Testing EGFR with Idylla on Cytological Specimens of Lung Cancer: A Review

The current standard of care for advanced non-small-cell lung cancer is based on detecting actionable mutations that can benefit from targeted therapy. Comprehensive genetic tests can have long turn-around times, and because EGFR mutations are the most prevalent actionable mutation, a quick detection would enable a prompt initiation of targeted therapy. Furthermore, the scarcity of diagnostic material means that sometimes only cytologic material is available. The Idylla™ EGFR assay is a real-time PCR–based method able to detect 51 EGFR mutations in 2.5 h. Idylla is validated for use only on FFPE sections, but some researchers described their experiences with cytological material. We reviewed the relevant literature, finding four articles describing 471 cases and many types of cytological input material: smears, cell-block sections, suspensions, and extracted DNA. The sensitivity, specificity, and limit of detection appear comparable to those obtained with histological input material, with one exception: the usage of scraped stained smears as input may reduce the accuracy of the test. In conclusion, usage of cytological material as input to the Idylla EGFR test is possible. A workflow where common mutations are tested first and fast, leaving rarer mutations for subsequent comprehensive profiling, seems the most effective approach.     

Notch Signaling Regulation in Autoinflammatory Diseases

Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders.     

Crystallization of 2D Hybrid Organic–Inorganic Perovskites Templated by Conductive Substrates

2D hybrid organic–inorganic perovskites are valued in optoelectronic applications for their tunable bandgap and excellent moisture and irradiation stability. These properties stem from both the chemical composition and crystallinity of the layer formed. Defects in the lattice, impurities, and crystal grain boundaries generally introduce trap states and surface energy pinning, limiting the ultimate performance of the perovskite; hence, an in-depth understanding of the crystallization process is indispensable. Here, a kinetic and thermodynamic study of 2D perovskite layer crystallization on transparent conductive substrates are provided—fluorine-doped tin oxide and graphene. Due to markedly different surface structure and chemistry, the two substrates interact differently with the perovskite layer. A time-resolved grazing-incidence wide-angle X-ray scattering (GIWAXS) is used to monitor the crystallization on the two substrates. Molecular dynamics simulations are employed to explain the experimental data and to rationalize the perovskite layer formation. The findings assist substrate selection based on the required film morphology, revealing the structural dynamics during the crystallization process, thus helping to tackle the technological challenges of structure formation of 2D perovskites for optoelectronic devices.     

Conditioning of Rh/α-Al2O3 catalysts for H2 production via CH4 partial oxidation at high space velocity

Experimental evidence and literature indications suggest that the process of methane partial oxidation over Rh catalysts is structure sensitive. Crystal phases and Rh cluster size are thus expected to affect the final catalytic performance. In this work, it is observed that outstanding performances are obtained when the as-prepared catalysts are conditioned through repeated runs at increasing temperature and O₂/CH₄ = 0.56. Catalysts slowly activate, that is CH₄ conversion and synthesis gas selectivity progressively grow with time on stream. On the basis of TPO and CH₄ decomposition measurements, this phenomenon is herein explained as the result of a surface reconstruction driven by the repeated exposition to the reaction at high temperature; it is thought that such reconstruction tends to eliminate defect sites and disfavors C-deposition reactions (extremely fast over steps and kinks). Conditioning with O₂-enriched feed streams makes conditioning faster, since the accumulation of surface C-species is suppressed; however, the catalyst is eventually less active than a catalyst conditioned with standard feed mixtures. As an alternative, accumulation of carbon can be suppressed and surface reconstruction proceeds faster if the catalyst is directly exposed to the reaction at high temperature for several hours.     

How to control the selectivity in the reduction of NOx with H2 over Pt-Ba/Al2O3 Lean NOx Trap catalysts

The reduction process of NO_x species stored over Pt-Ba/Al₂O₃ Lean NO_x Trap systems is analysed in this paper when H₂ is used as a reductant. The effect of different experimental conditions (temperature, reductant concentration, adsorption lengths, etc.) is addressed and discussed in relation to the selectivity and the efficiency of the reduction process.     

Transient kinetic study of the SCR-DeNOx reaction

The unsteady-state kinetics of the selective catalytic reduction (SCR) of NO with NH₃ is studied over V₂O₅–WO₃/TiO₂ model catalysts by means of the transient response method. NH₃ strongly adsorbs onto the catalyst surface whereas NO does not adsorb appreciably. A dynamic mathematical model based on a Temkin-type desorption process for NH₃ and a SCR reaction rate with a complex dependence on the ammonia surface coverage is well suited to represent the data.     

Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment.     

Impact of fluorinated vinylene units on supramolecular organization and optical properties of poly(p-phenylenedifluorovinylene) thin films as a class of blue band gap conjugated polymers

This study is an investigation on the interplay between supramolecular organization and optical properties of thin films of conjugated polymers with fluorinated vinylene units such as poly[2-(2-ethylhexyloxy)-5-methoxy]-1,4-phenylenedifluorovinylene (MEH-PPDFV) and poly(2-methoxy-5-propyloxysulfonatephenylenedifluorovinylene) (MPS-PPDFV), which are both PPV polymers with fluorinated double bonds with alkoxy chains in the 2 and 5 positions. MEH-PPDFV is the fluorinated version of the widely investigated MEH-PPV, and MPS-PPDFV is characterized by the presence of ionic alkoxy side chains. This interplay is elucidated exploiting atomic force microscopy, spectroscopic ellipsometry and photoluminescence to obtain complementary information. It is demonstrated that the presence of F-atoms in the vinylene units of the MEH-PPDFV yields a blue optical band gap with the maximum of the fundamental HOMO-LUMO transition and of the room temperature photoluminescence at 3.74 eV (331 nm) and at 2.71 eV (458 nm), respectively. The blue-absorption and emission in the thin films are ascribed to the fact that fluorine atoms on the vinylene units prevent π-stacking of polymeric chains. Furthermore, the dependence of morphology, anisotropy in optical properties and photoluminescence properties of films on deposition methodology is also discussed. MEH-PPDFV also emits homogeneous blue-greenish electroluminescence at 2.46 eV (504 nm).     

Modal and stress analysis of gear train design in portal axle using finite element modeling and simulation

The portal axle is a gearbox that is specially designed for off-road driving conditions. It is installed between the wheel and the axle shaft to give higher ground clearance to the vehicle. The modeling and simulation of spur gears in portal axle is important to predict the actual motion behavior. However, gear train design in portal axle is difficult to study comprehensively due to their relatively low cost and short product life cycle. In this study, modal analysis of portal axle is simulated using finite element method (FEM). Modal analysis is simulated on three different combinations of gear train system commonly designed for portal axle. The three gear trains being analyzed are gear train without idler gear, one idler gear and two idler gears. FEM static stress analysis is also simulated on three different gear trains to study the gear teeth bending stress and contact stress behavior of the gear trains in different angular positions from 0° to 18°. The single and double pair gear teeth contact are also considered. This methodology serves as a novel approach for gear train design evaluation, and the study of gear stress behavior in gear train which is needed in the small workshop scale industries.