tbuckley/cabot-search huggingface dataset:
Efficacy of Imatinib in Aggressive Fibromatosis: Results of a Phase II Multicenter Sarcoma Alliance for Research through Collaboration (SARC) Trial
Authors: Rashmi Chugh, J. Kyle Wathen, Shreyaskumar R. Patel, Robert G. Maki, Paul A. Meyers, Scott M. Schuetze, Dennis A. Priebat, Dafydd G. Thomas, Jon A. Jacobson, Brian L. Samuels, Robert S. Benjamin, Laurence H. Baker
Journal: Clinical Cancer Research (2010)

Aggressive fibromatoses (AF; desmoid tumors) are rare clonal neoplastic proliferations of connective tissues that can be locally aggressive despite wide surgical resection and/or radiation therapy. The Sarcoma Alliance for Research through Collaboration (SARC) initiated a prospective phase II trial to investigate the outcome of patients treated with imatinib, a multiple tyrosine kinase inhibitor, in patients with AF, or 1 of 10 sarcoma subtypes. Here, we report specifically on the outcome of patients with AF as well as evaluations undertaken to examine the mechanism of imatinib.Patients ≥10 years old with desmoid tumors that were not curable by surgical management or in whom curative surgery would lead to undesirable functional impairment were eligible. Imatinib was prescribed at 300 mg twice daily [body surface area (BSA) ≥ 1.5 m(2)], 200 mg twice daily (BSA = 1.0-1.49 m(2)), or 100 mg twice daily (BSA < 1.0 m(2)). Response outcomes at 2 and 4 months were assessed. Tissue specimens were analyzed by immunohistochemistry for expression of cKIT, platelet-derived growth factor receptor α (PDGFRα), PDGFRβ, AKT, PTEN, FKHR, and β-catenin. Tumor DNA was analyzed for PDGFRα exon 18 and APC mutations by allelic discrimination PCR.Fifty-one patients were enrolled. The median number of prior regimens was 1. Kaplan-Meier estimates of 2- and 4-month progression-free survival rates were 94% and 88%, respectively, and 1-year progression-free survival was 66%. Objective response rate was 6% (3 of 51). Expression and polymorphisms of target proteins were identified in tissue samples, but no significant correlation with outcome was observed using the samples available.Imatinib may have a role in the management of unresectable or difficult to resect desmoid tumors.
Systematic sports medical prophylactic evaluations in the countries of the former USSR
Authors: P Mustafins, A Landyr, I Schybria, J Istomina, T Gurevich
Journal: British Journal of Sports Medicine (2011)

Background Periodic health evaluations for athletes are widely discussed in the sports medical literature, and are intended to screen for underlying cardiovascular disease, identify sports injury risk factors and posture disturbances, as well as exercise induced physiological conditions. Objective To review the systematic the athletes' periodic health evaluations in the territories of the former USSR. Participants Selected sports medicine outpatient centres (SMC) and sports medicine physicians in Russia and Estonia. Methods We reviewed the structure and outcome of the yearly visits at the participating SMCs, and the sports medicine educational curriculum at the University of Tartu in Estonia. Results Periodic health evaluations for athletes have been conducted since 1949. The system integrates the facilities (sports medical centers) and the education of the sports physicians. Outpatient check ups of the athletes coming from all the levels of sport were conducted at the SMC. At one time over 500 SMCs existed, involving sports physicians, surgeons, neurologists, otolaryngologists, ophthalmologists, dentists and gynaecologists. Anthropometric data were collected, in addition to EKG, physical work capacity testing, and laboratory measurements – depending on the athletes' level and on a kind of sport. As a current sample, an annual amount of visits to the physicians per single regional SMC was 99 601 (Yekaterinburg Sports medical centre (Russia), prophylactic check ups and treatments, year 2009). The specific program of sports physician education at the University of Tartu in Estonia began in 1959. The program comprised the standard MD curriculum plus additional courses on sports theory, sports physiology, sports cardiology, exercise stress testing, sports injury, and rehabilitation. A total of 818 physicians were trained through 1995 – when the program was closed after the breakup of the USSR. Although still in existence in Russia, in many other countries the system has been downscaled or phased out. Conclusions To our knowledge, the system described was the largest state-sponsored sports medical prophylactic approach in the world. Although in many instances there was no proof of the cost effectiveness of this approach, many elements of the athletes' periodic health evaluations and education of the sports physicians we describe should be considered as precursors of today's modern sports medicine programs.
Tumor necrosis factor-α regulatesin vivo nitric oxide synthesis and induces liver injury during endotoxemia
Authors: Brian G. Harbrecht, Mauricio Di Silvio, A. J. Demetris, Richard L. Simmons, Timothy R. Billiar
Journal: Hepatology (1994)

Tumor necrosis factor-alpha is a principal mediator of the pathophysiological effects of endotoxemia and endotoxin shock. Tumor necrosis factor-alpha also contributes to the stimulation of nitric oxide synthesis by the induction of the enzyme nitric oxide synthase in a variety of tissues. Although the importance of tumor necrosis factor-alpha in the induction of nitric oxide synthase activity in vitro is well known, its role in in vivo nitric oxide synthesis has not been convincingly established. We were interested in determining whether tumor necrosis factor-alpha plays a significant role in the in vivo induction of nitric oxide synthesis. In Corynebacterium parvum-primed mice, lipopolysaccharide injection resulted in elevated serum tumor necrosis factor-alpha levels early and increased hepatic enzyme release (641 +/- 80 IU AST/L; 22.7 +/- 1.9 IU ornithine carbamoyltransferase per liter) and plasma nitrite and nitrate (804 +/- 84 mumol/L) 5 hr after lipopolysaccharide injection. Polyclonal rabbit anti-mouse anti-tumor necrosis factor-alpha reduced in vivo tumor necrosis factor-alpha levels (1 hr, 7,332 +/- 1,492 U tumor necrosis factor-alpha per milliliter) and reduced nitric oxide synthesis as measured by plasma nitrite and nitrate (352 +/- 69 mumol/L). Polyclonal rabbit anti-mouse anti-tumor necrosis factor-alpha also reduced lipopolysaccharide-induced hepatic enzyme release (428 +/- 33 IU AST/L; 16.0 +/- 2.5 IU ornithine carbamoyltransferase per liter). NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthesis, also decreased plasma nitrite and nitrate (104 +/- 9 mumol/L) but increased the lipopolysaccharide-induced hepatic injury (797 +/- 66 IU AST/L; 33.1 +/- 2.1 IU ornithine carbamoyltransferase per liter).(ABSTRACT TRUNCATED AT 250 WORDS)
Severe acute respiratory syndrome: Clinical outcome after inpatient outbreak of SARS in Singapore
Authors: Y.-M. Tan
Journal: BMJ (2003)

<h3>Objectives</h3> Physical activity is fundamental in diabetes management for good metabolic control. This study aimed to identify barriers to performing leisure time physical activity and explore differences based on gender, age, marital status, employment, education, income and perceived stages of change in physical activity in adults with type 2 diabetes in Oman. <h3>Design</h3> Cross-sectional study using an Arabic version of the ‘Barriers to Being Active’ 27-item questionnaire. <h3>Setting</h3> Seventeen primary health centres randomly selected in Muscat. <h3>Participants</h3> Individuals&gt;18 years with type 2 diabetes, attending diabetes clinic for &gt;2 years and with no contraindications to performing physical activity. <h3>Primary and secondary outcome measures</h3> Participants were asked to rate how far different factors influenced their physical activity under the following categories: fear of injury, lack of time, social support, energy, willpower, skills, resources, religion and environment. On a scale of 0–9, barriers were considered important if scored ≥5. <h3>Results</h3> A total of 305 questionnaires were collected. Most (96%) reported at least one barrier to performing leisure time physical activity. Lack of willpower (44.4%), lack of resources (30.5%) and lack of social support (29.2%) were the most frequently reported barriers. Using χ<sup>2</sup> test, lack of willpower was significantly different in individuals with low versus high income (54.2%vs40%, P=0.002) and in those reporting inactive versus active stages of change for physical activity (50.7%vs34.7%, P=0.029), lack of resources was significantly different in those with low versus high income (40%vs24.3%, P=0.004) and married versus unmarried (33.8%vs18.5%, P=0.018). Lack of social support was significant in females versus males (35.4%vs20.8%, P=0.005). <h3>Conclusions</h3> The findings can inform the design on physical activity intervention studies by testing the impact of strategies which incorporate ways to address reported barriers including approaches that enhance self-efficacy and social support.
Diverse Associations between <i>ESR1</i> Polymorphism and Breast Cancer Development and Progression
Authors: Shian-ling Ding, Jyh-Cherng Yu, Shou-Tung Chen, Giu-Cheng Hsu, Huan-Ming Hsu, Jar Yi Ho, Yu Hsin Lin, Chien-Ching Chang, Cathy S.J. Fann, Chun-Wen Cheng, Pei-Ei Wu, Chen-Yang Shen
Journal: Clinical Cancer Research (2010)

To test the hypothesis that polymorphisms of ESR1, the gene encoding estrogen receptor alpha (ERalpha), are associated with susceptibility, clinical phenotype, and progression of breast cancer.A case-control study was done on 940 patients with incident breast cancer and 1,547 healthy female controls. Fifteen single-nucleotide polymorphisms (SNP) selected from chr6:152,170,379-152,466,100 (exons 1-8 of the ESR1 gene, excluding flanking sequences), reflecting major polymorphisms of this gene, were genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility and between cases with different clinical phenotypes to determine the role of ESR1 polymorphism in cancer progression.SNPs located in one cluster in intron 1 and one haplotype, based on these SNPs, showed a significant association with breast cancer susceptibility. The tumorigenic contribution of these intron 1 SNPs was more obvious in combination with reproductive risk factors (P for interaction <0.05). One of these intron 1 SNPs was also significantly associated with low ERalpha expression in tumors. Interestingly, the same intron 1 SNPs showed a correlation with worse clinical phenotypes, including poor differentiation of tumor cells and a late stage. These intron 1 SNPs also showed a significant association with the 5-year breast cancer-specific survival rate of patients, but had opposite effects in ERalpha-negative and ERalpha-positive early-stage patients.Our findings provide support for diverse roles of ESR1 polymorphism in determining susceptibility in different stages of breast cancer. The differences between the important ESR1 SNPs identified in Chinese women in this study and those identified in studies on Western women with breast cancer suggest different roles of ERalpha in these two populations.
Murine gamma interferon activates the release of a macrophage-derived Ia-inducing factor that transfers Ia inductive capacity.
Authors: E B Walker, V Maino, M Sanchez-Lanier, N Warner, C Stewart
Journal: The Journal of Experimental Medicine (1984)

In this report we demonstrate that when the murine macrophage tumor cell line P- 388D1 is incubated for 48-72 h with either concanavalin A-stimulated rat spleen cell supernatant or cloned murine immune interferon (IFN-gamma), the cultured cells release a cell-free factor activity that in turn induces the cell surface expression of Ia antigen on the murine monocyte cell line WEHI-3. This IFN-gamma-stimulated, Ia-inducing activity cannot be blocked with an anti-IFN-gamma heteroantiserum that does block the induction of Ia expression on WEHI-3 by both cloned murine IFN-gamma and rat Con A supernatant. The Ia-inducing factor ( IaIF ) generated from P- 388D1 after stimulation by IFN-gamma does not demonstrate any antiviral activity. The P- 388D1 -derived IaIF is not shed plasma membrane Ia glycoprotein molecules, as demonstrated by the inability of the active component to bind specifically to an anti-I-Ad affinity column or to a protein A column after the active supernatant is first treated with an excess of anti-I-E/Cd,k monoclonal antibody.
Intramyocardial Transplantation of Autologous Myoblasts : Can Tissue Processing Be Optimized?
Authors: B. Pouzet, J.-T. Vilquin, A. A. Hagege, M. Scorsin, E. Messas, M. Fiszman, K. Schwartz, P. Menasche
Journal: Circulation (2000)

Autologous skeletal myoblast (SM) transplantation improves function of infarcted myocardium, but pretransplantation cultures remain a complex process. This study assessed whether it could be optimized by muscle preconditioning with the local anesthetic bupivacaine or even bypassed with the use of the so-called mince technique.Muscle preconditioning consisted of intramuscular injections of the tibialis anterior of rats, 2 days before harvest. After 7 days of culture, the number of available myoblasts was significantly increased compared with nonconditioned controls (1 683 147 versus 85 300, P:=0.0013). The mince technique was then assessed. A myocardial infarction was created in 66 rats by coronary artery ligation. One week later, rats were reoperated on and intramyocardially injected with culture medium alone (controls, n=23), autologous cultured SM (3.5 x 10(6), n=21), or autologous muscle minced into a fine slurry, which was immediately transplanted (n=22). All muscles had been preconditioned. Left ventricular function was assessed by 2D echocardiography. Whereas end-diastolic volumes expanded over time in all groups, left ventricular ejection fraction (%, mean+/-SEM) was increased only in the cultured SM-transplanted group at 1 (P:=0. 0006) and 2 months (P:=0.0008) versus baseline (37.52+/-1.92 and 40. 92+/-2.17 versus 30.34+/-1.74), with a significant additional benefit between 1 and 2 months (P:=0.0069).Cell culture remains mandatory for SM transplantation to be successful but, in a clinical perspective, this process can be made more expeditious by preharvest muscle conditioning with bupivacaine, which greatly enhances the baseline cell yield.
Transmural Heterogeneity of Calcium Handling in Canine
Authors: Kenneth R. Laurita, Rodolphe Katra, Barbara Wible, Xiaoping Wan, Michael H. Koo
Journal: Circulation Research (2003)

Spatial heterogeneity of the action potential and its influence on arrhythmia vulnerability is known. However, heterogeneity of intracellular calcium handling and, in particular, its effect on the electrophysiological substrate is less clear. Using optical mapping techniques, calcium transients and action potentials were recorded simultaneously from ventricular sites across the transmural wall of the arterially perfused canine left ventricular wedge preparation during steady-state baseline pacing and rapid pacing. During baseline pacing, the decay of intracellular calcium to diastolic levels and calcium transient duration were slower (70%, P &lt;0.005) and longer (20%, P &lt;0.005), respectively, closer to the endocardial surface compared with the epicardial surface. Tissue samples isolated from the left ventricular wall demonstrate that sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a) expression was significantly less in the subendocardial and midmyocardial layers compared with the subepicardial layer. In contrast, no significant difference in the transmural expression of Na + -Ca 2+ exchanger was observed. During rapid pacing, calcium transient alternans and increased levels of diastolic intracellular calcium were significantly greater ( P &lt;0.01) closer to the endocardium (101%±62% and 41%±15%, respectively) compared with the epicardium (12%±7% and 12%±14%, respectively). In conclusion, cells closer to the endocardium exhibit a slower decay of intracellular calcium compared with cells near the epicardium, which may be due in part to reduced expression of SERCA2a. As a possible consequence, calcium transient alternans and increased diastolic levels of intracellular calcium may occur preferentially closer to the endocardial surface.
The Leabra architecture: Specialization without modularity
Authors: Alexander A. Petrov, David J. Jilk, Randall C. O'Reilly
Journal: Behavioral and Brain Sciences (2010)

Abstract The posterior cortex, hippocampus, and prefrontal cortex in the Leabra architecture are specialized in terms of various neural parameters, and thus are predilections for learning and processing, but domain-general in terms of cognitive functions such as face recognition. Also, these areas are not encapsulated and violate Fodorian criteria for modularity. Anderson's terminology obscures these important points, but we applaud his overall message.
Clinical Decision Support and Appropriateness of Antimicrobial Prescribing
Authors: Matthew H. Samore, Kim Bateman, Stephen C. Alder, Elizabeth Hannah, Sharon Donnelly, Gregory J. Stoddard, Bassam Haddadin, Michael A. Rubin, Jacquelyn Williamson, Barry Stults, Randall Rupper, Kurt Stevenson
Journal: JAMA (2005)

ContextThe impact of clinical decision support systems (CDSS) on antimicrobial prescribing in ambulatory settings has not previously been evaluated.ObjectiveTo measure the added value of CDSS when coupled with a community intervention to reduce inappropriate prescribing of antimicrobial drugs for acute respiratory tract infections.Design, Participants and SettingCluster randomized trial that included 407 460 inhabitants and 334 primary care clinicians in 12 rural communities in Utah and Idaho (6 with 1 shared characteristic and 6 with another), and a third group of 6 communities that served as nonstudy controls. The preintervention period was January to December 2001 and the postintervention period was January 2002 to September 2003. Acute respiratory tract infection diagnoses were classified into groups based on indication for antimicrobial use. Multilevel regression methods were applied to account for the clustered design.InterventionSix communities received a community intervention alone and 6 communities received community intervention plus CDSS that were targeted toward primary care clinicians. The CDSS comprised decision support tools on paper and a handheld computer to guide diagnosis and management of acute respiratory tract infection.Main Outcome MeasureCommunity-wide antimicrobial usage was assessed using retail pharmacy data. Diagnosis-specific antimicrobial use was compared by chart review.ResultsWithin CDSS communities, 71% of primary care clinicians participated in the use of CDSS. The prescribing rate decreased from 84.1 to 75.3 per 100 person-years in the CDSS arm vs 84.3 to 85.2 in community intervention alone, and remained stable in the other communities (P = .03). A total of 13 081 acute respiratory tract infection visits were abstracted. The relative decrease in antimicrobial prescribing for visits in the antibiotics "never-indicated" category during the post-intervention period was 32% in CDSS communities and 5% in community intervention-alone communities (P = .03). Use of macrolides decreased significantly in CDSS communities but not in community intervention–alone communities.ConclusionCDSS implemented in rural primary care settings reduced overall antimicrobial use and improved appropriateness of antimicrobial selection for acute respiratory tract infections.Trial RegistrationClinicalTrials.gov Identifier: NCT00235703.
Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus
Authors: L Barile-Fabris
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Severe neurological involvement in systemic lupus erythematosus (NPSLE) is one of the most dreadful complications of the disease. <b>Objective:</b> To identify the best drug, dose, and treatment. <b>Patients and methods:</b> The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria, with incident (no more than 15 days) onset of severe NP manifestations such as seizures, optic neuritis, peripheral or cranial neuropathy, coma, brainstem disease, or transverse myelitis. Induction treatment with 3 g of IV methylprednisolone (MP) followed by either IV monthly cyclophosphamide (Cy) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year. The primary end point was response to treatment: at least 20% improvement from basal conditions on clinical, laboratory, or specific neurological testing variables. <b>Results:</b> Overall, a response rate of 75% was observed. Of the 32 patients studied, 18/19 receiving Cy and 7/13 receiving MP responded to treatment (p&lt;0.03). <b>Conclusions:</b> Cy seems to be more effective than MP in the treatment of acute, severe NPSLE.
Nuclear factor-κB in glioblastoma: insights into regulators and targeted therapy
Authors: Kirk E. Cahill, Ramin A. Morshed, Bakhtiar Yamini
Journal: Neuro-Oncology (2015)

Nuclear factor-κB (NF-κB) is a ubiquitous transcription factor that regulates multiple aspects of cancer formation, growth, and treatment response. Glioblastoma (GBM), the most common primary malignant tumor of the central nervous system, is characterized by molecular heterogeneity, resistance to therapy, and high NF-κB activity. In this review, we examine the mechanisms by which oncogenic pathways active in GBM impinge on the NF-κB system, discuss the role of NF-κB signaling in regulating the phenotypic properties that promote GBM and, finally, review the components of the NF-κB pathway that have been targeted for treatment in both preclinical studies and clinical trials. While a direct role for NF-κB in gliomagenesis has not been reported, the importance of this transcription factor in the overall malignant phenotype suggests that more rational and specific targeting of NF-κB-dependent pathways can make a significant contribution to the management of GBM.