The Damaging Outcome of the POLAR Phase III Trials Was Due to Avoidable Time-Dependent Redox Interaction between Oxaliplatin and PledOx

On 2 July 2021, highly negative results were reported from the POLAR A and M phase III trials in patients with colorectal cancer, treated with an oxaliplatin-based regimen and co-treated with calmangafodipir (CaM; PledOx®; PledPharma AB/Egetis Therapeutics AB) or placebo. The results revealed persistent chemotherapy-induced peripheral neuropathy (CIPN) in 54.8% of the patients treated with PledOx, compared with 40.0% of the patients treated with the placebo (p < 0.05), i.e., a 37% increase in incidence of the side effect that the trial was aimed to prevent. The damaging outcome of the trials differed diametrically from an in-parallel conducted mice study and from a clinical trial with mangafodipir, the active ingredient of CaM. According to the authors of the POLAR report, the etiology of the profound increase in CIPN in the PledOx arm is unclear. However, these devastating effects are presumably explained by intravenous administrations of PledOx and oxaliplatin being too close in time and, thereby, causing unfavorable redox interactions between Mn2+ and Pt2−. In the mice study as well as in the preceding phase II clinical trial (PLIANT), PledOx was administered 10 min before the start of the oxaliplatin infusion; this was clearly an administration procedure, where the devastating interactions between PledOx and oxaliplatin could be avoided. However, when it comes to the POLAR trials, PledOx was administered, for incomprehensible reasons, “on Top of Modified FOLFOX6” at day one, i.e., after the two-hour oxaliplatin infusion instead of before oxaliplatin. This is a time point when the plasma concentration of oxaliplatin and Pt2+-metabolites is at its highest, and where the risk of devastating redox interactions between PledOx and oxaliplatin, in turn, is at its highest.

Morphological Studies of Composite Spin Crossover@SiO2 Nanoparticles

Spin crossover (SCO) iron (II) 1,2,4-triazole-based coordination compounds in the form of composite SCO@SiO2 nanoparticles were prepared using a reverse microemulsion technique. The thickness of the silica shell and the morphology of the as obtained core@shell nanoparticles were studied by modifying the polar phase/surfactant ratio (ω), as well as the quantity and the insertion phase (organic, aqueous and micellar phases) of the tetraethylorthosilicate (TEOS) precursor, the quantity of ammonia and the reaction temperature. The morphology of the nanoparticles was monitored by transmission electron microscopy (TEM/HRTEM) while their composition probed by combined elemental analyses, thermogravimetry and EDX analyses. We report that not only the particle size can be controlled but also the size of the silica shell, allowing for interesting perspectives in post-synthetic modification of the shell. The evolution of the spin crossover properties associated with the change in morphology was investigated by variable temperature optical and magnetic measurements.

Potential of X-band polarimetric SAR co-polar phase difference for Arctic snow depth estimation

Changes in snowpack associated with climatic warming has drastic impacts on surface energy balance in the cryosphere. Yet, traditional monitoring techniques, such as punctual measurements in the field, do not cover the full snowpack spatial and temporal variability, which hampers efforts to upscale measurements to the global scale. This variability is one of the primary constraints in model development. In terms of spatial resolution, active microwaves (synthetic aperture radar—SAR) can address the issue and outperform methods based on passive microwaves. Thus, high spatial resolution monitoring of snow depth (SD) would allow for better parameterization of local processes that drive the spatial variability of snow. The overall objective of this study is to evaluate the potential of the TerraSAR-X (TSX) SAR sensor and the wave co-polar phase difference (CPD) method for characterizing snow cover at high spatial resolution. Consequently, we first (1) quantified the spatio-temporal variability of the geophysical properties of the snowpack in an Arctic catchment, we then (2) studied the links between snow properties and CPD, considering ground vegetation. Snow depth (SD) could be extracted using the CPD when certain conditions are met. A high incidence angle (> 30°) with a high Topographic Wetness Index (TWI) (> 7.0) showed correlation between SD and CPD (R-squared up to 0.72). Further, future work should address a threshold of sensitivity to TWI and incidence angle to map snow depth in such environments and assess the potential of using interpolation tools to fill in gaps in SD information on drier vegetation types.

In Vitro Cell Interactions on PVDF Films: Effects of Surface Morphology and Polar Phase Transition

In recent years, several studies have validated the use of piezoelectric materials for in situ biological stimulation, opening new interesting insights for bio-electric therapies. In this work, we investigate the morphological properties of polyvinylidene fluoride (PVDF) in the form of microstructured films after temperature-driven phase transition. The work aims to investigate the correlations between morphology at micrometric (i.e., spherulite size) and sub-micrometric (i.e., phase crystallinity) scale and in vitro cell response to validate their use as bio-functional interfaces for cellular studies. Morphological analyses (SEM, AFM) enabled evidence of the peculiar spherulite-like structure and the dependence of surface properties (i.e., intra-/interdomain roughness) upon process conditions (i.e., temperature). Meanwhile, chemical (i.e., FTIR) and thermal (i.e., DSC) analyses highlighted an influence of casting temperature and polymer solution on apolar to polar phases transition, thus affecting in vitro cell response. Accordingly, in vitro tests confirmed the relationship between micro/sub-microstructural properties and hMSC response in terms of adhesion and viability, thus suggesting a promising use of PVDF films to model, in perspective, in vitro functionalities of cells under electrical stimuli upon mechanical solicitation.

Directed synthesis of a hybrid improper magnetoelectric multiferroic material

Preparing materials which simultaneously exhibit spontaneous magnetic and electrical polarisations is challenging as the electronic features which are typically used to stabilise each of these two polarisations in materials are contradictory. Here we show that by performing low-temperature cation-exchange reactions on a hybrid improper ferroelectric material, Li2SrTa2O7, which adopts a polar structure due to a cooperative tilting of its constituent TaO6 octahedra rather than an electronically driven atom displacement, a paramagnetic polar phase, MnSrTa2O7, can be prepared. On cooling below 43 K the Mn2+ centres in MnSrTa2O7 adopt a canted antiferromagnetic state, with a small spontaneous magnetic moment. On further cooling to 38 K there is a further transition in which the size of the ferromagnetic moment increases coincident with a decrease in magnitude of the polar distortion, consistent with a coupling between the two polarisations.

Interactions of Ruddlesden-Popper Phases and Migration-Induced Field-Stabilized Polar Phase in Strontium Titanate

This work focuses on the validation of a possible connection of the known Ruddlesden-Popper (RP) phases and the novel concept of the migration-induced field-stabilized polar (MFP) phase. To study this subject, model structures of RP phases in bulk strontium titanate are analyzed by means of density functional theory (DFT). The obtained geometries are compared to experimental MFP data. Good agreement can be found concerning atomic displacements in the pm range and lattice strain inferred by the RP phases. Looking at the energy point of view, the defect structures are on the convex hull of the Gibb’s free energy. Although the dynamics to form the discussed defect models are not addressed in detail, the interplay and stability of the described defect model will add to the possible structure scenarios within the near-surface region of strontium titanate. As a result, it can be suggested that RP phases generally favor the MFP formation.

Stabilization of Ferroelectric Phase in Highly Oriented Quinuclidinium Perrhenate (HQReO4) Thin Films

The low-temperature processability of molecular ferroelectric (FE) crystals makes them a potential alternative for perovskite oxide-based ferroelectric thin films. Quinuclidinium perrhenate (HQReO4) is one such molecular FE crystal that exhibits ferroelectricity when crystallized in an intermediate temperature phase (ITP). However, bulk HQReO4 crystals exhibit ferroelectricity only for a narrow temperature window (22 K), above and below which the polar phase transforms to a non-FE phase. The FE phase or ITP of HQReO4 should be stabilized in a much wider temperature range for practical applications. Here, to stabilize the FE phase (ITP) in a wider temperature range, highly oriented thin films of HQReO4 were prepared using a simple solution process. A slow evaporation method was adapted for drying the HQReO4 thin films to control the morphology and the temperature window. The temperature window of the intermediate temperature FE phase was successfully widened up to 35 K by merely varying the film drying temperature between 333 and 353 K. The strategy of stabilizing the FE phase in a wider temperature range can be adapted to other molecular FE materials to realize flexible electronic devices.