Future of Telemedicine in Radiation Oncology.

Telemedicine allows providers and patients to communicate without being in the same room through video platforms or telephone. Like the increased use of telework for businesses, telemedicine exploded during the pandemic. While many workplaces and clinics have returned to some level of in-person interactions, the convenience and comfort have given telemedicine staying power. Patients can be seen from the comfort of their homes; family members can join from the same or a different location. Driving, obtaining childcare, or taking time off from work is unnecessary. Pediatric patients' parents can pull them into the conversation at appropriate times and avoid the awkwardness of having them leave for portions of the discussion. Because virtual visits are more efficient for everyone, they can often be scheduled sooner than an in-person visit. While not every visit can be done without the patient physically with the provider, many can. This is particularly true for cancer patients, who often have several visits with multiple providers. For immunocompromised patients, there is an added benefit of avoiding exposure from travel and a hospital visit. Oncology and radiation oncology practices have widely adopted telemedicine. While legal and logistical barriers exist in some areas of the world, these are sure to be resolved to make this medicine feasible for all in the modern era.

Additional consensus recommendations for conducting complex innovative trials of oncology agents: a post-pandemic perspective.

In our 2020 consensus paper, we devised ten recommendations for conducting Complex Innovative Design (CID) trials to evaluate cancer drugs. Within weeks of its publication, the UK was hit by the first wave of the SARS-CoV-2 pandemic. Large CID trials were prioritised to compare the efficacy of new and repurposed COVID-19 treatments and inform regulatory decisions. The unusual circumstances of the pandemic meant studies such as RECOVERY were opened almost immediately and recruited record numbers of participants. However, trial teams were required to make concessions and adaptations to these studies to ensure recruitment was rapid and broad. As these are relevant to cancer trials that enrol patients with similar risk factors, we have added three new recommendations to our original ten: employing pragmatism such as using focused information sheets and collection of only the most relevant data; minimising negative environmental impacts with paperless systems; and using direct-to-patient communication methods to improve uptake. These recommendations can be applied to all oncology CID trials to improve their inclusivity, uptake and efficiency. Above all, the success of CID studies during the COVID-19 pandemic underscores their efficacy as tools for rapid treatment evaluation.

Innovative Drying Technologies for Biopharmaceuticals.

In the past two decades, biopharmaceuticals have been a breakthrough in improving the quality of lives of patients with various cancers, autoimmune, genetic disorders etc. With the growing demand of biopharmaceuticals, the need for reducing manufacturing costs is essential without compromising on the safety, quality, and efficacy of products. Batch Freeze-drying is the primary commercial means of manufacturing solid biopharmaceuticals. However, Freeze-drying is an economically unfriendly means of production with long production cycles, high energy consumption and heavy capital investment, resulting in high overall costs. This review compiles some potential, innovative drying technologies that have not gained popularity for manufacturing parenteral biopharmaceuticals. Some of these technologies such as Spin-freeze-drying, Spray-drying, Lynfinity® Technology etc. offer a paradigm shift towards continuous manufacturing, whereas PRINT® Technology and MicroglassificationTM allow controlled dry particle characteristics. Also, some of these drying technologies can be easily scaled-up with reduced requirement for different validation processes. The inclusion of Process Analytical Technology (PAT) and offline characterization techniques in tandem can provide additional information on the Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) during biopharmaceutical processing. These processing technologies can be envisaged to increase the manufacturing capacity for biopharmaceutical products at reduced costs.

Effective delivery of Complex Innovative Design (CID) cancer trials-A consensus statement.

The traditional cancer drug development pathway is increasingly being superseded by trials that address multiple clinical questions. These are collectively termed Complex Innovative Design (CID) trials. CID trials not only assess the safety and toxicity of novel anticancer medicines but also their efficacy in biomarker-selected patients, specific cancer cohorts or in combination with other agents. They can be adapted to include new cohorts and test additional agents within a single protocol. Whilst CID trials can speed up the traditional route to drug licencing, they can be challenging to design, conduct and interpret. The Experimental Cancer Medicine Centres (ECMC) network, funded by the National Institute for Health Research (NIHR), Cancer Research UK (CRUK) and the Health Boards of Wales, Northern Ireland and Scotland, formed a working group with relevant stakeholders from clinical trials units, the pharmaceutical industry, funding bodies, regulators and patients to identify the main challenges of CID trials. The working group generated ten consensus recommendations. These aim to improve the conduct, quality and acceptability of oncology CID trials in clinical research and, importantly, to expedite the process by which effective treatments can reach cancer patients.

Formulation and characterisation of dissolving microneedles for the transdermal delivery of therapeutic peptides.

The highly effective barrier properties of the stratum corneum (SC) limit the application of transdermal delivery to relatively small, lipophilic molecules. Microneedles (MNs) however, offer a route to effectively deliver a wide range of pharmaceuticals through the skin, bypassing the SC in a non-invasive and pain-free manner. This study presents a dissolving MN system composed of polyvinylpyrrolidone (PVP) and trehalose to encapsulate active pharmaceutical peptides within the MN matrix. Rapid systemic delivery is then achieved once the needles have penetrated the SC and dissolved in the interstitial fluid of the skin. A variety of characterisation techniques were carried out to determine the optimum formulation. A model peptide, polymyxin B, was then incorporated into the MN system and delivered through porcine skin. In addition, the activity of the model drug was monitored during all stages of the formulation process.

Development of a novel antimicrobial seaweed extract-based hydrogel wound dressing.

The objective of this study was to develop a novel antimicrobial seaweed wound dressing. The seaweed extract was active against nine clinically-relevant wound pathogens. A hydrogel formulation was prepared using polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), followed by addition of 1% seaweed extract. The antimicrobial properties of the novel dressing were tested using agar diffusion assays, with release-profiles examined using gel leaching and gel transfer assays. The dressing was found to be effective against the same microbial strains as the seaweed extract, with similar efficacy to the commonly used silver-based dressing, Acticoat(®). Antimicrobial release-profile assays revealed that the dressing was effective in inhibiting 70-90% of the bacterial population within the first 30 min, followed by a long, sustained released up to 97 h, without leaving a residue following five subsequent transfers of the dressing. Antimicrobial activity was stable for up to 6 months of storage at 4 °C, but activity was reduced slightly after 15 weeks. Following autoclave sterilization, the dressing displayed a slower release profile compared to a non-autoclaved counterpart. Hence, the seaweed dressing may have commercial applications, potentially competing with silver-based dressings at a lower cost per-application. This is the first report of development of a seaweed-based antimicrobial dressing.

Photoinduced ligand isomerisation in a pyrazine-containing ruthenium polypyridyl complex.

Photochemically-induced ligand rearrangements for the N2 and N4 coordination isomers of the complex [Ru(bpy)(2)(Hpztr)](2+) and its deprotonated analogue [Ru(bpy)(2)(pztr)](+), where bpy is 2,2'-bipyridyl and Hpztr is pyrazine-1,2,4-triazole ligand, are reported. (1)H NMR spectroscopic and HPLC studies indicate that in acetone and acetonitrile the complexes are photostable when the triazole ring is deprotonated. Irradiation of the protonated N2 isomer in acetone results in formation of the N4 isomer, with the N4 isomer being photostable. In acetonitrile both isomers show photolability of the triazole-based ligand and full dissociation to form [Ru(bpy)(2)(CH(3)CN)(2)](2+) is observed. The activation parameters for the population of the (3)MC state from the lowest (3)MLCT manifold, as obtained from temperature-dependent emission lifetime studies, are reported and their relevance to the observed photochemical behaviour is considered. The results obtained are discussed in relation the analogous pyridine-triazole complexes.

Specificity of cytoplasmic dynein subunits in discrete membrane-trafficking steps.

The cytoplasmic dynein motor complex is known to exist in multiple forms, but few specific functions have been assigned to individual subunits. A key limitation in the analysis of dynein in intact mammalian cells has been the reliance on gross perturbation of dynein function, e.g., inhibitory antibodies, depolymerization of the entire microtubule network, or the use of expression of dominant negative proteins that inhibit dynein indirectly. Here, we have used RNAi and automated image analysis to define roles for dynein subunits in distinct membrane-trafficking processes. Depletion of a specific subset of dynein subunits, notably LIC1 (DYNC1LI1) but not LIC2 (DYNC1LI2), recapitulates a direct block of ER export, revealing that dynein is required to maintain the steady-state composition of the Golgi, through ongoing ER-to-Golgi transport. Suppression of LIC2 but not of LIC1 results in a defect in recycling endosome distribution and cytokinesis. Biochemical analyses also define the role of each subunit in stabilization of the dynein complex; notably, suppression of DHC1 or IC2 results in concomitant loss of Tctex1. Our data demonstrate that LIC1 and LIC2 define distinct dynein complexes that function at the Golgi versus recycling endosomes, respectively, suggesting that functional populations of dynein mediate discrete intracellular trafficking pathways.