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First-in-human to proof-of-concept: why experimental medicine studies remain essential in human physiology and drug developmentNARA Subscribed
Experimental medicine studies, small, mechanistically focused investigations, have historically driven key discoveries in human physiology and pharmacology. Despite their foundational role, these studies are increasingly marginalised in today’s drug development environment due to economic pressures, regulatory conservatism, and an overemphasis on statistical endpoints from large-scale trials. This article traces the historical...
Interpretable deep learning reveals spatiotemporal MRI features of brain aging that align with neurodegenerationNARA Subscribed
Cortical thinning and atrophy are hallmarks of brain aging that have been characterized using magnetic resonance imaging (MRI). Brain aging involves many neuroanatomic features whose effects on brain structure remain unexplored. To address this challenge, we trained interpretable deep neural networks (DNNs) to estimate brain age (BA) from T 1 -weighted ( T 1 w) MRI. By identifying MRI features unapparent to humans, DNNs can fi...
Alzheimer’s disease (AD) disproportionately affects women and carriers of the apolipoprotein E ε4 allele (APOE4), yet little is known about how sex and APOE interact to influence white matter (WM) integrity during disease progression. We integrated diffusion MRI and matched blood transcriptomic data to investigate these interactions and their underlying biological mechanisms. WM microstructure was quantified using diffusion te...
Nonlinear thinking in ecology and evolution: applying the threshold elemental ratio across levels of ecological organizationNARA Subscribed
Nonlinear dynamics govern ecological processes; thus, understanding thresholds is important for measuring and forecasting the effects of climate change and management of natural resources. However, identifying whether and how such thresholds transfer across ecological levels of organization remains challenging. We argue for a broadening of a foundational organismal concept from ecological stoichiometry theory, the threshold el...
Particles are a key component of aquatic light climate due to their attenuation of light. Near the water surface, waves and sheared currents can induce a preferential orientation of nonspherical particles that alters their inherent optical properties and the associated light attenuation. This modeling study focuses on how particle shape, and the corresponding preferential orientation, impacts the light climate in an aquatic en...
Predicting the progression of MCI and Alzheimer’s disease on structural brain integrity and other features with machine learningNARA Subscribed
Machine learning (ML) on structural MRI data shows high potential for classifying Alzheimer’s disease (AD) progression, but the specific contribution of brain regions, demographics, and proteinopathy remains unclear. Using Alzheimer’s Disease Neuroimaging Initiative (ADNI) data, we applied an extreme gradient-boosting algorithm and SHAP (SHapley Additive exPlanations) values to classify cognitively normal (CN) older adults, th...
Transformation of Ritonavir Nanocrystal Suspensions into a Redispersible Drug Product via Vacuum Drum DryingNARA Subscribed
The present study explored vacuum drum drying (VDD) as potential drying technique for the solidification of crystalline ritonavir nanosuspensions prepared by wet-ball milling. In detail, the impact of drying protectants (mannitol, lactose, trehalose) added to the ritonavir nanosuspension was assessed in dependence of the drum temperature with respect to processibility via VDD, resulting intermediate powder properties, remainin...
Phenotyping in the era of genomics: MaTrics—a digital character matrix to document mammalian phenotypic traitsNARA Subscribed
A new and uniquely structured matrix of mammalian phenotypes, MaTrics ( Ma mmalian Tr aits for Comparative Genom ics ) in a digital form is presented. By focussing on mammalian species for which genome assemblies are available, MaTrics provides an interface between mammalogy and comparative genomics. MaTrics was developed within a project aimed to find genetic causes of phenotypic traits of mammals using Forward Genomics. This...
Imaging of plant current pathways for non-invasive root Phenotyping using a newly developed electrical current source density approachNARA Subscribed
Aims The flow of electric current in the root-soil system relates to the pathways of water and solutes, its characterization provides information on the root architecture and functioning. We developed a current source density approach with the goal of non-invasively image the current pathways in the root-soil system. Methods A current flow is applied from the plant stem to the soil, the proposed geoelectrical approach images t...