tbuckley/cabot-search huggingface dataset:
Abstract 15797: Bariatric Procedures in Patients With Left Ventricular Assist Devices: Insights From the Nationwide Inpatient Sample
Authors: Vanessa Blumer, Marat Fudim, Gabriel A Hernandez, Miguel Ortiz, Adam DeVore, Chetan B Patel, Sandra Chaparro
Journal: Circulation (2018)

Background: Morbidly obese patients with end-stage heart failure (HF) are routinely ineligible for heart transplantation. Left ventricular assist devices (LVAD) are commonly used in an attempt to a...
Abstract 4797: A novel Diiminoquinone targets colorectal cancer stem cells
Authors: Alissar Monzer, Nayri Jabotian, Jie S. Zhu, Mark J. Kurth, Wassim Abou Kheir, Makhlouf Haddadin, Hala Gali-Muhtasib
Journal: Cancer Research (2019)

Abstract 5-Fluorouracil (5-Fu) remains the standard chemotherapy for metastatic colorectal cancer, but drug resistance and unpredictable cardiotoxicity limit its effectiveness. The high recurrence rates and common resistance are thought to be due to a population of self-renewing cancer stem cells (CSCs). In this study, we synthesized four novel heterocyclic compounds that are similar in structure with quinones and tested their anticancer activity against HCT116 human colon cancer cells in 2D monolayer and 3D sphere cultures. In 2D, all compounds caused significant inhibition of colon cancer cell viability at concentrations non-cytotoxic to normal human FHs74Int intestinal cell lines. In 3D cultures, these heterocycles eradicated the self-renewal ability of the highly resistant cancer stem cells and inhibited colon sphere formation in first generation (G1), as well as subsequent generations. This study represents the first documentation of the activity of these novel heterocyclic compounds, particularly compound 6a, abbreviated as DIQ-3, which we propose to be an effective treatment strategy to prevent colon cancer recurrence by targeting colorectal CSCs. Our findings provide the basis for suggesting these non-toxic and stable compounds for additional testing against cancer. Citation Format: Alissar Monzer, Nayri Jabotian, Jie S. Zhu, Mark J. Kurth, Wassim Abou Kheir, Makhlouf Haddadin, Hala Gali-Muhtasib. A novel Diiminoquinone targets colorectal cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4797.
Abstract 1641: Generation and evaluation of medical synthetic data
Authors: Andre R. Goncalves, Priyadip Ray, Braden Soper, Madhumita Myneni, Jennifer L. Stevens, Linda M. Coyle, Ana Paula Sales
Journal: Cancer Research (2019)

Abstract While machine learning (ML) has shown some promise in medical research, its actual impact has been limited relative to other application domains. One reason for this disparity is the lack of high-quality, patient-level data available to the broader ML research community. Such datasets are often not made available due to protections around patient privacy. To overcome these obstacles, high-quality, synthetic datasets could be leveraged to accelerate methodological developments in the application of ML to biomedical research. Clinical data in the form of electronic health records present a rich data source to be used for synthetic data generation. Such data can be high dimensional and predominantly categorical, which poses multiple challenges from a modeling perspective. In this paper, we evaluate four classes of synthetic data generation techniques, as well as several metrics for evaluating the quality of the synthetic data. While the results and discussions are broadly applicable to medical data, for demonstration purposes we generate synthetic datasets from the publicly available Surveillance Epidemiology and End Results (SEER) program. Specifically, our cohort consists of breast cancer cases diagnosed in the year of 2010, which includes over 26000 individual cases. Finally, we discuss the trade-offs of the different methods and metrics, providing guidance on considerations for the generation and usage of synthetic medical data. Citation Format: Andre R. Goncalves, Priyadip Ray, Braden Soper, Madhumita Myneni, Jennifer L. Stevens, Linda M. Coyle, Ana Paula Sales. Generation and evaluation of medical synthetic data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1641.
Abstract 18181: Pulse Oximetry: A Simple and Novel Marker for Calculating the Rate of Chest Compressions in Porcine Models of Cardiac Arrest
Authors: Fu Yangyang, Jun Xu, Feng Sun, Huadong Zhu, Xuezhong Yu
Journal: Circulation (2017)

Introduction: Pulse oximetry, which noninvasively detects the blood flow of peripheral tissue, has achieved widespread clinical use. We have noticed that the pulse waveform frequency can reflect th...
Abstract 3542: Turbolase: A radically streamlined high throughput sample prep to sequencing workflow
Authors: Dustin Masser, Robert Stedtfeld, Justin Lenhart, Vladimir Makarov, Laurie Kurihara
Journal: Cancer Research (2019)

Abstract Normalase is a novel enzymatic library normalization method that eliminates library quantification and manual concentration adjustment of each sample prior to library pooling, and the uniform sample processing eliminates numerous error-prone pipetting steps. When combined with Swift 2S Turbo rapid library kits, a highly streamlined ‘Turbolase’ workflow is created that is readily automated on the Hamilton Star and other platforms, where simple bulk processing improves throughput and reduces cost for NGS laboratories. Swift 2S Turbo kits comprise two enzymatic steps and a single purification that completes DNA fragmentation, end repair and adapter ligation. This is followed by standard library amplification using Normalase PCR primers to condition the libraries and produce a required minimum yield in excess of the 4 nM final concentration. This is followed by a single purification and two 15-minute Normalase incubation steps that; 1) enzymatically select 4 nM of each library, and 2) enzymatically normalize each library to 4 nM within a single pool. The pools can then be directly sequenced without further purification. Normalase allows for greater than 10-fold variation in input quantity, while generating less than 10% variation in sample representation within a pool resulting in optimal cluster density and sample balance for Illumina sequencing. Because of the unique workflow, Normalase also eliminates index hopping for libraries sequenced on patterned flow cells. The ‘Turbolase’ workflow is compatible with full-length indexed adapters that have been added by ligation as well as workflows that require indexing PCR primers to complete library construction during library amplification. Normalase is also compatible with library preparation kits available from other vendors. Normalase for pooling of libraries for pre-hybridization capture is currently under development, which will make multiplexed hybridization capture protocols streamlined and robust from library generation to sequencing. Citation Format: Dustin Masser, Robert Stedtfeld, Justin Lenhart, Vladimir Makarov, Laurie Kurihara. Turbolase: A radically streamlined high throughput sample prep to sequencing workflow [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3542.
CD20 Antibodies of Human IgA Isotype Mediate CDC, and ADCC By Myeloid Effector Cells
Authors: Anna Kretschmer, Stefan Lohse, Thies Rösner, Marco J.H. Jansen, Christian Kellner, Matthias Peipp, Mark S Cragg, Ameera Alsadeq, Denis M Schewe, Jeanette H.W. Leusen, Thomas Valerius
Journal: Blood (2016)
Risk of childhood psychiatric disorders in children of refugee parents with post-traumatic stress disorder: a nationwide, register-based, cohort study
Authors: Maj Back Nielsen, Jessica Carlsson, Martin Køster Rimvall, Jørgen Holm Petersen, Marie Norredam
Journal: The Lancet Public Health (2019)

BackgroundChildren of refugees are often exposed to the consequences of parental post-traumatic stress disorder (PTSD), potentially leaving them vulnerable to intergenerational transmission of psychopathology. The present study aimed to determine whether parental PTSD is associated with childhood psychiatric morbidity among children of refugees.MethodsThis study is a two-generation nationwide cohort study using the Danish Immigration Services database. We followed up children younger than 18 years with at least one refugee parent until psychiatric contact, end of the study, their 18th birthday, emigration, or death. We excluded children if their parents were diagnosed only with psychiatric diagnoses other than PTSD or if they had received a psychiatric contact before parental PTSD diagnosis. Information on parental PTSD and offspring psychiatric morbidity was obtained from the Danish Psychiatric Central Research Register. We used Cox proportional hazards regression models to assess the risk of psychiatric contacts among children of refugees with PTSD compared with children of refugees with no psychiatric diagnosis.FindingsBetween Jan 1, 1995, and Dec 31, 2015, 102 010 refugees obtained residency permission in Denmark and 62 239 biological children of refugees were born in Denmark before Dec 31, 2015. 51 793 were eligible and included in the study (median follow-up 7·15 years [IQR 3·37–11·78]); of these, 1307 (2·5%) children had a psychiatric contact. 7486 (14·5%) children of refugees were exposed to parental PTSD. Parental PTSD significantly increased the risk of psychiatric contact in offspring (hazard ratio 1·49 [95% CI 1·17–1·89] for paternal PTSD, p=0·0011; 1·55 [1·20–2·01] for maternal PTSD, p=0·00084) after adjustment for sociodemographic variables.InterpretationChildren of refugees exposed to parental PTSD are at increased risk of psychiatric morbidity. Targeted screening and interventions are necessary to prevent psychiatric morbidity and ensure access to adequate care.FundingSection for Immigrant Medicine, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre.
Abstract 17646: Echo-derived Diastolic Strain Rate is Associated With T2* in End Stage Liver Disease
Authors: Jeffrey M Tyler, David R Anderson, Neil Mehta, Karen Ordovas, Elyse Foster, Gabriel Brooks, Atif N Qasim
Journal: Circulation (2016)

Introduction: Cardiac MRI-derived T2* correlates well with myocardial iron deposition and helps identify those at risk for major cardiac complications after liver transplant (LT). Cardiac MRI may n...
Abstract 4181: Awareness of human papillomavirus (HPV) infection among men and women with oral cancer
Authors: Assia Miller, Latrice Rollins, Ananya Banerjee
Journal: Cancer Research (2019)

Abstract Background There is a high level of public awareness of association human papillomavirus (HPV) infection and genital cancer. Though recent research showed that 26 million Americans have oral HPV infection, the information on awareness of association HPV infection with oral cancer among men and women is limited. Methods The objective of our study was to assess population awareness of and knowledge about the association between HPV and oral cancer among men and women. We obtained cross-sectional data from the National Cancer Institute's Health Information National Trends Surveys (HINTS 2007-2015, N=25,410). We applied a Wald chi-square test to examine the association of HPV awareness in participants with oral cancer compared to participants with other forms of cancer stratified by gender. Results: Among men with oral cancer (N=10) 16 % were aware of HPV while among men with other forms of cancer (N=3557) 44% were aware of HPV (p=0.0924). Among women with oral cancer (N=5) 56 % were aware of HPV while among women with other forms of cancer (N=5631) 64% were aware of HPV (p=7971). Conclusion: There is decreased awareness and knowledge of HPV in men with oral cancer promoting opportunities to target communication about a vaccine. Citation Format: Assia Miller, Latrice Rollins, Ananya Banerjee. Awareness of human papillomavirus (HPV) infection among men and women with oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4181.
Evaluation of USPSTF Lung Cancer Screening Guidelines Among African American Adult Smokers
Authors: Melinda C. Aldrich, Sarah F. Mercaldo, Kim L. Sandler, William J. Blot, Eric L. Grogan, Jeffrey D. Blume
Journal: JAMA Oncology (2019)

The United States Preventive Services Task Force (USPSTF) recommends low-dose computed tomography screening for lung cancer. However, USPSTF screening guidelines were derived from a study population including only 4% African American smokers, and racial differences in smoking patterns were not considered.To evaluate the diagnostic accuracy of USPSTF lung cancer screening eligibility criteria in a predominantly African American and low-income cohort.The Southern Community Cohort Study prospectively enrolled adults visiting community health centers across 12 southern US states from March 25, 2002, through September 24, 2009, and followed up for cancer incidence through December 31, 2014. Participants included African American and white current and former smokers aged 40 through 79 years. Statistical analysis was performed from May 11, 2016, to December 6, 2018.Self-reported race, age, and smoking history. Cumulative exposure smoking histories encompassed most recent follow-up questionnaires.Incident lung cancer cases assessed for eligibility for lung cancer screening using USPSTF criteria.Among 48 364 ever smokers, 32 463 (67%) were African American and 15 901 (33%) were white, with 1269 incident lung cancers identified. Among all 48 364 Southern Community Cohort Study participants, 5654 of 32 463 African American smokers (17%) were eligible for USPSTF screening compared with 4992 of 15 901 white smokers (31%) (P < .001). Among persons diagnosed with lung cancer, a significantly lower percentage of African American smokers (255 of 791; 32%) was eligible for screening compared with white smokers (270 of 478; 56%) (P < .001). The lower percentage of eligible lung cancer cases in African American smokers was primarily associated with fewer smoking pack-years among African American vs white smokers (median pack-years: 25.8 [interquartile range, 16.9-42.0] vs 48.0 [interquartile range, 30.2-70.5]; P < .001). Racial disparity was observed in the sensitivity and specificity of USPSTF guidelines between African American and white smokers for all ages. Lowering the smoking pack-year eligibility criteria to a minimum 20-pack-year history was associated with an increased percentage of screening eligibility of African American smokers and with equitable performance of sensitivity and specificity compared with white smokers across all ages (for a 55-year-old current African American smoker, sensitivity increased from 32.2% to 49.0% vs 56.5% for a 55-year-old white current smoker; specificity decreased from 83.0% to 71.6% vs 69.4%; P < .001).Current USPSTF lung cancer screening guidelines may be too conservative for African American smokers. The findings suggest that race-specific adjustment of pack-year criteria in lung cancer screening guidelines would result in more equitable screening for African American smokers at high risk for lung cancer.
Abstract 4853: M6123 is an ADCC-enhanced and selective monovalent antagonist of FGFR1 showing antitumor activity in preclinical lung cancer models
Authors: Christina Esdar, Christel Iffland, Astrid Zimmermann, Angela Lim, Michael Sanderson, Andree Blaukat
Journal: Cancer Research (2019)

Abstract Despite the considerable progress made with immunotherapies and targeted therapies, lung cancer remains a devastating disease with a high medical need for more effective and safer therapeutic options. Targeted therapies have delivered meaningful benefit to subsets of lung adenocarcinoma patients harboring specific oncogenic driver alterations but have not yet been extensively explored in other lung cancer subtypes. In the case of lung squamous carcinoma and small-cell lung cancer, amplification and overexpression of FGFR1 have been described as potential oncogenic drivers.Several small molecule tyrosine kinase inhibitors of the FGFR family are in clinical development but initial reports have suggested limited therapeutic benefit of these agents when applied as monotherapy in FGFR1-amplified lung cancer patients. To overcome toxicities associated with pan-FGFR inhibition, such as dysregulation of FGF23-mediated phosphate homeostasis, M6123 was developed as an FGFR1-selective biological antagonist. An immunization campaign in OmniRats® led to the identification of the fully human, potent and highly selective FGFR1 antibody A08 which was converted into the monovalent FGFR1 antagonist M6123 based on the proprietary SEED platform. Furthermore, M6123 was engineered for enhanced ADCC effector function. In contrast to bivalent FGFR1 antibodies, M6123 was well tolerated in mice, with no signs of body weight loss. Of note, M6123 did not interfere with hormonal FGF23 signaling in mice, a severe side effect of FGFR kinase inhibitors. Concentration-dependent inhibition of FGFR1 auto-phosphorylation was demonstrated in FGFR1-overexpressing lung cancer cells both in vitro and in vivo. Moreover, M6123 monotherapy had strong antitumor activity in specific FGFR1-expressing cell line- and patient-derived xenograft models, whilst combination with chemotherapy significantly enhanced efficacy. In summary, M6123 is a unique and clearly differentiated selective FGFR1 antagonist which warrants further testing in preclinical models to refine a predictive biomarker strategy for selection of potentially sensitive lung cancer patients. Citation Format: Christina Esdar, Christel Iffland, Astrid Zimmermann, Angela Lim, Michael Sanderson, Andree Blaukat. M6123 is an ADCC-enhanced and selective monovalent antagonist of FGFR1 showing antitumor activity in preclinical lung cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4853.
Safety and efficacy of once-weekly carfilzomib (K) dosing in frail patients (pts): A subgroup analysis from the phase 3 A.R.R.O.W. study.
Authors: Maria-Victoria Mateos, Heinz Ludwig, Shaji Kumar, Cara Ann Rosenbaum, Mei Huang, Amanda Goldrick, Julie Blaedel, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2019)

8027 Background: A.R.R.O.W. demonstrated superior progression-free survival (PFS) with once-weekly K (70 mg/m 2 )-dexamethasone (Kd70) vs twice-weekly K (27 mg/m 2 )-dexamethasone (Kd27) in relapsed and refractory multiple myeloma (RRMM) pts, regardless of age. Weekly Kd70 is US-approved for relapsed or refractory MM (1–3 prior therapy lines). For a comprehensive fitness measure, frailty scales were developed incorporating age, comorbidities, and functional status. (Palumbo Blood 2015; Facon Blood 2015). Here we assessed post hoc pt outcomes by frailty status. Methods: PFS and safety were assessed by treatment arm and a frailty algorithm incorporating age, medical history–derived Charlson Comorbidity Index, and ECOG performance status; pts with frailty scores of 0, 1, or ≥2 were classified as fit, intermediate (int), or frail, respectively. PFS was assessed with the Kaplan-Meier method. Safety was assessed in pts who received ≥1 treatment dose. Results: Pt distribution by frailty status was generally balanced between arms (Table). Once-weekly Kd70 vs twice-weekly Kd27 resulted in median PFS for fit, int, and frail pts of 15.7 vs 5.7 (mos; HR 0.53 [95% CI, 0.33–0.86]), 11.1 vs 7.7 mos (HR 0.81 [95% CI, 0.55–1.19]), and 10.3 vs 6.6 mos (HR 0.76 [95% CI, 0.49–1.16]), respectively. Rates of grade ≥3 treatment-emergent adverse events (TEAEs) of interest were similar between treatment arms across frailty subgroups (Table). In the once-weekly Kd70 subgroups, there was no grade ≥3 peripheral neuropathy (PN); grade ≥3 cardiac failure rates were ≤4%. Conclusions: Once-weekly Kd70 resulted in PFS benefits vs twice-weekly Kd27 with a favorable benefit/risk profile regardless of frailty score as defined. These results support weekly Kd70 as a treatment option for both fit and frail RRMM pts. Clinical trial information: NCT02412878. [Table: see text]
Abstract 4943: Leveraging single-cell sequencing to discover novel exhaustion markers of CD8 T cells
Authors: Xiaoshan Shi, Savita Jayaram, Kayla Lee, Keshav Bhojak, Vasumathi Kode, Mridul Chaudhary, Ashwini Patil, Ravi Gupta, Amit Chaudhuri, Papia Chakraborty
Journal: Cancer Research (2019)

Abstract Therapeutic revival of tumor-specific exhausted T cells using checkpoint blockade antibodies has improved clinical outcomes in cancer significantly. Notwithstanding a high overall response rate to these drugs, long-term benefit is realized by a small fraction of the treated patients. A mechanistic explanation of relapse comes from the recent findings that in both murine and human cancers intratumoral T cells exist in a wide spectrum of functional states – from fully functional at one end of the spectrum, to fully dysfunctional at the other end. Therefore, tumor response to checkpoint inhibitors is determined by the ratio of functional to dysfunctional state of T cells, which in turn is modulated by a wide array of immune-suppressive signals present within the tumor microenvironment. Dissecting the T cell functional states can significantly enhance our understanding of patient responses to immunotherapy drugs and can be used to develop targeted and personalized strategies for restoring antitumor immunity. A key challenge to this problem is that the transcriptional signatures of dysfunctional exhausted T cells are closely intertwined with the activated/effector CD8+ T cell states. This is not surprising, since T cell dysfunction arises following chronic T cell activation. Developing unique markers of T cell exhaustion from in vivo models has not been successful. In this study, we present data to show how single cell transcriptomics on a 10x Genomics platform can identify T cell functional states following antigen-stimulation in an ex vivo T cell activation system. In particular, we identified functional gene clusters and molecular networks that are unique to CD8+ T cell exhausted state. The combined expression of our T cell exhaustion gene signature correlated with poor prognosis when applied to TCGA data of over 1500 tumors from many different cancers. Furthermore, the molecular pathways identified in this study provide opportunities to develop novel therapeutic interventions specially targeting dysfunctional T cells in cancers thereby enhancing the efficacy of checkpoint inhibitors. Citation Format: Xiaoshan Shi, Savita Jayaram, Kayla Lee, Keshav Bhojak, Vasumathi Kode, Mridul Chaudhary, Ashwini Patil, Ravi Gupta, Amit Chaudhuri, Papia Chakraborty. Leveraging single-cell sequencing to discover novel exhaustion markers of CD8 T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4943.