Miracle-dz/UniFAR-FTUs huggingface dataset:
Review of tegaserod in the treatment of irritable bowel syndrome

Tegaserod is a drug in a new class of compounds called aminoguanidine indoles and is structurally similar to serotonin (5-HT) with modifications that make the drug selective for the 5-HT4 receptor. Tegaserod has a stimulatory effect on gastrointestinal (GI) motility that has been demonstrated in animal studies and in healthy adults. Tegaserod also increases GI secretion and reduces rectal sensitivity. Tegaserod is currently approved by the FDA for the treatment of women with constipation-predominant irritable bowel syndrome (C-IBS). Eight large Phase III clinical trials involving > 5000 IBS patients support the clinical efficacy of tegaserod in this group of patients. Patients who were treated with tegaserod had an overall improvement in IBS symptoms (Subject’s Assessment of Global Relief) as well as in secondary end points, such as abdominal pain and discomfort, stool consistency, change in bowel movements and relief of bloating. Tegaserod was well-tolerated. The most common adverse reaction in clinical trials was diarrhoea, which was usually temporary and mild, although severe diarrhoea requiring hospitalisation has been rarely (< 1%) reported.
Effect of excess levels of lysine and leucine in wheat-based, amino acid-fortified diets on the mRNA expression of two selected cationic amino acid transporters in pigs.

An experiment was conducted to evaluate the effect of excess levels of Leu and Lys on the expression of b(0,+) and CAT-1 mRNA in jejunum, liver and the muscles Longissimus dorsi (LDM) and Semitendinosus (STM). Twenty pigs with an average initial BW of 16.4 ± 1.7 kg were used in a Randomized Complete Block. Dietary treatments (T) were as follows: T1, basal diet; T2, basal plus 3.5 g l-Lys/kg diet; T3, basal plus 1.5 g l-Leu/kg diet; T4, basal plus 3.5 g l-Lys plus 1.5 g l-Leu/kg diet. Diets in T1 and T3 met 100% the requirement of Lys for pigs within the 10 to 20 kg body weight range; diets in T2 and T4 contained 35% excess of Lys. Also, diets in T1 and T2 supplied 104%, whereas diets in T3 and T4 supplied 116% the requirement of Leu. The expression of b(0,+) in jejunum was reduced (p = 0.002) because of the supplementation of l-Leu, but l-Lys supplementation had no effect (p = 0.738). In contrast, the expression of b(0,+) in STM (p = 0.012) and liver (p = 0.095) was reduced by the high level of Lys, but Leu had no effect (p > 0.100). CAT-1 expression in STM increased by high Lys (p = 0.023) and Leu (p = 0.007) levels. In liver, the expression of CAT-1 substantially increased (p = 0.001) because of Lys. In conclusion, excess levels of dietary Lys and Leu affect the expression of cationic amino acid transporters, and this effect varies depending on the studied tissue.
What is the Relation (If Any) between a Firm's Corporate Governance Arrangements and Its Financial Performance?

We present a model to test the null hypothesis that firms organize their corporate governance arrangements optimally given the constraints they face. Following the literature, the model rejects the null if the conditional correlation between governance and performance is significantly different from zero. Our model provides a clean test of this hypothesis by controlling for measurement errors in all observed variables and avoiding simultaneous equation biases by casting our model as a reduced-form bivariate equation. We model governance, performance and the constraints on the firm’s investment decisions as latent variables. Our estimate of the conditional correlation between our measures of governance and performance is statistically speaking equal to zero, which therefore provides empirical support for the in-equilibrium view proposed by Demsetz (1983), of corporate governance Arrangements.
CARMA1‐mediated NF‐κB and JNK activation in lymphocytes

Summary: Activation of transcription factor nuclear factor‐κB (NF‐κB) and Jun N‐terminal kinase (JNK) play the pivotal roles in regulation of lymphocyte activation and proliferation. Deregulation of these signaling pathways leads to inappropriate immune response and contributes to the development of leukemia/lymphoma. The scaffold protein CARMA1 [caspase‐recruitment domain (CARD) membrane‐associated guanylate kinase (MAGUK) protein 1] has a central role in regulation of NF‐κB and the JNK2/c‐Jun complex in both B and T lymphocytes. During last several years, tremendous work has been done to reveal the mechanism by which CARMA1 and its signaling partners, B cell CLL‐lymphoma 10 and mucosa‐associated lymphoid tissue 1, are activated and mediate NF‐κB and JNK activation. In this review, we summarize our findings in revealing the roles of CARMA1 in the NF‐κB and JNK signaling pathways in the context of recent advances in this field.
AmpD, essential for both β‐lactamase regulation and cell wall recycling, is a novel cytosolic N‐acetylmuramyl‐L‐alanine amidase

In enterobacteria, the ampD gene encodes a cytosolic protein which acts as a negative regulator of β‐lactamase expression. It is shown here that the AmpD protein is a novel N‐acetylmuramyl‐L‐alanine amidase (E.C.3.5.1.28) participating in the intracellular recycling of peptido‐glycan fragments. Surprisingly, AmpD exhibits an exclusive specificity for substrates containing anhydro muramic acid. This anhydro bond is mainly found in the peptidoglycan degradation products formed by the periplasmic lytic transglycosylases and thus might behave as a‘recycling tag’allowing the enzyme to distinguish these fragments from the newly synthesized peptidoglycan precursors. The AmpD substrate (or substrates) which accumulates in the absence of the corresponding enzymatic activity acts as an intracellular positive effector for β‐lactamase expression and might represent an element of a communication network between the chromosome and the cell wall peptidoglycan.
Gynecologic Cancer InterGroup (GCIG) Consensus Review for Mullerian Adenosarcoma of the Female Genital Tract

Mullerian adenosarcomas of the female genital tract are rare malignancies, originally described in the uterus, the most common site of origin, but they may also arise in extrauterine locations. Uterine adenosarcomas make up 5% of uterine sarcomas and tend to occur in postmenopausal women. They are usually low-grade tumors and are characterized by a benign epithelial component with a malignant mesenchymal component, which is typically a low-grade endometrial stromal sarcoma but can also be a high-grade sarcoma. Tumors that exhibit a high-grade sarcomatous overgrowth have a worse outcome. Adenosarcomas have been described as being midway along the spectrum between benign adenofibromas and carcinosarcomas. They generally have a good prognosis with the exception of deeply invasive tumors or those with high-grade sarcomatous overgrowth. Extrauterine adenosarcomas also have a higher risk for recurrence. In view of their rarity, there have not been any clinical trials in mullerian adenosarcomas and relatively little research. This article reviews the current knowledge and provides recommendation for the management of mullerian adenosarcomas.
A compact shorted patch rectenna design with harmonic rejection properties

This paper presents a compact design of shorted patch rectenna with the harmonic rejection properties for the applications of wireless power transmission. In order to improve the power conversion efficiency (PCE), the harmonic rejection filter (HRF) is replaced by etching a U-shape slot resonator on the shorted patch antenna. As a result, this method may improve the PCE without sacrificing the capability of higher order harmonic noise rejection.
Differential cellular and subcellular distribution of glutamate transporters in the cat retina

Retrieval of glutamate from extracellular sites in the retina involves at least five excitatory amino acid transporters. Immunocytochemical analysis of the cat retina indicates that each of these transporters exhibits a selective distribution which may reflect its specific function. The uptake of glutamate into Müller cells or astrocytes appears to depend upon GLAST and EAAT4, respectively. Staining for EAAT4 was also seen in the pigment epithelium. The remaining transporters are neuronal with GLT-1α localized to a number of cone bipolar, amacrine, and ganglion cells and GLT-1v in cone photoreceptors and several populations of bipolar cells. The EAAC1 transporter was found in horizontal, amacrine, and ganglion cells. Staining for EAAT5 was seen in the axon terminals of both rod and cone photoreceptors as well as in numerous amacrine and ganglion cells. Although some of the glutamate transporter molecules are positioned for presynaptic or postsynaptic uptake at glutamatergic synapses, others with localizations more distant from such contacts may serve in modulatory roles or provide protection against excitoxic or oxidative damage.
The estimation of genetic relationships using molecular markers and their efficiency in estimating heritability in natural populations

Molecular marker data collected from natural populations allows information on genetic relationships to be established without referencing an exact pedigree. Numerous methods have been developed to exploit the marker data. These fall into two main categories: method of moment estimators and likelihood estimators. Method of moment estimators are essentially unbiased, but utilise weighting schemes that are only optimal if the analysed pair is unrelated. Thus, they differ in their efficiency at estimating parameters for different relationship categories. Likelihood estimators show smaller mean squared errors but are much more biased. Both types of estimator have been used in variance component analysis to estimate heritability. All marker-based heritability estimators require that adequate levels of the true relationship be present in the population of interest and that adequate amounts of informative marker data are available. I review the different approaches to relationship estimation, with particular attention to optimizing the use of this relationship information in subsequent variance component estimation.
Small LDL, atherogenic dyslipidemia, and the metabolic syndrome.

A high serum cholesterol has been increasingly acknowledged as being a major risk factor for coronary heart disease (CHD). Several types of evidence support the cholesterol-CHD link; these encompass research in laboratory animals, epidemiological studies, findings of premature CHD in genetic forms of hypercholesterolemia, laboratory investigations, and clinical trials of cholesterol-lowering therapy. Most people with a high serum cholesterol also have elevated LDL because much of the serum cholesterol is transported in LDL. The concept therefore has emerged that LDL is the predominant atherogenic lipoprotein. The National Cholesterol Education Program (NCEP)1 specifically designated LDL cholesterol as the primary target of cholesterol-lowering therapy. This assignment of priority to LDL cholesterol seems to be fully vindicated by recent clinical trials.2 3 4 These trials tested HMG CoA reductase inhibitors (statins), which mainly lower LDL, for effects on coronary morbidity and mortality. Statin therapy in these trials produced astonishing reductions in new coronary events; these reductions almost certainly were a result of concomitant decreases in LDL levels. Among the different risk factors for CHD, a raised LDL level appears to be primary. Strong evidence indicates that high LDL concentrations initiate atherogenesis and promote atherosclerosis at every stage. The remarkable finding that LDL-lowering therapy reduces risk for subsequent coronary events even in patients with advanced atherosclerotic disease discloses a role for LDL in late stages of atherogenesis.2 3 4 Moreover, populations devoid of some elevations of LDL levels exhibit relatively low prevalence of CHD even when other coronary risk factors, eg, cigarette smoking, hypertension, and diabetes mellitus, are common.5 An elevated LDL thus is at the core of atherogenesis. Table 1⇓ classifies LDL-cholesterol levels according to NCEP guidelines; approximate corresponding values for total cholesterol also are listed. In the United States, most CHD occurs in patients who have borderline …
Hybrid local search algorithms on Graph Coloring Problem

Hybridization of local search algorithms yield promising algorithms for combinatorial optimization problems such as Graph Coloring Problem (GCP). This paper presents a new meta-heuristic Simulated Annealing with Backtracking (SABT) and shows the effect of hill climber and tabu search on SABT for solving GCP. The algorithm proposed merges the power of simulated annealing approach and backtracking mechanism. Some hill climbers are integrated for fine tuning and also tabu search is integrated for avoiding from redundant search. Several tests are run on a collection of benchmarks from DIMACS challenge suite and promising results are obtained. A comparison of SABT framework with some other state-of-the-art algorithms is presented along with an analysis of the performance of the algorithm.
Pulmonary 64-MDCT angiography with 30 mL of IV contrast material: vascular enhancement and image quality.

OBJECTIVE The objective of our study was to determine whether vascular enhancement and image quality can be preserved in pulmonary CT angiography (CTA) performed on a 64-MDCT scanner with 30 mL of IV contrast material. MATERIALS AND METHODS This retrospective matched-cohort study compared image quality of pulmonary CTA performed using 30 mL of IV contrast material versus 100 mL of IV contrast material. CT images of 50 patients (46 men, four women; mean age, 66 years) who underwent pulmonary CTA on a 64-MDCT scanner using a low dose (30 mL) of iodixanol 320 and another 50 patients (49 men, one woman; mean age, 65 years) who underwent pulmonary CTA using a regular dose (100 mL) of contrast material during the same time period were selected for review. The 30- and 100-mL pulmonary CTA studies were retrospectively evaluated by two thoracic radiologists in random order. Attenuation values were recorded over the main, right main, selected lobar, segmental, and subsegmental pulmonary arteries. Image quality was also subjectively assessed using visual scores on a scale from 1 (nondiagnostic) to 5 (excellent). RESULTS The average attenuation measurements of the main, right main, selected lobar, segmental, and subsegmental pulmonary arteries were 260, 262, 280, 316, and 338 HU, respectively, on the 30-mL studies and 313, 301, 316, 344, and 349 HU, respectively, on the 100-mL studies. The average visual score was 4.0 for both the 30- and 100-mL groups. A visual score of 4 or 5 was given to 82% of studies in the 30-mL group and 78% of studies in the 100-mL group. CONCLUSION Contrast agent dose for pulmonary CTA using a 64-MDCT scanner can be significantly reduced without compromising diagnostic image quality.
Lack of association of increased antibody levels to mycobacterial hsp65 with rheumatoid arthritis: results from a study of disease discordant twin pairs.

OBJECTIVES--To investigate the role of humoral immunity to mycobacterial hsp65 in the aetiology of rheumatoid arthritis. METHODS--Levels of IgG antibodies to recombinant mycobacterial hsp65 were measured by enzyme linked immunosorbent assay (ELISA) in serum samples of 152 twin pairs discordant for RA and in serum samples from 62 normal blood donors. RESULTS--No significant differences between antibody levels in the subjects with RA compared either with their unaffected twins or with a group of normal blood donors was observed. In the monozygotic twins there was a strong but negative association between levels of antibody to hsp65 and disease status. Zygosity, sex, and HLA status did not significantly affect levels of antibody to hsp65. CONCLUSION--Previous reports of an association between hsp65 and RA were not confirmed.
Effects of a Cardiovascular Risk Reduction Intervention With Psychobehavioral Strategies for Korean Adults With Type 2 Diabetes and Metabolic Syndrome

Background: Type 2 diabetes mellitus (DM) and metabolic syndrome are associated with high risk of cardiovascular disease (CVD) and depression. Although lifestyle modifications including regular exercise and weight control are recommended as a primary approach to glycemic control and CVD risk reduction for people with DM and/or metabolic syndrome, little is known concerning the effects of CVD risk reduction interventions using psychobehavioral strategies in this population. Objective: This pilot study investigated the effects of a 16-week CVD risk reduction intervention in Korean adults with type 2 DM and metabolic syndrome. Methods: A prospective, pretest and posttest, controlled, quasi-experimental design enrolled a convenience sample of 43 Korean adults with type 2 DM and metabolic syndrome at a university hospital. The adults in the intervention group participated in a 16-week CVD risk reduction intervention consisting of 150 minutes of regular exercise per week; 200- to 300-kcal reduced daily diet for weight control; one-on-one psychobehavioral counseling based on constructs from the Transtheoretical Model such as processes of change, self-efficacy, and decisional balance; and telephone coaching for behavioral modification. Participants in the control group received a booklet with basic diabetic education as part of their routine care. Repeated-measures analysis of variance was used for analyzing the effects of the CVD risk reduction intervention on cardiometabolic risk factors including the UK Prospective Diabetes Study score for 10-year CVD risk, glycated hemoglobin (HbA1c), and depression. Results: The intervention group showed significant reductions (P < .05) at 16 weeks, compared with the control group on the UK Prospective Diabetes Study fatal risk scale (−1.73% vs −0.04%), triglycerides (−38.5 vs −15.1 mg/dL), fasting plasma glucose (−29.24 vs +1.77 mg/dL), HbA1c (−0.37% vs +0.17%), and depression (score, −3.24 vs 1.40) measurements. Conclusions: This pilot study yielded evidence for the beneficial impact of the CVD risk reduction intervention for Korean adults with type 2 DM and metabolic syndrome on improved glycemic control, reduced CVD risk, and depression.
Health markers in obese adolescents improved by a 12-week recreational soccer program: a randomised controlled trial

Abstract The effects of a recreational soccer program (RSP) upon body composition, heart rate variability (HRV), biochemical markers, cardio-respiratory fitness, and endothelial function in obese adolescents were investigated. A randomised controlled clinical trial was conducted with 30 adolescents aged 12–17 years and body mass index (BMI) >2 standard deviations of WHO reference values, which were assigned to RSP (n = 10, 2 girls) and obese control (n = 10, 4 girls) groups. The 12-week RSP included 60-min sessions performed 3 times/week. BMI, waist circumference, blood pressure, blood glucose, lipid profile, insulin, C-reactive protein, HRV, and maximal oxygen consumption (VO2peak) were evaluated following standardised procedures. Body composition was determined by dual-energy X-ray absorptiometry and endothelial function by venous occlusion plethysmography. After intervention, RSP exhibited significant reductions in BMI (−0.7 ± 0.2 kg · m–2), waist circumference (−8.2 ± 1.4 cm), %body fat (−2.2 ± 0.4%), systolic blood pressure (−5.0 ± 2.3 mmHg), total cholesterol (−16.2 ± 5.8 mg · dL−1), triglycerides (−20.5 ± 12.9 mg · dL−1), C-reactive protein (−0.06 ± 0.01 mg · dL−1), insulin resistance (HOMA-IR, −1.4 ± 0.6), and sympathetic activity (LF, −13.9 ± 6.6 un) vs. controls (P < 0.05). Significant increase was observed in parasympathetic activity (HF, 13.9 ± 6.6 un), VO2peak (7.9 ± 2.8 ml · kg−1 · min−1), and high-density lipoprotein cholesterol (11.0 ± 6.3 mg · dL−1) (P < 0.05). Vascular conductance (19.5 ± 8.1 ml · min−1 · 100 ml, P = 0.005) increased and vascular resistance (−5.9 ± 2.4 ml · min−1 · 100 ml, P = 0.041) decreased in RSP, but not in controls. A 12-week recreational soccer intervention was effective to improve biochemical, cardiovascular, and fitness health markers in obese adolescents.
Children in clinical trials: towards evidence-based pediatric pharmacotherapy using pharmacokinetic-pharmacodynamic modeling

ABSTRACT Introduction: In pediatric pharmacotherapy, many drugs are still used off-label, and their efficacy and safety is not well characterized. Different efficacy and safety profiles in children of varying ages may be anticipated, due to developmental changes occurring across pediatric life. Areas covered: Beside pharmacokinetic (PK) studies, pharmacodynamic (PD) studies are urgently needed. Validated PKPD models can be used to derive optimal dosing regimens for children of different ages, which can be evaluated in a prospective study before implementation in clinical practice. Strategies should be developed to ensure that formularies update their drug dosing guidelines regularly according to the most recent advances in research, allowing for clinicians to integrate these guidelines in daily practice. Expert commentary: We anticipate a trend towards a systems-level approach in pediatric modeling to optimally use the information gained in pediatric trials. For this approach, properly designed clinical PKPD studies will remain the backbone of pediatric research.
ASYMMETRIC GENERALIZATION BETWEENTHE DISCRIMINATIVE STIMULUS EFFECTS OF NICOTINE AND COCAINE

The discriminative stimulus effects of nicotine and cocaine were studied, alone and in combination, in rats. Two sets of rats were trained to press one lever when injected intraperitoneally (i.p.) with either nicotine (0.1 mg/kg = 0.6 micromol/kg, Set 1) or cocaine (8.9 mg/kg base = 29.4 micromol/kg, Set 2), and another lever when injected with saline. Rats learned to discriminate drug from saline, and maintained discriminative control throughout the study (at > 85% drug-appropriate responding). In accordance with most previous findings, cocaine only partially substituted for nicotine (maximum = 41% nicotine-lever responding). The nicotinic agonist, nornicotine, produced dose-related, near-full substitution for nicotine (maximum = 76% nicotine-lever responding), whereas the peripherally acting nicotinic agonist, methylcarbamylcholine, did not substitute for nicotine. The muscarinic receptor agonist pilocarpine also failed to substitute for nicotine. However, in the cocaine-trained rats, nicotine substituted fully for cocaine in a dose-dependent manner, demonstrating that cross-generalization between the two drugs is not symmetrical. Finally, administration of each drug as a pre-treatment to the other yielded inconsistent increases in each drug's discriminative stimulus effects. The results are congruent with the view that the discriminative stimulus effects of nicotine and cocaine share common features, but the asymmetric pattern of cross-generalization and the interactions revealed in the combination tests also suggest that there are important differences between them.