tbuckley/cabot-search huggingface dataset:
Polymeric drug delivery for the treatment of glioblastoma
Authors: S. D. Wait, R. S. Prabhu, S. H. Burri, T. G. Atkins, A. L. Asher
Journal: Neuro-Oncology (2015)

Glioblastoma (GBM) remains an almost universally fatal diagnosis. The current therapeutic mainstay consists of maximal safe surgical resection followed by radiation therapy (RT) with concomitant temozolomide (TMZ), followed by monthly TMZ (the "Stupp regimen"). Several chemotherapeutic agents have been shown to have modest efficacy in the treatment of high-grade glioma (HGG), but blood-brain barrier impermeability remains a major delivery obstacle. Polymeric drug-delivery systems, developed to allow controlled local release of biologically active substances for a variety of conditions, can achieve high local concentrations of active agents while limiting systemic toxicities. Polymerically delivered carmustine (BCNU) wafers, placed on the surface of the tumor-resection cavity, can potentially provide immediate chemotherapy to residual tumor cells during the standard delay between surgery and chemoradiotherapy. BCNU wafer implantation as monochemotherapy (with RT) in newly diagnosed HGG has been investigated in 2 phase III studies that reported significant increases in median overall survival. A number of studies have investigated the tumoricidal synergies of combination chemotherapy with BCNU wafers in newly diagnosed or recurrent HGG, and a primary research focus has been the integration of BCNU wafers into multimodality therapy with the standard Stupp regimen. Overall, the results of these studies have been encouraging in terms of safety and efficacy. However, the data must be qualified by the nature of the studies conducted. Currently, there are no phase III studies of BCNU wafers with the standard Stupp regimen. We review the rationale, biochemistry, pharmacokinetics, and research history (including toxicity profile) of this modality.
Sexual harassment and abuse in sport: the role of the team doctor: Table 1
Authors: Saul Marks, Margo Mountjoy, Madalyn Marcus
Journal: British Journal of Sports Medicine (2011)

Sexual harassment and abuse occur in all sports and at all levels with an increased risk at the elite level. The physical and psychological consequences of sexual harassment and abuse are significant for the athlete, their team and for the health and integrity of sport in general. The sports medicine health professional has an integral role to play in the prevention of sexual harassment and abuse in sport. This paper provides sport healthcare professionals with a practical guide on prevention strategies and advice on the recognition and management of suspected abuse.
Enzyme-Linked Immunosorbent Spot Assay Analysis of Peripheral Blood Lymphocyte Reactivity to Donor HLA-DR Peptides
Authors: Nader Najafian, Alan D. Salama, Eugenia V. Fedoseyeva, Gilles Benichou, Mohamed H. Sayegh
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Chronic allograft dysfunction, which is the most common cause of late allograft failure, is in part caused by an ongoing immune response orchestrated by T lymphocytes primed by the indirect pathway of allorecognition. The low frequencies of such T cells have made it difficult to study indirect alloreactivity by using currently available assays. The development of a sensitive, clinically useful method of measuring indirect alloreactivity among human renal transplant recipients was thus attempted. Furthermore, in a pilot immunologic study, the contribution of the indirect pathway was studied in two groups of renal transplant recipients, i.e., patients with no prior acute rejection episodes and stable renal function ("stable" patients) and patients with at least one previous episode of biopsy-proven acute rejection, who were thus at risk for the development of chronic rejection ("high-risk" patients). The frequencies of type 1 T helper (interferon-γ-producing) and type 2 T helper (interleukin-5- and -10-producing) peripheral blood lymphocytes reactive with a panel of synthetic peptides (corresponding to sequences from donor HLA-DR molecules) were determined for renal transplant recipients and normal control subjects by using an enzyme-linked immunosorbent spot assay (ELISPOT). Among recipients of DR-mismatched allografts, a cut-off value of 60 interferon-γ spots/106 cells significantly (P = 0.02) separated stable patients (creatinine concentration, 1.1 ± 0.3 mg/dl) from high-risk patients (creatinine concentration, 2.3 ± 1.7 mg/dl). This is the first demonstration that the enzyme-linked immunosorbent spot assay can be used to monitor indirect alloreactivity to donor HLA-DR peptides among renal transplant recipients. These data provide the rationale for the prospective study of indirect alloreactivity among transplant recipients, to allow predictions of which patients would be at risk for the development of chronic rejection and thus allow appropriate planning of future interventions.
Therapy of Small Subcutaneous B-Lymphoma Xenografts with Antibodies Conjugated to Radionuclides Emitting Low-Energy Electrons
Authors: Rosana B. Michel, Adriane V. Rosario, Philip M. Andrews, David M. Goldenberg, M. Jules Mattes
Journal: Clinical Cancer Research (2005)

Radionuclides emitting low-energy electrons (Auger and conversion electrons of <50 keV) are potentially useful for cancer therapy when conjugated to an antibody, because they can irradiate the cell to which they bind while producing relatively little irradiation of surrounding cells and tissues. We showed previously the ability of such antibody conjugates to treat micrometastatic, disseminated human B-lymphoma in a severe combined immunodeficient mouse model using an anti-CD74 antibody. In this study, we have evaluated the ability of such conjugates to treat s.c. tumors.Severe combined immunodeficient mice were injected s.c. with Raji, Daudi, or RL B-lymphoma human tumor cells. Antibodies to CD74, CD20, or HLA-DR were radiolabeled with (111)In or (125)I and injected i.v. at various times starting at day 5, and tumor growth was monitored. Controls included the testing of unlabeled antibodies, labeled nonreactive antibodies, and a combination of the two.Therapy of s.c. B-lymphoma was more difficult than therapy of tumor cells that had been injected i.v. Although large, macroscopic tumors were not effectively treated, therapy was effective on s.c. Daudi tumors on day 36 after injection of this slowly growing tumor, with an (111)In anti-CD74 antibody given in two doses. An anti-CD20 antibody labeled with either (111)In or (125)I was able to effectively treat s.c. RL tumors when given as late as day 16 after tumor inoculation. The largest tumors that were effectively treated were macroscopic thin discs (<2 mm in diameter) growing on the mesentery.These results extend previous evidence that antibody conjugates with emitters of low-energy electrons can be effective therapeutic agents for micrometastatic cancer.
Engineering‐Aligned 3D Neural Circuit in Microfluidic Device
Authors: Seokyoung Bang, Sangcheol Na, Jae Myung Jang, Jinhyun Kim, Noo Li Jeon
Journal: Advanced Healthcare Materials (2015)

The brain is one of the most important and complex organs in the human body. Although various neural network models have been proposed for in vitro 3D neuronal networks, it has been difficult to mimic functional and structural complexity of the in vitro neural circuit. Here, a microfluidic model of a simplified 3D neural circuit is reported. First, the microfluidic device is filled with Matrigel and continuous flow is delivered across the device during gelation. The fluidic flow aligns the extracellular matrix (ECM) components along the flow direction. Following the alignment of ECM fibers, neurites of primary rat cortical neurons are grown into the Matrigel at the average speed of 250 μm d −1 and form axon bundles approximately 1500 μm in length at 6 days in vitro (DIV). Additionally, neural networks are developed from presynaptic to postsynaptic neurons at 14 DIV. The establishment of aligned 3D neural circuits is confirmed with the immunostaining of PSD‐95 and synaptophysin and the observation of calcium signal transmission.
Report XCV. UPON THE BACTERIOLOGY OF THE SUMMER DIARRHOEA OF INFANTS
Authors: H. d. R. Morgan
Journal: BMJ (1906)

THE diarrhoeal diseases of infancy, on account of their appalling mortality, demand the most careful and thorough investigation.A large number of inquiries have been made in various directions with reference to the predisposing and etio- logical factors in these diseases, for example, the influence of seasonal and hygienic conditions, of natural and artifloial feeding, of milk pasteurization, etc. 1
Prevention of Radiation-Induced Salivary Hypofunction Following hKGF Gene Delivery to Murine Submandibular Glands
Authors: Changyu Zheng, Ana P. Cotrim, Anne Rowzee, William Swaim, Anastasia Sowers, James B. Mitchell, Bruce J. Baum
Journal: Clinical Cancer Research (2011)

Salivary glands are significantly affected when head and neck cancer patients are treated by radiation. We evaluated the effect of human keratinocyte growth factor (hKGF) gene transfer to murine salivary glands on the prevention of radiation-induced salivary hypofunction.A hybrid serotype 5 adenoviral vector encoding hKGF (AdLTR(2)EF1α-hKGF) was constructed. Female C3H mice, 8 weeks old, were irradiated by single (15 Gy) or fractionated (6 Gy for 5 days) doses to induce salivary hypofunction. AdLTR(2)EF1α-hKGF or AdControl was administered (10(8) - 10(10) particles per gland) to both submandibular glands (SG) by retrograde ductal instillation before irradiation (IR). Salivary flow was measured following pilocarpine stimulation. Human KGF levels were measured by ELISA. SG cell proliferation was measured with bromodeoxyuridine labeling. Endothelial and progenitor or stem cells in SGs were measured by flow cytometry. The effect of SG hKGF production on squamous cell carcinoma (SCC VII) tumor growth was assessed.In 3 separate single-dose IR experiments, salivary flow rates of mice administered the AdLTR(2)EF1α-hKGF vector were not significantly different from nonirradiated control mice (P > 0.05). Similarly, in 3 separate fractionated IR experiments, the hKGF-expressing vector prevented salivary hypofunction dramatically. Transgenic hKGF protein was found at high levels in serum and SG extracts. AdLTR(2)EF1α-hKGF-treated mice showed increased cell proliferation and numbers of endothelial cells, compared with mice treated with AdControl. hKGF gene transfer had no effect on SCC VII tumor growth ± radiation.hKGF gene transfer prevents salivary hypofunction caused by either single or fractionated radiation dosing in mice. The findings suggest a potential clinical application.
Ionic basis of action potential prolongation of hypertrophied cardiac myocytes isolated from hypertensive rats of different ages
Authors: E. Cerbai, M. Barbieri, Q. Li, A. Mugelli
Journal: Cardiovascular Research (1994)

Journal Article Ionic basis of action potential prolongation of hypertrophied cardiac myocytes isolated from hypertensive rats of different ages Get access Elisabetta Cerbai, Elisabetta Cerbai Department of Preclinical and Clinical Pharmacology, Via le G B Morgagni 65, I-50134 Firenze, Italy: A Mugelli; Institute of Pharmacology, University of Ferrara, Ferrara, Italy: E Cerbai, M Barbieri, Q Li. Correspondence to Professor Mugelli. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mario Barbieri, Mario Barbieri Department of Preclinical and Clinical Pharmacology, Via le G B Morgagni 65, I-50134 Firenze, Italy: A Mugelli; Institute of Pharmacology, University of Ferrara, Ferrara, Italy: E Cerbai, M Barbieri, Q Li. Search for other works by this author on: Oxford Academic PubMed Google Scholar Qi Li, Qi Li Department of Preclinical and Clinical Pharmacology, Via le G B Morgagni 65, I-50134 Firenze, Italy: A Mugelli; Institute of Pharmacology, University of Ferrara, Ferrara, Italy: E Cerbai, M Barbieri, Q Li. Search for other works by this author on: Oxford Academic PubMed Google Scholar Alessandro Mugelli Alessandro Mugelli Department of Preclinical and Clinical Pharmacology, Via le G B Morgagni 65, I-50134 Firenze, Italy: A Mugelli; Institute of Pharmacology, University of Ferrara, Ferrara, Italy: E Cerbai, M Barbieri, Q Li. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 8, August 1994, Pages 1180–1187, https://doi.org/10.1093/cvr/28.8.1180 Published: 01 August 1994 Article history Received: 23 December 1993 Accepted: 07 March 1994 Published: 01 August 1994
Autophagy Control by the VEGF-C/NRP-2 Axis in Cancer and Its Implication for Treatment Resistance
Authors: Marissa J. Stanton, Samikshan Dutta, Heyu Zhang, Navatha S. Polavaram, Alexey A. Leontovich, Pia Hönscheid, Frank A. Sinicrope, Donald J. Tindall, Michael H. Muders, Kaustubh Datta
Journal: Cancer Research (2012)

A major contributor to cancer mortality is recurrence and subsequent metastatic transformation following therapeutic intervention. Therefore, in order to develop new treatment modalities and improve the efficacy of current ones, it is important to understand the molecular mechanisms that promote resistance to therapy in cancer cells. One pathway contributing to therapy resistance is autophagy, a self-digestive process that can eliminate unnecessary or damaged organelles to protect cancer cells from death. We have found that the VEGF-C/NRP-2 axis is involved in the activation of autophagy, which helps cancer cell survival following treatment. Inhibition of mTOR complex 1 activity by this axis is the underlying mechanism for the activation of autophagy. Furthermore, we identified two VEGF-C/NRP-2-regulated genes, LAMP-2 and WDFY-1, that have previously been suggested to participate in autophagy and vesicular trafficking. Upregulation of WDFY-1 following VEGF-C or NRP-2 depletion contributes to cytotoxic drug-mediated cell death. Together, these data suggest a link between the VEGF-C/NRP-2 axis and cancer cell survival despite the presence of chemotherapy-induced stress. Effective targeting of this pathway may lead to the development of new cancer therapies.
Phosphatidylinositol 3′-Kinase/AKT Signaling Is Activated in Medulloblastoma Cell Proliferation and Is Associated with Reduced Expression of <i>PTEN</i>
Authors: Wolfgang Hartmann, Boris Digon-Söntgerath, Arend Koch, Anke Waha, Elmar Endl, Indra Dani, Dorota Denkhaus, Cynthia G. Goodyer, Niels Sörensen, Otmar D. Wiestler, Torsten Pietsch
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Medulloblastomas represent the most frequent malignant brain tumors of childhood. They are supposed to originate from cerebellar neural precursor cells. Recently, it has been shown that Sonic Hedgehog–induced formation of medulloblastoma in an animal model is significantly enhanced by activation of the phosphatidylinositol 3′-kinase (PI3K) signaling pathway. Experimental Design: To examine a role for PI3K/AKT signaling in the molecular pathogenesis of human medulloblastoma, we did an immunohistochemical study of the expression of Ser473-phosphorylated (p)-AKT protein in 22 medulloblastoma samples: All samples displayed p-AKT expression. To investigate if an activated PI3K/AKT pathway is required for medulloblastoma cell growth, we treated five human medulloblastoma cell lines with increasing concentrations of the PI3K inhibitor LY294002 and analyzed cellular proliferation and apoptosis. The antiproliferative effect could be antagonized by overexpressing constitutively active AKT. As the activation of PI3K/AKT signaling may be associated with alterations of the PTEN gene located at 10q23.3, a chromosomal region subject to frequent allelic losses in medulloblastoma, we screened PTEN for mutations and mRNA expression. Results: Proliferation of all of the medulloblastoma cell lines was dependent on PI3K/AKT signaling, whereas apoptosis was not prominently affected. Allelic loss was detected in 16% of the cases. One medulloblastoma cell line was found to carry a truncating mutation in the PTEN coding sequence. Even more important, PTEN mRNA and protein levels were found to be significantly lower in medulloblastomas compared with normal cerebellar tissue of different developmental stages. Reduction of PTEN expression was found to be associated with PTEN promoter hypermethylation in 50% of the tumor samples. Conclusions: We conclude that activation of the PI3K/AKT pathway constitutes an important step in the molecular pathogenesis of medulloblastoma and that dysregulation of PTEN may play a significant role in this context.
Paediatric exercise science and medicine: Eds Neil Armstrong, Willem van Mechelen. (Pp 472; pound59.95.) Oxford: Oxford University Press, 2000. ISBN 0-19-262977.
Authors: Mary Claire McGovern
Journal: British Journal of Sports Medicine (2002)

Although this book arrived for review during the summer, light, easy beach reading it is not. Its qualities are encyclopaedic rather than Mills and Boon!

Edited by Neil Armstrong and Willem van Mechelen, the first two sections deal with paediatric exercise science and the last three with paediatric exercise medicine. Each part has between 6 and 12 chapters, written by a variety of …
Proposal to drop depression from GP quality indicators sparks outcry
Authors: A. O'Dowd
Journal: BMJ (2011)

Several mental health organisations have reacted angrily to proposals that some target indicators on depression in the Quality and Outcomes Framework (QOF) for GPs in England should be dropped.

QOF, the Department of Health’s incentive scheme that rewards GPs for how well they care for patients, is being updated, with the intention of improving the quality of care across general practice.

The National Institute for Health and Clinical Excellence (NICE), which now leads on changes to QOF, published its proposed indicators for 2012-13 on 1 August.

The new “menu” of 18 indicators will help target resources where they are most needed and deliver the best outcomes among patients, said NICE. Each new indicator has been piloted across a range of general practices and is based on up to date evidence, it …
HIV Treatment as Prevention: Principles of Good HIV Epidemiology Modelling for Public Health Decision-Making in All Modes of Prevention and Evaluation
Authors: Wim Delva, David P. Wilson, Laith Abu-Raddad, Marelize Gorgens, David Wilson, Timothy B. Hallett, Alex Welte
Journal: PLoS Medicine (2012)

Public health responses to HIV epidemics have long relied on epidemiological modelling analyses to help prospectively project and retrospectively estimate the impact, cost-effectiveness, affordability, and investment returns of interventions, and to help plan the design of evaluations. But translating model output into policy decisions and implementation on the ground is challenged by the differences in background and expectations of modellers and decision-makers. As part of the PLoS Medicine Collection "Investigating the Impact of Treatment on New HIV Infections"—which focuses on the contribution of modelling to current issues in HIV prevention—we present here principles of "best practice" for the construction, reporting, and interpretation of HIV epidemiological models for public health decision-making on all aspects of HIV. Aimed at both those who conduct modelling research and those who use modelling results, we hope that the principles described here will become a shared resource that facilitates constructive discussions about the policy implications that emerge from HIV epidemiology modelling results, and that promotes joint understanding between modellers and decision-makers about when modelling is useful as a tool in quantifying HIV epidemiological outcomes and improving prevention programming.
The quality of home spirometry in school children with asthma
Authors: D C Wensley
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Handheld electronic spirometers provide the opportunity for more comprehensive monitoring of lung function at home than has hitherto been available. The aim of this study was to assess the quality of spirometric data collected at home by 90 asthmatic schoolchildren aged 7–14 years. <h3>METHODS</h3> After training, children carried out twice daily recordings at home for four consecutive periods of 4 weeks using a data storage spirometer (Vitalograph), encouraged by 4-weekly visits from a research nurse. Compliance (proportion of blows recorded at correct time of day), technical quality (by machine criteria), and valid data recorded (the multiple of compliance and technical ability) were assessed. <h3>RESULTS</h3> Mean compliance declined from 81.4% to 70.4% (p&lt;0.001) between the first and last month, although the technical quality of the manoeuvres (81.9% and 80.1%, respectively) did not change significantly (p=0.48). <h3>CONCLUSIONS</h3> There was a steady reduction of valid data over the four periods (from 73.6% to 64.3%, 59.7%, and 57.6%) with wide individual differences. Even under ideal conditions, home spirometry provides an incomplete (and therefore potentially biased) picture of long term changes in pulmonary function.
Reward, Addiction, Withdrawal to Nicotine
Authors: Mariella De Biasi, John A. Dani
Journal: Annual Review of Neuroscience (2011)

Nicotine is the principal addictive component that drives continued tobacco use despite users' knowledge of the harmful consequences. The initiation of addiction involves the mesocorticolimbic dopamine system, which contributes to the processing of rewarding sensory stimuli during the overall shaping of successful behaviors. Acting mainly through nicotinic receptors containing the α4 and β2 subunits, often in combination with the α6 subunit, nicotine increases the firing rate and the phasic bursts by midbrain dopamine neurons. Neuroadaptations arise during chronic exposure to nicotine, producing an altered brain condition that requires the continued presence of nicotine to be maintained. When nicotine is removed, a withdrawal syndrome develops. The expression of somatic withdrawal symptoms depends mainly on the α5, α2, and β4 (and likely α3) nicotinic subunits involving the epithalamic habenular complex and its targets. Thus, nicotine taps into diverse neural systems and an array of nicotinic acetylcholine receptor (nAChR) subtypes to influence reward, addiction, and withdrawal.
Equitable Selection of Kidney Recipients
Authors: H. Peyton Young
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The increased number and success of kidney transplantations has focused national attention on the equity of the system by which recipients are selected. In an attempt to address the equity issue, the United Network for Organ Sharing recently adopted the point system of Starzl et al<sup>1</sup>for selecting cadaver kidney recipients. Several authors have taken issue with the way in which the factors in the formula by Starzl et al are weighted.<sup>2,3</sup>We draw attention to another problem with the formula that seems to have escaped notice: as patients at the head of the line receive transplants, the order among the remaining patients may shift. This bizarre result calls the equity of the method into question. The allocation formula described by Starzl et al assigns point values to each patient based on waiting time and other factors. These are combined into a "priority index"