tbuckley/cabot-search huggingface dataset:
Abstract P398: Relative versus Absolute Neighborhood Economic Conditions and Risk of Stroke in a United States National Cohort
Authors: Erica Twardzik, Yeonwoo Kim, Suzanne E Judd, Manish Verma, Solveig Argeseanu Cunningham, Virginia J Howard, Dawn Kleindorfer, Natalie Colabianchi
Journal: Circulation (2020)

Introduction: Neighborhood economic conditions are important predictors of incident stroke. Neighborhood economic conditions can be characterized differently but studies have not identified which characterizations are most predictive of incident stroke. Previous work has suggested that the income distribution within the population may be more relevant for chronic disease than the absolute value of median income of the population. This project aims to estimate the effects of neighborhood income and neighborhood income inequality on incidence stroke. Hypothesis: Neighborhood income inequality and absolute neighborhood income will predict incident stroke above and beyond demographic characteristics and individual socioeconomic status. Methods: We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national longitudinal study of black and white older adults (N=29,443). Baseline median household income and the Gini coefficient of income inequality at the Census Tract level were obtained from the 2000 decennial census. Both variables were standardized to have a mean of 0 and a standard deviation of 1; z-score of median household income was multiplied by -1 (representing neighborhood income deprivation) to allow for comparability. Using Cox Proportional Hazards analysis we examined the risk of stroke associated with these exposures in separate models. Model 1 was unadjusted, Model 2 was adjusted for demographic characteristics (age, race, sex, marital status), and Model 3 was adjusted for individual socioeconomic characteristics (household income and education). Results: Within Model 1, neighborhood income deprivation (HR: 1.18; 95% CI 1.11-1.24) and neighborhood income inequality (HR: 1.10; 95% CI: 1.05-1.16) were both significantly associated with risk of stroke. The association persisted in Model 2: neighborhood income deprivation (HR: 1.13; 95% CI 1.07-1.20) and neighborhood income inequality (HR: 1.06; 95% CI: 1.00-1.11). Within Model 3, neighborhood income deprivation maintained its positive association (HR: 1.06; 95% CI 1.00-1.13), while neighborhood income inequality was no longer predictive of stroke risk (HR:1.04; 95% CI 0.99-1.10). Conclusions: Neighborhood income deprivation and neighborhood income inequality were similar predictors of incident stroke. The effect of absolute economic resources in a Census Tract was slightly larger than the relative economic standards within a Census Tract. There is a need to investigate other characterizations of neighborhood economic conditions, such as residential income segregation. The findings from this project suggest that there are multiple policy levels that can be used to decrease incident stroke, through decreasing income inequality and improving the absolute economic conditions of deprived neighborhoods.
Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration
Authors: Elisabeth H. Thijssen, Renaud La Joie, Amy Wolf, Amelia Strom, Ping Wang, Leonardo Iaccarino, Viktoriya Bourakova, Yann Cobigo, Hilary Heuer, Salvatore Spina, Lawren VandeVrede, Xiyun Chai, Nicholas K. Proctor, David C. Airey, Sergey Shcherbinin, Cynthia Duggan Evans, John R. Sims, Henrik Zetterberg, Kaj Blennow, Anna M. Karydas, Charlotte E. Teunissen, Joel H. Kramer, Lea T. Grinberg, William W. Seeley, Howie Rosen, Bradley F. Boeve, Bruce L. Miller, Gil D. Rabinovici, Jeffrey L. Dage, Julio C. Rojas, Adam L. Boxer
Journal: Nature Medicine (2020)
Hyperbranched lipoid-based lipid nanoparticles for bidirectional regulation of collagen accumulation in liver fibrosis
Authors: Jian-Bin Qiao, Qian-Qian Fan, Cheng-Lu Zhang, Jaiwoo Lee, Junho Byun, Lei Xing, Xiang-Dong Gao, Yu-Kyoung Oh, Hu-Lin Jiang
Journal: Journal of Controlled Release (2020)
UGT1A1 genotype influences clinical outcome in patients with intermediate-risk acute myeloid leukemia treated with cytarabine-based chemotherapy
Authors: Johana Díaz-Santa, Rocío Rodríguez-Romanos, Gemma Osca, Marta Pratcorona, Ana Garrido, Rosa Coll, Carla Moret, Lourdes Escoda, Mar Tormo, Inma Heras, Montse Arnan, Susanna Vives, Olga Salamero, Natàlia Lloveras, Joan Bargay, Antònia Sampol, David Cruz, Antoni Garcia, Teresa Quiñones, Jordi Esteve, Jorge Sierra, David Gallardo
Journal: Leukemia (2020)
Sorin Memo 3D弁輪形成リングの長軸サドル型柔軟性と短軸楕円状安定性:三次元REAL VIEW解析からの洞察
Authors: Tsuneto Akira, Eishi Kiyoyuki, Hashizume Koji, Miura Takashi, Tanigawa Kazuyoshi, Yamachika Shiro, Uchida Yuri, Minami Takako, Koide Yuji, Ikeda Satoshi, Kawano Hiroaki, Maemura Koji
Journal: Circulation (2014)
The combination of capecitabine (C), irinotecan (I) and oxaliplatin (O) (XELOXIRI) as first line treatment of metastatic colorectal cancer (MCRC): Preliminary results of a pilot study by the Gruppo Oncologico Nord-Ovest (G.O.N.O.)
Authors: G. Masi, S. Bursi, F. Loupakis, M. Barletta, G. Baldi, A. Antonuzzo, C. Sonaglio, E. Pfanner, I. Petrini, A. Falcone
Journal: Journal of Clinical Oncology (2007)

4096 Background: FOLFOXIRI demonstrated manageable toxicities and improved activity and efficacy compared to FOLFIRI in MCRC in a phase III trial by the G.O.N.O. group. Oral C has demonstrated similar efficacy to 5-FU and might substitute 5-FU in the FOLFOXIRI regimen. Methods: The G.O.N.O. started a pilot study to evaluate the combination of escalating doses of C with fixed doses of I, O (XELOXIRI) in metastatic and not resectable CRC patients (pts). The objectives of the study are the definition of the recommended dose (RD) of C in combination with I and O, safety and activity of the combination and analysis of plasma pharmacokinetics. The planned treatment in the first 3 patients was: I 165 mg/sqm over 1-h on day 1, O 85 mg/sqm over 2-h on day 1 and C 2,500 mg/sqm/die from day 1 to 7, repeated every 2 weeks. C dose was increased to 3,000 mg/sqm/die or decreased to 2,000 mg/sqm/die in subsequent groups of 3 to 6 pts on the basis of the observed dose limiting toxicities (DLT). Results: Up today 33 patients have been enrolled. Main patients characteristic are: sex (M/F) = 22/11, PS (0/1/2) = 28/4/1, age (median/range) = 65/42–76, sites of disease (single/multiple) = 18/15. The DLT was G3–4 diarrhea that was observed in 2 out 6 patients receiving C at 2500 mg/sqm, in 2 out 3 patients receiving C at 3,000 mg/sqm and in 1 out 6 patients receiving C at 2,000 mg/sqm. This last dose was defined the RD. Among the 23 patients treated at the RD main G3–4 toxicities were: diarrhea 17%, neutropenia 26%, thrombocytopenia 9%, neurotoxicity 4%. One toxic death for diarrhea and sepsis occurred. Up today 21 out of the 23 patients (2 patients too early) treated at the RD are assessable for response (ITT analysis) and 15 RP, 3 SD and 3 treatment failures have been observed with a response rate of 71% (95% CI: 48–89%). At a median follow-up of 10.3 months median PFS is 9.0+ months and median OS isn’t yet reached. Conclusions: XELOXIRI is a feasible regimen with diarrhea being the DLT. The recommended dose of C is 2,000 mg/sqm. At the RD toxicity is manageable and preliminary results in terms of activity are promising. Partially supported by Fondazione ARCO. No significant financial relationships to disclose.
A mathematical model for pharmacodynamics of an albumin-bound nanoparticle formulation of paclitaxel
Authors: Ardith El-Kareh, Amanda Baker, Alfred Gallegos
Journal: Cancer Research (2007)

1569  A mathematical model is developed to compare the pharmacodynamics of paclitaxel formulated as an albumin-bound nanoparticle with that of conventional paclitaxel (administered with polyoxyethylated castor oil). The model considers the several forms of paclitaxel present in vivo (free, plasma-protein bound, sequestered in polyoxyethylated castor oil micelles, and nanoparticle-bound), and accounts for drug pharmacokinetics, transport across the microvessel wall and into tumor tissue, cellular uptake and cellular pharmacodynamics. Spatially heterogeneous concentrations in the tumor extracellular and intracellular spaces, due to transport obstacles including low diffusivity, protein binding and cellular uptake, are accounted for. MTT assays were performed to measure response of SKOV-3 ovarian carcinoma cells to both conventional and albumin-bound nanoparticle paclitaxel for a wide range of exposure concentrations (0.1-10000 nM) and times (1 - 48 hours). Cellular pharmacodynamics of albumin-bound nanoparticle paclitaxel is described mathematically by extending a model previously developed for standard paclitaxel, with model parameters determined from these data. Only a small difference in pharmacodynamics of the two drugs at the cellular level was found, despite the much larger size of the nanoparticle (around 130 nm); the model suggests that this is due to cellular uptake equilibating rapidly for both forms, with passage through the cell cycle being the rate-limiting step for cell kill. Additional model parameters, including effective microvascular permeabilities for free and bound paclitaxel, are deduced from literature data. Differences in plasma pharmacokinetics between the albumin-bound nanoparticle and the standard form of paclitaxel are found to be a more important determinant of tumor drug uptake than gp60-activated albumin transcytosis across the endothelial layer.
Abstract 19: Cost-effectiveness of the Stepwise Approach to Diabetes Prevention in India
Authors: Duygu Islek, Mary Beth Weber, Ranjit Mohan Anjana, Viswanathan Mohan, Lisa R Staimez, Ranjani Harish, K.M. Venkat Narayan, Michael Laxy, Mohammed K Ali
Journal: Circulation (2020)

Introduction: Expert guidelines recommend a stepwise approach (lifestyle modification followed by addition of metformin in those not meeting goals) in high-risk people to delay progression to diabetes. However, there is scant evidence on the cost-effectiveness of implementing stepwise diabetes prevention. We estimated the 3-year within trial cost-effectiveness of a stepwise diabetes prevention approach in the Diabetes Community Lifestyle Improvement Program (D-CLIP) study in Chennai, India. Hypothesis: We assessed the cost-effectiveness of a stepwise diabetes prevention approach in India. Methods: The D-CLIP study was a randomized, controlled, translation trial in 578 overweight/obese Asian Indian adults with isolated impaired glucose tolerance (IGT) and/or isolated impaired fasting glucose (IFG), comparing a 6-month lifestyle modification curriculum and stepwise addition of metformin vs. standard lifestyle advice. We assessed direct medical costs including costs to deliver the intervention, general health care utilization, and direct non-medical costs. We also calculated costs for screening which included identifying and recruiting eligible individuals with IGT and/or IFG. Health effects were measured as absolute reductions in cumulative diabetes risk and in quality adjusted life years (QALYs) gained. Generalized linear regressions models adjusted for age, sex and baseline levels were fitted to estimate incremental costs and health effects. Bootstrapping was applied to describe the uncertainty around incremental cost-effectiveness ratios (ICER). Results: Over 3 years, the intervention resulted in incremental direct medical costs of 211 USD; incremental direct non-medical costs of 34 USD, an absolute diabetes risk reduction of 10.2%, and incremental QALYs gained of 0.098 per person. The absolute diabetes risk reduction in people with IFG was 6.4%, with IGT was 9% and with both IFG and IGT was 8.1%. ICERs from a multi-payer perspective (including the screening costs) averaged 4,275 USD per diabetes case prevented/delayed. That figure was 5,220 USD in people with IFG, 2,627 USD with IGT and 3,312 USD with both IFG and IGT. ICERs from a multi-payer perspective (including the screening costs) averaged 4,472 USD per QALY gained. That figure was 4,589 USD in people with IFG, 4,270 USD with IGT and 4,335 USD with both IFG and IGT. ICERs from a societal perspective were slightly higher. In the sensitivity analysis, with the scenario of a 50% increase/decrease in screening and intervention costs, from a multi-payer perspective, the average of ICERs varied 1,907 to 6,420 USD per diabetes case prevented, from 1,995 to 6,715 USD per QALY gained. Conclusions: In conclusion, a stepwise approach for diabetes prevention is likely to be cost-effective over a three-year time horizon.
NCCTG phase II trial N0531of weekly nab-paclitaxel (nab-p) in combination with gemcitabine (gem) in patients with metastatic breast cancer (MBC)
Authors: V. Roy, B. R. LaPlant, G. G. Gross, C. L. Bane, F. M. Palmieri, E. A. Perez
Journal: Journal of Clinical Oncology (2007)

1048 Background: Previous trials with p plus gem show significant antitumor activity in MBC. Nab-p has lower toxicity compared to p with similar therapeutic effects. This study assessed proportion of confirmed tumor responses and toxicity profile of this combination. Methods: Single stage phase II study enrolled patients (pts) with measurable MBC eligible for 1 st line chemotherapy (chemo). Pts treated (tx) with nab-p 125 mg/m 2 followed by gem 1,000 mg/m 2 days 1 and 8 of 21 day cycle. Dose modifications allowed for both drugs. Primary endpoint was proportion of confirmed responses; complete response (CR), partial response (PR) by RESIST criteria on two consecutive evaluations at least 6 weeks apart. 41 evaluable pts required to test the null hypothesis that the confirmed response rate was at most 40% against the alternative of at least 60%. Results: 50 pts enrolled 11/05 to 5/06. Median age 56 (29–86). 40 pts (80%) visceral disease, 34 (68%) ER positive, 28 (56%) PR positive, 1 (2%) HER2 positive, 1 (2%) prior trastuzumab treatment (tx). 25 (50%) had prior adjuvant chemo, including 15 (30%) prior taxane. Median follow-up 7 mos (3–12). Median of 6 cycles of tx completed (1–15). 41 pts discontinued tx, due to progression (41%), pt refusal (27%), adverse events (17%), alternate tx (7%). Confirmed response rate 48% (95% CI: 34–63%): 4 CR, 20 PR. Median duration of response 6.6 mos (95% CI: 5.7, not reached), median progression-free survival (PFS) 7.9 mos (95% CI: 5.3–9.3). Rate of overall survival (OS) at 6 mos 91% (95% CI: 84–100%), 6 month PFS 58% (95% CI: 45–74%). Median OS not reached. 30 pts required dose delays on total of 52 cycles, mostly due to hematologic AEs. 9 pts (19%) had grade (gr) 4 adverse event (AE), 32 (67%) had maximum gr 3 AE. Most common gr 3/4 AEs: neutropenia (52%), fatigue (26%), anemia (14%), dyspnea (14%), thrombocytopenia (12%). Four pts had gr 3 neuropathy. Conclusions: Nab-paclitaxel in combination with gem has clear activity in patients with MBC. Manageable hematologic, but no other significant toxicities. Study ongoing to correlate efficacy with caveolin-1 levels with results expected Spring 2007. Follow up study of this combination with an anti-angiogenesis agent is in development. No significant financial relationships to disclose.
Abstract 10101: Patient-specific Analysis Predicts Preferential Accumulation of VCAM-1 Targeted Nanoparticles Near Atherosclerotic Plaque
Authors: Shaolie S Hossain, Daniel Chavarria, Aaron Baker, Thomas J Hughes
Journal: Circulation (2019)

Introduction: Detection and treatment of vulnerable plaques, the ones prone to rupture and cause heart attacks, remain a huge unmet clinical need. Inflammation is one of the known precursors to pla...
Abstract P3-10-20: Targeting the tyrosine phosphatase SHP2 is efficacious against HER2-positive breast cancer
Authors: Yehenew Agazie, Zachary Hartman
Journal: Cancer Research (2020)

Abstract Accumulating evidence suggests that the Src homology phosphotyrosyl phosphatase 2 (SHP2) is a bona fide oncogene. These conclusions are primarily based on the positive role of SHP2 in receptor tyrosine kinase (RTK) signaling in multiple systems. Because overexpression of the human epidermal growth factor receptor 2 (HER2) is one of the primary causes of BC, we investigated the potential of SHP2 targeting in this subtype of BC. We have used our recently patented SHP2 inhibitor called WGMDY (US 9,932,288) for targeting SHP2 under cell culture and in vivo conditions. We have also used the recently reported allosteric SHP2 inhibitor called SHP099 particularly in the cell culture studies. We found that HER2-positive BC cells are highly sensitive to SHP2 inhibition with WGMDY as determined by loss of viability in 2D, transformation in soft agar, and cancer stem cell properties in suspension cultures. Similar results were obtained with SHP099 albeit at a reduced rate. Analysis of protein and RNA extracts showed inhibition of the Ras-ERK and the PI3K-Akt signaling pathways by WGMDY, but SHP099 tend to activate Akt signaling. In addition, WGMDY blocked overexpression of the HER2 protein in HER2-positive BC cells. As such, we focused on WGMDY for the in vivo efficacy studies. The results showed that WGMDY induces regression of preformed tumors in a concentration dependent manner. Histopathology analyses of tumors showed induction of necrosis in treated samples. Hence, WGMDY has a promising anti-cancer effects in HER2-positive BC. Citation Format: Yehenew Agazie, Zachary Hartman. Targeting the tyrosine phosphatase SHP2 is efficacious against HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-10-20.
Abstract P368: Western and Prudent Diet Patterns are Associated With Risk of Developing Non-cancer Related Venous Thromboembolism
Authors: So Yun Yi, Lyn M Steffen, Pamela L Lutsey, Mary Cushman, Aaron R Folsom
Journal: Circulation (2020)

Background: Results are inconsistent from published studies about the association between dietary intake and risk of incident venous thromboembolism (VTE). Therefore we proposed to study the association between diet patterns and incident non-cancer related VTE. We hypothesized that a Western diet pattern is positively associated, and a Prudent diet pattern is inversely associated with incident non-cancer related VTE. Methods: In the Atherosclerosis Risk in Communities (ARIC) Study, 14,873 middle-aged men and women were followed for incident VTE over an average of 22 years between 1987 and 2015. VTE cases were ascertained via annual phone calls and community hospital surveillance. Hospital records were reviewed to validate cases. Dietary intake was assessed by food frequency questionnaire at baseline and year 6. The Western and the Prudent diet pattern scores were derived by principal components analysis. In separate proportional hazards regression analyses, associations of quintiles of the Western and the Prudent diet pattern scores with risk of developing non-cancer related VTE were examined, adjusting for demographic characteristics, lifestyle factors, body mass index, and diabetes. Results: Hazard ratios (95% confidence intervals) of incident non-cancer related VTE (n=634) across quintiles of the Prudent diet pattern score were 1.0 (reference), 0.99 (0.78-1.26), 0.79 (0.61-1.02), 0.66 (0.51-0.87), and 0.81 (0.61-1.07), p trend =0.01 (see Figure). Across quintiles of the Western diet pattern score, hazard ratios (95% CI) of incident non-cancer related VTE were 1.0 (reference), 1.14 (0.88-1.47), 1.20 (0.92-1.56), 1.10 (0.82-1.47), and 1.63 (1.17-2.28), p trend =0.02. Conclusions: In this community-based cohort, a Prudent diet pattern was associated with a lower risk of developing non-cancer related VTE, whereas higher risk was associated with a Western diet pattern.
Abstract P238: Incorporating Measured Blood Pressures Into A Code Based Case Definition For Evaluating Trends In Hypertensive Disorders Of Pregnancy
Authors: Zoe Bider-Canfield, Kristi Reynolds, Cecilia Portugal, Lyndsay Avalos, Sascha Dublin, Thomas Easterling, Susan Shortreed, Craig T Cheetham
Journal: Circulation (2020)

Introduction: Epidemiologic studies of hypertension in pregnancy traditionally rely on diagnosis codes to identify cases. Electronic medical records make it possible to incorporate measured blood pressures (BPs) into case definitions. Our aim was to examine hypertension trends in pregnancy comparing two methodologies: 1) Traditional and 2) BP-Augmented definitions. Methods: All pregnancies between 2009 -2014 were identified within an integrated healthcare delivery system. Hypertension case definitions were applied: 1) A Traditional definition based solely on delivery discharge diagnosis codes, and 2) A BP-Augmented definition using the following criteria during pregnancy: (a) two elevated outpatient BP measures (≥ 140/90 mmHg) on separate days, within 30 days of each other; (b) an antihypertensive medication fill plus a hypertension diagnosis code during pregnancy; or (c) a hospital discharge diagnosis of preeclampsia. Descriptive statistics were used to compare the two case definitions and temporal trends. Results: Of the 145,739 pregnancies, 13,637 [9.4%] met the Traditional definition and 14,225 [9.8%] met the BP-Augmented case definition (10,809 [7.4%] met both case definitions). There was a slight increase in hypertension prevalence over time based on both case definitions (figure). With the BP-Augmented definition, the prevalence increased from 9.5% of live births in 2009 to 9.8% of live births in 2014 (3% increase). For the traditional definition, the prevalence increased from 9.2% to 10.2% from 2009 to 2014 (11% increase). Conclusion: Results suggest that the prevalence of hypertension in pregnancy increased slightly from 2009-2014 with both case definitions. The two methods identified somewhat different populations with only 10,809 meeting both case definitions. Additional work is needed to validate the BP-Augmented definition’s predictive power to identify clinically important maternal and fetal outcomes.
Physical and Sexual Violence Among Gay, Lesbian, Bisexual, and Questioning Adolescents
Authors: Theodore L. Caputi, Chelsea L. Shover, Ryan J. Watson
Journal: JAMA Pediatrics (2020)

This cross-sectional study uses data from the National Youth Risk Behavior Surveys to quantify the risks of physical and sexual violence faced by sexual minority adolescents in the United States from 2014 to 2017.