tbuckley/cabot-search huggingface dataset:
Dysanapsis and the Spirometric Response to Inhaled Bronchodilators
Authors: Motahareh Vameghestahbanati, Miranda Kirby, François Maltais, Dennis Jensen, Dany Doiron, Wan C. Tan, Jean Bourbeau, Benjamin M. Smith, Yves Lacasse, Denis O’Donnell, Robert Cowie, Kenneth Chapman, Roger Goldstein, Darcy Marciniuk, Aaron Shawn, Andrea Benedetti, Paul Hernandez, Mark Fitzgerald, Teresa To, Hélène Perrault, Tanja Taivassalo, William Sheel, Peter Pare, James C. Hogg
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Dysanapsis and the Spirometric Response to Inhaled Bronchodilators." American Journal of Respiratory and Critical Care Medicine, 204(8), pp. 997–1001
Differential Impact of Signaling Inhibitor Treatment Versus Standard Chemoimmunotherapy on Chronic Lymphocytic Leukemia T Cells: Clinical Implications
Authors: Anna Vardi, Elisavet Vlachonikola, Evangelia Koravou, Chrysi Galigalidou, Katerina Gemenetzi, Evangelia Stalika, Andreas Agathangelidis, Michalis Iskas, Niki Stavroyianni, Achilles Anagnostopoulos, Kostas Stamatopoulos, Anastasia Hadzidimitriou
Journal: Blood (2017)
Upper tract urothelial malignancy in adults less than 50 years of age with visible haematuria: A 5-year review of CT urography
Authors: L. Boyle, H. Burden, K. Warren, C. Brolund-Napier, S. Watson, N. Kaneria, F. Merchant, P. McCoubrie, M. Thornton
Journal: European Urology (2021)
Why imaginary worlds? The psychological foundations and cultural evolution of fictions with imaginary worlds
Authors: Edgar Dubourg, Nicolas Baumard
Journal: Behavioral and Brain Sciences (2021)

Imaginary worlds are extremely successful. The most popular fictions produced in the last few decades contain such a fictional world. They can be found in all fictional media, from novels (e.g., Lord of The Rings and Harry Potter) to films (e.g., Star Wars and Avatar), video games (e.g., The Legend of Zelda and Final Fantasy), graphic novels (e.g., One Piece and Naruto), and TV series (e.g., Star Trek and Game of Thrones), and they date as far back as ancient literature (e.g., the Cyclops Islands in The Odyssey, 850 BCE). Why such a success? Why so much attention devoted to non-existent worlds? In this paper, we propose that imaginary worlds co-opt our preferences for exploration, which have evolved in humans and nonhuman animals alike, to propel individuals toward new environments and new sources of reward. Humans would find imaginary worlds very attractive for the very same reasons, and under the same circumstances, as they are lured by unfamiliar environments in real life. After reviewing research on exploratory preferences in behavioral ecology, environmental esthetics, neuroscience, and evolutionary and developmental psychology, we focus on the sources of their variability across time and space, which we argue can account for the variability of the cultural preference for imaginary worlds. This hypothesis can, therefore, explain the way imaginary worlds evolved culturally, their shape and content, their recent striking success, and their distribution across time and populations.
Cost Conversations About Atrial Fibrillation Care—Who Is Talking the Talk?
Authors: Ishani Ganguli, Nitya Thakore
Journal: JAMA Network Open (2021)

Celia C. Kamath, PhD; Rachel Giblon, MS; Marlene Kunneman, PhD; Alexander I. Lee, BS; Megan E. Branda, MS; Ian G. Hargraves, PhD; Angela L. Sivly, CCRP; Fernanda Bellolio, MD, MS; Elizabeth A. Jackson, MD, MPH; Bruce Burnett, MD; Haeshik Gorr, MD; Victor D. Torres Roldan, MD; Gabriella Spencer-Bonilla, MD, MSc; Nilay D. Shah, PhD; Peter A. Noseworthy, MD; Victor M. Montori, MD, MSc; Juan P. Brito, MD, MSc; Shared Decision Making for Atrial Fibrillation (SDM4AFib) Trial Investigators; Alexander Haffke; Amy Stier; Anjali Thota; Annie LeBlanc; Benjamin Simpson; Claudia Zeballos-Palacios; Derek Vanmeter; Emma Behnken; Erik Hess; Henry Ting; James Hamilton IV; Joel Anderson; Jonathan Inselman; Jule Muegge; Kirsten Fleming; Marc Olive; Mark Linzer; Miamoua Vang; Michael Ferrara; Mike Wambua; Paige Organick; Renee Cabalka; Sara Poplau; Takeki Suzuki; Carol Abullarade; Lisa Harvey; Shelly Keune; Timothy Smith; Shannon Stephens; Bryan Barksdale; Theresa Hickey; Roma Peters; Memrie Price; Connie Watson; Douglas Wolfe; Gordon Guyatt; Brian Haynes; George Tomlinson; Paul Daniels; Bernard Gersh; Thomas Jaeger; Robert McBane
Executives with White Coats — The Work and World View of Managed-Care Medical Directors
Authors: T Bodenheimer, L Casalino
Journal: New England Journal of Medicine (1999)

Part 1 of this article discussed the career paths of managed-care medical directors in both HMOs and provider organizations and described their work in the area of utilization management. In this second part, we resume the description of the work of medical directors.Quality ImprovementTop-level medical directors spend a substantial proportion of their time on quality improvement. This activity has grown in importance as a result of the rise to prominence of the National Committee for Quality Assurance (NCQA) and its Health Plan Employer Data and Information Set (HEDIS). Many HMOs seek NCQA accreditation and strive to score high . . .
Abstract 3156: Over-expression of CEACAM6 negatively modulates the tumor microenvironment in pancreatic cancer
Authors: Ritu Pandey, Yuliang Chen, Mihir Patil, Patrick J. Conway, Aisha Al-Khinji, Daruka Mahadevan
Journal: Cancer Research (2021)

Abstract Background: CEACAM6 is a cell adhesion receptor of the Ig-family over-expressed exclusively in primates and human pancreatic ductal adenocarcinoma (PDA). It is present in all subtypes and is enriched classical activated stroma subtype. CEACAM6 has multifaceted roles in KRAS mutant PDA and is a poor prognostic maker (Pandey et al. Sci Rep 2019). We report here in PDA, high CEACAM6 modulates the tumor microenvironment with an immunosuppressive landscape. Methods: RNA-Seq data of PDA patient samples from TCGA and GEO were obtained, normalized and log transformed for analysis. Tumor samples were stratified into cohorts of high and low CEACAM6. Pearson correlation coefficient is utilized to identify CEACAM6 correlated genes and enrichment of signaling pathways. The two cohorts were scored by ESTIMATE for stromal and immune population. Abundance of different cell populations were calculated utilizing MCPcounter and ConsensusTME methods. All analysis was performed using R (v 4.3). Results: High CEACAM6 PDA samples had both stromal and immune components. Half of the high expressing samples had a higher immune score vs stromal score. The other half had both high or both low, immune and stromal score. Investigating the immune genes that are utilized for scoring, we found several immune genes differentially expressed in high CEACAM6 (up-regulated genes - ADAM8, IL2RG, LYZ, SELPLG involved in innate immunity) compared to low CEACAM6 samples. Genes under expressed in high CEACAM6 samples were CD27, NKG7, IL18RAP, LILRB1, KLKRK1 involved in promoting immune response and cell protection. Overall TCGA PDA samples have lower enrichment of immune cells compared to higher enrichment of fibroblasts, endothelial cells, macrophages, monocytes and dendritic cells. The NK cells are overall low in PDA but enriched in some lower CEACAM6 samples. Plasma cells, B-cells, CD8 cells, NK cells, Cytotoxic T-cells, Tγδ-cells have very poor representation in higher CEACAM6 samples but present in some low CEACAM6 expressing samples. Some of the TCGA PDA samples have T-reg cells but high CEACAM6 do not enrich of T-reg cells. High CEACAM6 samples are enriched for metabolic pathways. Conclusions: CEACAM6 over-expressed in PDA have pathologic functions which include reshaping the stroma, suppressing host immunity and inhibiting apoptosis. An anti-CEACAM6 Mab increases apoptosis, necrosis and anti-tumor activity in PDA. Citation Format: Ritu Pandey, Yuliang Chen, Mihir Patil, Patrick J. Conway, Aisha Al-Khinji, Daruka Mahadevan. Over-expression of CEACAM6 negatively modulates the tumor microenvironment in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3156.
Abstract 1524: Peripheral blood mononuclear cells engineered via microfluidic Cell Squeeze® technology to generate APCs that drive mutant-KRas-specific CD8+ T cell responses
Authors: Defne Yarar, Carolyne Smith, Amritha Ramakrishnan, Scott Loughhead, Armon Sharei, Katherine Seidl, Howard Bernstein
Journal: Cancer Research (2021)

Abstract KRAS mutations are shared across multiple cancer types and are most commonly found in cancers of the lung, pancreas, and colon. While recently developed drugs blocking signaling driven by KRAS G12C mutations have shown promise in the clinic, there is a great need for therapies targeting the more common G12V and G12D mutations. We utilize our microfluidic Cell Squeeze® technology to deliver antigens directly into the cytosol of peripheral blood mononuclear cells (PBMCs) for the generation of cancer antigen-targeted cellular vaccines. This method bypasses the need for cross-presentation and directly enables efficient antigen presentation on MHC-I in multiple cell types. Murine and human in vitro studies have demonstrated that this allows SQZ PBMCs to drive CD8+ T cell activation. Here, we demonstrate the delivery of various antigens, including KRas-derived peptides containing the most common mutations (G12D and G12V) to PBMC cell subsets. In addition, we find that human PBMCs squeezed with either KRasG12V or KRasG12D peptides can specifically stimulate KRasG12V- and KRasG12D- reactive CD8+ T cell responders. When KRasG12V and KRasG12D peptides are co-delivered via microfluidic squeezing, the human PBMCs enable activation of CD8+ T cells of both specificities. This work with KRasmutant-presenting human PBMCs lays a strong foundation for developing a potentially potent cell therapy to treat KRASmutant associated cancers. Citation Format: Defne Yarar, Carolyne Smith, Amritha Ramakrishnan, Scott Loughhead, Armon Sharei, Katherine Seidl, Howard Bernstein. Peripheral blood mononuclear cells engineered via microfluidic Cell Squeeze® technology to generate APCs that drive mutant-KRas-specific CD8+ T cell responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1524.
Abstract 13355: Impact of Imaging-Guided Emergency Percutaneous Coronary Intervention on Stent Strut Condition After Drug-Eluting Stents Implantation
Authors: Takuya Nakamura, Yutaka Goryo, Enomoto Masashi, Isojima Takuya, Takitsume Akihiro, Hiroyuki Kawata
Journal: Circulation (2019)

Introduction: Recently using the imaging modality, intravascular ultrasound (IVUS) and optical coherence tomography (OCT), for percutaneous coronary intervention (PCI) has developed and used for op...
Abstract 514: Specific anti-HER2 host immunity conferred by HER2-targeted antibody drug conjugate therapy and checkpoint blockade
Authors: You Qin, Hannah E. Dobson, Frank I. Comer, Alfred E. Chang, Max S. Wicha, Qiao Li
Journal: Cancer Research (2021)

Abstract Using HER2-targeted antibody drug conjugates (ADC), we tested the therapeutic efficacy, direct impact on cancer stem cells (CSCs), and potential added benefit when combined with PD-L1 blockade in immunocompetent mouse tumor models. Two murine mammary tumor models were used in this study: D2F2/E2, a cell line resulting from stable transfection of parental D2F2 murine mammary tumor cells with wild-type human HER2, and 4T1-HER2, derived from parental 4T1 by stable transduction with wild-type human HER2. We demonstrate that HER2-targeted ADC treatment induced both cellular and humoral anti-HER2 adaptive immune responses which effectively targeted both bulk tumor and cancer stem cells. We recently investigated induction of host immunity using a tumor re-challenge strategy in tumor free animals subjected to ADC or ADC + anti-PD-L1 therapy. D2F2/E2 tumor-bearing mice were treated with ADC or ADC + anti-PD-L1 to generate tumor free mice. These tumor free animals were re-challenged with the relevant tumor D2F2/E2 or irrelevant tumor WT 4T1 respectively. While all the tumor free animals re-challenged with WT 4T1 showed aggressive tumor growth, ADC-treated tumor free animals re-challenged with D2F2/E2 demonstrated significantly (p&amp;lt;0.0001) slower tumor growth compared with the age-matched naive mice, and this protection was significantly (p=0.0078) enhanced in ADC + anti-PD-L1-treated tumor free animals, resulting in completely rejection of the re-challenge and thus documenting immunological memory formation. B cell activation was obvious by the significant upregulation of Ki67 and GL7 CD86 on both CD45+CD19+ tumor-infiltration lymphocytes (TILs) and splenocytes. B cell differentiation was evident by the upregulation of GL7 on both TILs and splenocytes, as well as the expression of CD138 on splenotytes. We found that IgG1 was the predominant isotype in treated mice vs. IgG2a, IgG2b, IgG3, and ADC + anti-PD-L1 dual treatment drastically increased the amount of IgG1 in serum. In addition, ADC+ anti-PD-L1 dual treatment significantly increased the frequency of CD8+IFNγ+ cells in TILs. Both ADC alone (p=0.0004) and ADC+anti-PD-L1 dual treatment (p=0.01) significantly decreased CD4+FoxP3+ regulatory T cells. These results provide evidence that HER2-targeted ADC + anti-PD-L1 immunotherapy-induced B cell activation and differentiation along with the modulation of T cell subsets could confer host anti-HER2 immunity. Citation Format: You Qin, Hannah E. Dobson, Frank I. Comer, Alfred E. Chang, Max S. Wicha, Qiao Li. Specific anti-HER2 host immunity conferred by HER2-targeted antibody drug conjugate therapy and checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 514.
Abstract 882: Associations of genetically predicted blood protein biomarkers with pancreatic ductal adenocarcinoma risk: A study using comprehensive protein genetic prediction models
Authors: Dalia Ghoneim, Jingjing Zhu, Jihwan Ha, Praveen Surendran, Qizhi Cathy Yao, Tao Liu, Sarah Fahle, Adam Butterworth, Chong Wu, Lang Wu
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with few known risk factors and biomarkers. Identification of biomarkers is critical for understanding the pathogenesis of this deadly cancer and identifying high-risk individuals for close surveillance. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of protein biomarkers usually in small set(s) of samples. To identify novel circulating protein biomarkers of PDAC, we studied 8,275 cases and 6,723 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium. Leveraging genome and plasma proteome data of 2,841 healthy European descendants included in the INTERVAL study, we established models using four methods (best linear unbiased predictor, elastic net, LASSO, and top1) to predict protein levels based on genetic variants. For each protein, of the four sets of models developed, the model showing the highest prediction performance (R2) was retained. We selected 2,164 built protein models with a prediction performance (R2) of &amp;gt;0.01 for association analyses with PDAC risk. We observed associations between predicted concentrations of 14 proteins and PDAC risk at a false discovery rate of &amp;lt; 0.05, including those of eight proteins that showed a significant association after Bonferroni correction (2.31 × 10-5). These include Histo-blood group ABO system transferase encoded by ABO, which has been previously implicated as a potential target gene of PDAC risk variant identified in GWAS. Besides eight proteins that were previously reported in our earlier study using protein quantitative trait loci as instruments, we identified six novel proteins which have not been identified in previous studies. Six of the identified proteins showed positive associations and eight showed inverse associations (P-values from 2.62 × 10-4 to 5.71 × 10-21). In conclusion, we identified 14 protein biomarker candidates for PDAC risk, which if validated in future studies, may contribute to the etiological understanding of PDAC development. Citation Format: Dalia Ghoneim, Jingjing Zhu, Jihwan Ha, Praveen Surendran, Qizhi Cathy Yao, Tao Liu, Sarah Fahle, Adam Butterworth, Chong Wu, Lang Wu. Associations of genetically predicted blood protein biomarkers with pancreatic ductal adenocarcinoma risk: A study using comprehensive protein genetic prediction models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 882.
Abstract CT257: Phase 3 multicenter randomized trial of PSMA PET/CT prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: Study Protocol
Authors: Jeremie Calais, Shaojun Zhu, Nader Hrimas, Matthias Eiber, Boris Hadaschik, Martin Stuschke, Ken Herrmann, Johannes Czernin, Amar U. Kishan, Nicholas G. Nickols, David Elashoff, Wolfgang Fendler
Journal: Cancer Research (2021)

Abstract Background: Definitive radiation therapy (dRT) is an effective initial treatment of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). PSMA PET/CT is superior to standard of care imaging (CT, MRI, bone scan) for detecting regional and distant metastatic PCa. PSMA PET/CT thus has the potential to guide patient selection and the planning for dRT and improve patient outcomes. Methods: This is a multicenter randomized phase 3 trial (NCT04457245). We will randomize 312 patients to proceed with standard dRT (control Arm, n=150), or undergo a PSMA PET/CT scan at the study site (both 18F-DCFPyL and 68Ga-PSMA-11 can be used) prior to dRT planning (intervention arm, n = 162). dRT will be performed at the treating radiation oncologist facility. In the control arm, dRT will be performed as routinely planned. In the intervention arm, the treating radiation oncologist can incorporate PSMA PET/CT findings into the RT planning. Androgen deprivation therapy (ADT) is administered per discretion of the treating radiation oncologist and may be modified as a result of the PSMA PET/CT results. We assume that approximately 8% of subjects randomized to the PSMA PET arm will be found to have M1 disease and thus will be more appropriate candidates for long-term systemic or multimodal therapy, rather than curative intent dRT. PET M1 patients will thus not be included in the primary endpoint analysis. The primary endpoint is the success rate of patients with unfavorable IR and HR PCa after standard dRT versus PSMA PET-based dRT. Secondary Endpoints (whole cohort) include progression free survival (PFS), metastasis-free survival after initiation of RT, overall survival (OS), % of change in initial treatment intent and Safety. Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa who receive dRT. In this trial the incorporation of PSMA PET/CT may improve the success rate of curative intent radiotherapy in two ways: to optimize patient selection as a biomarker and to personalizes the radiotherapy plan. Citation Format: Jeremie Calais, Shaojun Zhu, Nader Hrimas, Matthias Eiber, Boris Hadaschik, Martin Stuschke, Ken Herrmann, Johannes Czernin, Amar U. Kishan, Nicholas G. Nickols, David Elashoff, Wolfgang Fendler. Phase 3 multicenter randomized trial of PSMA PET/CT prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: Study Protocol [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT257.
Predictors of development and duration of Delayed Graft Function (DGF) in marginal kidneys preserved with Hypothermic Pulsatile Machine Perfusion (HPMP)
Authors: A. Dominguez, M. Ruiz Hernández, V. Gómez Dos Santos, J.A. López Plaza, C. Sánchez Guerrero, F.J. Burgos Revilla
Journal: European Urology (2021)
Abstract 1012: <i>In vitro</i> antitumor effect of AZD4547 in ovarian cancer cell lines
Authors: Ji Hae Seo, Seungmee Lee, Chi-Heum Cho, So-Jin Shin
Journal: Cancer Research (2021)

Abstract Of all the gynecological cancer, ovarian cancer is the most fatal malignancy. In particular, strong chemotherapy resistance in ovarian cancer raises the need for new therapeutic strategy. Since fibroblast growth factor (FGF) signaling pays an important role in malignant transformation, tumor growth, angiogenesis, and chemoresistance, fibroblast growth factor receptor (FGFR) inhibitors are being assessed in clinical trials for several FGFR-driven cancer. FGFRs is known to be highly dysregulated in ovarian cancer, however the effect of FGFR inhibition in ovarian cancer has not been elucidated. In this study, we investigated the anti-tumor effects of AZD4547, an FGFR1-4 inhibitor, in various types of ovarian cancer cell line. AZD4547 markedly inhibited proliferation and stimulated apoptosis of ovarian cancer cells. In addition, AZD4547 inhibited cell migration and invasion under non-toxic condition. Moreover, AZD4547 reduced the sphere forming ability and the self-renewal capacities of ovarian cancer stem cells (CSCs) which are strongly resistant to paclitaxel. Furthermore, AZD4547 exhibited anti-angiogenic effect on human umbilical vein endothelial cells. Based on these anti-tumor effect of AZD4547 in ovarian cancer cell lines, we suggests AZD4547 as a promising agent for ovarian cancer treatment. Citation Format: Ji Hae Seo, Seungmee Lee, Chi-Heum Cho, So-Jin Shin. In vitro antitumor effect of AZD4547 in ovarian cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1012.