Miracle-dz/UniFAR-FTUs huggingface dataset:
A population pharmacokinetic analysis of sildenafil citrate in patients with erectile dysfunction.

AIMS To analyse the pharmacokinetics of sildenafil citrate in patients with erectile dysfunction in order to characterize covariate relationships and assist in the development of rational dosage strategies. METHODS A population pharmacokinetic sampling strategy was incorporated into five phase III clinical study protocols. Overall, 2077 patients, 1335 of whom received sildenafil, were asked to take an additional dose of study drug before their scheduled clinic visits on four or five occasions throughout the study duration. A single plasma sample was obtained at random times postdose (range 1--7 h), and a total of 4582 samples were assayed (average 3.4 samples per individual). RESULTS For the population average patient (age 58 years; aspartate transaminase [AST], 24 IU l(-1); weight, 87 kg; not receiving CYP3A4 potential inhibitors), typical values for sildenafil (mean +/- SE) were 58.5 +/- 1.4 l h(-1) for apparent clearance (CL/F), 310 +/- 6.92 l for volume of distribution (V/F), and 2.6 +/- 0.176 h(-1) for first-order absorption constant (ka). The value for ka is associated with meal consumption within 2 h predose, at all other times ka was equivalent to an instantaneous bolus administration. The interindividual variabilities were 29% for CL/F, 20% for V/F, and 210% for ka. Over a dose range of 25--100 mg sildenafil, the pharmacokinetics exhibited dose proportionality. There was evidence of nonproportionality (40% increase on average) in relative bioavailability with respect to the 200-mg dose (P<0.001) relative to the other doses. Age, AST concentration, and co-administration with CYP3A4 potential inhibitors significantly influenced CL/F of sildenafil (P<0.001, for each relationship). For age and AST, the extent of the linear relationships (extrapolated from population average values) included a 4% decrease in CL/F for every decade increase and a 6% decrease in CL/F for every 10-unit increase, respectively. Following co-administration of CYP3A4 potential inhibitors, a 14% decrease in CL/F was estimated. Only body weight was found to significantly (P<0.001) influence V/F (a 6% increase in V/F for every 10-kg increase). CONCLUSIONS The pharmacokinetics of, and covariate influences on, sildenafil in patients with erectile dysfunction were shown to be consistent with those demonstrated in phase I volunteer studies.
Clinical and EEG Asymmetries in Juvenile Myoclonic Epilepsy

Summary: We reviewed records of 85 patients with juvenile myoclonic epilepsy (JME) for significant asymmetries in clinical seizures or the EEG. We noted asymmetries in 26 of 85 patients (30.6%). Only 2 patients had both clinical and EEG asymmetries; 12 had clinical asymmetries and 12 had EEG asymmetries exclusively. Analysis of patients with and without asymmetries showed no statistically significant differences in comparisons of sex, age at seizure onset, family history of epilepsy, seizure type, or response to treatment. The delay in diagnosis was greater in JME patients with asymmetries (9.5 years) than in JME patients with no asymmetries (7.5 years), but this difference was not statistically significant. Fourteen of the 26 patients with asymmetries (53.8%) were initially misdiagnosed as having partial seizures. Asymmetries in JME patients are not only common, but are also a frequent cause of misdiagnosis.
Music mixing preferences of cochlear implant recipients: A pilot study

Abstract Objective: Music perception and appraisal are generally poor in cochlear implant recipients. Simple musical structures, lyrics that are easy to follow, and clear rhythm/beat have been reported among the top factors to enhance music enjoyment. The present study investigated the preference for modified relative instrument levels in music with normal-hearing and cochlear implant subjects. Design: In experiment 1, test subjects were given a mixing console and multi-track recordings to determine their most enjoyable audio mix. In experiment 2, a preference rating experiment based on the preferred relative level settings in experiment 1 was performed. Study sample: Experiment 1 was performed with four postlingually deafened cochlear implant subjects, experiment 2 with ten normal-hearing and ten cochlear implant subjects. Results: A significant difference in preference rating was found between normal-hearing and cochlear implant subjects. The latter preferred an audio mix with larger vocals-to-instruments ratio. In addition, given an audio mix with clear vocals and attenuated instruments, cochlear implant subjects preferred the bass/drum track to be louder than the other instrument tracks. Conclusions: The original audio mix in real-world music might not be suitable for cochlear implant recipients. Modifying the relative instrument level settings potentially improves music enjoyment.
Electromigration diffusivity spectrometry: A way for simultaneous determination of diffusion coefficients from mixed samples

A novel method was proposed for simultaneous measurement of diffusion coefficients, (D), from mixed samples by electrophoresis and termed electromigration‐based diffusivity spectrometry. After theoretical treatment, D‐equation for practical use has been deduced. With a modified CE system built in laboratory, electromigration‐based diffusivity spectrometry has been realized and validated to suit for fast and accurate determination of diffusivities of mixed aromatic amino acids, phenols and aromatic organic acid, giving diffusivity spectra by peak area versus D, much similar to mass spectra. The precision of the measurement was found to critically depend on pH value of running buffer, which should be so selected that the analytes and internal standards could be charged at above 0.5e. The standards have to be selected at an electric flux far from each other and from analytes. In these cases, sample and running buffer concentrations, voltage and system temperature were found to have only negligible impact on the determination. In our test, the obtained measuring precision was generally kept within 1% for five runs, and the measured values of D agreed well with those from literature, with a deviation of less than 2.2% after the right use of calibration standards.
Matrix converter modulation strategies: a new general approach based on space-vector representation of the switch state

In this paper, a novel representation of the switch state of a three-phase to three-phase matrix converter is presented. This approach, based on space-vector notation, simplifies the study of the modulation strategies, leading to a complete general solution of the problem and providing a very useful unitary point of view. The already established strategies can be considered as particular cases of the proposed general solution. Using this approach, it can be verified that the space-vector modulation technique, owing to the intrinsic two degrees of freedom, represents the general solution of the modulation problem of matrix converters. This technique can be considered the best solution for the possibility to achieve the highest voltage transfer ratio and to optimize the switching pattern through a suitable use of the zero configurations.
Polymorphism at the rad Gene Is Not Associated With NIDDM in Finns

Recently, a trinucleotide repeat polymorphism at the rad (ras associated with diabetes) locus (RAD1) on chromosome 16q was described in association with NIDDM in white Americans. In an attempt to replicate this finding, we screened RAD1 and another microsatellite marker at the D16S265 loci, which is located near the rad locus, with a radioactive polymerase chain reaction method in 290 unrelated Finnish NIDDM patients and 270 control subjects and related the findings to measures of insulin sensitivity. Both groups were randomly selected from the western (189 NIDDM patients and 184 control subjects) and southern (101 NIDDM and 86 control subjects) parts of Finland. The allele frequency distributions of RAD1 and D16S265 did not differ between NIDDM patients and control subjects in the studied population groups. The genotype distribution was also analyzed by structural classes of the RAD1 polymorphism, and no difference was detected between the NIDDM and control groups. In addition, carriers of allele classes I, II, and IV (reported to be preferentially associated with NIDDM in white Americans) did not differ from the class III homozygotes with respect to age at onset of NIDDM, BMI, or rates of insulin-stimulated glucose disposal. In conclusion, we found no association between the rad locus and NIDDM or insulin resistance in Finnish NIDDM patients.
Comparisons between fat measurements by dual-energy X-ray absorptiometry, underwater weighing and magnetic resonance imaging in healthy women.

OBJECTIVE To compare the results of measurements of total and regional fat by dual-energy X-ray absorptiometry (DXA), underwater weighing (UWW) and magnetic resonance imaging (MRI) in women. DESIGN 13 volunteer pre-menopausal women measured with a Norland XR26 HS DXA instrument, hydrodensitometry equipment and a 0.08 Tesla MRI scanner. SETTING Aberdeen Royal Infirmary. RESULTS There were high correlations between measurements of total-body fat by the different techniques, but poor agreement. The mean values of fat as a percentage of the total body mass were UWW = 28.6%, DXA = 40.0%, MRI = 23.0%, although the MRI excluded the head, forearms and feet, estimated from the DXA measurements to contain 8% of the body fat. Although the correlations were apparently linear in the ranges examined, those including the Norland DXA had high intercepts. Bland and Altman plots showed no dependence of the differences on the degree of fatness. Evidence was obtained from in vivo comparisons and phantom measurements that the fat calibration of the Norland DXA had changed during a three year period, suggesting that fat calibration errors contributed to the MRI/DXA differences. Previous comparisons between the Norland DXA and other brands indicate that Hologic and Lunar instruments would show a closer agreement with MRI and UWW. Profiles of fat distribution along the body showed variations in the DXA/MRI ratio, particularly in the chest, with the DXA pattern thought to be the less accurate. The DXA measurements of bone mineral, fat and lean tissue were used to demonstrate the variable proportion of bone in fat-free tissue, leading to errors in UWW. CONCLUSIONS Each method has its assumptions, which are often not sufficiently appreciated. Each method may be useful for testing and improving the assumptions in the other methods. No method can yet be regarded as a satisfactory reference technique.
UCHL1 regulates ubiquitination and recycling of the neural cell adhesion molecule NCAM

The neural cell adhesion molecule (NCAM) is involved in neural development and in plasticity in the adult brain. NCAM140 and NCAM180 isoforms are transmembrane proteins with cytoplasmic domains that differ only in an alternatively spliced exon in the NCAM180 isoform. Both isoforms can interact with several extracellular and cytoplasmic molecules mediating NCAM‐dependent functions. Most identified intracellular interaction partners bind to both isoforms, NCAM140 and NCAM180. To identify further intracellular interaction partners specifically binding to NCAM180 the cytosolic domain of human NCAM180 was recombinantly expressed and applied onto a protein macroarray containing the protein library from human fetal brain. We identified the ubiquitin C‐terminal hydrolase (UCHL1) which has been described as a de‐ubiquitinating enzyme as a potential interaction partner of NCAM180. Since NCAM180 and NCAM140 are ubiquitinated, NCAM140 was included in the subsequent experiments. A partial colocalization of both NCAM isoforms and UCHL1 was observed in primary neurons and the B35 neuroblastoma cell line. Overexpression of UCHL1 significantly decreased constitutive ubiquitination of NCAM180 and NCAM140 whereas inhibition of endogenous UCHL1 increased NCAM's ubiquitination. Furthermore, lysosomal localization of NCAM180 and NCAM140 was significantly reduced after overexpression of UCHL1 consistent with a partial colocalization of internalized NCAM with UCHL1. These data indicate that UCHL1 is a novel interaction partner of both NCAM isoforms that regulates their ubiquitination and intracellular trafficking.
Functional recovery in rat spinal cord injury induced by hyperbaric oxygen preconditioning

Abstract Background: It is a common belief that neurosurgical interventions can cause inevitable damage resulting from the procedure itself in surgery especially for intramedullary spinal cord tumors. The present study was designed to examine if hyperbaric oxygen preconditioning (HBO-PC) was neuroprotective against surgical injuries using a rat model of spinal cord injury (SCI). Methods: Sprague–Dawley rats were randomly divided into three groups: HBO-PC group, hypobaric hypoxic preconditioning (HH-PC) control group, and normobaric control group. All groups were subjected to SCI by weight drop device. Rats from each group were examined for neurological behavior and electrophysiological function. Tissue sections were analyzed by using immunohistochemistry, TdT-mediated dUTP-biotin nick end labeling, and axonal tract tracing. Results: Significant neurological deficits were observed after SCI and HBO-PC and HH-PC improved neurological deficits 1 week post-injury. The latencies of motor-evoked potential and somatosensory-evoked potential were significantly delayed after SCI, which was attenuated by HBO-PC and HH-PC. Compared with normobaric control group, pretreatment with HBO and hypobaric hypoxia significantly reduced the number of TdT-mediated dUTP-biotin nick end labeling-positive cells, and increased nestin-positive cells. HBO-PC and HH-PC enhanced axonal growth after SCI. Conclusions: In conclusion, preconditioning with HBO and hypobaric hypoxia can facilitate functional recovery and suppress cell apoptosis after SCI and may prove to be a useful preventive strategy to neurosurgical SCI.
Distribution of the invasive plant species Heracleum sosnowskyi Manden. in the Komi Republic (Russia)

Abstract Occurrences of the invasive plant species Heracleum sosnowskyi Manden. in the Komi Republic (northeastern part of European Russia) were recorded and published in the Global Biodiversity Information Facility (GBIF http://www.gbif.org) using the RIVR information system (http://ib.komisc.ru/add/rivr/en). RIVR stands for “Rasprostranenie Invasionnyh Vidov Rastenij” [Occurrence of Invasion Plant Species]. This citizen science project aims at collecting occurrence data about invasive plant species with the help of citizen scientists. Information can be added by any user after a simple registration (concept) process. However, the data published in GBIF are provided only by professional scientists. The total study area is approximately 19,000 km2. The GBIF resource contains 10894 Heracleum sosnowskyi occurrence points, each with their geographical coordinates and photographs of the plants in the locus of growth. The preliminary results of species distribution modelling on the territory of European North-East Russia presented.
The Preparation and Characterization of Pyrolysis Bio-Oil-Resorcinol-Aldehyde Resin Cold-Set Adhesives for Wood Construction

Resorcinol-formaldehyde (RF) resin is a kind of excellent exterior-grade wood structural adhesive, which can be conveniently cold-set for various applications. In order to decrease the production cost, pyrolysis bio-oil from renewable bioresources was used to replace resorcinol to synthesize the bio-oil-resorcinol-aldehyde (BRF) resin. The effect of replacing resorcinol with bio-oil on the properties, bonding performance, and characterization of resorcinol-aldehyde resin was comparatively investigated. A higher solid content and viscosity, albeit a lower shear strength, was found when the replacement ratio of bio-oil increased. The bonding performance of BRF with 10 and 20 wt % bio-oil was close to that of the pure RF resin. However, the trends of being less cross-linked, more easily decomposed, but more porous were found when the substitution ratio of bio-oil was higher than 20 wt %. Interestingly, it was found that the wood failure values of the BRF resins with bio-oil of no more than 20 wt % were slightly higher than that of the pure RF resin. On the whole, BRF resins with 20 wt % bio-oil is recommended as a wood structural adhesive, comprehensively considering the bio-oil substitution ratio and resin properties. The results obtained here showed that pyrolysis bio-oil is a promising green raw material for the production of RF resin with lower cost.
Bibliodrama as Therapy within the Church

This paper is a qualitative content analysis exploring how Bibliodrama is therapeutic as a potential therapeutic method to be used with the church population. The Bibliodrama referred to in this paper is the dramatization of Biblical scripture for therapeutic purposes. Two seminal Bibliodrama texts, Peter Pitzele’s (1998) Scripture Windows: Toward a Practise of Bibliodrama and Bjorn Krondorfer’s (1992) Body and Bible: Interpreting and Experiencing Biblical Narratives were explicitly and implicitly coded for the existence of Irvin Yalom’s (1995) therapeutic factors and Phil Jones’ (2007) dramatherapy core therapeutic processes. The author found over half of Yalom’s eleven therapeutic factors and Jones’ eight core processes to be explicitly present within the coded texts. Thus, Bibliodrama appears to contain many of the basic therapeutic elements outlined by Jones and Yalom and therefore may be a beneficial therapeutic method to employ with the church population.
Kurzfassung der aktualisierten S3-Leitlinie der DGVS und des Kompetenznetzwerkes CED zur Diagnostik und Behandlung des Morbus Crohn

Der Morbus Crohn (MC) betrifft besonders jungere Patienten und hat eine Pravalenz von ca. 200/105. Da der klinische Verlauf, das Befallsmuster und das Ausmas an extraintestinalen Manifestationen variabel sind, sind eine komplexe Diagnostik und eine abgestufte Therapie notwendig. Die Versorgungskosten fur den MC belaufen sich auf knapp 1600 Euro pro Monat, davon 2/3 aufgrund von Arbeitsausfall, Erwerbs- und Berufsunfahigkeit [12] . Der Versuch, die Versorgung von Patienten mit CED durch Leitlinien zu verbessern, hat damit nicht nur eine medizinische, sondern auch eine gesundheitsokonomische Dimension. Die uberarbeitete Leitlinie basiert auf der fruheren DGVS-Leitlinie sowie der Leitlinie der European Crohn's and Colitis Organization (ECCO) [16][17]. Die methodische Grundlage war das Leitlinien-Manual des Arztlichen Zentrums fur Qualitat in der Medizin [4], DELBI (http://www.delbi.net), die Oxford CEBM Levels of Evidence (http://www.cebm.net), die Methodik der Colitis ulcerosa-Leitlinie und die ECCO-Leitlinie. Die vorliegende Kurzfassung hat zum Ziel, die wesentlichen, klinisch relevanten Empfehlungen zu nennen, insbesondere bei Abweichungen zur fruheren Leitlinie. Sie erfullt die methodischen Kriterien einer evidenzbasierten Konsensus-Leitlinie (Stufe 3). Auf die Darstellung von Besonderheiten (Kinder und Jugendliche; Fertilitat und Schwangerschaft) wurde in dieser Kurzfassung verzichtet, es wird auf die in Kurze erscheinende vollstandige Leitlinie verwiesen.
THUIR at TREC 2004: Genomics Track

This is the first time that THUIR participates in TREC Genomics Track. We took part in both Ad hoc retrieval task and Categorization task. Based on our retrieval system TMiner, our research in the Ad hoc retrieval task focuses on: (1) Category of organism retrieval strategy; (2) Primary Feature Model; (3) Query Expansion (QE) technology; (4) Result fusion method. Five official runs have been submitted at triage task in the Categorization task. Unigrams are used as features in Vector Space Model, and the high dimension feature vectors are trained and classified by SVM classifier with RBFs as the kernel function. Three ways are taken to improve the classifier: (1) Perform feature selection to reduce the dimension of feature vectors; (2) Weight the important features; (3) Balance between the positive dataset and the negative dataset.
Telotristat etiprate, a novel inhibitor of serotonin synthesis for the treatment of carcinoid syndrome

Excessive serotonin secretion is the hallmark of carcinoid syndrome. It leads to diarrhea, cramping, abdominal pain, wheezing and flushing. It is also associated with serious cardiac valve disease and lower life expectancy. Efforts to control serotonin production in carcinoid syndrome are currently limited to the use of somatostatin analogues and antitumor therapies such as surgery, radiation, or embolization. A significant proportion of patients still suffer from excess serotonin production and its debilitating symptoms. This review addresses the development of telotristat etiprate, a novel serotonin synthesis inhibitor currently being investigated in carcinoid syndrome. Early clinical studies support the conduct of TELESTAR, a Phase III pivotal trial that may determine whether telotristat etiprate will become the first approved serotonin synthesis inhibitor.
Multichannel InSAR DEM Reconstruction Through Improved Closed-Form Robust Chinese Remainder Theorem

Interferometric synthetic aperture radar (InSAR) multichannel system, which produces more than one interferogram in a multifrequency or multibaseline configuration, allows us to reconstruct highly sloped and discontinuous terrain height profiles. In this letter, a novel method based on a closed-form robust Chinese remainder theorem (CRT) is presented to solve the height reconstruction problem. Proper reference remainder selection and remainder differential process, which do not exist in the traditional CRT, are adopted to improve the robustness of the height reconstruction. We also modify the method by exploiting statistical characteristics of interferometric phase and the combined information of InSAR interferograms. Moreover, a special weighted mean filtering method is adopted to get a better result. Experimental results prove the effectiveness of the method.
Parasitic Metrification in the Modern Hebrew stress system

L'article fournit une analyse de l'accent du nom en hebreu moderne dans le cadre de la theorie de la grille metrique. Deux propositions nouvelles sont avancees, elles concernent le concept de la metrification parasite, capable de predire le placement de l'accent deplace, et la regle supplementaire s'appliquant a la distribution de l'accent secondaire. Ces propositions etant necessaires pour une explication de l'accent en hebreu moderne, l'auteur souhaite les incorporer dans la theorie de la grille metrique.
Discrimination between the enzymatic activities of Candida albicans pleomorphic forms determined using the api® ZYM test

Enzymatic activity profiles for two morphotypes of 37 Candida albicans clinical isolates were compared. Yeast and hyphal forms were grown using yeast extract‐peptone‐glucose broth or undiluted human serum, respectively. Both morphotypes were documented under scanning electron microscopy. The api® ZYM (BioMérieux, France) test was used to evaluate the enzymatic activity profiles for particular pleomorphic forms. None of the examined enzymatic activities showed good agreement (kappa, κ > 0.80) for the two morphotypes of the tested strains. Only leucine arylamidase activity in blastoconidia and hyphae of 35 out of 37 strains appeared to be in significant agreement (κ = 0.770). This phenomenon should be explored further for clinical benefits. For morphotypes of all tested strains, activity profiles of 11 hydrolytic enzymes demonstrated weak agreement (κ = 0.044–0.197). Moreover, satisfactory (κ = 0.218–0.348) and moderate agreement (κ = 0.413–0.479) were noted for enzymatic activity values of five and two enzymes, respectively. The distinct differences in activity profiles of hydrolytic enzymes between hyphae and blastoconidia is suggested to be related to the specific roles of these two morphotypes in particular steps of pathogenesis. Moreover, both morphotypes should be examined by strain biotyping methods. Beta‐N‐hexosaminidase (HexNAcase) activity assessed by the api® ZYM test and on CHROMagar Candida® medium (Becton Dickinson, USA) is also discussed.