Biology subjects

Marshall, T.

Publications and source records attributed to Marshall, T..

3 recordsLinked to original sources

bioRxiv2024

Preliminary report on the molecular epidemiology of mpox, South Africa 2024

Mpox is an emerging viral infection and has since May 2022 been reported in a multi-country outbreak involving predominantly previously non-endemic countries. In addition, the number of cases of mpox is also rising in some endemic countries in Western and Central Africa. The disease is a notifiable medical condition in South Africa, with no cases reported before 2022. However, in 2022, coinciding with the peak of a multi-country mpox outbreak, five mpox cases were diagnosed in the country. Genomic sequencing and analysis revealed the presence of a monkeypox virus variant, which was circulating during the multi-country outbreak, namely Clade IIb sub-lineage B.1.7 (hMPXV). After the fifth case was reported in 2022, there were no cases detected for the following 20 months. In May 2024, mpox cases were again detected in South Africa leading to concerns that the virus may have been silently transmitting in the country since 2022. Genomic sequencing and analysis for 22 mpox cases reported during May to September 2024, were compared with sequences obtained from mpox cases reported in South Africa in 2022, and cases that have been reported globally. It was found that the sequences of the 2024 cases analysed in this study, clustered with Clade IIb hMPXV and sub-lineage B.1.20 and B.1.6 sequences. The results indicate that the detection of mpox cases in South Africa was an extension of the ongoing multi-country outbreak. Detection of different sub-lineages of hMPXV indicates reintroductions of the virus in the country since 2022, with local transmission of Clade IIb B1.20 hMPXV.

microbiology↗

bioRxiv2024

Combining Scalable Organ Chip Platform with Deep Learning-Based Imaging Analysis for Cancer Therapeutic Screening

Functional precision oncology represents an emerging approach to genomic approaches by testing treatment options directly on patient-derived models. Current assays, including the use of patient-derived xenograft (PDX) and patient-derived organoid (PDOs), faces major barriers in clinical use due to technical challenges, such as standardization, cost, assay time, scalability, and faithful mimicry of patient tumor microenvironment (TME). Here, we introduce an Organ Chip (OC) device constructed entirely from thermoplastic materials, free of porous membrane or other barrier structures, and optimized for high-content imaging (HCI). This automation-compatible device supports tissue-specific extracellular matrices and coculture for a wide spectrum of organ and disease types, including the TME. As a proof-of-concept, we demonstrate the growth of pancreatic, lung, and colon cancer cell lines and primary lung cancer cells and the testing of cancer drugs in these models. HCI-based phenotypic profiling enabled accurate quantification of drug response, with better performance than traditional biochemical assays. Moreover, we developed a deep-learning method for assessing drug responses using bright field images. The integration of a low-cost, scalable, and faithful OC models with automatic high-content image analysis represents a significant stride towards functional precision oncology and cancer drug discovery.

bioengineering↗

bioRxiv2023

Rapid Prototyping of Thermoplastic Microfluidic 3D Cell Culture Devices by Creating Regional Hydrophilicity Discrepancy

Microfluidic three-dimensional cell culture devices that enable the recapitulation of key aspects of organ structures and functions in vivo represent a promising preclinical platform to improve translational success during drug discovery. Essential to these engineered devices is the spatial patterning of cells from different tissue types within a confined microenvironment. Traditional fabrication strategies lack the scalability, cost-effectiveness, and rapid prototyping capabilities required for industrial applications, especially for processes involving thermoplastic materials. Here, we introduce an approach to pattern fluid guides inside microchannels by establishing differential hydrophilicity using pressure-sensitive adhesives as masks and a subsequent selective coating with a biocompatible polymer. We identified optimal coating conditions using polyvinylpyrrolidone, which resulted in rapid and consistent hydrogel flow in both the open-chip prototype and the fully bonded device containing additional features for medium perfusion. We tested the suitability of our device for dynamic 3D cell culture by growing human hepatocytes in the device under controlled fluid flow for a 14-day period. Additionally, we demonstrated the potential of using our device for pharmaceutical high-throughput screening applications, such as predicting drug-induced liver injury. Our approach offers a facile strategy of rapid prototyping thermoplastic microfluidic organ chips with varying geometries, microstructures, and substrate materials.

bioengineering↗