tbuckley/cabot-search huggingface dataset:
Correlation of force-length area with oxygen consumption in ferret papillary muscle.
Authors: R Hisano, G Cooper
Journal: Circulation Research (1987)

The ventricular systolic pressure-volume area correlates well with myocardial oxygen consumption. However, in isolated muscle preparations, there are experimental data based on both mechanical and energetic measurements that suggest that the pressure-volume area concept may not obtain. In the present study, force-length area, the analog of pressure-volume area for a linear muscle, was examined in the ferret papillary muscle preparation under a wide range of loading conditions. There were two major findings: first, force-length area is closely correlated with oxygen consumption (r = 0.94-0.98); this correlation is better than those for such other indexes as peak force and force-time integral. Furthermore, this relation of oxygen consumption with force-length area is independent of the mode of contraction (isometric or shortening), while the relations with the other indexes are not. Second, quick release imposed after end-systole during isometric contraction was found to curtail oxygen consumption. The first finding, the optimal correlation of force-length area with oxygen consumption, suggests both that the correlation of pressure-volume area with oxygen consumption on the ventricular level arises from a basic property of cardiac muscle and that force-length area may be the best mechanical index to use in calculating regional oxygen consumption for a ventricular segment. The second finding, however, suggests that the time-varying elastance model, on which the concepts of pressure-volume area and force-length area are based, may not provide a complete description of the mechanical basis of cardiac muscle energetics, especially during the isometric contraction.
Na <sup>+</sup> Channel I–II Loop Mediates Parallel Genetic and Phosphorylation-Dependent Gating Changes
Authors: Donald M. Bers, Anthony W. Herren
Journal: Circulation (2012)

this issue of Circulation, Koval et al 1 show that 2 arrhythmogenic human cardiac Na ϩ channel (hNa V 1.5) variants mimic the altered channel gating effects induced by Ca 2ϩ -calmodulin-dependent protein kinase (CaMKII).They also show that phosphorylation of an adjacent CaMKII target site on Na V 1.5 is enhanced in human heart failure (HF) samples and in the border zone of postinfarcted canine hearts.
MPs support NHS reform as health bill passes first parliament debate
Authors: A. O'Dowd
Journal: BMJ (2011)

Large scale change to the NHS in England came a step closer this week as MPs passed the Health and Social Care Bill in its first debate stage on 31 January.

Planned changes that will see GP commissioning consortiums taking control of most of the NHS budget and the abolition of primary care trusts and strategic health authorities were the subject of an often angry six hour debate in the House of Commons. But the bill was comfortably passed after 321 MPs voted for it and 235 voted against in its second reading.

Unease at the proposed changes among the medical profession continues, however, as shown by a new survey of doctors published by the Royal College of General Practitioners. The results show that 61% of GPs disagree with the general direction of the reforms.

At the start of the parliamentary debate the health secretary for England, Andrew Lansley, said, “While the previous government increased funding for the National Health Service to the European average, it did not act similarly to increase its …
Adjuvant Interferon in High-Risk Melanoma: The AIM HIGH Study—United Kingdom Coordinating Committee on Cancer Research Randomized Study of Adjuvant Low-Dose Extended-Duration Interferon Alfa-2a in High-Risk Resected Malignant Melanoma
Authors: B.W. Hancock, K. Wheatley, S. Harris, N. Ives, G. Harrison, J.M. Horsman, M.R. Middleton, N. Thatcher, P.C. Lorigan, J.R. Marsden, L. Burrows, M. Gore
Journal: Journal of Clinical Oncology (2003)

Purpose To evaluate low-dose extended duration interferon alfa-2a as adjuvant therapy in patients with thick (≥ 4 mm) primary cutaneous melanoma and/or locoregional metastases. Patients and Methods In this randomized controlled trial involving 674 patients, the effect of interferon alfa-2a (3 megaunits three times per week for 2 years or until recurrence) on overall survival (OS) and recurrence-free survival (RFS) was compared with that of no further treatment in radically resected stage IIB and stage III cutaneous malignant melanoma. Results The OS and RFS rates at 5 years were 44% (SE, 2.6) and 32% (SE, 2.1), respectively. There was no significant difference in OS or RFS between the interferon-treated and control arms (odds ratio [OR], 0.94; 95% CI, 0.75 to 1.18; P = .6; and OR, 0.91; 95% CI, 0.75 to 1.10; P = .3; respectively). Male sex (P = .003) and regional lymph node involvement (P = .0009), but not age (P = .7), were statistically significant adverse features for OS. Subgroup analysis by disease stage, age, and sex did not show any clear differences between interferon-treated and control groups in either OS or RFS. Interferon-related toxicities were modest: grade 3 (and in only one case, grade 4) fatigue or mood disturbance was seen in 7% and 4% respectively, of patients. However, there were 50 withdrawals (15%) from interferon treatment due to toxicity. Conclusion The results from this study, taken in isolation, do not indicate that extended-duration low-dose interferon is significantly better than observation alone in the initial treatment of completely resected high-risk malignant melanoma.
Persistent GB Virus C Infection and Survival in HIV-Infected Men
Authors: Carolyn F. Williams, Donna Klinzman, Traci E. Yamashita, Jinhua Xiang, Philip M. Polgreen, Charles Rinaldo, Chenglong Liu, John Phair, Joseph B. Margolick, Dietmar Zdunek, Georg Hess, Jack T. Stapleton
Journal: New England Journal of Medicine (2004)

GB virus C (GBV-C), which is not known to be pathogenic in humans, replicates in lymphocytes, inhibits the replication of human immunodeficiency virus (HIV) in vitro, and has been associated with a decreased risk of death among HIV-positive persons in some, but not all, studies. Previous studies did not control for differences in the duration of HIV or GBV-C infection.
Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents
Authors: Andreas Palagyi, Kornelia Neveling, Ursula Plinninger, Andreas Ziesch, Bianca-Sabrina Targosz, Gerald U Denk, Stephanie Ochs, Antonia Rizzani, Daniel Meier, Wolfgang E Thasler, Helmut Hanenberg, Enrico N De Toni, Florian Bassermann, Claus Schäfer, Burkhard Göke, Detlev Schindler, Eike Gallmeier
Journal: Molecular Cancer (2010)

Abstract Background Inactivation of the Fanconi anemia (FA) pathway through defects in one of 13 FA genes occurs at low frequency in various solid cancer entities among the general population. As FA pathway inactivation confers a distinct hypersensitivity towards DNA interstrand-crosslinking (ICL)-agents, FA defects represent rational targets for individualized therapeutic strategies. Except for pancreatic cancer, however, the prevalence of FA defects in gastrointestinal (GI) tumors has not yet been systematically explored. Results A panel of GI cancer cell lines was screened for FA pathway inactivation applying FANCD2 monoubiquitination and FANCD2/RAD51 nuclear focus formation and a newly identified FA pathway-deficient cell line was functionally characterized. The hepatocellular carcinoma (HCC) line HuH-7 was defective in FANCD2 monoubiquitination and FANCD2 nuclear focus formation but proficient in RAD51 focus formation. Gene complementation studies revealed that this proximal FA pathway inactivation was attributable to defective FANCC function in HuH-7 cells. Accordingly, a homozygous inactivating FANCC nonsense mutation (c.553C &gt; T, p.R185X) was identified in HuH-7, resulting in partial transcriptional skipping of exon 6 and leading to the classic cellular FA hypersensitivity phenotype; HuH-7 cells exhibited a strongly reduced proliferation rate and a pronounced G2 cell cycle arrest at distinctly lower concentrations of ICL-agents than a panel of non-isogenic, FA pathway-proficient HCC cell lines. Upon retroviral transduction of HuH-7 cells with FANCC cDNA, FA pathway functions were restored and ICL-hypersensitivity abrogated. Analyses of 18 surgical HCC specimens yielded no further examples for genetic or epigenetic inactivation of FANCC , FANCF , or FANCG in HCC, suggesting a low prevalence of proximal FA pathway inactivation in this tumor type. Conclusions As the majority of HCC are chemoresistant, assessment of FA pathway function in HCC could identify small subpopulations of patients expected to predictably benefit from individualized treatment protocols using ICL-agents.
Functional predictions from inference and observation in sequence-based inflammatory bowel disease research
Authors: Folker Meyer, William L Trimble, Eugene B Chang, Kim M Handley
Journal: Genome biology (2012)

Meta-omics approaches such as metagenomics, metatranscriptomics and metaproteogenomics have the potential to improve our understanding of how the human microbiome affects digestive health and disease. See research article http://www.genomebiology.com/2012/13/9/R79
NEUROTROPHINS: Mediators and Modulators of Pain
Authors: Sophie Pezet, Stephen B. McMahon
Journal: Annual Review of Neuroscience (2006)

The neurotrophin family of neurotrophic factors are well-known for their effects on neuronal survival and growth. Over the past decade, considerable evidence has accumulated from both humans and animals that one neurotrophin, nerve growth factor (NGF), is a peripheral pain mediator, particularly in inflammatory pain states. NGF is upregulated in a wide variety of inflammatory conditions, and NGF-neutralizing molecules are effective analgesic agents in many models of persistent pain. Such molecules are now being evaluated in clinical trials. NGF regulates the expression of a second neurotrophin, brain-derived neurotrophic factor (BDNF), in nociceptors. BDNF is released when nociceptors are activated, and it acts as a central modulator of pain. The chapter reviews the evidence for these roles (and briefly the effects of other neurotrophins), the range of conditions under which they act, and their mechanism of action.
Archaea sister group of Bacteria? Indications from tree reconstruction artifacts in ancient phylogenies
Authors: H. Brinkmann, H. Philippe
Journal: Molecular Biology and Evolution (1999)

The 54-kDa signal recognition particle and the receptor SR alpha, two proteins involved in the cotranslational translocation of proteins, are paralogs. They originate from a gene duplication that occurred prior to the last universal common ancestor, allowing one to root the universal tree of life. Phylogenetic analysis using standard methods supports the generally accepted cluster of Archaea and Eucarya. However, a new method increasing the signal-to-noise ratio strongly suggests that this result is due to a long-branch attraction artifact, with the Bacteria evolving fastest. In fact, the Archaea/Eucarya sisterhood is recovered only by the fast-evolving positions. In contrast, the most slowly evolving positions, which are the most likely to retain the ancient phylogenetic signal, support the monophyly of prokaryotes. Such a eukaryotic rooting provides a simple explanation for the high similarity of Archaea and Bacteria observed in complete-genome analysis, and should prompt a reconsideration of current views on the origin of eukaryotes.
Continuous Aortic Flow Augmentation
Authors: Marvin A. Konstam, Barbara Czerska, Michael Böhm, Ron M. Oren, Jerzy Sadowski, Sanjaya Khanal, William T. Abraham, Andrae Wasler, Johannes B. Dahm, Antonello Gavazzi, Sinisa Gradinac, Victor Legrand, Paul Mohacsi, Gerhard Poelzl, Branislav Radovancevic, Adrian B. Van Bakel, Michael R. Zile, Barry Cabuay, Krzysztof Bartus, Piet Jansen
Journal: Circulation (2005)

Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation (CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy.We studied 24 patients (12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA (mean+/-SD 1.34+/-0.12 L/min) was achieved through percutaneous (n=19) or surgical (n=5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413+/-453 to 1136+/-381 dyne.s.cm(-5) at 72 hours (P=0.0008). Pulmonary capillary wedge pressure decreased from 28.5+/-4.9 to 19.8+/-7.0 mm Hg (P<0.0001), and cardiac index (excluding augmented aortic flow) increased from 1.97+/-0.44 to 2.27+/-0.43 L.min(-1).m(-2) (P=0.0013). Serum creatinine trended downward during treatment (overall P=0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation.In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial.
Malignant Infiltration of the Liver Presenting as Acute Liver Failure
Authors: Nicole E. Rich, Corron Sanders, Randall S. Hughes, Robert J. Fontana, R. Todd Stravitz, Oren Fix, Steven H. Han, Willscott E. Naugler, Atif Zaman, William M. Lee
Journal: Clinical Gastroenterology and Hepatology (2014)
Effect of Magnetic vs Sham-Magnetic Insoles on Plantar Heel Pain
Authors: Mark H. Winemiller, Robert G. Billow, Edward R. Laskowski, W. Scott Harmsen
Journal: JAMA (2003)

Despite anecdotal reports, rigorous scientific evidence of the effectiveness of magnetic insoles for the pain of plantar fasciitis is lacking.To determine whether magnetic insoles provide greater subjective improvement for treatment of plantar heel pain compared with identical nonmagnetized insoles.Randomized, double-blind, placebo-controlled trial conducted from February 12, 2001, to November 9, 2001, of a volunteer sample of 101 adults with diagnoses of plantar heel pain for at least 30 days from a multispecialty group practice clinic in Rochester, Minn. Daily pain diaries were kept for 8 weeks.Cushioned insoles, with either active bipolar magnets or sham magnets, which were worn daily by the participants for 8 weeks.Reported average daily foot pain (by metered visual analog scale [VAS] and by categorical response of change from baseline) at 4 and 8 weeks, and impact of insoles on employment performance and enjoyment.No significant between-group differences were found on any outcome variables studied when comparing active vs sham magnets. Both the nonmagnetic and magnetic groups reported significant improvements in morning foot pain intensity, with mean (SD) VAS scores improving from 6.9 (2.3) and 6.7 (2.0), respectively, at baseline to 3.9 (2.6) for each group at 8 weeks (P =.94). At 8 weeks, 33% of the nonmagnetic group and 35% of the magnetic group reported being all or mostly better (P =.78). At baseline, foot pain interfered moderately with participants' employment enjoyment (mean VAS, 4.2) and improved in both groups by 8 weeks (1.3 and 1.5, respectively; P =.68).Static bipolar magnets embedded in cushioned shoe insoles do not provide additional benefit for subjective plantar heel pain reduction when compared with nonmagnetic insoles.
Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis
Authors: H R. Schumacher
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess the safety and efficacy of etoricoxib, a selective cyclo-oxygenase-2 inhibitor, in comparison with indometacin in the treatment of acute gouty arthritis. <b>Design:</b> Randomised, double blind, active comparator controlled trial. <b>Setting:</b> 43 outpatient study centres in 11 countries. <b>Participants:</b> 142 men and eight women (75 patients per treatment group) aged 18 years or over presenting with clinically diagnosed acute gout within 48 hours of onset. <b>Interventions:</b> Etoricoxib 120 mg administered orally once daily versus indometacin 50 mg administered orally three times daily, both for 8 days <b>Main outcome measures:</b> Patients9 assessment of pain in the study joint over days 2 to 5 (primary end point); investigators9 and patients9 global assessments of response to treatment and tenderness of the study joint (key secondary end points). <b>Results:</b> Etoricoxib showed efficacy comparable to indometacin. Patients9 assessment of pain in the study joint (0-4 point Likert scale, "no pain" to "extreme pain") over days 2 to 5 showed a least squares mean change from baseline of −1.72 (95% confidence interval −1.90 to −1.55) for etoricoxib and −1.83 (−2.01 to −1.65) for indometacin. The difference between treatment groups met prespecified comparability criteria. All other efficacy end points, including those reflecting reduction in inflammation and analgesia, provided corroborative evidence of comparable efficacy. Significant pain relief was evident at the first measurement, 4 hours after the first dose of treatment. Prespecified safety analyses revealed that drug related adverse experiences occurred significantly less frequently with etoricoxib (22.7%) than with indometacin (46.7%) (P=0.003), although overall adverse experience rates were similar between the two treatment groups. <b>Conclusion:</b> Etoricoxib 120 mg once daily provides rapid and effective treatment for acute gouty arthritis comparable to indometacin 50 mg three times daily. Etoricoxib was generally safe and well tolerated in this study.
A randomized phase II study with two schedules of the novel indoloquinone EO9 in non-small-cell lung cancer: A study of the EORTC Early Clinical Studies Group (ECSG)
Authors: N. Pavlidis, A.R. Hanauske, T. Gamucci, J. Smyth, M. Lehnert, A. te Velde, J. Lan, J. Verweij
Journal: Annals of Oncology (1996)
The use of medication and nutritional supplements during FIFA World Cups 2002 and 2006
Authors: P Tscholl, A Junge, J Dvorak
Journal: British Journal of Sports Medicine (2008)

Objective: To examine medication use in male top-level football players prior to and during international tournaments. Design: Prospective survey. Material: 2944 team physicians’ reports on players’ medication intake. Methods: Each team physician was asked to document all medication and nutritional supplements taken in the 72 h prior to each match. Results: A total of 10 384 substances were reported (1.8 substances/player/match); 4450 (42.9%) of these were medicinal and 5934 (57.1%) nutritional supplements. The medications prescribed most frequently were non-steroidal anti-inflammatory agents (n = 2092; 20.1%); more than half of the players took these at least once during a tournament and more than 10% prior to every match (156 out of 1472). β-2-Agonists were reported for 1.4% (n = 20) and inhaled corticosteroids for 1.6% (n = 23) of participating players. Injected corticosteroids were reported for 73 players. Conclusions: The high intake of medication in international football – especially of non-steroidal anti-inflammatory drugs – is alarming and should be addressed. The results raise questions as to whether the medication was taken solely for therapeutic reasons. In view of the potential side effects, more restrictive recommendations for sport need to be developed.
Clinical Trials in Coronary Angiogenesis: Issues, Problems, Consensus
Authors: Michael Simons, Robert O. Bonow, Nicolas A. Chronos, David J. Cohen, Frank J. Giordano, H. Kirk Hammond, Roger J. Laham, William Li, Marylin Pike, Frank W. Sellke, Thomas J. Stegmann, James E. Udelson, Todd K. Rosengart
Journal: Circulation (2000)

Abstract —The rapid development of angiogenic growth factor therapy for patients with advanced ischemic heart disease over the last 5 years offers hope of a new treatment strategy based on generation of new blood supply in the diseased heart. However, as the field of therapeutic coronary angiogenesis is maturing from basic and preclinical investigations to clinical trials, many new and presently unresolved issues are coming into focus. These include in-depth understanding of the biology of angiogenesis, selection of appropriate patient populations for clinical trials, choice of therapeutic end points and means of their assessment, choice of therapeutic strategy (gene versus protein delivery), route of administration, and the side effect profile. The present article presents a summary statement of a panel of experts actively working in the field, convened by the Angiogenesis Foundation and the Angiogenesis Research Center during the 72nd meeting of the American Heart Association to define and achieve a consensus on the challenges facing development of therapeutic angiogenesis for coronary disease.
Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Authors: Paul M Ridker, Eleanor Danielson, Francisco A.H. Fonseca, Jacques Genest, Antonio M. Gotto, John J.P. Kastelein, Wolfgang Koenig, Peter Libby, Alberto J. Lorenzatti, Jean G. MacFadyen, Børge G. Nordestgaard, James Shepherd, James T. Willerson, Robert J. Glynn
Journal: New England Journal of Medicine (2008)

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.
European Consensus Conference for external quality assessment in molecular pathology
Authors: J.H. van Krieken, A.G. Siebers, N. Normanno, F. Blackhall, E. Boone, G. Botti, F. Carneiro, I. Celik, F. Ciardiello, F. Magrassi, A. Lanzara, I.A. Cree, Z.C. Deans, E. Dequeker, A. Edsjö, P.J.T.A. Groenen, O. Kamarainen, H.H. Kreipe, J.H. van Krieken, M.J.L. Ligtenberg, A. Marchetti, S. Murray, N. Normanno, F.J.M. Opdam, S.D. Patterson, S. Patton, C. Pinto, E. Rouleau, E. Schuuring, A.G. Siebers, S. Sterck, M. Taron, S. Tejpar, W. Timens, E. Thunnissen, P.M. van de Ven
Journal: Annals of Oncology (2013)
PI3K/mTOR Inhibitor PF-04691502 Antitumor Activity Is Enhanced with Induction of Wild-Type TP53 in Human Xenograft and Murine Knockout Models of Head and Neck Cancer
Authors: Amanda Herzog, Yansong Bian, Robert Vander Broek, Bradford Hall, Jamie Coupar, Hui Cheng, Anastasia L. Sowers, John D. Cook, James B. Mitchell, Zhong Chen, Ashok B. Kulkarni, Carter Van Waes
Journal: Clinical Cancer Research (2013)

Phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway activation is often associated with altered expression or mutations of PIK3CA, TP53/p73, PTEN, and TGF-β receptors (TGFBR) in head and neck squamous cell carcinomas (HNSCC). However, little is known about how these alterations affect response to PI3K/mTOR-targeted agents.
Predictors of Benefit in Colorectal Cancer Treated With Cetuximab: Are We Getting “Lost in TranslationAL”?
Authors: Chiara Cremolini, Fotios Loupakis, Annamaria Ruzzo, Giuseppe Perrone, Eliana Rulli, Bruno Vincenzi, Giuseppe Tonini, Francesco Graziano, Andrea Onetti Muda, Alfredo Falcone
Journal: Journal of Clinical Oncology (2010)