It has been shown that by using a Lagrange multiplier field to ensure that the classical equations of motion are satisfied, radiative effects beyond one-loop order are eliminated. It has also been ...shown that through the contribution of some additional ghost fields, the effective action becomes form invariant under a redefinition of field variables, and furthermore, the usual one-loop results coincide with the quantum corrections obtained from this effective action. In this paper, we consider the consequences of a gauge invariance being present in the classical action. The resulting gauge transformations for the Lagrange multiplier field as well as for the additional ghost fields are found. These gauge transformations result in a set of Faddeev–Popov ghost fields arising in the effective action. If the gauge algebra is closed, we find the Becci–Rouet–Stora–Tyutin (BRST) transformations that leave the effective action invariant.
We consider the Einstein–Cartan theory with the tetrad eμa and spin connection ωμab taken as being independent fields. Diffeomorphism invariance and local Lorentz invariance result in there being two ...distinct gauge transformations in this approach, and consequently two ghost fields arise when employing the usual Faddeev–Popov quantization procedure. Our choice of gauge fixing retains the gauge invariances of the background field. We show that the gauge algebra is closed even in the presence of torsion, and the resulting BRST invariance can be found for the effective action. We also derive the Slavnov–Taylor identities, which reflect the BRST symmetries of this theory.
•We quantized the Einstein–Cartan theory in first order form using the Faddeev–Popov procedure, modified to accommodate two gauge invariances.•We showed that the gauge algebra is closed, even in a space–time with torsion.•We obtained the BRST transformations that leave the effective action invariant.•We found the corresponding Slavnov–Taylor identities.
Chagas disease (CD) is one of the main neglected tropical diseases that promote relevant socioeconomic impacts in several countries. The therapeutic options for the treatment of CD are limited, and ...parasite resistance has been reported. Piplartine is a phenylpropanoid imide that has diverse biological activities, including trypanocidal action. Thus, the objective of the present work was to prepare a collection of thirteen esters analogous to piplartine (
-
) and evaluate their trypanocidal activity against
Of the tested analogues, compound
((
)-furan-2-ylmethyl 3-(3,4,5-trimethoxyphenyl)acrylate) showed good activity with IC
values = 28.21 ± 5.34 μM and 47.02 ± 8.70 μM, against the epimastigote and trypomastigote forms, respectively. In addition, it showed a high rate of selectivity to the parasite. The trypanocidal mechanism of action occurs through the induction of oxidative stress and mitochondrial damage. In addition, scanning electron microscopy showed the formation of pores and leakage of cytoplasmic content. Molecular docking indicated that
probably produces a trypanocidal effect through a multi-target mechanism, including affinity with proteins CRK1, MPK13, GSK3B, AKR, UCE-1, and UCE-2, which are important for the survival of the parasite. Therefore, the results suggest chemical characteristics that can serve for the development of new trypanocidal prototypes for researching drugs against Chagas disease.
The use of histamine-2 receptor antagonists (H2RA) in neonates is still debated because of possible risk of infection, necrotizing enterocolitis (NEC) and increased mortality.
To review whether the ...use of H2RA in neonates admitted to neonatal intensive care units (NICU) is associated with infection, NEC or mortality.
We performed a systematic search in PubMed, Web of Science and SCOPUS databases using the terms "histamine-2 receptor antagonists", "infection", "necrotizing enterocolitis", "mortality", "neonates" and related terms to identify studies published up to April 30, 2017. We included studies conducted in hospitalized neonates and exposed to H2RA. The primary outcomes were infection, NEC and mortality. We included reports of infections with clinical signs and positive culture, and NEC according to Bell stages (stage ≥II) based on standardised clinical and radiologic criteria. Among 1,144 studies identified, 10 fulfilled the selection criteria. Information extracted included study design, sample size and number of participants, along with the outcomes of interest. We conducted a meta-analysis of adjusted data and pooled estimates of infection, NEC and mortality are reported as odds ratios (OR) and 95% confidence intervals (95%CI).
Ten studies were analysed. There were substantial associations between H2RA and infection (pooled OR: 2.09; 95%CI: 1.35-3.24; P = 0.001) and NEC (pooled OR: 2.81, 95%CI: 1.19-6.64; P = 0.02) but not with the mortality risk (pooled OR: 1.76; 95%CI: 0.50-6.16; P: 0.38).
Current evidence suggests that H2RA is associated with an increased risk of infection and NEC, but not with mortality in neonates admitted to NICU. The use of H2RA in neonates must be stringently considered when necessary.
Aims
Metaplastic breast carcinoma (MBC) is a rare type of triple‐negative breast cancer that shows vast histological and genetic heterogeneity. Osseous differentiation can be found in different ...subtypes of MBC. Whether MBCs with osseous differentiation are underpinned by specific genetic alterations has yet to be defined. The aim of this study was to investigate the repertoire of somatic mutations and copy number alterations (CNAs) in three MBCs with extensive osseous differentiation.
Methods and results
Tumour and normal DNA samples from three MBCs with extensive osseous differentiation were subjected to whole‐exome sequencing. Somatic mutations, CNAs and mutational signatures were determined by use of a validated bioinformatics pipeline. Our analyses revealed clonal TP53 hotspot mutations associated with loss of heterozygosity of the wild‐type allele coupled with mutations affecting genes related to the Wnt and/or the phosphoinositide 3‐kinase–AKT–mammalian target of rapamycin pathways in all cases analysed. All cases showed a dominant mutational signature 1, with two cases showing a secondary signature 3 in addition to other features of homologous recombination DNA repair defects. The oncostatin M receptor gene, which plays a role in mesenchymal differentiation and bone formation, was found to be mutated in two MBCs with extensive osseous differentiation and in none of 35 previously published 35 MBCs.
Conclusion
Our findings suggest that MBCs with osseous differentiation have somatic mutations similar to those of other forms of MBC.
ABSTRACT
Astrometric studies and orbital modelling of planetary moons have contributed significantly to advancing our understanding of their orbital dynamics. These studies require precise positions ...measured over extended periods. In this paper, we present the results of the 2021 Brazilian Jovian mutual phenomena campaign. The data correspond to eight events between Galilean satellites, in addition to a rare eclipse of Thebe, an inner satellite, totalling nine events. A geometric model along with the DE440/JUP365 ephemerides was used to reproduce the events and simulate the light curves. A Monte Carlo method and chi-squared statistics were used to fit the simulated light curves to the observations. The reflectance model adopted for our simulations was the complete version of the Oren–Nayer model. The average uncertainty of the relative positions of the Galilean satellites was 5 mas (15 km) and for the inner Thebe satellite 32 mas (96 km). The seven mutual events (nine independent observations) here analysed represent an addition of 17 per cent events (10 per cent light curves) with respect to the 2021 international mutual phenomena campaign.
Furthermore, our result of Thebe eclipse is only the second measurement published to date. Our results contribute to the ephemeris data base, being fundamental to improving satellite orbits and thus minimizing their uncertainties.
The Parnaíba River is the main river in the Parnaíba Delta basin, the largest delta in the Americas. About 18 polycyclic aromatic hydrocarbons (PAHs) were identified and the environmental risk ...associated with the sediments was evaluated. The study found that PAHs levels ranged from 5.92 to 1521.17 ng g–1, which was classified as low to high pollution, and that there were multiple sources of pollution along the river, with pyrolytic sources predominating, mainly from urban activity such as trucking, although the influence of rural activity cannot be ruled out. PAHs correlated with black carbon and organic matter and showed high correlation with acenaphthylene, phenanthrene, pyrene, benzo(a)anthracene, chrysene, benzo(ghi)perylene, and ∑PAHs. The benzo(a)pyrene levels were classified as a risk to aquatic life because the threshold effect level and the probable effect level were exceeded. In addition, the sediments were classified as slightly contaminated with a benzo(a)pyrene toxicity equivalent value of 108.43 ng g–1. Thus, the priority level PAH exhibited carcinogenic and mutagenic activity that posed a potential risk to human health.
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•Unprecedented research which assessed contamination by PAHs of the main river in the Delta of the Americas.•Some 18 polycyclic aromatic hydrocarbons (PAHs) were identified.•Source characterization of PAHs showed distinct sources mainly related to urban activity, linked to pyrolytic processes.
We examine the self-consistency of the first-order formulation of the Yang-Mills theory. By comparing the generating functional Z before and after integrating out the additional field Fμνa, we derive ...a set of structural identities that must be satisfied by the Green's functions at all orders. These identities, which hold in any dimension, are distinct from the usual Ward identities and are necessary for the internal consistency of the first-order formalism. They relate the Green's functions involving the fields Fμνa, to Green's functions in the second-order formulation which contain the gluon strength tensor fμνa. In particular, such identities may provide a simple physical interpretation of the additional field Fμνa.
Aims
Breast adenomyoepitheliomas (AMEs) are uncommon tumours. Most oestrogen receptor (ER)‐positive AMEs have mutations in phosphoinositide 3‐kinase (PI3K) pathway genes, whereas ER‐negative AMEs ...usually harbour concurrent mutations affecting the HRAS Q61 hotspot and PI3K pathway genes. Here, we sought to determine the sensitivity and specificity of RAS Q61R immunohistochemical (IHC) analysis for detection of HRAS Q61R mutations in AMEs.
Methods and results
Twenty‐six AMEs (14 ER‐positive; 12 ER‐negative) previously subjected to massively parallel sequencing (n = 21) or Sanger sequencing (n = 5) of the HRAS Q61 hotspot locus were included in this study. All AMEs were subjected to IHC analysis with a monoclonal (SP174) RAS Q61R‐specific antibody, in addition to detailed histopathological analysis. Nine ER‐negative AMEs harboured HRAS mutations, including Q61R (n = 7) and Q61K (n = 2) mutations. Five of seven (71%) AMEs with HRAS Q61R mutations were immunohistochemically positive, whereas none of the AMEs lacking HRAS Q61R mutations (n = 17) were immunoreactive. RAS Q61R immunoreactivity was restricted to the myoepithelium in 80% (4/5) of cases, whereas one case showed immunoreactivity in both the epithelial component and the myoepithelial component. RAS Q61R immunohistochemically positive AMEs were associated with infiltrative borders (P < 0.001), necrosis (P < 0.01) and mitotic index in the epithelial (P < 0.05) and myoepithelial (P < 0.01) components. RAS Q61R IHC assessment did not reveal Q61K mutations (0/2).
Conclusions
IHC analysis of RAS Q61R shows high specificity (100%) and moderate sensitivity (71%) for detection of HRAS Q61R mutations in breast AMEs, and appears not to detect HRAS Q61K mutations. IHC analysis of RAS Q61R may constitute a useful technique in the diagnostic workup of ER‐negative AMEs.
Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients' quality of life, like sexual dysfunction, osteoporosis, ...weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects.
Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded.
There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy.
This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.
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