tbuckley/cabot-search huggingface dataset:
An Enzyme‐Sensitive PEG Hydrogel Based on Aggrecan Catabolism for Cartilage Tissue Engineering
Authors: Stacey C. Skaalure, Stanley Chu, Stephanie J. Bryant
Journal: Advanced Healthcare Materials (2014)

A new cartilage‐specific degradable hydrogel based on photoclickable thiol‐ene poly(ethylene glycol) (PEG) hydrogels is presented. The hydrogel crosslinks are composed of the peptide, CRDTEGE‐ARGSVIDRC, derived from the aggrecanase‐cleavable site in aggrecan. This new hydrogel is evaluated for use in cartilage tissue engineering by encapsulating bovine chondrocytes from different cell sources (skeletally immature (juvenile) and mature (adult) donors and adult cells stimulated with proinflammatory lipopolysaccharide (LPS)) and culturing for 12 weeks. Regardless of cell source, a twofold decrease in compressive modulus is observed by 12 weeks, but without significant hydrogel swelling indicating limited bulk degradation. For juvenile cells, a connected matrix rich in aggrecan and collagen II, but minimal collagens I and X is observed. For adult cells, less matrix, but similar quality, is deposited. Aggrecanase activity is elevated, although without accelerating bulk hydrogel degradation. LPS further decreases matrix production, but does not affect aggrecanase activity. In contrast, matrix deposition in the nondegradable hydrogels consists of aggrecan and collagens I, II, and X, indicative of hypertrophic cartilage. Lastly, no inflammatory response in chondrocytes is observed by the aggrecanase‐sensitive hydrogels. Overall, it is demonstrated that this new aggrecanase‐sensitive hydrogel, which is degradable by chondrocytes and promotes a hyaline‐like engineered cartilage, is promising for cartilage regeneration.
Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis.
Authors: K D O'Brien, M D Allen, T O McDonald, A Chait, J M Harlan, D Fishbein, J McCarty, M Ferguson, K Hudkins, C D Benjamin
Journal: Journal of Clinical Investigation (1993)

Endothelial attachment is the initial step in leukocyte recruit- ment into developing atherosclerotic lesions.To determine whether vascular cell adhesion molecule-i (VCAM-1) expres- sion may play a role in inflammatory cell recruitment into hu- man atherosclerotic lesions, immunohistochemistry was performed with a polyclonal rabbit antisera, raised against recom- binant human VCAM-1, on 24 atherosclerotic coronary plaques and 11 control coronary segments with nonatherosclerotic diffuse intimal thickening from 10 patients.Immunophe- notyping was performed on adjacent sections to identify smooth muscle cells, macrophages, and endothelial cells.To confirm VCAM-1-expressing cell types, double immunostaining with VCAM-1 antisera and each of the cell-specific markers and in situ hybridization were performed.All atherosclerotic plaques contained some VCAM-1, com- pared to 45% of control segments.VCAM-1 was found infrequently on endothelial cells at the arterial lumen in both plaques (21%) and in control segments (27%), but was preva- lent in areas of neovascularization and inflammatory infiltrate in the base of plaques.Double immunostaining and in situ hy- bridization confirmed that most VCAM-1 was expressed by subsets of plaque smooth muscle cells and macrophages.The results document the presence of VCAM-1 in human atherosclerosis, demonstrate VCAM-1 expression by human smooth muscle cells in vivo, and suggest that intimal neovasculature may be an important site of inflammatory cell recruitment into advanced coronary lesions.(
Expression and Clinical Significance of Androgen Receptor in Triple-Negative Breast Cancer
Authors: Yuka Asano, Shinichiro Kashiwagi, Kento Kurata, Tamami Morisaki, Satoru Noda, Hidemi Kawajiri, Tsutomu Takashima, Naoyoshi Onoda, Masahiko Ohsawa, Kosei Hirakawa
Journal: Annals of Oncology (2014)
Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2007 and 2011 staging systems: a pooled analysis of individual patient data
Authors: Joan B Soriano, Bernd Lamprecht, Ana S Ramírez, Pablo Martinez-Camblor, Bernhard Kaiser, Inmaculada Alfageme, Pere Almagro, Ciro Casanova, Cristobal Esteban, Juan J Soler-Cataluña, Juan P de-Torres, Marc Miravitlles, Bartolome R Celli, Jose M Marin, Milo A Puhan, Patricia Sobradillo, Peter Lange, Alice L Sternberg, Judith Garcia-Aymerich, Alice M Turner, MeiLan K Han, Arnulf Langhammer, Linda Leivseth, Per Bakke, Ane Johannessen, Nicolas Roche, Don D Sin
Journal: The Lancet Respiratory Medicine (2015)
Management of pulmonary embolism: recent evidence and the new European guidelines
Authors: Stavros V. Konstantinides, Adam Torbicki
Journal: European Respiratory Journal (2014)

New European guidelines represent a comprehensive, multidisciplinary approach to pulmonary embolism http://ow.ly/CFai2Venous thromboembolism (VTE), which encompasses deep vein thrombosis and its most dangerous complication, acute pulmonary embolism (PE), represents a major threat for the health, the well-being and, under certain circumstances, the life of a large number of patients worldwide.With its acute and long-term complications, VTE also poses a substantial economic burden on national health systems.Alarmingly, since the risk of VTE approximately doubles with each decade after 40 years of age, it is to be expected that an ever larger number of individuals in ''industrialised'', ageing societies will be diagnosed with the disease in the years to come.In 2014, the results of landmark clinical trials and cohort studies, particularly those published in the preceding 6 years, were included in the update of the European Society of Cardiology (ESC) guidelines on the management of PE [1].In the 2014 ESC guidelines, which were endorsed by the European Respiratory Society (ERS), several recommendations regarding diagnostic strategies and algorithms were retained and their validity reinforced and extended.In parallel, new data extending our knowledge with regards to optimal risk assessment and risk-adapted patient treatment led to major revisions in the recommendations in these latter areas, and new sections on the long-term sequelae of PE as well as its management in specific patient populations were added.The present article summarises and highlights the most relevant new aspects of the 2014 version as compared with the previous European guidelines published in 2008.
The predetermination of embryonic sex using flow cytometrically separated X and Y spermatozoa
Authors: D. Cran
Journal: Human Reproduction Update (1996)

A review is given of the predetermination of sex in various domestic animals and in the human using sperm samples enriched for X- and Y-chromosome bearing spermatozoa obtained by flow cytometry and cell sorting. A comparison of other putative methods of sperm separation is made. In separating human X and Y spermatozoa, measurements of the DNA content in each individual gamete using the Hoechst fluorochrome 33342 remains the only validated method. The difference in DNA content between human X and Y spermatozoa is 2.8%, and cell sorters have been adapted to take account of this and the asymmetrical nature of the sperm head. DNA analyses and PCR have been used to validate the method for animal spermatozoa. In the human, fluorescence in-situ hybridization (FISH) has confirmed sorting accuracy. Many correctly-diagnosed normal offspring have been born in various animal species and any potential mutagenic or cytotoxic effects are being closely monitored as are the cost and efficiency of the technology.
Randomized Intergroup Trial of Cisplatin-Paclitaxel Versus Cisplatin-Cyclophosphamide in Women With Advanced Epithelial Ovarian Cancer: Three-Year Results
Authors: M. J. Piccart
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel–cisplatin regimen than for those on a standard cyclophosphamide–cisplatin regimen. Before considering the paclitaxel–cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. Methods: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan–Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. Results: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P = .01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P = .0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P = .0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. Conclusions: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel–cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.
Regulation of Skeletal Muscle Physiology and Metabolism by Peroxisome Proliferator-Activated Receptor δ
Authors: Ewa Ehrenborg, Anna Krook
Journal: Pharmacological Reviews (2009)

Agonists directed against the α and γ isoforms of the peroxisome proliferator-activated receptors (PPARs) have become important for the respective treatment of hypertriglyceridemia and insulin resistance associated with metabolic disease. PPARδ is the least well characterized of the three PPAR isoforms. Skeletal muscle insulin resistance is a primary risk factor for the development of type 2 diabetes. There is increasing evidence that PPARδ is an important regulator of skeletal muscle metabolism, in particular, muscle lipid oxidation, highlighting the potential utility of this isoform as a drug target. In addition, PPARδ seems to be a key regulator of skeletal muscle fiber type and a possible mediator of the adaptations noted in skeletal muscle in response to exercise. In this review we summarize the current status regarding the regulation, and the metabolic effects, of PPARδ in skeletal muscle.
Carbonic Anhydrase 9 Expression Increases with Vascular Endothelial Growth Factor–Targeted Therapy and Is Predictive of Outcome in Metastatic Clear Cell Renal Cancer
Authors: Grant D. Stewart, Fiach C. O’Mahony, Alexander Laird, Sukaina Rashid, Sarah A. Martin, Lel Eory, Alexander L.R. Lubbock, Jyoti Nanda, Marie O’Donnell, Alan Mackay, Peter Mullen, S. Alan McNeill, Antony C.P. Riddick, Michael Aitchison, Daniel Berney, Axel Bex, Ian M. Overton, David J. Harrison, Thomas Powles
Journal: European Urology (2014)

Background: There is a lack of biomarkers to predict outcome with targeted therapy in metastatic clear cell renal cancer (mccRCC).This may be because dynamic molecular changes occur with therapy.Objective: To explore if dynamic, targeted-therapy-driven molecular changes correlate with mccRCC outcome.Design, setting, and participants: Multiple frozen samples from primary tumours were taken from sunitinib-naı ¨ve (n = 22) and sunitinib-treated mccRCC patients (n = 23) for protein analysis.A cohort (n = 86) of paired, untreated and sunitinib/pazopanibtreated mccRCC samples was used for validation.Array comparative genomic hybridisation (CGH) analysis and RNA interference (RNAi) was used to support the findings.Intervention: Three cycles of sunitinib 50 mg (4 wk on, 2 wk off).Outcome measurements and statistical analysis: Reverse phase protein arrays (training set) and immunofluorescence automated quantitative analysis (validation set) assessed protein expression.Results and limitations: Differential expression between sunitinib-naı ¨ve and treated samples was seen in 30 of 55 proteins ( p < 0.05 for each).The proteins B-cell CLL/ lymphoma 2 (BCL2), mutL homolog 1 (MLH1), carbonic anhydrase 9 (CA9), and mechanistic target of rapamycin (mTOR) (serine/threonine kinase) had both increased intratumoural variance and significant differential expression with therapy.The validation cohort confirmed increased CA9 expression with therapy.Multivariate analysis showed high CA9 expression after treatment was associated with longer survival (hazard ratio: 0.48; 95% confidence interval, 0.26-0.87;p = 0.02).Array CGH profiles revealed sunitinib
Yield of Routine Provocative Cardiac Testing Among Patients in an Emergency Department–Based Chest Pain Unit
Authors: Luke K. Hermann, David H. Newman, W. Andrew Pleasant, Dhanadol Rojanasarntikul, Daniel Lakoff, Scott A. Goldberg, W. Lane Duvall, Milena J. Henzlova
Journal: JAMA Internal Medicine (2013)

The American Heart Association recommends routine provocative cardiac testing in accelerated diagnostic protocols for coronary ischemia. The diagnostic and therapeutic yield of this approach are unknown.To assess the yield of routine provocative cardiac testing in an emergency department-based chest pain unit.We examined a prospectively collected database of patients evaluated for possible acute coronary syndrome between March 4, 2004, and May 15, 2010, in the emergency department-based chest pain unit of an urban academic tertiary care center.Patients with signs or symptoms of possible acute coronary syndrome and without an ischemic electrocardiography result or a positive biomarker were enrolled in the database.All patients were evaluated by exercise stress testing or myocardial perfusion imaging.Demographic and clinical features, results of routine provocative cardiac testing and angiography, and therapeutic interventions were recorded. Diagnostic yield (true-positive rate) was calculated, and the potential therapeutic yield of invasive therapy was assessed through blinded, structured medical record review using American Heart Association designations (class I, IIa, IIb, or lower) for the potential benefit from percutaneous intervention.In total, 4181 patients were enrolled in the study. Chest pain was initially reported in 93.5%, most (73.2%) were at intermediate risk for coronary artery disease, and 37.6% were male. Routine provocative cardiac testing was positive for coronary ischemia in 470 (11.2%), of whom 123 underwent coronary angiography. Obstructive disease was confirmed in 63 of 123 (51.2% true positive), and 28 (0.7% overall) had findings consistent with the potential benefit from revascularization (American Heart Association class I or IIa).In an emergency department-based chest pain unit, routine provocative cardiac testing generated a small therapeutic yield, new diagnoses of coronary artery disease were uncommon, and false-positive results were common.
A nomogram for assessment of breathing patterns during treadmill exercise
Authors: J Naranjo, R A Centeno, D Galiano, M Beaus
Journal: British Journal of Sports Medicine (2005)

To assess the breathing patterns of trained athletes under different conditions. The hypothesis is that the breathing pattern during a progressive treadmill exercise is independent of the protocol, at least in healthy people, and can be assessed using a nomogram.A total of 43 male and 21 female athletes from different sports were studied. They performed one of two different protocols (steps or ramp) on a treadmill. The two protocols started at the same speed and had the same rate of increase in work. During the test, the expired air was analysed for CO2 and O2. Ventilation (VE) was continuously recorded, and tidal volume (Vt) and breathing frequency (BF) at the same intensity were analysed for both protocols, as well as Vt/T(i) and T(i)/T(tot).No significant differences were observed in Vt and BF between the two protocols in either the men or women at any level (confidence intervals up to 0.958 in all the groups). T(i)/T(tot) remained constant, and all increases in VE were strongly related to the respective increases in Vt/T(i). Plots of data for men and women showed a curvilinear relation between Vt and BF which could be fitted with an exponential function with a strong correlation (R2 = 0.98 for men and 0.97 for women).Graphic expression of Vt v BF is a useful nomogram for the routine assessment of ventilatory response during exercise in healthy trained subjects.
A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse
Authors: Isabelle Aubin, Carolyn P Adams, Sibylle Opsahl, Dominique Septier, Colin E Bishop, Nathalie Auge, Robert Salvayre, Anne Negre-Salvayre, Michel Goldberg, Jean-Louis Guénet, Christophe Poirier
Journal: Nature Genetics (2005)
Roles of Fungal Sensitization in Severe Asthmatic Patients
Authors: Katsunori Masaki, Koichi Fukunaga, Takashi Kamatani, Kengo Ohtsuka, Takae Tanosaki, Masako Matsusaka, Hiroki Kabata, Soichiro Ueda, Yusuke Suzuki, Koichiro Asano, Tomoko Betsuyaku, Takao Mochimaru
Journal: Journal of Allergy and Clinical Immunology (2015)
Is asymptomatic malaria really asymptomatic? Hematological, vascular and inflammatory effects of asymptomatic malaria parasitemia
Authors: Quirijn de Mast, Judith Brouwers, Din Syafruddin, Teun Bousema, Amrish Y. Baidjoe, Philip G. de Groot, Andre J. van der Ven, Rob Fijnheer
Journal: Journal of Infection (2015)
Four Cases of Nephrolithotomy
Authors: F. Imlach
Journal: BMJ (1889)

symptoms were great restlessness, anxiety, and giddiness, the patients complaining also of " pins and needles " in the legs and feet.In another case, a girl taking 3 grammes daily for chorea became on the third morning drowsy, giddy, and finally delirious, with laboured,slow breathing, these symptoms lasting for about five hours.Dr. Jennings also records a case in which a maniacal condition followed the administration of large doses of the drug.It is striking how closely many of these symptoms resemble those which we have been able to produce in animals.The foregoing research was conducted in the laboratory of Dr. Lauder Brunton at St. Bartholomew's Hospital, and to him we owe our very warm thanks for the use of it, and still more for his kindness in aiding us at all times with his advice and suggestions as to means of procedure.
Increased cell loss in the human jejunum induced by laxatives (ricinoleic acid, dioctyl sodium sulphosuccinate, magnesium sulphate, bile salts).
Authors: J F Bretagne, N Vidon, C L'Hirondel, J J Bernier
Journal: Gut (1981)

Two conjugated bile salts (10 mmol/l sodium glycocholate, 10 mmol/l sodium taurodeoxycholate) and three laxatives (30 mmol/l magnesium sulphate, 10 mmol/l ricinoleic acid, 2 mmol/l dioctyl sodium sulphosuccinate) were tested on seven subjects with no intestinal lesions in 14 experiments by intestinal perfusion of the jejunum. A 25 cm segment was studied. Each solution was perfused at the rate of 10 ml/min. Water and electrolyte fluxes, losses of deoxyribonucleic acid (DNA), and intestinal cell enzyme activity were measured in the fluids collected. All the laxatives and bile salts tested (except sodium glycocholate) induced water and electrolyte secretion, a rise in intraluminal DNA loss, and enzyme activity. It was possible to establish a significant correlation (p less than 0.001) between the amounts of water fluxes and DNA loss under the effect of dioctyl sodium sulphosuccinate and ricinoleic acid.
Estimated GFR Reporting Influences Recommendations for Dialysis Initiation
Authors: K. Scott Brimble, Rajnish Mehrotra, Marcello Tonelli, Carmel M. Hawley, Clare Castledine, Stephen P. McDonald, Vicki Levidiotis, Azim S. Gangji, Darin J. Treleaven, Peter J. Margetts, Michael Walsh
Journal: Journal of the American Society of Nephrology (2013)

Automated reporting of estimated GFR (eGFR) with serum creatinine measurement is now common. We surveyed nephrologists in four countries to determine whether eGFR reporting influences nephrologists' recommendations for dialysis initiation. Respondents were randomly allocated to receive a survey of four clinical vignettes that included either serum creatinine concentration only or serum creatinine and the corresponding eGFR. For each scenario, the respondent was asked to rank his or her likelihood of recommending dialysis initiation on a modified 8-point Likert scale, ranging from 1 ("definitely not") to 8 ("definitely would"). Analysis of the 822 eligible responses received showed that the predicted likelihood of recommending dialysis increased by 0.55 points when eGFR was reported (95% confidence interval, 0.33 to 0.76), and this effect was larger for eGFRs >5 ml/min per 1.73 m(2) (P<0.001). Subgroup analyses suggested that physicians who had been in practice ≥13 years were more affected by eGFR reporting (P=0.03). These results indicate that eGFR reporting modestly increases the likelihood that dialysis is recommended, and physicians should be aware of this effect when assessing patients with severe CKD.
Effect of Acute Psychological Stress on Prefrontal GABA Concentration Determined by Proton Magnetic Resonance Spectroscopy
Authors: Gregor Hasler, Jan Willem van der Veen, Christian Grillon, Wayne C. Drevets, Jun Shen
Journal: American Journal of Psychiatry (2010)

Objective: Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain's major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. Method: A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3×3×2-cm3 voxel selected from the medial prefrontal cortex. Results: Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. Conclusions: This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABA-ergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation.