Biology subjects

Ursu, R.

Publications and source records attributed to Ursu, R..

3 recordsLinked to original sources

bioRxiv2026

Morphologic intratumoral heterogeneity from routine whole-slide histopathology is prognostic for survival in primary central nervous system lymphoma: development in the LOC Network and international external validation

Background: Clinical scores incompletely capture outcomes in primary central nervous system lymphoma (PCNSL). We quantified morphologic heterogeneity in pretreatment hematoxylin and eosin (H\&E) whole slides. Patients and methods: Three independent cohorts of immunocompetent, HIV- and EBV-negative patients treated recently were analyzed: LOC 2023 (122 slides), phase III BLOCAGE-01 (245 slides; NCT02313389), and external Barcelona (BCN; 41 slides). UNI embeddings, prototype learning, spatial metrics, and elastic-net Cox regression defined ITH-C. Results: Models achieved bootstrap-corrected concordance of 0.797--0.834. Age-, sex-, and KPS-adjusted ITH-C HRs were 1.29 (95\% CI 1.01--1.64), 1.27 (1.07--1.51), and 2.13 (1.35--3.37), respectively. Adding ITH-C increased MSKCC C-index from 0.671 to 0.717, 0.560 to 0.593, and 0.588 to 0.706. Spatial transcriptomics linked ITH-C to immune programs. Conclusions: Routine H\&E encodes prognostic spatial heterogeneity in PCNSL. ITH-C complements clinical scores, supporting prospective risk stratification.

bioinformatics↗

bioRxiv2025

A lobule-specific neuronal representation of song temporal structure in the songbird cerebellum

The cerebellum is involved in the acquisition and production of speech as revealed by clinical evidence and imaging studies, but its specific role however remains unclear. Songbirds provide a unique model to study the neural mechanisms of speech learning and production. Recent evidence highlights a contribution of the cerebellum to syllable duration in songbirds. Here, we aim at better understanding how and which cerebellar circuits may contribute to the tight control of syllable duration in zebra finches. We first confirmed that lesions in the lateral cerebellum affect syllable duration. We then recorded neuronal activity in the various cerebellar lobules in response to song playback and during singing with or without auditory feedback perturbation. We found that many cerebellar lobules receive non-selective auditory information locked to syllable boundaries during song playback, both in anaesthetized and awake behaving birds. During singing, cerebellar neurons in several lobules display song-locked responses with varying degrees of alignment to their playback responses and no alteration during auditory feedback perturbation. Singing-related activity tends to correlate with the fluctuations in syllable duration rather than any acoustic song feature. Importantly, neurons in lobule IV of the cerebellum are largely unaffected by auditory stimulation but display syllable-locked firing rate modulations during singing that precisely encode syllable boundaries with a sharp and tight increase in firing at syllable onsets and offsets. Altogether, our findings reveal cerebellar signals that may contribute to the control of the duration of vocal elements during singing, possibly serving as a forward model of song temporal features.

neuroscience↗

bioRxiv2024

Neural population dynamics during sleep in a songbird vocal circuit resemble sharp wave ripple activity

Similar to motor skill learning in mammals, vocal learning in songbirds requires a set of interconnected brain areas that make up an analogous basal ganglia-thalamocortical circuit known as the anterior forebrain pathway (AFP). Although neural activity in the AFP has been extensively investigated during awake singing, very little is known about its neural activity patterns during other behavioral states. Here, we used chronically implanted Neuropixels probes to investigate spontaneous neural activity in the AFP during natural sleep and awake periods in male zebra finches. We found that during sleep, neuron populations in the pallial region LMAN (lateral magnocellular nucleus of the nidopallium) spontaneously exhibited synchronized bursts that were characterized by a negative sharp deflection in the local field potential (LFP) and a transient increase in gamma power. LMAN population bursts occurred primarily during non-rapid eye movement (NREM) sleep and were highly reminiscent of sharp-wave ripple (SWR) activity observed in rodent hippocampus. We also examined the functional connectivity within the AFP by calculating the pairwise LFP coherence. As expected, delta and theta band coherence within LMAN and Area X was higher during sleep compared to awake periods. Contrary to our expectations, we did not observe strong coherence between LMAN and Area X during sleep, suggesting that the input from LMAN into Area X is spatially restricted. Overall, these results provide the first description of spontaneous neural dynamics within the AFP across behavioral states. Significance statementAlthough cortical and basal ganglia circuits are known to be required for learning in both mammals and birds, little is known about the ongoing spontaneous activity patterns within these circuits, or how they are modulated by behavioral state. Here we prove the first description of cortical-basal ganglia network activity during sleep and awake periods in birds. Within the pallial area LMAN, we observed population-wide bursting events that were highly reminiscent of hippocampal sharp-wave ripple (SWR) activity, suggesting that large-scale population events have diverse functions across vertebrates.

neuroscience↗