Significance: The Centers for Disease Control and Prevention has recently reported an increasing number of clinically cases of lung injury following use of vaping products. The cause(s) of this growing epidemic of vaping-associated pulmonary injury remain unidentified, although vitamin E acetate has been identified as one possible causative agent. In this research, a combined analytical, theoretical, and experimental study has shown that the vaping of vitamin E acetate has the potential to produce exceptionally toxic ketene gas, which may be a contributing factor to the upsurge in lung injuries associated with vaping products. Our important results will help inform medical practitioners, research scientists, and the public, which may assist in bringing this medical crisis under control.

The use of NIR-fluorescence imaging to demarcate tumour boundaries for real-time guidance of their surgical resection has a huge untapped potential. However, fluorescence imaging using molecular fluorophores, even with a targeting biomolecule attached, has a major shortcoming of signal interference from non-specific background fluorescence outside the region of interest. This poor selectivity necessitates prolonged time delays to allow clearance of background fluorophore and retention within the tumour prior to image acquisition. In this report, an innovative approach to overcome this issue is described in which cancer targeted off to on bio-responsive NIR-fluorophores are utilised to switch-on first within the tumour. Bio-responsive cRGD, iRGD and PEG conjugates have been synthesised using activated ester/amine or maleimide/thiol couplings to link targeting and fluorophore components. Their off to on emission responses were measured and compared with an always-on non-responsive control with each bio-responsive derivative showing large fluorescence enhancement values. Live cell imaging experiments using metastatic breast cancer cells confirmed in vitro bio-responsive capabilities. An in vivo assessment of MDA-MB 231 tumour imaging performance for bio-responsive and always-on fluorophores was conducted with monitoring of fluorescence distributions over 96 h. As anticipated, the always-on fluorophore gave an immediate, non-specific and very strong emission throughout whereas the bio-responsive derivatives initially displayed very low fluorescence. All three bio-responsive derivatives switched on within tumours at time points consistent with their conjugated targeting groups. cRGD and iRGD conjugates both had effective tumour turn-on in the first hour, though the cRGD derivative had superior specificity for tumour over the iRGD conjugate. The pegylated derivative had similar switch-on characteristics but over a much longer period, taking 9 h before a significant emission was observable from the tumour. Evidence for in vivo active tumour targeting was obtained for the best performing cRGD bio-responsive NIR-AZA derivative from competitive binding studies. Overall, this cRGD-conjugate has the potential to overcome the inherent drawback of targeted always-on fluorophores requiring prolonged clearance times and shows excellent potential for clinical translation for intraoperative use in fluorescence guided tumour resections.

Glioblastoma (GBM) is the most aggressive adult brain tumour with a dismal 2-year survival rate of 26–33%. Maximal safe resection plays a crucial role in improving patient progression-free survival (PFS). Neurosurgeons have the significant challenge of delineating normal tissue from brain tumour to achieve the optimal extent of resection (EOR), with 5-Aminolevulinic Acid (5-ALA) the only clinically approved intra-operative fluorophore for GBM. This review aims to highlight the requirement for improved intra-operative imaging techniques, focusing on fluorescence-guided imaging (FGS) and the use of novel dyes with the potential to overcome the limitations of current FGS. The review was performed based on articles found in PubMed an.d Google Scholar, as well as articles identified in searched bibliographies between 2001 and 2022. Key words for searches included ‘Glioblastoma’ + ‘Fluorophore’+ ‘Novel’ + ‘Fluorescence Guided Surgery’. Current literature has favoured the approach of using targeted fluorophores to achieve specific accumulation in the tumour microenvironment, with biological conjugates leading the way. These conjugates target specific parts overexpressed in the tumour. The positive results in breast, ovarian and colorectal tissue are promising and may, therefore, be applied to intracranial neoplasms. Therefore, this design has the potential to produce favourable results in GBM by reducing the residual tumour, which translates to decreased tumour recurrence, morbidity and ultimately, mortality in GBM patients. Several preclinical studies have shown positive results with targeted dyes in distinguishing GBM cells from normal brain parenchyma, and targeted dyes in the Near-Infrared (NIR) emission range offer promising results, which may be valuable future alternatives.

Vaping involves the heating of chemical solutions (e-liquids) to high temperatures prior to lung inhalation. A risk exists that these chemicals undergo thermal decomposition to new chemical entities, the composition and health implications of which are largely unknown. To address this concern, a graph-convolutional neural network (NN) model was used to predict pyrolysis reactivity of 180 e-liquid chemical flavours. The output of this supervised machine learning approach was a dataset of probability ranked pyrolysis transformations and their associated 7307 products. To refine this dataset, the molecular weight of each NN predicted product was automatically correlated with experimental mass spectrometry (MS) fragmentation data for each flavour chemical. This blending of deep learning methods with experimental MS data identified 1169 molecular weight matches that prioritized these compounds for further analysis. The average number of discrete matches per flavour between NN predictions and MS fragmentation was 6.4 with 92.8% of flavours having at least one match. Globally harmonized system classifications for NN/MS matches were extracted from PubChem, revealing that 127 acute toxic, 153 health hazard and 225 irritant classifications were predicted. This approach may reveal the longer-term health risks of vaping in advance of clinical diseases emerging in the general population.