Future Perspectives in Detecting EGFR and ALK Gene Alterations in Liquid Biopsies of Patients with NSCLC

Non-small-cell lung cancer (NSCLC) is a major cause of death worldwide. Alterations in such genes as EGFR and ALK are considered important biomarkers in NSCLC due to the existence of targeted therapies with specific tyrosine kinase inhibitors (TKIs). However, specific resistance-related mutations can occur during TKI treatment, which often result in therapy inefficacy. Liquid biopsies arise as a reliable tool for the early detection of these types of alterations, allowing a non-invasive follow-up of the patients. Furthermore, they can be essential for cancer screening, initial diagnosis and to check surgery success. Despite the great advantages of liquid biopsies in NSCLC and the high input that next-generation sequencing (NGS) approaches can provide in this field, its use in oncology is still limited. With improvement of assay sensitivity and the establishment of clinical guidelines for liquid biopsy analysis, it is expected that they will be used in routine procedures. This review focuses on the usefulness of liquid biopsies of NSCLC patients as a means to detect alterations in EGFR and ALK genes and in disease management, highlighting the impact of NGS methods.     

Hydrogen production through catalytic low-temperature bio-ethanol steam reforming

As a provider of our energy requirements, hydrogen seems to be one of most promising fuels, in particular when used to feed PEM fuel cells. When produced from a renewable source, it has got the potential to reduce the dependence on non-renewable fossil fuels and lower the amount of harmful emissions. Ethanol steam-reforming (ESR) reaction is an interesting option to obtain a H₂- and CH₄-rich stream with a low content of CO, combining the deep knowledge of the technology with the advantage of the biomass-derived feedstock. Thermodynamic analysis has indicated that the most interesting operating range to enhance the H₂ production and minimize CO and coke formation requires low pressure, high temperature, and high water-to-ethanol molar ratio. On the other hand, despite its endothermic nature, ESR could be carried out at low temperature, to increase overall thermal efficiency, even if at these conditions the catalyst's deactivation, due to coking and sintering phenomena, is not negligible. The main objective of this study is to investigate on the activity, stability, and durability of bimetallic Pt–Ni and Pt–Co catalysts supported on CeO₂ for low-temperature bio-ESR reaction. The catalysts have been prepared through different methods and with an optimized metal's content. They have also been characterized with various physico-chemical characterization tests, and the catalytic studies have been carried out in a lab-scale apparatus. While evaluating the effects on the catalysts' performances of preparation method, reaction temperature, space time, and water-to-ethanol molar ratio, the selected catalysts were found effective for the production of H₂ by steam reforming at low temperature. In particular, the Pt/Ni/CeO₂ catalyst shows a perfect agreement with equilibrium calculations yet at low contact times, although some carbon deposition occurs. Also the cobalt-based catalysts appear attractive. The relative rates of carbon growth versus gasification have been studied, and ascending water contents were used to study the effect of steam addition in the feed stream. An in-depth investigation of the reaction mechanism and the evaluation of the kinetic parameters will be crucial to complete the study of the proposed process.     

Candida colonization index in patients admitted to an ICU

Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI ≥ 0.5. Three patients developed candidemia; they had CI ≥ 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients.     

Methane reforming of syngas produced by co-gasification of coal and wastes. Effect of catalysts and of experimental conditions

Syngas obtained by co-gasification of coal and wastes was hot cleaned in two catalytic reactors, which allowed destroying tar and gaseous hydrocarbons with more than one carbon atom. H₂S and NH₃ contents were also significantly reduced, but CH₄ concentrations varying between 2% and 10% and small amounts of H₂S (below 100 ppmv) were still found in syngas, depending on coal type and waste composition. This paper studies the effect of experimental conditions on CH₄ destruction by reforming reactions in absence and in presence of catalysts. The effect of experimental conditions (temperature, steam flow rate and syngas composition) on CH₄ destruction and on CO conversion into CO₂ in the absence of catalyst was studied first, using the Equilibrium Reactor model from CHEMKIN modelling software. The selected experimental conditions were then tested in a fixed bed reactor with and without catalyst and the results obtained were consistent with CHEMKIN Equilibrium Reactor model predictions. Commercial Ni-based catalysts were tested (G-90 B5 and G 56B from C&CS). These catalysts were capable of significantly reducing CH₄ content, by promoting reforming reactions. At the experimental conditions used and in absence of steam, G 56B seems to be more effective in CH₄ conversion, as lower CH₄ contents were obtained. In presence of steam both catalysts were capable of completely destroying CH₄. Both catalysts also promoted WGS (water gas shift) reaction to some extent, though they are not specific catalysts for this reaction. Thus, a high increase in H₂ content was observed, due to its formation by both reforming and WGS reactions. For a complete conversion of CO into CO₂ and H₂ a specific catalyst for WGS reaction is still needed.     

Four-Dimensional Gallant–Lambert–Vanstone Scalar Multiplication

The GLV method of Gallant, Lambert, and Vanstone (CRYPTO 2001) computes any multiple kP of a point P of prime order n lying on an elliptic curve with a low-degree endomorphism Φ (called GLV curve) over $\mathbb{F}_{p}$ as $$kP = k_1P + k_2\varPhi(P) \quad\text{with } \max \bigl\{ |k_1|,|k_2| \bigr\} \leq C_1\sqrt{n} $$ for some explicit constant C ₁>0. Recently, Galbraith, Lin, and Scott (EUROCRYPT 2009) extended this method to all curves over $\mathbb{F}_{p^{2}}$ which are twists of curves defined over $\mathbb{F}_{p}$ . We show in this work how to merge the two approaches in order to get, for twists of any GLV curve over $\mathbb{F}_{p^{2}}$ , a four-dimensional decomposition together with fast endomorphisms Φ,Ψ over $\mathbb{F}_{p^{2}}$ acting on the group generated by a point P of prime order n, resulting in a proven decomposition for any scalar k∈[1,n] given by $$kP=k_1P+ k_2\varPhi(P)+ k_3\varPsi(P) + k_4\varPsi\varPhi(P) \quad \text{with } \max_i \bigl(|k_i| \bigr)< C_2\, n^{1/4} $$ for some explicit C ₂>0. Remarkably, taking the best C ₁,C ₂, we obtain C ₂/C ₁<412, independently of the curve, ensuring in theory an almost constant relative speedup. In practice, our experiments reveal that the use of the merged GLV–GLS approach supports a scalar multiplication that runs up to 1.5 times faster than the original GLV method. We then improve this performance even further by exploiting the Twisted Edwards model and show that curves originally slower may become extremely efficient on this model. In addition, we analyze the performance of the method on a multicore setting and describe how to efficiently protect GLV-based scalar multiplication against several side-channel attacks. Our implementations improve the state-of-the-art performance of scalar multiplication on elliptic curves over large prime characteristic fields for a variety of scenarios including side-channel protected and unprotected cases with sequential and multicore execution.     

Bulky lymphadenopathy in acute myeloid leukemia

Two cases of acute myeloid leukemia (AML) presenting with bulky adenopathy are reported. Both patients were febrile at admission and showed massive and diffuse lymph node involvement, hepatomegaly, and splenomegaly. Erythematopapular leukemic skin lesions were present in one case at the onset and developed in the other at the time of relapse. Anemia, thrombocytopenia, and moderate leukocytosis were present in both. The presence of immature cells in peripheral blood and bone marrow allowed a rapid diagnosis of AML, FAB M1, in one patient. In the other case, owing to the paucity of immature cells in peripheral blood and bone marrow, lymph node biopsy with histology, imprint cytology, and immunocytochemistry were essential for the diagnosis (AML, FAB M2, with trilineage dysplasia and basophilic involvement). Both patients achieved complete remission (CR), followed by an early relapse 3 months later. They underwent allogeneic bone marrow transplantation (BMT) from HLA identical siblings. One patient is actually alive and in CR at 6 months after BMT; the other patient showed a leukemic regrowth after transplantation and died 4 months later.     

Steroid receptor enhancement by natural interferon-beta in advanced breast cancer

In the current study we investigated the effect of two different doses of natural interferon-beta (IFN-beta) on steroid hormone receptors in 45 patients with advanced breast cancer. IFN-beta seems to regulate the receptor mechanisms, inducing in cutaneous metastases an increase of oestrogen and progesterone receptors. Moreover, using IFN-beta and tamoxifen as a combined therapy in 23 receptor-positive patients, no negative interference of the two drugs was observed and no relevant side-effects due to the treatment were noticed. The modulation of steroid receptor content by IFN-beta in advanced breast cancer might represent an interesting way to ameliorate the clinical responsiveness to anti-oestrogens.     

Reproducing stone monument photosynthetic-based colonization under laboratory conditions

In order to understand the biodeterioration process occurring on stone monuments, we analyzed the microbial communities involved in these processes and studied their ability to colonize stones under controlled laboratory experiments. In this study, a natural green biofilm from a limestone monument was cultivated, inoculated on stone probes of the same lithotype and incubated in a laboratory chamber. This incubation system, which exposes stone samples to intermittently sprinkling water, allowed the development of photosynthetic biofilms similar to those occurring on stone monuments. Denaturing gradient gel electrophoresis (DGGE) analysis was used to evaluate the major microbial components of the laboratory biofilms. Cyanobacteria, green microalgae, bacteria and fungi were identified by DNA-based molecular analysis targeting the 16S and 18S ribosomal RNA genes. The natural green biofilm was mainly composed by the Chlorophyta Chlorella, Stichococcus, and Trebouxia, and by Cyanobacteria belonging to the genera Leptolyngbya and Pleurocapsa. A number of bacteria belonging to Alphaproteobacteria, Bacteroidetes and Verrucomicrobia were identified, as well as fungi from the Ascomycota. The laboratory colonization experiment on stone probes showed a colonization pattern similar to that occurring on stone monuments. The methodology described in this paper allowed to reproduce a colonization equivalent to the natural biodeteriorating process.     

Effect of catalysts in the quality of syngas and by-products obtained by co-gasification of coal and wastes. 2: Heavy metals, sulphur and halogen compounds abatement

This paper analyses the formation of sulphur and halogens compounds during co-gasification of low grade coals with different types of wastes that include: pine, petcoke and polyethylene (PE) with the aim of taking profit of waste energy value with the smallest possible impact on the environment. The influence of different types of catalysts or sorbents was studied: calcined dolomite, dolomite enriched with nickel, olivine, nickel and magnesium oxides, zinc oxide and cobalt and molybdenum oxides. The presence of dolomite led to the lowest HCl, HF and H₂S concentrations in the syngas produced. ZnO also gave rise to significant decrease in H₂S concentration, though higher concentrations were obtained than those with dolomite. It was found that when catalysts or sorbents were used, a significant fraction of sulphur, halogens and heavy metals were trapped in the solid residue left behind in the bed and cyclone. Higher temperatures increased the volatility of some metals and sulphur. Leachability assays of solids showed that small quantities of and Cl⁻ could be released and most metals were not leachable, although the use of dolomite slightly increased metals leachability, because of the higher alkaline nature of residual solids produced.