P16 and HPV Genotype Significance in HPV-Associated Cervical Cancer—A Large Cohort of Two Tertiary Referral Centers

The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; p = 0.032) were associated with better survival. HPV16 (HR: 0.63; p = 0.0174) and α-9 genera (HR: 0.57; p = 0.0286) were associated with less relapse. In the multivariate analysis, only the International Federation of Gynecology and Obstetrics (FIGO) stage retained an independent prognostic value. HPV16, α-9 genera and p16 overexpression were associated with better survival, although not as independent prognostic factors. Patients with p16-negative HPV-associated CC were older, presented with advanced disease and had worse prognosis.     

Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms

Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PA^high, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PA^high at higher risk of progression and death.     

New and Emerging Targeted Therapies for Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease deriving from the hair follicles. The formation of inflammatory nodules, abscesses, fistulas, and sinus tracts is characterized by a large inflow of key pro-inflammatory mediators, such as IFN-γ, TNF-α, IL-1, IL-17, and IL-12/23. Adalimumab is currently the only Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved biologic therapy for moderate to severe HS in adults and adolescents. However, the long-term effectiveness of this TNF-α inhibitor in HS patients has shown to be highly variable. This review aims to review the evidence for emerging therapies that target the main pro-inflammatory cytokines in HS pathogenesis. A review of the literature was conducted, using the PubMed and Google Scholar repositories, as well as Clinicaltrials.gov. Presently, the most promising biologics in phase III trials are anti-IL-17 antibodies, secukinumab, and bimekizumab. Furthermore, an anti-IL-1 biologic, bermekimab, is currently in phase II trials, and shows encouraging results. Overall, the clinical efficacies of all new targeted therapies published up to this point are limited. More studies need to be performed to clarify the precise molecular pathology, and assess the efficacy of biological therapies for HS.     

Fuel size effect on pinewood combustion in a packed bed

In this paper, particle size effect on pinewood combustion in a stationary packed bed was investigated. Mass loss rate, temperature profile at different bed locations and gas compositions in the out-of-bed flue gases were measured at a fixed primary air flow rate. Pinewood cubes was fired with size ranging from 5 to 35 mm. A unique numerical model applicable to thermally thick particles was proposed and relevant equations were solved to simulate the non-homogeneous characteristics of the burning process. It is found that at the operating conditions of the current study, smaller particles are quicker to ignite than larger particles and have distinctive combustion stages; burning rate is also higher with smaller fuel size; and smaller fuels have a thinner reaction zone and result in both higher CO and CH₄ concentrations in the out-of-bed flue gases; on the other hand, larger particles produced a higher flame temperature and result in higher H₂ concentration in the flue gases. Larger particles also cause the combustion process becoming more transient where the burning rate varies for most part of the combustion process.     

Mathematical model of gentamicin sulfate release from a bioactive textile material as a transdermal system under in vitro conditions

A mathematical model was developed to estimate the release of gentamicin sulfate from a bioactive textile material as a transdermal system for wound dressing. The gentamicin sulfate released from the antibiotic/chitosan hydrogel complexes was measured in vitro by the Franz diffusion cell technique. The diffusive transport of gentamicin sulfate through three connected compartments, that is, chitosan hydrogel, membrane, and solution, was considered by the formulation of a model based on Fick's second law. Initially, the total amount of gentamicin sulfate was placed within an already swollen chitosan hydrogel. The value of the diffusivity coefficient of the drug through the chitosan hydrogel was calculated for every initial amount of the active substance. For the initial concentration of gentamicin sulfate, which was lower than 2.81 × 10⁴ μg/mL, the diffusion coefficient was approximately constant. A higher amount of gentamicin sulfate in the hydrogel reduced its own transport as a consequence of an increase in the intensity of the interaction field between the molecules of gentamicin sulfate. The model provides the possibility of optimizing the process of drug release by ensuring a compromise between a higher value of the diffusivity coefficient and a desirable amount of gentamicin sulfate and a constant concentration within the solution over 48 h. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Fluorine containing self‐crosslinking acrylic latexes with reduced flammability and their application as polymer binders for heterogeneous cation‐exchange membranes

In this study, self‐crosslinking core–shell latexes comprising copolymerized perfluorethyl groups and a novel flame retardant based on phosphazene derivative were prepared by the semi‐continuous non‐seeded emulsion polymerization of 2,2,2‐trifluorethyl methacrylate, methyl methacrylate, butyl acrylate, methacrylic acid, and hexaallylamino‐cyclo‐triphosphazene as main monomers. For interfacial crosslinking, diacetone acrylamide was copolymerized into the shell layer of latex particles to provide sites for subsequent reaction with adipic acid dihydrazide. The heterogeneous cation‐exchange membranes were obtained by dispersing commercial strong acid cation‐exchange resin powder in the latex binder and casting the mixture followed by keto‐hydrazide crosslinking reaction. It was found that the increased concentration of fluorine atoms and phosphazene units in the macromolecular structure of interfacially crosslinked emulsion polymers resulted in a significant enhancement of their flame resistance and shape stability in aqueous environment. Moreover, the easily prepared heterogeneous cation‐exchange membranes based on latexes with higher amounts of fluorine and phosphazene units were shown to exhibit satisfactory physicochemical and electrochemical properties. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45467.     

Trace metals in the marine bivalve Macoma balthica in the westerschelde estuary, The Nertherlands. Part 3: Variability of the role of cytosol in metal uptake by the clams

Tellinid clams Macoma balthica were sampled every 2 months for 2.5 years at two locations from the Westerschelde estuary (The Netherlands) and submitted to in vitro short-term exposure to Cd, Cu and Zn. Total and heat-stable cytosolic metal concentrations have been measured before and after exposure to study the effects of the sampling season on metal uptake by the bivalve. We observed much higher uptakes of Cd and, to a lesser extent, Cu in winter than in summer, while Zn appears to be constantly regulated. These phenomena are amplified in the cytosol, especially for Cd, a non-essential element, for which the concentrations after exposure can reach 35–45 μg·g⁻¹ (dry wt.) in winter, but only a maximum of 0.5 μg·g⁻¹ in summer, all natural values being between 0.01 and 0.1 μg·g⁻¹ on average. The contents (μg) of the various elements, either at the total or at the cytosolic level, are not constant, hence showing that the seasonal body weight fluctuation of the clams (dilution or concentration effect) is not the only parameter responsible for the metal uptake variability. Furthermore, we have shown that the proportion of cytosolic metal is not constant, but increases with the absolute cytosolic concentration up to 35–40. Therefore, the cytosolic phase of the cells plays a growing role in Cd, Cu and Zn storage as long as their total concentration increases.     

Pelletised fuel production from coal tailings and spent mushroom compost – Part II. Economic feasibility based on cost analysis

Due to the growing market for sustainable energy, in order to increase the quality of the fuels, pellets are being produced from various materials such as wood and other biomass energy crops, and municipal waste. This paper presents the results from an economic feasibility study for pellet production using blends of two residue materials: coal tailings from coal cleaning and spent mushroom compost (SMC) from mushroom production. Key variables such as the mixture composition, raw material haulage and plant scale were considered and the production costs were compared to coal and biomass energy prices. For both wet materials, the moisture content was the critical parameter that influenced the fuel energy costs. The haulage distance of the raw materials was another factor that can pose a high risk. The results showed that the pellet production from the above two materials can be viable when a less energy-intensive drying process is utilised. Potential market outlets and ways to lower the costs are also discussed in this paper.