Biology subjects

Lim, J. T.

Publications and source records attributed to Lim, J. T..

3 recordsLinked to original sources

bioRxiv2026

Estimating spatially adjusted temperature-dependent time-varying reproduction numbers for vector-borne diseases

Estimating the effective reproduction number is crucial for understanding and managing infectious disease outbreaks. For vector-borne diseases like dengue, transmission depends on environmental and spatial conditions: temperature affects the extrinsic incubation period in mosquitoes, altering transmission timing, while spatial proximity can lead to clusters of transmission. We integrated a temperature-dependent (TD) generation time (GT) distribution and a spatial decay function weighting transmission likelihood by distance into the Wallinga & Teunis estimation framework. Simulations compared scenarios where the true generation time for spatially adjusted disease cases were TD or temperature independent (TI), versus their corresponding model assumptions. Daily reproduction numbers (Rt) estimated were evaluated via percent error against true values. We found error to be predominantly driven by variance rather than bias, indicating that stochastic uncertainty in infector assignment was the primary driver of inaccuracies rather than systematic model miscalibration. Assuming a spatial weighting function assigning higher probabilities of transmission to geographically close infector-infectee pairs (Gaussian spatial decay) percent errors measuring deviation between estimated and true Rt outperformed those of alternative spatial kernels. Mis-specifying temperature-dependence under a Gaussian spatial kernel yielded higher errors when the ground truth was TD (16-38% vs 36-58% deviation), and similar errors when it was TI (32-52% vs 35-56% deviation), indicating limited sensitivity to temperature dependence when it was not present in the underlying transmission process. Application to dengue case data in Singapore showed that spatially adjusted models produced more variable Rt trajectories than time-series smoothing approaches, with Gaussian decay yielding more stable estimates than exponential decay and the TD model producing modest refinements, suggesting that explicitly modeling spatial heterogeneity and TD transmission dynamics increases responsiveness to even fluctuations in case counts. Our framework is robust across climates, shown by simulations using a broader temperature range, and suggests a useful application in retrospective analyses.

ecology↗

bioRxiv2024

Wolbachia incompatible insect technique program optimization over large spatial scales using a process-based model of mosquito metapopulation dynamics

BackgroundWolbachia incompatible insect technique (IIT) programs have been shown in field trials to be highly effective in suppressing populations of mosquitoes that carry diseases such as dengue, chikungunya and Zika. However, the frequent and repeated release of Wolbachia-infected male mosquitoes makes such programs resource-intensive. While the need for optimization is recognized, potential strategies to optimize releases and reduce resource utilization have not been fully explored. MethodsWe developed a process-based model to study the spatial-temporal metapopulation dynamics of mosquitoes in a Wolbachia IIT program, which explicitly incorporates climatic influence in mosquito life-history traits. We then used the model to simulate various scale-down and redistribution strategies to optimize the existing program in Singapore. Specifically, the model was used to study the trade-offs between the intervention efficacy outcomes and resource requirements of various release program strategies, such as the total number of release events and the number of mosquitoes released. ResultsWe found that scaling down releases in existing sites from twice a week to only once a week yielded minimal changes in suppression efficacy (from 91% to 85%), while requiring 45% fewer mosquitoes and release events. Additionally, redistributing mosquitoes from already suppressed areas and releasing them in new areas once a week led to a greater total suppressive efficacy (88% compared to 65%) while also yielding a 16% and 14% reduction in the number of mosquitoes and release events required respectively. ConclusionsBoth scale-down and redistribution strategies can be implemented to significantly reduce program resource requirements without compromising the suppressive efficacy of IIT. These findings will inform planners on ways to optimize existing and future IIT programs, potentially allowing for the wider adoption of this method for mosquito-borne disease control.

ecology↗

bioRxiv2023

Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma

Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine cutaneous malignancy arising from either ultraviolet-induced mutagenesis or Merkel cell polyomavirus (MCPyV) integration. Despite extensive research, our understanding of the molecular mechanisms driving the transition from normal cells to MCC remains limited. To address this knowledge gap, we assessed the impact of inducible MCPyV T antigens on normal human fibroblasts by performing RNA sequencing. Our data uncovered changes in expression and regulation of Wnt signaling pathway members. Building on this observation, we bioinformatically evaluated various Wnt pathway perturbagens for their ability to reverse the MCC gene expression signature and identified pyrvinium pamoate, an FDA-approved anthelminthic drug known for its anti-tumor activity in other cancers. Leveraging transcriptomic, network, and molecular analyses, we found that pyrvinium targets multiple MCC vulnerabilities. Pyrvinium not only reverses the neuroendocrine features of MCC by modulating canonical and non-canonical Wnt signaling but also inhibits cancer cell growth by activating p53-mediated apoptosis, disrupting mitochondrial function, and inducing endoplasmic reticulum stress. Finally, we demonstrated that pyrvinium reduces tumor growth in an MCC mouse xenograft model. These findings offer a new understanding of the role of Wnt signaling in MCC and highlight the utility of pyrvinium as a potential treatment for MCC.

cancer biology↗