Miracle-dz/UniFAR-FTUs huggingface dataset:
Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics

Donepezil is the leading compound for the treatment of Alzheimer’s disease (AD) in more than 50 countries. As compared with other conventional acetylcholinesterase inhibitors (AChEIs), donepezil is a highly selective and reversible piperidine derivative with AChEI activity that exhibits the best pharmacological profile in terms of cognitive improvement, responders rate (40%–58%), dropout cases (5%–13%), and side-effects (6%–13%) in AD. Although donepezil represents a non cost-effective treatment, most studies convey that this drug can provide a modest benefit on cognition, behavior, and activities of the daily living in both moderate and severe AD, contributing to slow down disease progression and, to a lesser exetnt, to delay institutionalization. Patients with vascular dementia might also benefit from donepezil in a similar fashion to AD patients. Some potential effects of donepezil on the AD brain, leading to reduced cortico-hippocampal atrophy, include the following: AChE inhibition, enhancement of cholinergic neurotransmission and putative modulation of other neurotransmitter systems, protection against glutamate-induced excitotoxicity, activation of neurotrophic mechanisms, promotion of non-amyloidodgenic pathways for APP processing, and indirect effects on cerebrovascular function improving brain perfusion. Recent studies demonstrate that the therapeutic response in AD is genotype-specific. Donepezil is metabolized via CYP-related enzymes, especially CYP2D6, CYP3A4, and CYP1A2. Approximately, 15%–20% of the AD population may exhibit an abnormal metabolism of AChEIs; about 50% of this population cluster would show an ultrarapid metabolism, requiring higher doses of AChEIs to reach a therapeutic threshold, whereas the other 50% of the cluster would exhibit a poor metabolism, displaying potential adverse events at low doses. In AD patients treated with a multifactorial therapy, including donepezil, the best responders are the CYP2D6-related extensive (EM)(*1/*1, *1/*10) (57.47%) and intermediate metabolizers (IM)(*1/*3, *1/*5, *1/*6, *7/*10) (25.29%), and the worst responders are the poor (PM) (*4/*4)(9.20%) and ultra-rapid metabolizers (UM) (*1×N/*1) (8.04%). Pharmacogenetic and pharmacogenomic factors may account for 75%–85% of the therapeutic response in AD patients treated with donepezil and other AChEIs metabolized via enzymes of the CYP family. The implementation of pharmacogenetic protocols can optimize AD therapeutics.
The Effect of Antigen Stimulation on the Migration of Mature T Cells from the Peripheral Lymphoid Tissues to the Thymus

Although the maturation and export of T cells from the thymus has been extensively studied, the movement of cells in the opposite direction has been less well documented. In particular, the question of whether T cells which have been activated by antigen in the periphery are more likely to return to the thymus had been raised but not clearly answered. We examined this issue by activating T cells present in the periphery with their cognate antigen, and assessing migration to the thymus. TCR-transgenic cells from OT-I mice (Thy1.2+), which recognise the ovalbumin peptide OVA257–264 in the context of H-2Kb, were transferred into otherwise unmanipulated Thy1.1+ C57BL/6 mice. Recipient mice were injected i.v. with 5 μg peptide (SIINFEKL) approximately 24 hours later. The numbers of donor-derived (Thy1.2+) cells in the thymus and peripheral lymphoid tissue were determined. The results clearly show increased numbers of transgenic cells in the thymus 3 days after antigenic stimulation. However, since numbers of transgenic cells increased in the spleen and LN in about the same proportion, the data do not support the notion that there is highly increased selective migration of activated T cells to the thymus. Rather, they suggest that a sample of peripheral cells enters the thymus each day, and that the mature immigrants detected in the thymus merely reflect the contents of the peripheral T cell pool.
A corpus for the evaluation of lossless compression algorithms

A number of authors have used the Calgary corpus of texts to provide empirical results for lossless compression algorithms. This corpus was collected in 1987, although it was not published until 1990. The advances with compression algorithms have been achieving relatively small improvements in compression, measured using the Calgary corpus. There is a concern that algorithms are being fine-tuned to this corpus, and that small improvements measured in this way may not apply to other files. Furthermore, the corpus is almost ten years old, and over this period there have been changes in the kinds of files that are compressed, particularly with the development of the Internet, and the rapid growth of high-capacity secondary storage for personal computers. We explore the issues raised above, and develop a principled technique for collecting a corpus of test data for compression methods. A corpus, called the Canterbury corpus, is developed using this technique, and we report the performance of a collection of compression methods using the new corpus.
Immunoelectron microscopic localization of type 1 plasminogen activator inhibitor on the surface of activated endothelial cells

Immunogold EM was employed to compare the distribution of type 1 plasminogen activator inhibitor (PAI-1) on the surface of agonist- activated human umbilical vein endothelial cells (HUVECs) with that of control, unactivated cells. As previously observed, (Schleef, R.R., T.J. Podor, E. Dunne, J. Mimuro, and D.J. Loskutoff. J. Cell Biol. 110:155-163), analysis of cross-sections of nonpermeabilized control HUVEC monolayers stained first with affinity-purified rabbit antibodies to PAI-1 and then with gold-conjugated goat anti-rabbit IgG, revealed the presence of relatively few gold particles (less than 1-2% of the total) on the apical cell surface. The majority of gold particles were detected primarily in the extracellular matrix between the culture substratum and the cell membrane. In contrast, treatment of HUVECs with tumor necrosis factor alpha (TNF alpha; 200 U/ml, 24 h) or with lipopolysaccharide (LPS; 10 micrograms/ml, 24 h) resulted in an increased staining of PAI-1 not only in the extracellular matrix, but also on the apical cell surface (10-fold increase). Immunoabsorption of the rabbit anti-PAI-1 with purified PAI-1, or treatment of HUVECs with tissue-type plasminogen activator (2.5 micrograms/ml, 2 h, 4 degrees C) reduced the amount of staining both on the apical surface and in the extracellular matrix of agonist-activated HUVECs by 80-95%. The topographical location of PAI-1 on the cell surface was examined further by coupling immunogold staining with high resolution surface replication. Transmission EM of surface replicas from TNF alpha- or LPS- activated HUVECs revealed a general increase in PAI-1 staining both on planar regions and within indentations of the apical cell surface. Nonactivated HUVECs revealed PAI-1-specific immunogold particles only in areas of exposed extracellular matrix between the cells and occasionally at regions of cell-cell contacts. Analysis of activated bovine aortic endothelial cells by immuno-electron microscopy, immunologic assays, and flow cytometry revealed similar increases in surface PAI-1. These increases in surface PAI-1 could be detected by 3 h and continued over a 24-h period. The expression of PAI-1 on the luminal surface of endothelial cells during immune or inflammatory reactions could reduce endothelial fibrinolytic activity, thus, promoting the localized, pathologic formation of intravascular thrombi.
Context Effects from Bodily Sensations: Examining Bodily Sensations Induced by Flooring and the Moderating Role of Product Viewing Distance

When consumers shop, the flooring underfoot can prompt bodily sensations-a sense of comfort from soft carpeting or fatigue from hard tile flooring. Like moods, such bodily sensations may foster context effects on the products shoppers observe. However, whereas moods prompt only assimilation effects, we demonstrate that consumers' bodily sensations can produce either assimilation, contrast, or no context effects. Further, consumers' viewing distance from a product can determine the direction of such effects. Evidence attests that these effects are (a) prompted by bodily sensations, not conceptual knowledge, (b) rather limited in scope, and (c) reversible in direction under certain circumstances. (c) 2009 by JOURNAL OF CONSUMER RESEARCH, Inc.
The Impact of Low-Grade Brain Tumors on Verbal Fluency Performance Bram Goldstein

Verbal fluency has traditionally represented left hemispheric function, based on large acquired lesion studies. However, recent functional imaging studies have demonstrated bilateral hemispheric activation during phonemic and semantic word generation tasks. We examined 25 left hemisphere (LH) and 26 right hemisphere (RH) low-grade brain tumor patients on semantic and phonemic fluency. Patients were also assigned to a combined anterior (left and right) group (n=26) or a combined posterior (left and right) group (n=20) and compared with normal controls (NC; n=57). We hypothesized that there would be greater left than right hemispheric phonemic and semantic fluency impairments. We also hypothesized that there would be greater anterior, specifically left anterior, than posterior impairments on phonemic fluency given their respective retrieval and initiation requirements. Finally, it was predicted that the LH patients, particularly the left posterior group, would exhibit the greatest semantic fluency impairments. Results indicated that on semantic fluency, the LH group produced significantly fewer semantic fluency responses compared to the RH group, but the expected left posterior and left frontal group differences were not found. There were no significant patient group differences associated with phonemic fluency. While we encountered semantic fluency impairments in this brain tumor population, we did not find the extensive deficits associated with the distinct or localized brain regions previously reported in the literature.
Surgery and Risk of Sporadic Creutzfeldt-Jakob Disease in Denmark and Sweden: Registry-Based Case-Control Studies

Background: Epidemiologic evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains controversial. Methods: From Danish and Swedish registries we selected 167 definite and probable sCJD cases (with onset between 1987 and 2003) and 3,059 controls (835 age-, sex-, and residence-matched, and 2,224 unmatched). Independent of case/control status, surgical histories were obtained from National Hospital Discharge Registries. Surgical procedures were categorized by body system group and lag time to onset of sCJD. Exposure frequencies were compared using logistic regression. Results: A history of any major surgery, conducted ≧20 years before sCJD onset, was more common in cases than both matched (OR = 2.44, 95% CI = 1.46–4.07) and unmatched controls (OR = 2.25, 95% CI = 1.48–3.44). This observation was corroborated by a linear increase in risk per surgical discharge (OR = 1.57, 95% CI = 1.13–2.18; OR = 1.50, 95% CI = 1.18–1.91). Surgery of various body systems, including peripheral vessels, digestive system and spleen, and female genital organs, was significantly associated with increased sCJD risk. Conclusions: A variety of major surgical procedures constitute a risk factor for sCJD following an incubation period of many years. A considerable number of sCJD cases may originate from health care-related accidental transmission.
Association of Sand Dust Particles with Pulmonary Function and Respiratory Symptoms in Adult Patients with Asthma in Western Japan Using Light Detection and Ranging: A Panel Study

Light detection and ranging (LIDAR) can estimate daily volumes of sand dust particles from the East Asian desert to Japan. The objective of this study was to investigate the relationship between sand dust particles and pulmonary function, and respiratory symptoms in adult patients with asthma. One hundred thirty-seven patients were included in the study. From March 2013 to May 2013, the patients measured their morning peak expiratory flow (PEF) and kept daily lower respiratory symptom diaries. A linear mixed model was used to estimate the correlation of the median daily levels of sand dust particles, symptoms scores, and PEF. A heavy sand dust day was defined as an hourly concentration of sand dust particles of >0.1 km−1. By this criterion, there were 8 heavy sand dust days during the study period. Elevated sand dust particles levels were significantly associated with the symptom score (0.04; 95% confidence interval (CI); 0.03, 0.05), and this increase persisted for 5 days. There was no significant association between PEF and heavy dust exposure (0.01 L/min; 95% CI, −0.62, 0.11). The present study found that sand dust particles were significantly associated with worsened lower respiratory tract symptoms in adult patients with asthma, but not with pulmonary function.
Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer

Background A multifunctional telodendrimer-based micelle system was characterized for delivery of imaging and chemotherapy agents to mouse tumor xenografts. Previous optical imaging studies demonstrated qualitatively that these classes of nanoparticles, called nanomicelles, preferentially accumulate at tumor sites in mice. The research reported herein describes the detailed quantitative imaging and biodistribution profiling of nanomicelles loaded with a cargo of paclitaxel. Methods The telodendrimer was covalently labeled with 125I and the nanomicelles were loaded with 14C-paclitaxel, which allowed measurement of pharmacokinetics and biodistribution in the mice using microSPECT/CT imaging and liquid scintillation counting, respectively. Results The radio imaging data showed preferential accumulation of nanomicelles at the tumor site along with a slower clearance rate than paclitaxel formulated in Cremophor EL (Taxol®). Liquid scintillation counting confirmed that 14C-labeled paclitaxel sequestered in nanomicelles had increased uptake by tumor tissue and slower pharmacokinetics than Taxol. Conclusion Overall, the results indicate that nanomicelle-formulated paclitaxel is a potentially superior formulation compared with Taxol in terms of water solubility, pharmacokinetics, and tumor accumulation, and may be clinically useful for both tumor imaging and improved chemotherapy applications.
Platelet-activating factor acetylhydrolase is not associated with carotid intima-media thickness in hypercholesterolemic Sicilian individuals.

BACKGROUND Atherosclerosis is a complex, chronic disease that usually arises from the converging action of several pathogenic processes, including hypertension, hyperlipidemia, obesity, and the accumulation of oxidized LDL. Platelet-activating factor acetylhydrolase (PAF-AH) is a LDL- and HDL-bound enzyme that hydrolyzes and inactivates PAF and prevents LDL-cholesterol oxidation, thus delaying the onset of atherosclerotic disease. METHODS We evaluated the relationship between variants of the PAF-AH gene polymorphisms Arg92His, Ile198Thr, and Ala379Val and the presence of carotid atherosclerosis in 190 hypercholesterolemic Sicilian individuals. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The participants were classified according to having normal (< or =1 mm) or abnormal (> or =1 mm) IMT and were also investigated for physical characteristics and biochemical indices, including PAF-AH activity. RESULTS PAF-AH activity and LDL concentrations were significantly correlated in hypercholesterolemic patients, but plasma PAF-AH activity and HDL were not significantly correlated in either IMT group. No significant differences were detected among the PAF-AH gene polymorphisms in both groups after correction for age, sex, body mass index, plasma glucose and lipid concentrations, PAF-AH activity, blood pressure, and smoking habits. The analysis of PAF-AH genotype distribution showed no significant differences in percentage of 92, 198, and 379 genotypes in both IMT groups. CONCLUSION Our data provided no evidence that PAF-AH polymorphisms influence PAF-AH activity and atherosclerosis in hypercholesterolemic Sicilian patients.
State and Trait Effects on Individual Differences in Children’s Mathematical Development

Substantial longitudinal relations between children’s early mathematics achievement and their much later mathematics achievement are firmly established. These findings are seemingly at odds with studies showing that early educational interventions have diminishing effects on children’s mathematics achievement across time. We hypothesized that individual differences in children’s later mathematical knowledge are more an indicator of stable, underlying characteristics related to mathematics learning throughout development than of direct effects of early mathematical competency on later mathematical competency. We tested this hypothesis in two longitudinal data sets, by simultaneously modeling effects of latent traits (stable characteristics that influence learning across time) and states (e.g., prior knowledge) on children’s mathematics achievement over time. Latent trait effects on children’s mathematical development were substantially larger than state effects. Approximately 60% of the variance in trait mathematics achievement was accounted for by commonly used control variables, such as working memory, but residual trait effects remained larger than state effects. Implications for research and practice are discussed.
Effectiveness of a Social Marketing Campaign Promoting Use of a Sexual Health Text Service by Teens

Sexual health text message services are becoming an increasingly popular way to provide adolescents with accurate sexual health information, but promotion of such services is often limited. This study uses three quantitative methods (service use data, a text message–based questionnaire, and an in-school online survey) to assess the effectiveness of an in-school social marketing campaign promoting a sexual health text message service that connects teens directly with a health educator. The 3-month campaign was associated with increased service use, but use was still relatively low. Follow-up qualitative work that included focus groups and interviews found a number of barriers to use. Teens indicated they did not have sexual health questions, did not think of the service, or were unsure how to use it. Teens also brought up additional barriers such as concern over parents seeing the messages. Implications for text message service providers and health educators are discussed.
Assessment of Psychopathy in a Population of Incarcerated Adolescent Offenders

The reliability, validity, and factor structure of a modified version of the Psychopathy ChecklistRevised (PCL-R) for adolescents was investigated, completed using file information only, in a sample of incarcerated Black and White male adolescents. Interrater reliability and internal consistency were high, and confirmatory factor analyses and coefficients of congruence showed that the factor structure in this sample resembled the 2-factor solution found in adults. No significant racial differences were found for reliability or mean PCL-R scores. In addition, relationships between PCL-R scores and psychometric measures and behavioral indicators of maladjustment were similar to those previously found in adult populations. The construct of psychopathy, as defined by the PCLR modified for use with adolescents, appears applicable to both Black and White adolescent male offenders. The study gives evidence for the structural and substantive validity of the modified PCLR in this population. The Psychopathy Checklist--Revised (PCL-R; Hare, 1991 ) has proven reliable and useful in subgrouping adult offenders who are incarcerated, White, and male. This study examined the usefulness of this instrument with a population of incarcerated Black and White male adolescent offenders.
Spatially Structured Activity in Synaptically Coupled Neuronal Networks: I. Traveling Fronts and Pulses

We consider traveling front and pulse solutions to a system of integro-differential equations used to describe the activity of synaptically coupled neuronal networks in a single spatial dimension. Our first goal is to establish a series of direct links between the abstract nature of the equations and their interpretation in terms of experimental findings in the cortex and other brain regions. This is accomplished first by presenting a biophysically motivated derivation of the system and then by establishing a framework for comparison between numerical and experimental measures of activity propagation speed. Our second goal is to establish the existence of traveling pulse solutions using more rigorous methods. Two techniques are presented. The first, a shooting argument, reduces the problem from finding a specific solution to an integro-differential equation system to finding any solution to an ODE system. The second, a singular perturbation argument, provides a construction of traveling pulse solutions un.
Noise and the Common Sense Informatic Situation for a Mobile Robot

Any model of the world a robot constructs on the basis of its sensor data is necessarily both incomplete, due to the robot's limited window on the world, and uncertain, due to sensor and motor noise. This paper supplies a logical account of sensor data assimilation in which such models are constructed through an abductive process which hypothesises the existence, locations, and shapes of objects. Noise is treated as a kind of non-determinism, and is dealt with by a consistency-based form of abduction.
Myocardial Scars Are an Underestimated Cardiovascular Burden in Patients with Internal Carotid Artery Stenosis

Background: Patients with internal carotid artery (ICA) stenosis have an increased incidence of coronary heart disease. Evidence about the incidence of clinically silent myocardial infarction (MI) in these patients is limited. Contrast-enhanced cardiac magnetic resonance (CMR) imaging allows for the detection of minor myocardial damage. Objective: We tested whether patients with ICA stenosis exhibit a relevant incidence of silent MI when assessed by CMR. Methods: In a single-center study, 77 consecutive patients (age 68 ± 7 years) with suspected ICA stenosis were imaged prospectively with a combined MRI protocol including T1, T2, diffusion-weighted imaging, fluid-attenuated inversion recovery, and contrast-enhanced MR angiography (CEMRA) imaging of the brain and a short (11 min) CMR protocol with left ventricular function and late gadolinium enhancement imaging. Blinded to any clinical information, two readers evaluated the cardiac and neuroradiologic examinations. Results: Of 154 imaged ICA, 85 presented with stenosis and 17 were occluded. In 7 patients, the suspected ICA stenosis could not be confirmed by CEMRA. In the remaining 70 patients with ICA stenosis, 34.3% had cerebral lesions (15.7% with a homodynamic pattern,18.6% with territorial infarction). CMR detected MI in 29 (41%) patients, whereas ECG and medical history enabled diagnosis in only 7 (10%) patients. Conclusions: ICA stenosis patients have a higher incidence of myocardial scars proving silent MI when detected by contrast-enhanced CMR than clinically expected. Whether the presence and extent of silent MIs detected by CMR affect peri-interventional risk and prognosis of ICA stenosis patients remains to be evaluated in a large patient cohort with long-term follow-up.