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Funk, E. M.

Publications and source records attributed to Funk, E. M..

3 recordsLinked to original sources

Set-up, validation, evaluation, and cost-benefit analysis of an AI-assisted assessment of responsible research practices in a sample of life science publications

The (semi-)automated screening of publications for diverse quality and transparency criteria is at the core of systematic literature assessment. Typically, the assessment process involves two initial reviewers and one additional reviewer for cases that require reconciliation. Here, we explore to what extent this process can be assisted by Large Language Models (LLMs). Specifically, whether LLMs are capable of assessing responsible research practices (RRPs) in scientific papers in a robust way. We employed proprietary LLMs to assess an initial set of 37 papers across ten RRPs. The same papers were also reviewed by three human reviewers. We iteratively redesigned prompts to increase model accuracy compared to human ratings which we treated as the gold standard. The resulting pipeline was validated on an additional set of 15 papers. We show that LLM accuracy is comparable to single human reviewer performance (90% for LLM vs 86% for a single human reviewer). However, performance strongly depended on the specific RRPs with accuracy ranging from 40% to 100%. LLMs exhibited an affirmative bias, making more errors when practices were not reported in the papers. Overall, we show how such an approach potentially replaces one human reviewer, enabling AI-assisted assessment of research papers. We discuss how dataset imbalances, validation procedures, and implementation time limit the broad applicability of such approaches. Through this, we develop initial guidance on the utility of proprietary LLMs in evidence synthesis.

scientific communication and education↗

Nanobody immunolabelling and three-dimensional imaging reveals spatially restricted LYVE1 expression by kidney lymphatic vessels in mice

Lymphatic vessels are complex three-dimensional (3D) structures that facilitate tissue fluid clearance and regulate immune responses in health and inflammatory contexts. Recent advances in wholemount immunolabelling and 3D imaging have provided insights into organ-specific heterogeneity of lymphatic structure and function. However, the visualisation of lymphatic vessels deep within an intact organ remains a challenge. We hypothesised that nanobodies, single-domain antibodies raised in camelid species, would result in improved labelling of lymphatics in intact mouse organs, without loss of information due to organ sectioning or inadequate penetration. We generated and characterised nanobody clones targeting lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), a marker of lymphatic capillaries. Nanobodies were superior at penetrating whole mouse organs and enhanced labelling of lymphatics compared with a conventional anti-LYVE1 polyclonal antibody. Utilising this new tool, we found that kidney lymphatics; an organ in which labelling of lymphatics is challenging, have spatially restricted LYVE1 expression compared with lymphatics of skin, heart, and lung. The timing of this LYVE1 spatial restriction coincides with the early postnatal period in mice. Our findings highlight an unexpected, organ-specific characteristic of kidney lymphatic vessels, whilst providing a novel experimental tool for characterisation, isolation, or perturbation of lymphatic vessels in health and disease.

immunology↗

A unique subset of pericystic endothelium associates with aberrant microvascular remodelling and impaired blood perfusion early in polycystic kidney disease

Hallmarks of autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney anomaly, include expanding fluid-filled epithelial cysts, inflammation, and fibrosis. Despite previous work showing the potential of vascular-based therapies, renal microvascular alterations in ADPKD, and their timing, are poorly understood. Using single-cell transcriptomics of human kidney microvasculature, we identify a population of endothelial cells adjacent to cysts in ADPKD. This pericystic endothelium, distinguishable by its expression of osteopontin (SPP1), has a distinct molecular profile compared to the common endothelial cell injury signature in other kidney diseases. SPP1+ pericystic endothelium was also present in an orthologous mouse model of ADPKD before overt kidney functional decline. By interrogating geometric, topological and fractal properties from three-dimensional imaging of early ADPKD mouse kidneys, we show that pericystic endothelium associates with disorganisation and non-uniformity of the renal cortical microvasculature. Concurrently, we detected region-specific reductions in cortical blood flow within ADPKD murine kidneys using arterial spin labelling. We conclude that ADPKD kidneys contain a unique subset of endothelium manifesting with aberrant remodelling and impaired blood perfusion. Its detection, prior to renal functional decline, advocates the vasculature as a therapeutic target to modulate or preserve renal function in early ADPKD.

pathology↗