tbuckley/cabot-search huggingface dataset:
Seasonal variation of selected performance parameters in epee fencers.
Authors: Y Koutedakis, A Ridgeon, N C Sharp, C Boreham
Journal: British Journal of Sports Medicine (1993)

In this study, anthropometric measurements were carried out on seven British international male épée fencers, using a maximal treadmill running test, a 20-s Wingate-type test, and isokinetic dynamometry. Testing was conducted on two occasions, 5 to 6 months apart, during mid-off-season (preparation) and mid-in-season (competition) periods. Maximal oxygen intake (VO2max) and maximal respiratory exchange ratio (Rmax) were among the parameters obtained from the treadmill test, while peak and mean anaerobic power outputs were measured during a 20-s maximal effort. Knee extensor and flexor muscle forces from both dominant (leading) and non-dominant (trailing) legs were assessed at 1.04, 3.14 and 4.19 rad sec-1. Statistical analyses revealed lower mean VO2max (P < 0.05) and mean Rmax values (P < 0.02) at the in-season assessments compared with off-season. In-season testing also demonstrated significantly lower peak torques for both dominant and non-dominant knee extensors compared with off-season assessments at all velocities (P < 0.05 to P < 0.004). Furthermore, in-season peak torque for the non-dominant leg flexors was lower (P < 0.03) at 4.19 rad sec-1 than off-season. We conclude that current training practices may account for the observed seasonal variations in performance related physiological parameters in fencers.
Genetic Alterations in Signaling Pathways in Melanoma
Authors: Frank G. Haluska, Hensin Tsao, Helen Wu, Frank S. Haluska, Alexander Lazar, Vikas Goel
Journal: Clinical Cancer Research (2006)

Abstract Alterations in the RAS signaling cascade are almost uniformly present in melanoma. RAS itself is only infrequently mutated in melanoma although downstream of RAS lie BRAF on the mitogen-activated protein kinase pathway and PTEN on the protein kinase B/Akt pathway. These genes are often altered in melanomas; indeed, the most frequent target of mutation in melanomas is BRAF, which is mutated in ∼60% to 70% of superficial spreading melanomas. These mutations occur in a background that is not normal, with the CDKN2A locus also typically being mutated. We review herein the data that suggest that the distribution of the signaling mutations is important. In general, melanomas carry a mutated NRAS, a mutated BRAF, or concurrent BRAF and PTEN mutations. These data support the hypothesis that the biochemical functions of RAS are portioned by mutations in the pathways lying downstream. Moreover, these mutations have no apparent relationship to the patterns of alteration of CDKN2A and its downstream effectors. Thus, the data also suggest that successful exploitation of mutations in melanoma will be dependent on understanding not only mutations and their frequency but their genetic context as well.
Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors
Authors: A. Hrobjartsson, A. S. S. Thomsen, F. Emanuelsson, B. Tendal, J. Hilden, I. Boutron, P. Ravaud, S. Brorson
Journal: BMJ (2012)

<b>Objective</b> To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes. <b>Design</b> Systematic review of trials with both blinded and non-blinded assessment of the same binary outcome. For each trial we calculated the ratio of the odds ratios—the odds ratio from non-blinded assessments relative to the corresponding odds ratio from blinded assessments. A ratio of odds ratios &lt;1 indicated that non-blinded assessors generated more optimistic effect estimates than blinded assessors. We pooled the individual ratios of odds ratios with inverse variance random effects meta-analysis and explored reasons for variation in ratios of odds ratios with meta-regression. We also analysed rates of agreement between blinded and non-blinded assessors and calculated the number of patients needed to be reclassified to neutralise any bias. <b>Data Sources</b> PubMed, Embase, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press, and Google Scholar. <b>Eligibility criteria for selecting studies</b> Randomised clinical trials with blinded and non-blinded assessment of the same binary outcome. <b>Results</b> We included 21 trials in the main analysis (with 4391 patients); eight trials provided individual patient data. Outcomes in most trials were subjective—for example, qualitative assessment of the patient’s function. The ratio of the odds ratios ranged from 0.02 to 14.4. The pooled ratio of odds ratios was 0.64 (95% confidence interval 0.43 to 0.96), indicating an average exaggeration of the non-blinded odds ratio by 36%. We found no significant association between low ratios of odds ratios and scores for outcome subjectivity (P=0.27); non-blinded assessor’s overall involvement in the trial (P=0.60); or outcome vulnerability to non-blinded patients (P=0.52). Blinded and non-blinded assessors agreed in a median of 78% of assessments (interquartile range 64-90%) in the 12 trials with available data. The exaggeration of treatment effects associated with non-blinded assessors was induced by the misclassification of a median of 3% of the assessed patients per trial (1-7%). <b>Conclusions</b> On average, non-blinded assessors of subjective binary outcomes generated substantially biased effect estimates in randomised clinical trials, exaggerating odds ratios by 36%. This bias was compatible with a high rate of agreement between blinded and non-blinded outcome assessors and driven by the misclassification of few patients.
Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals
Authors: Patrick J Brennan, Raju V V Tatituri, Manfred Brigl, Edy Y Kim, Amit Tuli, Joseph P Sanderson, Stephan D Gadola, Fong-Fu Hsu, Gurdyal S Besra, Michael B Brenner
Journal: Nature Immunology (2011)
Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm
Authors: Shunichi Homma, John L.P. Thompson, Patrick M. Pullicino, Bruce Levin, Ronald S. Freudenberger, John R. Teerlink, Susan E. Ammon, Susan Graham, Ralph L. Sacco, Douglas L. Mann, J.P. Mohr, Barry M. Massie, Arthur J. Labovitz, Stefan D. Anker, Dirk J. Lok, Piotr Ponikowski, Conrado J. Estol, Gregory Y.H. Lip, Marco R. Di Tullio, Alexandra R. Sanford, Vilma Mejia, Andre P. Gabriel, Mirna L. del Valle, Richard Buchsbaum
Journal: New England Journal of Medicine (2012)

It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm.
Increased rate of spinal trabecular bone loss in patients with inflammatory bowel disease.
Authors: R J Motley, E O Crawley, C Evans, J Rhodes, J E Compston
Journal: Gut (1988)

The rate of spinal trabecular bone loss during one year was measured in 54 patients with inflammatory bowel disease. The mean change in spinal bone mineral content was -5.1 mg/ml K2HPO4, representing 3% of the initial bone mineral content. The rate of bone loss showed a significant negative correlation with body mass index (r = -0.276, p less than 0.05) but no other significant correlations were found with other clinical or biochemical indices, including the total amount of prednisolone taken during the course of the study. Eleven patients had bone loss greater than 15 mg/ml/year; these included four non-steroid treated patients, two of whom had disease confined to the large bowel. The results indicate rapid rates of bone loss in some patients with inflammatory bowel disease over the course of one year. Although steroid therapy and malnutrition are likely to be contributory factors in some patients, other, as yet unidentified, risk factors also operate. The rapid bone loss observed in some patients emphasises the need for effective prophylactic regimes.
Circulatory effects of potassium, glucose and insulin following open-heart surgery
Authors: R. D. Bradley, M. A. Branthwaite
Journal: Thorax (1970)

The cardiovascular effects of an acute infusion of potassium, glucose and insulin (PGI) were investigated in 10 subjects following valve replacement surgery. All required circulatory support with isoprenaline and no additional improvement in cardiac function could be demonstrated following PGI. Pressures in both atria rose out of proportion to the volume infused and there were biochemical changes which suggested that haemodilution had occurred. These findings were attributed to the administration of hypertonic dextrose solution and this also resulted in hyperglycaemia, glycosuria and an osmotic diuresis.
Management of Total Anomalous Pulmonary Venous Return
Authors: GALAL EL-SAID, CHARLES E. MULLINS, DAN G. MCNAMARA
Journal: Circulation (1972)

The effects of age, type of return, presence of pulmonary venous obstruction, obstruction to left heart filling, systemic arterial oxygen saturation (Ao O 2 %), pulmonary-to-systemic flow ratio (Q p /Q p ), pulmonary-to-systemic resistance ratio (R p /R s %), and mean pulmonary artery-to-mean systemic arterial pressure ratio (MPAP/MSAP%) in 35 cases of total anomalous pulmonary venous return seen in the last 5 years, were studied in relation to prognosis and management. The surgical mortality was increased in patients with anomalous venous return to the right common cardinal system (right superior vena cava and azygos vein) regardless of age and was significantly lower in patients over 6 months of age and in those who had preoperative intensive medical management. No relation was found between surgical mortality and Ao O 2 %, R p /R s , MPAP/MSAP%, or the presence of pulmonary venous obstruction. The small size of the left atrium rather than the small size of the left ventricle is felt to be one of the reasons for operative failure. The importance of obstruction to left heart filling at the atrial level was stressed. Until technics for surgical treatment of this group of anomalies in early infancy become more successful, we recommend balloon atrial septostomy in combination with intensive medical management as effective palliative treatment for most of these patients in the first 6 months of life.
Serum Peptidome Profiling Revealed Platelet Factor 4 as a Potential Discriminating Peptide Associated with Pancreatic Cancer
Authors: Georg Martin Fiedler, Alexander Benedikt Leichtle, Julia Kase, Sven Baumann, Uta Ceglarek, Klaus Felix, Tim Conrad, Helmut Witzigmann, Arved Weimann, Christof Schütte, Johann Hauss, Markus Büchler, Joachim Thiery
Journal: Clinical Cancer Research (2009)

Mass spectrometry-based serum peptidome profiling is a promising tool to identify novel disease-associated biomarkers, but is limited by preanalytic factors and the intricacies of complex data processing. Therefore, we investigated whether standardized sample protocols and new bioinformatic tools combined with external data validation improve the validity of peptidome profiling for the discovery of pancreatic cancer-associated serum markers.For the discovery study, two sets of sera from patients with pancreatic cancer (n = 40) and healthy controls (n = 40) were obtained from two different clinical centers. For external data validation, we collected an independent set of samples from patients (n = 20) and healthy controls (n = 20). Magnetic beads with different surface functionalities were used for peptidome fractionation followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Data evaluation was carried out by comparing two different bioinformatic strategies. Following proteome database search, the matching candidate peptide was verified by MALDI-TOF MS after specific antibody-based immunoaffinity chromatography and independently confirmed by an ELISA assay.Two significant peaks (m/z 3884; 5959) achieved a sensitivity of 86.3% and a specificity of 97.6% for the discrimination of patients and healthy controls in the external validation set. Adding peak m/z 3884 to conventional clinical tumor markers (CA 19-9 and CEA) improved sensitivity and specificity, as shown by receiver operator characteristics curve analysis (AUROC(combined) = 1.00). Mass spectrometry-based m/z 3884 peak identification and following immunologic quantitation revealed platelet factor 4 as the corresponding peptide.MALDI-TOF MS-based serum peptidome profiling allowed the discovery and validation of platelet factor 4 as a new discriminating marker in pancreatic cancer.
Analysis of V beta 17a expression in new mouse strains bearing the V beta a haplotype.
Authors: J W Kappler, E Kushnir, P Marrack
Journal: The Journal of Experimental Medicine (1989)

A set of new mouse strains were produced that carry the V beta a haplotype of the TCR-alpha/beta and any of a number of different H-2 haplotypes on backgrounds derived from related C57BL, C57L, and C57BR mice. Study of V beta 17a expression in these mice confirms the association between the presence of IE and the deletion of V beta 17a+ T cells. A second H-2 gene causing deletion of V beta 17a+ T cells was mapped in these mice to the K end of H-2k, and H-2 influences on the level of selection of CD4+ V beta 17a+ T cells were indicated.
Four-Year Angiographic and Intravascular Ultrasound Follow-Up of Patients Treated With Sirolimus-Eluting Stents
Authors: J. Eduardo Sousa, Marco A. Costa, Alexandre Abizaid, Fausto Feres, Ana C. Seixas, Luiz F. Tanajura, Luiz A. Mattos, Robert Falotico, Judith Jaeger, Jeffrey J. Popma, Patrick W. Serruys, Amanda G.M.R. Sousa
Journal: Circulation (2005)

Despite the proven superiority of sirolimus-eluting stents (SESs) compared with bare stents in the first year after implantation, long-term outcomes of patients treated with these novel devices remain unknown. Our goal was to evaluate the clinical, angiographic, and intravascular ultrasound (IVUS) outcomes of patients treated with SESs 4 years after implantation.The study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR; n=15] and fast release [FR; n=15]). Twenty-six patients underwent 4-year angiographic and IVUS follow-up and had matched assessments at all time points (index and 4-, 12-, 24-, and 48-month follow-up). One death occurred during the study period in a patient with a patent SES. There were no target-vessel revascularizations or thromboses between 2- and 4-year follow-up examinations. There was no stent thrombosis, target-lesion revascularization, death, or myocardial infarction in the SR group up to 4 years. Cumulative event-free survival rate was 87% for the total population (80% in the FR group and 93% in the SR group). In-stent late loss was slightly greater in the FR group (0.41+/-0.49 mm) than the SR group (0.09+/-0.23) after 4 years. One patient in the FR group had a 52% in-stent restenosis lesion. Percent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 4 years (FR=9.1% and SR=5.7%).This study confirms the longevity of the optimal outcomes observed in patients treated with sirolimus-eluting Bx Velocity stents 4 years after implantation. In-stent lumen dimensions remained essentially unchanged at 4-year follow-up, particularly in the population treated with the currently available SES (SR formulation).
Temporal trends and ethnic variations in asthma mortality in Singapore, 1976-1995
Authors: T P Ng, W. C Tan
Journal: Thorax (1999)

A study was undertaken to examine temporal trends and ethnic differences in the asthma mortality rate in Singapore.Asthma mortality rates in Singapore were estimated from vital data for the years from 1976 to 1995. Trends in sex and age specific (5-14, 15-34, 35-59, 60+ years) rates were obtained for four periods (1976-80, 1981-85, 1986-90, 1991-95) and for Chinese, Malay, and Indian subjects for the years when these data were available (1989-95).An increase in asthma mortality was observed in children aged 5-14 years from 0.21 per 100,000 person years in 1976-80 to 0.72 per 100,000 person years in 1991-95. No increases were noted in the other age groups but a small decrease was observed in the 1991-95 period for the 35-59 year age group. Marked ethnic differences in mortality rates were observed. In the group aged 5-34 years the asthma mortality rates were 0.5 per 100,000 in Chinese subjects, 1.3 per 100,000 in Indians, and 2.5 per 100,000 in Malay subjects. Similar 2-4 fold differences were observed in all other age groups.Apart from genetic factors, environmental exposures and medical care factors which influence asthma prevalence and severity are most likely to be the causes of the observed temporal trends and ethnic differences in the asthma mortality rate in Singapore, but further studies are needed to elucidate these more fully.
Acute haemodynamic effects of nifedipine at rest and during maximal exercise in patients with chronic cor pulmonale.
Authors: H Singh, M J Ebejer, D A Higgins, A H Henderson, I A Campbell
Journal: Thorax (1985)

The pulmonary hypertension of cor pulmonale can be reversed by sustained correction of hypoxia but continuous oxygen treatment poses problems in clinical practice. Alternative methods of relieving pulmonary vasoconstriction have therefore been explored. Eight patients with chronic cor pulmonale (five of them men) were studied to measure the haemodynamic effects of the calcium antagonist nifedipine, both at rest and on maximal, symptom limited exercise. The mean duration of exercise was unchanged by nifedipine (7.8 (SD 3.3) compared with 7.3(3.1) min). Cardiac output rose from 5.2(1.5) l min-1 to 8.6(3.3) 1 min-1 on exercise. Nifedipine increased resting cardiac output by 26%, but did not influence maximal exercise output. It did not significantly alter resting mean pulmonary artery pressure but reduced the level during exercise from 67(15) to 52(11) mm Hg. Nifedipine lowered resting pulmonary vascular resistance (PVR) by 32% and exercise PVR by 28%. It reduced supine mean systemic arterial pressure by 17%, standing pressure by 22%, and pressure at the maximal exercise level by 20%. Nifedipine lowered supine systemic vascular resistance (SVR) by 35%, standing SVR by 28%, and exercise SVR by 20%. Haemodynamic changes were achieved without adverse symptoms, alteration in arterial PO2, or impairment of calculated oxygen delivery. Nifedipine therefore reduced both pulmonary and systemic vasomotor tone at rest and during exercise. It did not alter exercise tolerance, which is probably limited by underlying respiratory disease. It seems possible therefore that nifedipine could delay the development of cor pulmonale, although this hypothesis remains to be tested.
The Propeptide Mediates Formation of Stromal Stores of PROMIC-1: Role in Determining Prostate Cancer Outcome
Authors: Asne R. Bauskin, David A. Brown, Simon Junankar, Krishan K. Rasiah, Sarah Eggleton, Mark Hunter, Tao Liu, Dave Smith, Tamara Kuffner, Greg J. Pankhurst, Heiko Johnen, Pamela J. Russell, Wade Barret, Phillip D. Stricker, John J. Grygiel, James G. Kench, Susan M. Henshall, Robert L. Sutherland, Samuel N. Breit
Journal: Cancer Research (2005)

Abstract The extracellular matrix (ECM) is a reservoir of cellular binding proteins and growth factors that are critical for normal cell behavior, and aberrations in the ECM invariably accompany malignancies such as prostate cancer. Carcinomas commonly overexpress macrophage inhibitory cytokine 1 (MIC-1), a proapoptotic and antitumorigenic transforming growth factor–β superfamily cytokine. Here we show that MIC-1 is often secreted in an unprocessed propeptide containing form. It is variably processed intracellularly, with unprocessed forms being secreted from several tumor lines, including prostate carcinoma lines, PC-3 and LNCaP. Once secreted, only unprocessed proMIC-1 binds ECM, demonstrating for the first time the occurrence of extracellular stores of MIC-1. The propeptide mediates this association via its COOH-terminal 89 amino acids. Xenograft models bearing tumors secreting various engineered forms of MIC-1 show that the propeptide regulates the balance between ECM stores and circulating serum levels of mature MIC-1 in vivo. The absence of propeptide results in ∼20-fold increase in serum MIC-1 levels. The significance of stromal MIC-1 stores was evaluated in prostate cancer tissue cores, which show major variation in stromal levels of MIC-1. Stromal MIC-1 levels are linked to prostate cancer outcome following radical prostatectomy, with decreasing stromal levels providing an important independent predictor of disease relapse. In low-grade localized prostate cancer (Gleason sum score ≤ 6), the level of MIC-1 stromal stores was the best predictor of future relapse when compared with all other clinicopathologic variables. The secretion and ECM association of unprocessed proMIC-1 is likely to play a central role in modulating local bioavailability of MIC-1 which can affect patient outcome in prostate cancer and other epithelial tumors.
Metabolically biotinylated adenovirus for cell targeting, ligand screening, and vector purification
Authors: M.Brandon Parrott, Kristen E Adams, George T Mercier, Hoyin Mok, Samuel K Campos, Michael A Barry
Journal: Molecular Therapy (2003)

Development of cell-targeting vectors is an important focus for gene therapy. While some ligands can be genetically inserted into virus capsid proteins for cell targeting, for many ligands, this approach can disrupt either ligand function or vector function. To address this problem for adenovirus type 5 vectors, the fiber capsid protein was genetically fused to a biotin acceptor peptide (BAP). Adenovirus particles bearing this BAP were metabolically biotinylated during vector production by the endogenous biotin ligase in 293 cells to produce covalently biotinylated virions. The resulting biotinylated vector could be retargeted to new receptors by conjugation to biotinylated antibodies using tetrameric avidin (K(d) = 10(-15) M). The biotinylated vector could also be purified by biotin-reversible binding on monomeric avidin (K(d) = 10(-7) M). Finally, this vector was used as a ligand screening platform for dendritic cells in which a variety of structurally diverse protein, carbohydrate, and nucleic acid ligands were easily added to the vector using the biotin-avidin interaction. This work demonstrates the utility of metabolically biotinylated viruses for ligand screening, vector targeting, and virus purification applications.
Expression of cryptantigen Th on paroxysmal nocturnal hemoglobinuria erythrocytes in association with a hemolytic exacerbation.
Authors: H Nakakuma, M Hidaka, S Nagakura, Y Nishimura, N Iwamoto, K Horikawa, T Kawaguchi, T Kagimoto, K Takatsuki
Journal: Journal of Clinical Investigation (1995)

Paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes lack complement regulatory membrane proteins and are susceptible to complement. Although the critical role of complement in intravascular hemolysis in PNH is accepted, the precise mechanism of complement activation in vivo is unknown. Accordingly, in a PNH patient who was suffering from a hemolytic precipitation soon after a common cold-like upper respiratory infection, we analyzed the erythrocytes with lectins and by flow cytometry to detect membrane alteration that lead to complement activation. The lectin reactivity of erythrocytes showed the expression of cryptantigen Th. The patient serum at the time of the hemolysis induced the expression of Th on erythrocytes from PNH patients and from healthy volunteers in vitro, whereas neither the patient serum after recovery from the hemolysis nor blood type-matched control serum from healthy donor showed this activity. Moreover, autologous serum selectively hemolyzed Th+ PNH erythrocytes, but not Th- PNH erythrocytes, or Th+ control erythrocytes. Hemolysis was not observed either in complement-inactivated serum or in blood type-matched cord blood serum, which lacks natural antibodies to cryptantigens. These findings indicate that the immunoreaction of infection-induced Th with natural antibody on PNH erythrocytes is a trigger of the complement activation, leading to intravascular hemolysis.