tbuckley/cabot-search huggingface dataset:
Effect of leukapheresis on efficient CTC enrichment for comprehensive molecular characterization and clinical diagnostics.
Authors: Nikolas H. Stoecklein, Dieter Niederacher, Stefan A. Topp, Luisa Zacarias Föhrding, Christian Vay, Wolfram Trudo Knoefel, Nikola S. Kasprowicz, Philip Gm Hepp, Svjetlana Mohrmann, Wolfgang Janni, Antje Stratmann, Thomas Krahn, Ellen Honisch, Katharina Raba, Johannes C. Fischer
Journal: Journal of Clinical Oncology (2012)

e21020 Background: Circulating tumor cells (CTCs) are promising biomarkers for diagnosis and systemic therapy. However, their infrequent detection rates limit currently their clinical use. Here we tested whether leukapheresis could be a suitable method to increase CTC yields and detection rates by increasing dramatically the analyzed blood volume. Methods: We screened 3x10 6 PBMNCs of 48 historical leukapheresis products harvested from 24 breast cancer patients in the setting of high-dose chemotherapy and from a non-cancer control group (n=10), respectively, with a standard immuno-assay using an anti-cytokeratin antibody (A45/BB3) to detect CTCs. Detected CTCs were isolated, their genomic DNA amplified, and the whole genome screened for chromosomal aberrations using comparative genomic hybridization (CGH) (n=48). To validate the CTC detection frequencies in leukapheresis products, we initiated a prospective pilot-study and performed leukapheresis in 13 cancer patients (breast and pancreatic cancer). 1 mL of the leukapheresis product (total volume: up to 150 ml) was analyzed using the CellSearch® system as well as 7.5 ml peripheral blood taken from the same patients. Results: 44/48 (91.7%) of leukapheresis samples contained CTCs with a median count of 3.0 in 3x10 6 PBMNC (range: 1-35 CTCs). None of the 10 analyzed healthy controls displayed CTCs. We successfully performed single cell CGH of 48 CTCs from 19 patients revealing aberrant CGH profiles in 56% with gains and losses typical for breast cancer. Interestingly, CTCs with high aberration numbers were associated with early metastatic relapse. The validation study using CellSearch® in 13 cancer patients demonstrated in leukapheresis products significantly higher CTC detection frequencies (13/13 vs. 5/13) and CTC numbers (median: 13, range: 1-51 vs. median 0, range: 0-7; p&lt;0.001) compared to the matched peripheral blood samples. Conclusions: Our results indicated that leukapheresis provides CTC detection rates and yields at unprecedented scale. Thus we believe, that leukapheresis will help to exploit the full clinical potential of CTCs as biomarkers for diagnosis and systemic therapy.
ACCF/AHA New Insights Into the Methodology of Performance Measurement
Authors: John A. Spertus, Robert O. Bonow, Paul Chan, George A. Diamond, Joseph P. Drozda, Sanjay Kaul, Harlan M. Krumholz, Frederick A. Masoudi, Sharon-Lise T. Normand, Eric D. Peterson, Martha J. Radford, John S. Rumsfeld
Journal: Journal of the American College of Cardiology (2010)
Reply to Fabrizio Dal Moro's Letter to the Editor re: Vladimir Student Jr., Ales Vidlar, Michal Grepl, Igor Hartmann, Eva Buresova, Vladimir Student. Advanced Reconstruction of Vesicourethral Support (ARVUS) during Robot-assisted Radical Prostatectomy: One-year Functional Outcomes in a Two-group Randomised Controlled Trial. Eur Urol 2017;71:822–30: CoRPUS and ARVUS
Authors: Vladimir Student, Vladimir Student
Journal: European Urology (2017)
British Thoracic Society Oxygen Guidelines: another clinical brick in the wall
Authors: B Ronan O'Driscoll
Journal: Thorax (2017)

The world's first evidence-based guideline for emergency oxygen therapy was published by the British Thoracic Society (BTS) in 2008 and endorsed by 21 other societies and colleges.1 The key message in the guideline was very simple: clinicians were advised to avoid hypoxaemia and hyperoxaemia by prescribing a normal or near-normal target oxygen saturation of 94%–98% for most acutely unwell patients and to prescribe a lower range (usually 88%–92%) for patients at risk of hypercapnia, and to use high-concentration oxygen for some conditions such as carbon monoxide poisoning or the immediate management of critical illness. This guidance has informed worldwide clinical practice and research since 2008 and is cited by more than 500 publications. The guideline is now updated and extended with the support of 22 colleges and societies.2

Readers will want to know what is new in the 2017 update of the BTS emergency oxygen guideline, published as a supplement to this edition of Thorax .2 A concise version of the guideline is available in BMJ Open Respiratory Research.3 The evidence review methodology and grading of recommendations follows the National Institute for Health and Care Excellence accredited BTS guideline production process which is based on Scottish Intercollegiate Guidelines Network (SIGN) methodology and adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument.4 The evidence base for the guideline has been updated to August 2013 with bespoke literature searches (and extended to late 2016 for key references). The remit of the guideline is wider now than in 2008. The new guideline covers emergency …
Erratum to: Rapid transcriptional plasticity of duplicated gene clusters enables a clonally reproducing aphid to colonise diverse plant species
Authors: Thomas C. Mathers, Yazhou Chen, Gemy Kaithakottil, Fabrice Legeai, Sam T. Mugford, Patrice Baa-Puyoulet, Anthony Bretaudeau, Bernardo Clavijo, Stefano Colella, Olivier Collin, Tamas Dalmay, Thomas Derrien, Honglin Feng, Toni Gabaldón, Anna Jordan, Irene Julca, Graeme J. Kettles, Krissana Kowitwanich, Dominique Lavenier, Paolo Lenzi, Sara Lopez-Gomollon, Damian Loska, Daniel Mapleson, Florian Maumus, Simon Moxon, Daniel R. G. Price, Akiko Sugio, Manuella van Munster, Marilyne Uzest, Darren Waite, Georg Jander, Denis Tagu, Alex C. C. Wilson, Cock van Oosterhout, David Swarbreck, Saskia A. Hogenhout
Journal: Genome biology (2017)
Mortality in elderly patients with subclinical hyperthyroidism [4] (multiple letters)
Authors: J. J. Díez, P. Iglesias, A. D. Toft, G. J. Beckett, P. B S Fowler, Ville Pettilä, Kornél Simon, James V. Parle, Patrick Maisonneuve, Michael C. Sheppard, Peter Boyle, Jayne A. Franklyn, Th B. Twickler, M. J M Cramer, H. P F Koppeschaar, W. R. De Vries, D. W. Erkelens, B. Biondi, E. A. Palmieri, S. Filetti, G. Lombardi, S. Fazio
Journal: The Lancet (2002)
Abstract 312: Molecular Characterization and Prospective Isolation of Human Secondary Heart Field Progenitors From Pluripotent Stem Cells
Authors: zaniar ghazizadeh, Faranak Fattahi, Mehdi Sharifi, Sara Tale Ahmad, Parisa Shabani, Shahab Mirshahvaladi, Hossein Baharvand, Nasser Aghdami, Ghasem H Salekdeh
Journal: Circulation Research (2015)

The secondary heart field (SHF) progenitors ultimately contributes to diverse cardiovascular cell types through the formation of an early, multipotent heart progenitor pool and are marked by expression of ISL1, a LIM-homeodomain transcription factor. Human SHF can be derived from human pluripotent stem cells but their characterization has been limited due to the inefficiency of the differentiation protocols and lack of a proper reporter or surface marker based purification system. Using genetic tools and antibiotic selection we were able to purify ISL1+ cells for global gene expression analysis to identify key pathways that SHF identity. Genetic and small molecule based manipulation of these pathways alter ISL1 induction in differentiating cultures. Further proteomic analysis of enriched ISL1+ cells identified a hit surface marker that enables prospective isolation of ISL1+ secondary heart field progenitor cells with more than 90% purity. Purified SHF cells were multipotent and differentiate into pacemaker cells, endothelial and smooth muscle cells as well as mature beating cardiomyocytes. Finally transplantation of hPSC-derived purified SHF progenitors using this surface marker, restored myocardial function and regenerated infarcted area in mice myocardial infarction model.
Rationale and Design of a Phase III Safety Trial of Idarucizumab in Children Receiving Dabigatran Etexilate for the Treatment and Secondary Prevention of Venous Thromboembolism
Authors: Manuela Albisetti, Arno Schlosser, Martina Brueckmann, Savion Gropper, Stephan Glund, Igor Tartakovsky, Leonardo R. Brandão, Paul A Reilly
Journal: Blood (2016)
Oleandrin-mediated inhibition of human tumor cell proliferation: Importance of Na, K- ATPase α subunits as drug targets
Authors: Peiying Yang, David Menter, Carrie Cartwright, Diana Chan, Susan Dixon, Milind Suraokar, Gabriela Mendoza, Norma Llansa, Andrew Dannenberg, Robert Newman
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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Oleandrin is a cardiac glycoside that affects the Na, K-ATPase pump and calcium influx in heart muscle. Although known for treatment of congestive heart failure and cardiac arrythmias, the potential use of cardiac glycosides for control of malignant disease is less well appreciated. We investigated the selective inhibition by oleandrin on growth of human and mouse pancreatic cancer cells. Oleandrin potently inhibited proliferation of human pancreatic cancer cells (e.g. IC50 of 10 nM), but demonstrated a much weaker potency against mouse pancreatic cancer Panc-02 cells (IC50 values often exceeded 500 nM oleandrin). Among the four human pancreatic cancer cell lines tested, the relative sensitivity to oleandrin based on the IC50 values was Panc-1 > MiaPaca > BxPC3 and much > Panc-02. The selective inhibition of cancer cell growth corresponded to the level of Na, K-ATPase α3 isoform protein expression. Human pancreatic cancer cell lines were found to differentially express varying levels of Na, K-ATPase α3 isoform protein, but rodent pancreatic cancer cells lacked discernable expression of this Na, K-ATPase isoform evidenced by the relative ratio of α3 to α1 to be Panc-1 (39.5) > MiaPaca (32.1) >> BxPc3 (0.07) >>> Panc-02 (0). A correlation was observed between a high ratio of α3 to α1 isoforms and the level of oleandrin uptake during inhibition of cell growth with resulting initiation of cell death. Inhibition of proliferation of α3 expressing Panc-1 cells by oleandrin was significantly reduced when expression was knocked down by α3 siRNA. These data suggest that the relative α3 isoform expression is an important determinant of cell sensitivity to cardiac glycoside-induced cell death in human tumor cells. Furthermore, while the expression of α1 isoform was very similar in both human normal and malignant colon tumor biopsy samples, 9 out of 14 tumors expressed α3 isoform protein and only 3 normal tissues contained levels of α3 isoform that could be barely detectable, suggesting that when the normal colon epithelial cells develop become malignant, the subunit phenotype shifts and the tumor becomes a better target for oleandrin treatment. In conclusion, our data suggest that the lack of α3 in rodent tumor cells may explain unresponsiveness to cardiac glycosides; the α3/α1 ratio may help predict which human tumors are likely be responsive to treatment with potent cardiac glycosides such as oleandrin.
Effects of long wave ultraviolet radiation on photosensitizing and related compounds. II
Authors: MILHIM D. ALANI, JAMES H. DUNNE
Journal: British Journal of Dermatology (2006)

The effects of long wave ultraviolet radiation (320–400 nm) on the binding of twenty‐five fluorescent photosensitizing and related compounds to the major saline soluble guinea‐pig epidermal proteins were studied. Binding before or after irradiation was detected on polyacrylamide disc gel electrophoresis by correlating the fluorescent migration pattern with the amido black counterstained pattern. Effects were seen only on photo‐allergic and structurally related compounds (phenothiazines and halogenated salicylanilides). The binding of five phenothiazine derivatives was detected only after irradiation. Ten of twelve halogenated salicylanilides were bound without irradiation, and eleven were bound following it. Ultraviolet exposure appeared to increase the amount of each halogenated salicylanilide that was bound and/or to alter the existing complex.
Prevalence of Elevated Cardiovascular Risks in Young Adults: A Cross-sectional Analysis of National Health and Nutrition Examination Surveys
Authors: Krishna K. Patel, Glen B. Taksler, Bo Hu, Michael B. Rothberg
Journal: Annals of Internal Medicine (2017)

The 2013 cholesterol management guidelines from the American College of Cardiology and American Heart Association (ACC/AHA) recommend lipid screening in all adults older than 20 years to identify those at increased risk for atherosclerotic cardiovascular disease (ASCVD). Statins may be considered for patients with elevated 10-year risk (>5%) or a low-density lipoprotein cholesterol (LDL-C) level of 4.92 mmol/L (190 mg/dL) or greater.To describe the prevalence of elevated ASCVD risk among nondiabetic adults younger than 50 years.Cross-sectional.NHANES (National Health and Nutrition Examination Survey), 1999 to 2000 through 2011 to 2012.Adults aged 30 to 49 years without known ASCVD or diabetes.10-year ASCVD risk was estimated by using the 2013 ACC/AHA ASCVD risk calculator. Participants were subdivided by age, sex, and history of smoking and hypertension. The percentages of adults in each subgroup with a 10-year ASCVD risk greater than 5% and of those with an LDL-C level of 4.92 mmol/L (190 mg/dL) or greater were estimated. Low-prevalence subgroups were defined as those in which a greater than 1% prevalence of elevated cardiovascular risk could be ruled out (that is, the upper 95% confidence bound for prevalence was ≤1%).Overall, 9608 NHANES participants representing 67.9 million adults were included, with approximately half (47.12%, representing 32 million adults) in low-prevalence subgroups. In the absence of smoking or hypertension, 0.09% (95% CI, 0.02% to 0.35%) of adult men younger than 40 years and 0.04% (CI, 0.0% to 0.26%) of adult women younger than 50 years had an elevated risk. Among other subgroups, 0% to 75.9% of participants had an increased risk. Overall, 2.9% (CI, 2.3% to 3.5%) had an LDL-C level of 4.92 mmol/L (190 mg/dL) or greater.No information was available regarding cardiovascular outcomes.In the absence of risk factors, the prevalence of increased ASCVD risk is low among women younger than 50 and men younger than 40 years.None.
High concordance of BAP1 and PBRM1 expression in patient-matched primary and metastatic ccRCC tumors.
Authors: Amanda Shreders, Richard Wayne Joseph, Daniel Serie, Payal Kapur, Thai Huu Ho, Jeanette Eckel-Passow, James Brugarolas, Alexander S. Parker
Journal: Journal of Clinical Oncology (2015)

507 Background: Clear cell renal cell carcinoma (ccRCC) is a well-described molecularly heterogeneous tumor. Herein, we assessed the concordance of two of the most commonly mutated genes in ccRCC, PBRM1 (~50%), and BAP1 (~15%), in patient-matched primary and metastatic tumors. Methods: One pathologist (PK) assessed PBRM1 and BAP1 protein expression using immunohistochemistry (IHC) in 99 patients with a primary and at least one metastatic ccRCC tumor available for analysis. All available metastatic tumors were analyzed. Results: A total of 99 patients (48 M0 and 51 M1) had both a primary tumor and at least one metastatic tumor available for analysis. There were a total of 158 metastases with one patient having up to 7 metastases available for analysis. The concordance between primary and patient-matched metastasis was 87% for PBRM1 and 99% for BAP1. We observed a similar concordance between patients with M0 versus M1 disease. Conclusions: While ccRCC is molecularly heterogeneous, PRBM1, and BAP1 are largely concordant between primary and metastatic lesions suggesting that PBRM1 and BAP1 are genetically truncal events in the molecular pathogenesis of ccRCC.
Breast cancer risk factors among women in same-sex relationships
Authors: Julia E. Heck, Sherri Sheinfeld Gorin
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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Background: It has been hypothesized that women who have sex with women (WSW) may be at higher risk for breast cancer based on a spectrum of risk factors, but few population-based data exist to describe risks among these women. The purpose of this study is to describe breast cancer-related health behaviors among women in same-sex relationships. Methods: In the pooled 1997-2002 National Health Interview Surveys, we identified persons living in a same-sex relationship (SSR) and individuals living in an opposite-sex relationship (OSR). We used weighted chi-square tests to compare SSR and OSR subjects with respect to body mass index, alcohol intake, parity, age at first birth, and oral contraceptive use (OCs); we then used weighted logistic regression modeling to compare risk factors while controlling for age, race, region, educational attainment, income, and urbanicity of residence. Results: The study sample included 261 SSR and 24,998 OSR women. SSR women were much less likely to have ever given birth (32.5% vs. 83.3%, p 30) compared to OSR (31.5% and 24.5%, p=0.03). SSR women were more likely to be current (69.8%) or former (17.8%) alcohol drinkers than were OSR women (62.1% and 13.9%, p=0.0008). After controlling for explanatory factors, SSR women were much less likely to have ever given birth (OR=0.10, 95%CI: 0.05-0.19) or ever used OCs (OR=0.23, 0.11-0.47). SSR women were more likely to be overweight or obese (OR=1.75, 1.27-2.41), and over twice as likely to be current or former alcohol drinkers (OR=2.23, 1.24-4.04). Conclusions: We recommend targeting WSW in breast screening programs.
The impact of sex on ropporin expression in multiple myeloma patients.
Authors: Raymond Wade, Saba Radhi, Maurizio Chiriva-Internati, Fred Hardwick, Jesse Mer, Amardeep Aulakh, Charles Saadeh, Yuefei Yu, Leonardo Mirandola, Kristopher Zepeda, Raffaella Chiaramonte, Michela Colombo, Natalia Platonova, Diane Duyen Thuy Nguyen, Nicholas D'Chuna, Venu Konala, Marjorie Jenkins, Jose A. Figueroa, Everardo Cobos
Journal: Journal of Clinical Oncology (2013)

e22052 Background: Multiple myeloma (MM) is a cancer of plasma cells wherein aberrant cells accumulate in the bone marrow leading to bone damage and interference with normal blood cell production. Although MM remains incurable, it is treatable. As with most forms of cancer, early detection is the key to improving prognosis and avoiding permanent damage. Cancer Testis Antigens (CTAs) are a class of proteins that are expressed in male gametogenic tissue but generally not in the somatic tissue of healthy adults. However, a number of cancer types have been shown to produce these proteins, and their expression has been correlated with malignancy. Ropporin is a specific CTA shown to be associated with MM, and this protein represents a potential target for MM diagnosis as well as immunotherapy. In this study, we examine the impact of sex on the expression of Ropporin, in MM patients. Methods: The expression of this particular CTA in MM patients was analyzed using PCR, ELISA, and immunohistochemistry in a cohort of 59 MM patients (37 male and 22 female). Results: 61% of MM patients were positive for Ropporin expression. When the data were broken down by sex, it was revealed that Roporrin expression was 81.8% in females and 48.6% in males. Interestingly, 50% of female patients as well as 78% of males expressing Ropporin were deceased. In addition, 100% of the deceased subjects in the cohort were Ropporin positive. Conclusions: Our results provide indications that sex can shift the expression of CTA in multiple myeloma. Furthermore, the data indicate CTA expression may affect the prognosis in MM patients. Further studies in a large cohort of patients are warranted to validate the correlation of CTA/ropporin in MM patients and sex.
HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS
Authors: Jean Dausset, Felix T. Rapaport, Frances D. Cannon, Joseph W. Ferrebee
Journal: The Journal of Experimental Medicine (1971)

The segregation of the canine DL-A leukocyte group antigen(s) b, c, d, e, f, g, h, k, l, and m has been traced in 141 consecutive matings in the Cooperstown Colony of beagles. All of the leukocyte antigen(s) were regularly transmitted en bloc from parent to offspring, with no instance of independent segregation. A total of 23 haplotypes, including six different DL-A antigen patterns (gl, bkhfm, bkcd, e, be, fgl) was observed. 31 different DL-A phenotypes were observed in a population of 100 mongrel dogs. A number of statistically significant positive and negative associations between individual DL-A antigenic components occurred in this population. The results support the concept of the DL-A system as a complex immunogenetic system governed by a single region (or locus) of an autosomal pair of chromosomes. Studies of skin, kidney, heart, and liver allografts in the Cooperstown Colony indicated that the longest allograft survivals occur under genetically and serologically defined conditions of donor-recipient DL-A compatibility. Skin and renal allografts generally behaved in parallel fashion, while cardiac allografts survived for longer periods of time (MST = 47.1 days) than kidneys (MST = 28.1 days) or skin (MST = 25.1 days) under conditions of DL-A identity. Heart transplants were rejected at a more rapid rate than kidney, however, in DL-A-incompatible donor-recipient combinations. Liver transplants were accorded the longest survival time (MST = 76.2 days) under conditions of DL-A identity, but were rejected at a rapid rate (MST = 5 days) in DL-A-incompatible nonlittermate donor-recipient pairs. The results provide further evidence that the DL-A system is the principal system of histocompatibility in the canine species. The differences in survival of different organs under similar conditions of donor-recipient DL-A compatibility suggest, however, the existence of a number of unknown variables which may also be capable of significantly affecting allograft behavior.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults
Authors: Mariell Jessup, William T. Abraham, Donald E. Casey, Arthur M. Feldman, Gary S. Francis, Theodore G. Ganiats, Marvin A. Konstam, Donna M. Mancini, Peter S. Rahko, Marc A. Silver, Lynne Warner Stevenson, Clyde W. Yancy
Journal: Circulation (2009)
Feasibility of Allogeneic Hematopoietic Cell Transplantation Among High-Risk AML Patients in First Complete Remission: Results of the Transplant Objective from the SWOG (S1203) Randomized Phase III Study of Induction Therapy Using Standard 7+3 Therapy or Idarubicin with High-Dose Cytarabine (IA) Versus IA Plus Vorinostat
Authors: John M. Pagel, Megan Othus, Guillermo Garcia-Manero, Min Fang, Jerald P. Radich, David A. Rizzieri, Guido Marcucci, Stephen A. Strickland, Mark Litzow, Mary Lynn Savoie, Stephen R. Spellman, Dennis L. Confer, Jeffrey Chell, Maria Brown, Bruno C. Medeiros, Mikkael A. Sekeres, Tara L. Lin, Geoffrey L. Uy, Bayard L Powell, Jonathan E. Kolitz, Richard A. Larson, Richard M. Stone, David F. Claxton, James Essell, Selina Luger, Sanjay R. Mohan, Anna Moseley, Harry P. Erba, Frederick R. Appelbaum
Journal: Blood (2016)