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[Character of proprioceptive information processing during learning in rats chronically intoxicated with alcohol].

A conditioned alimentary reflex was elaborated in rats placed into K-shaped maze after 8 months of intoxication with 35 degrees alcohol. The most important changes in experimental animals, as compared to intact ones, were revealed in the character of processing of proprioceptive information coming to the brain during learning. It was found that in the animals temporal relations between the processes of analysis and synthesis and the fixation of memory trace changed. Unlike intact animals, in "alcoholic" ones the new proprioceptive information as related to the previous experience was fixed in the long-term memory and only afterwards underwent analytic and synthetic processing. It is suggested that learning was not in enlarging the information capacity of each singled-out motor unit of full decision, but in their combination into one and only one decision.

Alcoholism

Deep learning-assisted, pathogenesis-informed lung histopathology scoring in preclinical mouse models of SARS-CoV-2 and influenza A infection.

INTRODUCTION: SARS-CoV-2 and influenza A virus (IAV) cause viral pneumonia, yet their lung lesions evolve with distinct spatial organization and resolution-phase architecture. In preclinical murine studies, H&E histopathology is a primary endpoint, but burden-focused semiquantitative scoring can miss pathogen- and phase-specific differences in lesion topology, compartmental involvement, inflammatory organization, and repair. We aimed to define virus- and phase-specific morphologic signatures and translate them into a practical, pathogenesis-informed scoring guide, supported by whole-slide convolutional neural network (CNN) analysis with class activation mapping (CAM). METHODS: Mice were infected under standardized conditions and evaluated during the early, peak-injury, and late phases of infection, corresponding to 2~3, 5~8, and 14 days post-infection (dpi), respectively. Lungs were assessed by H&E with semiquantitative scoring and by immunostaining to map viral antigen distribution and epithelial tropism. Whole-slide CNN models were trained for virus- and phase-specific classification, and CAM localized discriminative regions. RESULTS: Dose titration established reproducible lethal and sublethal infection conditions for both viruses. Viral antigen kinetics diverged, with SARS-CoV-2 peaking early and declining toward clearance by the resolution phase, whereas IAV peaked later and declined by the resolution phase, paralleling distinct injury-repair trajectories. CNN/CAM analysis distinguished virus- and phase-specific histologic patterns across the early, peak-injury, and resolution phases of infection and highlighted spatial signatures consistent with expert review. At the peak-injury phase, SARS-CoV-2 lungs showed broad alveolar/interstitial involvement, whereas IAV exhibited bronchocentric inflammatory organization. During the resolution phase, IAV showed prominent epithelial regeneration with remodeling-forward architecture, while SARS-CoV-2 more often retained localized residual inflammatory foci. Across both infections, tissue inflammatory composition shifted over time, with higher neutrophil representation during the peak-injury phase and a relative increase in lymphocytic representation during the resolution phase. Integrating lesion topology/distribution, edema, epithelial injury-regeneration, remodeling features, and lymphocyte predominance, we proposed a pathogen-resolved, phase-informed histopathology scoring guide with recommended evaluation windows for each model. CONCLUSION: Together, these findings define virus- and phase-specific morphologic programs that inform respiratory virus pathogenesis in mice and can be translated into practical scoring criteria for preclinical respiratory virus studies.

Animals

Primary care career choices and medical student learning styles.

The study reported here focused on the influence of medical students' learning styles (that is, how they prefer to receive and use information in learning and problem-solving situations) on (a) their choice of a medical career type and (b) their sources of information and influence in making that choice. The results suggest that those students with learning styles that are associated with primary care careers are also those who are dissatisfied with a traditional basic science curriculum and are influenced more than the average student by concrete work experiences, as well as identification with role models, in making a career decision. Among the implications of these results for medical school admissions, curricula, and faculty is the possibility that more students might consider primary care careers if more primary care experiences and role models were available in medical school.

Career Choice

Representation learning for multi-modal spatially resolved transcriptomics data.

MOTIVATION: Spatial transcriptomics enables in-depth molecular characterization of samples on a morphology and RNA level while preserving spatial location. Integrating the resulting multi-modal data is an unsolved problem, and developing new solutions in precision medicine depends on improved methodologies. RESULTS: We introduce AESTETIK, a convolutional deep learning model that jointly integrates spatial, transcriptomics, and morphology information to learn accurate spot representations. AESTETIK yielded substantially improved cluster assignments on widely adopted technology platforms (e.g. 10x Genomics™, NanoString™) across multiple datasets. We achieved performance enhancement on structured tissues (e.g. brain) with a 21% increase in median ARI over previous state-of-the-art methods. Notably, AESTETIK also demonstrated superior performance on cancer tissues with heterogeneous cell populations, showing a 2-fold increase in breast cancer, 79% in melanoma, and 21% in liver cancer. We expect that these advances will enable a multi-modal understanding of key biological processes. AVAILABILITY AND IMPLEMENTATION: AESTETIK is implemented in Python 3 and is available as open source software at http://www.github.com/ratschlab/aestetik. The Snakemake pipeline for reproducing the results is available at http://www.github.com/ratschlab/st-rep.

Spatial Transcriptomics

An image-based protein-ligand binding representation learning framework via multi-level flexible dynamics trajectory pre-training.

MOTIVATION: Accurate prediction of protein-ligand binding (PLB) relationships plays a crucial role in drug discovery, which helps identify drugs that modulate the activity of specific targets. Traditional biological assays for measuring PLB relationships are time consuming and costly. In addition, models for predicting PLB relationships have been developed and widely used in drug discovery tasks. However, learning more accurate PLB representations is essential to meet the stringent standards required for drug discovery. RESULTS: We propose an image-based PLB representation learning framework, called ImagePLB, which equips ligand representation learner (LRL) and protein representation learner (PRL) to accept 3D multi-view ligand images and protein graphs as input, respectively, and learns rich interaction information between ligand and protein through a binding representation learner (BRL). Considering the scarcity of protein-ligand pairs, we further propose a multi-level next trajectory prediction (MLNTP) task to pre-train ImagePLB on the 4D flexible dynamics trajectory of 16 972 complexes, including ligand level, protein level, and complex level, to learn information related to trajectories. Besides, by introducing trajectory regularization (TR), we effectively alleviate the problem of high (even almost identical) feature similarity caused by adjacent trajectories. Compared with the current state-of-the-art methods, ImagePLB has achieved competitive improvements on PLB-related prediction tasks, including protein-ligand affinity and efficacy prediction tasks. This study opens the door to the image-based PLB learning paradigm. AVAILABILITY AND IMPLEMENTATION: All data and implementation details of code can be obtained from https://github.com/HongxinXiang/ImagePLB.

Ligands

[Investigation of memory in experimental gerontology (author's transl)].

The possible transfer of learning performance by proteins and ribonucleic acids was studied. 140 male Sprague-Dawley rats aged 3 months and 68 aged 20 months were used. Proteins and ribonucleic acids were isolated from the brains of trained and untrained rats aged 3 months. The difference in learning performance was tested and the incorporation of the above-mentioned substances into the hippo-campus and the residual brain in the two age-groups was measured using radioactive labelled material. A specific transfer of learned information-contents on the molecular level was found only after transfer of proteins in both young and old rats; the results of the training are well correlated with those of the incorporation. The two age-groups differ especially with regard to the learning performance, expressed in the error number. In th older group the error number is significantly lower in contrast to the learning time, that is slightly shorter in the younger group. This can be explained by the differences between the incorporation of brain proteins of trained animals into animals of different age, as well as by the investigations of some authors, who distinguished between different modes of learning. The lower incorporation of labelled substance into the brains of old animals is remarkable; the conclusion is a lower turnover of these substances in the brain of old animals, especially of the ribonucleic-acids. Nevertheless the learning performance of complex information-contents is not impaired.

Aging

Strategy guidance and memory aiding in learning a problem-solving skill.

Guidance can help learners overcome the difficulties of getting started in a novel domain, but it is often ineffective in promoting learning and transfer. This article examines two aspects of guidance--communicating solution strategies for a problem domain and providing working memory support--in learning a novel problem-solving skill. Subjects in two experiments learned to troubleshoot simulated information networks. The learning environment varied in type of guidance provided--none, variable template, fixed template, and procedural instruction--and in availability of memory aiding. Variable-template guidance was effective when memory aiding was provided, and procedural instructions produced effective learning with or without memory aiding. However, fixed-template guidance was not effective, and there was no consistent effect of memory aiding in unguided, discovery learning conditions. The results have theoretical implications for the locus of guided-learning effects and suggest practical guidelines for the design of guided-learning environments.

Computer Communication Networks

Diazepam impairs retention of spatial information without affecting retrieval or cue learning.

We further investigated the effect of diazepam on the processing of spatial information in a water maze task. Diazepam significantly impaired the retention of spatial information in a group of rats trained to locate a hidden platform. In a free swim trial carried out after training, diazepam-treated rats showed no bias to the target quadrant. There was no effect of diazepam on retrieval of spatial information in well-trained rats, and diazepam was devoid of any effect on cue learning in the water maze. However, diazepam blocked latent place learning during cue training in the water maze. Our results indicate that the GABA-BZD receptor modulates spatial information processing and that diazepam specifically impairs the retention of spatial information without affecting retrieval or cue learning.

Animals

Storing covariance with nonlinearly interacting neurons.

A time-dependent, nonlinear model of neuronal interaction which was probabilistically analyzed in a previous article is shown here to be a natural generalization of the Hartline-Ratliff model of the Limulus retina. Although the primary physical variables in the model are the membrane potentials of neurons, the equations which govern the means and covariances of the membrane potentials are coupled through the average firing rates; as a consequence, the average firing rates control the selective storage and retrieval of covariance information. Motor learning in the cerebellar cortex is treated as a problem of covariance storage, and a predicition is made for the underlying synaptic plasticity: the change in synaptic strength between a parallel fiber and a Purkinje cell should be proportional to the covariance between discharges in the parallel fiber and the climbing fiber. Unlike previous proposals for synaptic plasticity, this prediction requires both facilitation and depression to occur (under different conditions) at the same synapse.

Cerebellum

An assessment of informative-counseling procedures for cleft palate children.

32 children with cleft palate and their mothers were interviewed for the purpose of learning what information they had about cleft and cleft management. Their responses were compared with standards specified by eight cleft palate specialists from four disciplines. The findings indicate that the specialists were somewhat inconsistent in what they expected the families to know about clefts and in their routine counseling procedures to provide the information. In general, the mothers had appropriate knowledge about clefts but predicted that their children knew more about clefts and cleft management than was actually the case. The children had less than adequate information about the general impact of a cleft, the etiology of clefts, the rationale for cleft management they had received, and future management of their problem. The results of the study indicate the need or more systematic procedures for providing information to the child with a cleft. The results also suggest the need for additional research about the general counseling process.

Adolescent

What makes information important and its influence on learning in self-directed study.

This study investigated what makes text-based information important and what is its influence on learning. College students studied an expository text following their own self-directed study procedures. Data from Exp. 1 (n = 60) and Exp. 2 (n = 40) showed that information was considered important if it (a) began and ended text, (b) began a paragraph, (c) appeared at somewhat equal intervals in text, and (d) contained enumerations of concepts. Subjects recalled information that (a) began the text and (b) contained examples of enumerations. It appeared that text-based variables established what was important and this influenced learning. Implications for the selective attention hypothesis and its volume-of-attention corollary, the cycles hypothesis, and the slot-filling hypothesis are discussed.

Achievement

Refining sequence-to-activity models by increasing model resolution.

Decoding the cis-regulatory syntax that controls gene expression is essential for improving our understanding of cell differentiation and disease. To identify regulatory motifs and their regulatory syntax, deep learning based sequence-to-activity (S2A) models learn transcription factor binding motifs and their combinations from DNA sequence by modeling measured chromatin accessibility. Previously, we developed AI-TAC, a S2A model that predicts chromatin accessibility across various immune cell types in multi-task fashion, effectively decoding the regulatory syntax underlying immune cell differentiation. While ATAC-seq is commonly used to measure regional accessibility, it also provides high-resolution profiles, the distribution of Tn5 insertion sites, that offer additional insights into the precise location and strength of TF binding sites. Here we demonstrate that modeling ATAC-seq profiles alongside accessibility consistently improves predictions of differential chromatin accessibility across cell types. Moreover, we also find that multi-task learning across related immune cell types consistently outperforms single-task models. To understand what additional information bpAITAC learns from ATAC-seq profiles, we systematically compare sequence attributions from models trained with and without ATAC-seq profiles. We identify novel motifs with strong effect sizes that emerge only when profile data is included. Our findings suggest that modeling ATAC-seq at base-pair resolution enables the model to learn a more nuanced and sensitive representation of the cis-regulatory syntax driving immune cell-specific chromatin landscapes.

ATAC-seq

The efficacy of inpatient education after myocardial infarction.

Nearly half a million Americans will survive an acute myocardial infarction (MI) this year. Nurses often question whether patients who have had an MI are able to absorb, retain, and use information given in the hospital. This review examines the research literature on inpatient education after MI published between 1975 and 1989 to determine (a) what information patients identify as most important, (b) whether inpatient education increases patients' knowledge, (c) whether anxiety prevents or diminishes learning in this setting, (d) whether inpatient education is able to produce lifestyle changes after discharge, and (e) which teaching methods are most effective. Patients identified risk factors as their primary concern. Most studies showed patients were able to learn new information, despite the presence of anxiety, particularly regarding activity after discharge. Inpatient education also stimulated some life-style change after discharge, most frequently in the areas of activity and smoking cessation. Several types of teaching methods were compared; audiovisual methods were found to be at least as effective as one-to-one patient teaching.

Health Behavior

Assessment of attention and memory efficiency in persons with solvent neurotoxicity.

Memory and attention were evaluated in 40 persons with a history of organic solvent exposure and 40 demographically similar controls. Exposed subjects, in comparison to controls, had reduced digit spans, were deficient at learning new information, and recall on a Brown-Peterson distractor test was especially low following a 30-sec interference interval. If original learning was considered, long-term recall was similar for both groups. On a test of sustained attention, the Continuous Performance Test, exposed subjects became less accurate over successive blocks, a pattern opposite to that seen in control subjects. The data suggest that the memory impairment following solvent exposure may result from deficient allocation of attentional resources due to the inability to deal effectively with an increase in processing load.

Attention

Developmental plasticity in neural circuits controlling birdsong: sexual differentiation and the neural basis of learning.

In many species of passerine songbirds, males learn their song during defined periods of life. Female song is often reduced or absent, as are the brain regions controlling song. Sexual differences in the brain arise because of the action of sex steroids, which trigger the formation of some neural pathways (especially the pathway from the higher vocal center to the robust nucleus) and prevent the atrophy of others in males. These neural changes occur during periods of developmental song learning and can recur during periods of learning in adult birds. The process of learning is correlated with major increases or decreases in the numbers of neurons in specific neuronal populations, suggesting that the formation or loss of specific neural pathways regulates the ability to learn. Species differences in sexual differentiation and learning allow informative cross-species comparisons of neural structure and behavior.

Animals