tbuckley/cabot-search huggingface dataset:
Impact of Candesartan on Nonfatal Myocardial Infarction and Cardiovascular Death in Patients With Heart Failure
Authors: Catherine Demers
Journal: JAMA (2005)

Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of myocardial infarction (MI), but it is not known whether angiotensin receptor blockers have the same effect.To assess the impact of the angiotensin receptor blocker candesartan on MI and other coronary events in patients with heart failure.The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, a randomized, placebo-controlled study enrolling patients (mean age, 66 [SD, 11] years) with New York Heart Association class II to IV symptoms who were randomly allocated to receive candesartan (target dose, 32 mg once daily) or matching placebo given in addition to optimal therapy for heart failure. Patients were enrolled from March 1999 through March 2001. Of 7599 patients allocated, 4004 (53%) had experienced a previous MI, and 1808 (24%) currently had angina. At baseline, 3125 (41%) were receiving an ACE inhibitor; 4203 (55%), a beta-blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic.The primary outcome of the present analysis was the composite of cardiovascular death or nonfatal MI in patients with heart failure receiving candesartan or placebo.During the median follow-up of 37.7 months, the primary outcome of cardiovascular death or nonfatal MI was significantly reduced in the candesartan group (775 patients [20.4%]) vs the placebo group (868 [22.9%]) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004; number needed to treat [NNT], 40). Nonfatal MI alone was also significantly reduced in the candesartan group (116 [3.1%]) vs the placebo group (148 [3.9%]) (HR, 0.77; 95% CI, 0.60-0.98; P = .03; NNT, 118). The secondary outcome of fatal MI, sudden death, or nonfatal MI was significantly reduced with candesartan (459 [12.1%]) vs placebo (522 [13.8%]) (HR, 0.86; 95% CI, 0.75-0.97; P = .02; NNT, 59). Risk reductions in cardiovascular death or nonfatal MI were similar across predetermined subgroups and the component CHARM trials. There was no impact on hospitalizations for unstable angina or coronary revascularization procedures with candesartan.In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI.
Adoptive transfer of allogeneic Epstein–Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boostsLMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma
Authors: P. Comoli, R. De Palma, S. Siena, A. Nocera, S. Basso, F. Del Galdo, R. Schiavo, O. Carminati, A. Tagliamacco, G.F. Abbate, F. Locatelli, R. Maccario, P. Pedrazzoli
Journal: Annals of Oncology (2003)
Alcohol Consumption, Mediating Biomarkers, and Risk of Type 2 Diabetes Among Middle-Aged Women
Authors: Joline W.J. Beulens, Eric B. Rimm, Frank B. Hu, Henk F.J. Hendriks, Kenneth J. Mukamal
Journal: Diabetes Care (2008)

The purpose of this study was to investigate whether adiponectin concentrations and biomarkers of inflammation, endothelial dysfunction, and insulin resistance mediate the association between alcohol consumption and diabetes.In a nested case-control study of 705 women with incident diabetes and 787 matched control subjects, we examined the adjusted relationship between baseline alcohol consumption and risk of diabetes before and after adjustment for markers of inflammation/endothelial dysfunction (C-reactive protein, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, tumor necrosis factor-alpha receptor 2, and interleukin-6), fasting insulin, and adiponectin concentrations.Alcohol consumption was associated with a decreased risk of diabetes (odds ratio per 12.5 g/day increment in alcohol use 0.58; 95% CI 0.49-0.69; P < 0.001). Adjustment for BMI attenuated the association by 25%. None of the markers of inflammation or fasting insulin appeared to account for >2% of the observed relationship. Without adjustment for BMI, these biomarkers individually explained slightly more of the association, but <10% in all cases. Adiponectin accounted for 25% in a fully adjusted model and for 29% without adjustment for BMI.In this population of women, alcohol consumption was inversely associated with risk of type 2 diabetes. Adiponectin appeared to be a mediator of this association, but circulating biomarkers of inflammation, endothelial dysfunction, and fasting insulin did not explain this association. These results suggest that further research is needed into the potentially mediating roles of other biomarkers affected by alcohol consumption.
Effect of urgent treatment for transient ischaemic attack and minor stroke on disability and hospital costs (EXPRESS study): a prospective population-based sequential comparison
Authors: Ramon Luengo-Fernandez, Alastair M Gray, Peter M Rothwell
Journal: The Lancet Neurology (2009)

BackgroundEvidence is available on the effectiveness and costs of treatments to reduce stroke risk in long-term secondary prevention. However, there are few data on the costs and outcomes of urgent assessment and treatment after the onset of transient ischaemic attack (TIA) or minor stroke. The Early use of eXisting PREventive Strategies for Stroke (EXPRESS) study showed that urgent assessment and treatment reduced the 90-day risk of recurrent stroke by about 80%. We now report the effect of the EXPRESS intervention on admissions to hospital, costs, and disability.MethodsEXPRESS was a prospective population-based before (phase 1: April 1, 2002, to Sept 30, 2004) versus after (phase 2: Oct 1, 2004, to March 31, 2007) study of the effect of early assessment and treatment of TIA or minor stroke on the risk of early recurrent stroke. This report assesses the effect of the introduction of the phase 2 clinic on admissions to hospital within 90 days, hospital bed-days, hospital costs, and 6-month new disability (progression from no disability before event [modified Rankin scale score ≤2 points] to disability at 6 months [modified Rankin scale score >2 points]) or death, compared with the phase 1 clinic. To assess the main predictors of these outcomes, multivariate regression analyses were done.FindingsThe 90-day risk of fatal or disabling stroke was reduced in phase 2 (1 of 281 vs 16 of 310; p=0·0005). Hospital admissions for recurrent stroke were also lower in phase 2 than in phase 1 (5 vs 25; p=0·001), which reduced the overall number of hospital bed-days compared with phase 1 (672 vs 1957 days; p=0·017). Hospital bed-days for admissions to hospital due to vascular causes were also lower in phase 2 (427 vs 1365 days; p=0·016), which generated savings of £624 per patient referred to the phase 2 clinic (p=0·028). Results from the multivariate analyses showed that assessment in phase 2 was an independent predictor of reduced disability, days in hospital, and costs.InterpretationUrgent assessment and treatment of patients with TIA or minor stroke who were referred to a specialist outpatient clinic reduced subsequent hospital bed-days, acute costs, and 6-month disability.FundingUK Department of Health; UK Medical Research Council; Dunhill Medical Trust; Stroke Association; BUPA Foundation; National Institute for Health Research; Thames Valley Primary Care Research Partnership; Oxford Partnership Comprehensive Biomedical Research Centre.
Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma
Authors: Hendrik Witt, Stephen C. Mack, Marina Ryzhova, Sebastian Bender, Martin Sill, Ruth Isserlin, Axel Benner, Thomas Hielscher, Till Milde, Marc Remke, David T.W. Jones, Paul A. Northcott, Livia Garzia, Kelsey C. Bertrand, Andrea Wittmann, Yuan Yao, Stephen S. Roberts, Luca Massimi, Tim Van Meter, William A. Weiss, Nalin Gupta, Wiesia Grajkowska, Boleslaw Lach, Yoon-Jae Cho, Andreas von Deimling, Andreas E. Kulozik, Olaf Witt, Gary D. Bader, Cynthia E. Hawkins, Uri Tabori, Abhijit Guha, James T. Rutka, Peter Lichter, Andrey Korshunov, Michael D. Taylor, Stefan M. Pfister
Journal: Cancer Cell (2011)
Nucleic Acid Aptamer-Guided Cancer Therapeutics and Diagnostics: the Next Generation of Cancer Medicine
Authors: Dongxi Xiang, Sarah Shigdar, Greg Qiao, Tao Wang, Abbas Z. Kouzani, Shu-Feng Zhou, Lingxue Kong, Yong Li, Chunwen Pu, Wei Duan
Journal: Theranostics (2014)

Conventional anticancer therapies, such as chemo- and/or radio-therapy are often unable to completely eradicate cancers due to abnormal tumor microenvironment, as well as increased drug/radiation resistance. More effective therapeutic strategies for overcoming these obstacles are urgently in demand. Aptamers, as chemical antibodies that bind to targets with high affinity and specificity, are a promising new and novel agent for both cancer diagnostic and therapeutic applications. Aptamer-based cancer cell targeting facilitates the development of active targeting in which aptamer-mediated drug delivery could provide promising anticancer outcomes. This review is to update the current progress of aptamer-based cancer diagnosis and aptamer-mediated active targeting for cancer therapy in vivo, exploring the potential of this novel form of targeted cancer therapy.
Response to Comment on: Richter et al. Serum Levels of the Adipokine Progranulin Depend on Renal Function. Diabetes Care 2013;36:410–414
Authors: Judit Richter, Thomas Ebert, Jens-Uwe Stolzenburg, Anja Dietel, Lisa Hopf, Janka Hindricks, Susan Kralisch, Jürgen Kratzsch, Mathias Fasshauer
Journal: Diabetes Care (2013)

We thank Dr. Triebel (1) for his comments regarding our recent findings on circulating progranulin in relation to renal function.

Concerning our data on progranulin in spot urine, the adipokine was quantified in samples of 29 sex-matched patients of each chronic kidney disease stage ( N = 145), which were randomly assigned using SPSS software version 18.0 (IBM, Armonk, NY). In these experiments, median urinary progranulin was only significantly lower in chronic kidney disease stage 4 as compared with stage 2 patients …
Promoting Smoking Cessation in the United States: Effect of Public Service Announcements on the Cancer Information Service Telephone line
Authors: J. P. Pierce, D. M. Anderson, R. M. Romano, H. I. Meissner, J. C. Odenkirchen
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Promoting Smoking Cessation in the United States: Effect of Public Service Announcements on the Cancer Information Service Telephone line Get access John P. Pierce, John P. Pierce * University of California (San Diego) Cancer Center *Correspondence to : John P. Pierce, Ph.D., UCSD Cancer Prevention Program, 0901, 2251 San Diego Ave., Ste. B-111, San Diego, CA 92110. Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Michael Anderson, D. Michael Anderson Divison of Cancer Prevention and Control, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Rose Mary Romano, Rose Mary Romano Office on Smoking and Health, Center for Chronic Disease Prevention and Health Promotion, Centers for Disease ControlAtlanta, Ga Search for other works by this author on: Oxford Academic PubMed Google Scholar Helen I. Meissner, Helen I. Meissner Divison of Cancer Prevention and Control, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar JoAnne C. Odenkirchen JoAnne C. Odenkirchen Divison of Cancer Prevention and Control, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 9, 6 May 1992, Pages 677–683, https://doi.org/10.1093/jnci/84.9.677 Published: 06 May 1992 Article history Received: 03 June 1991 Revision received: 25 November 1991 Accepted: 06 January 1992 Published: 06 May 1992
Advances in the Development of Cancer Therapeutics Directed against the RAS-Mitogen-Activated Protein Kinase Pathway
Authors: Judith S. Sebolt-Leopold
Journal: Clinical Cancer Research (2008)

Abstract Among mammalian mitogen-activated protein kinase (MAPK) signaling cascades, the extracellular signal-related kinase (ERK) pathway has received the most attention in the oncology drug discovery arena. By virtue of its central role in promoting proliferation, survival, and metastasis, this pathway directly affects both the formation and progression of human tumors. The identification of non–ATP-competitive inhibitors of the MAPK kinase MAPK/ERK kinase (MEK) resulted in the first demonstration that the ERK pathway could be effectively shut down in a highly selective fashion. Subsequent discovery of the oncogenic nature of B-raf kinase led to the escalation of drug discovery efforts revolving around MEK and RAF. The emergence of multiple drug candidates targeting these downstream kinases provides us with the means for validating the importance of the RAS-RAF-MEK-ERK signaling cascade in human tumors. This article highlights the lessons learned in the clinical evaluation of MAPK pathway inhibitors as anticancer agents and the complexities surrounding optimization of their therapeutic potential in light of the challenges posed by genetic heterogeneity within patient populations.
Increased airway closure is a determinant of airway hyperresponsiveness
Authors: D. G. Chapman, N. Berend, G. G. King, C. M. Salome
Journal: European Respiratory Journal (2008)

In order to investigate whether increased airway closure is a component of airway hyperresponsiveness (AHR), airway closure was compared during induced bronchoconstriction in 62 asthmatic, 41 nonasthmatic nonobese (control) and 20 nonasthmatic obese (obese) subjects. Airway closure and airway narrowing were measured by spirometry as percentage change in forced vital capacity (%ΔFVC) and change in forced expiratory ratio (ΔFER), respectively. Multiple regression analyses were used to assess the determinants of AHR, assessed by the dose response slope (DRS). The DRS was significantly increased in asthmatics compared with controls but did not differ between obese and controls. The spirometric predictors of logDRS were baseline FER, ΔFER, body mass index (BMI) and %ΔFVC. There was a negative relationship between BMI and logDRS in the regression, suggesting a protective effect. The present findings suggest that the extent of airway closure during induced bronchoconstriction is a determinant of airway hyperresponsiveness, independent of the level of airway narrowing. However, after adjusting for airway closure, obesity appears to protect against airway hyperresponsiveness.
Improving the quality and clinical relevance of diagnostic studies
Authors: Frans H Rutten, Karel G M Moons, Arno W Hoes
Journal: BMJ (2006)

Bachmann and colleagues show that few studies on diagnostic accuracy include calculations of sample size. Most such studies are too small to provide precise estimates of the overall sensitivity and specificity of a test, let alone for subgroups,1 and few studies have investigated this issue. We support the authors' recommendation that all diagnostic studies should calculate sample size at the planning phase, especially as straightforward methods are available for assessing simple proportions, such as sensitivity and specificity. However, they used the specificity and sensitivity of single tests to calculate sample size (understandable given the predominance …
HERPES ZOSTER: ITS CAUSE, AND ASSOCIATION WITH VARICELLA
Authors: R. C. Low
Journal: BMJ (1919)

BEFO.RE passing to tlle discussion of the l)robable cause of lherpes zoster and the relation of tlat disease to varicella, I slhall give a short note of casets whichl lhave comie unider my notice.My experienice is limited to tllree observations.CASE I.In October, 1915, I was asked to see a gentlemani suiffering from lherpes zoster affectinig tile skiii area supplied by tile first divisioni of the fifth nerve of the right side.He had a very severe attack, the whole right side of the face beinig swolleni atnd oedlemiiatous, the ri(ht eye completely closed, aud( the rigJht si(le of the forelhead and(i ainterior part of the scalp covered with a slotighliig and 5]sippuratinigf crtisted eruiption.Althoughi the eyelids were very swvoliel and the conijiunctiva oedematous and(l iinjected, there was no eruptioin oni or uleerationi of the corinea.Tlle paini was intense, accompalnie(d bir sleeplessness aiI a general feelinig of depressioni.rhe piatient was a strong otlherwise lhealtlhy man, age(d 43.He madle a slow recovery, the eye givinlg trouble for some time.Now (three years later) a scar is visible at the site of the previous eruption, and there is still a considerable degree of anaesthesia of that area.I nit1 uired as to whether lie hlad been in contact with a case of herpes zoster or varicella, bilt could trace no souirce of infectiotn.He had never suffered from chickeni-pox.Thlirteen dlays after the patient showed the tirst sign1s of herpes zoster two of his children developed typicAl chicken-pox, anid a fortnight after that other two also showed the same disease.These children were attending school when attacked, but so far as is known had not been in contact witht any case of chicken-pox. CASE 1m.Some months ago a patient under Dr. Norman Walker's charge in the skin wards of the Royal Infirmary, Edinburgh, suffering from lupus vulgaris developed a typical right-sided thoracic herpes zoster.TIvwo days later a childl in the same ward suffering from seborrhoeic dermatitis developed chicken- pox.Both these patients had beeni in hospital for several weeks previously, so that the infection was probably brought inlto the ward by visitors. CASE III.On October 24th, 1918, a child was admitted to the children's ward of the Deaconess Hospital suffering from tvpical herpes zoster on the right si(de of the body.On November 12th (that is, nineteen days later) another child( in the same ward de- veloped typical chicken-pox.This chiiId liad been in the ward sinice October 21st.
Can a Sex-Biased Human Demography Account for the Reduced Effective Population Size of Chromosome X in Non-Africans?
Authors: A. Keinan, D. Reich
Journal: Molecular Biology and Evolution (2010)

Sex-biased demographic events can result in asymmetries in female and male effective population size that can lead to different patterns of genetic variation on chromosome X than are expected based on the patterns on the autosomes. Previous studies point to a period around the time of the dispersal of anatomically modern humans out of Africa when chromosome X experienced a significant reduction in effective population size relative to the autosomes. Here, we explore whether a sex-biased demographic history could explain these observations. We use coalescent simulations to show that a model of primarily male migration during the out-of-Africa dispersal can produce the striking patterns that are observed when comparing patterns of genetic variation on the autosomes and chromosome X. The model involves a history in which after the founder population of non-Africans lost much of its genetic diversity, subsequent mostly male gene flow from an African source brought new diversity into the population. We also explore two additional models, one of sex-biased generation time and one of a substructured population during the dispersal out of Africa with primarily female migration among demes. These latter models cannot account for the magnitude of the observed reduction in chromosome X effective population size, although it is plausible that they played a more minor role in producing the striking chromosome X/autosome patterns.
Function of aquaporins in female and male reproductive systems
Authors: He-Feng Huang, Rong-Huan He, Chao-Chao Sun, Yu Zhang, Qing-Xia Meng, Ying-Ying Ma
Journal: Human Reproduction Update (2006)

The flow of water and some other small molecules across cell membranes is important in many of the processes underlying reproduction. The fluid movement is strongly associated with the presence of aquaporins (AQPs) in the female and male reproductive systems. It has been suggested that AQPs mediate water movement into the antral follicle and play important roles in follicle development. AQPs are known to be involved in the early stage of spermatogenesis, in the secretion of tubule liquid and in the concentration and storage of spermatozoa. Fluid reabsorption in some regions of the male reproductive tract is under steroid hormone control and could be mediated by various AQPs. Also AQPs take part in the processes of fertilization, blastocyst formation (as the pathway for transtrophoectodermal water movement during cavitation) and implantation. Alterations in the expression and function or regulation of AQPs have already been demonstrated in disorders of the male reproductive system, such as abnormal sperm motility, the abnormal epididymis and infertility seen in cystic fibrosis, and varicocele. This article extensively reviews the distribution of AQPs in mammalian reproductive tissues and discusses their possible physiological and pathophysiological roles.
Intact Suppression of Increased False Recognition in Schizophrenia
Authors: Anthony P. Weiss, Chad S. Dodson, Donald C. Goff, Daniel L. Schacter, Stephan Heckers
Journal: American Journal of Psychiatry (2002)

Recognition memory is impaired in patients with schizophrenia, as they rely largely on item familiarity, rather than conscious recollection, to make mnemonic decisions. False recognition of novel items (foils) is increased in schizophrenia and may relate to this deficit in conscious recollection. By studying pictures of the target word during encoding, healthy adults can suppress false recognition. This study examined the effect of pictorial encoding on subsequent recognition of repeated foils in patients with schizophrenia.The study included 40 patients with schizophrenia and 32 healthy comparison subjects. After incidental encoding of 60 words or pictures, subjects were tested for recognition of target items intermixed with 60 new foils. These new foils were subsequently repeated following either a two- or 24-word delay. Subjects were instructed to label these repeated foils as new and not to mistake them for old target words.Schizophrenic patients showed greater overall false recognition of repeated foils. The rate of false recognition of repeated foils was lower after picture encoding than after word encoding. Despite higher levels of false recognition of repeated new items, patients and comparison subjects demonstrated a similar degree of false recognition suppression after picture, as compared to word, encoding.Patients with schizophrenia displayed greater false recognition of repeated foils than comparison subjects, suggesting both a decrement of item- (or source-) specific recollection and a consequent reliance on familiarity in schizophrenia. Despite these deficits, presenting pictorial information at encoding allowed schizophrenic subjects to suppress false recognition to a similar degree as the comparison group, implying the intact use of a high-level cognitive strategy in this population.
Characterization of oncogenic pathways linked with T cell exclusion in urothelial bladder cancer
Authors: Randy F Sweis, Stefani Spranger, Jason J Luke, Thomas F Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Response to immunotherapies and improved survival are linked to a T cell-inflamed tumor microenvironment, which is characterized by expression of a chemokine and type I interferon gene signature and the presence of CD8+ tumor-infiltrating T cells. In urothelial bladder cancer,