Association between Changes in the Patterns of Antinuclear Autoantibodies during Immune Checkpoint Inhibition Therapy and the Development of Severe Immune Related Adverse Events

Immune-related adverse events (irAEs) are unpredictable autoimmune-like toxicities induced by immune checkpoint inhibitors (ICI). irAEs are a consequence of a breakdown in self-tolerance. ICIs can induce autoantibody formation, and the presence of antinuclear autoantibodies (ANAs) has been reported in patients who developed irAEs. Our goal was to compare ANA patterns by indirect immunofluorescence at different timepoints before (baseline) and after the initiation of ICI treatment and to analyze the role of ANA pattern changes as predictors of irAEs. This is a 2-year-follow-up prospective study of 152 consecutive patients with solid tumors treated with anti-PD-(L)1 blockade agents. They were included from September 2018 until March 2020 in the Hospital de la Santa Creu I Sant Pau (Barcelona, Spain). We grouped patients into three groups: ANA de novo (patients who showed new ANA patterns at any time after ICI initiation), ANA (ANA positive at baseline without changes in the ANA patterns after initiation of treatment) and non-ANA (ANA negative at baseline and after ICI initiation). We did not find any association between the appearance of ANAs and irAE rates or the number and types of irAEs. However, patients in the ANA de novo group showed higher severe irAE rates (grade ≥ 3) than the other groups. Additionally, in most of the patients with severe irAEs (83.3%), changes in ANA patterns preceded irAE onset. In conclusion, we found ANA induction during ICI therapies in 22 patients and our results suggest that the appearance of ANAs may predict the severity of the irAE.     

Circulating Tumor Cells in Colorectal Cancer: Detection Systems and Clinical Utility

Colorectal cancer (CRC) is the third most common cancer worldwide. The high mortality from CRC is mainly related to metastasis affecting distant organs and their function. Dissemination of tumor cells from the primary tumor and hematogeneous spread are considered crucial in the formation of tumor metastases. The analysis of circulating tumor cells (CTCs) and CTC clusters in the blood can be used for the early detection of invasive cancer. Moreover, CTCs have a prognostic significance in the monitoring of a malignant disease or the response to chemotherapy. This work presents an overview of the research conducted on CTCs with the aim of finding suitable detection systems and assessing the possibility of clinical applications in patients with CRC.     

The NaxMnO2 materials prepared by a glycine-nitrate method as advanced cathode materials for aqueous sodium-ion rechargeable batteries

Cathodic material for sodium-ion rechargeable batteries based on Na_xMnO₂ were synthesized by glycine nitrate method and subsequent annealing at high temperatures. Different crystal structures with different morphologies were obtained depending on the annealing temperature: hexagonal layeredα-Na_0.7MnO_2.05 nanoplates were obtained at 850 °C, while 3-D tunnel structured Na_0·4MnO₂ and Na_0·44MnO₂, both with rod-like morphology, were obtained at 800 °C and 900 °C, respectively. The investigations of the electrochemical behavior of obtained cathodic materials in aqueous NaNO₃ solution have shown that Na_0·44MnO₂ obtained at 900 °C has shown the best battery performance. Its initial discharge capacities are 123.5 mA h/g, 113.2 mA h/g, and 102.0 mA h/g at the high current densities of 1000, 2000 and 5000 mA/g, respectively.     

Bubble Evolution on Different Carbon Anode Designs in Cryolite Melt

Metallurgical and Materials Transactions B - The anode potential has been shown to be highly dependent on anode geometry and orientation in the Hall–Héroult process. This work is an...     

Corrosion behaviour of steel in mortar with wood biomass ash

The present study investigates the influence of partial cement substitution with biomass ash on the corrosion behaviour of steel embedded in the mortar. To evaluate this influence, corrosion parameters of steel in mortar exposed to tap water and 3.5 wt% NaCl solution were monitored over a period of 50 days. The electrochemical cell consisted of a steel plate as a working electrode, covered with a layer of mortar that was exposed to the testing solution. Open-circuit potential and linear polarisation were used to monitor changes in corrosion behaviour, whereas electrical impedance spectroscopy was used to evaluate the conductivity of the matrix. Additional to corrosion parameters, the chloride migration coefficient was tested after 28 days. On the basis of the results, it was observed that mortars with biomass ash provide equal or better protection for embedded steel, compared with the reference mortar. Mortars that performed slightly better than the reference mortar and other mortars were prepared with ashes with a higher amount of pozzolanic oxides.     

Reduced contamination and infection via inhibition of adhesion of foodborne bacteria to abiotic polystyrene and biotic amoeba surfaces

Adhesion of foodborne pathogens to materials of industrial surfaces is an important step in their transmission through the food chain. Adhesion is also a prerequisite for bacterial colonisation within a host, to enable intracellular invasion. We define a strategy to reduce contamination and infection by Listeria monocytogenes, Campylobacter jejuni and Escherichia coli using an ethanol extract of Alpinia katsumadai seeds (AlpE) and epigallocatechin gallate (EGCG) as anti‐adhesive agents. We show for the first time that AlpE and EGCG reduce adhesion of individual cultures to polystyrene (AlpE, up to 10.6%; EGCG, up to 39.7%) and to the amoeba Acanthamoeba castellanii (AlpE, up to 52.6%; EGCG, up to 53.4%). The combination of AlpE/EGCG significantly reduced C. jejuni adherence to the abiotic (45.5%) and biotic (52.2%) surfaces. Thus, using natural agents from plants at low doses, we can potentially reduce the primary source of food contamination and a frequent source of infections.     

eIF3a Destabilization and TDP-43 Alter Dynamics of Heat-Induced Stress Granules

Stress granules (SGs) are membrane-less assemblies arising upon various stresses in eukaryotic cells. They sequester mRNAs and proteins from stressful conditions and modulate gene expression to enable cells to resume translation and growth after stress relief. SGs containing the translation initiation factor eIF3a/Rpg1 arise in yeast cells upon robust heat shock (HS) at 46 °C only. We demonstrate that the destabilization of Rpg1 within the PCI domain in the Rpg1-3 variant leads to SGs assembly already at moderate HS at 42 °C. These are bona fide SGs arising upon translation arrest containing mRNAs, which are components of the translation machinery, and associating with P-bodies. HS SGs associate with endoplasmatic reticulum and mitochondria and their contact sites ERMES. Although Rpg1-3-labeled SGs arise at a lower temperature, their disassembly is delayed after HS at 46 °C. Remarkably, the delayed disassembly of HS SGs after the robust HS is reversed by TDP-43, which is a human protein connected with amyotrophic lateral sclerosis. TDP-43 colocalizes with HS SGs in yeast cells and facilitates cell regrowth after the stress relief. Based on our results, we propose yeast HS SGs labeled by Rpg1 and its variants as a novel model system to study functions of TDP-43 in stress granules disassembly.