Chemistry, manufacturing and controls strategies for using novel excipients in lipid nanoparticles.

Lipid nanoparticles (LNPs) for nucleic acid delivery often use novel lipids as functional excipients to modulate the biodistribution, pharmacokinetics, pharmacodynamics and efficacy of the nucleic acid. Novel excipients used in pharmaceutical products are subject to heightened regulatory scrutiny and often require data packages comparable to an active pharmaceutical ingredient. Although these regulatory requirements may help to ensure patient safety they also create economic and procedural barriers that can disincentivize innovation and delay clinical investigation.

Mercury and selenium in biological pump under upwelling-downwelling influence in Cabo Frio shelf, South Atlantic Ocean, Brazil.

The knowledge of metals concentration in upwelling areas are a concern due the higher productivity of these areas In Cabo Frio Upwelling-Downwelling System (CFUS) is high primary productivity area and has been identified as an Hg hotspot to biota in SE Brazil that has been susceptible to Hg inputs, due to growing industrialization in the region. To investigate the concentration of Hg and Se metals, as well as the trophic transfer of these metals, the present study investigated Hg and Se concentrations in 64 samples collected in net mesh of >20, >64, >150 and >300 μm, in 2012, in the region's water masses. Higher mean Hg concentrations were found in zooplankton, 0.

Human-in-the-loop active learning for goal-oriented molecule generation.

Machine learning (ML) systems have enabled the modelling of quantitative structure-property relationships (QSPR) and structure-activity relationships (QSAR) using existing experimental data to predict target properties for new molecules. These property predictors hold significant potential in accelerating drug discovery by guiding generative artificial intelligence (AI) agents to explore desired chemical spaces. However, they often struggle to generalize due to the limited scope of the training data.

The Minnesota Critical Care Working Group 1: Monitoring and Coordinating Statewide Critical Care Surge Response in the COVID-19 Pandemic, March 2020 Through July 1, 2021.

Background: In response to the COVID-19 pandemic and as part of the statewide health care coalition response, the Minnesota Critical Care Working Group (CCWG), composed of interprofessional leaders from the state's nine largest health systems, was established and entrusted to plan and coordinate critical care support for Minnesota from March 2020 through July 1, 2021.

Research Question: Can a statewide CCWG develop contingency and crisis-level surge strategies and indicators in response to the COVID-19 pandemic while evolving into a highly collaborative team?

Study Design And Methods: CCWG members (intensivists, ethicists, nurses, Minnesota Department of Health and Minnesota Hospital Association leaders) met by audio video conferencing as often as daily assessing COVID-19 and non-COVID-19 hospitalization data, developed surge indicators reflecting contingency vs crisis conditions, and planned responses collaboratively. A foundation of collaboration and teamwork developed which facilitated an effective statewide response.

How can Community Music Help Address Loneliness in Contexts of Social Marginalisation? Insights From Two Music for Social Connection Programs.

This study explores how participatory music programs can help build social connection for people experiencing loneliness in contexts of social marginalisation. Loneliness is a growing, global public health issue with social and structural drivers. There is an urgent need to investigate innovative approaches to programming that go beyond opportunities for social contact to address the multiple domains of loneliness.