The tidyomics ecosystem: Enhancing omic data analyses.

The growth of omic data presents evolving challenges in data manipulation, analysis, and integration. Addressing these challenges, Bioconductor 1 provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming 2 offers a revolutionary standard for data organisation and manipulation. Here, we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning, and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analysing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas 3 , spanning six data frameworks and ten analysis tools.

Capturing Hydrated Vanadium Ion Dynamics in Ionomer Nanocomposites Used for Redox Flow Batteries.

Herein, we employed high-flux backscattering spectroscopy to capture for the first time the motions of hydrated vanadyl ions in ionomer nanocomposites prepared by both solution-cast and in situ sol-gel condensation methods. Both local and jump diffusion coefficients of the hydrated vanadyl (VO2+) ions as well as the dynamic length scales of ion motions and the fraction of immobile hydrogen atoms were extracted from the scattering spectra. Notably, for solution-cast membranes, the jump and local diffusion coefficients of hydrated VO2+ ions were seen to decrease by over 10- and 4-fold, respectively, with the introduction of 10 mass % silica nanoparticles (SiNPs) compared to their neat counterparts. Further, the VO2+ diffusion coefficients were observed to decrease with thermal annealing, though the impact of annealing was less significant than that seen with the introduction of SiNPs. Finally, in general, thermal annealing and the introduction of SiNPs had no measurable impact on the fraction of immobile hydrogen atoms in both solution-cast and sol-gel ionomer nanocomposites. The data observed in this work, in conjunction with previous structural and chain dynamics studies on hydrated Nafion-SiNP nanocomposites, suggest that a combination of stiffening of the segmental dynamics as well as a decrease in available sulfonic acid groups facilitating transport leads to an overall decrease in mobility of vanadium ions in these ionomer nanocomposites.

Mariner: Explore the Hi-Cs.

MOTIVATION: 3D chromatin structure plays an important role in regulating gene expression and alterations to this structure can result in developmental abnormalities and disease. While genomic approaches like Hi-C and Micro-C can provide valuable insights in 3D chromatin architecture, the resulting data sets are extremely large and difficult to manipulate. RESULTS: Here, we present mariner, a rapid and memory efficient tool to extract, aggregate, and plot data from Hi-C matrices within the R/Bioconductor environment. Mariner simplifies the process of querying and extracting contacts from multiple Hi-C files using a parallel and block-processing approach. Modular functions allow complete workflow customization for advanced users, yet all-in-one functions are available for running the most common types of analyses. Finally, tight integration with existing Bioconductor infrastructure enables complete analysis and visualization of Hi-C data in R. AVAILABILITY: Available on GitHub at https://github.com/EricSDavis/mariner and on Bioconducter at https://www.bioconductor.org/packages/release/bioc/html/mariner.html. SUPPLEMENTARY INFORMATION: Supplementary figures are available at Bioinformatics online.

Racial/ethnic disparities in availability of volunteer unrelated donors for allogeneic transplantation.

ABSTRACT: Despite the global unrelated donor (URD) registry size, the degree to which URD availability is a transplant barrier is not established. We evaluated the availability of 3,843 URDs requested for 455 diverse adult patients (predominantly with acute leukemia). URDs for non-Europeans were more likely to be domestic and had markedly lower Donor Readiness scores. Of URDs requested for confirmatory HLA-typing (CT) alone (ie, without simultaneous workup), 1,894 of 3,529 (54%) were available. Availability of domestic URDs was 45%. Donor Readiness score was highly predictive of CT availability. More non-European patients (n = 120) than Europeans (n = 335) had >10 URDs requested and <5 available. Of workup requests (after CT or CT-workup), <70% (604/889 [68%]) were available. More non-Europeans had <2 URDs available. URD availability for CT was markedly worse for non-Europeans, with availabilities for African, non-Black Hispanic, and Asian patients being 150/458 (33%), 120/258 (47%), and 119/270 (44%), respectively, with further decrements in URD workup availability. Our data suggest the functional size of the URD pool is much smaller than appreciated, mandating major operational changes for transplant centers and donor registries. Likelihood of donor availability should have a high priority in donor selection. Considering patient ancestry and URD Donor Readiness scores, centers should pursue, and registries permit, simultaneous pursuit of many URDs and abandon futile searches. Patients should be informed about their likelihood of donor availability and alternative options. Finally, although registries should address high URD attrition and speed procurement, use of all HLA-disparate graft types is needed to facilitate timely transplant for all.

Improvement in non-24-h sleep-wake rhythm disorder in a sighted individual treated with a melatonin receptor agonist.

Non-24-hour sleep-wake rhythm disorder (N24SWD) typically presents in patients with visual impairments that disrupt the ability to entrain to the 24 hour solar cycle. We discuss a 43 year old sighted man who presented with periodic daytime hypersomnia and nighttime insomnia, occasionally leading to <3 hours of sleep per day. Previous polysomnography showed an apnea hypopnea index of 6.2 events per hour. A sleep log of 3 months showed irregular time of sleep onset, and an average of 3 hours of sleep per day. Wrist actigraphy confirmed N24SWD. A trial of tasimelteon 20 mg/day resulting in improved daytime hypersomnia (pre-Epworth Sleepiness Scale (ESS) = 21/24, post-ESS = 5/24; a score of > 10/24 is considered sleepy). Follow-up actigraphy showed marked resolution of phase delay with an average of five hours of sleep. The case demonstrates that tasimelteon is a possible treatment for N24SWD in sighted individuals.

Characterization of sleep efficiency transitions in family caregivers.

Family caregivers are at high risk of psychological distress and low sleep efficiency resulting from their caregiving responsibilities. Although psychological symptoms are associated with sleep efficiency, there is limited knowledge about the association of psychological distress with variations in sleep efficiency. We aimed to characterize the short- and long-term patterns of caregivers' sleep efficiency using Markov chain models and compare these patterns between groups with high and low psychological symptoms (i.e., depression, anxiety, and caregiving stress). Based on 7-day actigraphy data from 33 caregivers, we categorized sleep efficiency into three states, < 75% (S1), 75-84% (S2), and ≥ 85% (S3), and developed Markov chain models. Caregivers were likely to maintain a consistent sleep efficiency state from one night to the next without returning efficiently to a normal state. On average, it took 3.6-5.1 days to return to a night of normal sleep efficiency (S3) from lower states, and the long-term probability of achieving normal sleep was 42%. We observed lower probabilities of transitioning to or remaining in a normal sleep efficiency state (S3) in the high depression and anxiety groups compared to the low symptom groups. The differences in the time required to return to a normal state were inconsistent by symptom levels. The long-term probability of achieving normal sleep efficiency was significantly lower for caregivers with high depression and anxiety compared to the low symptom groups. Caregivers' sleep efficiency appears to remain relatively consistent over time and does not show rapid recovery. Caregivers with higher levels of depression and anxiety may be more vulnerable to sustained suboptimal sleep efficiency.

Anatomical Substrates of Rapid Eye Movement Sleep Rebound in a Rodent Model of Post-sevoflurane Sleep Disruption.

BACKGROUND: Previous research suggests that sevoflurane anesthesia may prevent the brain from accessing rapid eye movement (REM) sleep. If true, then patterns of neural activity observed in REM-on and REM-off neuronal populations during recovery from sevoflurane should resemble those seen after REM sleep deprivation. In this study, the authors hypothesized that, relative to controls, animals exposed to sevoflurane present with a distinct expression pattern of c-Fos, a marker of neuronal activation, in a cluster of nuclei classically associated with REM sleep, and that such expression in sevoflurane-exposed and REM sleep-deprived animals is largely similar. METHODS: Adult rats and Targeted Recombination in Active Populations mice were implanted with electroencephalographic electrodes for sleep-wake recording and randomized to sevoflurane, REM deprivation, or control conditions. Conventional c-Fos immunohistochemistry and genetically tagged c-Fos labeling were used to quantify activated neurons in a group of REM-associated nuclei in the midbrain and basal forebrain. RESULTS: REM sleep duration increased during recovery from sevoflurane anesthesia relative to controls (157.0 ± 24.8 min vs. 124.2 ± 27.8 min; P = 0.003) and temporally correlated with increased c-Fos expression in the sublaterodorsal nucleus, a region active during REM sleep (176.0 ± 36.6 cells vs. 58.8 ± 8.7; P = 0.014), and decreased c-Fos expression in the ventrolateral periaqueductal gray, a region that is inactive during REM sleep (34.8 ± 5.3 cells vs. 136.2 ± 19.6; P = 0.001). Fos changes similar to those seen in sevoflurane-exposed mice were observed in REM-deprived animals relative to controls (sublaterodorsal nucleus: 85.0 ± 15.5 cells vs. 23.0 ± 1.2, P = 0.004; ventrolateral periaqueductal gray: 652.8 ± 71.7 cells vs. 889.3 ± 66.8, P = 0.042). CONCLUSIONS: In rodents recovering from sevoflurane, REM-on and REM-off neuronal activity maps closely resemble those of REM sleep-deprived animals. These findings provide new evidence in support of the idea that sevoflurane does not substitute for endogenous REM sleep.

Whey Protein Supplementation and Type 2 Diabetes Mellitus Risk Factors: An Umbrella Systematic Review of Randomized Controlled Trials.

Emerging research suggests whey protein (WP) supplementation may modify type 2 diabetes mellitus (T2DM) risk factors, including glucose control. As systematic reviews and/or meta-analyses of randomized controlled trials (RCTs) gain importance in nutrition literature, we conducted an umbrella systematic review to chronicle published systematic reviews and/or meta-analyses of RCTs pertinent to WP supplementation and T2DM modifiable risk factors. This review was conducted in accordance with Preferred Reporting Items for Overviews of Reviews standards. Potentially eligible articles were identified via a systematic search of 5 electronic health research databases (PubMed, Cochrane Library, CINAHL [EBSCO], Scopus, and SPORTDiscus [EBSCO]). Included articles were assessed for quality using the "A MeaSurement Tool to Assess systematic Reviews 2" critical appraisal tool. Thirteen articles, representing 109 unique RCTs, of the 2205 identified articles met the inclusion criteria. Nine articles (69%) were deemed high quality, 2 (15%) moderate quality, and 2 (15%) low quality. Findings from this umbrella review of 13 systematic reviews, including 12 meta-analyses, suggest WP may lower hemoglobin A1c, homeostasis model assessment of insulin resistance, and fasting insulin in groups classified as overweight/obese or at risk for or with metabolic syndrome; blood triglycerides in groups classified as overweight/obese or at risk for or with metabolic syndrome; and blood pressure in groups classified as overweight/obese. WP did not differentially affect C-reactive protein, body weight, body mass index, or waist circumference, nor did it adversely affect any T2DM risk factors. Insufficient evidence precluded assessing the influence of WP on glucose control-related outcomes in groups classified at lower risk for T2DM. Information regarding WP dose, duration, or types was insufficient to draw conclusions. Collectively, evidence suggests WP supplementation may improve multiple clinical indicators of glucose control, along with triglycerides and blood pressure, in groups of adults at increased risk of developing T2DM.

Guiding the design of well-powered Hi-C experiments to detect differential loops.

Motivation: Three-dimensional chromatin structure plays an important role in gene regulation by connecting regulatory regions and gene promoters. The ability to detect the formation and loss of these loops in various cell types and conditions provides valuable information on the mechanisms driving these cell states and is critical for understanding long-range gene regulation. Hi-C is a powerful technique for characterizing 3D chromatin structure; however, Hi-C can quickly become costly and labor-intensive, and proper planning is required to ensure efficient use of time and resources while maintaining experimental rigor and well-powered results. Results: To facilitate better planning and interpretation of human Hi-C experiments, we conducted a detailed evaluation of statistical power using publicly available Hi-C datasets, paying particular attention to the impact of loop size on Hi-C contacts and fold change compression. In addition, we have developed Hi-C Poweraid, a publicly hosted web application to investigate these findings. For experiments involving well-replicated cell lines, we recommend a total sequencing depth of at least 6 billion contacts per condition, split between at least two replicates to achieve the power to detect differences in the majority of loops. For experiments with higher variation, more replicates and deeper sequencing depths are required. Values for specific cases can be determined by using Hi-C Poweraid. This tool simplifies Hi-C power calculations, allowing for more efficient use of time and resources and more accurate interpretation of experimental results. Availability and implementation: Hi-C Poweraid is available as an R Shiny application deployed at http://phanstiel-lab.med.unc.edu/poweraid/, with code available at https://github.com/sarmapar/poweraid.

Chromatin loop dynamics during cellular differentiation are associated with changes to both anchor and internal regulatory features.

Three-dimensional (3D) chromatin structure has been shown to play a role in regulating gene transcription during biological transitions. Although our understanding of loop formation and maintenance is rapidly improving, much less is known about the mechanisms driving changes in looping and the impact of differential looping on gene transcription. One limitation has been a lack of well-powered differential looping data sets. To address this, we conducted a deeply sequenced Hi-C time course of megakaryocyte development comprising four biological replicates and 6 billion reads per time point. Statistical analysis revealed 1503 differential loops. Gained loop anchors were enriched for AP-1 occupancy and were characterized by large increases in histone H3K27ac (over 11-fold) but relatively small increases in CTCF and RAD21 binding (1.26- and 1.23-fold, respectively). Linear modeling revealed that changes in histone H3K27ac, chromatin accessibility, and JUN binding were better correlated with changes in looping than RAD21 and almost as well correlated as CTCF. Changes to epigenetic features between-rather than at-boundaries were highly predictive of changes in looping. Together these data suggest that although CTCF and RAD21 may be the core machinery dictating where loops form, other features (both at the anchors and within the loop boundaries) may play a larger role than previously anticipated in determining the relative loop strength across cell types and conditions.

Equine Gunshot Euthanasia: Creation of a 3D-Printed Model with Integrated Sensors for Training.

Challenges and issues related to the use of pentobarbital euthanasia and disposal of animal remains within the US have recently been reviewed. Environmental and public health challenges increasingly necessitate consideration of alternative methods such as gunshots, an American Veterinary Medical Association (AVMA) "acceptable with conditions" method, for the humane euthanasia of horses. A recent study reported a correctly aimed gunshot provides a humane option for euthanizing horses. However, although aiming guidelines exist, studies examining bullet trajectories in animals euthanized by gunshot have reported that inadequate disruption of the brain is a serious welfare issue. Here, we report the development and production of a portable, reusable, equine gunshot euthanasia training model. Using 3D printing, an anatomically accurate model of an equine head has been developed, with external aiming landmarks and equipped with integrated laser sensors and LED eyes. The laser sensors are embedded in two specific anatomical tracts (pons and medulla) with aiming paths associated with the aiming landmarks to train correct aiming angle. The LED eyes are linked to the laser sensors to provide instant feedback on aiming accuracy. When a beam from a commercially available blue training gun laser travels along the correct aiming path and strikes the sensor inside the head, the lights in the model's eyes go out and there is an audible signal, providing immediate feedback on the accuracy of the shot. The model facilitates the training of veterinary personnel and first responders in successful gunshot euthanasia, providing instantaneous feedback on the likelihood of a shot causing immediate, humane death in a live animal.

Excellent leukemia control after second hematopoietic cell transplants with unrelated cord blood grafts for post-transplant relapse in pediatric patients.

Background: Patients with leukemia relapse after allogeneic hematopoietic cell transplant (HCT) have poor survival due to toxicity and disease progression. A second HCT often offers the only curative treatment. Methods: We retrospectively reviewed our bi-institutional experience (MSKCC-USA; Utrecht-NL) with unrelated cord blood transplantation (CBT) for treatment of post-transplant relapse. Overall survival (OS) and event-free survival (EFS) were evaluated using the Kaplan-Meier method, treatment-related mortality (TRM) and relapse were evaluated using the competing risk method by Fine-Gray. Results: Twenty-six patients age < 21 years received a second (n=24) or third (n=2) HCT with CB grafts during the period 2009-2021. Median age at first HCT (HCT1) was 11.5 (range: 0.9-17.7) years and all patients received myeloablative cytoreduction. Median time from HCT1 to relapse was 12.8 (range 5.5-189) months. At CBT, median patient age was 13.5 (range 1.4-19.1) years. Diagnoses were AML: 13; ALL: 4, MDS: 5, JMML: 2; CML: 1; mixed phenotype acute leukemia: 1. Sixteen patients (62%) were in advanced stage, either CR>2 or with active disease. Median time from HCT1 to CBT was 22.2 (range 7-63.2) months. All patients engrafted after CBT. Thirteen patients developed acute GvHD; 7 had grade III or IV. With a median survivor follow-up of 46.6 (range 17.4-155) months, 3-year OS was 69.2% (95% CI 53.6-89.5%) and 3-year EFS was 64.9% (95% CI 48.8-86.4%). Eight patients died, 3 of AML relapse and 5 due to toxicity (respiratory failure [n=4], GvHD [n=1]) at a median time of 7.7 (range 5.9-14.4) months after CBT. Cumulative incidence of TRM at 3 years was 19.2% (95% CI 4.1-34.4%). Notably, all TRM events occurred in patients transplanted up to 2015; no toxicity-related deaths were seen in the 16 patients who received CBT after 2015. Cumulative incidence of relapse was 15.9% (95% CI 1.6-30.2%) at 3 years, remarkably low for these very high-risk patients. Conclusions: Survival was very encouraging following CB transplants in pediatric patients with recurrent leukemia after first HCT, and TRM has been low over the last decade. CBT needs to be strongly considered as a relatively safe salvage therapy option for post-transplant relapse.

Proximity-dependent recruitment of Polycomb repressive complexes by the lncRNA Airn.

During mouse embryogenesis, expression of the long non-coding RNA (lncRNA) Airn leads to gene repression and recruitment of Polycomb repressive complexes (PRCs) to varying extents over a 15-Mb domain. The mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells that Airn expression induces long-range changes to chromatin architecture that coincide with PRC-directed modifications and center around CpG island promoters that contact the Airn locus even in the absence of Airn expression. Intensity of contact between the Airn lncRNA and chromatin correlated with underlying intensity of PRC recruitment and PRC-directed modifications. Deletion of CpG islands that contact the Airn locus altered long-distance repression and PRC activity in a manner that correlated with changes in chromatin architecture. Our data imply that the extent to which Airn expression recruits PRCs to chromatin is controlled by DNA regulatory elements that modulate proximity of the Airn lncRNA product to its target DNA.

Effects of Consuming Ounce-Equivalent Portions of Animal- vs. Plant-Based Protein Foods, as Defined by the Dietary Guidelines for Americans on Essential Amino Acids Bioavailability in Young and Older Adults: Two Cross-Over Randomized Controlled Trials.

BACKGROUND: The Dietary Guidelines for Americans (DGA) recommends consuming a variety of "Protein Foods" based on "ounce-equivalent" (oz-eq) portions. No study has assessed the same oz-eq portions of animal- vs. plant-based protein foods on essential amino acid (EAA) bioavailability for protein anabolism in young and older adults. OBJECTIVES: We assessed the effects of consuming two oz-eq portions of pork, eggs, black beans, and almonds on postprandial EAA bioavailability in young and older adults. METHODS: We conducted two investigator-blinded, randomized crossover trials in young (n = 30; mean age ± SD: 26.0 ± 4.9 y) and older adults (n = 25; mean age ± SD: 64.2 ± 6.6 y). Participants completed four testing sessions where they consumed a standardized meal with two oz-eq of either unprocessed lean pork, whole eggs, black beans, or sliced almonds. Blood samples were taken at baseline and 30, 60, 120, 180, 240, and 300 min postprandially. Plasma EAA bioavailability was based on postprandial integrated positive areas under the curve. RESULTS: Participant age did not affect EAA bioavailability among the four protein foods tested. Two oz-eq portions of pork (7.36 g EAA) and eggs (5.38 g EAA) resulted in greater EAA bioavailability than black beans (3.02 g EAA) and almonds (1.85 g EAA) in young and older adults, separately or combined (p < 0.0001 for all). Pork resulted in greater EAA bioavailability than eggs in young adults (p < 0.0001), older adults (p = 0.0007), and combined (p < 0.0001). There were no differences in EAA bioavailability between black beans and almonds. CONCLUSIONS: The same "oz-eq" portions of animal- and plant-based protein foods do not provide equivalent EAA content and postprandial bioavailability for protein anabolism in young and older adults.

Chronic Neurocognitive, Neuropsychological, and Pulmonary Symptoms in Outpatient and Inpatient Cohorts After COVID-19 Infection.

Neuropsychological symptoms associated with post-COVID-19 conditions may prevent patients from resuming normal activities at home or work. We report a retrospective, cross-sectional evaluation of neuropsychological and cardiopulmonary outcomes in 2 groups of patients: outpatients with mild enough infection to be spared from hospitalization and those who required inpatient admission. We hypothesized a dose-response model of post-COVID symptom severity in which persistent consequences would be more severe in those who experienced worse acute infections. In a dedicated COVID clinic, 321 patients were seen (33% outpatient, 67% inpatient). Outpatients skewed female, White, non-Hispanic, and younger. Outpatients had worse insomnia (measured with insomnia severity index) and were less able to resume their usual activities (EQ-5D-5L usual activities scale), despite inpatients experiencing worse cognition (Montreal Cognitive Assessment), having greater obesity (body mass index), decreased exercise tolerance (6-minute-walk distance), and more exertional oxygen desaturation. In both groups, insomnia worsened while cognition improved significantly with time from infection to testing while controlling for patient age; other variables did not. In logistic regression, female sex, higher MoCA score, EQ-5D-5L "usual activities" subscore, less oxygen desaturation with exertion, and longer time from infection remained as significant associations with outpatient status. Our study demonstrated that the functional sequelae of post-COVID-19 conditions in patients with mild acute disease have the potential to be as severe as that in patients who have recovered from severe illness.

Chromatin alternates between A and B compartments at kilobase scale for subgenic organization.

Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critically examine nuclear compartments and CTCF loop-proximal interactions using a combination of in situ Hi-C at unparalleled depth, algorithm development, and biophysical modeling. Producing a large Hi-C map with 33 billion contacts in conjunction with an algorithm for performing principal component analysis on sparse, super massive matrices (POSSUMM), we resolve compartments to 500 bp. Our results demonstrate that essentially all active promoters and distal enhancers localize in the A compartment, even when flanking sequences do not. Furthermore, we find that the TSS and TTS of paused genes are often segregated into separate compartments. We then identify diffuse interactions that radiate from CTCF loop anchors, which correlate with strong enhancer-promoter interactions and proximal transcription. We also find that these diffuse interactions depend on CTCF's RNA binding domains. In this work, we demonstrate features of fine-scale chromatin organization consistent with a revised model in which compartments are more precise than commonly thought while CTCF loops are more protracted.

Sleep Fragmentation, Electroencephalographic Slowing, and Circadian Disarray in a Mouse Model for Intensive Care Unit Delirium.

BACKGROUND: We aimed to further validate our previously published animal model for delirium by testing the hypothesis that in aged mice, Anesthesia, Surgery and simulated ICU conditions (ASI) induce sleep fragmentation, electroencephalographic (EEG) slowing, and circadian disarray consistent with intensive care unit (ICU) patients with delirium. METHODS: A total of 41 mice were used. Mice were implanted with EEG electrodes and randomized to ASI or control groups. ASI mice received laparotomy, anesthesia, and simulated ICU conditions. Controls did not receive ASI. Sleep was recorded at the end of ICU conditions, and hippocampal tissue was collected on EEG recording. Arousals, EEG dynamics, and circadian gene expression were compared with t tests. Two-way repeated measures analysis of variance (RM ANOVA) was used to assess sleep according to light. RESULTS: ASI mice experienced frequent arousals (36.6 ± 3.2 vs 26.5 ± 3.4; P = .044; 95% confidence interval [CI], 0.29-19.79; difference in mean ± SEM, 10.04 ± 4.62) and EEG slowing (frontal theta ratio, 0.223 ± 0.010 vs 0.272 ± 0.019; P = .026; 95% CI, -0.091 to -0.007; difference in mean ± SEM, -0.05 ± 0.02) relative to controls. In ASI mice with low theta ratio, EEG slowing was associated with a higher percentage of quiet wakefulness (38.2 ± 3.6 vs 13.4 ± 3.8; P = .0002; 95% CI, -35.87 to -13.84; difference in mean ± SEM, -24.86 ± 5.19). ASI mice slept longer during the dark phases of the circadian cycle (nonrapid eye movement [NREM], dark phase 1 [D1]: 138.9 ± 8.1 minutes vs 79.6 ± 9.6 minutes, P = .0003, 95% CI, -95.87 to -22.69, predicted mean difference ± SE: -59.28 ± 13.89; NREM, dark phase 2 (D2): 159.3 ± 7.3 minutes vs 112.6 ± 15.5 minutes, P = .006, 95% CI, -83.25 to -10.07, mean difference ± SE, -46.66 ± 13.89; rapid eye movement (REM), D1: 20.5 ± 2.1 minutes vs 5.8 ± 0.8 minutes, P = .001, 95% CI, -24.60 to -4.71, mean difference ± SE, -14. 65 ± 3.77; REM, D2: 21.0 ± 2.2 minutes vs 10.3 ± 1.4 minutes, P = .029, 95% CI, -20.64 to -0.76, mean difference ± SE, -10.70 ± 3.77). The expression of essential circadian genes was also lower in ASI mice (basic helix-loop-helix ARNT like [BMAL1] : -1.3 fold change; circadian locomotor output cycles protein kaput [CLOCK] : -1.2). CONCLUSIONS: ASI mice experienced EEG and circadian changes mimicking those of delirious ICU patients. These findings support further exploration of this mouse approach to characterize the neurobiology of delirium.