A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma

Malignant pleural mesothelioma remains difficult to treat, with high failure rates despite optimal therapy. We present a novel prospective trial combining proton therapy (PT) and photodynamic therapy (PDT) and the largest‐ever mesothelioma PT experience (n = 10). PDT photosensitizers included porfimer sodium (2 mg·kg^?1; 24 h drug‐light interval) or 2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide‐a (HPPH) (4 mg·m^?2;48 h) with wavelengths of 630 nm to 60J·cm^?2 and 665 nm to 15‐45J·cm^?2, respectively. With a median age of 69 years, patients were predominantly male (90%) with epithelioid histology (100%) and stage III‐IV disease (100%). PT was delivered to a median of 55.0 CGE/1.8‐2.0 CGE (range 50–75 CGE) adjuvantly (n = 8) or as salvage therapy (n = 2) following extended pleurectomy/decortication (ePD)/PDT. Two‐year local control was 90%, with distant and regional failure rates of 50% and 30%, respectively. All patients received chemotherapy, and four received immunotherapy. Surgical complications included atrial fibrillation (n = 3), pneumonia (n = 2), and deep vein thrombosis (n = 2). Median survival from PT completion was 19.5 months (30.3 months from diagnosis), and 1‐ and 2‐year survival rates were 58% and 29%. No patient experienced CTCAEv4 grade ≥2 acute or late toxicity. Our prolonged survival in very advanced‐stage patients compares favorably to survival for PT without PDT and photon therapy with PDT, suggesting possible spatial or systemic cooperativity and immune effect.     

Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes

In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d -enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.     

Exploring the state of science stereotypes: Systematic review and meta-analysis of the Draw-A-Scientist Checklist

This systematic review and meta-analysis examined recent articles that have used the 1995 Draw-A-Scientist Checklist (DAST-C). This study was focused on the current state of students' stereotypes of scientists and the appropriateness of the DAST-C as a tool to assess these perceptions. Articles included in the review were published between 2003 and 2018, resulting in n = 30 studies. Mean results across studies are presented to describe current stereotypes of scientists, and the current format of the DAST-C is evaluated. Findings suggest that students' perceptions of scientists have largely remained consistent across time: scientists are still perceived as Caucasian, middle-aged or elderly males who wear lab coats and work indoors. However, while the DAST-C is a generally appropriate measure to assess students' perceptions of scientists, recommended revisions to the DAST-C could assist in capturing more modern scientist stereotypes and culturally bound perceptions of scientists.     

Photodegradation actuated shape-changing hydrogels

Hydrogels are attractive materials for generating 4D shapes due to their ability to undergo pronounced volume changes in response to several stimuli, including light. We previously reported shape-changing hydrogels actuated by long-wave UV and visible light in the presence of live cells using poly(ethylene glycol) macromers incorporating different photodegradable ortho-nitrobenzyl (o-NB) groups. In this comprehensive study, we determine the effect of chemical structure of different o-NB macromers (which influences molar absorptivity and rate constant of degradation), composition (macromer weight percent), fabrication design (initial gel thickness) and environment (ionic strength of solution) on light-induced hydrogel folding. We demonstrate successful photopolymerization and subsequent photodegradation of hydrogels, multistep folding, and live-cell encapsulation. This hydrogel system may be useful as new tool in stem cell differentiation and developmental biology research, facilitating the in vitro investigation of processes that are sensitive to both physical and temporal stimuli.     

A Computational Study of Vicinal Fluorination in 2,3‐Difluorobutane: Implications for Conformational Control in Alkane Chains

A comprehensive conformational analysis of both 2,3‐difluorobutane diastereomers is presented based on density functional theory calculations in vacuum and in solution, as well as NMR experiments in solution. While for 1,2‐difluoroethane the fluorine gauche effect is clearly the dominant effect determining its conformation, it was found that for 2,3‐difluorobutane there is a complex interplay of several effects, which are of similar magnitude but often of opposite sign. As a result, unexpected deviations in dihedral angles, relative conformational energies and populations are observed which cannot be rationalised only by chemical intuition. Furthermore, it was found that it is important to consider the free energies of the various conformers, as these lead to qualitatively different results both in vacuum and in solvent, when compared to calculations based only on the electronic energies. In contrast to expectations, it was found that vicinal syn‐difluoride introduction in the butane and by extension, longer hydrocarbon chains, is not expected to lead to an effective stabilisation of the linear conformation. Our findings have implications for the use of the vicinal difluoride motif for conformational control.