Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and dynamics of mycophenolate mofetil after single‐dose oral administration in juvenile dachshunds

Mycophenolate mofetil (MMF) is recommended as an alternative/complementary immunosuppressant. Pharmacokinetic and dynamic effects of MMF are unknown in young-aged dogs. We investigated the pharmacokinetics and pharmacodynamics of single oral dose MMF metabolite, mycophenolic acid (MPA), in healthy juvenile dogs purpose-bred for the tripeptidyl peptidase 1 gene (TPP1) mutation. The dogs were heterozygous for the mutation (nonaffected carriers). Six dogs received 13 mg/kg oral MMF and two placebo. Pharmacokinetic parameters derived from plasma MPA were evaluated. Whole-blood mitogen-stimulated T-cell proliferation was determined using a flow cytometric assay. Plasma MPA Cmax (mean ± SD, 9.33 ± 7.04 μg/ml) occurred at <1 hr. The AUC0-∞ (mean ± SD, 12.84±6.62 hr*μg/ml), MRTinf (mean ± SD, 11.09 ± 9.63 min), T1/2 (harmonic mean ± PseudoSD 5.50 ± 3.80 min), and k/d (mean ± SD, 0.002 ± 0.001 1/min). Significant differences could not be detected between % inhibition of proliferating CD5+ T lymphocytes at any time point (p = .380). No relationship was observed between MPA concentration and % inhibition of proliferating CD5+ T lymphocytes (R = .148, p = .324). Pharmacodynamics do not support the use of MMF in juvenile dogs at the administered dose based on existing therapeutic targets.
Effects of various nucleosides on antiviral activity and metabolism of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil against herpes simplex virus types 1 and 2

Uptake of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) into herpes simplex virus type 1 (HSV-1)- and 2 (HSV-2)-infected cells was elevated about 190 to 40 times, compared with that into mock-infected human embryo lung fibroblast cells. Uptake was not enhanced by infection with thymidine kinase-negative HSV-1 and HSV-2 mutants, however. In HSV-1-infected cells, 9.7% of BV-araU was phosphorylated to BV-araU triphosphate, but only 1.1% was phosphorylated in HSV-2-infected cells. The antiviral effect, uptake, and turnover of BV-araU were inhibited significantly by thymidine (dThd), moderately by deoxyuridine, and not at all by deoxycytidine. On the other hand, the antiviral activity of acyclovir (ACV) was inhibited only by dThd. The effect of BV-araU was influenced by dThd and dThd phosphates (mono-, di-, and triphosphates), and the effect of ACV was influenced only by dThd, which competitively inhibited the phosphorylation of ACV to ACV monophosphate. The combination of 5-fluorodeoxyuridine (FUdR)-BV-araU or FUdR-ACV had a synergistic effect on HSV-1 and HSV-2 replication. The effect of FUdR on the turnover of BV-araU in HSV-1- and HSV-2-infected cells was analyzed by high-performance liquid chromatography. In HSV-1-infected cells, 86% of the BV-araU was phosphorylated to BV-araU triphosphate, but no effect was observed in HSV-2-infected cells, in which 98% of the BV-araU remained as BV-araU monophosphate.
Quality of life and its correlates in HIV/AIDS male outpatients receiving highly active antiretroviral therapy in Taiwan

Abstract Long‐term care of human HIV and AIDS cases has raised quality of life (QoL) issues. The aim of this study was to identify QoL in HIV/AIDS male outpatients receiving highly active antiretroviral therapy (HAART) and its correlates in Taiwan. In total, 41 HIV/AIDS male outpatients receiving HAART yet presenting few symptoms of infection, were recruited for the study. Their QoL levels were measured with the Taiwan version of the Short Form of the World Health Organization Quality of Life questionnaire (WHOQOL‐BREF). The relationships between QoL and demographic characteristics, social support, negative stressors, depression, characteristics of HIV infection, attitude toward HIV infection, and adverse effects of HAART, were examined. The results of the analysis reveal that multiple factors affect QoL for HIV/AIDS male outpatients receiving HAART, including severity of depression, deterioration of work function, inconvenience resulting from medication schedules and medical appointments, lack of social support, negative stressors, and adverse effects of HAART. The results provide screening factors so that clinicians can intervene to improve the QoL for their HIV patients.
Estimating the Effect of Voters’ Media Awareness on the 2016 US Presidential Election

We examine whether voter media awareness of the 2016 US Presidential election campaign influenced the election using a logit model to estimate the probability that a voter with certain characteristics votes for one of the two candidates. Our results indicate that the more active voters were on social media, the more likely they were to vote for Trump, and the more aware they were of the electoral campaign (watching TV, listening to the radio, reading newspapers, etc.) and the more interested they were in the news/politics, the less likely they were to vote for Trump. The impact of these variables was not as important as their sociodemographic characteristics.
Bone Remodeling at the Endocortical Surface of the Human Femoral Neck: A Mechanism for Regional Cortical Thinning in Cases of Hip Fracture

Endocortical remodeling and wall thickness (W.Th.) were measured in femoral neck bone from 12 female fracture cases (81.3 ± 1.5 years) and 12 sex‐matched controls (81.9 ± 1.9 years). Regionally, osteoid and eroded surface were increased, whereas W.Th. was reduced. These processes likely contribute to cortical bone loss seen in hip fracture.
‘Regulating the Poor’: Observations on the ‘Structural Coupling’ of Welfare, Criminal Justice and the Voluntary Sector in a ‘Big Society’

The article argues that the criminalizing tendency in contemporary social policy gets to the heart of how contemporary welfare systems work today. Analyses which point to criminalizing social policy (Rodger 2008), governing through crime (Simon 2007), cultures of control (Garland 2001) and the penalization of the poor (Wacquant 2009) all focus on what I will argue is actually the normal working of contemporary Western welfare systems. In the face of autonomous global economic processes, and largely uncontrollable macro-economic systems which place governments in a subordinate relationship to global financial forces, governance of present-day society is increasingly focused on the management of the behavioural dispositions of populations. In order to make these key themes and relationships visible, the article draws on Niklas Luhmann's functional structural systems theory and his concept of structural coupling to theorize the emerging policy relationships between the welfare system, the criminal justice system and civil society.
Intravenous paricalcitol for treatment of secondary hyperparathyroidism in children on hemodialysis.

BACKGROUND Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium x phosphorus (Ca x P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca x P product than calcitriol and has been used effectively in adult hemodialysis patients. STUDY DESIGN Double blind, placebo-controlled. SETTING & PARTICIPANTS Hemodialysis units and pediatric subjects receiving hemodialysis. INTERVENTION After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 mug/kg if initial intact parathyroid hormone [iPTH] level < 500 pg/mL [ng/L]; 0.08 mug/kg if initial iPTH level > 500 pg/mL [ng/L]). The dose was increased by 0.04 mug/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca x P product greater than 75 mg(2)/dL(2) (>6.04 mmol(2)/L(2)). OUTCOMES & MEASUREMENTS Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca x P product. RESULTS 60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca x P product values in either group. LIMITATIONS Low power to detect differences in safety between groups and a short-term study. CONCLUSION Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca x P product values during the course of the study.
Glycemic variability is higher in type 1 diabetes patients with microvascular complications irrespective of glycemic control.

BACKGROUND Increased glycemic variability (GV) may be associated with diabetes complications. Our study assessed the relationship between microvascular complications (MVCs) and GV calculated from continuous glucose monitoring (CGM) data in type 1 diabetes patients. SUBJECTS AND METHODS Thirty-two patients with type 1 diabetes (16 with and 16 without MVC) participated in this cross-sectional study. Vibration perception threshold (VPT), microalbuminuria, and fundoscopy were used to detect MVC. CGM data were recorded for 2 weeks and analyzed using proprietary software. Total SD (SDT), coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE) were compared. RESULTS Patients with any MVC had significantly higher GV, calculated from CGM, than patients without MVC (SDT, 4.1 ± 0.6 vs. 3.4 ± 0.8 mmol/L [P = 0.010]; CV, 0.43 ± 0.06 vs. 0.38 ± 0.08 [P = 0.032]; MAGE, 6.9 ± 1.2 vs. 5.9 ± 1.2 mmol/L [P = 0.014]) but comparable glycated hemoglobin (HbA1c) (70 ± 9 vs. 69 ± 10 mmol/mol [8.6 ± 0.8% vs. 8.5 ± 0.9%], difference not significant). No significant difference in GV was found between the two groups when using only self-monitored blood glucose (SMBG) data. A positive association was found between VPT and SDT in all patients (r = 0.51, P = 0.0026). CONCLUSIONS Patients with type 1 diabetes and any MVC had significantly higher GV calculated from CGM, but not from SMBG, than patients with comparable glycemic control but without complications. This supports the hypothesis that increased GV might be associated with MVC in type 1 diabetes and that HbA1c may not describe diabetes control completely.
Residual information to estimate uncertainty and improve the spectral linear mixing model solution

This paper proposes an analysis on the residual term resulting from the Linear Spectral Mixing Model (SLMM) solution in order to access model uncertainty. The framework employed here is based on analysis of data produced initially by unmixing of vegetation, bare soil and shade/water, whose are commonly used as standard endmembers. We suggest procedures to identify missing components in the mixture problem and automatically compute the spectral endmember values for these components directly from image data and residual information. The techniques proposed have been tested on real TM-Landsat. The results obtained promises and confirm the validity of the proposed approach.
ATP‐evoked calcium responses of radial glial (Müller) cells in the postnatal rabbit retina

Here we show that rabbit Müller cell differentiation from radial glial progenitor cells is accompanied by a decreasing capability to respond to specific stimuli (depolarization and extracellular adenosine 5′‐triphosphate [ATP]) with an elevation of intracellular calcium. Intracellular free calcium was recorded in retinal wholemounts from young (postnatal days [P] 2 to 31) and adult rabbits. Images were taken from the nerve fiber/ganglion cell layers where the endfeet of radial glial/ Müller cells can be identified after selective uptake of calcium‐sensitive dyes. The area of responding endfeet was determinded as the percentage of the total area occupied by Müller cell endfeet, as an estimate of the percentage of responding cells. In response to depolarization (50 mM potassium), an increase of intracellular free calcium occurred in 19% of cells from young postnatal retinae (P2–31) but only in 2% from adults. This depolarization‐induced calcium rise was caused both by a calcium influx from extracellular space and by an intracellular calcium release. The latter response was inhibited by the P2 receptor blocker pyridoxal phosphate 6‐azophenyl‐2′,4′‐disulfonic acid (PPADS), indicating that extracellular calcium‐independent ATP release into the extracellular space occurs during retinal depolarization. When extracellular ATP (200 μM) was applied, calcium responses were recorded in 83% of cells from young postnatal retinae (P2–6); in the course of further development, both the percentage of responding cells (7% in retinae from adult rabbits) and the amplitude of the calcium responses decreased. It is concluded that during the differentiation of immature radial glia into mature Müller cells, stimulus‐evoked intracellular calcium signaling mechanisms change. © 2002 Wiley‐Liss, Inc.
Cysteine‐rich secretory proteins are not exclusively expressed in the male reproductive tract

The Cysteine‐RIch Secretory Proteins (CRISPs) are abundantly produced in the male reproductive tract of mammals and within the venom of reptiles and have been shown to regulate ion channel activity. CRISPs, along with the Antigen‐5 proteins and the Pathogenesis related‐1 (Pr‐1) proteins, form the CAP superfamily of proteins. Analyses of EST expression databases are increasingly suggesting that mammalian CRISPs are expressed more widely than in the reproductive tract. We, therefore, conducted a reverse transcription PCR expression profile and immunohistochemical analyses of 16 mouse tissues to define the sites of production of each of the four murine CRISPs. These data showed that each of the CRISPs have distinct and sometimes overlapping expression profiles, typically associated with the male and female reproductive tract, the secretory epithelia of exocrine glands, and immune tissues including the spleen and thymus. These investigations raise the potential for a role for CRISPs in general mammalian physiology. Developmental Dynamics 237:3313–3323, 2008. © 2008 Wiley‐Liss, Inc.
Variability in the precore and core promoter region of the hepatitis B virus genome

There is increasing evidence that hepatitis B virus (HBV) infections with different genotypes and subgenotypes differ in response to treatment and long‐term prognosis. The differences emerge from variability within the genomes that leads to structural deviations at the pregenomic level and to changes at the translational level. Naturally occurring HBV strains covering the four major genotypes A–D were obtained from 393 patients and part of the genome was amplified using polymerase chain reaction (PCR), sequenced, and analyzed for mutational differences in the precore and core promoter regions. The study confirmed that core promoter and precore mutations occur at key positions (A1762T, G1764A, G1896A, and G1899A), and that the proportions of strains with seroconvertion in patients differ between the four HBV genotypes. A rare double mutation (C1857T together with G1897A) was observed, and C1856T was found together with the emerging G1898A mutation, which itself was found to be more widespread geographically than previously described. We found a novel mutation (T1850C), never before observed in human HBV strains but known from woodchuck hepatitis virus (WHV). A novel association of mutation C1773T with G1764T, C1766A, and G1757A was also found within a site already suggested to be a putative binding site for HNF‐3. This novel association is proposed by us to be of importance for additional binding of HNH‐2 to this site and is a better indicator of the emergence of the double mutation G1764T and C1766A than the G1757A mutation proposed previously. J. Med. Virol. 86:437–445, 2014. © 2013 Wiley Periodicals, Inc.
Characterization of two avian reoviruses that exhibit strain-specific quantitative differences in their syncytium-inducing and pathogenic capabilities.

We previously proposed that the conservation of the nonessential syncytium-inducing phenotype among all reported avian reovirus (ARV) isolates may reflect a mechanism for enhanced virus dissemination in vivo, which in turn could contribute to the natural pathogenicity of ARV. Direct testing of this hypothesis has been hampered by the lack of available virus strains with defined differences in their fusion-inducing capability. We now report on the characterization of two ARV strains, ARV-176 and ARV-138, that exhibited strain-specific differences in their fusogenic properties, which correlated with their pathogenic potential in embryonated eggs. Moreover, both virus strains possessed similar replicative abilities in cell culture, suggesting that the weakly fusogenic ARV-138 virus is specifically inhibited in its syncytium-inducing ability. To test the use of these viruses for reassortant studies aimed at assessing the role of cell fusion in viral pathogenesis, a preliminary genetic analysis was undertaken using a monoreassortant that contained nine genome segments from the parental ARV-138 virus and the S1 genome segment from the highly fusogenic and pathogenic ARV-176 parental virus. The monoreassortant possessed the full fusogenic potential of the ARV-176 parental virus and displayed enhanced embryo pathogenicity, providing the first genetic evidence implicating the ARV S1 genome segment in both syncytium formation and viral pathogenesis.
Molecular diagnosis of parathyroid carcinoma: a reality in the near future.

INTRODUCTION Parathyroid carcinoma (PC) is a rare endocrine malignancy that still suffers from a problem of delayed clinical diagnosis. Consequently, it usually is not recognized preoperatively and often is not conclusively identified during the operation either. AREAS COVERED The role played by parafibromin in the development of PC, representing an important advance in understanding the pathogenesis of this malignancy, is discussed. Through a careful search of the international literature, using "parathyroid carcinoma", "molecular genetics of parathyroid carcinoma" and "parathyroid tumorigenesis" as key words, other less mentioned molecular mechanisms are reappraised as potential molecular markers of PC; we also discuss their potential role in 20 parathyroid outgrowths. Finally, both the major efforts and the limitations of reported molecular diagnostic techniques and diagnostic markers are considered. EXPERT OPINION Currently, several critical issues still need to be addressed, such as the lack of: i) common criteria for the histopathological diagnosis of parathyroid malignancy and ii) timely appropriated preoperative diagnosis of PC. The latter issue would be of fundamental importance to assist the surgeon in performing a complete resection of all carcinomatous tissue at the time of the initial surgery, allowing for the greatest likelihood of a cure.
Schistosoma mansoni: a scanning electron microscope study of the developing schistosomulum

SUMMARY The surface morphology of schistosomula extracted from the skin, lungs and hepatic portal system (hps) of mice was investigated from Days 0 to 18 post-infection. Skin schistosomula and newly arrived schistosomula from the hps were of similar dimensions but were morphologically distinct. Lung schistosomula were considerably elongated with an estimated 53% increase in surface area compared to skin schistosomula. The pitted tegument of lung schistosomula was formed into ridges and troughs. These were compressed together in contracted individuals recovered from the hps on Day 10. The annular ridges were cross-linked by longitudinal septae which possibly prevent further elongation of the body. A regression of the spines between the mouth and the ventral sucker was observed in Day 2 skin schistosomula. In lung schistosomula only the spines at the anterior and posterior of the body remained. New spines were formed after the schistosomula reached the hps. It is suggested that the spines in the mid-region of the body are selectively disassembled and that their loss facilitates migration along the lumina of capillaries with the residual spines acting as anterior and posterior anchors. The mouth opening was enlarged in schistosomula from the hps recovered from Day 10 onwards. Skin schistosomula lost the cercarial apical tegumentary ridges between 24 and 48 h after penetration but a spineless protrusible area remained. After arrival in the hps this area became integrated into the anterior surface as the oral sucker developed around the sub-terminal mouth. The cercarial ciliated papillae were lost on penetration. The migrating schistosomulum had few visible sensory papillae but following arrival in the hps new papillae were observed.
Chemokine receptors are expressed widely by embryonic and adult neural progenitor cells

We investigated the expression and functions of chemokine receptors in neural progenitor cells isolated from embryonic and adult mice. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis demonstrated mRNA expression for most known chemokine receptors in neural progenitor cells grown as neurospheres from embryonic (E17) and adult (4‐week‐old) mice. The expression of CXCR4 receptors was demonstrated further in E17 neurospheres using immunohistochemistry, in situ hybridization, Northern blot analysis and fura‐2‐based Ca2+ imaging. Most neurospheres grown from E17 mice responded to stromal cell‐derived factor‐1 (SDF‐1/CXCL12) in Ca2+ imaging studies. In addition, immunohistochemical studies demonstrated that these neurospheres consisted of dividing cells that uniformly colocalized nestin and CXCR4 receptors. Differentiation of E17 neurospheres yielded astrocytes and neurons exhibiting several different phenotypes, including expression of calbindin, calretinin, gamma‐aminobutyric acid (GABA), and glutamate, and many also coexpressed CXCR4 receptors. In addition, neurospheres grown from the subventricular zone (SVZ) of 4‐week‐old mice exhibited large increases in Ca2+ in response to CXCL12 and several other chemokines. In comparison, neurospheres prepared from olfactory bulb of adult mice exhibited only small Ca2+ responses to CXCL12, whereas neurospheres prepared from hippocampus were insensitive to CXCL12, although they did respond to other chemokines. Investigations designed to investigate whether CXCL12 can act as a chemoattractant demonstrated that cells dissociated from E17 or adult SVZ neurospheres migrated toward an CXCL12 gradient and this was blocked by the CXCR4 antagonist AMD3100. These results illustrate widespread chemokine sensitivity of embryonic and adult neural progenitor cells and support the view that chemokines may be of general importance in control of progenitor cell migration in embryonic and adult brain. © 2004 Wiley‐Liss, Inc.
A framework based on fuzzy AHP-TOPSIS for prioritizing solutions to overcome the barriers in the implementation of ecodesign practices in SMEs

ABSTRACT Small and medium enterprises (SMEs) are under pressure to adopt sustainable practices in their business due to increasing environmental challenges. This study aims to identify and prioritize the solutions to overcome the barriers in the implementation of ecodesign practices in SMEs. This study helps the companies to develop and implement the strategies on priority using higher ranked solutions. In this study, a framework is proposed that is based on fuzzy analytical hierarchy process and fuzzy technique for order preference by similarity to ideal solution to rank the solutions that overcome the barriers in ecodesign implementation in SMEs. The proposed framework is illustrated by conducting a case study of an Indian ring and piston manufacturing company. This framework provides an effective support in the decision-making of the company for producing eco-friendly products through the implementation of ecodesign practices. Results of this study emphasize that training of designers to use different ecodesign tools is an essential practice for SMEs.