tbuckley/cabot-search huggingface dataset:
Genome-Wide Array-Based Comparative Genomic Hybridization Reveals Multiple Amplification Targets and Novel Homozygous Deletions in Pancreatic Carcinoma Cell Lines
Authors: Markus Heidenblad, Eric F. P. M. Schoenmakers, Tord Jonson, Ludmila Gorunova, Joris A. Veltman, Ad Geurts van Kessel, Mattias Höglund
Journal: Cancer Research (2004)

Abstract Pancreatic carcinomas display highly complex chromosomal abnormalities, including many structural and numerical aberrations. There is ample evidence indicating that some of these abnormalities, such as recurrent amplifications and homozygous deletions, contribute to tumorigenesis by altering expression levels of critical oncogenes and tumor suppressor genes. To increase the understanding of gene copy number changes in pancreatic carcinomas and to identify key amplification/deletion targets, we applied genome-wide array-based comparative genomic hybridization to 31 pancreatic carcinoma cell lines. Two different microarrays were used, one containing 3,565 fluorescence in situ hybridization-verified bacterial artificial chromosome clones and one containing 25,468 cDNA clones representing 17,494 UniGene clusters. Overall, the analyses revealed a high genomic complexity, with several copy number changes detected in each case. Specifically, 60 amplicons at 32 different locations were identified, most frequently located within 8q (8 cases), 12p (7 cases), 7q (5 cases), 18q (5 cases), 19q (5 cases), 6p (4 cases), and 8p (4 cases). Amplifications of 8q and 12p were mainly clustered at 8q23–24 and 12p11–12, respectively, whereas amplifications on other chromosome arms were more dispersed. Furthermore, our analyses identified several novel homozygously deleted segments located to 9p24, 9p21, 9q32, 10p12, 10q22, 12q24, and 18q23. The individual complexity and aberration patterns varied substantially among cases, i.e., some cell lines were characterized mainly by high-level amplifications, whereas others showed primarily whole-arm imbalances and homozygous deletions. The described amplification and deletion targets are likely to contain genes important in pancreatic tumorigenesis.
Privately managed NHS trust will survive despite slow progress in cutting deficit, Circle says
Authors: A. O'Dowd
Journal: BMJ (2012)

The first ever NHS trust in England to be franchised out to the private sector will succeed in the long term, despite making much slower than expected progress in cutting its large deficit, MPs have been assured.

Witnesses gave several such assurances during an angry evidence session of the parliamentary Public Accounts committee on 10 December as part of its inquiry into franchising of NHS trusts, but the committee said that it was still concerned about wasted public money.

In February this year the management of Hinchingbrooke Health Care NHS Trust in Cambridgeshire was franchised out to the private company Circle for 10 years—a first for the NHS—after the trust …
FIZZ1 potentiates the carbachol-induced tracheal smooth muscle contraction
Authors: H. Chen, B.A. Jacobson, L. Mason, S.F. Wolf, M.R. Bowman
Journal: European Respiratory Journal (2010)

FIZZ1 is an adipokine highly expressed under inflammatory conditions, and yet, little is known of its function. In this study we examine the expression and function of FIZZ1 in an ovalbumin mouse model of asthma. Trachea from naïve or ovalbumin-sensitised and -challenged mice were compared for transcriptional, functional and proteomic differences using gene microarrays, ex vivo tracheal contraction, immunohistochemistry and Western blot analysis. FIZZ1 was expressed in ovalbumin-treated, but not naïve, trachea. Naïve trachea incubated with recombinant FIZZ1 exhibited denuded epithelium and contractile hyperresponsiveness. The FIZZ1-incubated trachea also exhibited an associated increased expression of phospho-c-Raf, phospho-extracellular signal-regulated kinase 1/2, phospho-p38, MLCK and MLC-20. These data demonstrate that FIZZ1 regulates tracheal smooth muscle contraction through impairment of the epithelium and activation of the mitogen-activated protein kinase pathway in muscle.
Safety and efficacy analysis by histology of weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer
Authors: M.A. Socinski, I. Okamoto, J.K. Hon, V. Hirsh, S.R. Dakhil, R.D. Page, J. Orsini, N. Yamamoto, H. Zhang, M.F. Renschler
Journal: Annals of Oncology (2013)
Hepatic adenomas and oral contraceptives.
Authors: S Sherlock
Journal: Gut (1975)

Over the past 5 years there has been an increase in the number of reports of patients with hepatic adenomas, and an association has been found between these tumors and the use of oral contraceptives. Up to January 1975 46 patients have been reported with this association. The histology of the tumors varies, with several names having been applied to the variations. Adenoma or focal nodular hyperplasia seem to be the most appropriate terms. Most of the commonly used oral contraceptives have been involved. Usually the use of the contraceptive has been at least 2 years. In 1 case, adenoma was diagnosed 4 years after stopping use of the drug. Symptoms have been abdominal pain and an abdominal mass. The tumor may rupture with hemorrhage into the abdominal cavity creating an emergency. Hepatic arteriography has been used to make an early diagnosis. Biochemical tests remain normal. Needle biopsy is contraindicated; surgery is indicated, however. The lesion may be multiple. Hepatic adenoma should be suspected in any young woman with abdominal pain and enlargement of the liver. Ruptured hepatic adenoma should be considered in acute abdominal emergencies, in young women who are taking oral contraceptives, and in older women taking hormone replacements.
Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression
Authors: Stéphanie Sungalee, Emilie Mamessier, Ester Morgado, Emilie Grégoire, Philip Z. Brohawn, Christopher A. Morehouse, Nathalie Jouve, Céline Monvoisin, Cédric Menard, Guilhaume Debroas, Mustapha Faroudi, Violaine Mechin, Jean-Marc Navarro, Charlotte Drevet, Franziska C. Eberle, Lionel Chasson, Fannie Baudimont, Stéphane J. Mancini, Julie Tellier, Jean-Michel Picquenot, Rachel Kelly, Paolo Vineis, Philippe Ruminy, Bruno Chetaille, Elaine S. Jaffe, Claudine Schiff, Jean Hardwigsen, David A. Tice, Brandon W. Higgs, Karin Tarte, Bertrand Nadel, Sandrine Roulland
Journal: Journal of Clinical Investigation (2014)

It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)+ memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC transits before acquiring FL-associated developmental arrest and presenting as GC B cells with constitutive activation–induced cytidine deaminase (AID) mutator activity. Moreover, multiple reentries into the GC were necessary for the progression to advanced precursor stages of FL. Together, our results demonstrate that protracted subversion of immune dynamics contributes to early dissemination and progression of t(14;18)+ precursors and shapes the systemic presentation of FL patients.
Priming With Angiopoietin-1 Augments the Vasculogenic Potential of the Peripheral Blood Stem Cells Mobilized With Granulocyte Colony-Stimulating Factor Through a Novel Tie2/Ets-1 Pathway
Authors: Min-Seok Kim, Choon-Soo Lee, Jin Hur, Hyun-Jai Cho, Soo-In Jun, Tae-Youn Kim, Sae-Won Lee, Jung-Won Suh, Kyung-Woo Park, Hae-Young Lee, Hyun-Jae Kang, Dong-Soo Lee, Gou-Young Koh, Hironori Nakagami, Ryuichi Morishita, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2009)

The low engraftment rate of stem/progenitor cells infused via the intracoronary route to the ischemic myocardium is one of the most important factors limiting the efficacy of cell therapy. We investigated the concept of priming peripheral blood stem cells enriched by granulocyte colony-stimulating factor mobilization and apheresis ((mob)PBSCs) with angiopoietin-1 (Ang1), to enhance the engraftment into the ischemic tissue and neovasculogenic potential.The expression of Tie2, the Ang1 receptor, was significantly higher in (mob)PBSCs than naïve peripheral blood mononuclear cells (19.2+/-3.0% versus 1.2+/-0.8% versus 1.2+/-0.2%; P<0.001 for (mob)PBSCs from acute myocardial infarction (AMI) patients with granulocyte colony-stimulating factor treatment for 3 days versus peripheral blood mononuclear cells from AMI patients versus peripheral blood mononuclear cells from stable angina patients). After 4 hours of cartilage oligomeric matrix protein (COMP)-Ang1 stimulation, (mob)PBSCs committed to the endothelial lineage with the induction of CD31 and VE-cadherin expression, mediated by Tie2/Ets-1 pathway. Priming of (mob)PBSCs with COMP-Ang1 induced the expression of alpha4beta1 and alpha5beta1 integrins, which are also Ets-1 downstream molecules, leading to enhanced adhesion to endothelial cells or fibronectin. In a rabbit ear ischemia/reperfusion model, priming of (mob)PBSCs with COMP-Ang1 improved first-pass engraftment to the distal vascular bed after intraarterial delivery. In a murine ischemic hind-limb model, intravascular delivery of primed (mob)PBSCs enhanced both engraftment and neovascularization.The short-term priming with COMP-Ang1 may be a feasible and promising option to activate (mob)PBSCs by enhancing differentiation and adhesiveness and to improve the efficacy of cell therapy for ischemic diseases.
Criteria for Authorship in Bioethics
Authors: David B. Resnik, Zubin Master
Journal: The American Journal of Bioethics (2011)

Multiple authorship is becoming increasingly common in bioethics research. There are well-established criteria for authorship in empirical bioethics research but not for conceptual research. It is important to develop criteria for authorship in conceptual publications to prevent undeserved authorship and uphold standards of fairness and accountability. This article explores the issue of multiple authorship in bioethics and develops criteria for determining who should be an author on a conceptual publication in bioethics. Authorship in conceptual research should be based on contributing substantially to: (1) identifying a topic, problem, or issue to study; (2) reviewing and interpreting the relevant literature; (3) formulating, analyzing, and evaluating arguments that support one or more theses; (4) responding to objections and counterarguments; and (5) drafting the manuscript and approving the final version. Authors of conceptual publications should participate substantially in at least two of areas (1)–(5).
T cell ontogeny. Organ location of maturing populations as defined by surface antigen markers is similar in neonates and adults.
Authors: J J Haaijman, H S Micklem, J A Ledbetter, J L Dangl, L A Herzenberg, L A Herzenberg
Journal: The Journal of Experimental Medicine (1981)

Earlier studies have suggested that splenic T cell populations in nursling mice (less than 18 d of age) have Lyt cell surface antigens that identify them as less mature than their adult counterparts. Studies presented here, however, demonstrate that the expression of the Thy-1, Lyt-1, Lyt-2, and Lyt-3 T cell antigens is virtually identical in 14-d-old and adult T cell populations even though at 14 d, T cells constitute less than 10% of the total spleen cell population. Because the expression of these antigens on the immature (cortical) thymocyte population differs substantially from their expression on peripheral T cells, the maturity of splenic T cells as judged by these criteria is similar in nurslings and adults. Very few cells in the neonatal thymus 4 h after birth correspond, in terms of antigen expression, to the more mature (medullary) thymocyte population of adults, but such cells develop rapidly during the first few days of life. They are present, therefore, sufficiently early to serve as the immediate source of peripheral T cells, as they apparently do in the adult. This then suggests that the locations for the major T cell maturational events are established within the first 2 wk of life of the mouse and maintained as such thereafter. The use of monoclonal antibodies and quantitative immunofluorescence analysis in our studies probably explains the differences between our findings and those reported previously, which relied on cytotoxic depletion by alloantisera and complement to estimate the frequencies of cells carrying the Lyt differentiation antigens in nurslings.
Practice Recommendations in the Diagnosis, Management, and Prevention of Carbon Monoxide Poisoning
Authors: Neil B. Hampson, Claude A. Piantadosi, Stephen R. Thom, Lindell K. Weaver
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Section:ChooseTop of pageAbstract <<DiagnosisManagementPreventionConclusionsReferencesCITING ARTICLES
Tools to Promote Shared Decision Making in Serious Illness
Authors: C. Adrian Austin, Dinushika Mohottige, Rebecca L. Sudore, Alexander K. Smith, Laura C. Hanson
Journal: JAMA Internal Medicine (2015)

Serious illness impairs function and threatens survival. Patients facing serious illness value shared decision making, yet few decision aids address the needs of this population.To perform a systematic review of evidence about decision aids and other exportable tools that promote shared decision making in serious illness, thereby (1) identifying tools relevant to the treatment decisions of seriously ill patients and their caregivers, (2) evaluating the quality of evidence for these tools, and (3) summarizing their effect on outcomes and accessibility for clinicians.We searched PubMed, CINAHL, and PsychInfo from January 1, 1995, through October 31, 2014, and identified additional studies from reference lists and other systematic reviews. Clinical trials with random or nonrandom controls were included if they tested print, video, or web-based tools for advance care planning (ACP) or decision aids for serious illness. We extracted data on the study population, design, results, and risk for bias using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Each tool was evaluated for its effect on patient outcomes and accessibility.Seventeen randomized clinical trials tested decision tools in serious illness. Nearly all the trials were of moderate or high quality and showed that decision tools improve patient knowledge and awareness of treatment choices. The available tools address ACP, palliative care and goals of care communication, feeding options in dementia, lung transplant in cystic fibrosis, and truth telling in terminal cancer. Five randomized clinical trials provided further evidence that decision tools improve ACP documentation, clinical decisions, and treatment received.Clinicians can access and use evidence-based tools to engage seriously ill patients in shared decision making. This field of research is in an early stage; future research is needed to develop novel decision aids for other serious diagnoses and key decisions. Health care delivery organizations should prioritize the use of currently available tools that are evidence based and effective.
Anaplastic Large-Cell Lymphoma in Women With Breast Implants
Authors: Daphne de Jong
Journal: JAMA (2008)

Recently, we identified 2 patients with anaplastic large T-cell lymphoma (ALCL) negative for tyrosine kinase anaplastic lymphoma kinase (ALK-negative) in the fibrous capsule of silicone breast prostheses, placed for cosmetic reasons. Similar cases have been reported in the literature. Although an increased risk of ALCL in patients with breast prostheses has been speculated, no studies have been conducted so far.To determine whether ALCL risk is associated with breast prostheses.A search for all patients with lymphoma in the breast diagnosed in The Netherlands between 1990 and 2006 was performed through the population-based nationwide pathology database. Subsequently, we performed an individually matched case-control study. Conditional logistic regression analysis was performed to estimate the relative risk of ALCL associated with breast prostheses.Eleven patients with breast ALCL were identified in the registry. For each case patient with ALCL in the breast, we selected 1 to 5 controls with other lymphomas in the breast, matched on age and year of diagnosis. For all cases and controls (n = 35), pathological and clinical information was obtained with special emphasis on the presence of a breast prosthesis.Association between breast implants and ALCL of the breast.The 11 patients with ALCL of the breast were diagnosed between 1994 and 2006 at a median age of 40 years (range, 24-68 years). In 5 of these patients, bilateral silicone breast prostheses had been placed 1 to 23 years before diagnosis. All received prostheses for cosmetic reasons. Lymphoma classes of 35 eligible control patients were 12 diffuse large B-cell lymphomas, including 1 T-cell rich B-cell lymphoma; 5 Burkitt lymphomas; 10 mucosa-associated lymphoid tissue-type lymphoma; 3 follicular lymphomas; 3 peripheral T-cell lymphomas; and 2 indolent B-cell lymphomas, unclassified. One of 35 control patients had a breast implant placed before diagnosis of lymphoma. The odds ratio for ALCL associated with breast prostheses was 18.2 (95% confidence interval, 2.1-156.8).These preliminary findings suggest an association between silicone breast prostheses and ALCL, although the absolute risk is exceedingly low due to the rare occurrence of ALCL of the breast (11 cases in The Netherlands in 17 years). These findings require confirmation in other studies.
Comparison of Ustekinumab and Etanercept for Moderate-to-Severe Psoriasis
Authors: Christopher E.M. Griffiths, Bruce E. Strober, Peter van de Kerkhof, Vincent Ho, Roseanne Fidelus-Gort, Newman Yeilding, Cynthia Guzzo, Yichuan Xia, Bei Zhou, Shu Li, Lisa T. Dooley, Neil H. Goldstein, Alan Menter
Journal: New England Journal of Medicine (2010)

Biologic agents offer a range of new therapeutic options for patients with psoriasis; however, the relative benefit-risk profiles of such therapies are not well known. We compared two biologic agents, ustekinumab (an interleukin-12 and interleukin-23 blocker) and etanercept (an inhibitor of tumor necrosis factor alpha), for the treatment of psoriasis.We randomly assigned 903 patients with moderate-to-severe psoriasis to receive subcutaneous injections of either 45 or 90 mg of ustekinumab (at weeks 0 and 4) or high-dose etanercept (50 mg twice weekly for 12 weeks). The primary end point was the proportion of patients with at least 75% improvement in the psoriasis area-and-severity index (PASI) at week 12; a secondary end point was the proportion with cleared or minimal disease on the basis of the physician's global assessment. Assessors were unaware of the treatment assignments. The efficacy and safety of a crossover from etanercept to ustekinumab were evaluated after week 12.There was at least 75% improvement in the PASI at week 12 in 67.5% of patients who received 45 mg of ustekinumab and 73.8% of patients who received 90 mg, as compared with 56.8% of those who received etanercept (P=0.01 and P<0.001, respectively). Similarly, 65.1% of patients who received 45 mg of ustekinumab and 70.6% of patients who received 90 mg of ustekinumab had cleared or minimal disease according to the physician's global assessment, as compared with 49.0% of those who received etanercept (P<0.001 for both comparisons). Among patients who did not have a response to etanercept, 48.9% had at least 75% improvement in the PASI within 12 weeks after crossover to ustekinumab. One or more adverse events occurred through week 12 in 66.0% of patients who received 45 mg of ustekinumab and 69.2% of patients who received 90 mg of ustekinumab and in 70.0% who received etanercept; 1.9%, 1.2%, and 1.2%, respectively, had serious adverse events. Safety patterns were similar before and after crossover from etanercept to ustekinumab.The efficacy of ustekinumab at a dose of 45 or 90 mg was superior to that of high-dose etanercept over a 12-week period in patients with psoriasis. (ClinicalTrials.gov number, NCT00454584.)
Population genomics of the endangered giant Galápagos tortoise
Authors: Etienne Loire, Ylenia Chiari, Aurélien Bernard, Vincent Cahais, Jonathan Romiguier, Benoît Nabholz, Joao Lourenço, Nicolas Galtier
Journal: Genome biology (2013)

The giant Galápagos tortoise, Chelonoidis nigra, is a large-sized terrestrial chelonian of high patrimonial interest. The species recently colonized a small continental archipelago, the Galápagos Islands, where it has been facing novel environmental conditions and limited resource availability. To explore the genomic consequences of this ecological shift, we analyze the transcriptomic variability of five individuals of C. nigra, and compare it to similar data obtained from several continental species of turtles. Having clarified the timing of divergence in the Chelonoidis genus, we report in C. nigra a very low level of genetic polymorphism, signatures of a weakened efficacy of purifying selection, and an elevated mutation load in coding and regulatory sequences. These results are consistent with the hypothesis of an extremely low long-term effective population size in this insular species. Functional evolutionary analyses reveal a reduced diversity of immunity genes in C. nigra, in line with the hypothesis of attenuated pathogen diversity in islands, and an increased selective pressure on genes involved in response to stress, potentially related to the climatic instability of its environment and its elongated lifespan. Finally, we detect no population structure or homozygosity excess in our five-individual sample. These results enlighten the molecular evolution of an endangered taxon in a stressful environment and point to island endemic species as a promising model for the study of the deleterious effects on genome evolution of a reduced long-term population size.