tbuckley/cabot-search huggingface dataset:
Virologic Versus Cytologic Triage of Women With Equivocal Pap Smears: A Meta-analysis of the Accuracy To Detect High-Grade Intraepithelial Neoplasia
Authors: Marc Arbyn, Frank Buntinx, Marc Van Ranst, Evangelos Paraskevaidis, Pierre Martin-Hirsch, Joakim Dillner
Journal: JNCI Journal of the National Cancer Institute (2004)

The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear.Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intraepithelial neoplasia of grade II or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology.The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture II assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture II assay. The ratio of the sensitivity of the Hybrid Capture II assay to that of repeat cytology at a threshold of ASCUS or worse pooled from the four studies that used both triage tests was 1.16 (95% CI = 1.04 to 1.29). The specificity ratio was not statistically different from unity.The published literature indicates that the Hybrid Capture II assay has improved accuracy (higher sensitivity, similar specificity) than the repeat Pap smear using the threshold of ASCUS for an outcome of CIN2+ among women with equivocal cytologic results. The sensitivity of triage at higher cytologic cutoffs is poor.
Comparative Measurements of Hypoxia in Human Brain Tumors Using Needle Electrodes and EF5 Binding
Authors: Sydney M. Evans, Kevin D. Judy, Isolde Dunphy, W. Timothy Jenkins, Peter T. Nelson, Ruth Collins, E. Paul Wileyto, Kevin Jenkins, Stephen M. Hahn, Craig W. Stevens, Alexander R. Judkins, Peter Phillips, Birgit Geoerger, Cameron J. Koch
Journal: Cancer Research (2004)

Abstract Hypoxia is known to be an important prognostic marker in many human cancers. We report the use of two oxygen measurement techniques in human brain tumors and compare these data with semiquantitative histological end points. Oxygenation was measured using the Eppendorf needle electrode and/or EF5 binding in 28 brain tumors. These data were compared with necrosis, mitosis, and endothelial proliferation. In some tumors, absolute EF5 binding was converted to tissue pO2 based on in vitro calibrations. Eppendorf electrode readings could not be used to identify WHO grade 1/2 versus WHO grade 3/4 tumors, they could not differentiate grade 3 versus grade 4 glial-derived neoplasms, nor did they correlate with necrosis or endothelial proliferation scores. EF5 binding increased as the tumor grade increased and was significantly associated with necrosis and endothelial proliferation. There was no statistically significant correlation between the two hypoxia detection techniques, although both methods indicated similar absolute ranges of tissue pO2. There was substantial inter- and intratumoral heterogeneity of EF5 binding in WHO grade 4 glial neoplasms. The majority of cells in glial-derived tumor had levels of hypoxia that were mild to moderate (defined herein as 10% to 0.5% pO2) rather than severe (defined as approximately 0.1% pO2). Immunohistochemical detection of EF5 binding tracks histological parameters in adult brain tumors, with increased binding associated with increasing necrosis and endothelial proliferation. The proportion of moderately to severely hypoxic cells is relatively low, even in the high-grade tumors. Human brain tumors are dominated by oxic to moderately hypoxic cells.
Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection
Authors: Timothy D Planche, Kerrie A Davies, Pietro G Coen, John M Finney, Irene M Monahan, Kirsti A Morris, Lily O'Connor, Sarah J Oakley, Cassie F Pope, Mike W Wren, Nandini P Shetty, Derrick W Crook, Mark H Wilcox
Journal: The Lancet Infectious Diseases (2013)

Diagnosis of Clostridium difficile infection is controversial because of many laboratory methods, compounded by two reference methods. Cytotoxigenic culture detects toxigenic C difficile and gives a positive result more frequently (eg, because of colonisation, which means that individuals can have the bacterium but no free toxin) than does the cytotoxin assay, which detects preformed toxin in faeces. We aimed to validate the reference methods according to clinical outcomes and to derive an optimum laboratory diagnostic algorithm for C difficile infection.In this prospective, multicentre study, we did cytotoxigenic culture and cytotoxin assays on 12,420 faecal samples in four UK laboratories. We also performed tests that represent the three main targets for C difficile detection: bacterium (glutamate dehydrogenase), toxins, or toxin genes. We used routine blood test results, length of hospital stay, and 30-day mortality to clinically validate the reference methods. Data were categorised by reference method result: group 1, cytotoxin assay positive; group 2, cytotoxigenic culture positive and cytotoxin assay negative; and group 3, both reference methods negative.Clinical and reference assay data were available for 6522 inpatient episodes. On univariate analysis, mortality was significantly higher in group 1 than in group 2 (72/435 [16·6%] vs 20/207 [9·7%], p=0·044) and in group 3 (503/5880 [8·6%], p<0·001), but not in group 2 compared with group 3 (p=0·4). A multivariate analysis accounting for potential confounders confirmed the mortality differences between groups 1 and 3 (OR 1·61, 95% CI 1·12-2·31). Multistage algorithms performed better than did standalone assays.We noted no increase in mortality when toxigenic C difficile alone was present. Toxin (cytotoxin assay) positivity correlated with clinical outcome, and so this reference method best defines true cases of C difficile infection. A new diagnostic category of potential C difficile excretor (cytotoxigenic culture positive but cytotoxin assay negative) could be used to characterise patients with diarrhoea that is probably not due to C difficile infection, but who can cause cross-infection.
Inhibition of Neurotensin Receptor 1 Selectively Sensitizes Prostate Cancer to Ionizing Radiation
Authors: Nicholas C.K. Valerie, Eli V. Casarez, John O. DaSilva, Marya E. Dunlap-Brown, Sarah J. Parsons, George P. Amorino, Jaroslaw Dziegielewski
Journal: Cancer Research (2011)

Abstract Radiotherapy combined with androgen depletion is generally successful for treating locally advanced prostate cancer. However, radioresistance that contributes to recurrence remains a major therapeutic problem in many patients. In this study, we define the high-affinity neurotensin receptor 1 (NTR1) as a tractable new molecular target to radiosensitize prostate cancers. The selective NTR1 antagonist SR48692 sensitized prostate cancer cells in a dose- and time-dependent manner, increasing apoptotic cell death and decreasing clonogenic survival. The observed cancer selectivity for combinations of SR48692 and radiation reflected differential expression of NTR1, which is highly expressed in prostate cancer cells but not in normal prostate epithelial cells. Radiosensitization was not affected by androgen dependence or androgen receptor expression status. NTR1 inhibition in cancer cell–attenuated epidermal growth factor receptor activation and downstream signaling, whether induced by neurotensin or ionizing radiation, establish a molecular mechanism for sensitization. Most notably, SR48692 efficiently radiosensitized PC-3M orthotopic human tumor xenografts in mice, and significantly reduced tumor burden. Taken together, our findings offer preclinical proof of concept for targeting the NTR1 receptor as a strategy to improve efficacy and outcomes of prostate cancer treatments using radiotherapy. Cancer Res; 71(21); 6817–26. ©2011 AACR.
Antioxidant Gene Polymorphisms and Susceptibility to a Rapid Decline in Lung Function in Smokers
Authors: Jian-Qing He, Jian Ruan, John E. Connett, Nicholas R. Anthonisen, Peter D. Paré, Andrew J. Sandford
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Oxidative stress is believed to play an important role in the pathogenesis of smoking-induced chronic obstructive pulmonary disease. We hypothesized that polymorphisms of antioxidant genes glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, and heme oxygenase-1 (HMOX1) would be associated with susceptibility to accelerated decline of lung function in smokers. We genotyped 621 subjects (299 rapid decliners [change in forced expiratory volume in 1 second (DeltaFEV(1)) = -152 +/- 2.5 ml/year] and 322 nondecliners [DeltaFEV(1) = +15 +/- 1.5 ml/year]) selected from among smokers followed for 5 years in the National Heart, Lung, and Blood Institute Lung Health Study. Because genotype frequencies were different between ethnic groups, we limited the association study to 594 whites (286 rapid decliners and 308 nondecliners). None of the genotypes studied had a statistically significant effect on decline of lung function when analyzed separately. There was an association between rapid decline of lung function and presence of all three GST polymorphisms (odds ratio [OR] = 2.83; p = 0.03). A combination of a family history of chronic obstructive pulmonary disease with GSTP1 105Ile/Ile genotype was also associated with rapid decline of lung function (OR = 2.20; p = 0.01). However, due to the multiple comparisons that were made, these associations may represent type 1 error. There was no association between HMOX1 (GT)n alleles and the rate of decline in lung function in smokers.
Factors associated with relapse in smoking cessation
Authors: Teresa Gomes, Ines Ladeira, Miguel Guimaraes, Albertina Correia, Julia Valério, Ivone Pascoal
Journal: European Respiratory Journal (2012)

Background: Smoking cessation is cost effective, but the maintenance of abstinence is a challenge.  Objective: To determine factors associated with relapse in the first 12 months after cessation.  Method: Comparative study of 69 patients who relapsed with 80 patients who did not in that period. Demographic, socioeconomic, comorbidities, smoking history, friends/cohabitants smoking habits, Fagerstrom Scale, Test of Richmond, adherence to therapy, lapses (occasional use) and relapse were analyzed. Data analysis used SPSS,significance level p ≤ 0.05.  Results: There were no age or gender differences between groups. 38.3% reported the emotional factor as the reason for relapse. We found associations between the occurrence of relapse and male gender (OR 1.14,CI 0.42-1.79), primary school qualifications (OR 1.2,CI 0.48-1.84), being married (OR 2.13,CI 0.60-7.67), having children above 18 y-old (OR 2.59,CI 0.92-7.34), indoor smoking (OR 1.14,CI 0.59-2.19), smoking at work (OR 1.17,CI 0.53-2.56) smoker friends (OR 2.06,CI 1.01-4.12), presence of comorbidities (OR 1.43,CI 0.36-1.59), smoking habits onset before 18 y-old (OR 1.20,CI 0.43-1.69), no previous attempts (OR 1.98,CI 1.03-3.81), high dependency (OR 1.2,CI 0.52-2:28), no therapy adherence (OR 2.7,CI 0.18-2.78), withdrawal syndrome (OR 1.52,CI 0.71-3.26) and the occurrence of lapses (OR 9.26,CI 3.45-26.9). Multivariate analysis confirmed association between relapse and age of habits onset, occupational activity, contact with smokers, no previous attempts, high dependency, no adherence to therapy and the occurrence of lapses.  Conclusion  : The family socioeconomic status, smoking habits, dependence degree, treatment adherence and the occurrence of lapses were predictors of relapse.
Treating rheumatoid arthritis to target: recommendations of an international task force
Authors: J. S. Smolen, D. Aletaha, J. W. J. Bijlsma, F. C. Breedveld, D. Boumpas, G. Burmester, B. Combe, M. Cutolo, M. de Wit, M. Dougados, P. Emery, A. Gibofsky, J. J. Gomez-Reino, B. Haraoui, J. Kalden, E. C. Keystone, T. K. Kvien, I. McInnes, E. Martin-Mola, C. Montecucco, M. Schoels, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). <h3>Objective</h3> To develop recommendations for achieving optimal therapeutic outcomes in RA. <h3>Methods</h3> A task force of rheumatologists and a patient developed a set of recommendations on the basis of evidence derived from a systematic literature review and expert opinion; these were subsequently discussed, amended and voted upon by &gt;60 experts from various regions of the world in a Delphi-like procedure. Levels of evidence, strength of recommendations and levels of agreement were derived. <h3>Results</h3> The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with appropriate therapeutic adaptation to reach the desired state within 3 to a maximum of 6 months was recommended. Follow-up examinations ought to employ composite measures of disease activity which include joint counts. Additional items provide further details for particular aspects of the disease. Levels of agreement were very high for many of these recommendations (≥9/10). <h3>Conclusion</h3> The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion.
Role of wavefront curvature in propagation of cardiac impulse
Authors: Vladimir G Fast, André G Kléber
Journal: Cardiovascular Research (1997)

It is traditionally assumed that impulse propagation in cardiac muscle is determined by the combination of two factors: (1) the active properties of cardiac cell membranes and (2) the passive electrical characteristics of the network formed by cardiac cells. However, advances made recently in the theory of generic excitable media suggest that an additional factor—the geometry of excitation wavefronts—may play an important role. In particular, impulse propagation strongly depends on the wavefront curvature on a small spatial scale. In the heart, excitation wavefronts have pronounced curvatures in several situations including waves initiated by small electrodes, waves emerging from narrow tissue structures, and waves propagating around the sharp edges of anatomical obstacles or around a zone of functional conduction block during spiral wave rotation. In this short review we consider the theoretical background relating impulse propagation to wavefront curvature and we estimate the role of wavefront curvature in electrical stimulation, formation of conduction block, and the dynamic behavior of spiral waves.
Measuring quality of life in cancer patients.
Authors: K Donovan, R W Sanson-Fisher, S Redman
Journal: Journal of Clinical Oncology (1989)

The diagnosis and management of cancer can have a major impact on every aspect of a patient's quality of life. Despite its importance, quality of life is rarely a reported outcome in randomized clinical trials in cancer patients. Failure to collect quality-of-life information may reflect a lack of information among researchers and clinicians about the adequacy and relative merits of measures available for assessing quality of life. We reviewed the adequacy of the 17 existing scales for assessing quality of life in cancer patients against characteristics needed for an adequate measure. None of the existing measures met all of the criteria. Recommendations about the relative adequacy of existing scales were made.
Circulating microparticles generate and transport monomeric C-reactive protein in patients with myocardial infarction
Authors: Jonathon Habersberger, Frederik Strang, Amelie Scheichl, Nay Htun, Nicole Bassler, Ruusu-Maaria Merivirta, Philipp Diehl, Guy Krippner, Peter Meikle, Steffen U. Eisenhardt, Ian Meredith, Karlheinz Peter
Journal: Cardiovascular Research (2012)

AimsElevated serum C-reactive protein (CRP) following myocardial infarction (MI) is associated with poor outcomes. Although animal studies have indicated a direct pathogenic role of CRP, the mechanism underlying this remains elusive. Dissociation of pentameric CRP (pCRP) into pro-inflammatory monomers (mCRP) may directly link CRP to inflammation. We investigated whether cellular microparticles (MPs) can convert pCRP to mCRP and transport mCRP following MI.
Differential Signaling and Tumor Necrosis Factor Receptor–Associated Factor (Traf) Degradation Mediated by Cd40 and the Epstein-Barr Virus Oncoprotein Latent Membrane Protein 1 (Lmp1)
Authors: Kevin D. Brown, Bruce S. Hostager, Gail A. Bishop
Journal: The Journal of Experimental Medicine (2001)

Latent membrane protein 1 (LMP1) plays a critical role in B cell transformation by Epstein-Barr virus (EBV) and appears to mimic a constitutively active CD40 receptor. Intracellular tumor necrosis factor (TNF) receptor–associated factor (TRAF) adapter proteins, shown to contribute to signaling by both CD40 and LMP1, were recruited by both molecules to lipid-enriched membrane rafts. However, we found that TRAFs 2 and 3 were subsequently degraded after CD40- but not LMP1-induced signaling. This degradation was proteasome-dependent and required direct TRAF binding by CD40. Using a model system designed to directly compare the signaling potency of the cytoplasmic domains of LMP1 and CD40 in B lymphocytes, we found that LMP1 more potently activates c-Jun kinase and nuclear factor κB and induces higher levels of several B cell effector functions than does CD40. This suggests that LMP1 utilizes a modified CD40 signaling pathway. Failure to regulate TRAFs may contribute to the enhanced capacity of LMP1 to activate B cells as well as promote B cell transformation.
Transient MEK inhibitor-associated retinopathy in metastatic melanoma
Authors: U. Urner-Bloch, M. Urner, P. Stieger, N. Galliker, N. Winterton, A. Zubel, L. Moutouh-de Parseval, R. Dummer, S.M. Goldinger
Journal: Annals of Oncology (2014)
Lung function, clinical symptoms and mucociliary clearance in smokers: Frequency and correlation
Authors: Ana Paula Coelho Figueira Freire, Dionei Ramos, Renata Marques David, Bruna Spolador de Alencas Silva, Giovana Navarro Bertolini, Rômulo Araújo Fernandes, Murilo Sannomia Ito, Paula Roberta da Silva Pestana, Fernanda Maria Machado Rodrigues, Ercy Mara Cipulo Ramos
Journal: European Respiratory Journal (2013)

Smoking is considered to be the leading cause of preventable death in the world. There is an association of smoking and clinical respiratory symptoms in individuals who have not been diagnosed with any respiratory diseases. Aims: evaluate frequency and correlate clinical symptoms, lung function and mucociliary clearance in smokers. Methods:73 smokers aged between 40 and 70 years old, inserted in a smoking cessation program were divided in: Smoker group (n=47) with normal lung function and Obstrutive Group: smokers with obstructive disorders (n=26). They underwent an evaluation for clinical symptoms assessment (dyspnea, fatigue and cough) and measurement of exhaled carbon monoxide (COex) and nasal mucociliary clearance (MC). Results: A negative correlation (r =-0,39) between MC and lung function (FEF25-75% estimated) in the obstructive group has been identified. In the smoker group, 59,6% of individuals were symptomatic, and out of these 19,1% presented all clinical symptoms evaluated. Besides in the group with obstructive disorders, it was identified that 61,5% of individuals were symptomatic and out of them, 30,8% reported all clinical symptoms. Moreover, there was a higher predominance of females in both groups (smokers: 68,1% and 57,7% in obstructive group) and clinical symptoms in smokers of 51 to 60 years old. Conclusion: Although many smokers showed normal lung function, it could be observed that they present clinical symptoms which may generate significant impact on their health condition. This finding allows us to act in a preventive manner in order to provide guidance about the importance of smoking cessation and the need to minimize the harmful effects of tobacco consumption.
Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophaegeal varices, and hyperdynamic circulation.
Authors: Ren-Shin Lin, Fa-Yauh Lee, Shou-Dong Lee, Yang-Te Tsai, Han Chieh Lin, Lu Rei-Hwa, Hsu Wan-Ching, Huang Cheng-Chun, Wang Sun-Sang, Lo Kwang-Juei
Journal: Journal of Hepatology (1995)
The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry
Authors: M Michallet, M Sobh, D Milligan, S Morisset, D Niederwieser, V Koza, T Ruutu, N H Russell, L Verdonck, N Dhedin, A Vitek, M Boogaerts, L Vindelov, J Finke, V Dubois, A van Biezen, R Brand, T de Witte, P Dreger
Journal: Leukemia (2010)
Aminoacid constitution of two gastrins isolated from Zollinger-Ellison tumour tissue
Authors: R. A. Gregory, H. J. Tracy, K. L. Agarwal, M. I. Grossman
Journal: Gut (1969)

Two peptides which are potent stimulants of gastric acid secretion are isolated from Zollinger-Ellison tumour tissue. They have aminoacid constitutions identical with those of human gastrin types I and II as isolated from human antral mucosa, and they are present in similar proportions. Their electrophoretic and chromatographic behaviour corresponds to that of human gastrins. Evidence is presented in respect of the one isolated in greater amount that its aminoacid sequence is probably identical with that of human gastrin type I.