Miracle-dz/UniFAR-FTUs huggingface dataset:
Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor κB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells

Aims Genistein, an isoflavone derivative found in soy, is known as a promising treatment for rheumatoid arthritis (RA). However, the detailed molecular mechanism of genistein in suppression of proinflammatory cytokine production remains ambiguous. The aim of this work was to evaluate the signal pathway by which genistein modulates inflammatory cytokine expression. Materials and methods MH7A cells were stimulated with tumor necrosis factor (TNF)-α and incubated with genistein, and interleukin (IL)-1β, IL-6, and IL-8 production was measured by enzyme-linked immunosorbent assay. Nuclear translocation of nuclear factor (NF)-κB was measured by a confocal fluorescence microscopy. The intracellular accumulation of reactive oxygen species (ROS) was monitored using the fluorescent probe 5-6-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate. Signal-transduction protein expression was measured by Western blot. Results Genistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-α-induced NF-κB translocation as well as phosphorylation of IκB kinase-α/β and IκBα, and also suppressed TNF-α-induced AMPK inhibition. The production of IL-1β, IL-6, and IL-8 induced by TNF-α was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might inhibit IL-1β, IL-6, and IL-8 production induced by TNF-α. In addition, we also found that pretreatment with the adenosine monophosphate-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside obviously inhibited TNF-α-induced proinflammatory cytokine production. These observations suggest that the inhibitory effect of genistein on TNF-α-induced proinflammatory cytokine production is dependent on AMPK activation. Conclusion These findings indicate that genistein suppressed TNF-α-induced inflammation by inhibiting the ROS/Akt/NF-κB pathway and promoting AMPK activation in MH7A cells.
A Response to Jason et al. (2009), “Evaluating the Centers for Disease Control’s Empirical Chronic Fatigue Syndrome Case Definition”

The recent article by Jason, Najar, Porter, and Reh, “Evaluating the Centers for Disease Control’s Empirical Chronic Fatigue Syndrome Case Definition” (2009; Journal of Disability Policy Studies, 20:2, 93—100) attempted to critically explore several pertinent issues concerning diagnosing chronic fatigue syndrome (CFS). Most of these issues have been brewing since international adoption of the 1994 CFS case definition by Fukuda et al., and it is high time to address them in a peer-reviewed and public forum.
Hyperfamiliarity in Dementia and Mild Cognitive Impairment.

INTRODUCTION Hyperfamiliarity, a phenomenon in which feelings of familiarity are evoked by novel stimuli, is well described in epilepsy and the lesioned brain. Abnormality of familiarity in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have also been described in the literature, but more from a neuropsychological approach perspective. Currently, there is a lack of study on the real-life experience of familiarity abnormality in dementia and MCI. Our aim was to compare the occurrence of hyperfamiliarity among dementia and MCI. MATERIALS AND METHODS We recruited 73 participants, 29 with AD, 10 with vascular dementia, 7 with MCI and 27 healthy controls, and administered a questionnaire to assess hyperfamiliarity frequency. RESULTS Hyperfamiliarity was observed in real-life in cognitive impairment, but was unrelated to its severity or underlying aetiology. CONCLUSION This study highlights the similar rate of occurrence of hyperfamiliarity in the daily life of individuals with cognitive impairment. Future research should examine neuropsychological correlations and mechanisms that contribute to such observations.
Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease

Background— Recent clinical trials found that high-dose statin therapy, compared with conventional-dose statin therapy, reduces the risk of cardiovascular events in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). However, the actual benefit and cost-effectiveness of high-dose statin therapy are unknown. Methods and Results— We designed a Markov model to compare daily high-dose with conventional-dose statin therapy for hypothetical 60-year-old cohorts with ACS and stable CAD over patient lifetime. Pooled estimates for major clinical end points (all-cause mortality, myocardial infarction, stroke, rehospitalization, and revascularization) from relevant clinical trials were incorporated. Incremental benefit was quantified as quality-adjusted life-years (QALYs). Threshold analyses determined at what price difference high-dose statins would yield incremental cost-effective ratios below $50 000, $100 000, and $150 000 per QALY gained. In ACS patients, a high-dose versus conventional-dose statin strategy resulted in a gain of 0.35 QALYs. In threshold analyses, a high-dose statin strategy consistently yielded incremental cost-effective ratios below $30 000 per QALY even under conservative model assumptions. In stable CAD patients, a high-dose statin strategy yielded a gain of only 0.10 QALYs and was sensitive to model assumptions about statin efficacy. The daily cost difference between a high- and conventional-dose statin would need to be <$1.70, $2.65, and $3.55 to yield incremental cost-effective ratios below $50 000, $100 000, and $150 000 per QALY. Conclusions— High-dose statin therapy is potentially highly effective and cost-effective in patients with ACS. In patients with stable CAD, however, the cost-effectiveness of high-dose statin therapy is highly sensitive to model assumptions about statin efficacy and cost. Use of high-dose statins can be supported on health economic grounds in patients with ACS, but the case is less clear for patients with stable CAD.
Suppression of mutations in the core of the Tetrahymena ribozyme by spermidine, ethanol and by substrate stabilization.

We have previously described a collection of mutations in conserved residues of the core of the Tetrahymena self-splicing intron. Most of these single base substitutions have less than 10% of the activity of their parental intron derivative [Couture, S. , et al., (1990) J. Mol. Biol., 215, 345-358]. We examined the effect of two agents known to stabilize RNA structure, spermidine and ethanol, on the activity of many of these mutant RNAs. In the presence of either 5 mM spermidine or 20% ethanol most substitution mutations were partially or completely suppressed. These conditions also increased the temperature optima of both wild-type and mutant ribozymes. In addition, we find that mutations are also suppressed by a high concentration of GTP, a substrate in the reaction which is bound specifically by the intron. Thus we observe a general suppression of mutations in an RNA enzyme (ribozyme) by spermidine, ethanol and by substrate stabilization. These results are consistent with the idea that most mutations destabilize the folded structure of the ribozyme and can be suppressed by any of a variety of stabilizing influences.
Interpreting the MMPI-2-RF

The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) is one of the most widely used personality measures in psychological and neuropsychological practice. As outlined in Chapter 1 of Interpreting the MMPI-2-RF, minimal content change was made when revising the Minnesota Multiphasic Personality Inventory (MMPI) to create the MMPI-2. The authors of Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) were aware of the long research history of the MMPI and wished to maximize the comparability of the MMPI with the MMPI-2. However, the authors were also aware that some long-standing psychometric weaknesses of the MMPI continued with the MMPI-2. Most notably the scales are quite heterogeneous and significantly intercorrelated with one another (due to item overlap and the presence of a general construct they named demoralization). As soon as the MMPI-2 was complete, the authors moved forward with a more substantial restructuring of the measure, with the goal of improving these psychometric weaknesses. As a result, the MMPI-2 Clinical Scales were restructured in 2003 (Tellegen et al., 2003), and the restructured version of the entire MMPI-2, the MMPI-2-RF, was released in 2008 (Ben-Porath & Tellegen, 2008; Tellegen & Ben-Porath, 2008). When I received Dr. Ben-Porath’s book I was concerned that this would merely be a book presentation of the information provided in the interpretation and technical manuals (referenced above) for the MMPI-2-RF. I was pleasantly surprised that this is not the case and that the information contained in Dr. Ben-Porath’s book is much richer. After review of the history of the MMPI/MMPI-2 and its criticisms, Chapters 2, 3, and 4 provide more detail on the specific weaknesses the restructuring was designed to address; the process by which the restructuring was undertaken; the theoretical underpinnings for the constructs in the restructuring; and the empirical findings of each resulting Restructured Clinical (RC) scale (Chapter 2), substantive scale (Chapter 3), and validity scale (Chapter 4). This inclusion of the theoretical
Efficacy of intralesional triamcinolone injections for benign refractory oesophageal strictures at Counties Manukau Health, New Zealand.

BACKGROUND AND AIMS Refractory benign strictures of the oesophagus can present a significant clinical challenge and may require repeated attempts at dilatation. Intralesional triamcinolone injections have been used in a limited number of studies to aid in the dilatation of benign, refractory oesophageal strictures. It is hypothesised that intralesional steroid injection inhibits the scar formation, thereby reducing the need for dilatations. The purpose of this study was to assess if steroid injection reduces the need for serial endoscopic dilatations and aids in maintaining oesophageal patency. METHOD We report a case series of 25 patients with refractory oesophageal strictures. The mean age was 75 years and range between 41-95 years. The etiology of strictures consisted of peptic (68%), anastomotic (4%), radiation induced (16%) and eosinophilic oesophagitis (12%). Majority (75%) were distal in location. Triamcinolone (40-80 mg) was injected via 25-gauge sclerotherapy catheter in a four quadrantic manner in aliquots of 0.5 ml each into the proximal end of the stricture and also into the stricture itself after dilatation. Dilatation was carried out with over the guidewire Savary-Gilliard or through the scope (CRE) Balloon dilators depending upon the preference of the endoscopist. Dilatations were continued every 4-6 weeks until asymptomatic and/or endoscopic resolution of stricture. Periodic Dilatation Index (PDI) was calculated by the number of dilatations required over the duration of time in months. RESULTS The number of dilatations reduced from mean of 3.12 to 1.41 in the peptic strictures but there was no decrease in the other groups. However, the triamcinolone injection resulted in reducing the periodic dilatation index in all groups except the eosinophilic oesophagitis. The rate ratio of PDI before and after intralesional triamcinolone injection use being 0.45 with 95% confidence interval [0.30 -0.68] (p=0.0005). Furthermore triamcinolone injections showed a trend to increase the maximal achieved diameter of the strictures. CONCLUSION This study demonstrates the efficacy of triamcinolone intralesional steroids in reducing the requirement for repeated dilatations in refractory peptic strictures of oesophagus. Strictures related to eosinophilic oesophagitis failed to demonstrate similar efficacy.
The UNIX time-sharing system

UNIX∗ is a general-purpose, multi-user, interactive operating system for the larger Digital Equipment Corporation PDP-11 and the Interdata 8/32 computers. It offers a number of features seldom found even in larger operating systems, including (i) A hierarchical file system incorporating demountable volumes, (ii) Compatible file, device, and inter-process I/O, (iii) The ability to initiate asynchronous processes, (iv) System command language selectable on a per-user basis, (v) Over 100 subsystems including a dozen languages, (vi) High degree of portability. This paper discusses the nature and implementation of the file system and of the user command interface.
Adenosine Treatment Attenuates Cytokine Interleukin-6 Responses to Endotoxin Challenge in Healthy Volunteers

Anti-inflammatory effects of adenosine were evaluated in two randomized, double-blind, placebo-controlled studies. In one study healthy male volunteers received no endotoxin (adenosine study, n = 10), in the other intravenous endotoxin (4 ng/kg, endotoxin study n = 11) was given. All subjects were treated with adenosine infusion (40 &mgr;g/kg/min) and placebo (saline) infusion in a crossover design. Heart rate, body temperature, blood pressure and plasma cytokines (tumor necrosis factor [TNF]-&agr;, interleukin [IL]-6, IL-10, and soluble TNF receptors I and II), nitric oxide oxidation products, nitrite and nitrate, as well as superoxide anions were determined. There were no significant changes of any measured parameter after adenosine treatment alone. Endotoxin elicited clinical signs of an inflammatory reaction, prominent release of all cytokines and O2− synthesis by neutrophils (N-formyl-methionin-leucyl-phenylalanin-stimulated cells measured by cytochrome C reduction). The plasma IL-6 response to endotoxin was attenuated by adenosine, as IL-6 increased from 0.9 (0.8–1.6) to 1345 (743–1906) pg/mL (median; 25–75th percentiles) with adenosine infusion, and from 0.8 (0.5–1) to 1,959 (1,344–2,505) pg/mL with placebo (P = 0.0065). There was no significant influence of adenosine infusion on the other variables examined. In conclusion, systemic adenosine infusion counteracts the release of IL-6 in healthy volunteers, indicating an anti-inflammatory effect of adenosine which should be further explored.
How the body in action shapes the self

In the present paper we address the issue of the role of the body in shaping our basic self-awareness. It is generally taken for granted that basic bodily self-awareness has primarily to do with proprioception. Here we challenge this assumption by arguing from both a phenomenological and a neurophysiological point of view that our body is primarily given to us as a manifold of action possibilities that cannot be reduced to any form of proprioceptive awareness. By discussing the notion of affordance and the spatiality of the body we show that both have to be construed in terms of the varying range of our power for action. Finally, we posit that the motor roots of our bodily self-awareness shed new light on both the common ground for and the distinguishing criterium between self and other. The proper- ties of the mirror mechanism indicate that the same action possibili- ties constituting our bodily self also allow us to make sense of other bodily selves inasmuch as their action possibilities can be mapped onto our own ones. Our proposal may pave the way towards a general deconstruction of the different layers at the core of our full-fledged sense of self and others.
Hepatoblastoma

Hepatoblastoma (HBL) represents the most common primary hepatic tumor in children. Although the cytologic features of this tumor have been amply elucidated on fine‐needle aspiration, exfoliative cytomorphologic characteristics have not been reported. The authors reviewed the cytopathologic features of six serous cavity fluids (SCF) from four patients with histologically proven HBL.
Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial.

CONTEXT Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease. OBJECTIVE To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD. DESIGN Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications. SETTING Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium. PARTICIPANTS Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled. INTERVENTIONS Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo. MAIN OUTCOME MEASURES The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death). RESULTS The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group. CONCLUSION The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.
Protein kinase A reduces voltage-dependent Na+ current in Xenopus oocytes

The voltage-dependent Na+ channel of the brain is a good substrate for phosphorylation by the cAMP-dependent protein kinase (protein kinase A, or PKA), but the physiological effects of PKA on Na+ channels are poorly documented. We studied modulation by PKA of voltage-dependent Na+ channels expressed in Xenopus oocytes injected with RNA coding for the alpha-subunit of the channel protein (rat brain type IIA and its variant VA200), using the two electrode voltage-clamp technique. Intracellularly injected cAMP or catalytic subunit of PKA, or extracellularly applied forskolin, inhibited the Na+ current by 20–30%. The effect of cAMP was attenuated by prior injection of PKA inhibitors. Injection of small doses of protein phosphatase 2A increased the Na+ current by 10%, whereas larger doses of protein phosphatase 1 and alkaline phosphatase were without effect. The inhibition by PKA showed little voltage dependence, being only slightly stronger at holding potentials at which the availability of the channels was reduced. The voltage dependence of activation and inactivation processes was not altered by cAMP. Similar effects were exerted by forskolin and cAMP on the Na+ channels expressed after the injection of heterologous (total) RNA from rat brain. Thus, PKA modulates the Na+ channel by a mechanism that does not involve major changes in the voltage dependency of the current and is exerted on the channel-forming alpha-subunit.
A numerical method to derive accurate temperature coefficients of material constants from high-temperature SAW measurements: application to langasite

The design of wireless SAW sensors for hightemperature applications requires accurate knowledge of the constitutive materials' physical properties in the desired temperature range. In particular, it is crucial to use reliable temperature coefficients of the stiffness, piezoelectric, dielectric, and expansion constants of the propagation medium to achieve correct simulations of the considered devices. Currently, the best-suited piezoelectric material for high-temperature SAW applications is langasite (LGS). Unfortunately, the available coefficients do not allow for precise prediction of the temperature dependence of LGS-based SAW devices above 300°C. A novel method, based on a simulated annealing algorithm coupled with a Rayleigh wave simulation program, was developed to find optimal LGS temperature coefficients. This approach has proven to yield accurate results up to at least 800°C.
A Common Parsing Scheme for Left-and Right-Branching Languages

This paper presents some results of an attempt to develop a common parsing scheme that works systematically and realistically for typologically varied natural languages. The scheme is bottom-up, and the parser scans the input text from left to right. However, unlike the standard LR(k) parser or Tomita's extended LR(1) parser, the one presented in this paper is not a pushdown automaton based on shift-reduce transition that uses a parsing table. Instead, it uses integrated data bases containing information about phrase patterns and parse tree nodes, retrieval of which is triggered by features contained in individual entries of the lexicon. Using this information, the parser assembles a parse tree by attaching input words (and sometimes also partially assembled parse trees and tree fragments popped from the stack) to empty nodes of the specified tree frame, until the entire parse tree is completed. This scheme, which works effectively and realistically for both left-branching languages and right-branching languages, is deterministic in that it does not use backtracking or parallel processing. In this system, unlike in ATN or in LR(k), the grammatical sentences of a language are not determined by a set of rewriting rules, but by a set of patterns in conjunction with procedures and the meta rules that govern the system's operation.
Rho-GTPase signaling in leukocyte extravasation

Leukocyte transendothelial migration (TEM) is one of the crucial steps during inflammation. A better understanding of the key molecules that regulate leukocyte extravasation aids to the development of novel therapeutics for treatment of inflammation-based diseases, such as atherosclerosis and rheumatoid arthritis. The adhesion molecules ICAM-1 and VCAM-1 are known as central mediators of TEM. Clustering of these molecules by their leukocytic integrins initiates the activation of several signaling pathways within the endothelium, including a rise in intracellular Ca2+, activation of several kinase cascades, and the activation of Rho-GTPases. Activation of Rho-GTPases has been shown to control adhesion molecule clustering and the formation of apical membrane protrusions that embrace adherent leukocytes during TEM. Here, we discuss the potential regulatory mechanisms of leukocyte extravasation from an endothelial point of view, with specific focus on the role of the Rho-GTPases.