tbuckley/cabot-search huggingface dataset:
Abstract 2842: Neutrophil migration towards tumor-conditioned media correlates with the malignant potential of breast tumor cells
Authors: Lauren Hein, Shuvasree SenGupta, Yang Xu, Carole Parent
Journal: Cancer Research (2020)

Abstract During tumor development, neutrophils and other immune cells infiltrate the tumor niche. Neutrophils have been shown to have primarily pro-tumorigenic effects, and high levels of circulating neutrophils are indicative of a poor prognosis. Tumor-associated neutrophils (TANs) migrate to tumors by sensing chemical gradients produced by tumor cells; however, the mechanisms by which tumors and TANs interact and impact each other remain to be determined. It has been shown that malignant breast tumors, such as triple-negative breast tumors, harbor more TANs compared to less aggressive breast tumors. We hypothesize that neutrophil recruitment to the tumor niche depends on tumor-secreted, chemotactic factors that are primarily produced by malignant breast tumors. To test this, we used a panel of breast cancer cells grown in monolayers and more physiologically-relevant tumor spheroids, which were formed over the course of four days using the hanging-drop method. We characterized the size and morphology of the spheroids, which were generated from the poorly metastatic BT474 cells, as well as the highly malignant BT549 cells, MDA-MB-231 cells, and M4 cells of the MCF-10A cell series. We then compared the ability of tumor-conditioned media (TCM) isolated from either monolayers or spheroids to stimulate the migration of primary human neutrophils using transwell assays. We found that, compared to TCM isolated from control or poorly metastatic cell lines, the TCM derived from highly malignant cancer cells robustly stimulated the migration of neutrophils. These data indicate that breast cancer cells secrete factors with unique profiles that have varying potentials to recruit neutrophils. We are in the process of identifying specific tumor-secreted factors in the TCM using mass spectrometry. Additionally, we are assessing how the presence of neutrophils affects cancer cell migration and invasion by utilizing a coculture system in which tumor spheroids and primary neutrophils are imaged in real time. We reason that understanding the role of TANs during breast cancer progression will provide insight into novel therapeutic approaches, particularly in the context of highly metastatic forms of the disease. Citation Format: Lauren Hein, Shuvasree SenGupta, Yang Xu, Carole Parent. Neutrophil migration towards tumor-conditioned media correlates with the malignant potential of breast tumor cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2842.
UK’s record on pandemic deaths
Authors: Veena S Raleigh
Journal: BMJ (2020)

UK's record on pandemic deathsRecent changes in definition can't disguise the UK's poor international ranking Veena S Raleigh senior fellowThe grim daily count of covid-19 deaths in the UK is nearing single digits. 1 Although what's around the corner is unpredictable, it's timely to take stock after the recent tsunami of deaths.Evidence of the UK's higher overall death toll during the first wave of the pandemic relative to comparable countries is unequivocal.England had the highest excess all-cause mortality rate among 23 European countries in the first five months of 2020 compared with 2015-19, followed by Spain and Scotland, with mortality being spread throughout the country in contrast to the more localised patterns in Europe. 2 England also had the second (after Spain) highest peak of excess all-cause mortality and the slowest fall to normal levels-so the longest period of excess deaths.The contrasts with Norway, Finland, Denmark, Austria, and some eastern European countries, where no excess mortality was observed throughout 2020, are even sharper.
Gender Differences in Endowed Chairs in Medicine at Top Schools
Authors: Jessica A. Gold, Danielle Roubinov, Lena S. Jia, Kent A. Griffith, John M. Carethers, Christina Mangurian, Reshma Jagsi
Journal: JAMA Internal Medicine (2020)

Kara J. Denby, MD; Natalie Szpakowski, MD; Julie Silver, MD; Mary Norine Walsh, MD; Steve Nissen, MD; Leslie Cho, MD
Abstract 4474: A quantitative flow cytometry method for the measurement of HLA-DR expression level on monocyte subsets
Authors: Wei Huang
Journal: Cancer Research (2020)

Abstract There is growing evidence that solid tumor cancer is often associated with a systemic immunosuppressive environment which correlates with poor responses to immunotherapy. The frequency of CD14+HLA-DRlo/neg monocytes, also called monocytic myeloid derived suppressor cells (M-MDSCs), is often used as a flow cytometry based biomarker for the measurement of the level of immunosuppression in cancer immunotherapy research. While this approach has been demonstrated to work in clinical investigation studies with well-controlled cytometer settings and analysis methods, it is difficult to produce consistent results and compare measurements from different laboratories due to lack of standardization. The BD Horizon™ Dri Monoset panel is designed to measure the absolute counts and relative frequency of classical, intermediate and nonclassical monocyte subsets for research use. The assay uses whole blood samples analyzed by flow cytometry using a consensus reagent panel and gating strategy published by an international organization. When used in combination with BD Quantibrite™ beads, the level of HLA-DR expression on each subset of monocytes can be quantified in antibody bound per cell (ABC) units independent of the cytometer used to perform the assay. Evaluating 10 normal blood donor samples, our data demonstrates using the BD Horizon™ Dri Monoset panel in combination with BD Quantibrite beads, quantification of HLA-DR expression level on monocyte subsets provides consistent flow cytometry results. Disclaimers: For Research Use Only. Not for use in diagnostic or therapeutic procedures. Class 1 Laser Product. BD, the BD Logo, Horizon, and Quantibrite are trademarks of Becton, Dickinson and Company. © 2019 BD and its subsidiaries. All rights reserved. Citation Format: Wei Huang. A quantitative flow cytometry method for the measurement of HLA-DR expression level on monocyte subsets [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4474.
Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel
Authors: Richard Hansen, Susanna Meade, R Mark Beattie, Marcus Kh Auth, Nick Croft, Philip Davies, David Devadason, Conor Doherty, Jenny Epstein, Lucy Howarth, Fevronia Kiparissi, Rafeeq Muhammed, Vinay Shivamurthy, Christine Spray, Michael P Stanton, Franco Torrente, Arun Urs, David Wilson, Peter M Irving, Mark Samaan, Jochen Kammermeier
Journal: Gut (2020)

Objective Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn’s and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison. Design We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases. Panellists rated the appropriateness of interventions for ASC in the context of the COVID-19 pandemic. Results were discussed at a moderated meeting prior to a second survey. Results Panellists recommended patients with ASC have a SARS-CoV-2 swab and expedited biological screening on admission and should be isolated. A positive swab should trigger discussion with a COVID-19 specialist. Sigmoidoscopy was recommended prior to escalation to second-line therapy or colectomy. Methylprednisolone was considered appropriate first-line management in all, including those with symptomatic COVID-19. Thromboprophylaxis was also recommended in all. In patients requiring second-line therapy, infliximab was considered appropriate irrespective of SARS-CoV-2 status. Delaying colectomy due to SARS-CoV-2 infection was considered inappropriate. Corticosteroid tapering over 8–10 weeks was deemed appropriate for all. After successful corticosteroid rescue, thiopurine maintenance was rated appropriate in patients with negative SARS-CoV-2 swab and asymptomatic patients with positive swab but uncertain in symptomatic COVID-19. Conclusion Our COVID-19-specific adaptations to paediatric ASC guidelines using a RAND panel generally support existing recommendations, particularly the use of corticosteroids and escalation to infliximab, irrespective of SARS-CoV-2 status. Consideration of routine prophylactic anticoagulation was recommended.
Abstract 5294: Clinical utility of a multigene panel for hematologic malignancies
Authors: Sevcan Tug Bozdogan, Cagla Rencuzogullari, Cem Mujde, Atil Bisgin
Journal: Cancer Research (2020)

Abstract Molecular profiling helps to diagnose, classify and guide the treatment of hematologic neoplasms. Thus NGS is the most powerful diagnostics tool to serve clinical management needs. In this study, we analyzed a multi-gene panel for genes associated with diagnostic, prognostic and therapeutic utilities for hematologic neoplasms. A total of 37 samples of myeloid and lenfoid were analyzed in GeneReader NGS system through a targeted multi-gene panel consisting of ASXL1, CALR, CBL, CEBPA, CSF3R, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, RUNX1, SETBP1, SF3B1, SH2B3, SRSF2, TET2, TP53, U2AF1, ZRSR2. QCI-Analyze and QCI-Interpret were used for bioinformatic analyses. Each sample generated 2.176.058 million reads on average, and minimum of 99.5 % mapped reads to the reference reads. Total of 38 reportable variants of 16 genes were detected in 21 patients. The positivity rate was 70.5% (12 of 17) in myeloid group while its 90% (9 of 10 patients) in lymphoid group.In conclusion, our study shows the high sensitivity and specificity of the NGS technology that facilitates the identification of actionable genetic alterations on multiple genes simultaneously to avoid time-consuming multi-step procedures in hematologic malignancies. Citation Format: Sevcan Tug Bozdogan, Cagla Rencuzogullari, Cem Mujde, Atil Bisgin. Clinical utility of a multigene panel for hematologic malignancies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5294.
A low-cost endoscopy trainer for novice endoscopy training in COVID-19
Authors: Chieh Sian Koo, Kewin Tien Ho Siah, How Cheng Low, Calvin Jianyi Koh
Journal: Endoscopy (2020)

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted gastroenterology and endoscopy training. Nonurgent endoscopies have been postponed; trainees have been redeployed; and trainee participation in endoscopies that are still being executed has also been limited [1].
Abstract A22: Patient-derived organoids recapitulate response heterogeneity in head and neck cancer
Authors: Vincent-Chong Vui King, Erin C. Tracy, Heinz Baumann, Pamela A Hershberger, Mukund Seshadri
Journal: Clinical Cancer Research (2020)

Abstract Patient-derived organoids (PDOs) are considered to be a cost-effective, high-throughput preclinical platform for studying cancer biology and evaluating novel therapeutics. While PDOs have been established and characterized for breast, prostate, colon, and pancreatic cancers, PDO models of head and neck squamous cell carcinomas (HNSCC) are limited. To address this paucity, in the present study, we established a panel of PDO models of HNSCC. Five HNSCC samples (3 larynx, 1 tongue, 1 parotid) were procured from donor patients following informed consent and processed to establish organoids. Histologic (H&amp;E) and immunohistochemical evaluation (p16, cytokeratin) was performed along with assessment of PDO response to the alkylating agent, cisplatin, and two tyrosine kinase inhibitors, erlotinib and afatinib. Histologic analyses of established organoids revealed nested cells of squamous cell carcinoma with high N/C ratio similar to donor surgical tumor tissue. Immunohistochemistry revealed strong pan cytokeratin and absence of p16 staining in all samples. Paired PDO and PDX models also successfully retained the squamous histology. Dose-response curves revealed substantial variation in therapeutic profiles of the three agents across the organoid panel. While the IC50 of cisplatin was comparable across the larynx organoids, 2 larynx organoids were sensitive to the two TKIs while one was resistant, exhibiting ~5-fold higher IC50 values. The tongue organoid was relatively sensitive to all agents while the parotid SCC organoid was sensitive to EGFR TKIs but relatively resistant to cisplatin. Collectively, these results demonstrate the ability of organoid models to recapitulate the histologic architecture and response heterogeneity of human HNSCC. Investigation into the molecular profiles of our PDO panel is under way in our laboratory and will enable further development of organoids as a robust platform for evaluation of precision therapeutics against HNSCC. Citation Format: Vincent-Chong Vui King, Erin C. Tracy, Heinz Baumann, Pamela A Hershberger, Mukund Seshadri. Patient-derived organoids recapitulate response heterogeneity in head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A22.
Do-Not-Resuscitate Orders among Patients with ESKD Admitted to the Intensive Care Unit: A Bird’s Eye View
Authors: Jennifer S. Scherer, Ann M. O’Hare
Journal: Journal of the American Society of Nephrology (2020)

The goal of advance care planning (ACP) is to help elucidate, clarify, and communicate patients’ values, goals, and care preferences.[1][1] Engaging patients and their families in an iterative and ongoing process of ACP can help to ensure that they receive care that is congruent with their core
Abstract 3214: BART: An integrative bioinformatics toolkit and web server for functional transcription factor prediction
Authors: Zhenjia Wang, Wenjing Ma, Yifan Zhang, Neal E. Magee, Yang Chen, Chongzhi Zang
Journal: Cancer Research (2020)

Abstract The goal of this bioinformatics tool is to predict functional transcription factors (TFs) from various queries of target genomic features. TFs play a key role in regulating gene expression in a dynamic chromatin structure. From a target gene set or a genomic region set, it is challenging to identify functional TFs that regulate these genes or bind in these regions, because of complexity of enhancer distributions and insufficient specificity of DNA sequence motifs. Here, we present BART (Binding Analysis for Regulation of Transcription), an interactive bioinformatics toolkit and web server to predict functional TFs that regulate a set of co-regulated genes or associate with a genomic profile. From a gene set, BART first uses a machine learning approach to generate a genome-wide cis-regulatory profile by leveraging hundreds of publicly available ChIP-seq profiles for active enhancer histone mark H3K27ac and DNase-seq profiles for genome-wide cis-regulatory elements. Then it identifies a list of TFs whose binding profiles most correlate with the cis-regulatory profile by comparing with tens of thousands of ChIP-seq datasets. BART can also identify TFs associated with differential chromatin interaction from a pair of three-dimensional (3D) genomic datasets, such as Hi-C. BART integrates over 12,000 ChIP-seq datasets for over 900 TFs for human and over 500 TFs for mouse to make accurate predictions. We demonstrate that BART outperforms existing methods in identifying the true TF from target gene sets. BART can be useful for any researcher in studying cancer gene regulation and cancer epigenetics, and demonstrates the power of utilizing public data for computational biology research. BART web server is freely available at: http://bartweb.org. Citation Format: Zhenjia Wang, Wenjing Ma, Yifan Zhang, Neal E. Magee, Yang Chen, Chongzhi Zang. BART: An integrative bioinformatics toolkit and web server for functional transcription factor prediction [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3214.
Abstract 3627: Comparison of genetic profiles of small and large duct type intrahepatic cholangiocarcinoma with distal extrahepatic cholangiocarcinoma
Authors: Hayeon Kim, Soo Yeon Lee, Aeree Kim, Baek-hui Kim, Chung-yeul Kim
Journal: Cancer Research (2020)

Abstract Cholangiocarcinoma comprises epithelial malignancy that occurs in various sites in the biliary tree. Cholangiocarcinoma is categorized into intrahepatic, perihilar, and distal bile duct carcinomas according to its anatomical position. According to the fifth edition of World Health Organization Classification of Tumors, intrahepatic cholangiocarcinoma (ICC) is further classified into small- and large duct types on histopathological basis. We analyzed molecular profiles of different types of cholangiocarcinoma by next-generation sequencing (NGS). We utilized the Oncomine Comprehensive Assay (OCA) panel v2 on the IonTorrent™ NGS platform to explore genetic differences among the two histologic types of ICC and distal extrahepatic cholangiocarcinoma (DEC). Formalin-fixed paraffin-embedded tumor tissues were obtained from 25 patients who underwent surgical resection of cholangiocarcinoma in Korea University Guro Hospital between 2010 and 2018. We analyzed 7 and 8 small- and large duct type ICCs and 10 DECs. NGS assay of the included cases showed distinct genetic alterations between ICC and DEC, which were enriched in different biological pathways. Unsupervised hierarchical clustering analysis showed two distinct groups. The first group consisted of 12 cases (9 DECs and 3 large duct type ICCs). The second group included 13 cases (7 large duct type and 6 small duct type ICCs). Molecular alteration patterns of a subset of large duct type ICCs were more closely related to DECs than small duct type ICCs. All included small duct type ICCs were considered genetically distinct from DECs. Our study suggested an association between anatomical and histopathological classifications of intra- and extrahepatic cholangiocarcinomas. Citation Format: Hayeon Kim, Soo Yeon Lee, Aeree Kim, Baek-hui Kim, Chung-yeul Kim. Comparison of genetic profiles of small and large duct type intrahepatic cholangiocarcinoma with distal extrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3627.
Can nanoparticles and nano‒protein interactions bring a bright future for insulin delivery?
Authors: Ting Zhang, James Zhenggui Tang, Xiaofan Fei, Yanping Li, Yi Song, Zhiyong Qian, Qiang Peng
Journal: Acta Pharmaceutica Sinica B (2020)

Insulin therapy plays an essential role in the treatment of diabetes mellitus. However, frequent injections required to effectively control the glycemic levels lead to substantial inconvenience and low patient compliance. In order to improve insulin delivery, many efforts have been made, such as developing the nanoparticles (NPs)-based release systems and oral insulin. Although some improvements have been achieved, the ultimate results are still unsatisfying and none of insulin-loaded NPs systems have been approved for clinical use so far. Recently, nano‒protein interactions and protein corona formation have drawn much attention due to their negative influence on the in vivo fate of NPs systems. As the other side of a coin, such interactions can also be used for constructing advanced drug delivery systems. Herein, we aim to provide an insight into the advance and flaws of various NPs-based insulin delivery systems. Particularly, an interesting discussion on nano‒protein interactions and its potentials for developing novel insulin delivery systems is initiated.
Abstract 2856: An intelligent boosting to amplify signal with isobaric labeling (iBASIL) strategy for precise quantitative single-cell proteomics analysis
Authors: Chia-Feng Tsai, Rui Zhao, Ronald Moore, Sarah Williams, Kendall Schultz, Paul Piehowski, Ljiljana Pasa-Tolic, Karin Rodland, Richard Smith, Tujin Shi, Ying Zhu, Ying Zhu, Tao Liu
Journal: Cancer Research (2020)

Abstract Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection (e.g., our recent boosting to amplify signal with isobaric labeling (BASIL) approach) has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have systematically evaluated and optimized the BASIL approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of single cells. This improved, intelligent BASIL (iBASIL) approach enables comprehensive and quantitative single-cell proteomics analysis by carefully controlling the boosting-to-sample ratio and optimizing MS automatic gain control and ion injection time settings. Using standard LC-MS platforms, iBASIL enabled precise quantification of 800-1,200 proteins from single FACS-isolated cells (depending on the cell type). Moreover, coupling iBASIL to nanoscale fractionation enabled identification of &amp;gt;3,000 proteins and reliable quantification of &amp;gt;2,000 proteins while readily separating single cells from 3 different acute myeloid leukemia cell lines. We believe iBASIL has broad utility for comprehensive and precise quantitative single-cell proteomics for systems biology and biomedical research, as well as for comprehensive proteomic analysis of size-limited clinical specimens that cannot be readily accessed by regular proteomics platforms. It also has the potential to be adapted for phosphoproteome analysis of as few as 100 cells. Citation Format: Chia-Feng Tsai, Rui Zhao, Ronald Moore, Sarah Williams, Kendall Schultz, Paul Piehowski, Ljiljana Pasa-Tolic, Karin Rodland, Richard Smith, Tujin Shi, Ying Zhu, Ying Zhu, Tao Liu. An intelligent boosting to amplify signal with isobaric labeling (iBASIL) strategy for precise quantitative single-cell proteomics analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2856.