Hypoxia extreme events in a changing climate: Machine learning methods and deterministic simulations for future scenarios development in the Venice Lagoon.

Climate change pressures include the dissolved oxygen decline that in lagoon ecosystems can lead to hypoxia, i.e. low dissolved oxygen concentrations, which have consequences to ecosystem functioning including biogeochemical cycling from mild to severe disruption.

Mercury cycling in contaminated coastal environments: modeling the benthic-pelagic coupling and microbial resistance in the Venice Lagoon.

Anthropogenic activities have been releasing mercury for centuries, and despite global efforts to control emissions, concentrations in environmental media remain high. Coastal sediments can be a long-term repository for mercury, but also a secondary source, and competing processes in marine ecosystems can lead to the conversion of mercury into the toxic and bioaccumulative species methylmercury, which threatens ecosystem and human health. We investigate the fate and transport of three mercury species in a coastal lagoon affected by historical pollution using a novel high-resolution finite element model that integrates mercury biogeochemistry, sediment dynamics and hydrodynamics.

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ.

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.

We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery.