Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunization-based scores as independent prognostic predictors in soft tissue sarcoma patients

Background: The purpose of this study was to examine and compare the prognostic value of different immunization-based scoring systems in patients with soft tissue sarcoma (STS). Methods: We conducted a retrospective study evaluating a cohort of 165 patients diagnosed with STS between July 2007 and July 2014. The relative Glasgow prognostic score (GPS) of these patients was calculated using 3 different systems: the traditional GPS system (tGPS), the modified GPS system 1 (m1GPS), and the modified GPS system 2 (m2GPS). Then, we evaluated the relationships between each GPS system and clinicopathological characteristics. The mean follow-up for survivors in the cohort was 73.7 months as of March 2015. Results: The most favorable overall survival (OS) rate was associated with the score 0 groups, and the poorest progression-free survival (PFS) rate was associated with the score 2 groups, regardless of which system was used to calculate the score. Specifically, the m1GPS provided the greatest accuracy in predicting OS and PFS. Moreover, the same effect was observed in a separate analysis restricted to patients with metastases. Remarkably, in patients with a score of 2 as measured by all 3 systems, local treatment resulted in a poorer prognosis compared to patients with a score of 2 who did not receive local treatment. Conclusion: The GPS is a valuable prognostic marker and has the capability to predict the appropriate treatment strategy for STS patients with metastases. The modified GPS systems demonstrated superior prognostic and predictive value compared with the traditional GPS system.
Evaluation of Proinflammatory Cytokine and Neopterin Levels in Women with Papillary Thyroid Carcinoma

Introduction Papillary thyroid cancer is a disease that has been associated with chronic inflammation. The purpose of this study is to measure the production of the proinflammatory cytokines IL-1β, IL-6 and IL-8 and neopterin, which is a novel biomarker for cellular immune response in papillary thyroid cancer. Materials and methods The serum IL-1β, IL-6, IL-8 and neopterin values of 31 papillary thyroid cancer patients undergoing bilateral total thyroidectomy were measured before and 20 days after surgery. The values were compared with those of 39 healthy controls. Results Serum IL-1β levels were similar across groups. IL-6 (p<0.001), IL-8 (p = 0.015) and neopterin levels (p = 0.002) were higher in presurgical samples and returned to normal following surgery. Conclusions The proinflammatory cytokines IL-6 and IL-8, but not IL-1β, were produced in greater amounts in papillary thyroid cancer. Serum neopterin seems to be a valid biological marker supporting the presence of papillary thyroid cancer.
Holography for Non-Critical Superstrings

We argue that a class of ``non-critical superstring'' vacua is holographically related to the (non-gravitational) theory obtained by studying string theory on a singular Calabi-Yau manifold in the decoupling limit $g_s\to 0$. In two dimensions, adding fundamental strings at the singularity of the CY manifold leads to conformal field theories dual to a recently constructed class of $AdS_3$ vacua. In four dimensions, special cases of the construction correspond to the theory on an NS5-brane wrapped around a Riemann surface.
Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate

MSX1 has been proposed as a gene in which mutations may contribute to non-syndromic forms of cleft lip and/or cleft palate. Support for this comes from human linkage and linkage disequilibrium studies, chromosomal deletions resulting in haploinsufficiency, a large family with a stop codon mutation that includes clefting as a phenotype, and the Msx1 phenotype in a knockout mouse. This report describes a population based scan for mutations encompassing the sense and antisense transcribed sequence of MSX1 (two exons, one intron). We compare the completed genomic sequence of MSX1 to the mouse Msx1 sequence to identify non-coding homology regions, and sequence highly conserved elements. The samples studied were drawn from a panethnic collection including people of European, Asian, and native South American ancestry. The gene was sequenced in 917 people and potentially aetiological mutations were identified in 16. These included missense mutations in conserved amino acids and point mutations in conserved regions not identified in any of 500 controls sequenced. Five different missense mutations in seven unrelated subjects with clefting are described. Evolutionary sequence comparisons of all known Msx1 orthologues placed the amino acid substitutions in context. Four rare mutations were found in non-coding regions that are highly conserved and disrupt probable regulatory regions. In addition, a panel of 18 population specific polymorphic variants were identified that will be useful in future haplotype analyses of MSX1. MSX1 mutations are found in 2% of cases of clefting and should be considered for genetic counselling implications, particularly in those families in which autosomal dominant inheritance patterns or dental anomalies appear to be cosegregating with the clefting phenotype.
Impact of vitamin D administration on immunogenicity of trivalent inactivated influenza vaccine in previously unvaccinated children

As vitamin D (VD) has a significant regulatory effect on innate and adaptive immunity, the aim of this prospective, randomized, single-blinded, placebo-controlled study was to measure the impact of VD administration on the immune response to trivalent influenza vaccination (TIV). A total of 116 children (61 males, 52.6%; mean age 3.0 ± 1.0 y) with a history of recurrent acute otitis media (AOM), who had not been previously vaccinated against influenza, were randomized to receive daily VD 1,000 IU or placebo by mouth for four months. All of them received two doses of TIV (Fluarix, GlaxoSmithKline Biologicals) one month apart, with the first dose administered when VD supplementation was started. There was no difference in seroconversion or seroprotection rates, or antibody titers, in relation to any of the three influenza vaccine antigens between the VD and placebo groups, independently of baseline and post-treatment VD levels. The safety profile was also similar in the two groups. These data indicate that the daily administration of VD 1,000 IU for four months from the time of the injection of the first dose of TIV does not significantly modify the antibody response evoked by influenza vaccine.
Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle

Background Mastitis is a major disease of dairy cattle. Given the recent emergence of methicillin-resistant Staphylococcus aureus as a cause of bovine mastitis, new intramammary (IMA) treatments are urgently required. Lasalocid, a member of the polyether ionophore class of antimicrobial agents, has not been previously administered to cows by the IMA route and has favorable characteristics for development as a mastitis treatment. This study aimed to develop an IMA drug delivery system (IMDS) of lasalocid for the treatment of bovine mastitis. Methods Minimum inhibitory concentrations (MICs) were determined applying the procedures recommended by the Clinical and Laboratory Standards Institute. Solid dispersions (SDs) of lasalocid were prepared and characterized using differential scanning calorimetry and Fourier transform infrared spectroscopy. IMDSs containing lasalocid of micronized, nano-sized, or as SD form were tested for their IMA safety in cows. Therapeutic efficacy of lasalocid IMDSs was tested in a bovine model involving experimental IMA challenge with the mastitis pathogen Streptococcus uberis. Results Lasalocid demonstrated antimicrobial activity against the major Gram-positive mastitis pathogens including S. aureus (MIC range 0.5–8 μg/mL). The solubility test confirmed limited, ion-strength-dependent water solubility of lasalocid. A kinetic solubility study showed that SDs effectively enhanced water solubility of lasalocid (21–35-fold). Polyvinylpyrrolidone (PVP)-lasalocid SD caused minimum mammary irritation in treated cows and exhibited faster distribution in milk than either nano or microsized lasalocid. IMDSs with PVP-lasalocid SD provided effective treatment with a higher mastitis clinical and microbiological cure rate (66.7%) compared to cloxacillin (62.5%). Conclusion Lasalocid SD IMDS provided high cure rates and effectiveness in treating bovine mastitis with acceptable safety in treated cows.
Prediction of Waste Performance in a Geologic Repository

The rate of dissolution of low-solubility species from waste forms in a geologic repository can be calculated from a theoretical analysis of the time-dependent rate of mass transfer by diffusion and convection into the groundwater surrounding the waste, assuming a concentration at the waste-form surface equal to the solubility of the radioelement. The predicted steady-state dissolution rates are considerably below those observed in laboratory leaching experiments with borosilicate glass and with other waste forms, indicating that the solid-liquid chemical reaction rates measured in the laboratory experiments are greater than the rates of diffusive-convective mass transfer in the concentration boundary layer surrounding the waste form in a geologic repository. The steady-state mass transfer rate can be increased, and the time to reach steady state decreased, by sufficiently short half lives of the dissolving species. The mass-transfer theory has been extended to include the effect of time-dependent solubilities, diffusion coefficients, and retardation coefficients, which provides a means of calculating the time-dependent dissolution of low-solubility species from waste exposed to groundwater during the period of repository heating. The transient and steady-state diffusion of radionuclides through a finite backfill layer separating a finite waste solid and porous rock has been analyzed, including the effectsmore » of radioactive decay. The results show that the break-through time and rate of radionuclide release depend on properties of the backfill and surrounding rock and on the waste form dimensions. Peak far-field concentrations of more soluble radionuclides such as cesium-135, with suitably long radionuclide transport times and sufficiently large axial dispersion, are shown to be insensitive to dissolution rate. Equivalent phenomena occur in fracture-flow radionuclide transport. 36 references, 16 figures, 2 tables. « less
Attenuation of aortic banding-induced cardiac hypertrophy by propranolol is independent of β-adrenoceptor blockade

Objective Racemic propranolol attenuates cardiac hypertrophy secondary to abdominal aortic banding-induced pressure overload by a mechanism independent of its effect on cardiac work load. This was only observed, however, using doses of propranolol that were much higher than those needed to induce β-adrenoceptor blockade. Thus, the question remains as to whether the antihypertrophic effect of propranolol depends on its ability to antagonize cardiac β-adrenoceptor-mediated action (positive chronotropic effect, trophic effect) or on β-adrenoceptor-independent action. Methods In a rat model of chronic pressure overload induced by abdominal aortic banding, we evaluated the effects on left ventricular hypertrophy (LVH) of the propranolol isomers, l-propranolol and d-propranolol, which compared to l-isomer is approximately 50-fold less potent as a β-adrenoceptor antagonist, but is similarly potent as a membrane-stabilizer, as well as of timolol, a non-selective β-adrenergic antagonist devoid of membrane stabilizing activity, and disopyramide, which is a membrane stabilizer, but not a β-adrenoceptor blocker. Results Compared to sham-operated rats, banded rats had 30% greater left ventricular to body weight (LVW/BW) ratio (P < 0.01). The increase in LVW/BW ratio was significantly attenuated by treatment with 40 and 80 (but not 10) mg/kg per day of l-propranolol. Left ventricular hypertrophy was also prevented by d-propranolol, 40 and 80 mg/kg per day, and disopyramide, 50 mg/kg per day, whereas timolol, 30 and 60 mg/kg per day, showed no antihypertrophic effect. In separate groups of banded rats in which the reduction in heart rate induced by propranolol (80 mg/kg per day) was prevented by chronic cardiac pacing at 375 b.p.m. , hypertrophy was again prevented, indicating that the effects of l-propranolol on LVH are not related to a reduction in cardiac work load. Conclusions In the aortic banding-induced model of LVH: (i) the antihypertrophic effect of propranolol is independent of its β-adrenergic blocking activity; and Iii) since disopyramide and D-propranolol also proved to be able to antagonize banding-induced LVH, the hypothesis is proposed that membrane-stabilizing activity, among the ancillary properties of propranolol, most likely accounts for the antihypertrophic effect of this drug.
Inhibitory Receptors Are Expressed by Trypanosoma cruzi-Specific Effector T Cells and in Hearts of Subjects with Chronic Chagas Disease

We had formerly demonstrated that subjects chronically infected with Trypanosoma cruzi show impaired T cell responses closely linked with a process of T cell exhaustion. Recently, the expression of several inhibitory receptors has been associated with T cell dysfunction and exhaustion. In this study, we have examined the expression of the cytotoxic T lymphocyte antigen 4 (CTLA-4) and the leukocyte immunoglobulin like receptor 1 (LIR-1) by peripheral T. cruzi antigen-responsive IFN-gamma (IFN-γ)-producing and total T cells from chronically T. cruzi-infected subjects with different clinical forms of the disease. CTAL-4 expression was also evaluated in heart tissue sections from subjects with severe myocarditis. The majority of IFN-γ-producing CD4+ T cells responsive to a parasite lysate preparation were found to express CTLA-4 but considerably lower frequencies express LIR-1, irrespective of the clinical status of the donor. Conversely, few IFN-γ-producing T cells responsive to tetanus and diphtheria toxoids expressed CTLA-4 and LIR-1. Polyclonal stimulation with anti-CD3 antibodies induced higher frequencies of CD4+CTAL-4+ T cells in patients with severe heart disease than in asymptomatic subjects. Ligation of CTLA-4 and LIR-1 with their agonistic antibodies, in vitro, reduces IFN-γ production. Conversely, CTLA-4 blockade did not improved IFN-γ production in response to T. cruzi antigens. Subjects with chronic T. cruzi infection had increased numbers of CD4+LIR-1+ among total peripheral blood mononuclear cells, relative to uninfected individuals and these numbers decreased after treatment with benznidazole. CTLA-4 was also expressed by CD3+ T lymphocytes infiltrating heart tissues from chronically infected subjects with severe myocarditis. These findings support the conclusion that persistent infection with T. cruzi leads to the upregulation of inhibitory receptors which could alter parasite specific T cell responses in the chronic phase of Chagas disease.
A reverse-type sandwich enzyme-linked immunosorbent assay for detecting antibodies to Borna disease virus

To investigate whether there is an epidemiological correlation between Borna disease virus (BDV) infection and human neuropsychiatric diseases, we established a reverse-type sandwich enzyme-linked immunosorbent assay (RS-ELISA) for detecting specific antibodies to BDV. In this assay, microplate wells were coated dispersely with BDV p40 antigen, followed by the addition of test samples at a low dilution and then the biotinylated p40. A preformed complex of streptavidin and horseradish peroxidase-conjugated biotin and an enzyme substrate were used to measure the captured biotinylated p40. Theoretically, RS-ELISA should specifically detect anti-BDV antibodies without nonspecific signals; such signals possibly occur in conventional serological assays. Additionally, the RS-ELISA could be applied under the same protocols to test samples from a variety of animals. By using anti-BDV rat and rabbit sera, the assay was standardized so that it had high specificity and sensitivity. When we used the RS-ELISA to determine the presence of anti-BDV antibodies in plasma from 70 patients with chronic schizophrenia as well as 40 healthy individuals in the Tokyo area of Japan, no plasma sample was found to possess specific antibodies to BDV p40, indicating no association between BDV infection and the disease in our testing population. A negative reaction was also shown for the sera that had previously been judged to be seropositive for BDV by an immunofluorescence or immunoblot test. These findings suggested that false-positive cases of infection due to nonspecific reactions may be included in previous seroepidemiological information with regard to BDV.
Computational strategies toward the modelling of the intervertebral disc

Lumbar back pain has considerable socio-economical impacts, motivating a recently increasing interest from the research community. Yet, mechanisms triggering pain are not fully understood and this considerably hinders the development of efficient treatments and therapies. The objective of this thesis is to participate to the general understanding of the biomechanics of the spine through the development of computational strategies for the intervertebral disc. The intervertebral disc is a complex structure mainly comprised of the nucleus pulposus and the annulus fibrosus. The nucleus pulposus is the gelatinous core of the disc, which consists of a charged and hydrated extra-cellular matrix and an ionised interstitial fluid. It is enclosed in the annulus fibrosus which is formed by concentric layers of aligned collagen fibre sheets, oriented in an alternating fashion. A biphasic swelling model has been derived using mixture theory for soft, hydrated and charged tissues in order to capture the salient characteristics of the disc's behaviour. The model fully couples the solid matrix under finite deformations with the ionised interstitial fluid. The nucleus is assumed to behave isotropically while the effects of the collagen fibres in the annulus fibrosus are accounted for with a transversely isotropic model. The fixed negative charges of the proteoglycans, which induce an osmotic pressure responsible for the swelling capabilities of the disc, are constitutively modelled under the simplifying Lanir hypothesis. A Newton-Raphson solver was specifically built to solve the resulting nonlinear system of equations, together with a verification procedure to ensure successful implementation of the code. This was first reduced to the one dimensional case in order to demonstrate the appropriateness of the biphasic swelling model. The three dimensional model exhibited numerical instabilities, manifesting in the form of non-physical oscillations in the pressure field near boundaries, when loads and free-draining boundary conditions are simultaneously applied. As an alternative to considerable mesh refinement, these spurious instabilities have been addressed using a Galerkin Least-Square formulation, which has been extended for finite deformations. The performance and limitations of the GLS framework, which drastically reduces the pressure discrepancies and prevents the oscillations from propagating through the continuum, are demonstrated on numerical examples. Finally, the current state of the model's development is assessed, and recommendations for further improvements are proposed.
E‐learning at work: theoretical underpinnings and pedagogical challenges

Purpose – First, to explore the application of e‐learning as a medium for workplace learning, as a form of adult learning and organisational learning from a theoretical point of view, second, to review empirical studies on recent solutions to pedagogical problems encountered in workplace learning in general and in e‐learning in particular, and finally, to consider the challenges facing the further development of e‐learning solutions targeted at the workplace.Design/methodology/approach – The paper reviews theories of adult learning, workplace learning and organisational learning and brings out main pedagogical implications of these theories from an e‐learning point of view. Some empirical studies in which electronic networks and communication tools have been utilised in workplace learning are also described.Findings – The development of successful e‐learning solutions for the use of work organizations requires integrating research knowledge from different sources: theories of the learning organization, so.
Edinburgh Research Explorer Identification and characterization of human cytomegalovirus-encoded microRNAs

MicroRNAs (miRNAs) are an extensive class of noncoding genes that regulate gene expression through posttranscriptional repression. Given the potential for large viral genomes to encode these transcripts, we examined the human cytomegalovirus AD169 genome for miRNAs using a bioinformatics approach. We identiﬁed 406 potential stem-loops, of which 110 were conserved between chimpanzee cytomegalovirus and several strains of human cytomegalovirus. Of these conserved stem-loops, 13 exhibited a signiﬁcant score using the MiRscan algorithm. Examination of total RNA from human cytomegalovirus-infected cells demonstrated that 5 of the 13 predicted miRNAs were expressed during infection. These studies demonstrate that human cytomegalovirus encodes multiple conserved miRNAs and suggest that human cytomegalovirus may utilize an miRNA strategy to regulate cellular and viral gene function. MicroRNAs (miRNAs) are a large class of noncoding RNAs involved in posttranscriptional regulation through RNA inter-ference. A number of recent studies have identiﬁed virally encoded miRNAs using either biochemical cloning
Dietary Intake of Calcium and Phosphorus and Serum Concentration in Relation to the Risk of Coronary Artery Calcification in Asymptomatic Adults

Objective— The current data regarding the association between calcium and phosphorus and cardiovascular disease are lacking. The aim of this study was to explore whether dietary calcium and phosphorus intake and their serum levels are associated with the prevalence of coronary artery calcification (CAC) using cardiac computed tomography in asymptomatic participants without a history of chronic kidney disease or cardiovascular disease. Approach and Results— A cross-sectional study was performed in 23 652 Korean participants (40.8±7.3 years, male 83.5%) without chronic kidney disease (estimated glomerular filtration rate≥60 mL/min per 1.73 m2) or clinically overt cardiovascular disease, who underwent cardiac computed tomographic estimation of CAC scores as part of a general health checkup in addition to completing a self-administered food frequency questionnaire. We assessed the relationship of dietary calcium and phosphorus intake and serum levels with CAC scores using both multivariate-adjusted Tobit models and multinomial logistic regression models. Neither dietary calcium nor phosphorus intake was consistently associated with CAC scores. However, the serum calcium, phosphorus, and calcium–phosphorus product levels were significantly associated with the CAC score ratios. In multivariable-adjusted models, the CAC score ratios (95% confidence intervals) comparing the highest quartiles of serum calcium, phosphorus, and calcium–phosphorus product levels to the lowest quartiles were 1.89 (1.36–2.64), 3.33 (2.55–4.35), and 3.98 (3.00–5.28), respectively (P for trend <0.001). Conclusions— Elevated serum levels of calcium, phosphorus, and calcium–phosphorus product, but not dietary consumption, are associated with increased CAC scores. Our findings should be explored in further research.