tbuckley/cabot-search huggingface dataset:
Abstract 313: Examining the role of ABCA1 cholesterol transporter in ovarian cancer spheroids
Authors: Rebekka Williams, Amanda Russell, Angelika Bongers, Sharon Sagnella, Christopher Fife, Wendy Jessup, Anna DeFazio, Georgia Chenevix-Trench, Michelle Haber, Murray Norris, Michelle Henderson
Journal: Cancer Research (2015)

Abstract Epithelial ovarian cancer (EOC) is a devastating disease which accounts for a large proportion of gynaecological cancer-related deaths. Poor survival is largely due to late diagnosis of the disease which typically presents with peritoneal dissemination. In order to achieve reduced tumor burden and improved survival, it is imperative to identify new prognostic markers and potential therapeutic targets. Recent work by our group identified high ATP- Binding Cassette A1 (ABCA1) transporter expression as being associated with poor outcome in EOC. ABCA1 has been widely studied as a cholesterol transporter, however there is little research investigating its potential roles in cancer biology. The aim of this work was to ascertain whether ABCA1 may promote aggressive characteristics in EOC. siRNA-mediated suppression of ABCA1 in EOC cell lines led to reduced colony forming ability, growth and migration by comparison with controls. By culturing EOC cell lines (Skov3, 27/87 and HEY) in a 3-dimensional spheroid model, we have shown that ABCA1 suppression significantly reduced overall spheroid volume (p = ≤0.0003, ANOVA with Dunnett's multiple comparison test). In Skov3 and 27/87 spheroids, reduced volume was associated with cell death; however in HEY spheroids, ABCA1 suppression significantly reduced cell numbers in the absence of detectable cell death (p = ≤0.0002, ANOVA with Dunnett's multiple comparison test). Detailed characterisation of spheroid architecture revealed an increased volume-to-cell ratio in those depleted of ABCA1, indicating a lower degree of compaction compared to controls. It was further observed that whilst HEY spheroids derived from control siRNA-transfected cells develop a prominent necrotic core this feature was dramatically impaired by ABCA1 suppression. Compaction and core necrosis are both well-documented processes in spheroid biology that are indicative of cellular contractility and a hypoxic tumour environment, both key characteristics of more aggressive, chemo-resistant and recurrent tumors. Collectively these data suggest that ABCA1 may be involved in regulating multiple processes associated with aggressive and invasive characteristics of EOC, highlighting ABCA1 as a potential therapeutic target. Citation Format: Rebekka Williams, Amanda Russell, Angelika Bongers, Sharon Sagnella, Christopher Fife, Wendy Jessup, Anna DeFazio, Georgia Chenevix-Trench, Michelle Haber, Murray Norris, Michelle Henderson. Examining the role of ABCA1 cholesterol transporter in ovarian cancer spheroids. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 313. doi:10.1158/1538-7445.AM2015-313
Head of NHS England warns of tough year ahead
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The head of NHS England has warned of a “bloody tough” year ahead for the health service, as he urged people not to “rewrite history” in terms of representing how much funding the NHS has called for over the course of this parliament.

In his keynote speech to the NHS Confederation’s conference in Manchester this week, the chief executive of NHS England, Simon Stevens, set out his “home truths” about the scale of funding pressure on the health service.

This included clarifying that the NHS’s own Five Year Forward View called for extra funding from the government ranging from £8bn (€10bn; $11.3bn) to £21bn, depending on investment in social care and prevention.

This figure has …
Systemic TLR2 agonist exposure regulates hematopoietic stem cells via cell-autonomous and cell-non-autonomous mechanisms
Authors: A C Herman, D A Monlish, M P Romine, S T Bhatt, S Zippel, L G Schuettpelz
Journal: Blood Cancer Journal (2016)

Abstract Toll-like receptor 2 (TLR2) is a member of the TLR family of receptors that play a central role in innate immunity. In addition to regulating effector immune cells, where it recognizes a wide variety of pathogen-associated and nonpathogen-associated endogenous ligands, TLR2 is expressed in hematopoietic stem cells (HSCs). Its role in HSCs, however, is not well understood. Furthermore, augmented TLR2 signaling is associated with myelodysplastic syndrome, an HSC disorder characterized by ineffective hematopoiesis and a high risk of transformation to leukemia, suggesting that aberrant signaling through this receptor may have clinically significant effects on HSCs. Herein, we show that systemic exposure of mice to a TLR2 agonist leads to an expansion of bone marrow and spleen phenotypic HSCs and progenitors, but a loss of HSC self-renewal capacity. Treatment of chimeric animals shows that these effects are largely cell non-autonomous, with a minor contribution from cell-autonomous TLR2 signaling, and are in part mediated by granulocyte colony-stimulating factor and tumor necrosis factor-α. Together, these data suggest that TLR2 ligand exposure influences HSC cycling and function via unique mechanisms from TLR4, and support an important role for TLR2 in the regulation of HSCs.
THE DOCTOR'S DEFENSE
Authors: Richard H S Tur
Journal: JAMA (1921)

The paper takes as its point of departure a relatively recent case which attracted publicity in Britain, concerning a doctor charged with (but acquitted of) the murder of his terminally ill patient, and critically examines the criminal law of England and Wales relating to homicide in the context of medical practice. While similar issues obviously arise in many other countries, no comparative study is attempted in the paper. However, the arguments which have been presented are of more than local interest. From an analysis of this case and others, it appears that there is in common law something which can be called the doctor s defense. It holds that a doctor may, when caring for a patient who is suffering great pain, lawfully administer pain-killing drugs, despite the fact that, as the doctor well knows, one certain or highly probable consequence will be to shorten the patient s life. Current justifications for this defense are either incoherent or too weak. Some require that different conceptions of intention be deployed, depending on whether the agent is a doctor or not. Others rely on the philosophically controversial doctrine of double effect. Still others invoke an implausible notion of minimal causation. All these justifications apply readily enough to morally and factually easy cases, but fail in hard cases where the need for some justification is most pressing. These justifications seem incapable of providing adequate guidance to prosecutors or trial judges. Absent principled and transparent justification, the English criminal justice system exhibits different outcomes on what appear to be broadly similar facts. It is disturbing that the law is uncertain and incapable of giving adequate guidance. A doctor, compelled by conscience to intervene to end a person s life, should certainly be ready and willing to face rigorous legal scrutiny, but the law applied should not be arbitrary and random, nor should the outcome turn solely or chiefly on prosecutorial discretion or the predilections of the trial judge. The hope is to find a better rationale for the doctor s defense through an analysis of professional ethics and the concept of a recourse role.
Nuclear Cardiology
Authors: B L Zaret, F J Wackers
Journal: New England Journal of Medicine (1993)

Over the past two decades there has been substantial growth in the applications of nuclear cardiology to both clinical practice and research. The use of nuclear imaging techniques in the noninvasive study of cardiovascular disease is well established. Advances have been made in both radiopharmaceutical agents and instrumentation. In addition, there has been an increasing understanding of the role of nuclear cardiology in the diagnosis and management of cardiac disease1. At its inception, nuclear cardiology focused on issues of diagnostic accuracy and precision in identifying patients with coronary artery disease. In recent years, because of prompt and aggressive risk . . .
Freeze-dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA
Authors: Tania Furst, George R. Dakwar, Elisa Zagato, Anna Lechanteur, Katrien Remaut, Brigitte Evrard, Kevin Braeckmans, Geraldine Piel
Journal: Journal of Controlled Release (2016)
Evidence from Toxicology: The Most Essential Science for Prevention
Authors: Daniele Mandrioli, Ellen Kovner Silbergeld
Journal: Environmental Health Perspectives (2015)

The most essential goal of medicine and public health is to prevent harm (primum non nocere). This goal is only fully achieved with primary prevention, which requires us to identify and prevent harms prior to human exposure through research and testing that does not involve human subjects. For that reason, public health policies place considerable reliance on nonhuman toxicological studies. However, toxicology as a field has often not produced efficient and timely evidence for decision making in public health. In response to this, the U.S. National Research Council called for the adoption of evidence-based methods and systematic reviews in regulatory decision making. The U.S. Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the European Food Safety Agency (EFSA) have recently endorsed these methods in their assessments of safety and risk.In this commentary we summarize challenges and problems in current practices in toxicology as applied to decision making. We compare these practices with the principles and methods utilized in evidence-based medicine and health care, with emphasis on the record of the Cochrane Collaboration.We propose a stepwise strategy to support the development, validation, and application of evidence-based toxicology (EBT). We discuss current progresses in this field produced by the Office of Health Assessment and Translation (OHAT) of the National Toxicology Program and the Navigation Guide works. We propose that adherence to the Cochrane principles is a fundamental prerequisite for the development and implementation of EBT.The adoption of evidence-based principles and methods will enhance the validity, transparency, efficiency, and acceptance of toxicological evidence, with benefits in terms of reducing delays and costs for all stakeholders (researchers, consumers, regulators, and industry).Mandrioli D, Silbergeld EK. 2016. Evidence from toxicology: the most essential science for prevention. Environ Health Perspect 124:6-11; http://dx.doi.org/10.1289/ehp.1509880.
Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Authors: Joseph Grosso, Christine E. Horak, David Inzunza, Diana M. Cardona, Jason S. Simon, Ashok Kumar Gupta, Vindira Sankar, Jong-Soon Park, Georgia Kollia, Janis M. Taube, Robert Anders, Maria Jure-Kunkel, Jim Novotny, Clive R. Taylor, Xiaoling Zhang, Therese Phillips, Pauline Simmons, John Cogswell
Journal: Journal of Clinical Oncology (2013)

3016 Background: The immune checkpoint receptor programmed death-1 (PD-1) negatively regulates T-cell activation. In a phase I study, nivolumab, a PD-1 receptor blocking antibody, demonstrated durable clinical activity. Evaluation of the expression of the PD-1 ligand, PD-L1, by IHC with the 5H1 Ab suggested a correlation between pretreatment tumor PD-L1 expression and clinical response (Topalian et al, NEJM 2012). Methods: 304 pts with non-small cell lung cancer (NSCLC, n=127), melanoma (MEL, n=107), renal cell (RCC, n=34), colorectal (n=19) or prostate cancer (n=17) received nivolumab between 2008-2012 (0.1−10 mg/kg IV Q2W) during dose escalation and/or cohort expansion. Formalin-fixed paraffin-embedded tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed to explore potential pharmacodynamic/ predictive biomarkers associated with nivolumab therapy. Tumor surface PD-L1 expression was evaluated by IHC using an automated assay based on a sensitive and specific PD-L1 mAb (28-8) distinct from 5H1. PD-L1 positivity (PD-L1+) was defined as ≥5% cell membrane staining of any intensity. Lymphocyte subsets in PBMC were measured using flow cytometry. Results: Tumor membrane PD-L1 was measured in 101 MEL and NSCLC pts. 17/38 (45%) of MEL and 31/63 (49%) of NSCLC biopsies were PD-L1+. A numerically higher objective response rate (ORR), longer progression-free survival (PFS), and overall survival (OS) was seen with PD-L1+ in MEL pts (Table).Analysis of the association of PD-L1 expression with ORR, PFS and OS in NSCLC is ongoing. A correlative analysis of pt response with pre-/post-dose levels of lymphocytes will be presented. Conclusions: These data, using a novel, automated PD-L1 IHC assay and mAb, support the hypothesis of tumor PDL1+ predicting activity of nivolumab in advanced cancer, which is being prospectively assessed in phase III trials. Clinical trial information: NCT00730639. [Table: see text]
Soundings: Challenge and change
Authors: Colin Douglas
Journal: BMJ (2003)

Here in Auchendreich, far removed from the frenetic pace of events common in the great teaching centres, we pride ourselves on taking the longer view. This is in part a feature of the innate stolidity of the semi-rural Scot, and in part a matter of evidence based realism: our flagship new hospital, opened only last May, was, after all, in its planning stages for more than 30 years.

So at all levels there is recognition that it takes time to achieve real change in complex healthcare systems, and our chief executive's rather low key new year message acknowledged this.

Few were surprised to learn that DreichNet 2000, our long awaited area-wide total IM&T solution—offering real-time clinical imaging facilities, management level videoconferencing, and airline style booking systems even for our most remote psychogeriatric day hospital—is not now expected to go live much before mid-2005.

The imminent departure of our area head of IT to a challenging new role with the betting industry, and the still unexplained disappearance of her former live in partner—upon whose software company the whole system depended—should, the chief executive explained, be seen positively: a real opportunity to step up the momentum of the project, currently being overseen on a part time basis by Miss MacPherson, formerly chief records officer with the old Auchendreich Healthcare Trust, who has kindly agreed to postpone her retirement for at least six months.

IT apart, there were one or two points in the new year message that gave grounds for concern. A new finance director, an exiled Scot working somewhere in England, will not now be joining us, having been offered a greatly improved package by his current employer.

On a more positive note, our deputy medical director, recently promoted to a post in the west that will allow him to spend more time with his 10 metre ocean racer, is to be replaced by an innovative job share involving a consultant and a general practitioner: a widely hailed and progressive appointment, which will become effective as soon as issues arising from their contemporaneous and unexpectedly prolonged maternity leave can be resolved. But as our chief executive put it, up-scaling both our flexibility and our productivity will be key to success in the Greater Auchendreich Health Board Area in the year 2003.
Induction of rapid mood cycling during L-dopa treatment in a bipolar patient
Authors: G N Ko, J F Leckman, G R Heninger
Journal: American Journal of Psychiatry (1981)

The authors report a longitudinal case study of a woman with a history of bipolar affective disorder in which L-dopa shortened the manic-depressive cycle length when administered in a double-blind trial. This finding suggests a dopaminergic mechanism specifically in changing the frequency of cycling between depression and mania.
EPN-17AN ANALYSIS OF INTRACRANIAL EPENDYMOMAS FOR SURVIVAL AND PROGNOSTIC FACTORS
Authors: Takahisa Katsuki, Yoshiki Arakawa, Maki Yamaguchi, Sachiko Minamiguchi, Yohei Mineharu, Masaharu Tanji, Masahiro Kagawa, Susumu Miyamoto
Journal: Neuro-Oncology (2016)
Immunology of Cultivated Mammalian Cells. I. Species Specificity Determined by Hemagglutination&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: K. Gerhard Brand, M.D., Jerome T. Syverton, M.D.
Journal: JNCI Journal of the National Cancer Institute (1960)

Guinea pigs were immunized with human cell strains EE and HeLa, rabbit cell strains CRE and ERK-1, and tertiary cultures of domestic rabbit and rhesus monkey kidney. Antiserums to CRE and rabbit kidney cells agglutinated rabbit but not human erythrocytes. Antiserums to EE, HeLa, and ERK-1 cells agglutinated human but not rabbit erythrocytes. Induced hemagglutinins were distinguished from natural heterophil hemagglutinins and blood group-specific antibodies by absorption of serums with cells or erythrocytes and by agglutination inhibition with whole or disrupted cells or erythrocytes. Guinea pigs hyper-immunized with cells within the groups (a) EE, HeLa, and ERK-1 and (b) CRE and rabbit kidney exhibited anamnestic courses of hemagglutinin production; hyperimmunization between groups produced primary responses to secondary immunization. Guinea pigs injected with 1000 : 1 mixtures of EE and CRE cells produced hemagglutinins for rabbit as well as human erythrocytes. Antiserums to human and ERK-1 cells contained some induced agglutinins for rhesus monkey erythrocytes; antiserums to rhesus kidney cells contained agglutinins for rhesus and cynomolgus erythrocytes, but not human erythrocytes. Antiserums to calf-serum culture medium agglutinated calf erythrocytes weakly and irregularly. Antiserums contained no induced agglutinins for erythrocytes of other species.
포스터전시 : 만성 C형 간염 환자에서 페그 인터페론과 리바비린 병합 요법으로 치료 중 ALT 변화에 따른 반응의 차이 (초)
Authors: 김윤정, 권영란, 서혜진, 이경인, 김은수, 장병국, 정우진, 박경식, 조광범, 황재석
Journal: Clinical and Molecular Hepatology (2010)
LG-30ADOLESCENT/YOUNG ADULT OLIGODENDROGLIOMA – WHEN DOES THE “TIME CLOCK” TO PROGRESSION START?
Authors: Pournima Navalkele, Diana S. Osorio, Mohamed S. AbdelBaki, Jeffrey Leonard, Daniel R. Boue', Christopher R. Pierson, Carl Boesel, Fahd Al Sufiani, Jerome Rusin, Lisa Martin, Nicholas Zumberge, E. Steve Roach, Jonathan L. Finlay
Journal: Neuro-Oncology (2016)
Psychiatric aspects of dwarfism
Authors: J S Brust, C V Ford, D L Rimoin
Journal: American Journal of Psychiatry (1976)

Sixteen adult dwarfs - 11 with achondroplasia and 5 with hypopituitarism - were studied by means of psychiatric interviews and psychological tests. There were no significant differences between the two groups; in general, the subjects had achieved a satisfactory life adjustment despite the stress of having bodies uniquely different from those of the general population. They had secure identities as "little people" and successfully used coping mechanisms such as a sense of humor and a pleasant interpersonal style. Male dwarfs tended to experience more emotional distress than female dwarfs.
Fracture of the Month 29 Number
Authors: O E AUFRANC, W N JONES, W H HARRIS
Journal: JAMA (1962)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
LG-06MANAGEMENT OF PRIMARY THALAMIC LOW-GRADE GLIOMA IN PEDIATRIC PATIENTS: RESULTS OF THE MULTICENTER TREATMENT STUDIES HIT-LGG 1996 AND SIOP-LGG 2004
Authors: Tineke Boesten, Nicolas Gerber, Daniela Kandels, Amedeo Azizi, Rene Schmidt, Monika Warmuth-Metz, Torsten Pietsch, Rolf-Dieter Kortmann, Astrid Gnekow, Michael Grotzer
Journal: Neuro-Oncology (2016)
NS-34THE SURGICAL TREATMENT OF PINEAL REGION TUMOR IN INFANTS UNDER THREE YEARS
Authors: Jie Ma, Yang Zhao, Qifeng Li, Lianping Sun, Feng Jiang, Qinchuan Liang
Journal: Neuro-Oncology (2016)

NS-34. THE SURGICAL TREATMENT OF PINEAL REGION TUMOR IN INFANTS UNDER THREE YEARS Jie Ma, Yang Zhao, Qifeng Li, Lianping Sun, Feng Jiang, and Qinchuan Liang; Department of Pediatric Neurosurgery, Shanghai Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China BACKGROUND AND OBJECTIVE: Pineal region tumors in infants and toddlers (, 3 yearsold ) are achallenge for surgery,demonstratingdismal clinical outcomes. To explore a reasonable treatment plan, this paper reviewed the operative treatment of pineal region tumors under 3 years old in my hospital. METHODS: A retrospective study was done on 13 patients with pineal region tumors under 3 years-old. The clinical characteristic, surgical approach and prognosiswere reviewed.All of the patientswereoperated onvia infratentorial supracerebellar approach (n 1⁄4 8), trans-frontal-callosal-interforniceal approach (n 1⁄4 2), paramedian infratentoria approach (n 1⁄4 1), combined approach (n 1⁄4 2). RESULTS: Tumor was totally removed in 8 patients, subtotally resected in3 and partially resected in 2. After surgery no patients fell in coma or died. Two patients died with abandoning treatment due to infection. Followed-up timewas3-30 months, 9 cases had resumed normal life, 2 cases died with recurrence. CONCLUSION: Microsurgery is the prior option for children with pineal region tumor under 3 years, and favorable resection rate has been achieved in this series. Proper approach depended on every individual entitle successful resection. Neuro-Oncology 18:iii127–iii134, 2016. doi:10.1093/neuonc/now078.34 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.