tbuckley/cabot-search huggingface dataset:
Keeping up appearances: the importance of maintaining health status in COPD
Authors: Lorcan McGarvey
Journal: Thorax (2015)

One of the real strengths of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was that it confirmed something that seemed so obvious that no one ever felt the need to say it! So, we now know that if the patient with COPD sitting in front of you in the outpatient clinic has frequent exacerbations then, guess what? Over time, chances are they will continue to exacerbate.1 In the same way, it seems pretty obvious that maintaining or improving the health status of a patient with COPD over the course of any given year would be associated with a better outcome in subsequent years. Well, despite the fact that we have been measuring health status in some shape or form in patients with COPD for almost 30 years, it surprised me that we had no real proof that this was indeed the case.2 ,3 The article by Wilke and colleagues in this month's Thorax finally provides real evidence as to the importance of achieving something that we no doubt have taken for granted as likely to be beneficial.4

In this study, the investigators used the St George's Respiratory Questionnaire (SGRQ) total score recorded in ECLIPSE cohort participants at baseline and …
Tackle mechanisms and match characteristics in women’s elite football tournaments
Authors: P Tscholl, D O’Riordan, C W Fuller, J Dvorak, A Junge
Journal: British Journal of Sports Medicine (2007)

Several tools have been used for assessing risk situations and for gathering tackle information from international football matches for men but not for women.To analyse activities in women's football and to identify the characteristics and risk potentials of tackles.Retrospective video analysis.Video recordings of 24 representative matches from six women's top-level tournaments were analysed for tackle parameters and their risk potential.3531 tackles were recorded. Tackles in which the tackling player came from the side and stayed on her feet accounted for nearly half of all challenges for the ball in which body contact occurred. 2.7% of all tackles were classified as risk situations, with sliding-in tackles from behind and the side having the highest risk potential. Match referees sanctioned sliding-in tackles more often than other tackles (20% v 17%, respectively). Tackle parameters did not change in the duration of a match; however, there was an increase in the number of injury risk situations and foul plays towards the end of each half.Match properties provide valuable information for a better understanding of injury situations in football. Staying on feet and jumping vertically tackle actions leading to injury were sanctioned significantly more times by the referee than those not leading to injury (p<0.001), but no such difference was seen for sliding-in tackles (previously reported to have the highest injury potential in women's football). Therefore, either the laws of the game are not adequate or match referees in women's football are not able to distinguish between sliding-in tackles leading to and those not leading to injury.
AZD2171 Shows Potent Antitumor Activity Against Gastric Cancer Over-Expressing Fibroblast Growth Factor Receptor 2/Keratinocyte Growth Factor Receptor
Authors: Masayuki Takeda, Tokuzo Arao, Hideyuki Yokote, Teruo Komatsu, Kazuyoshi Yanagihara, Hiroki Sasaki, Yasuhide Yamada, Tomohide Tamura, Kazuya Fukuoka, Hiroshi Kimura, Nagahiro Saijo, Kazuto Nishio
Journal: Clinical Cancer Research (2007)

Abstract Purpose: AZD2171 is an oral, highly potent, and selective vascular endothelial growth factor signaling inhibitor that inhibits all vascular endothelial growth factor receptor tyrosine kinases. The purpose of this study was to investigate the activity of AZD2171 in gastric cancer. Experimental Design: We examined the antitumor effect of AZD2171 on the eight gastric cancer cell lines in vitro and in vivo. Results: AZD2171 directly inhibited the growth of two gastric cancer cell lines (KATO-III and OCUM2M), with an IC50 of 0.15 and 0.37 μmol/L, respectively, more potently than the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. Reverse transcription-PCR experiments and immunoblotting revealed that sensitive cell lines dominantly expressed COOH terminus–truncated fibroblast growth factor receptor 2 (FGFR2) splicing variants that were constitutively phosphorylated and spontaneously dimerized. AZD2171 completely inhibited the phosphorylation of FGFR2 and downstream signaling proteins (FRS2, AKT, and mitogen-activated protein kinase) in sensitive cell lines at a 10-fold lower concentration (0.1 μmol/L) than in the other cell lines. An in vitro kinase assay showed that AZD2171 inhibited kinase activity of immunoprecipitated FGFR2 with submicromolar Ki values (∼0.05 μmol/L). Finally, we assessed the antitumor activity of AZD2171 in human gastric tumor xenograft models in mice. Oral administration of AZD2171 (1.5 or 6 mg/kg/d) significantly and dose-dependently inhibited tumor growth in mice bearing KATO-III and OCUM2M tumor xenografts. Conclusions: AZD2171 exerted potent antitumor activity against gastric cancer xenografts overexpressing FGFR2. The results of these preclinical studies indicate that AZD2171 may provide clinical benefit in patients with certain types of gastric cancer.
TGM2 inhibition attenuates ID1 expression in CD44-high glioma-initiating cells
Authors: J. Fu, Q.-y. Yang, K. Sai, F.-r. Chen, J. C. S. Pang, H.-k. Ng, A.-l. Kwan, Z.-p. Chen
Journal: Neuro-Oncology (2013)

CD44 is a molecular marker associated with cancer stem cell populations and treatment resistance in glioma. More effective therapies will result from approaches aimed at targeting glioma cells high in CD44. Glioma-initiating cell lines were derived from fresh surgical glioblastoma samples. Expression of tissue transglutaminase 2 (TGM2) was attenuated through lentivirus-mediated short hairpin RNA knockdown. MTT assay [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] was used to evaluate the growth inhibition induced by TGM2 inhibitor. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling was used to evaluate cell apoptosis following TGM2 inhibition. CD44+ glioma stem cells were sorted by flow cytometry. A nude mice orthotopic xenograft model was used to evaluate the in vivo effect of TGM2 inhibitor. TGM2 was highly expressed in CD44-high glioblastoma tissues and tumor-derived glioma-initiating cell lines. TGM2 knockdown impaired cell proliferation and induced apoptosis in CD44-high glioma-initiating cell lines. Further studies indicated that expression of inhibitor of DNA binding 1 protein (ID1) is regulated by TGM2 and might be an important mediator for TGM2-regulated cell proliferation in CD44-high glioma-initiating cell lines. TGM2 inhibitor reduces ID1 expression, suppresses cell proliferation, and induces apoptosis in CD44-high glioma-initiating cell lines. Furthermore, TGM2 is highly expressed in CD44+ glioma stem cells, while pharmacological inhibition of TGM2 activity preferentially eliminates CD44+ glioma stem cells. Consistently, TGM2 inhibitor treatment reduced ID1 expression and induced apoptosis in our orthotopic mice xenograft model, which can be translated into prolonged median survival in tumor-bearing mice. TGM2 regulates ID1 expression in glioma-initiating cell lines high in CD44. Targeting TGM2 could be an effective strategy to treat gliomas with high CD44 expression.
Role of the Endothelium in the Vascular Effects of the Thrombin Receptor (Protease-Activated Receptor Type 1) in Humans
Authors: Ingibjörg J. Guðmundsdóttir, Ninian N. Lang, Nicholas A. Boon, Christopher A. Ludlam, David J. Webb, Keith A. Fox, David E. Newby
Journal: Journal of the American College of Cardiology (2008)
Safe and Cost Effective Use of Alteplase for the Clearance of Occluded Central Venous Access Devices
Authors: J. P. Timoney, M. G. Malkin, D. M. Leone, J. S. Groeger, M. L. Heaney, D. L. Keefe, M. Klang, C. D. Lucarelli, R. J. Muller, S. L. Eng, M. Connor, T. N. Small, A. E. Brown, L. B. Saltz
Journal: Journal of Clinical Oncology (2002)

To determine whether cryopreserved solutions of the thrombolytic agent alteplase could be used as a safe, effective, and economically reasonable alternative to urokinase in patients presenting with occluded central venous access devices (CVADs).Alteplase has been reported as an efficacious alternative to urokinase for treatment of occluded CVADs. However, the practicality of using alteplase as the thrombolytic of choice for this indication remained conjectural. To make this approach economically feasible, alteplase was diluted to 1 mg/mL and 2.5-mL aliquots were stored at -20 degrees C until use. A need to confirm that the cryopreserving and thawing of the reconstituted solution did not compromise the safety and efficacy reported from prior trials was recognized. A quality assessment initiative was undertaken to concurrently monitor the safety and efficacy of this approach. Patients presenting with occluded CVADs received a sufficient volume of the thawed alteplase solution to fill the occluded catheter(s). Data, including efficacy, adverse reactions, dwell time, and catheter type, were collected over a 5-month period.One hundred twenty-one patients accounting for 168 attempted clearances were assessable for safety and efficacy. One hundred thirty-six (81%) of the 168 catheter clearance attempts resulted in successful catheter clearance (95% confidence interval, 74% to 86%). No adverse events were reported.Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVADs when stored at -20 degrees C for 30 days. The ability to cryopreserve alteplase aliquots makes it an economically reasonable alternative to urokinase in the setting of CVAD occlusion.
Dynamic flow alterations dictate leukocyte adhesion and response to endovascular interventions
Authors: Yoram Richter, Adam Groothuis, Philip Seifert, Elazer R. Edelman
Journal: Journal of Clinical Investigation (2004)

Although arterial bifurcations are frequent sites for obstructive atherosclerotic lesions, the optimal approach to these lesions remains unresolved. Benchtop models of arterial bifurcations were analyzed for flow disturbances known to correlate with vascular disease. These models possess an adaptable geometry capable of simulating the course of arterial disease and the effects of arterial interventions. Chronic in vivo studies evaluated the effect of flow disturbances on the pattern of neointimal hyperplasia. Acute in vivo studies helped propose a mechanism that bridges the early mechanical stimulus and the late tissue effect. Side-branch (SB) dilation adversely affected flow patterns in the main branch (MB) and, as a result, the long-term MB patency of stents implanted in pig arteries. Critical to this effect is chronic MB remodeling that seems to compensate for an occluded SB. Acute leukocyte recruitment was directly influenced by the changes in flow patterns, suggesting a link between flow disturbance on the one hand and leukocyte recruitment and intimal hyperplasia on the other. It is often impossible to simultaneously maximize the total cross-sectional area of both branches and to minimize flow disturbance in the MB. The apparent trade-off between these two clinically desirable goals may explain many of the common failure modes of bifurcation stenting.
Hypercholesterolemia Causes Mechanical Weakening of Rabbit Atheroma
Authors: Mark D. Rekhter, Gary W. Hicks, David W. Brammer, Hussein Hallak, Erick Kindt, Jing Chen, Wendy S. Rosebury, Maureen K. Anderson, Paul J. Kuipers, Michael J. Ryan
Journal: Circulation Research (2000)

Abstract —Hypercholesterolemia may render atherosclerotic plaques prone to rupture. To test this hypothesis, catheters with matrix-covered balloons were implanted into the aorta of rabbits fed standard or 0.5% cholesterol chow (n=70). In 1 month, fibrous plaques developed around the balloon. Time-dependent accumulation of cholesteryl esters and free cholesterol was detected in the plaques of the cholesterol-fed group only. The pressure needed to rupture the plaque by balloon inflation was used as an index of plaque strength. Three months after the catheter implantation, the breaking pressure was 2.1 times lower ( P &lt;0.05) in cholesterol-fed rabbits. It was accompanied by collagen loss, as measured by plaque hydroxyproline content, but not with deficiency of collagen cross-linking. Sirius red staining showed preservation of collagen originally covering the balloon and accumulation of nascent collagen in the lesions of standard chow-fed rabbits. In the cholesterol-fed group, both mature and new collagen underwent degradation predominantly in the plaque shoulders. Collagen breakdown was associated with local accumulation of foamy macrophages. Gel zymography demonstrated relative enhancement of gelatinolytic activity at 92 and 72 kDa, as well as caseinolytic activity at 57, 45, and 19 kDa in the lipid-laden plaques. Lipid accumulation in the plaque was also associated with a loss of smooth muscle cells, the cellular source of the collagen fibers. The remaining smooth muscle cells showed increased collagen synthesis, although it was insufficient to counterbalance collagen degradation and cell loss. Thus, we have obtained direct evidence that hypercholesterolemia is accompanied by enhanced local collagen degradation, which is potentially responsible for plaque weakening.
Characterization of gP85gag as an antigen recognized by Moloney leukemia virus-specific cytolytic T cell clones that function in vivo.
Authors: F A van der Hoorn, T Lahaye, V Müller, M A Ogle, H D Engers
Journal: The Journal of Experimental Medicine (1985)

The gag membrane protein gP85gag, encoded by Moloney murine leukemia virus (M-MLV), was identified as a target molecule recognized by Moloney murine sarcoma virus--M-MLV (M-MSV--M-MLV)-specific cytolytic T lymphocyte (CTL) clones. Target cells infected with Ab-X-MLV, an M-MLV-derived mutant virus not encoding gP85gag, were not lysed by the CTL clones. The same CTL clones were shown previously to induce the destruction of M-MLV-induced tumor cells in the peritoneal cavity. We have now characterized CTL-resistant antigen-loss tumor cell variants that have lost the surface antigen, but which retain transcriptionally silent M-MLV genomes. A cloned antigen-loss variant that reverted in vitro to the CTL-susceptible phenotype reexpressed M-MLV genomes that had undergone an insertion event in the region of the viral DNA coding for the gag membrane protein. Intravenous injection of virus-specific CTL clones inhibited tumor formation in mice injected subcutaneously with M-MSV--M-MLV.
Level of asthma control among asthmatic children in Thessaloniki area in northern Greece
Authors: Katerina Chrysaidou, Fotios Kirvassilis, Nikolaos Karantaglis, Kaliopi Kontouli, Elpis Hatziagorou, John Tsanakas
Journal: European Respiratory Journal (2012)

Background:  In spite of the use of international guidelines for the diagnosis and treatment of asthma, there is continuing evidence of poor asthma control among asthmatic children. Level of asthma control has not been previously evaluated in Greece.   Aim : To evaluate the level of asthma control among asthmatic children in the city of Thessaloniki (Northern Greece).   Method:  Parents of children > 2 years old with doctor9s diagnosis of asthma interviewed by the same physician using a detailed questionnaire including asthma symptoms, limitation of activities, need for rescue medication, asthma exacerbations and emergency visits. 365 children were examined either in Asthma Clinic, or the Emergency Department from November 2010 to May 2011.   Results : Mean age of the children was 7.8 years. 93/365 (25.48%) of them achieved adequate control of asthma, as defined by GINA (Global Initiative for Asthma), 176/365 (48.22%) had partly controlled asthma, whereas uncontrolled asthma was found in the 96/365 (26.3%) of the children. 104/365 (30%) of the study population had used rescue medication for more than two days during the previous week, whereas 70/365 (19.2%) of them reported limitation of activities and 62/365 (17%) had nocturnal symptoms within the previous month.   Conclusions : One out four of the children suffering from asthma in Thessaloniki area achieves control of the disease. An increased use of rescue medication for more than two days was reported in 1/3 children, limitation of activities and nocturnal symptoms in around 1/5 of the children.
Mediastinal paraganglioma presenting as an intracardiac mass with superior vena caval obstruction.
Authors: S K Sharma, S Sharma, S Mukhopadhyay
Journal: Thorax (1993)

A case of mediastinal paraganglioma presenting with superior vena caval obstruction is reported. The tumour extended into the right atrium and ventricle. Tru-Cut biopsy under ultrasonographic guidance was performed safely to provide a diagnosis before death.
Nicorandil-associated perianal ulceration with prominent elastophagocytosis and flexural ulceration
Authors: T. Wong, F. Swain, E. Calonge
Journal: British Journal of Dermatology (2005)

Journal Article Nicorandil‐associated perianal ulceration with prominent elastophagocytosis and flexural ulceration Get access T. Wong, T. Wong Department of Dermatology, Luton and Dunstable Hospital, Luton LU4 0DZ, U.K. *St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K. E‐mail: Tracy.Wong@ldh‐tr.anglox.nhs.uk; tracy121976@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar F. Swain, F. Swain Department of Dermatology, Luton and Dunstable Hospital, Luton LU4 0DZ, U.K. *St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K. E‐mail: Tracy.Wong@ldh‐tr.anglox.nhs.uk; tracy121976@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar E. Calonge E. Calonge Department of Dermatology, Luton and Dunstable Hospital, Luton LU4 0DZ, U.K. *St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K. E‐mail: Tracy.Wong@ldh‐tr.anglox.nhs.uk; tracy121976@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 6, 1 June 2005, Pages 1360–1361, https://doi.org/10.1111/j.1365-2133.2005.06600.x Published: 01 June 2005
Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study
Authors: Prakash Deedwania, Philip Barter, Rafael Carmena, Jean-Charles Fruchart, Scott M Grundy, Steven Haffner, John JP Kastelein, John C LaRosa, Holly Schachner, James Shepherd, David D Waters
Journal: The Lancet (2006)
Efficacy and Safety of the Once-Weekly GLP-1 Receptor Agonist Albiglutide Versus Sitagliptin in Patients With Type 2 Diabetes and Renal Impairment: A Randomized Phase III Study
Authors: Lawrence A. Leiter, Molly C. Carr, Murray Stewart, Angela Jones-Leone, Rhona Scott, Fred Yang, Yehuda Handelsman
Journal: Diabetes Care (2014)

To evaluate weekly subcutaneous albiglutide versus daily sitagliptin in renally impaired patients with type 2 diabetes and inadequately controlled glycemia on a regimen of diet and exercise and/or oral antihyperglycemic medications.In this phase III, randomized, double-blind, multicenter, 52-week study, the primary study end point was HbA1c change from baseline at week 26 in patients with renal impairment, as assessed with estimated glomerular filtration rate and categorized as mild, moderate, or severe (≥60 to ≤89, ≥30 to ≤59, and ≥15 to ≤29 mL/min/1.73 m(2), respectively). Secondary end points included fasting plasma glucose (FPG), weight, achievement of treatment targets, hyperglycemic rescue, and safety.Baseline demographics were similar across treatment and renal impairment groups with overall mean age of 63.3 years, BMI of 30.4 kg/m(2), HbA1c of 8.2% (66 mmol/mol), and diabetes disease duration of 11.2 years. HbA1c change from baseline at week 26 was significantly greater for albiglutide than sitagliptin (-0.83% vs. -0.52%, P = 0.0003). Decreases in HbA1c, FPG, and weight were seen through week 52. Time to hyperglycemic rescue through week 52 was significantly longer for albiglutide than sitagliptin (P = 0.0017). Results of safety assessments were similar between groups, and most adverse events (AEs) were mild or moderate. The incidences of gastrointestinal AEs for albiglutide and sitagliptin were as follows: overall, 31.7%, 25.2%; diarrhea, 10.0%, 6.5%; nausea, 4.8%, 3.3%; and vomiting, 1.6%, 1.2%, respectively.Once-weekly albiglutide therapy in renally impaired patients with type 2 diabetes provided statistically superior glycemic improvement with almost similar tolerability compared with daily sitagliptin therapy.
Sunscreens as a preventative measure in melanoma: an evidence-based approach or the precautionary principle?
Authors: B.L. Diffey
Journal: British Journal of Dermatology (2009)

Meta-analyses of observational case-control studies have demonstrated no association between sunscreen use and the development of malignant melanoma.To postulate whether modern sunscreens are likely to be effective as a preventative agent in melanoma and, if so, how many cases might be avoided by their use.The potential number of melanomas prevented by encouraging the use of modern, high SPF, broad spectrum sunscreens during recreational summer exposure was estimated by combining the prevalence of their use with the relative risk of melanoma in nonusers compared with those people who regularly use these products.Notwithstanding the inherent uncertainties and assumptions that this approach involves, it is shown that significant numbers of melanomas might be avoided by regular sunscreen use during recreational summer sun exposure, and with them appreciable financial, social and emotional costs, even for very modest estimates of the benefit of broad-spectrum sunscreens.Despite the lack of evidence demonstrating the efficacy of modern sunscreens in preventing melanoma, it is argued that it would be irresponsible not to encourage their use, along with other sun protection strategies, as a means of combating the year-on-year rise in melanoma incidence.
Directional Evolution for Microsatellite Size in Maize
Authors: Y. Vigouroux
Journal: Molecular Biology and Evolution (2003)

Directional evolution in microsatellites is the tendency for microsatellites either to increase or to decrease in size over time between populations. We analyzed 99 microsatellite loci in a sample of 193 maize plants representing the entire pre-Columbian range of this crop for evidence of directional evolution. We took advantage of the known phylogeographic history of maize with the independent movement of maize from its ancestral location in Mexico to North and South America. We show that there is an increase in the average allele size of microsatellites in the geographically derived North and South American groups relative to the ancestral Mexican group. We also show that there is a negative correlation between average allele size and altitude in all three groups. Directional evolution in maize microsatellites can be explained by changes in the mutation rate over time and space, changes in the degree of mutational bias to a larger allele, demographic differences between the ancestral and geographically derived populations, and/or scenarios involving selection on microsatellite size. The occurrence of directional evolution for microsatellite size indicates that the estimation of population parameters with microsatellite data in maize should be done with caution.