tbuckley/cabot-search huggingface dataset:
Financial Incentives to Increase Colorectal Cancer Screening Uptake and Decrease Disparities
Authors: Beverly B. Green, Melissa L. Anderson, Andrea J. Cook, Jessica Chubak, Sharon Fuller, Kilian J. Kimbel, Jeffrey T. Kullgren, Richard T. Meenan, Sally W. Vernon
Journal: JAMA Network Open (2019)

Colorectal cancer screening rates are suboptimal, particularly among sociodemographically disadvantaged groups.To examine whether guaranteed money or probabilistic lottery financial incentives conditional on completion of colorectal cancer screening increase screening uptake, particularly among groups with lower screening rates.This parallel, 3-arm randomized clinical trial was conducted from March 13, 2017, through April 12, 2018, at 21 medical centers in an integrated health care system in western Washington. A total of 838 age-eligible patients overdue for colorectal cancer screening who completed a questionnaire that confirmed eligibility and included sociodemographic and psychosocial questions were enrolled.Interventions were (1) mail only (n = 284; up to 3 mailings that included information on the importance of colorectal cancer screening and screening test choices, a fecal immunochemical test [FIT], and a reminder letter if necessary), (2) mail and monetary (n = 270; mailings plus guaranteed $10 on screening completion), or (3) mail and lottery (n = 284; mailings plus a 1 in 10 chance of receiving $50 on screening completion).The primary outcome was completion of any colorectal cancer screening within 6 months of randomization. Secondary outcomes were FIT or colonoscopy completion within 6 months of randomization. Intervention effects were compared across sociodemographic subgroups and self-reported psychosocial measures.A total of 838 participants (mean [SD] age, 59.7 [7.2] years; 546 [65.2%] female; 433 [52.2%] white race and 101 [12.1%] Hispanic ethnicity) were included in the study. Completion of any colorectal screening was not significantly higher for the mail and monetary group (207 of 270 [76.7%]) or the mail and lottery group (212 of 284 [74.6%]) than for the mail only group (203 of 284 [71.5%]) (P = .11). For FIT completion, interventions had a statistically significant effect (P = .04), with a net increase of 7.7% (95% CI, 0.3%-15.1%) in the mail and monetary group and 7.1% (95% CI, -0.2% to 14.3%) in the mail and lottery group compared with the mail only group. For patients with Medicaid insurance, the net increase compared with mail only in FIT completion for the mail and monetary or the mail and lottery group was 37.7% (95% CI, 11.0%-64.3%) (34.2% for the mail and monetary group and 40.4% for the mail and lottery group) compared with a net increase of only 5.6% (95% CI, -0.9% to 12.2%) among those not Medicaid insured (test for interaction P = .03).Financial incentives increased FIT uptake but not overall colorectal cancer screening. Financial incentives may decrease screening disparities among some sociodemographically disadvantaged groups.ClinicalTrials.gov identifier: NCT00697047.
Classifying circulating, mutation bearing tumor cells from breast cancer patients.
Authors: William Strauss, Paul W. Dempsey, Jessamine Winer-Jones, Catherine Bingham, R. Katherine Alpaugh, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2013)

580 Background: The treatment of advanced breast cancer demands systemic therapies that can address disease heterogeneity and the development of treatment resistance without a “real-time” molecular window into disease biology. New technologies have focused on increased capture and molecular analysis of circulating tumor cells (CTCs) including cells undergoing epithelial mesenchymal transition (EMT). We conducted a pilot experiment to test the efficiency of capture and cytokeratin (CK) detection and the presence of single point variants (SNV) to determine the best utility of scoring alternatives for CTC. Methods: EpCAM expressing CTC were recovered from breast cancer patients using CellSearch (Veridex) and LiquidBiopsy (Cynvenio Biosystems). EpCAM recovery and CK scoring were indexed in spiked samples and in 12 inflammatory breast cancer (IBC) patient samples using antibodies against CKs 7, 8 or CKs 1-8, 10, 13-16, 18, 19. Additionally, LiquidBiopsy template was analyzed using an Ampliseq 1.0 panel on the IonTorrent PGM. SNV present in the CTC but not white blood cell (WBC) negative controls were identified and where possible, compared to tissue biopsy SNV analyzed using Foundation One (Foundation Medicine). Results: CTCs were detected using CellSearch 10/12 (83%) (range 0-2502 CTC/7.5ml) and LiquidBiopsy 12/12 (100%) (range 6-2800 CTC/7.5mL). More CK positive events were scored using CKs 1-8, 10, 13-16, 18, 19 than CKs 7, 8 in patient samples. Upon sequencing, shared germline polymorphisms were observed in CTC and WBC. Conversely, 1 or 2 SNV were detected in the Epcam selected population but not WBC controls from 6/12 patients (frequency 1.1%-2.1% with 520-5160x coverage) with SNV observed in TP53, MPL, PIK3ca, MET and IDH1. All but one of the PIK3ca mutations were absent in evaluable tissue biopsy. Conclusions: CTC recovery and scoring are two separate events. Altered CK detection emphasized the need to tailor CTC classification to specific disease settings. Sequence analysis showed one correlated SNV among 6 evaluable comparisons to tissue reflecting variable analysis as well as the biologic disparity of metastatic disease. This pilot demonstrates the feasibility of using CTC for molecular analysis.
Abstract 4279: Heterogeneous LC3A expression regulates lung cancer cell plasticity
Authors: Chia-Cheng Miao, Wen Hwang, Yu-Ting Chou
Journal: Cancer Research (2019)

Abstract Tumor metastasis is considered as the main cause that contributes to high mortality during lung cancer progression. Autophagy is a self-cleaning process to maintain cell integrity of intracellular organelles and proteins. To date, the role of autophagy in lung tumor metastasis remains elusive. Here, we report that lung tumors display a heterogeneous expression pattern of the autophagy mediator LC3A, the high expression of which is associated with low metastasis risk. We found a group of lung cancer cells contain differential LC3A expression levels and exhibit plasticity characterized by distinct proliferative and invasive properties. Immunofluorescence staining and immunoblotting assays revealed that LC3A-mediated autophagy is more active in highly proliferative but minimally invasive lung cancer cells than their lowly proliferative but highly invasive counterpart. Clonogenic analysis and cell cycle assays showed that LC3A silencing attenuated cellular growth, causing G1/S cell cycle arrest in highly proliferative lung cancer cells. Highly proliferative lung cancer cells exhibited a higher oxygen consumption rate, accompanied with an elevated oxygen species (ROS) level, compared to their lowly proliferative counterpart. Pharmacological inhibition of autophagy with chloroquine promoted the ROS production in highly proliferative lung cancer cells but not in the highly invasive counterpart. SOX2 expression enhanced LC3A expression and promoted proliferation but inhibited invasiveness in lung cancer cells. Knockdown of LC3A expression in SOX2-high proliferative cells enriched SOX2-low cells, exhibiting decreased proliferation but increased invasiveness. Combined, our findings provide substantial evidence to suggest that LC3A cooperates with SOX2 signaling to regulate lung cancer cell plasticity. Citation Format: Chia-Cheng Miao, Wen Hwang, Yu-Ting Chou. Heterogeneous LC3A expression regulates lung cancer cell plasticity [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 4279.
Prognostic metabolic markers in cutaneous melanoma
Authors: L. Nájera, M. Alonso‐Juarranz, M. Garrido, C. Ballestín, L. Moya, M. Martínez‐Díaz, R. Carrillo, A. Juarranz, F. Rojo, J.M. Cuezva, J.L. Rodríguez‐Peralto
Journal: British Journal of Dermatology (2019)

Melanoma is the most aggressive skin tumour, being the leading cause of death from skin cancer. Its incidence has increased more rapidly than for any of the top 10 cancers. A low percentage of patients with metastasis (meaning it has spread to other parts of the body) survive over one year after diagnosis, due to the lack of efficient therapy. Not all melanomas are the same, they can vary in how aggressive they are (how quickly they develop and potentially spread) and in their appearance. The authors of this study, from Spain, studied cultured (grown in the lab from a sample) melanoma cells with different aggressiveness features and patients with different types of melanoma lesions. They aimed to find metabolic markers in melanoma that could predict the evolution of the disease. Cellular metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. It is known that the metabolism of cancer cells is different from that of normal cells since they grow and divide rapidly, needing high‐energy supply. In this context, the authors found that proteins (enzymes) related with energy production are altered. These proteins are: the ATP synthase (β‐F1‐ATPase), the heat‐shock protein 60 (HSP60), the glycolytic glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and the pyruvate kinase M2 (PKM2). These proteins provide the bioenergetic signature (BEC index=β‐F1‐ATPase/HSP60/GAPDH ratio) of cancer. A reduction in BEC index correlates with the aggressiveness of cultured melanoma cells and tumours and worse overall survival in melanoma patients. The authors conclude that the level of metabolic enzymes and BEC status are markers of (indicators of) melanoma stage (how adavanced it is, e.g. if it has spread and by how much) and overall survival in melanoma patients.
Chloroquine as alternative antimalarial in systemic lupus erythematosus. Response to ‘2019 update of the EULAR recommendations for the management of SLE: don’t forget chloroquine’ by Figueroa-Parra <i>et al</i>
Authors: Antonis Fanouriakis, George K Bertsias, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2019)

Chloroquine as alternative antimalarial in systemic lupus erythematosus: response to '2019 update of the EULAR recommendations for the management of SLE: don't forget chloroquine' by Figueroa-Parra et alWe thank Drs Figueroa-Parra et al for their interest in our paper 1 and their comment regarding the value of chloroquine (CQ) as an alternative antimalarial in systemic lupus erythematosus (SLE). 2 As the authors point out, there are data, mostly for older studies, to support the efficacy of CQ in SLE. 3 Nevertheless, over the last 20 years, hydroxychloroquine (HCQ) has largely displaced CQ in the USA and in Europe, mainly due to concerns for potential higher retinal toxicity of the latter (although no studies have formally tested different CQ doses in relation to toxicity). 4Accordingly, the vast majority of recent literature on the multiple benefits of antimalarial therapy refers to the use of HCQ, 5 and there is general agreement that the latter should be the antimalarial of choice in SLE.Based on the above, the updated European League against Rheumatism recommendations for the management of lupus provide guidance reflecting current practice in the majority of settings and regions around the world.This being said, we acknowledge that in countries with significant cost differences between the two drugs, CQ may be considered as a justified alternative, 6 with diligent monitoring for toxic retinopathy according to the recommendations.
ECX as neoadjvuant chemotherapy for gastric cancer in South America.
Authors: Leandro Machado Colli, Antonio Carlos Godoy, Bruno Filardi, Jose Marcio Barros Figueiredo, José Sebastião Santos, Fabio Eduardo Zola, Liane Rapatoni, Fernanda Maris Peria
Journal: Journal of Clinical Oncology (2013)

e15190 Background: Gastric cancer is a common malignant disease with a high mortality rate. Neoadjuvant treatment is efficient, but not the first option for treatment in all countries. Studies of neadjuvant chemotherapy in gastric cancer in South American countries are lacking. The aim of this retrospective analysis was to investigate the use of the ECX (epirubicin, cisplatin, and capecitabine) regimen in the neoadjuvant therapy in a Brazilian population. Methods: 25 patients (median age, 61; range 36-78 years; 14 pts &gt;60 years) with locally advanced gastric adenocarcinoma received three courses of preoperative chemotherapy with epirubicin 50 mg/m², day 1, cisplatin 60 mg/m², day 1, and capecitabine 625 mg/m² bid, days 2-21, of a 21-day cycle. Toxicity was assessed by the Common Toxicity Criteria (CTC) after every cycle. Progression-free survival (PFS) was defined as time from diagnosis to disease progression assessed by CT. Results: 21 pts completed all three planned cycles of neoadjuvant chemotherapy. Four patients receiced surgery earlier than planned due to bleeding (1), toxicity (1), abdominal infection (1), and non-adherence to treatment (1). Three patients could not be operated due to disease progression. 70% of operated patients had curative resection with two pathologic complete response. Only six out 25 patients had disease progression and only two died after a median follow-up of 11.5 months (range 3.4-20.2). Median PFS and overall survival were not reached. Toxicities grade 3-4 were neutropenia (28%), febrile neutropenia (8%), bleeding (8%), and heart failure (6,2%). Conclusions: ECX is a efficacious neoadjuvant treatment in the Brazilian population and also well tolerated and safe. However, more studies with a larger South American population are needed.
Understanding Heterogeneity in Biologic Phenotypes of Acute Respiratory Distress Syndrome by Leukocyte Expression Profiles
Authors: Lieuwe D. J. Bos, Brendon P. Scicluna, David S. Y. Ong, Olaf Cremer, Tom van der Poll, Marcus J. Schultz
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Two biologic phenotypes of acute respiratory distress syndrome (ARDS) have been identified based on plasma protein markers in four previous studies.Objectives: To determine if blood leukocyte gene expression is different between the “reactive” and “uninflamed” phenotype.Methods: This is a new study adding blood leukocyte transcriptomics and bioinformatics analysis to an existing patient cohort of ARDS in patients with sepsis admitted to two ICUs during a 1.5-year period. Canonical pathway analysis was performed.Measurements and Main Results: A total of 210 patients with sepsis and ARDS were included, of whom 128 had a reactive and 82 an uninflamed phenotype. A total of 3,332/11,443 (29%) transcripts were significantly different between the phenotypes. Canonical pathway analysis showed upregulation of oxidative phosphorylation genes indicative of mitochondrial dysfunction (52% of genes in pathway). The uninflamed phenotype was characterized by upregulation of mitogen-activated protein kinase pathways.Conclusions: A third of genes are differentially expressed between biologic phenotypes of ARDS supporting the observation that the subgroups of ARDS are incomparable in terms of pathophysiology. These data provide additional support for biologic heterogeneity in patients with ARDS and suggests that a personalized approach to intervention focusing on oxidative phosphorylation is pivotal in this condition.
Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report
Authors: Haesook T. Kim, Kwang Woo Ahn, Zhen-Huan Hu, Matthew S. Davids, Virginia O. Volpe, Joseph H. Antin, Mohamed L. Sorror, Mazyar Shadman, Oliver Press, Joseph Pidala, William Hogan, Robert Negrin, Steven Devine, Joseph Uberti, Edward Agura, Richard Nash, Jayesh Mehta, Joseph McGuirk, Stephen Forman, Amelia Langston, Sergio A. Giralt, Miguel-Angel Perales, Minoo Battiwalla, Gregory A. Hale, Robert Peter Gale, David I. Marks, Mehdi Hamadani, Sid Ganguly, Ulrike Bacher, Hillard Lazarus, Ran Reshef, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Jean-Yves Cahn, Melhem Solh, Mohamed A. Kharfan-Dabaja, Nilanjan Ghosh, Ayman Saad, Mahmoud Aljurf, Harry C. Schouten, Brian T. Hill, Attaphol Pawarode, Tamila Kindwall-Keller, Nakhle Saba, Edward A. Copelan, Sunita Nathan, Amer Beitinjaneh, Bipin N. Savani, Jan Cerny, Michael R. Grunwald, Jean Yared, Baldeep M. Wirk, Taiga Nishihori, Saurabh Chhabra, Richard F. Olsson, Asad Bashey, Usama Gergis, Uday Popat, Ronald Sobecks, Edwin Alyea, Wael Saber, Jennifer R. Brown
Journal: Clinical Cancer Research (2019)

To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or ≥5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
Yesterday’s Child: How Gene Editing for Enhancement Will Produce Obsolescence—and Why It Matters
Authors: Robert Sparrow
Journal: The American Journal of Bioethics (2019)

Despite the advent of CRISPR, safe and effective gene editing for human enhancement remains well beyond our current technological capabilities. For the discussion about enhancing human beings to be worth having, then, we must assume that gene-editing technology will improve rapidly. However, rapid progress in the development and application of any technology comes at a price: obsolescence. If the genetic enhancements we can provide children get better and better each year, then the enhancements granted to children born in any given year will rapidly go out of date. Sooner or later, every modified child will find him- or herself to be "yesterday's child." The impacts of such obsolescence on our individual, social, and philosophical self-understanding constitute an underexplored set of considerations relevant to the ethics of genome editing.
Do patients clinically diagnosed with vascular malformations of 1 lower extremity benefit from imaging of both legs from pelvis to toe? A prospective MRI study
Authors: Veronika I. Teusch, Wibke Uller, Florentine Manger, Katharina Vill, Armin P. Piehler, René Müller-Wille, Holger Goessman, Simone Hammer, Walter A. Wohlgemuth
Journal: Journal of the American Academy of Dermatology (2019)
Abstract 3757: Probing glioblastoma and its microenvironment at single cell resolution
Authors: Sen Peng, Sanhita Rath, Saumya Bollam, Jenny Eschbacher, Shwetal Mehta, Nader Sanai, Michael Berens, Seungchan Kim, Harshil Dhruv
Journal: Cancer Research (2019)

Abstract Single-cell sequencing (scSeq) is a powerful tool to investigate cancer genomics at single cell resolution. Multiple studies have recently illuminated intratumoral heterogeneity in glioblastoma, however, the majority focused on molecular complexity of tumor cells, without taking into account unexplored host cell types that contribute to the microenvironment around GBM tumor. To address the glioblastoma microenvironment composition and potential tumor-host interactions, we performed deep coverage (176k average reads per cell) scSeq of freshly resected primary GBM patient tissue without implementing any tumor cell enrichment strategies. scSeq libraries for 902 cells were prepared using 10X Gemcode platform and sequenced on Illumina NextSeq 500. This run was of high quality with 2,663 median genes per cell and low mitochondrial gene percentage (median &amp;lt; 5%). We used Cell Ranger analysis pipelines and Seurat packages to classify individual cells into 10 clusters and visualize them using t-SNE two-dimensional projections. We then identified the signature gene set for each cluster, relative to all other cells. Pathway analysis of each cluster signature along with known GBM microenvironment cell signatures revealed glioma tumor population along with surrounding microglia/marcophages, astrocytes, pericytes, oligodendrocytes, T cells and endothelial cells. Cell type markers identified by single cell transcriptomics were validated by IHC analysis. Microenvironmental composition and single cell signature will be confirmed through single nuclei sequencing of preserved (Frozen) tumor sample. Our results demonstrate the cellular diversity of brain tumor microenvironment and lay a foundation to further investigate the individual tumor and host cell transcriptomes that are influenced not only by their cell identity but also by their interaction with surrounding microenvironment. Citation Format: Sen Peng, Sanhita Rath, Saumya Bollam, Jenny Eschbacher, Shwetal Mehta, Nader Sanai, Michael Berens, Seungchan Kim, Harshil Dhruv. Probing glioblastoma and its microenvironment at single cell resolution [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 3757.