Fibronectin concentration was determined in plasma from 97 patients with benign or malignant breast disease and from 62 controls. Median plasma fibronectin concentration (microgram FN/ml plasma) ...appeared to be significantly higher in patients with non-metastatic or metastatic breast cancer as compared to age-matched controls (P less than 0.01 and P less than 0.03, respectively); however, statistical significance disappeared when results were expressed as a function of total plasma protein content (microgram FN/mg total plasma protein). In patients with benign breast disease plasma fibronectin values were not significantly different from control levels. Our data indicate that the clinical usefulness of measuring FN in breast cancer patients appears to be very limited.
The effects of tamoxifen on plasma concentration of gonadotropins, prolactin (PRL), estrone (E1), estradiol-17 beta (E2), and sex hormone-binding globulin (SHBG) were studied in 40 postmenopausal ...breast cancer patients. In addition, the changes induced by the drug on endometrium and vaginal epithelium were investigated. After 6-8 weeks of tamoxifen treatment, a significant decrease in FSH, LH and PRL basal levels was observed, whereas the concentrations of E1 and E2 were not significantly affected. A significant increase in SHBG levels was induced by prolonged treatment with the drug. In addition, tamoxifen caused a partial estrogenization of vaginal smears, and a weak stimulatory effect on endometrium was also apparent. These findings indicate that tamoxifen produced agonistic effects on some targets and antagonistic effects on the others.
This special issue entitled “Celestial Mechanics: New Discoveries and Challenges for Space Exploration” presents a series of 27 contributions. Some of them are devoted to the analysis of periodic ...orbits in the solar system and methods for identifying chaos in non-linear dynamical systems. The topic of satellite attitude determination is also covered, as well as a study of orbital manoeuvres around a large body such as Titania. Researches on near-Earth asteroids are also presented, such as transfers to orbits around the Moon for space mining; prevention of a collision of the asteroid Apophis with the Earth and a dynamical study of a disc of particles around Apophis; the dynamical evolution, fates and lifetimes, besides orbital inclination evolution of current large Near Earth Objects (NEOs). Aerospace engineering is explored through the study of periodic lift and drag on the orbit of rectangular parallelepiped satellites, and also the analysis of orbits of a satellite observing the Earth. Further theoretical work concerned the application of the theory of functional connections via the change of variables and the analysis of the linear stability of a tether system using its Hamiltonian function is analyzed in this paper. Since the number of artificial debris in the near-Earth space has increased in the last decade, this topic has become a current problem, thus discussed in details. Solar sails were also researched in detail in this special issue, for example how solar sails can help with lunar flyby maneuvers. Finally, methods for investigating extra solar planetary systems were also applied.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hundreds of new electrochemical sensors are reported in literature every year. However, only a few of them makes it to the market. Manufacturability, or rather the lack of it, is the parameter that ...dictates if new sensing technologies will remain forever in the laboratory in which they are conceived. Inkjet printing is a low‐cost and versatile technique that can facilitate the transfer of nanomaterial‐based sensors to the market. Herein, an electroactive and self‐assembling inkjet‐printable ink based on protein‐nanomaterial composites and exfoliated graphene is reported. The consensus tetratricopeptide proteins (CTPRs), used to formulate this ink, are engineered to template and coordinate electroactive metallic nanoclusters (NCs), and to self‐assemble upon drying, forming stable films. The authors demonstrate that, by incorporating graphene in the ink formulation, it is possible to dramatically improve the electrocatalytic properties of the ink, obtaining an efficient hybrid material for hydrogen peroxide (H2O2) detection. Using this bio‐ink, the authors manufactured disposable and environmentally sustainable electrochemical paper‐based analytical devices (ePADs) to detect H2O2, outperforming commercial screen‐printed platforms. Furthermore, it is demonstrated that oxidoreductase enzymes can be included in the formulation, to fully inkjet‐print enzymatic amperometric biosensors ready to use.
Herein, an electroactive and self‐assembling inkjet‐printable ink based on protein‐stabilized nanoclusters and exfoliated graphene is reported. The engineered proteins used to formulate this ink are engineered to self‐assemble upon drying, forming stable biofilms. Using this bio‐ink, the authors manufactured disposable electrochemical paper‐based analytical devices (ePADs) to detect H2O2 and glucose, characterized by low cost and reduce environmental impact.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Mood disorders (major depressive disorder, MDD, and bipolar disorder, BD) are considered leading causes of life-long disability worldwide, where high rates of no response to treatment or relapse and ...delays in receiving a proper diagnosis (~60% of depressed BD patients are initially misdiagnosed as MDD) contribute to a growing personal and socio-economic burden. The immune system may represent a new target to develop novel diagnostic and therapeutic procedures but reliable biomarkers still need to be found.
In our study we predicted the differential diagnosis of mood disorders by considering the plasma levels of 54 cytokines, chemokines and growth factors of 81 BD and 127 MDD depressed patients. Clinical diagnoses were predicted also against 32 healthy controls. Elastic net models, including 5000 non-parametric bootstrapping procedure and inner and outer 10-fold nested cross-validation were performed in order to identify the signatures for the disorders.
Results showed that the immune-inflammatory signature classifies the two disorders with a high accuracy (AUC = 97%), specifically 92% and 86% respectively for MDD and BD. MDD diagnosis was predicted by high levels of markers related to both pro-inflammatory (i.e. IL-1β, IL-6, IL-7, IL-16) and regulatory responses (IL-2, IL-4, and IL-10), whereas BD by high levels of inflammatory markers (CCL3, CCL4, CCL5, CCL11, CCL25, CCL27, CXCL11, IL-9 and TNF-α).
Our findings provide novel tools for early diagnosis of BD, strengthening the impact of biomarkers research into clinical practice, and new insights for the development of innovative therapeutic strategies for depressive disorders.
•The immune-inflammatory signature classifies BD and MDD with a high accuracy.•BD was predicted mainly by pro-inflammatory markers.•MDD was predicted by high levels of both pro-inflammatory and regulatory markers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Androgen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM ...anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223.
Patients and methods
Low-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded.
Results
SM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis.
Conclusion
The present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Growth factors and cytokines released in the lung cancer microenvironment promote an epithelial-to-mesenchymal transition (EMT) that sustains the progression of neoplastic diseases. TGF
is one of the ...most powerful inducers of this transition, as it induces overexpression of the fibronectin receptor, αvβ6 integrin, in cancer cells which, in turn, is strongly associated with EMT. Thus, αvβ6 integrin receptors may be exploited as a target for the selective delivery of anti-tumor agents. We introduce three novel synthesized conjugates, in which a selective αvβ6 receptor ligand is linked to nintedanib, a potent kinase inhibitor used to treat advanced adenocarcinoma lung cancer in clinics. The αvβ6 integrin ligand directs nintedanib activity to the target cells of the tumor microenvironment, avoiding the onset of negative side effects in normal cells. We found that the three conjugates inhibit the adhesion of cancer cells to fibronectin in a concentration-dependent manner and that αvβ6-expressing cells internalized the conjugated compounds, thus permitting nintedanib to inhibit 2D and 3D cancer cell growth and suppress the clonogenic ability of the EMT phenotype as well as intervening in other aspects associated with the EMT transition. These results highlight αvβ6 receptors as privileged access points for dual-targeting molecular conjugates engaged in an efficient and precise strategy against non-small cell lung cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The classification of grades inside a material family should be based on the properties required by design procedures. This paper proposes a reclassification of spheroidal graphite ferritic pearlitic ...and ausferritic (ADI) ductile cast irons grades based on yield strength (YS), strength ratio (SR) UTS/YS and elongation at fracture (EF). In fact, these parameters are fundamental for the static assessment according to the procedures FKM Guideline and BS 7910:2005. Static assessment at room temperature, involving plastic deformation and depending on the wall thickness and stress state triaxiality, is here proposed as the most significant for the material classification. All other properties (e.g., fatigue under cyclic loads, high strain rates and temperature effect, etc.) should be reported with reference to the classification mentioned above. SR and EF control the plastic deformation at the notch tip, where maximum calculated elastic stress is redistributed. Minimum YS is usually assumed as the basic parameter for static and cyclic loading design. Because of the inverse relationship that exists between strength and ductility, Brinell hardness control and material quality index should be adopted as Material Quality Control tools, preventing from a too low EF. Fracture Toughness and its ratio with YS must be considered for preventing brittle fracture due to the presence of flaws. Fracture toughness definitions and available data are not sufficiently consistent for a correct comparison between different material grades. A surrogate Charpy energy measurement is indicated for an indirect estimate of toughness.
The Asian citrus psyllid (ACP) Diaphorina citri Kuwayama (Hemiptera: Liviidae) is the vector of Candidatus Liberibacter spp., the bacteria associated with huanglongbing (HLB), the most devastating ...disease of citrus worldwide. HLB management has heavily relied on insecticide applications to control the ACP, although there are efforts towards more sustainable alternatives. In previous work, our group assessed the potential bioactivity of different strains of Bacillus thuringiensis (Eubacteriales: Bacillaceae) (Bt) containing cry/cyt genes as feasible tools to control ACP nymphs. Here, we report an attempt to use the cry11A gene from Bt to produce transgenic sweet orange plants using two promoters. For the genetic transformation, ‘Hamlin’ and ‘Valencia’ sweet orange seedlings were used as sources of explants. Transgenic plants were detected by polymerase chain reaction (PCR) with specific primers, and the transgene copy number was confirmed by Southern blot analyses. Transcript expression levels were determined by qPCR. Mortality assays of D. citri nymphs were carried out in a greenhouse, and the effect of the events tested ranged from 22% to 43% at the end of the five-day exposure period. To our knowledge, this is the first manuscript reporting the production of citrus plants expressing the Bt cry11A gene for the management of D. citri nymphs.
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•Transgenic citrus plants express the cry11A gene constitutively in their phloem tissues.•Moderate level of Asian citrus psyllid mortality is obtained by the Bt citrus plants.•Citrus Bt can be a tool for Asian citrus psyllid management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ClC-5 is a Cl−/H+ antiporter that functions in endosomes and is important for endocytosis in the proximal tubule. The mechanism of transport coupling and voltage dependence in ClC-5 is unclear. ...Recently, a transport-deficient ClC-5 mutant (E268A) was shown to exhibit transient capacitive currents. Here, we studied the external and internal Cl− and pH dependence of the currents of E268A. Transient currents were almost completely independent of the intracellular pH. Even though the transient currents are modulated by extracellular pH, we could exclude that they are generated by proton-binding/unbinding reactions. In contrast, the charge movement showed a nontrivial dependence on external chloride, strongly supporting a model in which the movement of an intrinsic gating charge is followed by the voltage-dependent low-affinity binding of extracellular chloride ions. Mutation of the external Glu-211 (a residue implicated in the coupling of Cl− and proton transport) to aspartate abolished steady-state transport, but revealed transient currents that were shifted by ∼150 mV to negative voltages compared to E268A. This identifies Gluext as a major component of the gating charge underlying the transient currents of the electrogenic ClC-5 transporter. The molecular events underlying the transient currents of ClC-5 emerging from these results can be explained by an inward movement of the side chain of Gluext, followed by the binding of extracellular Cl− ions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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