Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Fenofibric Acid on Carotid Intima-Media Thickness in Patients With Mixed Dyslipidemia on Atorvastatin Therapy: Randomized, Placebo-Controlled Study (FIRST)

Objective—To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol, The Evaluation of Choline Fenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) trial evaluated the effects of fenofibric acid (FA) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin. Approach and Results—This multicenter, double-blind, placebo-controlled study was performed in patients with mixed dyslipidemia (fasting triglycerides, ≥150 mg/dL; high-density lipoprotein cholesterol, ⩽45 [men] or 55 mg/dL [women]; low-density lipoprotein cholesterol, ⩽100 mg/dL once and averaging ⩽105 mg/dL) and a history of coronary heart disease or risk equivalent. Patients on background atorvastatin (continued on starting dose or titrated to 40 mg, if needed) were randomized to FA 135 mg or placebo. The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT, measured by ultrasound. In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy, rate of change in posterior-wall cIMT was similar with FA plus atorvastatin (−0.006 mm/y) versus atorvastatin monotherapy (0.000 mm/y; P=0.22). FA plus atorvastatin was favored (P<0.05) in 5 of 24 prespecified subgroups: age ≥60 years, history of coronary artery disease, cIMT >0.795 mm, triglycerides 170 to 235 mg/dL, and statin use at entry. Adverse events were consistent with the known safety profiles of both drugs; however, FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy (6.5% versus 0.9%). Conclusions—Compared with atorvastatin monotherapy, FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia.
Digital Image Analysis Improves the Quality of Subjective HER-2 Expression Scoring in Breast Cancer

AimTo compare HER-2 scoring reproducibility by subjective and digital image analysis (DIA) scores with each other and with fluorescence in situ hybridization (FISH) assessed HER-2 amplification. MethodsHerceptest-stained Tissue Micro Arrays of 219 breast carcinomas were scored (DAKO protocol) by 3 observers (both independent and as consensus), scored by DIA and both scores were compared with FISH amplification results. ResultsInterobserver subjective scores reproducibility was good (κ 0.82 to 0.86) but therapeutically important 3+/2+discrepancies occurred in 11% to 16% of all 3+ cases. Subjective scores and FISH results differed considerably. Consensus scores by 3 pathologists correlated better with FISH, reducing the number of both Immunohistochemical (IHC) negative/FISH positives and IHC 3+/FISH negatives. DIA scores were well reproducible and correlated better with FISH amplification than did subjective scores. ConclusionsDIA scores were comparable with consensus scores between 3 expert pathologists, were very well reproducible and performed better in classifying IHC 3+/FISH+ cases than did subjective scores.
miR-718 represses proinflammatory cytokine production through targeting phosphatase and tensin homolog (PTEN)

Bacterial sepsis involves a complex interaction between the host immune response and bacterial LPS. LPS binds Toll-like receptor (TLR) 4, which leads to the release of proinflammatory cytokines that are essential for a potent innate immune response against pathogens. The innate immune system is tightly regulated, as excessive inflammation can lead to organ failure and death. MicroRNAs have recently emerged as important regulators of the innate immune system. Here we determined the function of miR-718, which is conserved across mammals and overlaps with the 5′ UTR of the interleukin 1 receptor-associated kinase (IRAK1) gene. As IRAK1 is a key component of innate immune signaling pathways that are downstream of most TLRs, we hypothesized that miR-718 helps regulate the innate immune response. Activation of TLR4, but not TLR3, induced the expression of miR-718 in macrophages. miR-718 expression was also induced in the spleens of mice upon LPS injection. miR-718 modulates PI3K/Akt signaling by directly down-regulating phosphatase and tensin homolog (PTEN), thereby promoting phosphorylation of Akt, which leads to a decrease in proinflammatory cytokine production. Phosphorylated Akt induces let-7e expression, which, in turn, down-regulates TLR4 and further diminishes TLR4-mediated proinflammatory signals. Decreased miR-718 expression is associated with bacterial burden during Neisseria gonorrhoeae infection and alters the infection dynamics of N. gonorrhoeae in vitro. Furthermore, miR-718 regulates the induction of LPS tolerance in macrophages. We propose a role for miR-718 in controlling TLR4 signaling and inflammatory cytokine signaling through a negative feedback regulation loop involving down-regulation of TLR4, IRAK1, and NF-κB.
Effects of melatonin and vitamin C on cigarette smoke–induced damage in the kidney

This study was carried out to investigate smoke-induced structural and biochemical changes and protective effects of co-administered melatonin and vitamin C in the kidney. Twenty-four Wistar adult female rats were used in this study. Animals were divided into four groups. The first group rats were used as control. The second group of rats inhaled cigarette smoke. Smile smoke inhaling third and fourth group rats received melatonin and vitamin C, respectively. At the end of experimental study, kidney tissues and blood samples were taken under ether anesthesia. Tissues were prepared and examined by light microscopy. Malondialdehyde and glutathione levels and catalase activity were determined. By light microscopic observation, a decrease of Bowman space of some renal corpuscles, foamy-like tubules, dilatation and congestion of the peritubuler vessels, and atrophy of the some renal corpuscles were observed in group II. In groups III and IV melatonin and vitamin C relatively protected the kidney tissue against smoke intoxication. Biochemical examination showed that malondialdehyde and glutathione levels and catalase activity in group II were higher than in group I. Melatonin and vitamin C injection to group III and IV caused a decrease in malondialdehyde and glutathione levels. Catalase activity did not change in these groups. We have shown that cigarette smoke inhalation caused structural changes in the kidney. However, melatonin and vitamin C administration produced in some degree protection against smoke-induced damage.
Red kidney bean lectin is a potent cholecystokinin releasing stimulus in the rat inducing pancreatic growth

Background—Lectins are proteins capable of specific binding to carbohydrates without altering their covalent structure. As an essential part of plants they are ingested in our daily diet. By binding to glycosyl side chains of receptors lectins can mimic or inhibit the action of the ligand. Oral administration of phytohaemagglutinin (PHA) in rats dose dependently induces growth of the small intestine and the pancreas by an unknown mechanism. Aims—To investigate the mechanism of PHA induced intestinal and pancreatic growth. Methods—Thirty day old male rats were pairfed for 10 days with lactalbumin as a control diet or lactalbumin plus PHA or purified soybean trypsin inhibitor (STI) as a positive control (42 mg/rat/day) with or without 20 μg of the cholecystokinin A (CCK-A) antagonist MK 329. To investigate further the effect of PHA on CCK release intestinal mucosal cells were isolated from rats which were continuously perfused in a perfusion apparatus. CCK release into the medium was assayed. Results—PHA and STI significantly stimulated growth of the pancreas and the small intestine. MK 329 blocked this growth effect in the pancreas but not in the small intestine. In vivo, PHA significantly increased CCK plasma levels from 0.75 to 6.67 (SEM 2.23) compared with 2.3 (0.35) pM in the control group. In addition, in vitro PHA dose dependently stimulated CCK release with a maximal effect at 100 ng/ml. Conclusion—In vivo and in vitro PHA is a potent stimulus for CCK release in the rat, thereby inducing pancreatic growth, whereas intestinal growth is stimulated by a CCK independent mechanism.
Measuring diagnostic agreement.

Diagnostic agreement tests the reliability and concordance of diagnostic systems. The introduction of measures of agreement with reputations for baserate independence (e.g., Yule's Y and Q), and new studies occasioned by the publication of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) and the International Classification of Diseases--10 (ICD-10; World Health Organization, 1992) make it necessary to study the relationship of illness baserates to measures of agreement. Testing diagnostic concordance for diagnoses of drug dependence from the third edition of the DSM (American Psychiatric Association, 1980) versus DSM-IV diagnoses of drug dependence under 3 baserate conditions, it was found that Yule's Y and Q proved as vulnerable to differences in baserates as kappa or percent agreement and that specificity covaried with baserate rather than being fixed, as most theoretical discussions assume. The uncritical use of Y and Q, therefore, is likely to lead to optimistic interpretations of agreement. Kappa should be preferred for most purposes, although an adjustment to the computational formulas for Y and Q is presented that can diminish their positive bias.
Caesar: a content router for high speed forwarding

Today, high-end routers forward hundreds of millions of packets per second by means of longest prefix match on forwarding tables with less than a million IP prefixes. Information-Centric Networking, a novel form of networking where content is requested by its name, poses a new challenge in the design of high-end routers: process at least the same amount of packets, assuming a forwarding table that contains hundreds of millions of content prefixes. In this work we design and preliminarily evaluate Caesar, the first content router that supports name-based forwarding at high speed. Caesar efficiently uses available processing and memory units in a high-end router to support forwarding tables containing a billion content prefixes with unlimited characters.
Canada lynx habitat and topographic use patterns in north central Washington: A reanalysis [Chapter 10]

We examined habitat selection by 22 lynx on the Okanogan National Forest in Washington, analyzing radio-telemetry data collected during two previous studies, 1981 through 1988. At a coarse scale, lynx showed little use of areas below 1,400 m or above 2,150 m. Within the zone between 1,400 and 2,150 m, lynx used areas with slopes <10% and moderate stream densities in winter. Selection for combinations of physical variables and vegetation types was stronger in winter versus summer, and lynx showed strong selection for lodgepole pine cover types in winter. Relative abundance of snowshoe hares measured from pellet counts on plots within the study area were highest within lodgepole pine and lowest within Douglas-fir cover types, and winter selectivity may have been influenced by abundance and distribution of hares. In summer, lynx avoided Douglas-fir cover types and selected northeast aspects; Douglas-fir tended to occur on southwest aspects, especially at higher elevations. Road densities in the study area did not have a significant effect on habitat selection, and lynx crossed roads at frequencies that did not differ from random expectation.
Infertility status of male individuals with abnormal spermiogram evaluated by cytogenetic analysis and in vitro sperm penetration assay.

BACKGROUND The possibility of a link between altered sperm morphology and functional ability, possibly reflected on the genetic level, is still a matter of controversy. MATERIAL/METHODS 60 infertile males with pathological spermiogram and 14 healthy individuals with confirmed in vivo fertility were selected for our study. Ejaculated sperm was assessed according to the standard criteria set by the World Health Organization, which constituted a basis for subgroup classification. The sperm penetration assay (SPA) using human sperm and hamster oocytes was subsequently performed with concomitant cytogenetic analysis of peripheral blood leukocytes (PBL). RESULTS More than 55% of infertile males with pathological spermiogram exhibited a decreased ability for penetration of the oocyte (SPAL30%). The lowest penetration ability was observed in the semen of patients with oligoasthenoteratozoospermia (OAT), of whom as many as 75% presented negative SPA values. We noted only 1 case of chromosome aberration (Robertsonian translocation) in the analyzed cohort of infertile patients. Strikingly, in the identified group of infertile patients with chromosome structural polymorphism (acrocentric chromosomes), we revealed a statistically significant decreased rate of sperm - oocyte penetration. CONCLUSIONS A causative link may exist between sperm malfunction and a specific feature of the chromosome variants detected in the blood leukocytes of infertile males with pathological spermiogram.
Physiotherapy rehabilitation following lumbar spinal fusion: a systematic review and meta-analysis of randomised controlled trials

Objective To evaluate the effectiveness of physiotherapy intervention following lumbar spinal fusion. Design Systematic review and meta-analysis. 2 independent reviewers searched information sources, assessed studies for inclusion and evaluated risk of bias. Quantitative synthesis using standardised mean differences was conducted on comparable outcomes across trials with similar interventions. Information sources Predefined terms were employed to search electronic databases. Additional studies were identified from key journals, reference lists, authors and experts. Eligibility criteria for included studies Randomised control trials published in English prior to 30 September 2011 investigating physiotherapy outpatient management of patients (>16 years), following lumbar spinal fusion, with measurements reported on one or more outcome of disability, function and health were included. Results 2 Randomised control trials (188 participants) from two countries were included. Both trials included a behavioural and an exercise intervention. 1 trial was evaluated as high risk of bias and one as unclear. 159 participants were incorporated in the meta-analysis. Although evidence from both trials suggested that intervention might reduce back pain short term (6 months) and long term (12 months and 2 years), and a behavioural intervention might be more beneficial than an exercise intervention, the pooled effects (0.72, 95% CI −0.25 to 1.69 at 6 months; 0.52, 95% CI −0.45 to 1.49 at 12 months and 0.75, 95% CI −0.46 to 1.96 at 2 years) did not demonstrate statistically significant effects. There was no evidence that intervention changes pain in the short (6 months) or long term (12 months and 2 years). The wide CI for pooled effects indicated that intervention could be potentially beneficial or harmful. Considerable heterogeneity was evident. Conclusions Inconclusive, very low-quality evidence exists for the effectiveness of physiotherapy management following lumbar spinal fusion. Best practice remains unclear. Limited comparability of outcomes and retrieval of only two trials reflect a lack of research in this area that requires urgent consideration.
Central and peripheral administration of endothelin-1 induces an increase in blood pressure in conscious trout.

The central and peripheral cardiovascular effects of endothelin (ET)-1 and ET-3 were investigated in conscious rainbow trout. Both intracerebroventricular and intra-arterial injections of ET-1 (6.25-25 pmol) but not ET-3 (25 pmol) caused a dose-dependent increase in mean dorsal aortic blood pressure and a concomitant decrease in heart rate. The hypertensive effects induced by intra-arterial and intracerebroventricular injection of ET-1 were associated with a significant ( P < 0.05) increase in systemic vascular resistance. Intracerebroventricular injection of ET-1 induced a twofold higher pressor response than that caused by intra-arterial injection of ET-1 and provoked a barostatic gain that was reduced by 2.5- to 3-fold compared with that calculated after intra-arterial administration of the peptide. The ET receptor antagonist bosentan significantly ( P< 0.05) attenuated these responses regardless of the route of administration. Finally, intra-arterial injection of ET-1 did not significantly modify plasma cortisol level. The present data demonstrate that intracerebroventricular and intra-arterial administration of very low doses of ET-1 produces hypertension in conscious trout. The lack of effect of ET-3 indicates that the hemodynamic actions of ET-1 are mediated both centrally and peripherally through ETAreceptors.
Update on the use of pramipexole in the treatment of Parkinson’s disease

Pramipexole is a non-ergot dopamine agonist shown to be efficacious in the treatment of Parkinson’s disease (PD). This review addresses the literature concerning pramipexole’s efficacy in treating motor and non-motor symptoms in PD, its impact on the development of dyskinesias and response fluctuations, the issue of neuroprotection, and the risk for developing adverse events such as increased somnolence, attacks of sudden onset of sleep, cardiac valvulopathy and impulse control disturbances.
Rhabdoid Meningioma: Grading and Prognostic Significance of This Uncommon Variant.

To the Editor: We read with great interest the paper by Vaubel et al entitled “Meningiomas with rhabdoid features lacking other histological features of malignancy: a study of 44 cases and review of the literature” (1). In that study, the authors analyzed the prognostic significance of rhabdoid morphology in 44 meningiomas with no other histological features of malignancy, that is, 20 or more mitoses per 10 high-power fields (HPF) and frank malignant cytology (2). They found that prognosis—in terms of survival and recurrence risk—was better in that cohort of patients than in patients with rhabdoid meningiomas with malignant histological features (2,3); however, survival was worse than that commonly observed in grade I and II meningiomas (2,4). Interestingly, tumor recurrence was significantly associated with the extent of surgical resection, while grade, extent of rhabdoid morphology and radiotherapy had no prognostic impact (1). The authors concluded
QUBIC: a qualitative biclustering algorithm for analyses of gene expression data

Biclustering extends the traditional clustering techniques by attempting to find (all) subgroups of genes with similar expression patterns under to-be-identified subsets of experimental conditions when applied to gene expression data. Still the real power of this clustering strategy is yet to be fully realized due to the lack of effective and efficient algorithms for reliably solving the general biclustering problem. We report a QUalitative BIClustering algorithm (QUBIC) that can solve the biclustering problem in a more general form, compared to existing algorithms, through employing a combination of qualitative (or semi-quantitative) measures of gene expression data and a combinatorial optimization technique. One key unique feature of the QUBIC algorithm is that it can identify all statistically significant biclusters including biclusters with the so-called ‘scaling patterns’, a problem considered to be rather challenging; another key unique feature is that the algorithm solves such general biclustering problems very efficiently, capable of solving biclustering problems with tens of thousands of genes under up to thousands of conditions in a few minutes of the CPU time on a desktop computer. We have demonstrated a considerably improved biclustering performance by our algorithm compared to the existing algorithms on various benchmark sets and data sets of our own. QUBIC was written in ANSI C and tested using GCC (version 4.1.2) on Linux. Its source code is available at: http://csbl.bmb. uga.edu/∼maqin/bicluster. A server version of QUBIC is also available upon request.
Hodological characterization of the medial amygdala in anuran amphibians

Early studies in anuran amphibians defined the amygdala as a single unit that only later could be subdivided into medial and lateral parts with the achievement of sensitive immunohistochemical and tracing techniques. However, the terminology used was often misleading when comparing with “homologous” amygdaloid nuclei in amniotes. Recently, the basal telencephalon of anurans has been demonstrated to be more complex than previously thought, and distinct amygdaloid nuclei were proposed on the basis of immunohistochemistry. Moreover, developmental data are increasing that support this notion. In the present study, we analyzed the patterns of afferent and efferent connections of the medial amygdala (MeA; formerly amygdala pars lateralis), considered as the main target of the vomeronasal information from the accessory olfactory bulb, as in other vertebrates. By means of axonal transport of dextran amines, the afferent and efferent connections of the MeA were traced in Rana perezi and Xenopus laevis under in vivo and in vitro conditions. Largely similar results were found in both species. The results showed abundant intratelencephalic and extratelencephalic connections that were readily comparable to those of other tetrapods. Most of these connections were reciprocal and, in particular, the strong relation of the MeA with the hypothalamus, via the stria terminalis, was demonstrated. Immunohistochemical techniques showed staining patterns that revealed abundant peptidergic afferents to the MeA, as well as minor inputs containing other neurotransmitters such as catecholamines. Double‐labeling experiments demonstrated that the peptidergic fibers that reach the MeA originate in the ventral hypothalamus, whereas the catecholaminergic innervation of the MeA arises in the caudal extent of the posterior tubercle. Taken together, the results about connectivity in our study support the comparison of the MeA in anurans with its counterparts (and similarly named) amygdaloid nuclei in amniotes. Most of the hodological features of the medial amygdala seem to be shared by those tetrapods with well‐developed vomeronasal systems. J. Comp. Neurol. 466:389–408, 2003. © 2003 Wiley‐Liss, Inc.