Limited Sustained Remission After Nucleos(t)ide Analog Withdrawal: Results From a Large, Global, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study).

INTRODUCTION: Complete viral suppression with nucleos(t)ide analogs (NAs) has led to a profound reduction in hepatocellular carcinoma and mortality among patients with chronic hepatitis B. Finite therapy yields higher rates of functional cure; however, initial hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) elevations are almost certain after treatment interruption. We aimed to analyze off-treatment outcomes beyond 12 months after NA cessation. METHODS: Patients with well-suppressed chronic hepatitis B who were hepatitis B e antigen-negative at NA cessation and remained off treatment without hepatitis B surface antigen (HBsAg) loss at 12 months were included (n = 945). HBV DNA and ALT fluctuations were allowed within the first 12 months. We used Kaplan-Meier methods to analyze outcomes beyond 12 months. Sustained remission was defined as HBV DNA <2,000 IU/mL and ALT <2× upper limit of normal (ULN) and an ALT flare as ALT ≥5× ULN. RESULTS: Cumulative probability of sustained remission was 29.7%, virological relapse was 65.2% with a mean peak HBV DNA of 5.0 ± 1.5 log 10 IU/mL, an ALT flare was 15.6% with a median peak ALT × ULN of 8.3 (5.7-11.3), HBsAg loss was 9.9% and retreatment was 34.9% at 48 months after NA cessation. A single occurrence of virological relapse or an ALT flare within the first 12 months off-treatment were associated with significantly lower rates of sustained remission beyond 12 months. DISCUSSION: Despite allowing for HBV DNA and ALT fluctuations within the first 12 months off-treatment, most patients without HBsAg loss did not maintain a sustained response thereafter. The best candidates for NA withdrawal are patients with low HBsAg levels at NA cessation, and those without profound or recurrent virological and biochemical relapses in the first off-treatment year.

Nursing Variables Predicting Readmissions in Patients With a High Risk: A Scoping Review.

Unplanned readmission endangers patient safety and increases unnecessary healthcare expenditure. Identifying nursing variables that predict patient readmissions can aid nurses in providing timely nursing interventions that help patients avoid readmission after discharge. We aimed to provide an overview of the nursing variables predicting readmission of patients with a high risk. The authors searched five databases-PubMed, CINAHL, EMBASE, Cochrane Library, and Scopus-for publications from inception to April 2023. Search terms included "readmission" and "nursing records." Eight studies were included for review. Nursing variables were classified into three categories-specifically, nursing assessment, nursing diagnosis, and nursing intervention. The nursing assessment category comprised 75% of the nursing variables; the proportions of the nursing diagnosis (25%) and nursing intervention categories (12.5%) were relatively low. Although most variables of the nursing assessment category focused on the patients' physical aspect, emotional and social aspects were also considered. This study demonstrated how nursing care contributes to patients' adverse outcomes. The findings can assist nurses in identifying the essential nursing assessment, diagnosis, and interventions, which should be provided from the time of patients' admission. This can mitigate preventable readmissions of patients with a high risk and facilitate their safe transition from an acute care setting to the community.

Active sensing with predictive coding and uncertainty minimization.

We present an end-to-end architecture for embodied exploration inspired by two biological computations: predictive coding and uncertainty minimization. The architecture can be applied to any exploration setting in a task-independent and intrinsically driven manner. We first demonstrate our approach in a maze navigation task and show that it can discover the underlying transition distributions and spatial features of the environment. Second, we apply our model to a more complex active vision task, whereby an agent actively samples its visual environment to gather information. We show that our model builds unsupervised representations through exploration that allow it to efficiently categorize visual scenes. We further show that using these representations for downstream classification leads to superior data efficiency and learning speed compared to other baselines while maintaining lower parameter complexity. Finally, the modular structure of our model facilitates interpretability, allowing us to probe its internal mechanisms and representations during exploration.

Exploring the Architectural Biases of the Canonical Cortical Microcircuit.

The cortex plays a crucial role in various perceptual and cognitive functions, driven by its basic unit, the canonical cortical microcircuit. Yet, we remain short of a framework that definitively explains the structure-function relationships of this fundamental neuroanatomical motif. To better understand how physical substrates of cortical circuitry facilitate their neuronal dynamics, we employ a computational approach using recurrent neural networks and representational analyses. We examine the differences manifested by the inclusion and exclusion of biologically-motivated inter-areal laminar connections on the computational roles of different neuronal populations in the microcircuit of two hierarchically-related areas, throughout learning. Our findings show that the presence of feedback connections correlates with the functional modularization of cortical populations in different layers, and provides the microcircuit with a natural inductive bias to differentiate expected and unexpected inputs at initialization. Furthermore, when testing the effects of training the microcircuit and its variants with a predictive-coding inspired strategy, we find that doing so helps better encode noisy stimuli in areas of the cortex that receive feedback, all of which combine to suggest evidence for a predictive-coding mechanism serving as an intrinsic operative logic in the cortex.

Temporal resolution of spike coding in feedforward networks with signal convergence and divergence.

Convergent and divergent structures in the networks that make up biological brains are found universally across many species and brain regions at various scales. Neurons in these networks fire action potentials, or "spikes", whose precise timing is becoming increasingly appreciated as large sources of information about both sensory input and motor output. While previous theories on coding in convergent and divergent networks have largely neglected the role of precise spike timing, our model and analyses place this aspect at the forefront. For a suite of stimuli with different timescales, we demonstrate that structural bottlenecks (small groups of neurons) post-synaptic to network convergence have a stronger preference for spike timing codes than expansion layers created by structural divergence. Additionally, we found that a simple network model with similar convergence and divergence ratios to those found experimentally can reproduce the relative contribution of spike timing information about motor output in the hawkmoth Manduca sexta. Our simulations and analyses suggest a relationship between the level of convergent/divergent structure present in a feedforward network and the loss of stimulus information encoded by its population spike trains as their temporal resolution decreases, which could be confirmed experimentally across diverse neural systems in future studies. We further show that this relationship can be generalized across different models and measures, implying a potentially fundamental link between network structure and coding strategy using spikes.

Stimulus type shapes the topology of cellular functional networks in mouse visual cortex.

On the timescale of sensory processing, neuronal networks have relatively fixed anatomical connectivity, while functional interactions between neurons can vary depending on the ongoing activity of the neurons within the network. We thus hypothesized that different types of stimuli could lead those networks to display stimulus-dependent functional connectivity patterns. To test this hypothesis, we analyzed single-cell resolution electrophysiological data from the Allen Institute, with simultaneous recordings of stimulus-evoked activity from neurons across 6 different regions of mouse visual cortex. Comparing the functional connectivity patterns during different stimulus types, we made several nontrivial observations: (1) while the frequencies of different functional motifs were preserved across stimuli, the identities of the neurons within those motifs changed; (2) the degree to which functional modules are contained within a single brain region increases with stimulus complexity. Altogether, our work reveals unexpected stimulus-dependence to the way groups of neurons interact to process incoming sensory information.

White matter microstructure of children with sensory over-responsivity is associated with affective behavior.

BACKGROUND: Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. METHODS: Children ages 8-12 years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. RESULTS: Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. CONCLUSION: White matter microstructure is related to affective behavior in children with SOR.