tbuckley/cabot-search huggingface dataset:
A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles
Authors: Nicola Low, Ashish Bavdekar, Lakshmanan Jeyaseelan, Siddhivinayak Hirve, Kavitha Ramanathan, Nicholas J. Andrews, Naseem Shaikh, Ramesh S. Jadi, Arunachalam Rajagopal, Kevin E. Brown, David Brown, James B. Fink, Oommen John, Pippa Scott, A. Ximena Riveros-Balta, Michel Greco, Rajeev Dhere, Prasad S. Kulkarni, Ana Maria Henao Restrepo
Journal: New England Journal of Medicine (2015)

Aerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent.We conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points.A total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of -9.3 percentage points [95% CI, -12.3 to -6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups.Aerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity. (Funded by the Bill and Melinda Gates Foundation; Measles Aerosol Vaccine Project Clinical Trials Registry-India number, CTRI/2009/091/000673.).
Inhibition of autoimmune neuropathological process by treatment with an iron-chelating agent.
Authors: N Bowern, I A Ramshaw, I A Clark, P C Doherty
Journal: The Journal of Experimental Medicine (1984)

Lewis rats that are primed with guinea pig spinal cord homogenized in complete Freund's adjuvant (GPSCH-CFA) develop overt symptoms of experimental allergic encephalomyelitis (EAE). Treatment with the iron-chelating agent, desferrioxamine B mesylate (DFOM), at various times before the onset of EAE, dramatically suppressed both the severity and duration of disease. When DFOM was administered to rats soon after the development of neurological signs, a rapid recovery occurred, though mild, transient symptoms could be seen approximately 1 wk after withdrawal of the drug. Treatment with DFOM was always accompanied by a diminution of T cell responsiveness on the part of the delayed-type hypersensitivity/helper subset and, on histological examination, an absence of inflammatory cells from lesions. Iron is believed to influence both the migration and function of immune effector cells. It can also act as a catalyst in the formation of free radicals, which are highly toxic agents causing tissue damage in sites of inflammation. The mechanisms underlying the effect of DFOM on the severity of EAE, and the possible implications for treatment of multiple sclerosis are discussed.
Alberta Physical Activity and Breast Cancer Prevention Trial: Sex Hormone Changes in a Year-Long Exercise Intervention Among Postmenopausal Women
Authors: Christine M. Friedenreich, Christy G. Woolcott, Anne McTiernan, Rachel Ballard-Barbash, Rollin F. Brant, Frank Z. Stanczyk, Tim Terry, Norman F. Boyd, Martin J. Yaffe, Melinda L. Irwin, Charlotte A. Jones, Yutaka Yasui, Kristin L. Campbell, Margaret L. McNeely, Kristina H. Karvinen, Qinggang Wang, Kerry S. Courneya
Journal: Journal of Clinical Oncology (2010)

We examined how an aerobic exercise intervention influenced circulating estradiol, estrone, sex hormone-binding globulin (SHBG), androstenedione, and testosterone levels, which may be involved in the association between physical activity and breast cancer risk.
The American Society of Clinical Oncology Cancer Foundation Grants Program: A 25-Year Report and a Look Toward the Future
Authors: Jennifer C. King, Theodore S. Lawrence, Sharon B. Murphy, Nancy E. Davidson, Robert J. Mayer
Journal: Journal of Clinical Oncology (2010)

The American Society of Clinical Oncology (ASCO) Grants Program began in 1984 with a single $16,000 grant to a young investigator for start-up research funding. In 2009, the Grants Program, now administered by The ASCO Cancer Foundation, awarded more than $6.5 million to 70 different investigators. This article, celebrating the 25th anniversary of this initiative, describes the history and evolution of the Grants Program, attempts to measure the impact of the program on clinical cancer research through an analysis of the career paths of past recipients, and addresses challenges that the program will face as it enters its second 25 years.
Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB–IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial
Authors: Jean-Yves Douillard, Rafael Rosell, Mario De Lena, Francesco Carpagnano, Rodryg Ramlau, Jose Luis Gonzáles-Larriba, Tomasz Grodzki, Jose Rodrigues Pereira, Alain Le Groumellec, Vito Lorusso, Claude Clary, Antonio J Torres, Jabrail Dahabreh, Pierre-Jean Souquet, Julio Astudillo, Pierre Fournel, Angel Artal-Cortes, Jacek Jassem, Leona Koubkova, Patricia His, Marcello Riggi, Patrick Hurteloup
Journal: The Lancet Oncology (2006)
EWS-FLI1 Suppresses NOTCH-Activated p53 in Ewing's Sarcoma
Authors: Jozef Ban, Idriss M. Bennani-Baiti, Max Kauer, Karl-Ludwig Schaefer, Christopher Poremba, Gunhild Jug, Raphaela Schwentner, Oskar Smrzka, Karin Muehlbacher, Dave N.T. Aryee, Heinrich Kovar
Journal: Cancer Research (2008)

Abstract Although p53 is the most frequently mutated gene in cancer, half of human tumors retain wild-type p53, whereby it is unknown whether normal p53 function is compromised by other cancer-associated alterations. One example is Ewing's sarcoma family tumors (ESFT), where 90% express wild-type p53. ESFT are characterized by EWS-FLI1 oncogene fusions. Studying 6 ESFT cell lines, silencing of EWS-FLI1 in a wild-type p53 context resulted in increased p53 and p21WAF1/CIP1 levels, causing cell cycle arrest. Using a candidate gene approach, HEY1 was linked to p53 induction. HEY1 was rarely expressed in 59 primary tumors, but consistently induced upon EWS-FLI1 knockdown in ESFT cell lines. The NOTCH signaling pathway targets HEY1, and we show NOTCH2 and NOTCH3 to be expressed in ESFT primary tumors and cell lines. Upon EWS-FLI1 silencing, NOTCH3 processing accompanied by nuclear translocation of the activated intracellular domain was observed in all but one p53-mutant cell line. In cell lines with the highest HEY1 induction, NOTCH3 activation was the consequence of JAG1 transcriptional induction. JAG1 modulation by specific siRNA, NOTCH-processing inhibition by either GSI or ectopic NUMB1, and siRNA-mediated HEY1 knockdown all inhibited p53 and p21WAF1/CIP1 induction. Conversely, forced expression of JAG1, activated NOTCH3, or HEY1 induced p53 and p21WAF1/CIP1. These results indicate that suppression of EWS-FLI1 reactivates NOTCH signaling in ESFT cells, resulting in p53-dependent cell cycle arrest. Our data link EWS-FLI1 to the NOTCH and p53 pathways and provide a plausible basis both for NOTCH tumor suppressor effects and oncogenesis of cancers that retain wild-type p53. [Cancer Res 2008;68(17):7100–9]
A Critical Pathway for Management of Patients with Acute Chest Pain Who Are at Low Risk for Myocardial Ischemia: Recommendations and Potential Impact
Authors: Graham Nichol
Journal: Annals of Internal Medicine (1997)

Use of resources for patients with acute chest pain may be improved with clinical strategies that integrate research, Bayesian analysis, and expert opinion.To 1) develop a critical pathway for management of patients with acute chest pain who are at low risk for complications of ischemic heart disease and 2) assess the potential effects of implementation of the pathway on patient safety and resource use.Evidence-based consensus and prospective cohort study.Urban teaching hospital.Patients at least 30 years of age who were seen in the emergency department for chest pain and who did not have a history of trauma or abnormalities on radiologic study.Physician-opinion leaders defined criteria for patient inclusion in the pathway and for remaining on the pathway after 6 or 12 hours of observation. Criteria were defined for appropriateness of direct admission, direct discharge, or 6 hours of observation followed by exercise treadmill testing.Number of patients admitted to the hospital, number of days that patients were hospitalized, and clinical outcome.2898 of 4585 patients (63%) were admitted to the hospital; of the 2898, 1152 (40%) were classified as potentially eligible for the pathway and 1068 (93%) had a benign clinical course during the initial observation period. The 1068 patients had a mean length of stay of 2.8 +/- 4.8 days. If 47% of these patients had been discharged after observation and exercise testing, implementation of the pathway would have reduced the number of admissions by 505 (17%) and days of hospitalization by 1407 (11%).Retrospective analysis suggests that a critical pathway for patients with acute chest pain may substantially reduce resource use. Prospective study is needed to ensure increased efficiency without increased adverse outcomes.
Growth of Head and Neck Squamous Cell Carcinoma in Nude Mice: Potentiation of Laryngeal Carcinoma by 17beta-Estradiol
Authors: K. D. Somers, M. Koenig, G. L. Schechter
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Growth of Head and Neck Squamous Cell Carcinoma in Nude Mice: Potentiation of Laryngeal Carcinoma by 17β-Estradiol Get access Kenneth D. Somers, Kenneth D. Somers Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark Koenig, Mark Koenig Search for other works by this author on: Oxford Academic PubMed Google Scholar Gary L. Schechter Gary L. Schechter 3Head and Neck Tumor Biology Program of the Departments of Microbiology/Immunology and Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical SchoolP.O. Box 1980, Norfolk, VA 23501. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 9, 6 July 1988, Pages 688–691, https://doi.org/10.1093/jnci/80.9.688 Published: 06 July 1988 Article history Received: 04 January 1988 Revision received: 04 April 1988 Accepted: 13 April 1988 Published: 06 July 1988
Bovine and human endothelial cell production of neutrophil chemoattractant activity in response to components of the angiotensin system.
Authors: H W Farber, D M Center, S Rounds
Journal: Circulation Research (1985)

Although there is growing evidence that angiotensin II affects macrophage-mediated inflammatory responses, it is unclear whether it can affect neutrophil-mediated inflammatory responses. Because vascular endothelial cells are capable of releasing neutrophil chemoattractant activity, we attempted to determine whether components of the angiotensin system could affect neutrophil-mediated responses indirectly by stimulating endothelial cells to release neutrophil chemoattractant substances. Cultured bovine and human endothelial cells incubated with angiotensin II released neutrophil chemoattractant activity. This activity appeared within 1 minute of exposure to angiotensin II, and was blocked by saralasin, an angiotensin II antagonist. Angiotensin I also caused release of neutrophil chemoattractant activity, but its effect required conversion to angiotensin II. Bradykinin, another substrate for angiotensin-converting enzyme, did not stimulate appearance of chemoattractant. Chemoattractant generation was not inhibited by indomethacin but was blocked by diethylcarbamazine and 5,8,11,14-eicosatetraynoic acid. This study demonstrates that angiotensin II may influence neutrophil accumulation, via production of neutrophil chemoattractant activity by vascular endothelial cells.
Smoking and Risk of Low- and High-Grade Prostate Cancer: Results from the REDUCE Study
Authors: Tammy Ho, Lauren E. Howard, Adriana C. Vidal, Leah Gerber, Daniel Moreira, Madeleine McKeever, Gerald Andriole, Ramiro Castro-Santamaria, Stephen J. Freedland
Journal: Clinical Cancer Research (2014)

Although the relationship between smoking and prostate cancer risk is inconsistent, some studies show that smoking is associated with prostate cancer mortality. Whether this reflects delayed diagnosis or direct smoking-related effects is unknown. REDUCE, which followed biopsy-negative men with protocol-dictated prostate-specific antigen (PSA)-independent biopsies at 2 and 4 years, provides an opportunity to evaluate smoking and prostate cancer diagnosis with minimal confounding from screening biases.Logistic regression was conducted to test the association between smoking and cancer on the first on-study biopsy (no cancer, low-grade Gleason 4-6, high-grade Gleason 7-10) in REDUCE.Of 6,240 men with complete data and ≥1 on-study biopsy, 2,937 (45.8%) never smoked, 929 (14.5%) were current smokers, and 2,554 (39.8%) were former smokers. Among men with negative first on-study biopsies, smokers were 36% less likely to receive a second on-study biopsy (P < 0.001). At first on-study biopsy, 941 (14.7%) men had cancer. Both current and former smoking were not significantly associated with either total or low-grade prostate cancer (all P > 0.36). Current (OR = 1.44, P = 0.028) but not former smokers (OR = 1.21, P = 0.12) were at increased risk of high-grade disease. On secondary analysis, there was an interaction between smoking and body mass index (BMI; Pinteraction = 0.017): current smokers with BMI ≤ 25 kg/m(2) had an increased risk of low-grade (OR = 1.54, P = 0.043) and high-grade disease (OR = 2.45, P = 0.002), with null associations for BMI ≥ 25 kg/m(2).Among men with elevated PSA and negative pre-study biopsy in REDUCE, in which biopsies were largely PSA independent, smoking was unrelated to overall prostate cancer diagnosis but was associated with increased risk of high-grade prostate cancer.
Systemic lupus erythematosus and genetic variation in the interleukin 1 gene cluster: a population based study in the southeastern United States
Authors: C G Parks
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Interleukin (IL)1α and IL1β, and their endogenous receptor antagonist (IL1Ra), have been related to the pathology of systemic lupus erythematosus (SLE), but the role of IL1 polymorphisms in the aetiology of SLE is unknown. <b>Objective:</b> To examine polymorphisms at IL1α −889(C→T), IL1α +4845(C→T), IL1β −511(C→T), IL1β +3953(G→T), and IL1Ra (86 bp VNTR) in a population based study of SLE in North Carolina and South Carolina. <b>Methods:</b> Genotypes from 230 cases who met ACR classification criteria, and from 275 controls matched for age, sex, and state, were analysed separately for African Americans and whites. Odds ratios (ORs) were estimated by logistic regression models for each locus alone and also after adjusting for polymorphisms at adjacent loci. <b>Results:</b> An increased risk of SLE for the IL1α −889C/C genotype compared with carriage of the −889T allele was found in both African Americans (OR = 3.1, p = 0.001) and whites (OR = 2.9, p = 0.005). In African Americans, carriage of the IL1β −511T allele was associated with a higher risk of SLE than carriage of the −511C/C genotype (OR = 2.4, p = 0.017), independent of variation at IL1α −889. <b>Conclusions:</b> The observed associations support the hypothesis that genetic variation in IL1 is involved in the aetiology of SLE and merit further investigation.
Intensive primary care treatment reduced cardiovascular risk factors at 1 year in screen-detected type 2 diabetes
Authors: C. Raina Elley
Journal: Annals of Internal Medicine (2009)

Source Citation Janssen PG, Gorter KJ, Stolk RP, Rutten GE. Randomised controlled trial of intensive multifactorial treatment for cardiovascular risk in patients with screen-detected type 2 diabetes: 1-year data from the ADDITION Netherlands study. Br J Gen Pract. 2009;59:43-8. 19105915
Can education and electronic prescription improve the use oxygen in acute clinical settings
Authors: Gareth Ebbon, Ajit Thomas, Shiva Bikmalla, Asad Ali, Vikas Punamiya, Ben Beauchamp, Rahul Mukherjee
Journal: European Respiratory Journal (2011)

Introduction:  Recent data on effects of hyperoxia in patients with coronary artery disease, brain injury [1] and post resuscitation patients [2] have shown increased mortality and morbidity. This calls for efforts to reduce unnecessary oxygen use in hospitals, which we instituted via targeted multidisciplinary education and widening the use of electronic prescription of oxygen between 2008 and 2010.   Method:  Cross-sectional point prevalence of oxygen prescribing practice was audited at our teaching hospital in November 2008 and November 2010 excluding Intensive care, paediatric and maternity wards. Between the 2 oxygen audits, we widened and improved electronic prescribing with a multidisciplinary training program on oxygen use for all caregivers.   Results:  At the Nov 2010 point of data collection, 185/1267 (15%) patients were on oxygen. Of these a clear valid oxygen prescription was noted in 149 (81%); 46% of saturations documented were within target range. The proportion of patients in hospital receiving oxygen had reduced from 28% (191/666) since 2008; the presciption rate improved from 57% to 81%.   Conclusion:  With the focus on education, increased awareness through local and national alerts and electronic prescriptions of oxygen, we have noted almost halving of in-hospital oxygen use and higher rates of oxygen prescription. There is however room for improvement in adherence to target oxygen saturation.   References:   1Jancin B. Hyperoxia may be harmful in traumatic brain injury.  Elsevier Global Medical News  (19th December 2006).  2Kilgannon et al. Association between Arterial Hyperoxia Following Resuscitation from Cardiac Arrest and In-Hospital Mortality. JAMA 2010; 303(21):2165-2171.
Surgical Treatment in Cases of Pulmonary Tuberculosis
Authors: H. M. Davies
Journal: BMJ (1923)

TIlE CHEST.IN considering the surgical treatment of pulmonary tuber- culosis, the first point that must be discussed is why and wlhen cases of tuberculosis of the lungs should be treated by operative measures.There are three reasons why surgical treatment may succeed in arresting the disease or in pro- longing life when other means have failed.1.If the resistance of the individual patient is such that it failed hlim only when extremely irun down in health, and
Clinical Trial of the Cytostatic Agent A-139 (2,5-Bis[1-Aziridinyl]-3,6-bis[2-methoxyethoxy]-p-benzoquinone)
Authors: Clyde O. Brindley, Jacob Colsky, Margarida M. Dederick, James F. Holland, Albert H. Owens, Bruce I. Shnider, Emil Frei, M. M. Hreshchyshyn, Hans B. Nevinny, Yuksel Uzer, Ralph Jones
Journal: Cancer Research (1960)

Summary  2,5-Bis[1-Aziridinyl]-3,6-bis(2-methoxyethoxy)-p-benzoquinone was given to a total of 89 patients with far advanced cancer in an attempt to determine the best dose regimen for clinical use. Hemopoietic depression was severe at each of the dose levels used when the drug was given daily intravenously. For comparable total dose per unit time, the hemopoietic depression was less severe when the drug was given once weekly intravenously. Gastrointestinal toxicity was usually mild with both intravenous and oral routes of administration.  Significant antitumor effects occurred with both oral and parenteral administration and were seen in seven out of 68 patients with measurable tumor masses; these included two cases of ovarian carcinoma and one each of lymphoma and of mammary, bronchiolar, uterine, and colon adenocarcinoma.
Risk factors for groin injury in sport: an updated systematic review
Authors: Jackie L Whittaker, Claire Small, Lorrie Maffey, Carolyn A Emery
Journal: British Journal of Sports Medicine (2015)

The identification of risk factors for groin injury in sport is important to develop and implement injury prevention strategies.To identify and evaluate the evidence examining risk factors for groin injury in sport.Nine electronic databases were systematically searched to June 2014. Studies selected met the following criteria: original data; analytic design; investigated a risk factor(s); included outcomes for groin injury sustained during sport participation. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed and two independent authors assessed the quality and level of evidence with the Downs and Black (DB) criteria and Oxford Centre of Evidence-Based Medicine model, respectively.Of 2521 potentially relevant studies, 29 were included and scored. Heterogeneity in methodology and injury definition precluded meta-analyses. The most common risk factors investigated included age, hip range of motion, hip adductor strength and height. The median DB score across studies was 11/33 (range 6-20). The majority of studies represented level 2 evidence (cohort studies) however few considered the inter-relationships between risk factors. There is level 1 and 2 evidence that previous groin injury, higher-level of play, reduced hip adductor (absolute and relative to the hip abductors) strength and lower levels of sport-specific training are associated with increased risk of groin injury in sport.We recommended that investigators focus on developing and evaluating preparticipation screening and groin injury prevention programmes through high-quality randomised controlled trials targeting athletes at greater risk of injury.