tbuckley/cabot-search huggingface dataset:
UniPep--a database for human N-linked glycosites: a resource for biomarker discovery.
Authors: Hui Zhang, Paul Loriaux, Jimmy Eng, David Campbell, Andrew Keller, Pat Moss, Richard Bonneau, Ning Zhang, Yong Zhou, Bernd Wollscheid, Kelly Cooke, Eugene C Yi, Hookeun Lee, Elaine R Peskind, Jing Zhang, Richard D Smith, Ruedi Aebersold
Journal: Genome biology (2006)

There has been considerable recent interest in proteomic analyses of plasma for the purpose of discovering biomarkers. Profiling N-linked glycopeptides is a particularly promising method because the population of N-linked glycosites represents the proteomes of plasma, the cell surface, and secreted proteins at very low redundancy and provides a compelling link between the tissue and plasma proteomes. Here, we describe UniPep http://www.unipep.org - a database of human N-linked glycosites - as a resource for biomarker discovery.
The Absence of Pericytes Does Not Increase the Sensitivity of Tumor Vasculature to Vascular Endothelial Growth Factor-A Blockade
Authors: Maya H. Nisancioglu, Christer Betsholtz, Guillem Genové
Journal: Cancer Research (2010)

Recent progress with therapies targeting endothelial cells has drawn attention also to the pericytes as potential target cells for antiangiogenic therapy. Published data suggest that pericytes might confer resistance to vascular endothelial growth factor (VEGF) withdrawal in tumors. This hypothesis has been supported by experiments using tumors with reversible transgenic expression of VEGF-A as well as by individual pharmacologically targeting VEGF and platelet-derived growth factor receptor signaling in endothelial cells and pericytes using receptor tyrosine kinase (RTK) inhibitors with different specificities. However, the RTK inhibitors applied thus far are not entirely specific to the mentioned pathways, and therefore, the effects putatively attributed to pericyte targeting might reflect other antitumor effects. Here, we have reinvestigated the putative benefits of doubly targeting endothelial cells and pericytes in the treatment of experimental tumors. For this purpose, we used two highly specific tools, the pericyte-deficient pdgfb(ret/ret) mouse and the recently developed specific anti-VEGF-A antibody G6-31, which neutralizes both murine and human VEGF-A. We generated B16, Lewis lung carcinoma, and T241 subcutaneous tumors in both pdgfb(ret/ret) and control mice and treated these mice with G6-31. Our results fail to show any improved effect of VEGF inhibition, as measured by tumor growth or decrease in vascular density, in pericyte-deficient tumors compared with controls. Our observations suggest that additional targeting of pericytes does not increase the antitumor effect already generated by anti-VEGF drugs.
The Prevalence of Multifurcations in Tree-space and Their Implications for Tree-search
Authors: Simon Whelan, Daniel Money
Journal: Molecular Biology and Evolution (2010)

Phylogenetic tree-search is a major aspect of many evolutionary studies. Several tree rearrangement algorithms are available for tree-search, but it is hard to draw general conclusions about their relative performance because many effects are data set specific and can be highly dependent on individual implementations (e.g., RAxML or phyml). Using only the structure of the rearrangements proposed by the Nearest Neighbor Interchange (NNI) algorithm, we show tree-search can prematurely terminate if it encounters multifurcating trees. We validate the relevance of this result by demonstrating that in real data the majority of possible bifurcating trees potentially encountered during tree-search are actually multifurcations, which suggests NNI would be expected to perform poorly. We also show that the star-decomposition algorithm is a special case of two other popular tree-search algorithms, subtree pruning and regrafting (SPR) and tree bisection and reconnection (TBR), which means that these two algorithms can efficiently escape when they encounter multifurcations. We caution against the use of the NNI algorithm and for most applications we recommend the use of more robust tree-search algorithms, such as SPR and TBR.
Genome-wide association meta-analysis identifies new endometriosis risk loci
Authors: Dale R Nyholt, Siew-Kee Low, Carl A Anderson, Jodie N Painter, Satoko Uno, Andrew P Morris, Stuart MacGregor, Scott D Gordon, Anjali K Henders, Nicholas G Martin, John Attia, Elizabeth G Holliday, Mark McEvoy, Rodney J Scott, Stephen H Kennedy, Susan A Treloar, Stacey A Missmer, Sosuke Adachi, Kenichi Tanaka, Yusuke Nakamura, Krina T Zondervan, Hitoshi Zembutsu, Grant W Montgomery
Journal: Nature Genetics (2012)
Radiofrequency Ablation vs Endoscopic Surveillance for Patients With Barrett Esophagus and Low-Grade Dysplasia
Authors: K. Nadine Phoa, Frederike G. I. van Vilsteren, Bas L. A. M. Weusten, Raf Bisschops, Erik J. Schoon, Krish Ragunath, Grant Fullarton, Massimiliano Di Pietro, Narayanasamy Ravi, Mike Visser, G. Johan Offerhaus, Cees A. Seldenrijk, Sybren L. Meijer, Fiebo J. W. ten Kate, Jan G. P. Tijssen, Jacques J. G. H. M. Bergman
Journal: JAMA (2014)

<h3>Importance</h3> Barrett esophagus containing low-grade dysplasia is associated with an increased risk of developing esophageal adenocarcinoma, a cancer with a rapidly increasing incidence in the western world. <h3>Objective</h3> To investigate whether endoscopic radiofrequency ablation could decrease the rate of neoplastic progression. <h3>Design, Setting, and Participants</h3> Multicenter randomized clinical trial that enrolled 136 patients with a confirmed diagnosis of Barrett esophagus containing low-grade dysplasia at 9 European sites between June 2007 and June 2011. Patient follow-up ended May 2013. <h3>Interventions</h3> Eligible patients were randomly assigned in a 1:1 ratio to either endoscopic treatment with radiofrequency ablation (ablation) or endoscopic surveillance (control). Ablation was performed with the balloon device for circumferential ablation of the esophagus or the focal device for targeted ablation, with a maximum of 5 sessions allowed. <h3>Main Outcomes and Measures</h3> The primary outcome was neoplastic progression to high-grade dysplasia or adenocarcinoma during a 3-year follow-up since randomization. Secondary outcomes were complete eradication of dysplasia and intestinal metaplasia and adverse events. <h3>Results</h3> Sixty-eight patients were randomized to receive ablation and 68 to receive control. Ablation reduced the risk of progression to high-grade dysplasia or adenocarcinoma by 25.0% (1.5% for ablation vs 26.5% for control; 95% CI, 14.1%-35.9%;<i>P</i> &lt; .001) and the risk of progression to adenocarcinoma by 7.4% (1.5% for ablation vs 8.8% for control; 95% CI, 0%-14.7%;<i>P</i> = .03). Among patients in the ablation group, complete eradication occurred in 92.6% for dysplasia and 88.2% for intestinal metaplasia compared with 27.9% for dysplasia and 0.0% for intestinal metaplasia among patients in the control group (<i>P</i> &lt; .001). Treatment-related adverse events occurred in 19.1% of patients receiving ablation (<i>P</i> &lt; .001). The most common adverse event was stricture, occurring in 8 patients receiving ablation (11.8%), all resolved by endoscopic dilation (median, 1 session). The data and safety monitoring board recommended early termination of the trial due to superiority of ablation for the primary outcome and the potential for patient safety issues if the trial continued. <h3>Conclusions and Relevance</h3> In this randomized trial of patients with Barrett esophagus and a confirmed diagnosis of low-grade dysplasia, radiofrequency ablation resulted in a reduced risk of neoplastic progression over 3 years of follow-up. <h3>Trial Registration</h3> trialregister.nl Identifier:NTR1198
Ibuprofen and Aspirin in Acute Rheumatic Fever
Authors: R. Larry Marshall
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I would like to clarify one point in the article "The Return of Acute Rheumatic Fever in Young Adults."1 The authors state that the one patient with rheumatic nodules responded to ibuprofen therapy. This patient presented to the hospital while taking ibuprofen and continued its use for a short period. His anti-inflammatory therapy was changed from ibuprofen to a delay-release, enteric-coated aspirin preparation. He required a daily dose of 5850 mg (80 mg/kg per day) to clear the arthritis. I point this out to emphasize that aspirin has been and should still be the indicated anti-inflammatory drug of choice for the arthritis of acute rheumatic fever so that no one may falsely be misled to believe this young man responded to the ibuprofen therapy alone.
Increased plasma S-adenosyl-homocysteine levels induce the proliferation and migration of VSMCs through an oxidative stress-ERK1/2 pathway in apoE−/− mice
Authors: Xiaoqin Luo, Yunjun Xiao, Fenglin Song, Yan Yang, Min Xia, Wenhua Ling
Journal: Cardiovascular Research (2012)

AimsAlthough S-adenosyl-homocysteine (SAH) is considered to be a more sensitive predictor of cardiovascular disease than homocysteine, the underlying mechanisms of its effects remain unknown. We investigated the in vivo and in vitro effects of SAH on vascular smooth muscle cells (VSMCs) proliferation and migration related to the development of atherogenesis in apolipoprotein E-deficient (apoE−/−) mice.
Inspiratory muscle training in chronic airflow limitation: effect on exercise performance
Authors: C Lisboa, C Villafranca, A Leiva, E Cruz, J Pertuze, G Borzone
Journal: European Respiratory Journal (1997)

The effect of inspiratory muscle training (IMT) on exercise capacity in patients with chronic airflow limitation (CAL) has been debated. The present study was planned to further investigate the effects of IMT on exercise performance. Twenty patients (aged 62+/-1 yrs; forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 36+/-2%) were trained 30 min daily for 6 days a week during 10 weeks, with either 30% (Group 1) or 10% (Group 2) of peak maximal inspiratory pressure (PI,max) as a training load. Exercise performance was evaluated by the distance walked in 6 min (6MWD) and by changes in oxygen consumption (V'O2) and minute ventilation (V'E) during a progressive exercise test. Changes in PI,max and dyspnoea were also measured. Results showed a significant increment in peak PI,max in both groups, whereas dyspnoea and 6MWD improved only in Group 1 (p<0.05 and p<0.01, respectively). No increment in maximal workload or in peak V'O2 was observed in either group. Patients in Group 1, however, showed a reduction in V'E and V'O2 for the same exercise. A correlation between changes in V'E and V'O2 during a workload of 75 kpm x min(-1) was observed in Group 1 (r=0.92; p<0.001). We conclude that inspiratory muscle training using a load of 30% peak maximal inspiratory pressure, improves dyspnoea, increases walking capacity and reduces the metabolic cost of exercise.
Lead in the placenta, membranes, and umbilical cord in relation to pregnancy outcome in a lead-smelter community.
Authors: P A Baghurst, E F Robertson, R K Oldfield, B M King, A J McMichael, G V Vimpani, N R Wigg
Journal: Environmental Health Perspectives (1991)

As part of a cohort study of the effects of chronic exposure to lead on pregnancy outcome and child development, lead concentrations in the umbilical cord and placental tissues (body and membranes) from 9 late fetal deaths, 23 preterm births, and 18 births associated with premature rupture of the amniotic membranes were compared with the lead concentrations in the tissues obtained at 22 normal births. Modest elevations in lead concentration were found in the placental body of late fetal deaths (stillbirths) and preterm births as well as in the cord tissue associated with preterm births and premature rupture of membranes. The geometric mean lead concentration in the membranes from late fetal deaths was 2.73 micrograms/g of dry tissue (95% confidence limits 0.69-10.8), which was 3.5 times higher than the mean found in normal births (0.78 micrograms/g, 95% confidence limits 0.61-1.00). The concentration in the membranes of preterm births was also significantly high, being 1.24 micrograms/G (0.91-1.67). Low correlations of membrane and antenatal blood lead concentrations suggest that other factors in addition to exposure to environmental lead may influence the amount of lead accumulated in the placental membranes.
Prevalence of asthma
Authors: H Ross Anderson
Journal: BMJ (2005)

Is no longer increasing in some countries, but the reasons for this are unclear 

A broad consensus exists that in most Western countries the prevalence of asthma increased over the last four decades of the 20th century. This is based largely on repeat studies of school age children. Evidence is emerging that in recent years this trend has flattened or fallen in some countries. For example, as part of the UK arm of the international study of asthma and allergies in childhood (ISAAC), repeat studies found that self reported symptoms of asthma in 13-14 year old children had fallen by about 20% in the United Kingdom between 1995 and 2002.1 This trend was also observed in the health survey for England between 1996 and 2001.2 Over the same period a similar fall in symptoms of asthma in 6-7 year old children reported by parents was seen in Melbourne.3 On the other hand, the only available repeat survey of preschool children noted …
Involvement of Renal Progenitor Tubular Cells in Epithelial-to-Mesenchymal Transition in Fibrotic Rat Kidneys
Authors: Shin Yamashita, Akito Maeshima, Yoshihisa Nojima
Journal: Journal of the American Society of Nephrology (2005)

Renal progenitor tubular cells (label-retaining cells [LRC]) were recently identified in normal kidneys by in vivo bromodeoxyuridine (BrdU) labeling. This study was conducted to examine the behavior of LRC in renal fibrosis. BrdU was injected intraperitoneally into normal rats daily for 7 d. After a 2-wk chase period, unilateral ureteral obstruction (UUO) was induced in these rats. In normal and contralateral kidneys, LRC were observed scattering among tubular epithelial cells. After UUO, the number of the LRC significantly increased, and most of them were positive for proliferating cell nuclear antigen (PCNA). In contrast, PCNA+ cells lacking BrdU label were rarely observed. It is interesting that LRC were detected not only in tubules but also in the interstitium after UUO. Laminin staining showed that a number of the LRC were adjacent to the destroyed tubular basement membrane. Some tubules, including LRC, lost the expression of E-cadherin after UUO. A large number of cell populations expressed vimentin, heat shock protein 47, or α-smooth muscle actin in the UUO kidneys, and each population contained LRC. None of the LRC was positive for these fibroblastic markers in contralateral kidneys. When renal tubules from BrdU-treated rats were cultured in the gel, some cells protruded from the periphery of the tubules and migrated into the gel. Most of these cells were BrdU+. Neither the total content of BrdU in the kidneys nor the number of LRC in bone marrow significantly changed after UUO. Collectively, these results suggest that LRC is a cell population that proliferates, migrates, and transdifferentiates into fibroblast-like cells during renal fibrosis.
Costs and Benefits of the National Cancer Institute Central Institutional Review Board
Authors: Todd H. Wagner, Christine Murray, Jacquelyn Goldberg, Jeanne M. Adler, Jeffrey Abrams
Journal: Journal of Clinical Oncology (2009)

In 2001, the National Cancer Institute (NCI) formed the Central Institutional Review Board (CIRB) to conduct a single human subjects review for its multisite phase III oncology trials. The goal of this study was to assess whether NCI's CIRB was associated with lower effort, time, and cost in processing adult phase III oncology trials.We conducted an observational study and compared sites affiliated with the NCI CIRB to unaffiliated sites that used their local IRB for review. Oncology research staff and IRB staff were surveyed to understand effort and timing. Response rates were 60% and 42%, respectively. Analysis of these survey data yielded information on effort, timing, and costs. We combined these data with CIRB operational data to determine the net savings of the CIRB using a societal perspective.CIRB affiliation was associated with faster reviews (33.9 calendar days faster on average), and 6.1 fewer hours of research staff effort. CIRB affiliation was associated with a savings of $717 per initial review. The estimated cost of running the CIRB was $161,000 per month. The CIRB yielded a net cost of approximately $55,000 per month from a societal perspective. Whether the CIRB results in higher or lower quality reviews was not assessed because there is no standard definition of review quality.The CIRB was associated with decreases in investigator and IRB staff effort and faster protocol reviews, although savings would be higher if institutions used the CIRB as intended.
Response to: Analyses Using Time-Dependent Pioglitazone Usage in Cox Models May Lead to Wrong Conclusions About Its Association With Cancer
Authors: Laurel Habel, Assiamira Ferrara, Warren B. Bilker, Charles P. Quesenberry, Joe V. Selby, Stephen K. Van Den Eeden, Brian L. Strom, James D. Lewis
Journal: Diabetes Care (2011)

We thank Yang and Chan (1) for their interest in our articles (2,3). They propose that our studies may be biased by use of time-varying exposures in Cox regression models.

If more severe hyperglycemia is associated both with increased cancer risk and with use of pioglitazone, and it is also affected by pioglitazone therapy (i.e., hyperglycemia is both a confounder and an intermediate variable), we agree that our use of the time-dependent …
Liver-Kidney Transplantation to Cure Atypical Hemolytic Uremic Syndrome
Authors: Jeffrey M. Saland, Piero Ruggenenti, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2008)

Atypical hemolytic uremic syndrome is often associated with mutations in genes encoding complement regulatory proteins and secondary disorders of complement regulation. Progression to kidney failure and recurrence with graft loss after kidney transplantation are frequent. The most common mutation is in the gene encoding complement factor H. Combined liver-kidney transplantation may correct this complement abnormality and prevent recurrence when the defect involves genes encoding circulating proteins that are synthesized in the liver, such as factor H or I. Good outcomes have been reported when surgery is associated with intensified plasma therapy. A consensus conference to establish treatment guidelines for atypical hemolytic uremic syndrome was held in Bergamo in December 2007. The recommendations in this article are the result of combined clinical experience, shared research expertise, and a review of the literature and registry information. This statement defines groups in which isolated kidney transplantation is extremely unlikely to be successful and a combined liver-kidney transplant is recommended and also defines those for whom kidney transplant remains a viable option. Although combined liver-kidney or isolated liver transplantation is the preferred therapeutic option in many cases, the gravity of risk associated with the procedure has not been eliminated completely, and assessment of risk and benefit requires careful and individual attention.
Dendritic Cell Maturation Overrules H-2d–Mediated Natural Killer T (Nkt) Cell Inhibition
Authors: Yoshinori Ikarashi, Rumiko Mikami, Albert Bendelac, Magali Terme, Nathalie Chaput, Masahiro Terada, Thomas Tursz, Eric Angevin, François A. Lemonnier, Hiro Wakasugi, Laurence Zitvogel
Journal: The Journal of Experimental Medicine (2001)

Given the broad expression of H-2 class Ib molecules on hematopoietic cells, antigen presentation pathways among CD1d expressing cells might tightly regulate CD1d-restricted natural killer T (NKT) cells. Bone marrow-derived dendritic cells (BM-DCs) and not adherent splenocytes become capable of triggering NK1.1(+)/T cell receptor (TCR)(int) hepatic NKT cell activation when (a) immature BM-DCs lack H-2D(b)-/- molecules or (b) BM-DCs undergo a stress signal of activation. In such conditions, BM-DCs promote T helper type 1 predominant CD1d-restricted NKT cell stimulation. H-2 class Ia-mediated inhibition involves more the direct H-2D(b) presentation than the indirect Qa-1(b) pathway. Such inhibition can be overruled by B7/CD28 interactions and marginally by CD40/CD40L or interleukin 12. These data point to a unique regulatory role of DCs in NKT cell innate immune responses and suggest that H-2 class Ia and Ib pathways differentially control NKT cell recognition of DC antigens.
Toll-like Receptor 7 Rapidly Relaxes Human Airways
Authors: Matthew G. Drake, Gregory D. Scott, Becky J. Proskocil, Allison D. Fryer, David B. Jacoby, Elad H. Kaufman
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Toll-like receptors (TLRs) 7 and 8 detect respiratory virus single-stranded RNA and trigger an innate immune response. We recently described rapid TLR7-mediated bronchodilation in guinea pigs.To characterize TLR7 expression and TLR7-induced airway relaxation in humans and in eosinophilic airway inflammation in guinea pigs. To evaluate the relaxant effects of other TLRs.Human airway smooth muscle strips were contracted with methacholine in vitro, and responses to TLR7 and TLR8 agonists were assessed. TLR7-mediated nitric oxide production was measured using a fluorescent indicator, and TLR7 expression was characterized using immunofluorescence. TLR7 signaling was also evaluated in ovalbumin-challenged guinea pigs.The TLR7 agonist imiquimod (R837) caused rapid dose-dependent relaxation of methacholine-contracted human airways in vitro. This was blocked by the TLR7 antagonist IRS661 and by inhibiting nitric oxide production but not by inhibiting prostaglandin production. TLR7 activation markedly increased fluorescence of a nitric oxide detector. TLR7 was expressed on airway nerves, but not airway smooth muscle, implicating airway nerves as the source of TLR7-induced nitric oxide production. TLR7-mediated relaxation persisted in inflamed guinea pigs airways in vivo. The TLR8 agonists polyuridylic acid and polyadenylic acid also relaxed human airways, and this was not blocked by the TLR7 antagonist or by blocking nitric oxide or prostaglandin production. No other TLRs relaxed the airways.TLR7 is expressed on airway nerves and mediates relaxation of human and animal airways through nitric oxide production. TLR7-mediated bronchodilation may be a new therapeutic strategy in asthma.
BMA rejects Tooke proposal for a sub-consultant grade
Authors: Adrian O'Dowd
Journal: BMJ (2007)

Doctors' leaders have rejected the idea of the NHS creating a new “inferior” grade of doctor with a specialist qualification but less expertise than a consultant.

The idea of a sub-consultant is unnecessary and would neither improve the care of patients nor save the NHS money, says the BMA in its response to the interim report from the inquiry into the reform of medical careers, chaired by John Tooke, head of the Peninsula Medical School.

Although the BMA welcomed the “excellent” work being done …