Miracle-dz/UniFAR-FTUs huggingface dataset:
Preference of Conjugated Bile Acids over Unconjugated Bile Acids as Substrates for OATP1B1 and OATP1B3

Bile acids, the metabolites of cholesterol, are signaling molecules that play critical role in many physiological functions. They undergo enterohepatic circulation through various transporters expressed in intestine and liver. Human organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3 contribute to hepatic uptake of bile acids such as taurocholic acid. However, the transport properties of individual bile acids are not well understood. Therefore, we selected HEK293 cells overexpressing OATP1B1 and OATP1B3 to evaluate the transport of five major human bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid) together withtheir glycine and taurine conjugates via OATP1B1 and OATP1B3. The bile acids were quantified by liquid chromatography-tandem mass spectrometry. The present study revealed that cholic acid, chenodeoxyxcholic acid, and deoxycholic acid were transported by OATP1B1 and OATP1B3, while ursodeoxycholic acid and lithocholic acid were not significantly transported by OATPs. However, all the conjugated bile acids were taken up rapidly by OATP1B1 and OATP1B3. Kinetic analyses revealed the involvement of saturable OATP1B1- and OATP1B3-mediated transport of bile acids. The apparent Km values for OATP1B1 and OATP1B3 of the conjugated bile acids were similar (0.74–14.7 μM for OATP1B1 and 0.47–15.3 μM for OATP1B3). They exhibited higher affinity than cholic acid (47.1 μM for OATP1B1 and 42.2 μM for OATP1B3). Our results suggest that conjugated bile acids (glycine and taurine) are preferred to unconjugated bile acids as substrates for OATP1B1 and OATP1B3.
Response of Cells to Ionizing Radiation

Ionizing radiation is encountered in our natural environment and is also generated and used by mankind, e.g., for medical uses. A better understanding of the biological effects of ionizing radiation will lead to better use of and better protection from radiation. In this chapter, the response of cells to radiation will be described and discussed. Some basic concepts of ionizing radiation will be briefly given in the beginning. The significant consequences of various types of radiation-induced DNA damages show that DNA is the principle target for biological effects of radiation. The misrepaired or unrepaired DNA damages, in particular DNA double strand breaks, will induce chromosomal aberrations and gene mutations. On the other hand, radiation-induced DNA double strand breaks play an important role in the induction of apoptosis and cell cycle arrest. Radiationinduced bystander response, adaptive response and genomic instability are currently “hot-pots” in the radiobiological research. These three phenomena indicate the complexity of cellular responses to radiation, and will be introduced and discussed in this chapter. BASICS OF RADIOBIOLOGY
Should there be separate parent and teacher-based categories of ODD? Evidence from a general population.

OBJECTIVE To examine the occurrence of oppositional defiant disorder (ODD) symptoms in a general population of boys and girls, as reported by parents and teachers, and to investigate differences in prevalence estimates, depending on how parents' and teachers' ratings were combined. METHOD Data were collected from 7007 children (aged 7-9) who participated in The Bergen Child Study (BCS), an ongoing population-based study of children's development and mental health. ODD symptoms were measured by the SNAP-IV (Swanson, Nolan, & Pelham-IV) Oppositional Defiant Disorder sub-scale (SNAP-IV ODD) that was distributed to parents and teachers. Co-occurring symptoms of mental health problems were measured by the Strengths and Difficulties Questionnaire (SDQ). RESULTS AND CONCLUSION Prevalence-estimates of ODD varied considerably depending on how ratings from parents and teachers were combined. Specific ODD symptoms occurred at very different rates depending on the rater and on the gender of the child being rated. Parents and teachers co-identified very few children with ODD. ODD identified by only one informant was associated with high levels of comorbid mental health problems and impairment according to both informants. The results support an informant-specific conceptualization of childhood ODD.
Type 2 diabetes mellitus and its risk factors among the rural Fulanis of Northern Nigeria.

BACKGROUND Information about diabetes mellitus (DM) from the rural populations in Nigeria, particularly among the rural Fulanis is limited. MATERIALS AND METHODS This was a cross-sectional study conducted in two rural districts of Sokoto State in Northern Nigeria. Using a modification of the WHO STEP wise approach to surveillance (STEPS) instrument, information on sociodemographic and anthropometric data was obtained. Either a casual or fasting plasma glucose (FPG) level was obtained in all subjects while oral glucose tolerance test was performed in a randomly selected group of 50 of the study participants. RESULTS Three hundred and ninety-three subjects participated in the study. The prevalence rates of DM, impaired fasting glycemia (IFG), and impaired glucose tolerance (IGT) were 0.8, 6.9, and 8%, respectively. The mean (SD) FPG was higher in males (5.1 ± 0.6 mmol/L) than in females (4.9 ± 0.6 mmol/l), but not statistically significantly (P = 0.20). The major risk factors for DM among the rural Fulani were obesity and increasing age. CONCLUSION The prevalence rates of DM and its principal risk factor obesity are low among the rural Nigerian Fulani. However, the prevalence of prediabetes is relatively high, a factor that may predispose to the future development of DM.
Comparing focal and global responses on multifocal electroretinogram with retinal nerve fibre layer thickness by spectral domain optical coherence tomography in glaucoma

Purpose To evaluate first and second order responses on multifocal electroretinogram (mfERG) and with retinal nerve fibre layer thickness (RNFL) on Cirrus spectral domain optical coherence tomography (SD-OCT) in glaucoma. Methods Patients (old and new) diagnosed with primary open angle glaucoma, primary angle closure glaucoma or normal tension glaucoma attending glaucoma services from November 2012 to January 2013 were screened. Ninety-seven eyes fulfilling inclusion criteria were evaluated by Humphrey visual field, Cirrus SD-OCT imaging and mfERG (Veris Science 5.1.10X; EDI, Redwood City, California, USA) for this observational cross-sectional study. The global and averaged quadrant-wise peak-to-trough amplitudes and peak implicit times of the first trough (N1), the first peak (P1) and the second trough (N2) of the mfERG were compared with average RNFL-full circle (FC) or quadrant RNFL thickness in early (mean deviation (MD) >−6 dB), moderate (MD −6 to −12 dB) and advanced glaucoma (MD <−12 dB). Results The RNFL-FC correlated with P1N2 amplitude on univariate analysis (r=0.7, p=0.004) and N2 amplitude (r=−0.4, p<0.001). Comparing relationships in different stages of glaucoma, P1N2 amplitude correlated significantly with RNFL-FC and superotemporal quadrant, RNFL-superior temporal (ST), in early and moderate glaucoma only. In contrast, the implicit time of P1N2 correlated significantly with RNFL-FC and RNFL-ST only in severe glaucoma while in earlier stages, this relationship did not hold true. On multivariate analysis, P1N2 amplitude correlated with age (β=−0.2, p<0.001), RNFL-FC (β=0.05, p=0.05), RNFL-ST (β=0.06, p=0.01) and cup-disc ratio (β=−3.2, p=0.006). Conclusions Of all responses on mfERG, P1N2 amplitude correlates well with RNFL-FC and RNFL-ST on SD-OCT and can be used for monitoring early and moderate glaucoma. Diffuse structural changes may best be reflected by changes in P1N2 implicit time owing to ceiling effect of the amplitude in all regions in severe glaucoma.
Annual reversal of the Equatorial intermediate current in the Pacific : observations and model diagnostics

Abstract A large reversal of zonal transport below the thermocline was observed over a period of 6 months in the western Pacific Ocean between 2°S and the equator [from 26.2 Sv (1 Sv ≡ 106 m3 s−1) eastward in October 1999 to 28.6 Sv westward in April 2000]. To document this reversal and assess its origin, an unprecedented collection of ADCP observations of zonal currents (2004–06), together with a realistic OGCM simulation of the tropical Pacific, was analyzed. The results of this study indicate that this reversal is the signature of intense annual variability in the subsurface zonal circulation at the equator, at the level of the Equatorial Intermediate Current (EIC) and the Lower Equatorial Intermediate Current (L-EIC). In this study, the EIC and the L-EIC are both shown to reverse seasonally to eastward currents in boreal spring (and winter for the L-EIC) over a large depth range extending from 300 m to at least 1200 m. The peak-to-peak amplitude of the annual cycle of subthermocline zonal currents at .
WORRY, WORRY PROCESSES AND DIMENSIONS OF DELUSIONS: AN EXPLORATORY INVESTIGATION OF A ROLE FOR ANXIETY PROCESSES IN THE MAINTENANCE OF DELUSIONAL DISTRESS

The efficacy of CBT for psychosis will be enhanced by a greater understanding of the mechanisms underlying symptoms. Therefore, an investigation is reported that examined a role for a neglected factor, anxiety, in the maintenance of delusional beliefs. It was hypothesized that processes responsible for chronic worry, as detailed by Wells’ (1994a) meta-cognitive model, contribute to delusional distress. Questionnaire measures of anxiety, chronic worry and of meta-worry and related processes were administered to individuals with persecutory delusions (N=15) and individuals with generalized anxiety disorder (GAD) (N=14). Evidence was found for the presence of dysfunctional meta-cognitive processes in the clinically anxious group, which adds to the growing support for the model of GAD. Moreover, it was found that many of the individuals with persecutory delusions had high levels of general worry, and the factors implicated in the meta-cognitive model of anxiety were also present in this group. The results indicated that delusional distress is not simply related to content but is associated with whether the individual experiences meta-worry concerning the control of delusion-relevant worries, that is, whether he or she worries about not being able to control thoughts about the belief. This is the first theoretical development of the important dimension of delusional distress.
Transcatheter aortic valve implantation: The transfemoral versus the transapical approach.

Transcatheter aortic valve implantation (TAVI) is emerging as a viable alternative to conventional surgical aortic valve replacement in high risk and surgically inoperable patients who have severe symptomatic aortic stenosis. A comprehensive review of this new technology has recently been published as an “expert consensus document” (1). This document, however, did not address the relative merits of the transapical versus the transfemoral approach to TAVI. The chosen approach is largely dictated by the quality and adequacy of the aortoiliac and femoral arteries and whether the vessels can support large catheter access. The relative merits of the transfemoral and transapical approaches continue to evolve. In this article, we aim to review the published results of TAVI in high risk or inoperable patients with severe aortic stenosis with an emphasis on comparing the outcomes between the transapical versus transfemoral techniques. It is estimated that TAVI has been employed in more than forty thousand patients worldwide and there is published data on over five thousand patients (1). Although most of this information has been obtained from registries and other observational studies, there is one prospective, multicenter, randomized study of the clinical outcomes after insertion of the Edwards SAPIEN transcatheter valve (2-5). This trial, called Placement of Aortic Transcatheter Valves (PARTNER), included two populations of patients with severe, symptomatic aortic stenosis: Cohort A, deemed at high risk for conventional surgery and Cohort B, considered surgically inoperable.
Modélisation des crues de bassins karstiques par réseaux de neurones. Cas du bassin du Lez (Hérault)

Les karsts sont l'une des formations aquiferes les plus presentes au monde. Exploites, ils fournissent de l'eau potable pour pres de 25% de la population mondiale. Cependant la forte heterogeneite de leur structure implique un comportement non-lineaire et les rendent particulierement difficiles a etudier, a simuler et a prevoir. Les reseaux de neurones formels sont des modeles d'apprentissage statistiques qui ont ete largement utilises en hydrologie de surface depuis les annees 1990, grâce a leurs proprietes de parcimonie et d'approximation universelle.Dans cette these, il est propose d'utiliser les reseaux de neurones pour etudier le comportement des aquiferes karstiques. L'aquifere du Lez est choisi pour appliquer le modele par reseaux de neurones. Cet aquifere, situe pres de l'agglomeration de Montpellier (400 000 habitant), est exploite pour fournir de l'eau potable a une grande partie de l'agglomeration.Dans un premier temps, un reseau de neurones « classique », de type boite noire, est applique a la simulation et a la prevision des debits de la source du Lez. Une methode de selection des entrees de pluie est proposee, couplant analyse par correlations croisees et methode de validation croisee. Les resultats montrent l'adequation du modele neuronal pour la simulation et la prevision du debit de la source d'un aquifere karstique complexe. Le test du modele est effectue sur les deux cycles hydrologiques comportant les crues les plus intenses de la base de donnees. Les hydrogrammes montrent que le modele neuronal a ete capable d'extrapoler puisque les debits prevus pour les crues majeures en test sont corrects et superieurs aux debits presents dans la base d'apprentissage du modele. La prevision est acceptable jusqu'a un horizon de prevision de un jour. Dans un second temps, une methode d'extraction des donnees contenues dans la boite noire est proposee. Afin de contraindre le modele neuronal a donner des valeurs physiquement interpretables, des connaissances a priori sur la geologie de l'aquifere sont incluses dans l'architecture du reseau de neurones. La methode KnoX (Knowledge eXtraction) proposee dans cette etude permet d'extraire du modele les contributions des differentes zones geologiques a la source du lez ainsi que les temps de reponse correspondants. L'application de la methode KnoX a un hydrosysteme fictif dont on controle en particulier les temps de reponse et les contributions des differents sous-hydrosystemes fictifs a permis de valider cette methode. Les resultats obtenus sur le bassin du Lez sont tres satisfaisants et en adequation avec les connaissances actuelles que l'on a sur ce systeme. De plus la methode a permis d'affiner ces connaissances, notamment l'infiltration retardee par des aquiferes perches et concernant la limite du bassin d'alimentation de la source du Lez. Enfin, la methode KnoX est generique et applicable a tout hydrosysteme pour lequel on dispose de mesures de pluie et de debit.
Conditioned hyperkinesia induced by cocaine in mice is dose-dependent but not correlated with the unconditioned response or the contextually-sensitized response

The aims of the study were to test whether drug dose is positively related to the magnitude of the conditioned response following sensitization to the behavioural effects of cocaine and to investigate the relationship between the conditioned response and cocaine-induced sensitization. Male mice (C57BL/6J) were first injected over seven successive days with either saline or cocaine at 2.5, 5, 10 or 20 mg/kg s.c. , in the testing room. On the test day, 24 h after the last injection, mice from all conditions were challenged with saline in the testing room to test for conditioned cocaine effects. Mice were video-recorded and various behaviours were later scored using a time-sampling technique. Cocaine-elicited orofacial stereotypy was significantly sensitized at the two highest doses and dose-dependently conditioned at the three highest doses. Cocaine-increased locomotion was sensitized at the three highest doses and significantly conditioned at 10 and 20 mg/kg. Cocaine-increased sniffing did not change over pretreatment at any dose, and was conditioned only at 10 mg/kg. Cocaine-decreased immobility also did not change over pretreatment at any dose, but was conditioned at 10 and 20 mg/kg. Concomitantly, rearing was reduced by cocaine at 10 and 20 mg/kg, without sensitization being induced, and it was reduced under saline challenge after 5 mg/kg cocaine, while cocaine-decreased grooming was sensitized at the three highest doses and conditioned at 10 and 20 mg/kg cocaine. There was a positive relation between the size of the conditioned response for orofacial stereotypy and the magnitude of the unconditioned stimulus (the doses), a result conforming to the Pavlovian account of the placebo effect. This could also be concluded from considering the behaviour patterns as components of a unique placebo effect (hyperkinetic syndrome), since orofacial stereotypy, very apparent at 20 mg/kg cocaine, interfered at that dose with the full-blown expression of locomotion and sniffing, both yielding (approximately) inverted U-shaped dose–effect curves. However, no correlation was found between the magnitude of the conditioned response and the amplitude of sensitization (the difference between the initial unconditioned non-sensitized response and the last unconditioned sensitized response), a finding which indicates that conditioned responding does not participate in the generation of the sensitized effects, contrary to the ‘excitatory conditioning model of contextual sensitization’.
Oxidative Stress and Neurodegeneration

Abstract: Oxidative stress is a well‐studied early response in chronic neurodegenerative diseases, including Alzheimer's disease, where neuronal loss can exceed 90% in the vulnerable neuronal population. Oxidative stress affects all classes of macromolecules (sugar, lipids, proteins, and DNA), leading inevitably to neuronal dysfunction. We observed that Nε‐(carboxymethyl)lysine (CML), the predominant advanced glycation end product that accumulates in vivo, along with its glycation‐specific precursor hexitol‐lysine, are increased in neurons from cases of Alzheimer's disease, especially those containing intracellular neurofibrillary pathology. The increase in hexitol‐lysine and CML can result from either lipid peroxidation or advanced glycation, whereas hexitol‐lysine is solely a product of glycation, suggesting that two distinct oxidative processes act in concert in the neuropathology of the disease. Furthermore, using olfactory neurons as an experimental model, we observed an increase in glycation products in neurons derived from Alzheimer's disease patients. Our findings support the idea that aldehyde‐mediated modifications, in concert with oxyradical‐mediated modifications, are critical early pathogenic factors in Alzheimer's disease.
Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD.

BACKGROUND Cardiovascular disease is a major cause of death in patients with chronic obstructive pulmonary disease (COPD) and predicts hospitalisation for acute exacerbation, in-hospital death and post-discharge mortality. Although beta blockers improve cardiovascular outcomes, patients with COPD often do not receive them owing to concerns about possible adverse pulmonary effects. There are no published data about beta blocker use among inpatients with COPD exacerbations. A study was undertaken to identify factors associated with beta blocker use in this setting and to determine whether their use is associated with decreased in-hospital mortality. METHODS Administrative data from the University of Alabama Hospital were reviewed and patients admitted between October 1999 and September 2006 with an acute exacerbation of COPD as a primary diagnosis or as a secondary diagnosis with a primary diagnosis of acute respiratory failure were identified. Demographic data, co-morbidities and medication use were recorded and subjects receiving beta blockers were compared with those who did not. Multivariate regression analysis was performed to determine predictors of in-hospital death after controlling for known covariates and the propensity to receive beta blockers. RESULTS 825 patients met the inclusion criteria. In-hospital mortality was 5.2%. Those receiving beta blockers (n = 142) were older and more frequently had cardiovascular disease than those who did not. In multivariate analysis adjusting for potential confounders including the propensity score, beta blocker use was associated with reduced mortality (OR = 0.39; 95% CI 0.14 to 0.99). Age, length of stay, number of prior exacerbations, the presence of respiratory failure, congestive heart failure, cerebrovascular disease or liver disease also predicted in-hospital mortality (p<0.05). CONCLUSIONS The use of beta blockers by inpatients with exacerbations of COPD is well tolerated and may be associated with reduced mortality. The potential protective effect of beta blockers in this population warrants further study.
Law and Intergenerational Relationships

Background: In any aging society, the sociolegal construction of intergenerational relationships is of great importance. This study conducts an international comparison of a specific judicial issue: whether active labor unions have the legal right to strike for the purpose of improving the benefits given to nonactive workers (specifically, pensioners). Method: A comparative case law methodology was used. The texts of three different Supreme Court cases—in the United States, Canada, and Israel—were analyzed and compared. Findings: Despite the different legal outcomes, all three court rulings reflect a disregard of known and relevant social gerontology theories of intergenerational relationships. Conclusion: Social gerontological theories can play an important role in both understanding and shaping judicial policies and assisting the courts in choosing their sociojudicial narratives.
Evaluation of Cucurbitacin-Based Gustatory Stimulant to Facilitate Cucumber Beetle (Coleoptera: Chrysomelidae) Management with Foliar Insecticides in Melons

ABSTRACT The bitter plant-derived compounds cucurbitacins are known to stimulate feeding of adult cucumber beetles (Coleoptera: Chrysomelidae). A cucurbitacin-based gustatory stimulant applied as a flowable bait combined with either spinosad or carbaryl was compared with foliar sprays of spinosad and carbaryl for controlling two cucumber beetle species (Diabrotica undecimpunctata undecimpunctata Mannerheim and Acalymma trivittatum Mannerheim) in honeydew melons (Cucumis melo L.). Field studies were conducted on the University of California—Davis plant pathology farm in 2008 and 2009. Beetle densities after applications and fruit damage from beetle feeding were compared among treatments. In addition, beetle survival was compared within field cages placed over the treated foliage infested with beetles. Using all three measures of efficacy, we determined that the addition of cucurbitacin bait had no effect on the level of cucumber beetle control with carbaryl in either 2008 or 2009. In both years, spinosad did not significantly reduce cucumber beetle densities in either field cages or field plots and did not reduce fruit damage relative to the untreated control. The addition of the bait to spinosad did not improve its efficacy. A laboratory bioassay of the spinosad formulation used in the field showed it had significant lethal effects on adults of both cucumber beetle species. Results indicated that the bait formulation used did not improve cucumber beetle control but may benefit from the addition of floral attractants or using a different type of cucurbitacin.