tbuckley/cabot-search huggingface dataset:
Re-engineering Vesicular Stomatitis Virus to Abrogate Neurotoxicity, Circumvent Humoral Immunity, and Enhance Oncolytic Potency
Authors: Alexander Muik, Lawton J. Stubbert, Roza Z. Jahedi, Yvonne Geiβ, Janine Kimpel, Catherine Dold, Reinhard Tober, Andreas Volk, Sabine Klein, Ursula Dietrich, Beta Yadollahi, Theresa Falls, Hrvoje Miletic, David Stojdl, John C. Bell, Dorothee von Laer
Journal: Cancer Research (2014)

As cancer treatment tools, oncolytic viruses (OV) have yet to realize what some see as their ultimate clinical potential. In this study, we have engineered a chimeric vesicular stomatitis virus (VSV) that is devoid of its natural neurotoxicity while retaining potent oncolytic activity. The envelope glycoprotein (G) of VSV was replaced with a variant glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP), creating a replicating therapeutic, rVSV(GP), that is benign in normal brain but can effectively eliminate brain cancer in multiple preclinical tumor models in vivo. Furthermore, it can be safely administered systemically to mice and displays greater potency against a spectrum of human cancer cell lines than current OV candidates. Remarkably, rVSV(GP) escapes humoral immunity, thus, for the first time, allowing repeated systemic OV application without loss of therapeutic efficacy. Taken together, rVSV(GP) offers a considerably improved OV platform that lacks several of the major drawbacks that have limited the clinical potential of this technology to date.
Response to Comment on Home et al. Predictive and Explanatory Factors of Change in HbA1c in a 24-Week Observational Study of 66,726 People With Type 2 Diabetes Starting Insulin Analogs. Diabetes Care 2014;37:1237–1245
Authors: Philip D. Home, Chunduo Shen, Mohammad I. Hasan, Zafar A. Latif, Jian-Wen Chen, Guillermo González Gálvez
Journal: Diabetes Care (2014)

We thank Esposito et al. (1) for their comments regarding our analysis (2). It is indeed logical that baseline insulin regimen should have some power in predicting HbA1c change, perhaps particularly in insulin-naive people with diabetes. The primary A1chieve results do report that the mean reduction in HbA1c associated with starting a basal insulin plus insulin aspart regimen was −2.8% (−31 mmol/mol) in insulin-naive participants, compared with −2.2% (−24 …
Enhanced hepatocyte-selective in vivo gene expression by stabilized galactosylated liposome/plasmid DNA complex using sodium chloride for complex formation
Authors: Shintaro Fumoto, Shigeru Kawakami, Yoshitaka Ito, Kosuke Shigeta, Fumiyoshi Yamashita, Mitsuru Hashida
Journal: Molecular Therapy (2004)

In this study, we demonstrated that the presence of an essential amount of sodium chloride (NaCl) during the formation of cationic liposome/plasmid DNA complexes (lipoplexes) stabilizes the lipoplexes according to the surface charge regulation (SCR) theory. Fluorescence resonance energy transfer analysis revealed that cationic liposomes in an SCR lipoplex (5 and 10 mM NaCl solution in lipoplex) increased fusion. Also, aggregation of SCR lipoplexes was significantly delayed after exposure to saline (150 mM NaCl) as a model of physiological conditions. After intraportal administration, the hepatic transfection activity of galactosylated SCR lipoplexes (5 and 10 mM NaCl solution in lipoplex) was approximately 10- to 20-fold higher than that of galactosylated conventional lipoplexes in mice. The transfection activity in hepatocytes of galactosylated SCR lipoplexes was significantly higher than that of conventional lipoplexes, and preexposure to competitive asialoglycoprotein-receptor blocker significantly reduced the hepatic gene expression, suggesting that hepatocytes are responsible for high hepatic transgene expression of the galactosylated SCR lipoplexes. Pharmacokinetic studies both in situ and in vivo demonstrated a higher tissue binding affinity and a greater expanse of intrahepatic distribution by galactosylated SCR lipoplexes. Moreover, enhanced transfection activity of galactosylated SCR lipoplexes was observed in HepG2 cells, and investigation of confocal microscopic images showed that the release of plasmid DNA in the cell was markedly accelerated. These characteristics partly explain the mechanism of enhanced in vivo transfection efficacy by galactosylated SCR lipoplexes. Hence, information in this study will be valuable for the future use, design, and development of ligand-modified lipoplexes for in vivo applications.
Inhibition of Human HT29 Colon Carcinoma Growth In Vitro and In Vivo by Swainsonine and Human Interferon-α2
Authors: James W. Dennis, Kay Koch, David Beckner
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Inhibition of Human HT29 Colon Carcinoma Growth In Vitro and In Vivo by Swainsonine and Human Interferon-α2 Get access James W. Dennis, James W. Dennis Search for other works by this author on: Oxford Academic PubMed Google Scholar Kay Koch, Kay Koch Search for other works by this author on: Oxford Academic PubMed Google Scholar David Beckner David Beckner Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 13, 5 July 1989, Pages 1028–1033, https://doi.org/10.1093/jnci/81.13.1028 Published: 05 July 1989 Article history Received: 29 December 1988 Revision received: 27 March 1989 Accepted: 31 March 1989 Published: 05 July 1989
Does early diagnosis really save lives?
Authors: Des Spence
Journal: BMJ (2012)

Recent studies have suggested that vitamin D3 may have an immunoregulatory role in vitro. The vitamin D3 metabolism in 35 patients with primary Sjögren9s syndrome was investigated by measuring blood concentrations of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) and 25-hydroxyvitamin D3 (25-OHD3), as well as phenotypes and blood concentrations of Gc globulin, the main vitamin D3 binding protein in the blood. 25-OHD3 concentrations were diminished, but those of 1 alpha,25-(OH)2D3 were normal. There was no significant difference between the distribution of Gc phenotypes in the patients with primary Sjögren9s syndrome and normal controls. Likewise, blood concentrations of Gc globulin corresponded to normal values. Among patients with increased concentrations of IgM rheumatoid factor there was a significant negative correlation between the serum titres of IgM rheumatoid factor and 25-OHD3 concentrations.
Efficacy of tricyclic drugs in treating child and adolescent depression: a meta-analysis
Authors: P Hazell, D O'Connell, D Heathcote, J Robertson, D Henry
Journal: BMJ (1995)

Cyclosporine is crucial for the prevention of organ allograft rejection and allogeneic graft-vs-host disease (GVHD). Despite its potent immunosuppressive activity, cyclosporine elicits a T cell-mediated autoimmune syndrome after autologous or syngeneic bone marrow transplantation, which has been termed syngeneic GVHD (SGVHD). Recent studies have shown that for disease manifestation, a cytoxan and radiation-sensitive T cell dependent host resistance mechanism must be eliminated, allowing the clonal expansion of autoreactive cells. This report characterizes the autoregulatory lymphocyte population, present in normal animals, capable of inhibiting the adoptive transfer of SGVHD. First, twice the number of unfractionated splenocytes from normal animals to those from autoimmune donors ensured complete inhibition of the adoptive transfer of immune reactivity. Second, the phenotype of this host resistance mechanism in normal splenocytes involves dual regulatory T cell subsets. A helper/inducer subset (W3/25+) must be cotransferred with a cytotoxic/suppressor subset (OX8+) in a ratio that approximates the normal ratio in normal unfractionated splenocytes in order to affect inhibition of the transfer of SGVHD. Moreover the specific inducer regulatory activity resides in the OX22-, W3/25+ subset of Th cells.
Hepatitis C virus core protein activates ERK and p38 MAPK in cooperation with ethanol in transgenic mice
Authors: Takeya Tsutsumi, Tetsuro Suzuki, Kyoji Moriya, Yoshizumi Shintani, Hajime Fujie, Hideyuki Miyoshi, Yoshiharu Matsuura, Kazuhiko Koike, Tatsuo Miyamura
Journal: Hepatology (2003)

In human chronic hepatitis C, alcohol intake is a synergistic factor for the acceleration of hepatocarcinogenesis. Recently, we showed a significant increase of reactive oxygen species (ROS) in hepatitis C virus (HCV) core–transgenic mice fed ethanol–containing diets. Because previous studies indicated that ROS is closely associated with mitogen–activated protein kinases (MAPK), we examined activities of c–Jun N–terminal kinase, p38 MAPK, and extracellular signal–regulated kinase (ERK) in the liver of core–transgenic and nontransgenic mice with short–term ethanol feeding. Activity of ERK and p38 MAPK was increased in core–transgenic mice compared with nontransgenic mice, whereas neither ERK nor p38 MAPK was activated in core–transgenic mice with normal diets. In addition, activity of cyclic–AMP and serum responsive element, downstream pathways of p38 MAPK and ERK, was also increased. Comparison of gene expression profiles by cDNA microarray and real–time PCR revealed that galectin–1, which is associated with cell transformation, was significantly increased in ethanol–fed core–transgenic mice. On the other hand, glutathione S–transferase (GST), which plays a key role in protecting cells from oxidative stress, was decreased. In conclusion, these results suggest that HCV core protein cooperates with ethanol for the activation of some MAPK pathways, and leads to the modulation of several genes, contributing to the pathogenesis of liver disease of HCV– infected patients with high ethanol consumption. (Hepatology 2003;38:820-828).
A simple electrocardiographic method to predict patency of the infarct-related artery after fibrinolytic therapy
Authors: Howard A. Cooper, James A. deLemos, Marc S. Sabatine, David A. Morrow, Graham C. Wong, Carolyn H. McCabe, Sabina A. Murphy, Michael Gibson, Robert P. Giugliano, Elliott M. Antman, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2003)
The Chinese herbal medicine formula MSSM-002 suppresses allergic airway hyperreactivity and modulates TH1/TH2 responses in a murine model of allergic asthma
Authors: Xiu-Min Li, Chih-Kang Huang, Teng-Fei Zhang, Ariel A. Teper, Kamal Srivastava, Brian H. Schofield, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2000)
Effects of Hydroxychloroquine on Symptomatic Improvement in Primary Sjögren Syndrome
Authors: Jacques-Eric Gottenberg, Philippe Ravaud, Xavier Puéchal, Véronique Le Guern, Jean Sibilia, Vincent Goeb, Claire Larroche, Jean-Jacques Dubost, Stéphanie Rist, Alain Saraux, Valérie Devauchelle-Pensec, Jacques Morel, Gilles Hayem, Pierre Hatron, Aleth Perdriger, Damien Sene, Charles Zarnitsky, Djilali Batouche, Valérie Furlan, Joelle Benessiano, Elodie Perrodeau, Raphaele Seror, Xavier Mariette
Journal: JAMA (2014)

Primary Sjögren syndrome is a systemic autoimmune disease characterized by mouth and eye dryness, pain, and fatigue. Hydroxychloroquine is the most frequently prescribed immunosuppressant for the syndrome. However, evidence regarding its efficacy is limited.To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sjögren syndrome: dryness, pain, and fatigue.From April 2008 to May 2011, 120 patients with primary Sjögren syndrome according to American-European Consensus Group Criteria from 15 university hospitals in France were randomized in a double-blind, parallel-group, placebo-controlled trial. Participants were assessed at baseline, week 12, week 24 (primary outcome), and week 48. The last follow-up date for the last patient was May 15, 2012.Patients were randomized (1:1) to receive hydroxychloroquine (400 mg/d) or placebo until week 24. All patients were prescribed hydroxychloroquine between weeks 24 and 48.The primary end point was the proportion of patients with a 30% or greater reduction between weeks 0 and 24 in scores on 2 of 3 numeric analog scales (from 0 [best] to 10 [worst]) evaluating dryness, pain, and fatigue.At 24 weeks, the proportion of patients meeting the primary end point was 17.9% (10/56) in the hydroxychloroquine group and 17.2% (11/64) in the placebo group (odds ratio, 1.01; 95% CI, 0.37-2.78; P = .98). Between weeks 0 and 24, the mean (SD) numeric analog scale score for dryness changed from 6.38 (2.14) to 5.85 (2.57) in the placebo group and 6.53 (1.97) to 6.22 (1.87) in the hydroxychloroquine group. The mean (SD) numeric analog scale score for pain changed from 4.92 (2.94) to 5.08 (2.48) in the placebo group and 5.09 (3.06) to 4.59 (2.90) in the hydroxychloroquine group. The mean (SD) numeric analog scale for fatigue changed from 6.26 (2.27) to 5.72 (2.38) in the placebo group and 6.00 (2.52) to 5.94 (2.40) in the hydroxychloroquine group. All but 1 patient in the hydroxychloroquine group had detectable blood levels of the drug. Hydroxychloroquine had no efficacy in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. During the first 24 weeks, there were 2 serious adverse events in the hydroxychloroquine group and 3 in the placebo group; in the last 24 weeks, there were 3 serious adverse events in the hydroxychloroquine group and 4 in the placebo group.Among patients with primary Sjögren syndrome, the use of hydroxychloroquine compared with placebo did not improve symptoms during 24 weeks of treatment. Further studies are needed to evaluate longer-term outcomes.clinicaltrials.gov Identifier: NCT00632866.
Melanomas in renal transplant recipients: the London experience, and invitation to participate in a European study*
Authors: V.L. Brown, R.N. Matin, R. Cerio, M.E. Leedham-Green, C.M. Proby, C.A. Harwood
Journal: British Journal of Dermatology (2006)

Journal Article Melanomas in renal transplant recipients: the London experience, and invitation to participate in a European study* Get access V.L. Brown, V.L. Brown Centre for Cutaneous Research, Institute of Cell and Molecular Science Search for other works by this author on: Oxford Academic Google Scholar R.N. Matin, R.N. Matin Centre for Cutaneous Research, Institute of Cell and Molecular Science Search for other works by this author on: Oxford Academic Google Scholar R. Cerio, R. Cerio Centre for Cutaneous Research, Institute of Cell and Molecular ScienceDepartment of Pathology, Bart's and the London Queen Mary's School of Medicine and Dentistry, London E1 2AT, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.E. Leedham‐Green, M.E. Leedham‐Green Centre for Cutaneous Research, Institute of Cell and Molecular Science Search for other works by this author on: Oxford Academic Google Scholar C.M. Proby, C.M. Proby Centre for Cutaneous Research, Institute of Cell and Molecular Science Search for other works by this author on: Oxford Academic Google Scholar C.A. Harwood C.A. Harwood Centre for Cutaneous Research, Institute of Cell and Molecular Science Correspondence: Catherine Harwood. E‐mail: caharwood@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 1, 1 January 2007, Pages 165–167, https://doi.org/10.1111/j.1365-2133.2006.07567.x Published: 01 January 2007
Conflicts of Interest, Continued
Authors: David A. Hyman
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The article by Dr Morreim<sup>1</sup>and the accompanying commentaries<sup>2,3</sup>on conflict of interest were most interesting. However, she utterly fails to explain why common law principles of the sort she describes have not already been effective at mandating disclosure and enforcing fiduciary duties. What evidence there is suggests that physicians have disregarded even explicit statutory requirements of disclosure (<i>Wall Street Journal</i>. March 1, 1989:A1, A6). The reason the common law approach will never work is that in these entrepreneurial arrangements, there is no potential plaintiff to raise these issues. Unlike an informed consent case, no damages are traceable to the failure to disclose. Thus, there is no incentive to bring suit, and no reason to comply with the common law. Dr Morreim also is mistaken in her assertion that the proposed federal initiatives may "occasion antitrust concerns." It is axiomatic that state action is immune
Issues in Using Human Variability Distributions to Estimate Low-Dose Risk
Authors: Kenny S. Crump, Weihsueh A. Chiu, Ravi P. Subramaniam
Journal: Environmental Health Perspectives (2009)

The National Research Council (NRC) Committee on Improving Risk Analysis Approaches Used by the U.S. EPA (Environmental Protection Agency) recommended that low-dose risks be estimated in some situations using human variability distributions (HVDs). HVD modeling estimates log-normal distributions from data on pharmacokinetic and pharmacodynamic variables that affect individual sensitivities to the toxic response. These distributions are combined into an overall log-normal distribution for the threshold dose (dose below which there is no contribution to a toxic response) by assuming the variables act independently and multiplicatively. This distribution is centered at a point-of-departure dose that is usually estimated from animal data. The resulting log-normal distribution is used to quantify low-dose risk.We examined the implications of various assumptions in HVD modeling for estimating low-dose risk.The assumptions and data used in HVD modeling were subjected to rigorous scrutiny.We found that the assumption that the variables affecting human sensitivity vary log normally is not scientifically defensible. Other distributions that are equally consistent with the data provide very different estimates of low-dose risk. HVD modeling can also involve an assumption that a threshold dose defined by dichotomizing a continuous apical response has a log-normal distribution. This assumption is shown to be incompatible (except under highly specialized conditions) with assuming that the continuous apical response itself is log normal. However, the two assumptions can lead to very different estimates of low-dose risk. The assumption in HVD modeling that the threshold dose can be expressed as a function of a product of independent variables lacks phenomenological support. We provide an example that shows that this assumption is generally invalid.In view of these problems, we recommend caution in the use of HVD modeling as a general approach to estimating low-dose risks from human exposures to toxic chemicals.
THE PREVENTIVE EFFECT OF THE NORDIC HAMSTRING EXERCISE ON HAMSTRING INJURIES IN AMATEUR SOCCER PLAYERS: A RANDOMIZED CONTROLLED TRIAL
Authors: N van der Horst, D Wouter Smits, J Petersen, E Goedhart, F Backx
Journal: British Journal of Sports Medicine (2014)

Background Hamstring injuries are the most common muscle injuries in male amateur soccer. Eccentric strength of the hamstrings is recognized as an important modifiable risk factor, leading to the development of preventive exercises such as the Nordic Hamstring Exercise. Objective This study aims to investigate the preventive effect of the Nordic Hamstring Exercise on the incidence and severity of hamstring injuries in male amateur soccer players. Design Cluster-randomized controlled trial with soccer teams as the unit of cluster. Setting Dutch first class amateur field soccer. Participants Male amateur soccer players (mean age 24.5 years, SD 3.8 years) from 40 teams were allocated to intervention (n=309 players) or control group (n=310 players). Risk factor assessment The intervention group was instructed to perform 25 sessions of the Nordic Hamstring Exercise within a period of 13 weeks during the first months of 2013. Both the intervention group and control group performed regular soccer training and were followed for hamstring injury incidence and severity during the calendar year 2013. At baseline, personal characteristics (e.g. age, injury history, field position) were gathered from all participants via questionnaire. Main outcome measurements Primary outcomes are initial and recurrent hamstring injury incidence (number of hamstring injuries) and injury severity (number of days injured). Results Interim analysis after intervention (2 months follow-up) show a total of 2 hamstring injuries in intervention group vs 12 hamstring injuries in control group (χ 2 =7.5, P&lt;.05). Regarding injury severity, no difference was found between intervention and control group ( t =0.3, P=.77). Conclusions Preliminary analyses during the summer break show substantial hamstring injury incidence reduction by incorporating the Nordic Hamstring Exercise in regular training. With a total follow-up of 9 months, final analyses (survival analyses including the number of injuries per 1000 playing hours) will be performed in January 2014.
Trauma services must improve
Authors: David O Kessel, Anthony A Nicholson
Journal: BMJ (2008)

The proposed algorithm in Jansen et al’s review reiterates old dogma1 2 and contributes to the UK having a higher trauma death rate than most developed countries. The authors failed to discuss why and how trauma services need to improve. The incidence of major trauma is relatively low in the UK and in the absence of coordinated trauma service provision the NHS response …
Comparison of the Numerical and Clinical Accuracy of Four Continuous Glucose Monitors
Authors: Boris Kovatchev, Stacey Anderson, Lutz Heinemann, William Clarke
Journal: Diabetes Care (2008)

In their comments on our assessment of the accuracy of four continuous glucose monitoring (CGM) sensors, Brauker and Matsubara (1) correctly point out that our presented studies employed hyperinsulinemic-euglycemic and hypoglycemic clamps, which tested the four devices (Guardian, DexCom 3-day sensor, Navigator, and Glucoday) close to the limits of their stated glucose range. We agree that such a test goes beyond evaluation of the devices per their …
MILK-MIXTURES AS FOOD FOR INFANTS.
Authors: EDWIN ROSENTHAL
Journal: JAMA (1898)

The ideal nourishment for a child is mother's milk. Nature and nature's laws have wisely ordained that the child, whose digestion is unsuitable to the foods of matured years, should be provided with nourishment which in the nature of things is most simple and bears with it the vital ingredients necessary to the child's growth. When, by certain causes, the natural method of feeding the infant is interfered with, artificial means are at hand to become the substitute for the mother and bring to the child such food as is alike acceptable to its taste and digestion, and which will add to its growth, prevent disease, and assure it a healthy childhood. As the feeding by the mother or the "wet nurse" is called the "natural" method, so is the other, by reason of its application, entitled the "artificial" method of nourishing, and the sucklings so reared are termed "bottle
ORALLY ADMINISTERED HEXAMETHONIUM CHLORIDE IN HYPERTENSION
Authors: John H. Moyer
Journal: JAMA (1953)

Causative factors in the development of hypertension are numerous; however, one common denominator in the hypertensive state appears to be sympathetic predominance over the vasoconstrictor mechanisms responsible for maintaining arterial blood pressure. Today, there are available a number of therapeutic agents that are capable of lowering the blood pressure by "blocking" the flow of nervous impulses over the sympathetic nervous system. The majority of these drugs are impractical for routine use, because of the development of tolerance or the presence of untoward side-effects or because they are destroyed in the gastrointestinal tract and must, therefore, be given parenterally. Despite this fact, great impetus has been given to the search for more effective agents that can be administered orally and that will lower the blood pressure on a long-term basis and thus arrest the progression of the disease. Frequently, original reports on potential hypotensive drugs are enthusiastic, yet, when the drugs