tbuckley/cabot-search huggingface dataset:
Cancer Surveillance Series: Interpreting Trends in Prostate Cancer Part III: Quantifying the Link Between Population Prostate-Specific Antigen Testing and Recent Declines in Prostate Cancer Mortality
Authors: R. Etzioni, J. M. Legler, E. J. Feuer, R. M. Merrill, K. A. Cronin, B. F. Hankey
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: The objective of this study was to investigate the circumstances under which dissemination of prostate-specific antigen (PSA) testing, beginning in 1988, could plausibly explain the declines in prostate cancer mortality observed from 1992 through 1994. METHODS: We developed a computer simulation model by use of information on population-based PSA testing patterns, cancer detection rates, average lead time (the time by which diagnosis is advanced by screening), and projected decreased risk of death associated with early diagnosis of prostate cancer through PSA testing. The model provides estimates of the number of deaths prevented by PSA testing for the 7-year period from 1988 through 1994 and projects what prostate cancer mortality for these years would have been in the absence of PSA testing. RESULTS: Results were generated by assuming a level of screening efficacy similar to that hypothesized for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Under this assumption, the projected mortality in the absence of PSA testing continued the increasing trend observed before 1991 only when it was assumed that the mean lead time was 3 years or less. Projected mortality trends in the absence of PSA screening were not consistent with pre-1991 increasing trends for lead times of 5 years and 7 years. CONCLUSIONS: When screening is assumed to be at least as efficacious as hypothesized in the PLCO trial, it is unlikely that the entire decline in prostate cancer mortality can be explained by PSA testing based on current beliefs concerning lead time. Only very short lead times would produce a decline in mortality of the magnitude that has been observed.
In silico identification and experimental validation of PmrAB targets in Salmonella typhimuriumby regulatory motif detection
Authors: Kathleen Marchal, Sigrid De Keersmaecker, Pieter Monsieurs, Nadja van Boxel, Karen Lemmens, Gert Thijs, Jos Vanderleyden, Bart De Moor
Journal: Genome biology (2004)

The PmrAB (BasSR) two-component regulatory system is required for Salmonella typhimurium virulence. PmrAB-controlled modifications of the lipopolysaccharide (LPS) layer confer resistance to cationic antibiotic polypeptides, which may allow bacteria to survive within macrophages. The PmrAB system also confers resistance to Fe3+-mediated killing. New targets of the system have recently been discovered that seem not to have a role in the well-described functions of PmrAB, suggesting that the PmrAB-dependent regulon might contain additional, unidentified targets.We performed an in silico analysis of possible targets of the PmrAB system. Using a motif model of the PmrA binding site in DNA, genome-wide screening was carried out to detect PmrAB target genes. To increase confidence in the predictions, all putative targets were subjected to a cross-species comparison (phylogenetic footprinting) using a Gibbs sampling-based motif-detection procedure. As well as the known targets, we detected additional targets with unknown functions. Four of these were experimentally validated (yibD, aroQ, mig-13 and sseJ). Site-directed mutagenesis of the PmrA-binding site (PmrA box) in yibD revealed specific sequence requirements.We demonstrated the efficiency of our procedure by recovering most of the known PmrAB-dependent targets and by identifying unknown targets that we were able to validate experimentally. We also pinpointed directions for further research that could help elucidate the S. typhimurium virulence pathway.
Simultaneous Measurements of Ca <sup>2+</sup> and Nitric Oxide in Bradykinin-Stimulated Vascular Endothelial Cells
Authors: Lothar A. Blatter, Ziad Taha, Stefan Mesaros, Philip S. Shacklock, Withrow G. Wier, Tadeusz Malinski
Journal: Circulation Research (1995)

Abstract The production of endothelium-derived relaxing factor (EDRF), known to be nitric oxide (NO), is triggered by a rise in the cytoplasmic calcium concentration ([Ca 2+ ] i ) subsequent to receptor binding of vasoactive agonists. In vascular endothelial cells, NO is synthesized from l -arginine by the Ca 2+ /calmodulin–dependent NO synthase. In this study, we report the first simultaneous measurements of [Ca 2+ ] i and [NO] at the level of single endothelial cells. In cultured bovine aortic endothelial cells, extracellular application of bradykinin (BK, 10 to 20 μmol/L) caused transient (sometimes oscillatory) increase in [Ca 2+ ] i , which was measured with the fluorescent Ca 2+ indicator fura 2 and fluorescence imaging microscopy. BK caused an increase in [Ca 2+ ] i , primarily through release from intracellular stores. Under identical experimental conditions, BK caused a transient increase in [NO], which was measured by application of a porphyrinic NO microsensor. [NO] peaked at ≈0.5 μmol/L. Simultaneous measurements of [Ca 2+ ] i and [NO] in BK-stimulated endothelial cells revealed that a transient increase in [Ca 2+ ] i was rapidly followed by an increase in [NO] that outlasted the [Ca 2+ ] i transient.
Effectiveness and safety of a second and third biological agent after failing etanercept in juvenile idiopathic arthritis: results from the Dutch National ABC Register
Authors: Marieke H Otten, Femke H M Prince, Janneke Anink, Rebecca ten Cate, Esther P A H Hoppenreijs, Wineke Armbrust, Yvonne Koopman-Keemink, Philomine A van Pelt, Sylvia Kamphuis, Simone L Gorter, Koert M Dolman, Joost F Swart, J Merlijn van den Berg, Nico M Wulffraat, Marion A J van Rossum, Lisette W A van Suijlekom-Smit
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Abstract</h3> The polysaccharide capsule of fungal pathogen <i>Cryptococcus neoformans</i> is a critical virulence factor that has historically evaded characterization. Polysaccharides remain attached to the cell as capsular polysaccharide (CPS) or are shed into the surroundings in the form of exopolysaccharide (EPS). While a great deal of study has been done examining the properties of EPS, far less is known about CPS. In this work, we detail the development of new physical and enzymatic methods for the isolation of CPS which can be used to explore the architecture of the capsule and removed capsular material. Sonication and glucanex digestion yield soluble CPS preparations, while French Press and modified glucanex digestion plus vortexing remove the capsule and cell wall producing polysaccharide aggregates that we call 'capsule ghosts.' The existence of capsule ghosts implies an inherent organization that allows it to exist independent of the cell wall surface. As sonication and glucanex digestion were noncytotoxic, it was possible to observe the cryptococcal cells rebuilding their capsule, revealing new insights into capsule architecture and synthesis consistent with a model in which the capsule is assembled from smaller polymers, which are then assemble into larger ones. <h3>Importance</h3> Characterization of the cryptococcal polysaccharide capsule relies on methods of isolation for its <i>in vitro</i> study. This study demonstrates that the capsule is susceptible to physical and enzymatic removal. The application of new methods yields insights into the anatomy, modular nature, and architecture of the capsule with both soluble CPS preparations and 'capsule ghosts.' Together these insights inform on a long-standing debate modeling capsular assembly wherein our data shows that the capsule is assembled by smaller polymers added distally rather than by proximal addition or by polymers spanning the entire capsule radius.
Regulator wants to do more to help prevent NHS trusts getting into trouble
Authors: A. O'Dowd
Journal: BMJ (2013)

One of the main NHS regulatory bodies wants to do more to help trusts that are in, or heading towards, serious financial trouble, MPs have heard.

Monitor, which regulates the health sector in England, warned that a growing number of NHS trusts were facing financial problems and would need help soon to prevent serious failures in the future.

The parliamentary health select committee held an evidence session on 26 November for its annual accountability hearing with Monitor, quizzing the organisation’s chief officers.

MPs asked the witnesses about the purpose of a report that Monitor published in October, Closing the NHS Funding Gap ,1 which warned about stagnant NHS funding over the next few years at the same time …
Improvement of histological biopsy diagnosis of hepatocellular carcinoma by genomic biomarkers?
Authors: R. Lamerz
Journal: Gut (2011)

Screening programmes have been developed for the surveillance of patients at risk of hepatocellular carcinoma (HCC; mainly liver cirrhosis) for the detection at an early stage, ie, suspicious liver nodules not larger than 2 cm in diameter often detected by ultrasound. Treatment indication needs a clear diagnosis for which one option is a biopsy often hampered by a relevant rate of false negatives and by a risk of bleeding and malignant seeding. Therefore, for the diagnosis of HCC imaging criteria are preferred requiring contrast enhancement and dynamic imaging. The recent update of the American Association for the Study of Liver Diseases (AASLD) guidelines in 20101 recommends for a nodule greater than 1 cm one single imaging technique to be used among CT and MRI, and in the case of non-diagnostic criteria the choice between a second technique or a biopsy.

Establishing HCC diagnosis at an ideal size of less than 2 cm relates to the transition from low to high grade dysplasia and very early HCC as described by the international working party classification2 and a final international diagnostic consensus.3 From two types of HCC less than 2 cm, early HCC has a vaguely nodular appearance, is well differentiated and corresponds to the very early HCC stage of the Barcelona Clinic Liver Cancer classification, with the absence of microvascular invasion excluding a clear imaging profile for diagnosis. …
Effect of a Cognitive Behavioral Intervention on Reducing Symptom Severity During Chemotherapy
Authors: Charles Given, Barbara Given, Mohammad Rahbar, Sangchoon Jeon, Ruth McCorkle, Bernadine Cimprich, Andrzej Galecki, Sharon Kozachik, Albert Brady, Mary Jo Fisher-Malloy, Kathy Courtney, Elizabeth Bowie
Journal: Journal of Clinical Oncology (2004)

To describe a randomized trial of a cognitive behavioral intervention on reducing symptom severity among patients diagnosed with solid tumors and undergoing a first course of chemotherapy and to determine whether the intervention had an additive or interactive effect on symptom severity in the presence of supportive care medications.Patients (N = 237) were accrued from comprehensive and community cancer centers, interviewed, and randomly assigned to either the experimental intervention (n = 118) or conventional care (n = 119). A symptom severity index, based on summed severity scores across 15 symptoms, was the primary outcome. Each patient's site of cancer, stage at diagnosis, chemotherapy protocols, and use of supportive medications were learned from medical records.Groups were equivalent at baseline, and attrition by characteristics by group was not different. The proportion of patients not receiving chemotherapy at 10 and 20 weeks did not differ by group. At the 10- and 20-week observations, there was a significant interaction between the experimental group and baseline symptom severity. Patients in the experimental group who entered the trial with higher symptom severity reported significantly lower severity at 10 and 20 weeks. Controlling for chemotherapy treatment status at follow-up and supportive care medications did not alter the effect of the experimental intervention.Compared with conventional care alone, the experimental intervention was effective among patients who entered the trial with higher levels of symptom severity. Age, sex, site or stage of cancer, and supportive medications did not modify the effect of this cognitive behavioral intervention on symptom severity.
Risk of Cardiovascular Mortality in Prostate Cancer Patients in the Rotterdam Randomized Screening Trial
Authors: Suzie J. Otto, Fritz H. Schröder, Harry J. de Koning
Journal: Journal of Clinical Oncology (2006)

To estimate the risk of cardiovascular disease (CVD) mortality in prostate cancer patients in the Rotterdam section of European Randomized Study of Screening for Prostate Cancer, in both arms, and to compare this with the risk in the general population.Standardized mortality ratios (SMRs) of cardiovascular mortality for 2,211 prostate cancer patients were calculated including analyses for treatment subgroups (surgery, radiotherapy, watchful waiting, and hormone therapy). Cardiovascular mortality was defined as death as a result of all CVD and as a result of coronary heart disease, acute myocardial infarction, other diseases of the heart, and cerebrovascular accidents. The prevalence of self-reported comorbidities at entry of the trial was evaluated as well.After a mean follow-up of 5.5 years, 258 prostate cancer patients (12%) had died. The SMR of all-cause mortality was 0.90 (95% CI, 0.79 to 1.01). The risk for cardiovascular mortality was low compared with that in the general population; the SMRs varied between 0.37 and 0.49. Low cardiovascular mortality risks were also seen within each treatment subgroup. CVD was the most frequently self-reported comorbidity at entry and prostate cancer patients undergoing radical prostatectomy reported the lowest rates (24%) compared with those receiving other therapies (40% to 42%).Although some self-selection has occurred, prostate cancer treatment did not increase the risk of dying as a result of cardiovascular causes in our cohort. The risk was significantly lower for all primary treatment modalities, suggesting that less emphasis should be put on CVD as a contraindication for aggressive (surgical) treatment for prostate cancer patients.
Haplotypes associated with COPD and its severity in Mexican mestizo population
Authors: Ramcés Falfán-Valencia, Gloria Pérez-Rubio, Juan Carlos Fernández-López, Alejandra Raírez-Venegas, Angel Camarena, Raúl Sansores
Journal: European Respiratory Journal (2013)

Background: COPD is a complex disease whose main risk factor is cigarette smoking, there is genetic component that predisposes to develop it; the objective of this study is to evaluate haplotypes associated with COPD and its severity in Mexican mestizo population.  Methods: We conducted a study with 299 patients with COPD (P-COPD) secondary to smoking and 531 smokers without COPD (SW-C), P-COPD were classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2010, in 2 groups, GOLD I+II and III+IV. It was designed a microarray (Illumina, CA, USA) with 1536 single nucleotide polymorphisms (SNPs); 251 were ancestry informative markers (AIMs), the rest were distributed in 24 candidate genomic regions. To describe the study population used SPSS; population stratification was performed by EIGENSOFT software, the structure of linkage disequilibrium and haplotype generation was performed using the software Haploview 4.2.  Results: We find haplotypes associated with COPD in 3 genes:  FAM69A ,  ZNF583  and  SLC9A8.   Analysis according GOLD, shows an haplotype in  IL6R  gene (I+II  vs  III+IV) associated to protection (p = 8.00E-03) and other to susceptibility in  ADAM19  (p = 7.40E-03), both genes encoding proteins involved in the inflammation process.  Conclusions: There are haplotypes associated with COPD and GOLD severity in Mexican mestizo population.
Lobar collapse due to endobronchial metastatic prostatic carcinoma: re-expansion with antiandrogen treatment.
Authors: H Taylor, S Braude
Journal: Thorax (1990)

A patient is described who presented with left upper lobe collapse due to endobronchial metastatic prostate carcinoma. Treatment with the oral antiandrogen cyproterone acetate resulted in resolution of the occluding endobronchial carcinoma and lobar re-expansion.
Conditional Probability of Survival in Patients With Newly Diagnosed Glioblastoma
Authors: Mei-Yin C. Polley, Kathleen R. Lamborn, Susan M. Chang, Nicholas Butowski, Jennifer L. Clarke, Michael Prados
Journal: Journal of Clinical Oncology (2011)

The disease outcome for patients with cancer is typically described in terms of estimated survival from diagnosis. Conditional probability offers more relevant information regarding survival for patients once they have survived for some time. We report conditional survival probabilities on the basis of 498 patients with glioblastoma multiforme receiving radiation and chemotherapy. For 1-year survivors, we evaluated variables that may inform subsequent survival. Motivated by the trend in data, we also evaluated the assumption of constant hazard.Patients enrolled onto seven phase II protocols between 1975 and 2007 were included. Conditional survival probabilities and 95% CIs were calculated. The Cox proportional hazards model was used to evaluate prognostic values of age, Karnofsky performance score (KPS), and prior progression 1-year post diagnosis. To assess the constant hazard assumption, we used a likelihood-ratio test to compare the Weibull and exponential distributions.The probabilities of surviving an additional year given survival to 1, 2, 3, and 4 years were 35%, 49%, 69%, and 93%, respectively. For patients who survived for 1 year, lower KPS and progression were significantly predictive of shorter survival (both P < .001), but age was not (hazard ratio, 1.22 for a 10-year increase; P = .25). The Weibull distribution fits the data significantly better than exponential (P = .02), suggesting nonconstant hazard.Conditional probabilities provide encouraging information regarding life expectancy to survivors of glioblastoma multiforme. Our data also showed that the constant hazard assumption may be violated in modern brain tumor trials. For single-arm trials, we advise using individual patient data from historical data sets for efficacy comparisons.
Geoffrey Donald Parbrook
Authors: E. P. A. Reid
Journal: BMJ (2013)

<h3>Background</h3> Over two-thirds of Natural American Spirit (NAS) smokers believe their cigarettes might be ‘less harmful’, but toxicological evidence does not support this belief. We assessed whether standardised packaging could reduce the possibility of erroneous inferences of ‘safety’ drawn from NAS cigarette packaging. <h3>Methods</h3> US adult smokers (n=909) were recruited to a between-subject survey experiment (3 brands×3 packaging/labelling styles) through Amazon Mechanical Turk and rated their perception of whether a randomly assigned cigarette package conveyed that the brand was ‘safer’ on a three-item scale (Cronbach’s α=0.92). We assessed whether NAS packs were rated higher on the ‘implied safety’ scale than two other brands and estimated the effect that plain packaging (ie, all branding replaced with a drab dark brown colour) and Australian-like packaging (ie, all branding replaced with a drab dark brown colour and a graphic image and text on 75% of the pack surface) had on perceptions of the NAS cigarette package. <h3>Results</h3> Smokers’ ratings of the standard NAS pack on the implied safety scale (mean=4.6; SD=2.9) were 1.9 times (P &lt;0.001) higher than smokers’ ratings of a Marlboro Red pack (mean=2.4; SD=2.3) and 1.7 times (P &lt;0.001) higher than smokers’ ratings of a Newport Menthol pack (mean=2.7; SD=2.4). These perceptions of implied safety were lower when plain packaging was used (Cohen’s d=0.66; P &lt;0.001) and much lower when Australian-like packaging was used (Cohen’s d=1.56; P &lt;0.001). <h3>Conclusion</h3> The results suggest that NAS cigarette packaging conveys that its cigarettes are ‘safer’ and that such perceptions are lower with standardised packaging, both with and without warning images.
AN ACID CITRATE-DEXTROSE SOLUTION WITH LOW WATER VOLUME AND LOW DEXTROSE CONCENTRATION 1
Authors: Max M. Strumia, Alton D. Blake, John J. McGraw, Miss Margaret Dolan, Miss Louise Colwell
Journal: Journal of Clinical Investigation (1947)

The blood preservative introduced by Loutit and Mollison (1) consisting essentially of a sodi- um citrate-dextrose mixture of relatively low pH, has proved superior to previously employed pre- serving fluids.The original formula and many subsequent modifications have a rather high volume.This produces considerable dilution of the plasma proteins.The purpose of this study, begun in June 1944, was to obtain an A.C.D. solution of lower volume, so as to maintain an optimal concentration of plasma proteins, maintain or improve the ca- pacity to preserve erythrocytes, and at the same time insure maximal stability of the resulting plasma.The first solution tested was one proposed by Rapport, as follows:Sodium citrate (trisodium dihydric) 1.66 grams Citric acid (monohydric) 0.59 gram Distilled water 100 ml.22.5 ml. of 15 per cent dextrose were added to 90 ml. of this solution, and the resulting solution was sterilized by autoclaving for 20 minutes at 120°C.This formula.canbe written as follows for the sake of comparison with other formulas: A.C.D. Rapoport Sodium citrate (trisodium dihydric) 1.50 grams Citric acid (monohydric) .55gram Dextrose 3.37 grams Water 112.5 ml.112.5 ml. of this solution were used for each 500 ml. of blood collected.The solution was cooled to 40 C. previous to use.
The Effect of Enzyme-Inducing Antiseizure Drugs on the Pharmacokinetics and Tolerability of Procarbazine Hydrochloride
Authors: Stuart A. Grossman, Kathryn A. Carson, Tracy T. Batchelor, Glenn Lesser, Tom Mikkelsen, Jane B. Alavi, Surasak Phuphanich, Tarek Hammour, Joy D. Fisher, Jeffrey G. Supko
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Procarbazine hydrochloride (PCB) is one of the few anticancer drugs with activity against high-grade gliomas. This study was conducted to determine if the maximum tolerated dose and pharmacokinetics of PCB are affected by the concurrent use of enzyme-inducing antiseizure drugs (EIASD). Experimental Design: Adults with recurrent high-grade glioma were divided into cohorts who were (+) and were not (−) taking EIASDs. PCB was given orally for 5 consecutive days each month. Six patients were evaluated at each dose level beginning with 200 mg/m2/d and escalated using the modified continual reassessment method. Toxicity and response were assessed. Pharmacokinetic studies were done with a new electrospray ionization mass spectrometry assay. Results: Forty-nine patients were evaluated. The maximum tolerated dose was 393 mg/m2/d for the +EIASD group and the highest dose evaluated in −EIASD patients was 334 mg/m2/d. Myelosuppression was the primary dose-limiting toxicity. Significant hepatic dysfunction occurred in three patients in the +EIASD cohort. Four partial responses (8%) and no complete responses were observed. PCB exhibited linear pharmacokinetics with no significant differences between the two cohorts. A marked increase in peak PCB levels was noted on day 5 relative to day 1, which was not attributable to drug accumulation. Conclusions: This study suggests that (a) EIASD use does not significantly affect the pharmacokinetics of PCB; (b) changes in the peak plasma concentration of PCB, consistent with decreased apparent oral clearance due to autoinhibition of hepatic metabolism, occur with daily dosing; and (c) severe hepatic dysfunction may accompany this administration schedule.