A curious case of retrogenesis in language: Automated analysis of language patterns observed in dementia patients and young children.

Introduction: While linguistic retrogenesis has been extensively investigated in the neuroscientific and behavioral literature, there has been little work on retrogenesis using computerized approaches to language analysis. Methods: We bridge this gap by introducing a method based on comparing output of a pre-trained neural language model (NLM) with an artificially degraded version of itself to examine the transcripts of speech produced by seniors with and without dementia and healthy children during spontaneous language tasks. We compare a range of linguistic characteristics including language model perplexity, syntactic complexity, lexical frequency and part-of-speech use across these groups. Results: Our results indicate that healthy seniors and children older than 8 years share similar linguistic characteristics, as do dementia patients and children who are younger than 8 years. Discussion: Our study aligns with the growing evidence that language deterioration in dementia mirrors language acquisition in development using computational linguistic methods based on NLMs. This insight underscores the importance of further research to refine its application in guiding developmentally appropriate patient care, particularly in early stages.

A Conversational Agent for Early Detection of Neurotoxic Effects of Medications through Automated Intensive Observation.

We present a fully automated AI-based system for intensive monitoring of cognitive symptoms of neurotoxicity that frequently appear as a result of immunotherapy of hematologic malignancies. Early manifestations of these symptoms are evident in the patient's speech in the form of mild aphasia and confusion and can be detected and effectively treated prior to onset of more serious and potentially life-threatening impairment. We have developed the Automated Neural Nursing Assistant (ANNA) system designed to conduct a brief cognitive assessment several times per day over the telephone for 5-14 days following infusion of the immunotherapy medication. ANNA uses a conversational agent based on a large language model to elicit spontaneous speech in a semi-structured dialogue, followed by a series of brief language-based neurocognitive tests. In this paper we share ANNA's design and implementation, results of a pilot functional evaluation study, and discuss technical and logistic challenges facing the introduction of this type of technology in clinical practice. A large-scale clinical evaluation of ANNA will be conducted in an observational study of patients undergoing immunotherapy at the University of Minnesota Masonic Cancer Center starting in the Fall 2023.

Isolation of Cardiomyocytes from Fixed Hearts for Immunocytochemistry and Ploidy Analysis.

The adult mammalian heart is composed of various cell types including cardiomyocytes, endothelial cells and fibroblasts. Since it is difficult to reliably identify nuclei of cardiomyocytes on histological sections, many groups rely on isolating viable cardiomyocytes prior to fixation to perform immunostaining. However, these live cardiomyocyte isolation techniques require optimization to maximize the yield, viability and quality of the samples, with inherent fluctuations from sample to sample despite maximum optimization. Here, we report a reproducible protocol, involving fixation prior to enzymatic digestion of the heart, which leads to maximum yield while preserving the in vivo morphology of individual cardiomyocytes. We further developed an automated analysis platform to determine the number of nuclei and DNA content per nucleus for individual cardiomyocytes. After exposing the chest cavity, the heart was arrested in diastole by perfusion with 60 mM KCl in PBS. Next, the heart was fixed in 4% paraformaldehyde (PFA) solution, and then digested with 60 mg/mL collagenase solution. After digestions, cells were singularized by trituration, and the cardiomyocyte fraction was enriched via differential centrifugation. Isolated cardiomyocytes were stained for Troponin T and α-actinin to assess purity of the obtained population. Furthermore, we developed an image analysis platform to determine cardiomyocyte nucleation and ploidy status following DAPI staining. Image based ploidy assessments led to consistent and reproducible results. Thus, with this protocol, it is possible to preserve native morphology of individual cardiomyocytes to allow immunocytochemistry and DNA content analysis while achieving maximum yield.