tbuckley/cabot-search huggingface dataset:
<i>KRAS</i> rs61764370 in Epithelial Ovarian Cancer–Response
Authors: Harvey A. Risch, Andrew Berchuck, Paul D.P. Pharoah
Journal: Clinical Cancer Research (2011)

Ratner and colleagues reported an association between rs61764370 and risk of epithelial ovarian cancer (EOC) in 2 small case–control studies (n < 1,000 in total; ref. 1). They also reported increased risk in BRCA1 mutation carriers (n = 23) and in women not carrying BRCA1/2 mutations but with family histories of the disease (n = 31), and an association with poorer survival. We attempted to replicate these findings in 8,669 EOC cases (249 with family histories) and 10,012 controls from 19 studies and examined prognosis in 5 studies with progression-free survival data and 18 with all-cause mortality data (2). We also analyzed 683 cases and 2,044 controls carrying BRCA1 mutations (2). These analyses completely failed to validate the original findings. This result was not surprising considering the high potential for false discovery in genetic association studies (3).Weidhaas and Slack assert that fundamental differences between our studies explain the discrepant results. First they claim differences between the “high-risk” populations. However, all BRCA1 carriers in our study were from “fully annotated” hereditary breast and ovarian cancer families. Differences between the 2 studies with regard to nonBRCA1/2-associated familial EOC are far more likely due to random error, given the few familial subjects in the Ratner study, than any of the trivial differences they describe. They also provide a multitude of theoretical differences that might account for discrepancies in risks of nonfamilial EOC. These are unlikely to be important and they provide no empirical evidence justifying their claims. Their only potentially salient point concerns possible bias that might occur in case–control studies that include prevalent cases and where the single-nucleotide polymorphism (SNP) is also associated with survival. We directly examined EOC survival without finding a significant association, nor did our results change when we restricted analyses to cases recruited within 18 months of diagnosis. The positive results in the original study by Ratner and colleagues (1) most likely arose by chance or from genotyping errors. In this regard, their data show evidence of significant deviation from Hardy–Weinberg equilibrium, but this was not reported in their study (1).rs61764370 testing, as currently marketed for risk assessment in BRCA1/2-negative familial subjects, is based on analysis of only 31 cases. The assertion of theoretical deficiencies in our analysis without empirical evidence for such claims does not refute the lack of adequate evidence in support of this clinical use. The existing data do not support the use of this KRAS SNP for ovarian cancer risk assessment.See the original Letter to the Editor, p. 6600No potential conflicts of interest were disclosed.
Increased lung to blood passage of polyethylene glycols after intratracheal instillation of ferritin and asbestos fibres in the rat
Authors: HG Folkesson, P Leanderson, BR Westrom, C Tagesson
Journal: European Respiratory Journal (1993)

Urinary recovery of intratracheally instilled polyethylene glycol polymers (PEG:s) in the molecular weight range 722-1294 Da (PEG 1000) was studied under normal conditions and during experimentally induced lung damage in rats. The urinary PEG recoveries were between 30-60% under normal conditions, with a selectivity for smaller PEG:s. No significant differences in the urinary PEG molecular weight profiles were found between 30 days old and adult rats; i.e. they had similar PEG 1162/810 (molecular weights) urinary recovery ratios (0.78 +/- 0.25 and 0.69 +/- 0.27, respectively, p > 0.05). In rats instilled with PEG 1000 and ferritin (5 mg.kg-1 body weight), the urinary recovery was increased for PEG:s with molecular weights greater than 1030 Da; i.e. a higher PEG 1162/810 recovery ratio (1.44 +/- 0.58, p < 0.01) was obtained. Rats instilled with PEG 1000 and crocidolite asbestos fibres (5 mg.kg-1 body weight) showed higher urinary recoveries for PEG:s greater than 854 Da, resulting in a higher PEG 1162/810 ratio (1.47 +/- 0.59, p < 0.01). By adding the iron-chelator, desferrioxamine, to the crocidolite-instillate, the urinary recoveries and the PEG 1162/810 ratio (0.97 +/- 0.47) were reduced, indicating a restored molecular weight selectivity of the lung. Thus, in rats, PEG 1000 passes via the respiratory tract in large amounts which is dependent on the molecular weight. This passage was increased after ferritin- or crocidolite instillation, indicating that the barrier function of the respiratory tract was impaired due to local tissue damage, and that iron may play an important role in this.
Effect of adalimumab on joint disease: features of patients with psoriatic arthritis detected by magnetic resonance imaging
Authors: A P Anandarajah, P Ory, D Salonen, C Feng, R L Wong, C T Ritchlin
Journal: Annals of the Rheumatic Diseases (2009)

Background: Bone marrow oedema (BMO), synovitis, effusion and joint erosion on magnetic resonance imaging (MRI) may be used as outcome measures in psoriatic arthritis (PsA). Objective: To assess the impact of adalimumab on BMO, synovitis, effusion and erosions in PsA, as measured by MRI. Methods: Fifteen patients with active PsA (⩾3 tender and ⩾3 swollen joints) were enrolled in an open-label pilot study. Each received adalimumab subcutaneously every other week for 24 weeks. MRI was obtained at baseline and 24 weeks. Results: MRI was available for 11 patients, pre and post-therapy. BMO and effusion scores improved markedly after 24 weeks of adalimumab, while no significant change was noted in erosion score. An unanticipated finding, however, was the lack of improvement in the MRI synovitis score. Conclusions: Improvement in BMO and unchanged erosion scores may explain the “anti-erosive” effects of adalimumab in PsA. Persistence of BMO and synovitis on MRI suggests ongoing disease activity and supports the continuation of long-term anti-TNF therapy.
Evaluation in man of fenclozic acid (I.C.I. 54,450: Myalex), a new anti-inflamatory agent. II. Clinical trial in patients with rheumatoid arthritis.
Authors: T M Chalmers, J H Kellgren, D S Platt
Journal: Annals of the Rheumatic Diseases (1969)

Samples taken 2 to 3 hrs after the dose indicated (10th day of treatment period); Results expressed as means ±S.E.
Public Health Assessment in the 1990s
Authors: M A Stoto
Journal: Annual Review of Public Health (1992)

In 1990, the Secretary of Health and Human Services unveiled Healthy People 2000: National Health Promotion and Disease Prevention Objectives (46), which is a milestone in public health. Healthy People 2000 identifies three national health goals: increase the span of healthy life, reduce health disparities among Americans, and achieve access to preventive services for all Americans. The report also details 300 specific objectives for health promo­ tion and disease prevention programs with quantitative targets to be achieved by the year 2000. Meeting these objectives requires agreement by public health statisticians on measures of individual and community health status to guide public health policy development and priorities, especially for state and .local areas, and improvement in the methods, for tracking these measures. Healthy People 2000 challenges public health practitioners to develop surveillance systems that are both meaningful in a public health sense and statistically sound. To clarify this challenge and outline some possible re­ sponses, I begin with some background on the public health assessment activities on which the year 2000 health objectives build and considerations that should guide public health assessment efforts. The next section presents general statistical issues in formulating measurable and meaningful objec­ tives. Other sections are devoted to two specific issues: the development of a small set of health status indicators that is both meaningful and feasible to monitor and special issues associated with setting objectives and determining appropriate targets for state and local areas.
A Prodrug-type, MMP-2-targeting Nanoprobe for Tumor Detection and Imaging
Authors: Yaping Wang, Tingting Lin, Wenyuan Zhang, Yifan Jiang, Hongyue Jin, Huining He, Victor C. Yang, Yi Chen, Yongzhuo Huang
Journal: Theranostics (2015)

Tumor-associated proteases (TAPs) have been intensively studied because of their critical roles in cancer development.As a case in point, expression of matrix metalloproteases (MMP) is significantly up-regulated in tumorigenesis, invasion, and metastasis among a majority of cancers.Here we present a prodrug-type, MMP-2-responsive nanoprobe system with high efficiency and low toxicity for detecting MMP-2-overexpressed tumors.The nanoprobe system is featured by its self-assembled fabrication and FRET effect.This prodrug-type nanoprobe is selectively activated by MMP-2, and thus useful for detection of the MMP-2-overexpressed cells and tumors.The nanoprobe system works successfully in various animal tumor models, including human fibrosarcoma and subcutaneous glioma xenograft.Furthermore, in order to overcome the blood brain barrier (BBB) and achieve brain tumor targeting, a transferrin-receptor targeting peptide (T7 peptide) is strategically incorporated into the nanoprobe.The T7-functionalized nanoprobe is capable of detecting the orthotopic brain tumor, with clear, real-time in vivo imaging.This method is promising for in vivo detection of brain tumor, and real-time monitor of a TAP (i.e., MMP-2).
B Cells of HIV-1–Infected Patients Bind Virions through Cd21–Complement Interactions and Transmit Infectious Virus to Activated T Cells
Authors: Susan Moir, Angela Malaspina, Yuexia Li, Tae-Wook Chun, Tomeka Lowe, Joseph Adelsberger, Michael Baseler, Linda A. Ehler, Shuying Liu, Richard T. Davey, Jo Ann M. Mican, Anthony S. Fauci
Journal: The Journal of Experimental Medicine (2000)

The impact of HIV-associated immunopathogenesis on B cells has been largely associated with indirect consequences of viral replication. This study demonstrates that HIV interacts directly with B cells in both lymphoid tissues and peripheral blood. B cells isolated from lymph node and peripheral blood mononuclear cells (PBMCs) of 4 and 23 chronically infected patients, respectively, demonstrated similar capacities to pass virus to activated HIV-negative PBMCs when compared with CD4(+) cells from the same patients. However, in contrast to T cells, virus associated with B cells was surface bound, as shown by its sensitivity to pronase and the staining pattern revealed by in situ amplification of HIV-1 RNA. Cell sorting and ligand displacing approaches established that CD21 was the HIV-binding receptor on B cells, and that this association was mediated through complement-opsonized virus. These B cells were also found to express significantly lower levels of CD21 compared with HIV-negative individuals, suggesting a direct perturbing effect of HIV on B cells. These findings suggest that B cells, although they themselves are not readily infected by HIV, are similar to follicular dendritic cells in their capacity to serve as extracellular reservoirs for HIV-1. Furthermore, B cells possess the added capability of circulating in peripheral blood and migrating through tissues where they can potentially interact with and pass virus to T cells.
Targeting iron uptake to control<i>Pseudomonas aeruginosa</i>infections in cystic fibrosis
Authors: Daniel J. Smith, Iain L. Lamont, Greg J. Anderson, David W. Reid
Journal: European Respiratory Journal (2012)

The aerobic Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen responsible for life-threatening acute and chronic infections in humans. As part of chronic infection P. aeruginosa forms biofilms, which shield the encased bacteria from host immune clearance and provide an impermeable and protective barrier against currently available antimicrobial agents. P. aeruginosa has an absolute requirement for iron for infection success. By influencing cell-cell communication (quorum sensing) and virulence factor expression, iron is a powerful regulator of P. aeruginosa behaviour. Consequently, the imposed perturbation of iron acquisition systems has been proposed as a novel therapeutic approach to the treatment of P. aeruginosa biofilm infection. In this review, we explore the influence of iron availability on P. aeruginosa infection in the lungs of the people with the autosomal recessive condition cystic fibrosis as an archetypal model of chronic P. aeruginosa biofilm infection. Novel therapeutics aimed at disrupting P. aeruginosa are discussed, with an emphasis placed on identifying the barriers that need to be overcome in order to translate these promising in vitro agents into effective therapies in human pulmonary infections.
Efficacy of oral prednisolone in active ankylosing spondylitis: results of a double-blind, randomised, placebo-controlled short-term trial
Authors: H Haibel, C Fendler, J Listing, J Callhoff, J Braun, J Sieper
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The efficacy of oral prednisolone in patients with active ankylosing spondylitis (AS) has not been studied to date. <h3>Methods</h3> In this double-blind, randomised, placebo-controlled trial, patients with AS with active disease despite taking non-steroidal antirheumatic drugs were randomised to three groups in which they were either treated with 20 mg (n=13) or 50 mg (n=12) of prednisolone, or placebo (n=14), administered orally every day for a total of 2 weeks. The primary endpoint was defined as a 50% improvement of the Bath AS Disease Activity Index (BASDAI) at week 2. <h3>Results</h3> The primary endpoint was reached in 33% and 27% of the patients treated with 50 and 20 mg of prednisolone, respectively, versus only 8% on placebo (p=0.16 and p=0.30). However, the mean improvement of BASDAI score was significantly higher in the 50 mg prednisolone compared to the placebo group (2.39±0.5 vs 0.66±0.49, p=0.03), while there was only a small change in the 20 mg group (1.19±0.53; p=0.41). The results for other outcome parameters were similar. <h3>Conclusions</h3> Oral prednisolone 50 mg per day, but not low dose prednisolone, showed a short-term response that was significantly higher than placebo. The clinical significance and the duration of this effect warrant further study. <h3>ClinicalTrials.gov Identifier</h3> NCT00244166
Tumour islet Foxp3<sup>+</sup> T-cell infiltration predicts poor outcome in nonsmall cell lung cancer
Authors: Dermot S. O'Callaghan, Elton Rexhepaj, Kathy Gately, Linda Coate, David Delaney, Dearbhaile M. O'Donnell, Elaine Kay, Finbarr O'Connell, William M. Gallagher, Kenneth J. O'Byrne
Journal: European Respiratory Journal (2015)

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis. Tumour- and stroma-infiltrating CD3 + , CD8 + and forkhead box P3 (Foxp3) + T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined. There was a positive association between overall survival and increased CD8 + TI/S ratio (hazard ratio (HR) for death 0.44, p&lt;0.001) but an inverse relationship between Foxp3 + TI/S ratio and overall survival (HR 4.86, p&lt;0.001). Patients with high CD8 + islet (HR 0.48, p&lt;0.001) and Foxp3 + stromal (HR 0.23, p&lt;0.001) counts had better survival, whereas high CD3 + and CD8 + stromal counts and high Foxp3 + islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8 + TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3 + TI/S ratio was associated with worse survival (HR 3.91, p&lt;0.001). Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.
Women, Acute Ischemic Heart Disease, and Antithrombotic Therapy
Authors: Robert A. Harrington
Journal: Circulation (2007)

here now exists an extensive and growing literature examining gender-based differences in the pathobiology, presentation, treatment patterns, and clinical outcomes of ischemic heart disease (IHD).IHD is a dominant mode of death for women, 1 and, for Ͼ20 years, more women than men die annually from IHD. 2 The first manifestation of IHD in women is frequently myocardial infarction or sudden cardiac death. 2 A better understanding of the spectrum of issues-from pathophysiology through implementation of evidence-based care-among women with IHD is a public health imperative. Article p 2822Recently, many observations have converged around a common set of themes in the care of women with IHD, especially acute IHD.Lansky et al 3 have pointed out that women with degrees of obstructive coronary artery disease comparable to those of men receive less revascularization.From the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines (CRUSADE) registry, we know that women presenting with high-risk non-ST-segment-elevation acute coronary syndromes (primarily myocardial infarction) are less likely than men to undergo an early invasive management strategy despite being at a higher baseline risk. 4Women with non-ST-segment-elevation acute coronary syndromes are less likely than men to receive recommended evidence-based medications and cardiac procedures, again despite being at higher baseline risk. 5owever, there are also challenges in evaluating and deciding on treatments for women presenting with acute coronary syndromes.Roe and colleagues 6 have shown that women presenting with non-ST-segment-elevation acute coronary syndromes have a greater likelihood of nonobstructive disease than do men, and the Women's Ischemia Syndrome Evaluation (WISE) investigators have compiled a substantial body of work suggesting that the pathobiology of IHD differs in women compared with men. 7All of this makes
Serum alpha-fetoprotein levels in acute viral hepatitis
Authors: M. C. Kew, L. R. Purves, I. Bersohn
Journal: Gut (1973)

Serum alpha-fetoprotein levels were measured serially by radioimmunoassay in 32 patients with acute viral hepatitis. With one exception, the levels were increased during the course of the illness. Raised concentrations of the protein occurred almost equally in patients with and without the hepatitis-B antigen. In the majority of patients the rise was modest but in seven levels were reached at which alpha-fetoprotein could be detected by immunodiffusion. Very high levels were more likely to occur in children. In eight patients the concentration increased as the serum glutamic pyruvic transaminase (SGPT) level, used as an index of hepatocyte damage, was returning to normal, a pattern which favoured increased synthesis of the protein during hepatocellular regeneration. In the remainder, the alpha-fetoprotein level paralleled that of SGPT, suggesting rather an acutephase reaction to liver injury.
TCT-618 Percutaneous Coronary Intervention In A Complex Patient Population: A Comparison of First- Versus Second-Generation Drug-Eluting Stent use on In-Hospital and 1-Year Outcomes
Authors: Joshua Loh, Hironori Kitabata, Israel Barbash, Danny Dvir, Salem Badr, Rebecca Torguson, Kenneth Kent, Lowell Satler, William Suddath, Augusto Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2012)
Medical supervision of sport diving in Scotland: reassessing the need for routine medical examinations
Authors: Stephen Glen, Steven White, James Douglas
Journal: British Journal of Sports Medicine (2000)

The value of diving medicals in preventing incidents is uncertain and there has been only limited evaluation of the fitness to dive guidelines in a sport diving population.To examine the need for routine diving medical examinations in the Scottish Sub-Aqua Club (SSAC) between 1991 and 1998.A medical examination of all SSAC divers is performed at entry and then every one to five years based on their age and medical condition This information was analysed in terms of questionnaire findings and examination abnormalities.There were 2,962 medical forms available for analysis. Examination abnormalities were found in 174 subjects (5.9% of the population), with obesity affecting 75 subjects (2.5%). There was a linear increase in mean body mass index (r2 = 0.92), and a significant difference between 1991 and 1998 (mean (SD) of 24.1 (3.07) and 25.02 (3.4) respectively, p = 0.002) which was not related to age or sex distribution. There was also a significant increase in the prevalence of smokers (chi2 = 4.02, p = 0.045). The most common specialist referral was for evaluation of asthma, with hypertension and obesity as the next most common reasons. Most subjects were allowed to dive, with only 43 (25%) being failed outright. Overall, no examination abnormality alone caused a subject to be classified unfit to dive, and referrals were prompted by the answers in the questionnaire.No significant unexpected abnormalities were found on clinical examination in this population of sport divers. Conditions that prevented subjects from diving were detected by the questionnaire, and this prompted referral for further assessment by the medical advisors. Routine medical examinations were of little value.
Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort
Authors: S. Schlesinger, K. Aleksandrova, T. Pischon, M. Jenab, V. Fedirko, E. Trepo, K. Overvad, N. Roswall, A. Tjønneland, M.C. Boutron-Ruault, G. Fagherazzi, A. Racine, R. Kaaks, V.A. Grote, H. Boeing, A. Trichopoulou, M. Pantzalis, M. Kritikou, A. Mattiello, S. Sieri, C. Sacerdote, D. Palli, R. Tumino, P.H. Peeters, H.B. Bueno-de-Mesquita, E. Weiderpass, J.R. Quirós, R. Zamora-Ros, M.J. Sánchez, L. Arriola, E. Ardanaz, M.J. Tormo, P. Nilsson, B. Lindkvist, M. Sund, O. Rolandsson, K.T. Khaw, N. Wareham, R.C. Travis, E. Riboli, U. Nöthlings
Journal: Annals of Oncology (2013)