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Biology subjects

Reis, B.

Publications and source records attributed to Reis, B..

3 recordsLinked to original sources

Dementia Language Models: a generalizable and controllable representation of cognitive impairment

We introduce Dementia Language Models (DLMs)--a generalizable and controllable representation of cognitive impairment through language--alongside an evaluation framework for establishing their validity and clinical grounding. DLMs created by large language models fine-tuned on a small clinical corpus successfully generated patient-like narratives across unseen tasks, received predicted MMSE scores in the impaired range, and produced narratives that neurologists identified with accuracy comparable to real transcripts. The models' internal representations themselves, as well as their non-linguistic decision-making, supported cognitive-state detection in unseen cohorts. The effect was controllable: moving from Healthy toward Dementia in weight space progressively worsened language and predicted MMSE scores while increasing dementia probability. DLMs could support clinician training, hypothesis generation, and scalable experimentation, reserving patient involvement for where it is truly needed.

neuroscience↗

In vitro and in vivo derived macrophages occupy distinct phenotypic states

Monocyte-derived macrophages (MDMs) are widely used to model human macrophage biology in vitro and standardized polarization conditions were proposed to recapitulate the different macrophage activation states. Although surface markers specific for distinct MDM populations have been identified, a systematic analysis of surface marker expression on these consensus MDM populations has not previously been reported. Here, we use mass cytometry to perform an in-depth characterization of MDM surface profiles and determine how these markers evolve with time. We also compared the phenotypes found in vitro with patient-derived tumor-associated macrophages (TAMs) and found that although MDMs and TAMs shared most markers investigated, the cell-surface signatures markedly differed in terms of expression levels and combinations. Our high-dimensional, single-cell analyses clarifies the surface expression profile of the core in vitro differentiated macrophage populations and highlights some limitations of the in vitro system to represent the complexity of in vivo polarized tumor-associated macrophage phenotypes. These findings provide new opportunities to improve the models used to study macrophage biology and give a pathway to improve our understanding of the in vivo complexity of these systems.

immunology↗

Newly recruited intraepithelial Ly6A+CCR9+CD4+ T cells protect against enteric viral infection

The intestinal epithelium comprises the bodys largest surface exposed to viruses. However, a role for intraepithelial T lymphocytes in resistance against viral infections remain elusive. By fate-mapping T cells recruited to the murine intestinal epithelium, we observed accumulation of CD4+ T cells after infection with murine norovirus (MNV) or mouse adenovirus type-2 (AdV), but not after reovirus infection. Intraepithelial CD4+ T cells recruited after MNV or AdV infection co-express Ly6A and CCR9, and exhibit T helper 1 and cytotoxic profiles. Although these cells display a diverse TCR repertoire, they conferred protection against AdV and MNV both in vivo and in an organoid co-culture model in an IFN-{gamma}-dependent manner. Ablation of the T cell receptor (TCR) or the transcription factor ThPOK in CD4+ T cells prior to infection prevented viral control, while TCR ablation during infection did not impact viral clearance. These results uncover a protective role for intraepithelial Ly6A+CCR9+CD4+ T cells against enteric viruses.

immunology↗