bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B51: Genetic etiology of ER low/HER2- breast tumors
Authors: Lovejoy Leann A. , Shriver Craig D. , Ellsworth Rachel E. 
Published: August 2018

Abstract
Background: In 2010, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) issued guidelines that tumors with &gt;1% positively staining cells should be considered ER positive. Numerous studies have demonstrated that tumors with 1-9% ER-positive cells (low staining) represent ER-negative intrinsic subtypes with outcomes similar to ER-negative tumors. Given the similarities between low-staining tumors and TNBC, we investigated whether low-staining tumors share a germline etiology with TNBC.
Methods: The Clinical Breast Care Project was queried to identify all tumors with percent ER-positive cells and HER2 data available. Genomic DNA was isolated from available blood samples from patients with HER2-negative tumors with either negative (TNBC) or low-staining (1-9%) ER status. Targeted sequencing was performed using the Illumina TruSight Cancer panel. Pathogenic mutations were identified using VariantStudio and classified as pathogenic, likely pathogenic, uncertain significance (VUS), likely benign, or benign using ClinVar.
Results: Low ER/HER2- tumors and TNBC represented 50 (2.7%) and 223 (12.2%) of the 1819 tumors in the database. Patients with low-staining tumors and TNBC did not differ significantly by age at diagnosis, ethnicity, family history, tumor stage, size, grade, or survival, and all the low ER/HER2- tumors with gene expression data available (n=17) were basal-like. Four (9%) of the women with low ER/HER2- tumors had pathogenic mutations in BRCA1 or BRCA2; an additional 4 (9%) had pathogenic mutations in the cancer predisposition genes BLM (n=2), FH (n=1), and MUTYH (n=1). Seven others had VUS in BRCA2, BRIP1, CHEK2, MSH2, MSH6, and SMAD4. Frequency of pathogenic mutations did not differ significantly (P=0.139) between low-staining tumors (18%) and TNBC (13%).
Discussion: Low ER/HER2- tumors share similar clinicopathologic characteristics and outcomes with TNBC and have a significant genetic component, with 9% of patients having BRCA1 or BRCA2 germline mutations and an additional 9% having mutations in other cancer-predisposing genes. These data suggest that while ASCO/CAP guidelines define low ER tumors as ER positive, women with low ER/HER2- tumors may benefit from the clinical care and genetic testing provided to women with TNBC.
The views expressed in this article are those of the author and do not reflect the official policy of the Department of Army/Navy/Air Force, the Department of Defense, or the U.S. Government.
Citation Format: Leann A. Lovejoy, Craig D. Shriver, Rachel E. Ellsworth. Genetic etiology of ER low/HER2- breast tumors [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B51.
Abstract B64: Sox10 drives tumor progression in breast cancer by reprogramming mammary tumor cells into a state of plasticity resembling primitive neural crest cells
Authors: Dravis Christopher , Wahl Geoffrey 
Published: August 2018

Abstract
Many foundational features of tumor malignancy such as tumor initiation, tumor heterogeneity, therapeutic resistance, and metastasis are driven through dysregulated cell plasticity. Thus, the development of strategies to counter mechanisms of reprogramming in cancer cells is a critical area of need in the field. To address this challenge, we have focused on discovering how cell plasticity is specified in normal mammary development and tissue, and how these processes may be co-opted to drive tumor progression in breast cancer. To facilitate the study of these complex phenomena, we have developed a CRISPR- and tissue engineering-based platform system to rapidly generate de novo, in vivo, mammary glands and mammary tumors that carry any conceivable genomic modification. Here, we have used this system to study the function of Sox10 in breast cancer, as we have previously shown that the transcription factor Sox10 is a critical mammary cell plasticity factor that labels and is functionally required for stem/progenitor activity in normal mammary cells. We now demonstrate that Sox10 is also a major plasticity factor in breast cancer. We find that Sox10 is expressed in both human breast cancer and multiple murine mammary tumor models, and demonstrate critical roles for Sox10 in driving both tumor initiation and progression. Sox10 expression in these tumors correlates with multiple indicators of elevated cell plasticity, which include features of de-differentiation and EMT, specific enrichment of mammary stem/progenitor identity, and expanded lineage potential compared to normal mammary cells. In addition to its role in specifying stem/progenitor activity in mammary cells, Sox10 is also a dominant specifier of neural crest cells, a primitive and highly plastic cell state found only in the early embryo. Strikingly, we find that Sox10+ mammary tumor cells also exhibit transcriptional and epigenetic features of neural crest cells that are not found in normal mammary cells. Collectively, these data reveal that Sox10 is a major plasticity factor that contributes to mammary tumor progression, and demonstrate the remarkable scope of cell state reprogramming that can occur during tumorigenesis when potent plasticity factors are dysregulated.
Note: This abstract was not presented at the conference.
Citation Format: Christopher Dravis, Geoffrey Wahl. Sox10 drives tumor progression in breast cancer by reprogramming mammary tumor cells into a state of plasticity resembling primitive neural crest cells [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B64.
Abstract IA12: Precision medicine for triple-negative breast cancer patients using a systems biology approach
Authors: Perou Charles M. 
Published: August 2018

Abstract
Triple-negative breast cancers (TNBC = ER-, PR-, and HER2-negative) are among the most clinically challenging because of their poor prognosis and paucity of approved treatment options. TNBC is composed of multiple disease subtype, with multiple classification systems having been developed. These methods are largely in agreement and identify four basic groups including basal-like, Claudin-low/mesenchymal, immune-infiltrated, and luminal-type (LAR). Each of these distinct patient subsets may require distinct therapeutic strategies, some of which will be discussed.
Within TNBC, the basal-like disease type predominates (70-80%), but again, all the intrinsic subtypes are also present. Interestingly, luminal/TNBC or HER2-enriched/TNBC show very similar gene expression patterns to luminal/ER+ or HER2-enriched/HER2+, except for expression of ERBB2 (and the genes in the 17q amplicon). Importantly, the distinction between basal-like versus non-basal-like within TNBC seems to be important for predicting 1) survival following (neo)adjuvant multiagent chemotherapy, 2) bevacizumab benefit in the neoadjuvant setting (CALGB40603), and 3) docetaxel vs. carboplatin benefit in the first-line metastatic setting (TNT Trial). In addition, genomic predictors of chemotherapy benefit for TNBC typically identify tumor and immune cell features as positive predictors of response, thus highlighting the importance of the microenvironment in response and survival, and highlighting the importance of methods that can account for both of these key features.
TNBC are also more common in younger women and African American women, which contributes to racial disparities in mortality due to breast cancer. Recent TCGA analyses suggest that there are few molecular differences in the somatic tumor landscape according to race, which suggests that access to health care and/or adherence to therapy may be the major contributors to differences in outcomes according to race. Overall, these data suggest that intrinsic molecular profiling, plus measures of the microenvironment, can provide clinically relevant information beyond current pathology-based classifications, which can assist in making more precise therapy recommendations for TNBC patients.
Citation Format: Charles M. Perou. Precision medicine for triple-negative breast cancer patients using a systems biology approach [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA12.
Abstract IA22: Integrating immunotherapy and targeted therapy in breast cancer
Authors: Zhao Jean 
Published: August 2018

Abstract
Therapeutic resistance is a major obstacle in the clinic for cancer treatment. Utilizing our novel genetically engineered mouse models (GEMMs) of cancer driven by inducible expression of oncogenic PIK3CA or HER2, coupled with pharmacologic approaches, we identified several significant resistance mechanisms to PI3K- or HER2-targeted therapy. For example, we found spontaneous focal amplification of Met and Myc, recurrent mutations in Ras and β-catenin, and compensatory activation of the MAPK pathway render resistance to PI3K inhibition. We recently identified Cyclin D1-CDK4 mediated resistance to HER2-targeted therapy through a signaling feedback loop. Beyond suppressing cell cycle progression, we found that CDK4/6 inhibitors promote antitumor immunity and increase cytotoxic T cell-mediated clearance of tumor cells, which is further enhanced by the addition of immune checkpoint blockade. More importantly, these results led to the design of clinical trials with CDK4/6 inhibitor in combination with HER2-targeted therapy and PD1 blockade for patients with metastatic, refractory HER2+ breast cancer. Parallel to GEMMs, we have led the efforts to establish and characterize novel cancer patient-derived xenograft (PDX) models, with an emphasis on brain metastases, an emerging clinical challenge. I will discuss how we have used these models to discover therapeutic strategies that integrate targeted therapy and immunotherapy to overcome resistance and to drive these discoveries to the clinical trials.
Citation Format: Jean Zhao. Integrating immunotherapy and targeted therapy in breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA22.
Abstract A61: Ascites-derived and tissue-derived ovarian cancer cell primary 3D cultures aimed for personalized medicine
Authors: Nanki Yoshiko , Hirasawa Akira , Nomura Hiroyuki , Okubo Aki , Itoh Manabu , Akahane Tomoko , Chiyoda Tatsuyuki , Kataoka Fumio , Tominaga Eiichiro , Aoki Daisuke 
Published: August 2018

Abstract
Objective: Ovarian cancer is a poor-prognosis gynecologic disease with over 220,000 diagnoses each year worldwide and a 5-year survival rate less than 40%. In this study, we present a method for isolation and characterization of ovarian cancer cells from patient-derived ascites and tissue samples by using three-dimensional (3D) cell culture.
Materials and Methods: Ascites and tissue samples were obtained from primary ovarian, peritoneal, and fallopian tube cancer patients intraoperatively. Samples were isolated and cultured within 6 hours after collection. After isolation, cells were resuspended in Matrigel and were placed at the center of each well. Optimized medium is added to each well. NanoCulture Plate LH96 (Low-Binding, MH pattern, 96-wells, Medical and Biological Laboratories Co., Ltd., Japan) were used for 3D cell culture. Plates were incubated at 37°C. The cultures were examined for metabolically active cells by ATP assay and medium changed on days 0, 1, 4, 7, 10, and 14.
Results: We successfully obtained ascites-derived primary cell cultures within 1-7 days from 100% (3/31) of the ascites samples and 62% (5/8) from tissue-derived primary cell cultures. Spheroids-like structures were formed in 30% (1/3) of ascites samples and 50% (4/8) of tissue samples. The tumorigenicity and invasiveness of the cells were demonstrated using new 3D spheroid model cultured in vitro by NanoCulture Plate LH96.
Conclusion: Primary ascites and tissue culture of ovarian cancer cells can successfully be cultured by 3D cell culture plates. We may apply this method for drug sensitivity testing; therefore, 3D cell culture has a potential to evaluate the sensitivity of candidate chemotherapeutic drug for individual patients.
Citation Format: Yoshiko Nanki, Akira Hirasawa, Hiroyuki Nomura, Aki Okubo, Manabu Itoh, Tomoko Akahane, Tatsuyuki Chiyoda, Fumio Kataoka, Eiichiro Tominaga, Daisuke Aoki. Ascites-derived and tissue-derived ovarian cancer cell primary 3D cultures aimed for personalized medicine. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr A61.
Abstract IA12: Acquired chemotherapy resistance in high-grade serous ovarian cancer patients
Authors: Christie Elizabeth L. , Beach Jessica , Etemadmoghadam Dariush , Garsed Dale , Patch Ann-Marie , Fereday Sian , Pattnaik Swetansu ,   Australian Ovarian Cancer Study, Brady Samuel , Bild Andrea , Bowtell David D.L. 
Published: August 2018

Abstract
High-grade serous ovarian cancer (HGSC) was one of the first cancer types subjected to comprehensive genomic analysis, and over the last 5-7 years gene expression and DNA sequence data have been generated from hundreds of samples. A large majority of this data has been obtained from surgical samples collected following primary debulking surgery or following a few cycles of neoadjuvant chemotherapy. By contrast, comparatively little data exist from patients who have been extensively treated with chemotherapy or newer targeted agents, such as antiangiogenics or PARP inhibitors (PARPi). Of particular interest are samples collected from patients whose cancer was initially responsive to treatment but has become resistant to therapy (acquired resistance) at the time of collection.
The presentation will describe data obtained from whole-genome (N=73 samples, 36 patients) and targeted (N=65 samples, 48 patients) sequence analysis of recurrent or end-stage HGSC samples, focusing in particular on two mechanisms of acquired resistance–fusions involving the ABCB1 gene and reversion of germline BRCA1/2 mutations. ABCB1 encodes the multidrug resistance transporter MDR1, also known as P-glycoprotein. Data will be presented on the frequency and mechanisms of ABCB1 deregulation in recurrent HGSC, and approaches to clinical intervention in fusion-positive patients. Reversions in BRCA1/2 appear to render tumors that were defective in homologous recombination (HR) repair, HR proficient and therefore may have important implications for likely treatment response. The presentation will also discuss approaches to evaluating reversion status in patients with mutation in BRCA1/2.
Citation Format: Elizabeth L. Christie, Jessica Beach, Dariush Etemadmoghadam, Dale Garsed, Ann-Marie Patch, Sian Fereday, Swetansu Pattnaik, Australian Ovarian Cancer Study, Samuel Brady, Andrea Bild, David D.L. Bowtell. Acquired chemotherapy resistance in high-grade serous ovarian cancer patients. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA12.
Karen Culture of Evangelism and Early Baptist Mission in Nineteenth Century Burma
Authors: Hayami Yoko 
Published: August 2018

Abstract
The success story of nineteenth-century Baptist missionary work among minority ethnic groups in Burma was one well-known facet of the early beginnings of modern Protestant missions. Behind this success was the extensive travel and evangelizing work done by native Karen Christians. In the face of the unexpected speed and zeal with which the Karen converts spread the gospel, to which I apply the term “culture of evangelism”, the Baptist mission in Burma was formed through an interactive process of continual self-reformulation, negotiation, and compromise on crucial matters such as baptism, ordination, self-support, division of roles, and language use. This has had far-reaching effects in shaping the Baptist churches in Myanmar today.
Enhancing the Data Coverage in the Integrated Global Radiosonde Archive
Authors: Durre Imke , Yin Xungang , Vose Russell S. , Applequist Scott , Arnfield Jeff 
Published: August 2018

AbstractThe Integrated Global Radiosonde Archive (IGRA) is a collection of historical and near-real-time radiosonde and pilot balloon observations from around the globe. Consisting of a foundational dataset of individual soundings, a set of sounding-derived parameters, and monthly means, the collection is maintained and distributed by the National Oceanic and Atmospheric Administration’s National Centers for Environmental Information (NCEI). It has been used in a variety of applications, including reanalysis projects, assessments of tropospheric and stratospheric temperature and moisture trends, a wide range of studies of atmospheric processes and structures, and as validation of observations from other observing platforms. In 2016, NCEI released version 2 of the dataset, IGRA 2, which incorporates data from a considerably greater number of data sources, thus increasing the data volume by 30%, extending the data back in time to as early as 1905, and improving the spatial coverage. To create IGRA 2, 40 data sources were converted into a common data format and merged into one coherent dataset using a newly designed suite of algorithms. Then, an overhauled version of the IGRA 1 quality-assurance system was applied to the integrated data. Last, monthly means and sounding-by-sounding moisture and stability parameters were derived from the new dataset. All of these components are updated on a regular basis and made available for download free of charge on the NCEI website.
The Dynamics of Insurance Development and Economic Growth in Nigeria
Authors: Nwosa Philip Ifeakachukwu , Mustapha Zainab Bolanle 
Published: August 2018

This study examined the dynamics of insurance development and economic growth in Nigeria for the period 1996–2014. Specifically, the study addressed two important issues: the impact of insurance development on economic growth and the causal nexus between insurance development and economic growth. The study utilised two techniques: ordinary least squares (OLS) and causality. The OLS regression estimate revealed that insurance development had an insignificant effect on economic growth, while the causality estimate showed a one-way causation from economic growth to insurance development. The study recommended that the government should put in place appropriate policies and regulations which would bring about sound development of the insurance sector. This would enhance the contribution of the insurance industry to the growth of the Nigerian economy. JEL Classification: E44, G22, O40
The Effectiveness of Public Spending on Education and Health Care in Indian Economy
Authors: Kundu Amit 
Published: August 2018

The present study endeavours to examine the role of government spending on the education and health sectors with regard to promoting the gross domestic product (GDP) of India over the last three decades. Johansen cointegration test confirmed the existence of cointegrating relation. The causal impact of education and health care spending on GDP was further examined in the study. Results of the estimated vector autoregression (VAR) models showed that public spending on education and public spending on health care have not been able to exert any impact on GDP. On the contrary, it is found that two-periods-lagged GDP Granger caused the government spending on health care. The variance decomposition analysis indicates that in India, education spending and health care spending may contribute just about 3 per cent and 15 per cent respectively in constituting a GDP growth profile in the coming future. Therefore, it is found that India’s fiscal system has a relatively low impact on the distribution of income as far as public spending on education and health care are concerned. JEL Classification: I25
Regional Manufacturing Disparity in India and the Role of Investment
Authors: Padhi Satya Prasad 
Published: August 2018

There is some evidence that an increase in the regional manufacturing disparity in India is associated with regional (panel data specific) embodiment hypothesis. The purpose of the present article is to provide different interpretations of such association. It endeavours to illustrate that the neoclassical perspective is best suited for universal applications (and long-run tendency towards global regional convergence), and the tweaking of such principles—to generate conditional convergence theories, just to explain persistence regional disparity—fails to convince. In this present context, the present article adopts an augmented Keynesian–Youngian thesis wherein the embodiment hypothesis not only explains the intrinsic possibility of the disparity but also makes clear why the so-called conditional variables (emphasised otherwise by the neoclassical attempts) differ regionally. JEL Codes: O11, O15, O47, R11, D29
A positive psychology–motivational interviewing intervention for patients with type 2 diabetes: Proof-of-concept trial
Authors: Celano Christopher M , Gianangelo Taylor A , Millstein Rachel A , Chung Wei-Jean , Wexler Deborah J , Park Elyse R , Huffman Jeff C 
Published: August 2018

Objective Eighteen million Americans with type 2 diabetes (T2D) do not follow recommended guidelines for physical activity. Motivational interviewing (MI) has had modest effects on activity and related behaviors in T2D. Positive psychological attributes (e.g., optimism) are associated with superior medical outcomes in T2D, and positive psychology (PP) interventions promote such attributes. There had been no study in T2D of a combined PP–MI intervention to promote well-being and health behavior adherence. We developed a novel, telephone-delivered, 16-week PP–MI intervention and explored its feasibility and impact in T2D patients in a single-arm, proof-of-concept trial. Method Participants completed PP-based exercises and MI-based physical activity goal-setting activities and reviewed these activities weekly with a study trainer for 16 weeks. Feasibility and acceptability were assessed via exercise completion rates and post-exercise ratings of ease/utility (0–10 scales). Impact was explored by examining changes in physical activity (via accelerometers and self-report), other health behaviors, psychological measures, and medical outcomes (e.g., hemoglobin A1c (A1C)) from baseline to 16 weeks, using paired t tests. Results Twelve participants enrolled, and 10 provided follow-up data. Seventy-eight percent of PP–MI activities were completed, and participants rated the PP–MI content and sessions as easy (mean = 8.2/10, standard deviation (SD) = 1.9) and useful (mean = 9.1/10, SD = 1.5). PP–MI was associated with improved adherence to health behaviors and overall self-care, variable effects on accelerometer-measured activity and psychological outcomes, and modest beneficial effects on body mass index and A1C. Conclusion Further testing of this intervention is warranted in a larger, controlled trial to assess its effects on important health outcomes.