Miracle-dz/UniFAR-FTUs huggingface dataset:
Colesevelam hydrochloride: a non-absorbed, polymeric cholesterol-lowering agent

Colesevelam hydrochloride (formerly known as Cholestagel® and re-named WelChol™, GelTex Pharmaceuticals, Inc. and Sankyo Parke-Davis) is a new, polymeric, high potency, water-absorbing hydrogel. It has been shown to be a safe and effective cholesterol-lowering agent with a non-systemic mechanism of action, good tolerability and minimal side effects. To date, the lipid-lowering activity of colesevelam has been evaluated in approximately 1400 subjects. Colesevelam reduces low density lipoprotein (LDL)-cholesterol levels, in a dose-dependent manner, by as much as 20% (median) in patients with hypercholesterolaemia. Dosing regimen evaluations indicate that colesevelam is effective at both once per day and twice daily dosing and that concurrent administration of colesevelam with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), specifically lovastatin, does not alter the absorption of the statin. Combination therapy with HMG-CoA reductase inhibitors, including lovastatin, simvastatin and atorvastatin, produces an additional reduction (8 - 16%) in LDL-cholesterol levels above that seen with the statin alone. The overall incidence of adverse effects with colesevelam alone and in combination with statins is comparable with that seen with placebo. Colesevelam lacks the constipating effect seen with typical bile acid sequestrants, a trait that would be expected to improve compliance with lipid-lowering therapy. Colesevelam, recently approved by the US FDA, represents a valuable non-absorbed alternative in the armamentarium against hypercholesterolaemia, both for monotherapy and combination therapy, as an adjunct to diet and exercise.
Application of Machine Learning for Optimization of 3-D Integrated Circuits and Systems

The 3-D integration helps improve performance and density of electronic systems. However, since electrical and thermal performance for 3-D integration is related to each other, their codesign is required. Machine learning, a promising approach in artificial intelligence, has recently shown promise for addressing engineering optimization problems. In this paper, we apply machine learning for the optimization of 3-D integrated systems where the electrical performance and thermal performance need to be analyzed together for maximizing performance. In such systems, modeling can be challenging due to the multiscale geometries involved, which increases computation time per iteration. In this paper, we show that machine learning can be applied to such systems where multiple parameters can be optimized to achieve the desired performance using the minimum number of iterations. These results have been compared with other promising optimization methods in this paper. The results show that on an average, 4.4%, 31.1%, and 6.9% improvement in temperature gradient, CPU time, and skew are possible using machine learning, as compared with other methods.
Accuracy of Cone Beam Computed Tomography Grayscale Density in Determining Bone Architecture in the Posterior Mandible: An In Vivo Study with Microcomputed Tomography Validation.

PURPOSE The aim of this study was to analyze the reliability of cone beam computed tomography (CBCT) in assessing the grayscale density (GSD) of bone by comparing it with microcomputed tomography (μ-CT) data. MATERIALS AND METHODS A total of 50 subjects with lost mandibular molars were included in the study. To assess the bone GSD, a previously fabricated template made of acrylic resin with a 2-mm-diameter metal rod was positioned, and CBCT was performed. The bone biopsies for μ-CT analysis were then obtained during implant surgery. The relationship between GSD assessed by CBCT and data from μ-CT analysis was studied using Spearman's rank correlation. RESULTS A total of 38 biopsies were available for μ-CT analysis. Positive correlations were identified between GSD and bone volumetric fraction (BV/TV) (r = 0.835, P < .001), bone volume (BV) (r = 0.353, P = .030), trabecular spacing (Tb.Sp) (r = -0.535, P = .001), and mean total volume (TV) (r = 0.470, P = .003). There was a clear positive linear correlation between normal values of GSD (< 700) and BV (r = 0.545). CONCLUSION This study demonstrated the correlation between GSD assessed by CBCT and bone density assessed by μ-CT in the posterior mandible. For areas of typical bone density, there seems to be a positive linear correlation between GSD assessed by CBCT and bone density assessed by μ-CT.
The minimal inhibitory synaptic currents evoked in neonatal rat motoneurones.

1. Tight‐seal whole‐cell recordings were made from lumbar motoneurones visually identified in thin slices of neonatal rat spinal cord. The inhibitory postsynaptic currents (IPSCs) were evoked by extracellular stimulation of a neighbouring internuncial neurone in the presence of glutamate receptor antagonists. 2. Glycinergic IPSCs were recorded in the presence of bicuculline. The IPSCs appeared in an all‐or‐none manner as the graded stimulus intensity exceeded a certain threshold. Their latencies showed a unimodal distribution with a mean of 0.81 ms at 37 degrees C. Thus, the observed IPSCs are suggested to be monosynaptically evoked unitary IPSCs. The mean conductance of unitary IPSCs was 2.9 +/‐ 1.2 nS (+/‐ S.D.). 3. When the external Ca2+ concentration ([Ca2+]o) was reduced, the number of failures in response to stimulation increased, thereby reducing the mean amplitude of IPSCs. The mean amplitude of IPSCs was linearly related to the [Ca2+]o (0.35‐1.4 mM) with a mean slope of 3.1 +/‐ 0.67 on double logarithmic co‐ordinates. 4. The amplitude of individual IPSCs decreased with decrease in [Ca2+]o. However, below 0.7 mM [Ca2+]o, the mean amplitude of IPSCs (excluding failures) reached a steady minimum level. The mean conductance of these IPSCs measured in 0.5 mM [Ca2+]o was 657 +/‐ 281 pS. 5. The minimal IPSCs had a coefficient of variation of 0.50 +/‐ 0.13. No clear correlation was observed between the rise time and the amplitude of minimal IPSCs evoked in individual motoneurones, indicating that the amplitude variability is not due to the different synaptic locations. 6. Spontaneous miniature IPSCs were recorded from motoneurones in the presence of tetrodotoxin. The miniature IPSCs had a mean conductance of 739 +/‐ 278 pS, being comparable to the minimal evoked IPSCs. 7. Under various internal and external Cl‐ concentration, the reversal potential of the IPSCs (EIPSC) approximately coincided with the Cl‐ equilibrium potential. A 730‐fold change in the potassium concentration gradient across the membrane did not affect the EIPSC. The permeability ratio of K+ to Cl‐ (Pk/PCl) was less than 0.05. 8. It is concluded that the IPSCs are carried almost exclusively by Cl‐ and that the minimal evoked IPSCs represent the quantal response of the transmitter.
The feasibility and acceptability of questionnaires and accelerometry for measuring physical activity and sedentary behaviour in adults with mental illness

Abstract Background: Adults with mental illness may have difficulties with data collection methods such as questionnaires and accelerometry. Aims: To assess the utility of questionnaires and accelerometry for assessing physical activity (PA) and sedentary behaviour (SB) in non-institutionalised adults with mental illness. Methods: Participants were recruited from outpatient clinics and community organisations. Participants completed PA and SB questionnaires, wore accelerometers for 7 d, and rated the ease/difficulty of completing study components. Recruitment numbers, adherence, and ease/difficulty ratings were examined. Ease/difficulty ratings were compared between study components, and between participants by distress level. Results: One hundred forty-two participants completed the questionnaires; they found it easier to report PA than reclining time (p = 0.017), and reclining time than sitting time (p < 0.001). Participants with high distress found it more difficult to report sitting time and PA than participants with low distress (p < 0.017). Ninety-nine participants (70%) completed the accelerometry; the majority (88%) met the minimum wear-time criteria. They found it easier to wear the monitor during the day than while sleeping (p < 0.001), and easier to complete accelerometry than questionnaires (p < 0.001). Conclusions: Accelerometry was more feasible for assessing SB than questionnaires. Questionnaires were feasible for assessing PA, but less acceptable for people experiencing high distress.
Isoflurane Attenuates Blood–Brain Barrier Disruption in Ipsilateral Hemisphere After Subarachnoid Hemorrhage in Mice

Background and Purpose— We examined effects of isoflurane, volatile anesthetics, on blood–brain barrier disruption in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice. Methods— Animals were assigned to sham-operated, SAH+vehicle–air, SAH+1%, or 2% isoflurane groups. Neurobehavioral function, brain water content, Evans blue dye extravasation, and Western blotting for sphingosine kinases, occludin, claudin-5, junctional adhesion molecule, and vascular endothelial cadherin were evaluated at 24 hours post-SAH. Effects of sphingosine kinase (N,N-dimethylsphingosine) or sphingosine-1-phosphate receptor-1/3 (S1P1/3) inhibitors (VPC23019) on isoflurane's action were also examined. Results— SAH aggravated neurological scores, brain edema, and blood–brain barrier permeability, which were prevented by 2% but not 1% isoflurane posttreatment. Two percent isoflurane increased sphingosine kinase-1 expression and prevented a post-SAH decrease in expressions of the blood–brain barrier-related proteins. Both N,N-dimethylsphingosine and VPC23019 abolished the beneficial effects of isoflurane. Conclusions— Two percent isoflurane can suppress post-SAH blood–brain barrier disruption, which may be mediated by sphingosine kinase 1 expression and sphingosine-1-phosphate receptor-1/3 activation.
Paramagnetic effect of supplemental oxygen on CSF hyperintensity on fluid-attenuated inversion recovery MR images.

BACKGROUND AND PURPOSE Oxygen has a known paramagnetic effect and increases CSF signal intensity on fluid-attenuated inversion recovery (FLAIR) MR images. The purposes of this study were to investigate the effect of supplemental oxygen on CSF signal intensity and the arterial partial pressure of oxygen and to determine the possible synergistic effect of oxygen and albumin on T1 shortening effect in vitro. METHODS Six healthy volunteers underwent FLAIR MR imaging of the brain before and during inhalation of 10 to 15 L/min of 100% oxygen for < or = 30 min. The signal intensity was measured in the subarachnoid spaces and various tissues and correlated with estimated arterial partial pressure of oxygen and arterial carbon dioxide pressure. In vitro measurements were also obtained by using two sets of saline-filled tubes with various concentrations of albumin, one of which was exposed to increased oxygen levels. In vitro T1 relaxation times were calculated to assess the possible synergistic effect of oxygen and albumin. RESULTS FLAIR images of healthy volunteers showed increased CSF signal intensity within the basal cisterns and sulci along the cerebral convexities. The CSF hyperintensity was observed immediately after the initiation of supplemental oxygen and remained stable during the oxygen administration. There was approximately a 4- to 5.3-fold increase in signal intensity with supplemental oxygen. The phantom experiments showed a T1 shortening effect of oxygen. Albumin significantly altered T1 relaxation time only at high concentrations of albumin. CONCLUSION Inhalation of increased levels of oxygen led to readily detectable CSF hyperintensity on FLAIR images of healthy volunteers. No significant synergetic effect of albumin and oxygen was noted.
Influence of temperament score and handling facility on stress, reproductive hormone concentrations, and fixed time AI pregnancy rates in beef heifers.

The objectives were (i) to evaluate the effect of temperament, determined by modified 2-point chute exit and gait score, on artificial insemination (AI) pregnancy rates in beef heifers following fixed time AI and (ii) to determine the effect of temperament on cortisol, substance-P, prolactin and progesterone at initiation of synchronization and at the time of AI. Angus beef heifers (n = 967) at eight locations were included in this study. At the initiation of synchronization (Day 0 = initiation of synchronization), all heifers received a body condition score (BCS), and temperament score (0 = calm; slow exit and walk or 1 = excitable; fast exit or jump or trot or run). Blood samples were collected from a sub-population of heifers (n = 86) at both synchronization initiation and the time of AI to determine the differences in serum progesterone, cortisol, prolactin and substance-P concentrations between temperament groups. Heifers were synchronized with 5-day CO-Synch+ controlled internal drug release (CIDR) protocol and were inseminated at 56 h after CIDR removal. Heifers were examined for pregnancy by ultrasound 70 days after AI to determine AI pregnancy. Controlling for synchronization treatment (p = 0.03), facility design (p = 0.05), and cattle handling facility design by temperament score interaction (p = 0.02), the AI pregnancy differed between heifers with excitable and calm temperament (51.9% vs 60.3%; p = 0.01). The alley-way with acute bends and turns, and long straight alley-way had lower AI pregnancy rate than did the semicircular alley-way (53.5%, 56.3% and 67.0% respectively; p = 0.05). The serum hormone concentrations differed significantly between different types of cattle handling facility (p < 0.05). The cattle handling facility design by temperament group interactions significantly influenced progesterone (p = 0.01), cortisol (p = 0.01), prolactin (p = 0.02) and substance-P (p = 0.04) both at the initiation of synchronization and at the time of AI. Inter- and intra-rater agreement for temperament scoring were moderate and good (Kappa = 0.596 ± 0.07 and 0.797 ± 0.11) respectively. The predictive value for calm and pregnant to AI was 0.87, and excited and non-pregnant to AI was 0.76. In conclusion, the modified 2-point temperament scoring method can be used to identify heifers with excitable temperament. Heifers with excitable temperament had lower AI pregnancy. Further, cattle handling facility design influenced the temperament and AI pregnancy.
Surface-based facial scan registration in neuronavigation procedures: a clinical study.

OBJECT Surface-based registration (SBR) with facial surface scans has been proposed as an alternative for the commonly used fiducial-based registration in image-guided neurosurgery. Recent studies comparing the accuracy of SBR and fiducial-based registration have been based on a few targets located on the head surface rather than inside the brain and have yielded contradictory conclusions. Moreover, no visual feedback is provided with either method to inform the surgeon about the estimated target registration error (TRE) at various target locations. The goals in the present study were: 1) to quantify the SBR error in a clinical setup, 2) to estimate the targeting error for many target locations inside the brain, and 3) to create a map of the estimated TRE values superimposed on a patient's head image. METHODS The authors randomly selected 12 patients (8 supine and 4 in a lateral position) who underwent neurosurgery with a commercial navigation system. Intraoperatively, scans of the patients' faces were acquired using a fast 3D surface scanner and aligned with their preoperative MR or CT head image. In the laboratory, the SBR accuracy was measured on the facial zone and estimated at various intracranial target locations. Contours related to different TREs were superimposed on the patient's head image and informed the surgeon about the expected anisotropic error distribution. RESULTS The mean surface registration error in the face zone was 0.9 +/- 0.35 mm. The mean estimated TREs for targets located 60, 105, and 150 mm from the facial surface were 2.0, 3.2, and 4.5 mm, respectively. There was no difference in the estimated TRE between the lateral and supine positions. The entire registration procedure, including positioning of the scanner, surface data acquisition, and the registration computation usually required < 5 minutes. CONCLUSIONS Surface-based registration accuracy is better in the face and frontal zones, and error increases as the target location lies further from the face. Visualization of the anisotropic TRE distribution may help the surgeon to make clinical decisions. The observed and estimated accuracies and the intraoperative registration time show that SBR using the fast surface scanner is practical and feasible in a clinical setup.
Multiphasic Scaffolds for Periodontal Tissue Engineering

For a successful clinical outcome, periodontal regeneration requires the coordinated response of multiple soft and hard tissues (periodontal ligament, gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered constructs for regeneration of the periodontium must be of a complex 3-dimensional shape and adequate size and demonstrate biomechanical stability over time. A critical requirement is the ability to promote the formation of functional periodontal attachment between regenerated alveolar bone, and newly formed cementum on the root surface. This review outlines the current advances in multiphasic scaffold fabrication and how these scaffolds can be combined with cell- and growth factor–based approaches to form tissue-engineered constructs capable of recapitulating the complex temporal and spatial wound-healing events that will lead to predictable periodontal regeneration. This can be achieved through a variety of approaches, with promising strategies characterized by the use of scaffolds that can deliver and stabilize cells capable of cementogenesis onto the root surface, provide biomechanical cues that encourage perpendicular alignment of periodontal fibers to the root surface, and provide osteogenic cues and appropriate space to facilitate bone regeneration. Progress on the development of multiphasic constructs for periodontal tissue engineering is in the early stages of development, and these constructs need to be tested in large animal models and, ultimately, human clinical trials.
De l'Imbo au Mirwa. Dynamique de l'occupation du sol, croissance urbaine et risques naturels dans la région de Bujumbura (Burundi)

Depuis la premiere moitie du XXeme siecle, le Burundi a connu de profondes mutations sociales, economiques, politiques et environnementales caracterisees, entre autres, par une forte croissance demographique et urbaine et par une pression croissante sur le milieu naturel et agricole. Apres une presentation des grands traits de la region d'etude, de l'histoire du peuplement et de l'utilisation du sol avant les annees 1950, ce travail analyse et caracterise les transformations recentes du milieu rural (de la naissance d'un paysage agraire entre les annees 1930-50 jusqu'a la situation actuelle) et les etapes de la croissance urbaine au travers de l'exemple de l'agglomeration de Bujumbura de 1925 a 2002. Est ensuite abordee la question heritee de ces evolutions de la recrudescence des risques naturels (inondation et mouvement de masse), de leurs occurrences davantage repetees et de leurs consequences de plus en plus lourdes. Une reflexion sur les fondements et les conditions de mise en œuvre et d'emergence d'une politique de prevention des risques naturels conclut ce travail.
Identification and Functional Separation of Retinoic Acid Receptor Neutral Antagonists and Inverse Agonists*

Inverse agonists are ligands that are capable of repressing basal receptor activity in the absence of an agonist. We have designed a series of C-1-substituted acetylenic retinoids that exhibit potent antagonism of retinoic acid receptor (RAR)-mediated transactivation. Comparison of these related retinoid antagonists for their ability to repress basal RAR transcriptional activity demonstrates that the identity of the C-1 substituent differentiates these ligands into two groups: RAR inverse agonists and neutral antagonists. We show that treatment of cultured human keratinocytes with a RAR inverse agonist, but not a RAR neutral antagonist, leads to the repression of the serum-induced differentiation marker MRP-8. While RAR-selective agonists also repress expression of MRP-8, cotreatment with a RAR inverse agonist and a RAR agonist results in a mutual repression of their individual inhibitory activities, indicating the distinct modes of action of these two disparate retinoids in modulating MRP-8 expression. Our data indicate that RARs, like β2-adrenoreceptors, are sensitive to inverse agonists and that this new class of retinoids will provide insight into the molecular mechanisms of RAR function in skin and other responsive tissues.
Lasting Effects of a 2-Year Diabetes Self-Management Support Intervention: Outcomes at 1-Year Follow-Up

Introduction Diabetes-related health improvements achieved from self-management education interventions are not sustained long-term. We examined the health effects at 1 year follow-up of a 2-year, empowerment-based, diabetes self-management support intervention designed for African Americans. Methods We collected data from 52 African American adults with type 2 diabetes who completed the 3-year study. The intervention consisted of weekly groups led by 2 health care professionals and emphasized experiential learning, emotional coping, problem solving, goal setting, and action planning; group discussion was guided by participant-identified self-management priorities and concerns. Measurements were taken at baseline, 24 months (postintervention), and 36 months (1 year follow-up) to assess glycemic control; weight; body mass index; serum cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels; systolic and diastolic blood pressure; self-care behaviors; diabetes-specific quality of life; and diabetes empowerment. Results Following the 2-year diabetes self-management support intervention, we found significant improvements for following a healthy diet (P = .03), spacing carbohydrates evenly across the day (P = .005), using insulin as recommended (P = .047), and achieving diabetes-specific quality of life (P = .02). At 1-year follow-up, not only did participants sustain the behavioral improvements made in the 2-year diabetes self-management support intervention, but they also demonstrated additional improvements in glycemic control (P < .001) and in serum cholesterol (P < .001) and low-density lipoprotein cholesterol levels (P = .001). Conclusion Participation in an empowerment-based diabetes self-management support intervention may have a positive and enduring effect on self-care behaviors and on metabolic and cardiovascular health.