P. Williams

We have developed a novel "real time" quantitative PCR method. The method measures PCR product accumulation through a dual-labeled fluorogenic probe (i.e., TaqMan Probe). This method provides very accurate and reproducible quantitation of gene copies. Unlike other quantitative PCR methods, real-time PCR does not require post-PCR sample handling, preventing potential PCR product carry-over contamination and resulting in much faster and higher throughput assays. The real-time PCR method has a very large dynamic range of starting target molecule determination (at least five orders of magnitude). Real-time quantitative PCR is extremely accurate and less labor-intensive than current quantitative PCR methods.

EphA family receptor tyrosine kinases and their ephrin-A ligands are involved in patterning axonal connections during brain development, but until now a role for these molecules in the mature brain had not been elucidated. Here, we show that both the EphA5 receptor and its ephrin-A ligands (2 and 5) are expressed in the adult mouse hippocampus, and the EphA5 protein is present in a phosphorylated form. Because there are no pharmacological agents available for EphA receptors, we designed recombinant immunoadhesins that specifically bind to the receptor binding site of the ephrin-A ligand (antagonist) or the ligand binding site of the EphA receptor (agonist) and thus target EphA function. We demonstrate that intrahippocampal infusion of an EphA antagonist immunoadhesin leads to impaired performance in two behavioral paradigms, T-maze spontaneous alternation and context-dependent fear conditioning, sensitive to hippocampal function, whereas activation of EphA by infusion of an agonist immunoadhesin results in enhanced performance on these tasks. Because the two behavioral tasks have different motivational, perceptual, and motor requirements, we infer the changes were not caused by these performance factors but rather to cognitive alterations. We also find bidirectional changes in gene expression and in electrophysiological measures of synaptic efficacy that correlate with the behavioral results. Thus, EphA receptors and their ligands are implicated as mediators of plasticity in the adult mammalian brain.

Objective: We sought to develop a classification algorithm to extract diagnoses from free-text radiology reports of brain imaging performed in patients with acute respiratory failure (ARF) undergoing invasive mechanical ventilation. Methods: We developed and fine-tuned Neu-RadBERT, a BERT-based model, to classify unstructured radiology reports. We extracted all the brain imaging reports (computed tomography and magnetic resonance imaging) from MIMIC-IV database, performed in patients with ARF. Initial manual labelling was performed on a subset of reports for various brain abnormalities, followed by fine-tuning Neu-RadBERT using three strategies: 1) baseline RadBERT, 2) Neu-RadBERT with Masked Language Modeling (MLM) pretraining, and 3) Neu-RadBERT with MLM pretraining and oversampling to address data skewness. We compared the performance of this model to Llama-2-13B, an autoregressive LLM. Results: The Neu-RadBERT model, particularly with oversampling, demonstrated significant improvements in diagnostic accuracy compared to baseline RadBERT for brain abnormalities, achieving up to 98.0% accuracy for acute brain injuries. Llama-2-13B exhibited relatively lower performance, peaking at 67.5% binary classification accuracy. This result highlights potential limitations of current autoregressive LLMs for this specific classification task, though it remains possible that larger models or further fine-tuning could improve performance. Conclusion: Neu-RadBERT, enhanced through target domain pretraining and oversampling techniques, offered a robust tool for accurate and reliable diagnosis of neurological conditions from radiology reports. This study underscores the potential of transformer-based NLP models in automatically extracting diagnoses from free text reports with potential applications to both research and patient care.