.72, p=0.06, median 14.8 vs 12.8 months, respectively). Overall survival data are immature. This analysis evaluates potential pharmacoeconomic impacts of adding X to DH. Methods: Direct medical costs during the study were estimated from the Italian health system perspective. Actual doses of both regimens were modeled from trial data. Grade 3/4 adverse events (AEs) and related medications were analyzed to estimate costs of treating major AEs. Other costs relating to laboratory tests and drug administration were assumed to be the same in both arms. Results: Total direct medical costs were slightly lower for XDH: €15250 vs €15570 for DH. As expected, the main cost drivers were drug costs: €14,370 vs €14,690, respectively. XDH and DH safety profiles were different: XDH resulted in more grade 3/4 non-hematologic AEs than DH (total: 77% vs 68%; hand-foot syndrome: 16% vs &lt;1%; diarrhea: 11% vs 4%, respectively), but less grade 3/4 neutropenia (54% vs 77%), complicated neutropenia (20% vs 24%) and febrile neutropenia (14% vs 23%). The estimated mean AE costs per patient were similar in both arms. Conclusion: With the convenience of oral therapy, adding X to DH does not increase the number and duration of infusion visits or increase costs. For patients, physicians and payers, XDH is a good alternative for the treatment of advanced/metastatic breast cancer. [Table: see text]