tbuckley/cabot-search huggingface dataset:
Eponyms and the Diagnosis of Aortic Regurgitation: What Says the Evidence?
Authors: Ajit N. Babu, Steven M. Kymes, Sharon M. Carpenter Fryer
Journal: Annals of Internal Medicine (2003)

Background: Chronic aortic regurgitation can lead to significant morbidity and mortality. For more than a century, numerous eponymous signs of aortic regurgitation have been described in textbooks and the literature. Purpose: To compare current textbook content with the peer-reviewed literature on the eponymous signs of aortic regurgitation and to assess the role of these signs in clinical practice. Data Sources: 11 textbooks, MEDLINE (1966 through October 2002), and bibliographies of textbooks and relevant papers. Study Selection: English-language reports that were related to the properties of a sign on physical examination, incorporated more than 10 adults, and did not involve prosthetic heart valves or acute aortic regurgitation. Data Extraction: Three investigators independently analyzed relevant textbook extracts and 27 reports, using predetermined qualitative review criteria. Data relating to diagnostic accuracy and properties of the index test were also extracted. Data Synthesis: Twelve eponymous signs were described as having varying degrees of importance by textbook authors. Only the Austin Flint murmur, the Corrigan pulse, the Duroziez sign, and the Hill sign had sufficient original literature for detailed review. Most reports were low quality, with varying sensitivities for all signs. Except for the Hill sign, specificity tended to be poor. Evidence for the Hill sign also suggested a correlation between the poplitealbrachial gradient and aortic regurgitation severity. Conclusions: Prominent textbook support of the eponymous signs of aortic regurgitation is not matched by the literature. Clinicians and educators should update and improve the evidence for these signs to ensure their relevance in current medical practice.
Summary of the British Thoracic Society Guidelines for advanced diagnostic and therapeutic flexible bronchoscopy in adults
Authors: I. A. Du Rand, P. V. Barber, J. Goldring, R. A. Lewis, S. Mandal, M. Munavvar, R. C. Rintoul, P. L. Shah, S. Singh, M. G. Slade, A. Woolley
Journal: Thorax (2011)

This new guideline covers the rapidly advancing field of interventional bronchoscopy using flexible bronchoscopy. It includes the use of more complex diagnostic procedures such as endobronchial ultrasound, interventions for the relief of central airway obstruction due to malignancy and the recent development of endobronchial therapies for chronic obstructive pulmonary disease and asthma. The guideline aims to help all those who undertake flexible bronchoscopy to understand more about this important area. It also aims to inform respiratory physicians and other specialists dealing with lung cancer of the procedures possible in the management and palliation of central airway obstruction. The guideline covers transbronchial needle aspiration and endobronchial ultrasound-guided transbronchial needle aspiration, electrocautery/diathermy, argon plasma coagulation and thermal laser, cryotherapy, cryoextraction, photodynamic therapy, brachytherapy, tracheobronchial stenting, electromagnetic navigation bronchoscopy, endobronchial valves for emphysema and bronchial thermoplasty for asthma.
Quantitative probabilistic functional diffusion mapping in newly diagnosed glioblastoma treated with radiochemotherapy
Authors: B. M. Ellingson, T. F. Cloughesy, A. Lai, P. L. Nghiemphu, L. M. Liau, W. B. Pope
Journal: Neuro-Oncology (2012)

Functional diffusion mapping (fDM) is a cancer imaging technique that uses voxel-wise changes in apparent diffusion coefficients (ADC) to evaluate response to treatment. Despite promising initial results, uncertainty in image registration remains the largest barrier to widespread clinical application. The current study introduces a probabilistic approach to fDM quantification to overcome some of these limitations. A total of 143 patients with newly diagnosed glioblastoma who were undergoing standard radiochemotherapy were enrolled in this retrospective study. Traditional and probabilistic fDMs were calculated using ADC maps acquired before and after therapy. Probabilistic fDMs were calculated by applying random, finite translational, and rotational perturbations to both pre-and posttherapy ADC maps, then repeating calculation of fDMs reflecting changes after treatment, resulting in probabilistic fDMs showing the voxel-wise probability of fDM classification. Probabilistic fDMs were then compared with traditional fDMs in their ability to predict progression-free survival (PFS) and overall survival (OS). Probabilistic fDMs applied to patients with newly diagnosed glioblastoma treated with radiochemotherapy demonstrated shortened PFS and OS among patients with a large volume of tumor with decreasing ADC evaluated at the posttreatment time with respect to the baseline scans. Alternatively, patients with a large volume of tumor with increasing ADC evaluated at the posttreatment time with respect to baseline scans were more likely to progress later and live longer. Probabilistic fDMs performed better than traditional fDMs at predicting 12-month PFS and 24-month OS with use of receiver-operator characteristic analysis. Univariate log-rank analysis on Kaplan–Meier data also revealed that probabilistic fDMs could better separate patients on the basis of PFS and OS, compared with traditional fDMs. Results suggest that probabilistic fDMs are a more predictive biomarker in terms of 12-month PFS and 24-month OS in newly diagnosed glioblastoma, compared with traditional fDM analysis.
Human Cardiac Myosin: Electron Microscopic Observations
Authors: JOHN A. CARNEY, ARNOLD L. BROWN
Journal: Circulation Research (1965)

Solutions of human cardiac myosin contain macromolecules which were visualized in the electron microscope by the shadow-casting technic. The dominant particle was observed to be rod-shaped, to have a globular expansion at one end, and to have a mean length of about 1500 Å. The molecule of human cardiac myosin was found to be morphologically similar to myosin molecules from canine cardiac muscle and rabbit skeletal muscle.
Intracerebral CpG Immunotherapy with Carbon Nanotubes Abrogates Growth of Subcutaneous Melanomas in Mice
Authors: Haitao Fan, Ian Zhang, Xuebo Chen, Leying Zhang, Huaqing Wang, Anna Da Fonseca, Edwin R. Manuel, Don J. Diamond, Andrew Raubitschek, Behnam Badie
Journal: Clinical Cancer Research (2012)

Recently, we showed that intratumoral delivery of low-dose, immunostimulatory CpG oligodeoxynucleotides conjugated with carbon nanotubes (CNT-CpG) was more effective than free CpG and not only eradicated intracranial (i.c.) gliomas but also induced antitumor immunity that protected mice from subsequent i.c. or systemic tumor rechallenge. Here, we examined whether the same "intracerebral immunotherapy" strategy could be applied to the treatment of metastatic brain tumors.Mice with both i.c. and s.c. melanomas were injected intratumorally with CNT-CpG into either location. Antitumor responses were assessed by flow cytometry, bioluminescent imaging, and animal survival.When given s.c., CNT-CpG response was mostly local, and it only modestly inhibited the growth of i.c. melanomas. However, i.c. CNT-CpG abrogated the growth of not only brain but also s.c. tumors. Furthermore, compared with s.c. injections, i.c. CNT-CpG elicited a stronger inflammatory response that resulted in more potent antitumor cytotoxicity and improved in vivo trafficking of effector cells into both i.c. and s.c. tumors. To investigate factors that accounted for these observations, CNT-CpG biodistribution and cellular inflammatory responses were examined in both tumor locations. Intracranial melanomas retained the CNT-CpG particles longer and were infiltrated by Toll-like receptor (TLR-9)-positive microglia. In contrast, myeloid-derived suppressive cells were more abundant in s.c. tumors. Although depletion of these cells before s.c. CNT-CpG therapy enhanced its cytotoxic responses, antitumor responses to brain melanomas were unchanged.These findings suggest that intracerebral CNT-CpG immunotherapy is more effective than systemic therapy in generating antitumor responses that target both brain and systemic melanomas.
Leptin consumption in the inflamed joints of patients with rheumatoid arthritis
Authors: M Bokarewa
Journal: Annals of the Rheumatic Diseases (2003)

Leptin has been shown to participate in bone remodelling and leptin substitution reported to have a protective effect in experimental septic arthritis.To assess leptin levels in inflamed joints and plasma of patients with RA.Leptin concentrations were assessed in matched blood and synovial fluid samples from 76 patients with RA. Blood samples from 34 healthy subjects acted as additional controls. Results were analysed and correlated with duration and activity of RA, x ray changes, and treatment at time of sampling.In patients with RA, leptin levels were significantly higher in plasma than in synovial fluid samples obtained simultaneously and higher than in control samples. Plasma and synovial fluid leptin levels correlated strongly. Locally in the joint, leptin levels were related to WBC count. Such a relation was not seen in the bloodstream. Leptin levels were not related to sex, age, or disease duration. Difference between leptin levels in plasma and synovial fluid was greater in non-erosive arthritis (5.1 (SEM 1.2) v 3.7 (0.9) ng/ml, p=0.006), than in patients with erosive joint disease (6.2 (1.0) v 5.4 (0.8) ng/ml, NS). Methotrexate treatment was associated with relatively high plasma leptin levels, while treatment with other DMARDs was associated with lower leptin levels than in patients receiving no DMARD treatment (p=0.0005).Leptin production was significantly increased in patients with RA compared with healthy controls. Synovial fluid leptin levels were significantly lower than in matched plasma samples, suggesting an in situ consumption of this molecule.
Increased Renal Angiopoietin-1 Expression in Folic Acid-Induced Nephrotoxicity in Mice
Authors: David A. Long, Adrian S. Woolf, Toshio Suda, Hai T. Yuan
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. Growth factors affect epithelial regeneration after acute renal injury, but less is known regarding the expression of vascular growth factors in this setting. A mouse model of folic acid (FA)-induced nephrotoxicity was used to study the expression of angiopoietins (Ang), factors that bind the Tie-2 receptor and modulate endothelial growth. Tubular damage was detected 1 d after FA administration; in the next 14 d, most tubules regenerated but patchy atrophy, with interstitial fibrosis, was also observed. Ang-1 immunostaining was detected between cortical tubules and in the vasa rectae of vehicle-treated animals. FA-induced nephropathy was associated with the acquisition of Ang-1 immunostaining in renal arterial walls and in a subset of injured cortical tubules that failed to stain with periodic acid-Schiff stain, which indicated that they were distal tubules. Renal Ang-1 protein levels were significantly increased after FA administration, compared with time-matched control values, as assessed by Western blotting. Capillaries between regenerating tubules expressed both Tie-2 and platelet-endothelial cell adhesion molecule. A subset of these endothelia expressed proliferating cell nuclear antigen, whereas capillary proliferation was absent in control samples. Therefore, FA-induced nephropathy is associated with increased Ang-1 protein expression in renal epithelia and arteries. In addition, Tie-2-expressing capillaries near damaged cortical tubules undergo proliferation. Further experiments are required to establish whether these events are functionally related.
Biosynthesis of Vitamin B<sub>2</sub> (Riboflavin)
Authors: A. Bacher, S. Eberhardt, M. Fischer, K. Kis, G. Richter
Journal: Annual Review of Nutrition (2000)

The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. The imidazole ring of GTP is hydrolytically opened, yielding a 4,5-diaminopyrimidine which is converted to 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione by a sequence of deamination, side chain reduction and dephosphorylation. Condensation of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione with 3,4-dihydroxy-2-butanone 4-phosphate obtained from ribulose 5-phosphate affords 6,7-dimethyl-8-ribityllumazine. Dismutation of the lumazine derivative yields riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, which is recycled in the biosynthetic pathway. The structure of the biosynthetic enzyme, 6,7-dimethyl-8-ribityllumazine synthase, has been studied in considerable detail.
Lung Cancer Screening With Low-Dose Computed Tomography: Costs, National Expenditures, and Cost-Effectiveness
Authors: Bernardo H. L. Goulart, Mark E. Bensink, David G. Mummy, Scott D. Ramsey
Journal: Journal of the National Comprehensive Cancer Network (2012)

A recent randomized trial showed that low-dose CT (LDCT) screening reduces lung cancer mortality. Health care providers need an assessment of the national budget impact and cost-effectiveness of LDCT screening before this intervention is adopted in practice. Using data from the 2009 National Health Interview Survey, CMS, and the National Lung Screening Trial (NLST), the authors performed an economic analysis of LDCT screening that includes a budget impact model, an estimate of additional costs per lung cancer death avoided attributed to screening, and a literature search of cost-effectiveness analyses of LDCT screening. They conducted a one-way sensitivity analysis, reporting expenditures in 2011 U.S. dollars, and took the health care payer and patient perspectives. LDCT screening will add $1.3 to $2.0 billion in annual national health care expenditures for screening uptake rates of 50% to 75%, respectively. However, LDCT screening will avoid up to 8100 premature lung cancer deaths at a 75% screening rate. The prevalence of smokers who qualify for screening, screening uptake rates, and cost of LDCT scan were the most influential parameters on health care expenditures. The additional cost of screening to avoid one lung cancer death is $240,000. Previous cost-effectiveness analyses have not conclusively shown that LDCT is cost-effective. LDCT screening may add substantially to the national health care expenditures. Although LDCT screening can avoid more than 8000 lung cancer deaths per year, a cost-effectiveness analysis of the NLST will be critical to determine the value of this intervention and to guide decisions about its adoption.
The discovery of language invariance and variation, and its relevance for the cognitive sciences
Authors: Luigi Rizzi
Journal: Behavioral and Brain Sciences (2009)

Abstract Modern linguistics has highlighted the fundamental invariance of human language: A rich invariant structure has emerged from comparative studies nourished by sophisticated formal models; languages also differ along important dimensions, but variation is constrained in severe and systematic ways. I illustrate this research direction in the domains of island constraints, word order restrictions, and the expression of referential dependencies. Both language invariance and language variability within systematic limits are highly relevant for the cognitive sciences.
Choline: Critical Role During Fetal Development and Dietary Requirements in Adults
Authors: Steven H. Zeisel
Journal: Annual Review of Nutrition (2006)

▪ Abstract Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.
Does Ca <sup>2+</sup> /Calmodulin-Dependent Protein Kinase δ <sub>c</sub> Activate or Inhibit the Cardiac Ryanodine Receptor Ion Channel?
Authors: Naohiro Yamaguchi, Gerhard Meissner
Journal: Circulation Research (2007)

he multifunctional Ca 2ϩ /calmodulin-dependent protein kinase II␦ (CaMKII␦) modulates cardiac muscle function by regulating Ca 2ϩ transport proteins and nuclear signaling molecules.Aberrant activity of CaMKII␦ is implicated in heart disease.In this issue, Yang et al 1 report that acute overexpression of constitutively active splice variant CaMKII␦ C phosphorylates the cardiac ryanodine receptor ion channel (RyR2) to decrease the rate of occurrence of local Ca 2ϩ release events (Ca 2ϩ sparks) and Ca 2ϩ waves in cultured rat cardiomyocytes.A dominant negative form of CaMKII␦ C was shown to have opposite effects.The cardiac ryanodine receptors are cation selective channels that release Ca 2ϩ from an intracellular Ca 2ϩ storing compartment, the sarcoplasmic reticulum (SR), during a cardiac muscle action potential, in a process known as excitation-contraction coupling. 2Released Ca 2ϩ cause cardiac muscle to contract.Sequestration of released Ca 2ϩ by the SR Ca 2ϩ -transporting ATPase and extrusion by the Na ϩ -Ca 2ϩ exchanger restore the myofibrillar Ca 2ϩ concentration from 10 -6 -10 -5 to Ϸ10 -7 M, causing muscle to relax.The RyR2s are regulated by a variety of effectors. 3During a cardiac action potential, closely apposed dihydropyridine-sensitive L-type Ca 2ϩ channels in the surface membrane and T-tubule mediate influx of Ca 2ϩ , which triggers massive release of Ca 2ϩ from SR by opening RyR2s.In addition to Ca 2ϩ , endogenous effectors such as Mg 2ϩ , ATP, reactive oxygen and nitrogen molecules regulate RyR2.RyR2 is also regulated by calmodulin, cAMP-dependent protein kinase A (PKA), calmodulindependent kinase II (CaMKII), protein kinase C, and protein phosphatases 1 and 2A.Phosphorylation of RyR2-Ser2030 by PKA 4 and Ser2809 by PKA 5,6 and CaMKII 5 has been described.Marks and colleagues 6 report that PKA-mediated phosphorylation of RyR2-Ser2809 causes a small subunit, FKBP12.6 or calstabin 2, to dissociate from RyR2, which results in a "leaky" SR channel, aberrant contractile function, and heart failure.But other laboratories fail to support this. 4,7,8Wehrens et al 9 identified a third RyR2 phosphorylation site.Mutagenesis suggests that CaMKII uniquely phosphorylates Ser2815 near S2809 on recombinant RyR2 ex-
High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis
Authors: Kassia S Weston, Ulrik Wisløff, Jeff S Coombes
Journal: British Journal of Sports Medicine (2013)

Background/Aim Cardiorespiratory fitness (CRF) is a strong determinant of morbidity and mortality. In athletes and the general population, it is established that high-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) in improving CRF. This is a systematic review and meta-analysis to quantify the efficacy and safety of HIIT compared to MICT in individuals with chronic cardiometabolic lifestyle diseases. Methods The included studies were required to have a population sample of chronic disease, where poor lifestyle is considered as a main contributor to the disease. The procedural quality of the studies was assessed by use of a modified Physiotherapy Evidence Base Database (PEDro) scale. A meta-analysis compared the mean difference (MD) of preintervention versus postintervention CRF (VO 2 peak) between HIIT and MICT. Results 10 studies with 273 patients were included in the meta-analysis. Participants had coronary artery disease, heart failure, hypertension, metabolic syndrome and obesity. There was a significantly higher increase in the VO 2 peak after HIIT compared to MICT (MD 3.03 mL/kg/min, 95% CI 2.00 to 4.07), equivalent to 9.1%. Conclusions HIIT significantly increases CRF by almost double that of MICT in patients with lifestyle-induced chronic diseases.
Effect of alpha-tocopherol on restenosis after angioplasty in a model of experimental atherosclerosis.
Authors: A M Lafont, Y C Chai, J F Cornhill, P L Whitlow, P H Howe, G M Chisolm
Journal: Journal of Clinical Investigation (1995)

The ability of alpha-tocopherol to reduce restenosis after angioplasty was tested in a rabbit model in which angioplasty was performed on established atherosclerotic lesions. Lesions induced by 4 wk of cholesterol feeding after focal desiccation of femoral arteries were balloon dilated. 3 wk after angioplasty, angiographically determined minimum luminal diameters were less in the untreated group (0.80 +/- 0.51 mm) than in the group treated with oral alpha-tocopherol beginning 19 d before angioplasty (1.38 +/- 0.29 mm; P < 0.01). The cross-sectional area of the intima-media was greater in the untreated group (1.18 +/- 0.48 mm2) than in the alpha-tocopherol group (0.62 +/- 0.25 mm2, P < 0.0001). These differences were not due to vasoconstriction or altered plasma cholesterol. Alpha-tocopherol thus reduced restenosis after angioplasty in this model. In rabbit vascular smooth muscle cells, oxidized low density lipoprotein stimulated DNA synthesis. Alpha-tocopherol treatment inhibited DNA synthesis stimulated by oxidized low density lipoprotein, but not by serum. The findings are consistent with the hypothesis that oxidized lipids can stimulate hyperplasia and that antioxidants may limit hyperplasia by inhibiting either the oxidation or the proliferative effects of oxidants on cells.
THE FATE OF MYCOBACTERIUM TUBERCULOSIS IN MOUSE TISSUES AS DETERMINED BY THE MICROBIAL ENUMERATION TECHNIQUE
Authors: Robert M. McCune, Ralph Tompsett, Walsh McDermott
Journal: The Journal of Experimental Medicine (1956)

Populations of tubercle bacilli of human origin exposed in vivo to pyrazinamide and a companion drug, vanished from the tissues of the mouse in so far as could be determined by microscopy, culture, or guinea pig subinoculation. The vanishing did not represent a complete elimination of the tubercle bacilli from all the animals. 90 days after the completion of treatment, tubercle bacilli could be cultured from approximately one-third of the animals examined at that time. This complete disappearance of the tubercle bacilli thus meets the definition of a truly latent infection in that the infection is present but is hidden beyond the limits of diagnostic reach. All but one of the strains of tubercle bacilli which survived in the animals and were detectable in the posttreatment period, were susceptible to pyrazinamide when tested under appropriate conditions in vitro. Only two factors could be identified which were essential for the uniform occurrence of the disappearance of tubercle bacilli: the administration of the pyrazinamide in a high daily dosage for at least eight of a total of 12 weeks of antimicrobial therapy; and the concurrent or prior exposure of the microbial populations to isoniazid or in some cases to other antituberculous drugs. The observations suggest that the ability of pyrazinamide-containing chemotherapies to bring about the disappearance of a tubercle bacillus is closely related to the occurrence of some alteration in the bacillus, essential for maximal pyrazinamide action, in response to environmental influences, including other antituberculous drugs present in the environment.