bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA14: Emerging priorities for the Center to Reduce Cancer Health Disparities in diversity workforce training and cancer health disparities research
Authors: Springfield Sanya A. 
Published: August 2020

Abstract
This panel presentation will provide an overview of the current training and research funding priorities at National Cancer Institute's (NCI) Center to Reduce Cancer Health Disparities (CRCHD). CRCHD is NCI's focal point for the training of competitive cancer researchers from diverse populations and supporting cancer health disparities research across the cancer continuum. The NCI's CRCHD's Continuing Umbrella of Research Experiences (CURE), Intramural CURE (iCURE), and the Partnerships to Advance Cancer Health Equity (PACHE) will be highlighted as successful models for diversity training and cancer health disparities research. The CURE Program supports extramural research training and education experiences for under-represented individuals beginning in middle school and continuing through to first academic appointment. The newly launched iCURE Program supports mentored research experiences within the NCI Intramural Research Program for students and fellows. In addition, the PACHE Program supports cancer and cancer health disparities research, education, and outreach through partnerships between Minority-Serving Institutions and NCI-designated Cancer Centers. New and established NCI funding opportunities in cancer health disparities research, including opportunities supporting both basic and translational research addressing cancer health disparities, will also be presented. Additionally, strategies will be explored for navigating successful cancer research careers and for developing competitive grant applications.
Citation Format: Sanya A. Springfield. Emerging priorities for the Center to Reduce Cancer Health Disparities in diversity workforce training and cancer health disparities research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA14.
Abstract IA45: Coverage ≠ access: State Medicaid policies and disparities in receiving high-quality cancer care
Authors: Halpern Michael T. 
Published: August 2020

Abstract
Medicaid is a joint state-federal program that provides health insurance coverage to certain low-income populations. While the federal government provides funding for at least half of each state's Medicaid costs and requires coverage for certain health care services, each state has broad flexibility to design its own Medicaid policies. These policies include reimbursement rates for medical care services, requirements for patient copayments, and duration of Medicaid enrollment before required eligibility recertification. Furthermore, following the 2012 Supreme Court decision, states can choose whether to participate in expansion of Medicaid to enroll individuals with incomes up to 138% of the Federal Poverty Level. As these policies differ substantially among states, Medicaid is not a single health insurance plan but a set of different plans for each state. Medicaid provides coverage for cancer screening and treatment for many low-income individuals. However, differences in state Medicaid policies may affect receipt of timely and high-quality cancer care for this underserved population. In addition, social determinants of health such as race/ethnicity, sex, and age may also affect receipt of cancer care among Medicaid beneficiaries. This presentation will review findings examining the effects of state Medicaid policies and individual characteristics on receiving cancer screening, treatment, supportive care, and survivorship care services among Medicaid beneficiaries. Using Medicaid claims and enrollment data, research has found that both state policies and social determinants of health can impact receipt of recommended cancer screenings and treatment for individuals with Medicaid coverage. The impacts of Medicaid policies vary for different types of cancer care services and among individuals with different types of cancer. State decisions to participate in Medicaid expansion also affect receipt of cancer care. These findings highlight the need for state Medicaid policies designed to improve access to cancer care and enhance outcomes among Medicaid beneficiaries. Given the large—and growing—Medicaid population, even small improvements in access to high-quality cancer care can translate into substantial changes in health outcomes.
Citation Format: Michael T. Halpern. Coverage ≠ access: State Medicaid policies and disparities in receiving high-quality cancer care [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA45.
Abstract IA51: Federally supported tools and resources to support data integration efforts for health disparities research
Authors: Moser Richard P. 
Published: August 2020

Abstract
The etiology of many cancer-related health disparities that continue to persist is oftentimes complex, interactive, and multifactorial. Because of this complexity and to understand these causes, it behooves cancer researchers to utilize data that represent different types and sources of these determinants measured at multiple levels of abstraction, from biology to policy. By incorporating these different data sources into their studies, researchers can answer novel (and better) cancer control research questions that cannot be answered with any one data set. To do these types of integrative analyses, however, researchers will most likely need to merge or link independent data, and this may be difficult or impossible if the data are too heterogeneous in regard to the instruments or measures used to represent variables in the data. To increase the ability to do data integration, it typically requires harmonized data that contain common data elements of the important constructs of interest. In this presentation, Dr. Moser will highlight tools and resources, especially those supported by the federal government, that can be used for data integration to conduct health disparities research. These tools include ontologies, standardized measures, collaborative sites, and data repositories that promote the use of common data elements to create or analyze harmonized data. This presentation will also mention National Institutes of Health (NIH) funding announcements that could be used to support data integration efforts and health disparities research.
Citation Format: Richard P. Moser. Federally supported tools and resources to support data integration efforts for health disparities research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA51.
Abstract 15: Imputing a more targeted therapy for triple-negative breast cancers
Authors: Gruener Robert F. , Greene Geoffrey L. , Huang R. Stephanie 
Published: August 2020

Abstract
Triple-negative breast cancer (TNBC) is a clinically defined subset of breast cancers that are inherently difficult to treat since, unlike the other breast cancer subtypes, they are defined by their lack of a distinct molecular target. Previously our lab developed a computational framework to impute drug response in patients that accurately mirrored the observed patient response. In short, this methodology involves building unsupervised linear regression models between cell line baseline gene expression values and the respective drug sensitivity metric (EC50 or AUC), which allows us to generate imputed sensitivity scores for cell line or patient tumor samples for which we have gene expression data. For this study, we applied this methodology to prospectively identify agents that are predicted to be more effective specifically in triple-negative breast cancer. We began by expanding the drug imputation training dataset to the Broad’s Cell Therapeutics Response Portal, which contains 545 drugs and over 1,000 cancer cell lines (CCLs) and imputed sensitivity in The Cancer Genome Atlas’s (TCGA’s) breast cancer cohort. Our imputation data indicated that TNBC tumors were expected to be comparatively sensitive to cell cycle pathway inhibitors. Among these compounds, the Wee1 inhibitor MK1775 (aka adavosertib and AZD1775) was identified for having the most significant predicted effect in TNBC patients compared to the receptor-positive patients. We were able to validate the accuracy of the MK1775 imputation model using traditional cross-validation approaches as well as in independent cell line dataset and showed that the measured and our predicted response to Wee1 inhibition strongly correlated. Additionally, we were able to uses our predicted MK1775 response scores to recapitulate the significant association between MK1775 response and p53 mutation status. We then looked to validate the efficacy of MK1775’s efficacy in TNBC cell line and xenograft experiments. We observed strong inhibition of cancer growth by MK1775 alone but also identified a combination effect between MK1775 and the TNBC standard-of-care agent paclitaxel as assayed by both in vitro viability experiments as well as in vivo tumor growth assays. We believe these results indicate that this methodology could generally be applied as a hypothesis-generating tool for identifying targeted agents for other disease subtypes as well as supporting the use of MK1775, especially in combination with paclitaxel, for TNBC.
Citation Format: Robert F. Gruener, Geoffrey L. Greene, R. Stephanie Huang. Imputing a more targeted therapy for triple-negative breast cancers [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 15.
Abstract 17: MBQ-167, a Rac/Cdc42 targeted therapeutic, in combination with paclitaxel for TNBC treatment
Authors: Ruiz-Calderon Jean , Lopez-Lopez Irmaris , Cruz-Collazo Ailed , Dharmawardhane Suranganie 
Published: August 2020

Abstract
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, with a high predisposition for locally advanced and metastatic cancer. While targeted therapies for TNBC are in various stages of development, current standard chemotherapies include taxanes such as paclitaxel and anthracycline agents. With the objective of specifically targeting invasive cancer, our group has been developing small-molecule inhibitors of the Rho GTPases Rac and Cdc42, which are known drivers of cancer cell invasion and metastasis. Of these, MBQ-167 inhibits both Rac and Cdc42 with IC50s of 103 and 78 nmol/L, respectively, and consequently inhibits p21-activated kinase (PAK) signaling, metastatic cancer cell proliferation, migration, tumor growth, and metastasis (Humphries-Bickley et al., Mol Cancer Ther 2017). We found that in addition to blocking HER2-type breast cancer progression, MBQ-167 is also highly effective against TNBC cell and tumor growth, as well as metastasis in mouse models. The purpose of this study was to test the efficacy of MBQ-167 in combination with the current chemotherapeutic paclitaxel. We hypothesized that the combination of paclitaxel and MBQ-167 is a rational strategy to inhibit tumor growth and metastasis in TNBC. To test this hypothesis, we administered a nontoxic dosage of individual MBQ-167, paclitaxel, or combined MBQ-167 and paclitaxel to immunocompromised mice bearing mammary fat pad tumors from GFP-tagged MDA-MB-468 or MDA-MB-231 human TNBC cells. Tumor growth was monitored weekly and metastasis was quantified at the end of the study. Treatment with MBQ-167 and/or paclitaxel resulted in reduced tumor growth by 70-80% in both models. In the MDA-MB-231 model, MBQ-167 paralleled paclitaxel treatment with a modest benefit in combined therapy. However, in the epidermal growth factor receptor (EGFR)-positive TNBC model MDA-MB-468, MBQ-167 alone or in combination significantly reduced metastasis to the lungs and spleen, while paclitaxel alone increased metastasis to the liver, lungs, and spleen. These results show that MBQ-167 is a promising antimetastatic agent that can be effective in combination with current chemotherapeutic agents.
Citation Format: Jean Ruiz-Calderon, Irmaris Lopez-Lopez, Ailed Cruz-Collazo, Suranganie Dharmawardhane. MBQ-167, a Rac/Cdc42 targeted therapeutic, in combination with paclitaxel for TNBC treatment [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 17.
Abstract IA02: The Treehouse Childhood Cancer Initiative
Authors: Haussler David 
Published: August 2020

Abstract
Each year over 4,000 children with cancer in the US lack adequate treatment options for their disease, underscoring the urgent need for new therapeutic targets and new therapies. Cancer genomic investigations focusing on the identification of recurrent DNA changes in tumors that could be targeted by therapies have been disappointing in the majority of pediatric cancers, as these diseases have lower rates of somatic mutation compared to adult cancers. To address this challenge, the UC Santa Cruz Genomics Institute launched the Treehouse Childhood Cancer Initiative, an innovative program that identifies novel therapeutic targets for difficult-to-treat pediatric cancers through leveraging the power of large, shared tumor RNA-sequencing datasets. Treehouse partners with pediatric cancer hospitals, including Lucille Packard Children’s Hospital at Stanford, UCSF Benioff Children’s Hospital, Children’s Hospital of Orange County, Nationwide Children’s Hospital, and British Columbia Children’s Hospital, to investigate whether the comparative RNA-seq approach is feasible and useful when applied to patients prospectively. A preliminary analysis of 126 patients from four hospitals showed that comparative RNA-seq analysis can identify druggable targets for over 74.3% of difficult-to-treat pediatric cancer patients, while state-of-the-art DNA analysis finds potential therapeutic options for only 45.9% of patients. Current work focuses on determining the clinical utility of the Treehouse approach.
Citation Format: David Haussler. The Treehouse Childhood Cancer Initiative [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr IA02.
Abstract IA19: The Drug Rediscovery Protocol: Getting the most out of approved drugs
Authors: Voest Emile E. 
Published: August 2020

Abstract
Large-scale genetic tumor profiling can identify increasing numbers of potentially actionable molecular variants for which approved anticancer drugs are available. In daily practice, however, when patients with such variants are treated with drugs outside of their approved label, successes and failures are not systematically collected or shared. Therefore, we initiated the Drug Rediscovery Protocol (DRUP), an innovative and adaptive precision oncology trial aimed at identifying signals of activity in cohorts of patients with defined tumor types and molecular variants, treated with anticancer drugs outside their approved label. Eligible patients have exhausted (or declined) standard therapies and have malignancies with potentially actionable variants for which no approved anticancer drugs are available. We use a stepwise approach per cohort of first 8 patients, and when at least one patient experienced clinical benefit that cohort expands to 24 patients. Presently, we have reviewed &gt;1,100 submitted patient cases and included and treated &gt;500 patients. We found an overall clinical benefit rate (defined as complete or partial response, or stable disease ≥16 weeks) of 29% although the formal analysis is per cohort. The potential of DRUP was illustrated by the identification of a successful cohort of patients with microsatellite instable tumors receiving nivolumab or durvalumab, and tumors with HRD treated with olaparib. Our results have led to a personalized reimbursement model for nivolumab in patients with MSI tumors that is supported by all regulatory parties. The DRUP hereby facilitates defined use of approved drugs beyond their label in (rare) cancer subgroups, identifies early signals of activity in these subgroups, accelerates clinical translation of new insights, and creates a publicly available knowledge-base for future decision making.
Citation Format: Emile E. Voest. The Drug Rediscovery Protocol: Getting the most out of approved drugs [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr IA19.
Hedgehog Pathway Inhibitors: A New Therapeutic Class for the Treatment of Acute Myeloid Leukemia
Authors: Jamieson Catriona , Martinelli Giovanni , Papayannidis Cristina , Cortes Jorge E. 
Published: August 2020

Abstract

Targeting Hedgehog (Hh) pathway components, such as Smoothened (SMO), is a developing strategy for the treatment of acute myeloid leukemia (AML) and for overcoming relapsed/refractory forms of this disease. Several SMO inhibitors are in clinical development for the treatment of various tumor types and the results from some clinical trials in AML have been reported. This review will discuss the role of Hh signaling in AML pathogenesis, describe the preclinical and clinical development of Hh pathway inhibitors for the treatment of AML, and examine the current evidence on Hh pathway inhibitor resistance and the implications for treatment selection in AML.

Significance:
In acute myeloid leukemia (AML), components of the Hedgehog (Hh) signaling pathway, such as Smoothened (SMO), have been implicated in the development, maintenance, and expansion of leukemic stem cells (LSC), as well as sensitization to chemotherapy and the development of drug resistance in AML. Observations in preclinical studies of AML, as well as from samples of patients with AML, demonstrate that Hh pathway inhibitors act primarily on the stem cell pathway as differentiation agents. The current data for hematologic malignancies indicate the potential for a synergistic effect when a Hh pathway inhibitor is administered in combination with chemotherapy or investigational agents. It is thought that Hh pathway inhibitors act as agents that reduce LSC dormancy and promote LSC differentiation, thus the newly dividing LSCs can then be targeted by other chemotherapeutic drugs.
Control DC link of single-phase dynamic voltage restorer
Authors: Toufik Toumi , Ahmed Allali , Othmane Abdelkhalek , Amine Soumeur Mohammed , Abdelfatah Nasri 
Published: August 2020

This paper is aimed to illustrate and expose the performance of single-phase voltage dynamic voltage restorer (DVR) control connected to the electrical distribution grid. This performance is easily expressed by compensating for the sags and the swells voltages, and regulating the voltage across the load by injecting a voltage component in series with the source voltage increased or decreased with respect to the source voltage the load-side waveforms are purely sinusoidal. The integration of serial and chopper converters makes the DVR capable of bidirectional power flow. The key to this topology is its ability to compensate for sagging and swelling of the voltage in the long run. The modeling of the DVR and the design of its controller is included in this document. Effectiveness of control systems and start-up sequence of DVR operation is verified by detailed simulation studies. The control method used in this work is based on the use of a booster chopper and two cascade loops to generate the PWM command to control the chopper. The effectiveness of the suggested method is confirmed by the MATLAB/SIMULINK® simulation results and some prototype experiments. These results show the capacity of the proposed DC link control.
Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All‐Cause Mortality in Clinical Trials of Time‐Constrained Dual‐Antiplatelet Therapy After Percutaneous Coronary Intervention
Authors: McClure John D. , Ramsay Jennifer C. , Berry Colin 
Published: August 2020

Background
The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events. A time‐constrained approach to DAPT has been recently investigated in 5 multicenter trials including GLOBAL LEADERS, STOPDAPT2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus‐Eluting Cobalt‐Chromium Stent‐2), SMART‐CHOICE, TWILIGHT (Ticagrelor With Aspirin or Alone in High‐Risk Patients After Coronary Intervention), and TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome).

Methods and Results
We undertook a pooled analysis of these trials to assess the overall associations between time‐constrained P2Y12 inhibitor monotherapy (aspirin‐free regimen) for bleeding events, major adverse cardiovascular events, and all‐cause mortality as compared to standard care with DAPT for at least 12 months post‐percutaneous coronary intervention. We implemented a DerSimonian and Laird random effects meta‐analysis using the metafor package in R. 32 361 randomized trial participants, including 16 898 (52.2%) who had a history of acute coronary syndrome, underwent percutaneous coronary intervention, and had outcome data available. P2Y12 inhibitor monotherapy from 1 to 3 months was associated with a reduced risk for bleeding (hazard ratio [HR] 0.60; 95% CI, 0.45‐0.81), including in the acute coronary syndrome group in which the magnitude of risk reduction was greatest (HR 0.50; 95% CI, 0.41‐0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the HR were also favorable for major adverse cardiovascular events (0.88; 95% CI, 0.77‐1.02) and all‐cause mortality (0.85; 95% CI, 0.71‐1.03).

Conclusions
Compared with DAPT for 12 months post‐percutaneous coronary intervention, P2Y12 inhibitor monotherapy from 1 to 3 months substantially reduces the risk of major and fatal bleeding and, in addition, confers potentially protective effects, for major adverse cardiovascular events and all‐cause mortality. Considering patient safety, the results support a strategy of DAPT for 1 to 3 months followed by aspirin‐free P2Y12 inhibitor monotherapy.