Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative bioavailability of three ibuprofen formulations in healthy human volunteers.

OBJECTIVE To assess the bioequivalence of three ibuprofen formulations (Test formulation: ibuprofen (400 mg capsule) manufactured by Cardinal Health Brasil 402 Ltda. (Sorocaba, Brazil) and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. (SA poundo Paulo, Brazil); Reference formulation (1): ibuprofen (AdvilA(R); 2 A 200 mg coated tablet) from Wyeth-Whitehall Ltda. (Itapevi, Brazil); Reference formulation (2): ibuprofen (AliviumA; 8 ml A 50 mg/ml solution) from Schering Plough S.A. (Rio de Janeiro, Brazil)) in 24 healthy volunteers of both sexes. METHODS The study was conducted using an open, randomized, three-period crossover design with at least 5-day washout interval. Plasma samples were obtained over a 24-h period. Plasma ibuprofen concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the ibuprofen plasma concentration vs. time curves: AUC(last), AUC(trunctmax), AUC(inf) and C(max). RESULTS The limit of quantification for ibuprofen was 0.1 microg A ml(1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference (1) percent ratios were 114.24% (90% CI = 105.67, 123.50%) for C(max), 98.97% (90% CI = 94.69, 103.44%) for AUC(last) and 99.40% (90% CI = 95.21, 103.78%) for AUC(inf). The geometric mean and respective 90% confidence interval (CI) for Test/Reference (2) percent ratios were 108.38% (90% CI = 100.19, 117.25%) for C(max), 100.79% (90% CI = 96.39, 105.40%) for AUC(last) and 101.26% (90% CI = 96.94, 105.77%) for AUC(inf); t(max) for the 400 mg Test capsule was shorter than that for the 2 A 200 mg Reference (1) tablets (p < 0.002). CONCLUSION Since the 90% CI for AUC(last), AUC(inf) and Cmax ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that ibuprofen formulation manufactured by Cardinal Health Brasil 402 Ltda. and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. is bioequivalent to the AdvilA and AliviumA formulations with regard to both the rate and the extent of absorption.
Does a clinician's sex influence treatment decisions?

PURPOSE As more women are entering health professions, the health care system is becoming more feminized. This investigation evaluated gender differences in clinicians' treatment preferences and decision making in a complex treatment situation. MATERIALS AND METHODS A questionnaire was developed containing clinical cases and statements to assess practitioners' opinions on treatment of periodontally involved maxillary molars and implant therapy with sinus grafting. Data were analyzed with respect to the clinicians' sex, and an overall logistic regression was performed to further investigate possible influences of age, office location, and specialty. RESULTS Three hundred forty questionnaires were evaluated (response rate: 35.1%). The mean age of female respondents (37%) was 42 years, and the mean age of male respondents was 46 years. Significantly fewer women reported performing implant placement (35% vs 63%), sinus grafting (16% vs 43%), and periodontal surgery (57% vs 68%). Female practitioners tended to refer more patients to specialists. Participants favored sinus grafting more often for their spouses than for themselves. Apart from a preference for regenerative periodontal surgery among women, no gender differences were observed for treatment decisions or views on general statements related to implant preference, tooth maintenance, or conventional reconstructive therapies. CONCLUSIONS With similar expert knowledge, treatment decisions were made irrespective of sex. While the majority of male care providers performed complex therapies themselves, female clinicians referred more patients to specialists.
Screening of binding activity of Streptococcus pneumoniae, Streptococcus agalactiae and Streptococcus suis to berries and juices

Antiadhesion therapy is a promising approach to the fight against pathogens. Antibiotic resistance and the lack of effective vaccines have increased the search for new methods to prevent infectious diseases. Previous studies have shown the antiadhesion activity of juice from cultivated cranberries (Vaccinium macrocarpon Ait.) against bacteria, especially E. coli. In this study, the binding of two streptococcal strains, Streptococcus pneumoniae and Streptococcus agalactiae, to molecular size fractions (FI, FII and FIII, <10 kDa, 10–100 kDa, and >100 kDa, respectively) of berries and berry and fruit juices from 12 plant species were studied using a microtiter well assay. For Streptococcus suis a hemagglutination inhibition assay was used. In general, binding activity was detected especially to wild cranberry (Vaccinium oxycoccos L.) and to other Vaccinium species. S. pneumoniae cells bound most to cranberry juice fraction FI and S. agalactiae cells to cranberry fraction FIII. Hemagglutination induced by S. suis was most effectively inhibited by cranberry fraction FII. NMR spectra of some characteristic active and non‐active fractions were also measured. They indicate that fractions FII and FIII contained proanthocyanidins and/or other phenolic compounds. The results suggest Vaccinium berries as possible sources of antiadhesives against bacterial infections. Copyright © 2009 John Wiley & Sons, Ltd.
Expressions of Grief on Facebook: Navigating Discomfort, Persistent Identity, and Public Memorialization

When someone dies, their online identity does not die with them. If a deceased Facebook user leaves behind a once active profile, friends and family members may choose to use this virtual space to express grief, interact with one another, and engage in active memorialization. Young adults who are traditionally marginalized in the grieving process can take advantage of the digital space to engage in mourning rituals. Through qualitative inquiry and in-depth interviews with 20 young adults who have dealt with the death of a friend or family member on Facebook, this study addresses phenomenological research questions concerning expression of grief on Facebook, what memorialization on Facebook entails, and how young adults interact with a deceased user’s profile. Grief theories and characteristics of social network sites (SNSs) are considered as concepts of thanatechnology and online community are explored. Emergent theme analysis shows that young adults can contribute to a dynamic memory archive associated with a friend’s identity by sharing stories and photographs on Facebook. Finding and giving support as well as maintaining a connection with the deceased are important to participants, who navigate a complicated hierarchy of acceptable expression, based on their relative closeness to the deceased. Participants also express varying levels of comfort and discomfort, related to appropriate expression and interaction with a persistent profile. This research study discusses the implications of such interaction, concluding that Facebook prevents users from addressing the fundamental reality of death and that the site can enable disingenuous expression of grief.
Pilot Study of Laser Doppler Measurement of Flow Variability in the Microcirculation of the Palatal Mucosa

Background. Histopathological alterations can arise when the denture-supporting mucosa experiences microbial and mechanical stress through the denture base and diagnosis of these diseases usually follows microvascular changes. Microcirculation measurement could allow for detection of such dysfunction and aid in the early diagnosis of palatal mucosa pathologies. Materials and Methods. We tested the sensitivity of laser Doppler for measuring the microcirculation of the palatal mucosa, assessing the median raphe (MR), Schroeder area (SA), and retroincisive papilla (RP). A Doppler PeriFlux 5000 System, containing a laser diode, was used. 54 healthy participants were recruited. We compare the measurements of PU (perfusion unit) using ANOVA test. Results. The numerical values for palatal mucosa blood flow differed significantly among the anatomical areas (p = 0.0167). The mean value of Schroeder area was 92.6 (SD: 38.4) and was significantly higher than the retroincisive papilla (51.9) (SD: 20.2) (p < 0.05), which in turn was higher than that of median raphe (31.9) (SD: 24.2) (p < 0.0001). Conclusion. Schroeder area appeared to have the greatest sensitivity, and vascular flow variability among individuals was also greatest in this region. We suggest that analysis of blood stream modification with laser Doppler of the palatal mucosa can help to detect onset signs of pathological alterations.
University of Birmingham Evolutionary Market Agents for Resource Allocation in Decentralised Systems

We introduce self-interested evolutionary market agents, which act on behalf of service providers in a large decentralised system, to adaptively price their resources over time. Our agents competitively co-evolve in the live market, driving it towards the Bertrand equilibrium, the non-cooperative Nash equilibrium, at which all sellers charge their reserve price and share the market equally. We demonstrate that this outcome results in even load-balancing between the service providers. Our contribution in this paper is twofold; the use of on-line competitive co-evolution of self-interested service providers to drive a decentralised market towards equilibrium, and a demonstration that load-balancing behaviour emerges under the assumptions we describe. Unlike previous studies on this topic, all our agents are entirely self-interested; no cooperation is assumed. This makes our problem a non-trivial and more realistic one.
Growth Hormone (GH) Treatment Up-Regulates GH Receptor mRNA Levels in Adipocytes from Patients with GH Deficiency and Prader-Willi Syndrome

ABSTRACT: We have investigated the effect of growth hormone (GH) treatment on GH receptor mRNA expression in five prepubertal children with Prader-Willi syndrome and in eight patients with GH deficiency. An adipose tissue needle biopsy was taken before and after 2–4 mo of GH treatment, and RNA was isolated from adipose tissue and from adipocytes. GH receptor mRNA levels were determined by an RNase protection/solution hybridization assay. To further assess the specificity of the assay for GH receptor mRNAs, RNA extracted from human adipose tissue was subjected to Northern blot analysis. GH treatment significantly increased GH receptor mRNA levels in adipose tissue and isolated adipocytes. Our results indicate that GH may have an important role in regulating the GH receptor in humans.
Work Engagement and the Positive Power of Meaningful Work

The application of positive psychology to the context of work has attracted enormous interest within both academic and practitioner domains over the past decade (e.g., Keyes & Haidt, 2003; Linley, Harrington, & Garcea, 2010; Luthans, 2002). From a practitioner perspective, there has been a proliferation of organizational development, human resource, talent management, leadership development, team development and coaching programs, initiatives, and interventions that have positive psychological principles at their core. The Gallup organization, for instance, has administered the Clifton Strengths Finder in thousands of organizations across the globe, aiming to help people learn about and build upon their talents and strengths to enhance all facets of their working experience (see Clifton & Harter, 2003).
Mutation scanning of the RET protooncogene using high-resolution melting analysis.

BACKGROUND Single-base pair missense mutations in exons 10, 11, 13, 14, 15, and 16 of the RET protooncogene are associated with the autosomal dominant multiple endocrine neoplasia type 2 (MEN2) syndromes: MEN2A, MEN2B, and familial medullary thyroid carcinoma. The current widely used approach for RET mutation detection is sequencing of the exons. METHODS Because RET mutations are rare and the majority are heterozygous mutations, we investigated RET mutation detection by high-resolution amplicon melting analysis. This mutation scanning technique uses a saturating double-stranded nucleic acid binding dye, LCGreen, and the high-resolution melter, HR-1, to detect heterozygous and homozygous sequence variations. Mutant genotypes are distinguished from the wild-type genotype by an altered amplicon melting curve shape or position. RESULTS Samples of 26 unique RET mutations, 4 nonpathogenic polymorphisms, or the wild-type genotype were available for this study. The developed RET mutation-scanning assay differentiated RET sequence variations from the wild-type genotype by altered derivative melting curve shape or position. A blinded study of 80 samples (derived from the 35 mutant, polymorphism, or wild-type samples) demonstrated that 100% of RET sequence variations were differentiated from wild-type samples. For exons 11 and 13, the nonpathogenic polymorphisms could be distinguished from the pathogenic RET mutations. Some RET mutations could be directly genotyped by the mutation scanning assay because of unique derivative melting curve shapes. CONCLUSION RET high-resolution amplicon melting analysis is a sensitive, closed-tube assay that can detect RET protooncogene sequence variations.
A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells

The anucleate prismoid fiber cells of the eye lens are densely packed to form a tissue in which the plasma membranes and their associated cytoplasmic coat form a single giant cell-cell adhesive complex, the cortex adhaerens. Using biochemical and immunoprecipitation methods in various species (cow, pig, rat), in combination with immunolocalization microscopy, we have identified two different major kinds of cortical complex. In one, the transmembrane glycoproteins N-cadherin and cadherin-11 [which also occur in heterotypic (`mixed') complexes] are associated with α- and β-catenin, plakoglobin (proportions variable among species), p120ctn and vinculin. The other complex contains ezrin, periplakin, periaxin and desmoyokin (and so is called the EPPD complex), usually together with moesin, spectrin(s) and plectin. In sections through lens fiber tissue, the short sides of the lens fiber hexagons appear to be enriched in the cadherin-based complexes, whereas the EPPD complexes also occur on the long sides. Moreover, high resolution double-label fluorescence microscopy has revealed, on the short sides, a finer, almost regular mosaicism of blocks comprising the cadherin-based, catenin-containing complexes, alternating with patches formed by the EPPD complexes. The latter, a new type of junctional plaque ensemble of proteins hitherto known only from certain other cell types, must be added to the list of major lens cortex proteins. We here discuss its possible functional importance for the maintenance of lens structure and functions, notably clear and sharp vision.
Multi-Criteria and Multi-Stage Facility Location Selection under Interval Type-2 Fuzzy Environment: A Case Study for a Cement Factory

AbstractThe study proposes a comprehensive and systematic approach for multi-criteria and multi-stage facility location selection problem. To handle with high and more uncertainty in the evaluation and selection processes, the problem is solved by using multi-criteria decision making technique with interval Type-2 fuzzy sets. The study contributes the facility location selection literature by introducing the application of fuzzy TOPSIS method with interval Type-2 fuzzy sets. Finally, the suggested approach is applied to a real life region and site selection problem of a cement factory.
Selecting Training Data for Cross-Corpus Speech Emotion Recognition: Prototypicality vs. Generalization

We investigate strategies for selection of databases and instances for training cross-corpus emotion recognition systems, that is, systems that generalize across different labelling concepts, languages and interaction scenarios. We propose objective measures for prototypicality based on distances in a large space of brute-forced acoustic features and show their relation to the expected performance in cross-corpus testing. We perform extensive evaluation on eight commonly used corpora of emotional speech reaching from acted to fully natural emotion and limited phonetic content to conversational speech. In the result, selecting prototypical training instances by the proposed criterion can deliver a gain of up to 7.5 % unweighted accuracy in cross-corpus arousal recognition, and there is a correlation of . 571 between the proposed prototypicality measure of databases and the expected unweighted accuracy in cross-corpus testing by Support Vector Machines.
Nonlinear relation between pulse pressure and coronary heart disease in patients with type 2 diabetes or hypertension

Objectives: Wide pulse pressure (PP) is an independent predictor of coronary heart disease (CHD). However, the linearity of the relation between PP and CHD was not examined before. We aimed to examine this relation in patients with type 2 diabetes and/or hypertension. Methods: A total of 3120 patients (including 2607 with diabetes and 1586 with hypertension) were followed for 7.8 years. Physician-adjudicated first hard CHD event was the primary outcome. Cox regression analysis was used to investigate the association between PP and incident CHD. Restricted cubic splines were used to investigate nonlinear relations. Results: Four spline covariates were defined between 30, 40, 50, 60, and 70 mmHg. The null-hypothesis of the linearity of the relation between PP and CHD was rejected (P value = 0.004). The second, third, and fourth spline covariates were significant (P value = 0.02, P value = 0.02 and P value = 0.01, respectively), supporting a nonlinear relation in corresponding PP intervals. Patients with PP less than 45 mmHg and PP more than 55 mmHg had increased risk of future CHD event, compared with those with PP between 45 and 55 mmHg [hazard ratio (HR) = 1.33 (1.00–1.77) and HR = 1.67 (1.23–2.27), respectively]. This remained significant after controlling for systolic, diastolic, or mean arterial pressures in wide PP group. However, adjustment for traditional cardiovascular risk factors (especially age) attenuated the relation in those with wide PP. Conclusion: The relation between PP and CHD is nonlinear in patients with type 2 diabetes and hypertension. Both narrow and wide PPs increase risk of future hard CHD events. The association between wide PP and CHD is independent from SBP, DBP, or mean arterial pressure.
The Power and Potential of Doxorubicin‐DNA Adducts

Doxorubicin (trade name Adriamycin) is a widely used anticancer agent which exhibits good activity against a wide range of tumors. Although the major mode of action appears to be normally as a topoisomerase II poison, it also exhibits a number of other cellular responses, one of which is the ability to form adducts with DNA. For adduct formation doxorubicin must react with cellular formaldehyde to form an activated Schiff base which is then able to form an aminal (N‐C‐N) linkage to the exocyclic amino group of guanine residues. The mono‐adducts form primarily at G of 5'‐GCN‐3' sequences where the chromophore of the drug is intercalated between the C and N base pair. The structure of the adducts has have been well defined by 2D NMR, mass spectrometry and X‐ray crystallography. The formation of these anthracycline adducts in cells grown in culture has been unequivocally demonstrated. The source of formaldehyde in cells can be endogenous, provided by coadministration of prodrugs that release formaldehyde or by prior complexation of anthracyclines with formaldehyde. Since the adducts appear to be more cytotoxic than doxorubicin alone, and also less susceptible to drug‐efflux forms of resistance, they offer new approaches to improving the anticancer activity of the anthracyclines. IUBMB Life, 57: 73‐81, 2005
Evidence for abrupt speciation in a classic case of gradual evolution

In contrast with speciation in terrestrial organisms, marine plankton frequently display gradual morphological change without lineage division (e.g., phyletic gradualism or gradual evolution), which has raised the possibility that a different mode of evolution dominates within pelagic environments. Here, we reexamine a classic case of putative gradual evolution within the Globorotalia plesiotumida–G. tumida lineage of planktonic foraminifera, and find both compelling evidence for the existence of a third cryptic species during the speciation event and the abrupt evolution of the descendant G. tumida. The third morphotype, not recognized in previous analyses, differs in shape and coiling direction from its ancestor, G. plesiotumida. This species dominates the globorotaliid population for 414,000 years just before the appearance of G. tumida. The first population of the descendant, G. tumida, evolves abruptly within a 44,000-year interval. A combination of morphological data and biostratigraphic evidence suggests that G. tumida evolved by cladogenesis. Our findings provide an unexpected twist on one of the best-documented cases of within-lineage phyletic gradualism and, in doing so, revisit the limitations and promise of the study of speciation in the fossil record.
Neuromuscular sequelae of critical illness.

Until recently, survival to hospital discharge was the primary outcome considered in reports concerning populations of critically ill patients. But a body of knowledge is now being developed about longer-term outcomes in survivors of critical illnesses, including reports about their health-related quality of life and conditions that impair that quality.1 The inherent challenge is to devise strategies for preventing or minimizing such sequelae. The article by Herridge and colleagues in this issue of the Journal 2 provides important new information pointing in a direction that could eventually lead to the development of such a strategy and charging us with expanding the .
The doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1

Significance Maintaining an intricate balance between continued progenitor proliferation and cell cycle exit/differentiation is pivotal for proper brain development. Disruption of this delicate process can lead to brain malformations, such as microlissencephaly. In this paper, we identify Dmrta2 (doublesex- and mab-3–related transcription factor a2, also known as Dmrt5) as an important transcription factor that helps regulate the fine tuning between cell cycle progression and neuronal differentiation. Mechanistically, this function of Dmrta2 involves direct transcriptional regulation of a known repressor of neurogenesis Hes1. Our findings thus add Dmrta2 to the complex regulatory machinery controlling cortical NPC maintenance, and provide an explanation for the microlissencephaly caused by Dmrta2 deficiency in model organisms and humans. The mechanisms that determine whether a neural progenitor cell (NPC) reenters the cell cycle or exits and differentiates are pivotal for generating cells in the correct numbers and diverse types, and thus dictate proper brain development. Combining gain-of-function and loss-of-function approaches in an embryonic stem cell-derived cortical differentiation model, we report that doublesex- and mab-3–related transcription factor a2 (Dmrta2, also known as Dmrt5) plays an important role in maintaining NPCs in the cell cycle. Temporally controlled expression of transgenic Dmrta2 in NPCs suppresses differentiation without affecting their neurogenic competence. In contrast, Dmrta2 knockout accelerates the cell cycle exit and differentiation into postmitotic neurons of NPCs derived from embryonic stem cells and in Emx1-cre conditional mutant mice. Dmrta2 function is linked to the regulation of Hes1 and other proneural genes, as demonstrated by genome-wide RNA-seq and direct binding of Dmrta2 to the Hes1 genomic locus. Moreover, transient Hes1 expression rescues precocious neurogenesis in Dmrta2 knockout NPCs. Our study thus establishes a link between Dmrta2 modulation of Hes1 expression and the maintenance of NPCs during cortical development.