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1. Wonder drugs and where to use them: a forecast of ivermectin's impact on malaria in Africa

   https://doi.org/10.1016/j.idm.2025.06.003  

   Greenhalgh, Scott; Roman, Ahmani; Provencher, Ashley (December 2025, Infectious Disease Modelling)

   A study in Burkina Faso revealed ivermectin inhibits malaria transmission by killing malaria parasites and mosquitoes. However, it is unknown what effect this drug will have on the malaria transmission intensities of the rest of sub-Saharan Africa (SSA). To address this issue, we created a mathematical model using malaria transmission data from 41 SSA countries to evaluate the antimalarial benefits of a mass drug administration (MDA) of ivermectin. To account for ivermectin's effect on malaria, we incorporate estimates of its ability to inhibit malaria transmission and kill mosquitoes. We consider scenarios where 0, 12.5 %, 25.0 %, and 50.0 % of the population receive ivermectin over five years and estimate malaria incidence averted, disability-adjusted life years saved, and the incremental cost-effectiveness ratio. Our findings show that an MDA of ivermectin to 12.5 %, 25 %, or 50 % of the population annually averts 248.7, 261.4, and 288.7 incidences per thousand people and saves 5.4, 5.7, and 6.3 disability-adjusted life years, respectively. These values indicate that an MDA of ivermectin would be cost-effective in 41, 18, and 6 countries, and very cost-effective in 22, 6, and 3 countries for the 12.5 %, 25 %, and 50 % scenarios. Altogether, our results indicate that ivermectin would prevent a substantial number of malaria incidences and save disability-adjusted life years in the majority of SSA. Therefore, an MDA of ivermectin would greatly aid in ongoing malaria control efforts and should be considered strongly as a complementary intervention to current malaria protocols. 

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2. Decadal impacts of wildfire fuel reduction treatments on ecosystem characteristics and fire behavior in alaskan boreal forests

   https://doi.org/10.1016/j.foreco.2023.121347  

   Boyd, Melissa A.; Walker, Xanthe J.; Barnes, Jennifer; Celis, Gerardo; Goetz, Scott J.; Johnstone, Jill F.; Link, Nicholas T.; Melvin, April M.; Saperstein, Lisa; Schuur, Edward A.G.; et al (October 2023, Forest Ecology and Management)

   Wildfire activity is increasing in boreal forests as climate warms and dries, increasing risks to rural and urban communities. In black spruce forests of Interior Alaska, fuel reduction treatments are used to create a defensible space for fire suppression and slow fire spread. These treatments introduce novel disturbance characteristics, making longer-term outcomes on ecosystem structure and wildfire risk reduction uncertain. We remeasured a network of sites where fuels were reduced through hand thinning or mechanical shearblading in Interior Alaska to assess how successional trajectories of tree dominance, understory composition, and permafrost change over ∼ 20 years after treatment. We also assessed if these fuel reduction treatments reduce modeled surface rate of fire spread (ROS), flame length, and fireline intensity relative to an untreated black spruce stand, and if surface fire behavior changes over time. In thinned areas, soil organic layer (SOL) disturbance promoted tree seedling recruitment but did not change over time. In shearbladed sites, by contrast, both conifer and broad-leaved deciduous seedling density increased over time and deciduous seedlings were 20 times more abundant than spruce. Thaw depth increased over time in both treatments and was greatest in shearbladed sites with a thin SOL. Understory composition was not altered by thinning but in shearbladed treatments shifted from forbs and horsetail to tall deciduous shrubs and grasses over time. Modeled surface fire behavior was constant in shearbladed sites. This finding is inconsistent with expert opinion, highlighting the need for additional fuels-specific data to capture the changing vegetation structure. Treatment effectiveness at reducing modeled surface ROS, flame length, and fireline intensity depended on the fuel model used for an untreated black spruce stand, pointing to uncertainties about the efficacy of these treatments at mitigating surface fire behavior. Overall, we show that fuel reduction treatments can promote low flammability, deciduous tree dominated successional trajectories, and that shearblading has strong effects on understory composition and permafrost degradation that persist for nearly two decades after disturbance. Such factors need to be considered to enhance the design, management, and predictions of fire behavior in these treatments. 

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3. Biotic Interactions in Experimental Antarctic Soil Microcosms Vary with Abiotic Stress

   https://doi.org/10.3390/soilsystems3030057  

   Shaw, E. Ashley; Wall, Diana H. (September 2019, Soil Systems)

   Biotic interactions structure ecological communities but abiotic factors affect the strength of these relationships. These interactions are difficult to study in soils due to their vast biodiversity and the many environmental factors that affect soil species. The McMurdo Dry Valleys (MDV), Antarctica, are relatively simple soil ecosystems compared to temperate soils, making them an excellent study system for the trophic relationships of soil. Soil microbes and relatively few species of nematodes, rotifers, tardigrades, springtails, and mites are patchily distributed across the cold, dry landscape, which lacks vascular plants and terrestrial vertebrates. However, glacier and permafrost melt are expected to cause shifts in soil moisture and solutes across this ecosystem. To test how increased moisture and salinity affect soil invertebrates and their biotic interactions, we established a laboratory microcosm experiment (4 community × 2 moisture × 2 salinity treatments). Community treatments were: (1) Bacteria only (control), (2) Scottnema (S. lindsayae + bacteria), (3) Eudorylaimus (E. antarcticus + bacteria), and (4) Mixed (S. lindsayae + E. antarcticus + bacteria). Salinity and moisture treatments were control and high. High moisture reduced S. lindsayae adults, while high salinity reduced the total S. lindsayae population. We found that S. lindsayae exerted top-down control over soil bacteria populations, but this effect was dependent on salinity treatment. In the high salinity treatment, bacteria were released from top-down pressure as S. lindsayae declined. Ours was the first study to empirically demonstrate, although in lab microcosm conditions, top-down control in the MDV soil food web. 

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4. Reduction of Metastasis via Epigenetic Modulation in a Murine Model of Metastatic Triple Negative Breast Cancer (TNBC)

   https://doi.org/10.3390/cancers14071753  

   Zylla, Jessica L.; Hoffman, Mariah M.; Plesselova, Simona; Bhattacharya, Somshuvra; Calar, Kristin; Afeworki, Yohannes; de la Puente, Pilar; Gnimpieba, Etienne Z.; Miskimins, W. Keith; Messerli, Shanta M. (April 2022, Cancers)

   This study investigates the effects of a dual selective Class I histone deacetylase (HDAC)/lysine-specific histone demethylase 1A (LSD1) inhibitor known as 4SC-202 (Domatinostat) on tumor growth and metastasis in a highly metastatic murine model of Triple Negative Breast Cancer (TNBC). 4SC-202 is cytotoxic and cytostatic to the TNBC murine cell line 4T1 and the human TNBC cell line MDA-MB-231; the drug does not kill the normal breast epithelial cell line MCF10A. Furthermore, 4SC-202 reduces cancer cell migration. In vivo studies conducted in the syngeneic 4T1 model, which closely mimics human TNBC in terms of sites of metastasis, reveal reduced tumor burden and lung metastasis. The mechanism of action of 4SC-202 may involve effects on cancer stem cells (CSC) which can self-renew and form metastatic lesions. Approximately 5% of the total 4T1 cell population grown in three-dimensional scaffolds had a distinct CD44high/CD24low CSC profile which decreased after treatment. Bulk transcriptome (RNA) sequencing analyses of 4T1 tumors reveal changes in metastasis-related pathways in 4SC-202-treated tumors, including changes to expression levels of genes implicated in cell migration and cell motility. In summary, 4SC-202 treatment of tumors from a highly metastatic murine model of TNBC reduces metastasis and warrants further preclinical studies. 

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5. Evaluation of fendiline treatment in VP40 system with nucleation-elongation process: a computational model of Ebola virus matrix protein assembly

   https://doi.org/10.1128/spectrum.03098-23  

   Liu, Xiao; Husby, Monica; Stahelin, Robert V; Pienaar, Elsje (April 2024, Microbiology Spectrum)

   Zhang, Leiliang (Ed.)

   Ebola virus (EBOV) infection is threatening human health, especially in Central and West Africa. Limited clinical trials and the requirement of biosafety level-4 laboratories hinder experimental work to advance our understanding of EBOV and the evaluation of treatment. In this work, we use a computational model to study the assembly and budding process of EBOV and evaluate the effect of fendiline on these processes in the context of fluctuating host membrane lipid levels. Our results demonstrate for the first time that the assembly of VP40 filaments may follow the nucleation-elongation theory, as this mechanism is critical to maintaining a pool of VP40 dimers for the maturation and production of virus-like particles (VLPs). We further find that this nucleation-elongation process is likely influenced by fluctuating phosphatidylserine (PS), which can complicate the efficacy of lipid-targeted therapies like fendiline, a drug that lowers cellular PS levels. Our results indicate that fendiline-induced PS reduction may actually increase VLP production at earlier time points (24 h) and under low fendiline concentrations (≤2 µM). However, this effect is transient and does not change the conclusion that fendiline generally decreases VLP production. In the context of fluctuating PS levels, we also conclude that fendiline can be more efficient at the late stage of VLP budding relative to earlier phases. Combination therapy with a VLP budding step-targeted drug may therefore further increase the treatment efficiency of fendiline. Finally, we also show that fendiline-induced PS reduction more effectively lowers VLP production when VP40 expression is high. Taken together, our results provide critical quantitative information on how fluctuating lipid levels (PS) affect EBOV assembly and egress and how this mechanism can be disrupted by lipid-targeting molecules like fendiline. Ebola virus (EBOV) infection can cause deadly hemorrhagic fever, which has a mortality rate of ~50%–90% without treatment. The recent outbreaks in Uganda and the Democratic Republic of the Congo illustrate its threat to human health. Though two antibody-based treatments were approved, mortality rates in the last outbreak were still higher than 30%. This can partly be due to the requirement of advanced medical facilities for current treatments. As a result, it is very important to develop and evaluate new therapies for EBOV infection, especially those that can be easily applied in the developing world. The significance of our research is that we evaluate the potential of lipid-targeted treatments in reducing EBOV assembly and egress. We achieved this goal using the VP40 system combined with a computational approach, which both saves time and lowers cost compared to traditional experimental studies and provides innovative new tools to study viral protein dynamics. 

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