tbuckley/cabot-search huggingface dataset:
Comprehensive characterization of single circulating rare cells through automated picking and high-throughput mRNA profiling in patients with pancreatic cancer.
Authors: Dong Uk Kim, Min Ji Lim, Yoonkyoung Cho
Journal: Journal of Clinical Oncology (2019)

271 Background: Circulating rare cells (CRCs) such as circulating tumor cells (CTCs), tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) play major roles in tumor progression. However, there are limited reports characterizing single CRCs comprehensively because of technical limitations including isolation and analysis of rare cells. We aimed to test the feasibility of the automated picking and mRNA profiling platforms of CRCs for evaluating the phenotypic heterogeneity of CRCs and the relationship between clinical outcomes and CRCs in patients with pancreatic cancer. Methods: CRCs were collected from 3ml of whole blood in 4 patients with pancreatic cancer using filter-based lab-on-a-disc platform. The filter membrane was transferred to ALS CellCelector (ALS, Germany) which is picking single nucleated CD45 negative cells to 96-well plate. The single cells were analyzed with the BioMark HD (Fluidigm, USA) which is digital PCR-based mRNA profiling for 48 markers such as epithelial, mesenchymal, stem-like, macrophage, fibroblast, oncogenic and immunogenic markers. Results: CRCs were detected in 3 of 4 patients (75%). Sixty-six-year-old female who had large pancreatic cancer with liver and lung metastasis presented 13 single rare cells including 7 epithelial CTCs with hematopoietic features (CD45 and CD14 positive), 3 mesenchymal CTCs, 2 stem-like CTCs, and 1 CAF. One epithelial CTC with hematopoietic features and one stem-like CTC were detected in 51-year-old male and 61-year-old female with metastatic pancreatic cancer, respectively. There was no CTC in 80-year-old male with localized pancreatic cancer. Conclusions: The automated picking and mRNA profiling platforms showed the feasibility of showing tumor heterogeneity and predicting clinical outcomes in patients with pancreatic cancer.
Correction: Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients with Melanoma Treated with Pembrolizumab
Authors: Richard W. Joseph, Jeroen Elassaiss-Schaap, Richard Kefford, Wen-Jen Hwu, Jedd D. Wolchok, Anthony M. Joshua, Antoni Ribas, F. Stephen Hodi, Omid Hamid, Caroline Robert, Adil Daud, Roxana Dronca, Peter Hersey, Jeffrey S. Weber, Amita Patnaik, Dinesh P. de Alwis, Andrea Perrone, Jin Zhang, S. Peter Kang, Scot Ebbinghaus, Keaven M. Anderson, Tara C. Gangadhar
Journal: Clinical Cancer Research (2018)
Contribution of airway eosinophils in airway wall remodeling in asthma: Role of <i><scp>MMP</scp>‐10</i> and <i><scp>MET</scp></i>
Authors: Chih‐Hsi S. Kuo, Stelios Pavlidis, Jie Zhu, Matthew Loza, Fred Baribaud, Anthony Rowe, Ioannis Pandis, David Gibeon, Uruj Hoda, Ana Sousa, Susan J. Wilson, Peter Howarth, Dominick Shaw, Stephen Fowler, Barbro Dahlen, Pascal Chanez, Norbert Krug, Thomas Sandstrom, Louise Fleming, Julie Corfield, Charles Auffray, Ratko Djukanovic, Peter J. Sterk, Yike Guo, Ian M. Adcock, Kian Fan Chung
Journal: Allergy (2019)

Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma.We analyzed the transcriptomic data from bronchial biopsies of 81 patients with moderate-to-severe asthma of the U-BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA. Transcription binding site analysis used the PRIMA algorithm. Localization of proteins was by immunohistochemistry.Using stringent false discovery rate analysis, MMP-10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils (HE) compared to low mucosal eosinophil (LE) numbers. Immunohistochemical analysis confirmed increased expression of MMP-10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less-stringent conditions (raw P-value < 0.05, log2 fold change > 0.5), we defined a 73-gene set characteristic of the HE compared to the LE group. Thirty-three of 73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CC-chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors, and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organization correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS-1 and SOX family proteins, that showed positive correlation with MMP10 and MET expression.Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP-10 likely play an important role in these processes.
Tailored multicomponent program for discomfort reduction in critically ill patients may decrease post-traumatic stress disorder in general ICU survivors at 1 year
Authors: Pierre Kalfon, Marine Alessandrini, Mohamed Boucekine, Stéphanie Renoult, Marie-Agnès Geantot, Stéphanie Deparis-Dusautois, Audrey Berric, Olivier Collange, Bernard Floccard, Olivier Mimoz, Amour Julien, René Robert, Juliette Audibert, Anne Renault, Arnaud Follin, Didier Thevenin, Nathalie Revel, Marion Venot, René-Gilles Patrigeon, Thomas Signouret, Mélanie Fromentin, Tarek Sharshar, Coralie Vigne, Julien Pottecher, Quentin Levrat, Achille Sossou, Maïté Garrouste-Orgeas, Jean-Pierre Quenot, Claire Boulle, Elie Azoulay, Karine Baumstarck, Pascal Auquier
Journal: Intensive Care Medicine (2019)
Abstract 12514: The Difference in Risk of Future Cardiovascular Events for Patients Presenting With Acute Coronary Syndrome Diminishes After 6 Months Compared to Non-Acute Coronary Syndrome Patients: The Intermountain Heart Collaborative Study
Authors: Tami L Bair, Heidi T May, Viet Le, Benjamin D Horne, Jeffrey L Anderson, Donald L Lappé, Joseph B Muhlestein
Journal: Circulation (2014)

Background: Pts presenting with acute coronary syndrome (ACS) are at an increased risk of future events. However, at what point in time, if at all, this difference in risk becomes that of non-ACS p...
Purine Release, Metabolism, and Signaling in the Inflammatory Response
Authors: Joel Linden, Friedrich Koch-Nolte, Gerhard Dahl
Journal: Annual Review of Immunology (2019)

ATP, NAD + , and nucleic acids are abundant purines that, in addition to having critical intracellular functions, have evolved extracellular roles as danger signals released in response to cell lysis, apoptosis, degranulation, or membrane pore formation. In general ATP and NAD + have excitatory and adenosine has anti-inflammatory effects on immune cells. This review focuses on recent advances in our understanding of purine release mechanisms, ectoenzymes that metabolize purines (CD38, CD39, CD73, ENPP1, and ENPP2/autotaxin), and signaling by key P2 purinergic receptors (P2X7, P2Y2, and P2Y12). In addition to metabolizing ATP or NAD + , some purinergic ectoenzymes metabolize other inflammatory modulators, notably lysophosphatidic acid and cyclic GMP-AMP (cGAMP). Also discussed are extracellular signaling effects of NAD + mediated by ADP-ribosylation, and epigenetic effects of intracellular adenosine mediated by modification of S-adenosylmethionine-dependent DNA methylation.
Final Results from a Non-Interventional Safety and Efficacy Study of a VWF/FVIII Concentrate (wilate®) in Patients with Von Willebrand Disease
Authors: Hassan M. Yaish, Maria Sol Cruz, Kay Decker, Eva M.K. Zetterberg, Sylvia Werner, Mariko Hashimoto, Sigurd Knaub, George M. Rodgers
Journal: Blood (2018)
BRAF and BIRC3 Mutations Stratify a Poor Prognostic Subgroup in FCR Treated Chronic Lymphocytic Leukemia
Authors: Fary Diop, Riccardo Moia, Chiara Favini, Elisa Spaccarotella, Lorenzo De Paoli, Alessio Bruscaggin, Valeria Spina, Michaela Cerri, Clara Deambrogi, Ahad Ahmed Kodipad, Simone Favini, Sruthi Sagiraju, Clive Jabangwe, Francesca Romana Mauro, Ilaria Del Giudice, Francesco Forconi, Agostino Cortelezzi, Francesco Zaja, Carlo Visco, Annalisa Chiarenza, Gian Matteo Rigolin, Roberto Marasca, Marta Coscia, Omar Perbellini, Alessandra Tedeschi, Luca Laurenti, Marina Motta, Giovanni Del Poeta, Antonio Cuneo, Valter Gattei, Robin Foa, Gianluca Gaidano, Davide Rossi
Journal: Blood (2017)
Abstract 16963: Cross-sectional Analysis of Lipoprotein(a) Cholesterol Concentration versus Particle Number
Authors: Vasanth Sathiyakumar, Jihwan Park, Seth S Martin, Steven R Jones
Journal: Circulation (2017)

Introduction: Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular disease. The International Federation of Clinical Chemistry recommends Lp(a)-particle number (Lp(a)-P) as the clinical standard for assessing Lp(a). However, an alternative measure is Lp(a)-C, the cholesterol content contained in core Lp(a) particles. Aim: We assessed the extent of patient-level discordance of Lp(a)-C and Lp(a)-P, as discordance suggests the possibility of additional information. Methods: A total of 177,887 patients with Lp(a)-C and Lp(a)-P values from the VLDL study were identified. Lp(a)-C was obtained by rapid ultracentrifugation (Vertical Auto Profile) while Lp(a)-P was measured via the Denka-Seiken assay. We log-transformed Lp(a)-C and Lp(a)-P and determined the Pearson correlation coefficient. The 80th percentile values for both variables were assessed and compared to literature-suggested cutpoints of 10 mg/dL for Lp(a)-C and 125 nmol/L for Lp(a)-P for elevated cardiovascular risk. Using these latter cutpoint...
Efficacy of Adjuvant Low Dose Rituximab and Plasma Exchange for Acquired TTP with Severe ADAMTS13 Deficiency — Results of the ART Study
Authors: J. Evan Sadler, Joshua Muia, Leili Dolatshahi, Lisa A. Westfield, Patricia Nieters, Anita Rodrigues, Ana G. Antun, Ara Metjian, Jeffrey I. Zwicker
Journal: Blood (2018)
Racial/ethnic disparities in the use of high-volume centers for hepatobiliary and pancreatic cancer surgery.
Authors: Susanna W de Geus, Teviah E. Sachs, Sing Chau W Ng, David B. McAneny, Jennifer F. Tseng
Journal: Journal of Clinical Oncology (2019)

457 Background: The impact of hospital volume on the outcomes of cancer surgery has been well established. The present studies investigates how race/ethnicity influences the utilization of high-volume centers for hepatobiliary and pancreatic surgery. Methods: Patients that underwent surgery for hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), ampullary adenocarcinoma (AC), or pancreatic ductal adenocarcinoma (PDAC) between 2006 and 2015 were identified from the National Cancer Data Base. Hospitals were divided into low- and high-volume centers based on the medium number of cancer surgeries per year. Multivariable logistic regression analyses predicting receipt of care at a low-volume center based on age, sex, race/ethnicity, comorbidities, insurance, income, travel distance, geographic location, urban/metro location, and tumor stage were performed. All analyses were performed separately by tumor type. Results: 8,962 patients with HCC, 2,119 with ICC, 3,973 with ECC, 5,125 with AC, and 25,231 with PDAC were identified. Non-Hispanic black patients were more likely to undergo resection for AC (vs. non-Hispanic white: AOR, 1.326; p = 0.0125) or PDAC (vs. non-Hispanic white: AOR, 1.187; p = 0.0002) at a low volume centers. Hispanic patients more often underwent surgery for ECC (vs. non-Hispanic white: AOR, 1.731; p &lt; 0.0001) or PDAC (vs. non-Hispanic white: 2.030; p &lt; 0.0001) cancer at a low-volume center. Patients of Asian descent were significantly less often treated for HCC at a low volume center (vs. non-Hispanic white: AOR, 0.644; p &lt; 0.0001) compared to non-Hispanic whites. Non-Hispanic black, Hispanic, or Asian race/ethnicity did not impact the likelihood of receiving care at a low volume center for any other tumor types. Conclusions: The results of this study suggest that race/ethnicity influences the likelihood of receiving care at a high-volume cancer center, even after controlling for other barriers to access to care, including insurance status, income and travel distance.
Abstract 16: Effect of Long-Term Selenium Supplementation on Mortality: Results From a Multiple-Dose Randomised Controlled Trial
Authors: Margaret Rayman, Kristian H Winther, Roberto Pastor-Barriuso, Frederick Cold, Marianne Thvilum, Saverio Stranges, Eliseo Guallar, Soren Cold
Journal: Circulation (2017)

Background: Selenium (Se) is an essential trace element that is incorporated into selenoproteins with a wide range of health effects. The concentration of selenoproteins plateaus at plasma Se concentrations ~125 μg/L, however, and it is unclear whether Se supplementation is beneficial above this plateau. Methods: In a double-blind, randomized, controlled trial of Se supplementation and mortality in Denmark, a population of moderately-low Se status, 491 men and women, 60-74 years of age, were treated with 100, 200, or 300 μg Se/d as Se-enriched yeast or placebo-yeast. From 2008-2009, active treatment was provided for 5 years and post-treatment follow-up for 10 additional years. During 6,871 person-years of follow-up, there were 158 deaths (31 during active treatment and 127 after treatment cessation). Results: The hazard ratio (95% confidence interval [CI]) for all-cause mortality comparing 300 μg Se/d to placebo was 1.62 (0.66 to 3.96) after 5 years of treatment and 1.59 (1.02 to 2.46) over the entire follow-up. Se doses of 100 and 200 μg/d non-significantly decreased mortality during the intervention period but their effects vanished after treatment cessation. The effects on cancer and cardiovascular mortality were similar but less precise than on all-cause mortality. Conclusions: A dose of 300 μg/d of Se (as high-Se yeast) taken for five years in a country with moderately-low Se status increased all-cause mortality 10 years later. Lower doses showed a non-significant reduction in mortality which dissipated after treatment discontinuation. Total Se intake (diet plus supplements) over 300 μg/d should be avoided.
Sensitization To Messor barbarus Ant In A Sample Of Patients With Hymenoptera Venom Hypersensitivity
Authors: Remedios Pérez Calderón, Nicola Giangrande, María Ángeles Gonzalo Garijo, Silvia Sánchez Vega, Mariana Marcos Fernández, Borja Bartolomé
Journal: Journal of Allergy and Clinical Immunology (2019)
Hepatic arterial infusion chemotherapy after sorafenib treatment in patients with advanced hepatocellular carcinoma who are unfit for regorafenib.
Authors: Takeshi Terashima, Tatsuya Yamashita, Noboru Takata, Kuniaki Arai, Eishiro Mizukoshi, Shuichi Kaneko
Journal: Journal of Clinical Oncology (2019)

355 Background: The RESORCE trial proved survival benefit of regorafenib on advanced hepatocellular carcinoma (aHCC) in the limiting cohort. This study aimed to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) as second-line treatment in patients with aHCC who are unfit for regorafenib. Methods: We studied consecutive 159 patients with aHCC treated with sorafenib in our institution from June 2009 to March 2018. We divided them into two groups according to the eligibility for RESORCE trial (Rego or non-Rego group) and investigated the efficacy of HAIC as post-sorafenib treatment. Moreover, we also analyzed the prognostic factors in each group. Results: When sorafenib treatment failed, 63 patients (39.6%) fulfilled key inclusion criteria of the RESORCE trial and were considered as fit for regorafenib treatment (Rego group). Among 96 remaining patients (non-Rego group), 34 patients (35.4%) were treated with HAIC after sorafenib. The objective response and the median progression-free survival of HAIC were 38.2% and 3.9 months, which were independent of the efficacy or treatment duration of sorafenib. The median survival of HAIC after sorafenib was 11.3 months which was significantly longer than that of 62 patients without HAIC (4.7 months; P = 0.023). Four factors, HAIC (HR 0.516), Child-Pugh A (HR 0.362), tumor size ≥35mm (HR 1.959), and AFP ≥200 (HR 1.728), were identified as independent prognostic factors after sorafenib in multivariate analysis. In Rego group, 14 patients were actually treated with regorafenib and their survival after sorafenib was longer than that of the patients without regorafenib and with HAIC (P &lt; 0.01 and P &lt; 0.01, respectively). In Rego group, regorafenib (HR 0.152), extrahepatic lesions (HR 2.160), and ≥10 intra-hepatic lesions (HR 2.099) were identified as prognostic factors after sorafenib in multivariate analysis. Conclusions: HAIC showed promising tumor response and patients’ outcome for the patients who are unfit for regorafenib. Further investigation is needed to compare HAIC with ramucirumab, cabozantinib or nivolumab.
Is ex vivo liver resection and autotransplantation a valid alternative treatment for end-stage hepatic alveolar echinococcosis in Europe?
Authors: Guido Beldi, Dominique Vuitton, Anja Lachenmayer, Bruno Heyd, Jean-François Dufour, Carine Richou, Daniel Candinas, Solange Bresson-Hadni
Journal: Journal of Hepatology (2019)
Near infrared imaging of epidermal growth factor receptor positive xenografts in mice with domain I/II specific antibody fragments
Authors: Wendy Bernhard, Ayman El-Sayed, Kris Barreto, Carolina Gonzalez, Humphrey Fonge, Clarence Ronald Geyer
Journal: Theranostics (2019)

Epidermal growth factor receptor (EGFR) is a transmembrane cell surface receptor that is frequently overexpressed and/or mutated in many cancers.Therapies targeting EGFR have poor outcomes due to the lack of reliable diagnostic tests to monitor EGFR.Current in vitro EGFR diagnostic methods are invasive, requiring biopsies, which limits tumor sampling and availability.EGFR molecular imaging provides non-invasive whole-body images capable of detecting primary tumors and metastases, which can be used to diagnose and monitor response to therapy.Methods: We evaluated properties of two anti-EGFR fragments, 8708 and 8709, as molecular-targeted imaging probes.8708 and 8709 are anti-EGFR antigen binding fragments (Fabs) that recognize domain I/II of EGFR, which is distinct from epitopes recognized by current anti-EGFR therapeutic antibodies.We used complementarity determining region sequences from 8708 and 8709 Fabs to generate an anti-EGFR IgG and (scFv)2 and scFv-Fc antibody fragments.We expressed, purified, and labeled the IgG and fragments with IRDye800CW and used them to image EGFR-positive and -negative xenografts in CD-1 nude mice.8709 scFv-Fc was also tested for competitive binding with the therapeutic anti-EGFR antibody nimotuzumab and for quantifying ratios of EGFR and EGFRvIII deletion mutant.Results: IRDye800CW-labeled 8708 (scFv)2 and 8709 scFv-Fc imaging probes showed high levels of accumulation and good retention in EGFR-positive xenografts, with peak accumulation occurring at 24 and 48 hours post injection, respectively.IRDye680RD-labeled 8709 scFv-Fc did not compete with IRDye800CW-labeled nimotuzumab for EGFR binding as assayed by flow cytometry using an EGFR-positive cell line.IRDye680RD-labeled 8709 scFv-Fc and IRDye800CW-labeled nimotuzumab used in combination were able to determine the ratio of cells expressing EGFR and a deletion mutant EGFRvIII.Conclusion: IRDye800CW-labeled 8708 (scFv)2 and 8709 scFv-Fc had desirable binding affinities, clearance times, and tumor accumulation to be used for imaging in combination with current EGFR targeted therapies.This study highlights the potential for using 8708 (scFv)2 and 8709 scFv-Fc as EGFR diagnostic and therapy monitoring tools.
Abstract 19644: Polypharmacy at Admission in Patients With Acute Heart Failure Has a Strong Prognostic Value
Authors: Takuya Mizukami, Mio Ebato, Miki Tsujiuchi, Sakura Nagumo, Hideyuki Maezawa, Hiroshi Suzuki
Journal: Circulation (2017)

Introduction: Acute decompensated heart failure (ADHF) treatment requires multi-drugs regimens in guidelines. Furthermore ADHF patients are known to have many comorbidities, and their number of med...
Universal Medicine Access through Lump-Sum Remuneration — Australia’s Approach to Hepatitis C
Authors: Suerie Moon, Elise Erickson
Journal: New England Journal of Medicine (2019)

Australia's agreement to spend about 1 billion Australian dollars (U.S.$766 million) over 5 years in exchange for an unlimited volume of hepatitis C drugs suggests that, under certain conditions, innovative approaches to payment can remove price as a barrier to access.
Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis
Journal: Allergy (1994)

This multicenter, double‐blind, double‐dummy, parallel‐group trial was initiated to compare the efficacy and tolerability of two antihistamines, topical levocabastine (eye‐drops and nasal spray) and oral loratadine, for the treatment of seasonal allergic rhinoconjunctivitis in the primary care setting. A total of 95 adult patients participated in the study with a treatment duration of 5 weeks. Forty‐seven patients were randomized to receive twice daily levocabastine eye‐drops and nasal spray plus an oral placebo, and 48 to receive once daily oral loratadine with placebo eye‐drops and nasal spray. Naphazoline eye‐drops and xylometazoline nasal spray were permitted as rescue medication. No statistically significant intergroup differences in therapeutic efficacy were observed. Symptom severity was comparable in the two treatment groups throughout the trial period. At the end of the study, 86% of levocabastine‐treated patients considered global therapeutic efficacy to be excellent or good, as compared with 77% of those who received loratadine. This difference was not statistically significant. There were no significant differences in the use of rescue medication or in the incidence or severity of adverse events in the two treatment groups. In conclusion, levocabastine eye‐drops and nasal spray appear to be as effective and well tolerated as oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis.