bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth of disc-like pseudo-bulges in SDSS DR7 since z = 0.1
Authors: Kumar Ankit , Kataria Sandeep Kumar
Published: May 2022

Cosmological simulations predict more classical bulges than their observational counterparts in the local Universe. Here, we quantify evolution of the bulges since z = 0.1 using photometric parameters of nearly 39 000 unbarred disc galaxies from SDSS DR7 which are well represented by two components. We adopted a combination of the Sérsic index and Kormendy relation to separate classical bulges and disc-like pseudo-bulges. We found that the fraction of pseudo-bulges (classical bulges) smoothly increases (decreases) as the Universe gets older. In the history of the Universe, there comes a point (z ≈ 0.016) when classical bulges and pseudo-bulges become equal in number. The fraction of pseudo-bulges rises with increasing bulge to disc half-light radius ratio until Re/Rhlr ≈ 0.6 suggesting that a concentrated disc is the most favourable place for pseudo-bulge formation. The mean ellipticity of pseudo-bulges is always greater than that of classical bulges and it decreases with decreasing redshift, indicating that the bulges tend to be more axisymmetric with evolution. Also, the massive bulges are progressing towards axisymmetry at steeper rate than the low-mass bulges. There is no tight correlation of bulge Sérsic index evolution with other photometric properties of the galaxy. Using the sample of multicomponent fitting of S4G data and N-body galaxy models, we have verified that our results are consistent or even more pronounced with multicomponent fitting and high-resolution photometry.
Inference of cell state transitions and cell fate plasticity from single-cell with MARGARET
Authors: Pandey Kushagra , Zafar Hamim
Published: May 2022

Despite recent advances in inferring cellular dynamics using single-cell RNA-seq data, existing trajectory inference (TI) methods face difficulty in accurately reconstructing the cell-state manifold and cell-fate plasticity for complex topologies. Here, we present MARGARET (https://github.com/Zafar-Lab/Margaret) for inferring single-cell trajectory and fate mapping for diverse dynamic cellular processes. MARGARET reconstructs complex trajectory topologies using a deep unsupervised metric learning and a graph-partitioning approach based on a novel connectivity measure, automatically detects terminal cell states, and generalizes the quantification of fate plasticity for complex topologies. On a diverse benchmark consisting of synthetic and real datasets, MARGARET outperformed state-of-the-art methods in recovering global topology and cell pseudotime ordering. For human hematopoiesis, MARGARET accurately identified all major lineages and associated gene expression trends and helped identify transitional progenitors associated with key branching events. For embryoid body differentiation, MARGARET identified novel transitional populations that were validated by bulk sequencing and functionally characterized different precursor populations in the mesoderm lineage. For colon differentiation, MARGARET characterized the lineage for BEST4/OTOP2 cells and the heterogeneity in goblet cell lineage in the colon under normal and inflamed ulcerative colitis conditions. Finally, we demonstrated that MARGARET can scale to large scRNA-seq datasets consisting of ∼ millions of cells.
RNF4 controls the extent of replication fork reversal to preserve genome stability
Authors: Ding Linli , Luo Yi , Tian Tian , Chen Xu , Yang Yulan , Bu Min , Han Jinhua , Yang Bing , Yan Haiyan , Liu Ting , Wu Mengjie , Zhang Guofei , Xu Yipeng , Zhu Shaoxing , Huen Michael S Y , Mao Genxiang , Huang Jun
Published: May 2022

Replication fork reversal occurs via a two-step process that entails reversal initiation and reversal extension. DNA topoisomerase IIalpha (TOP2A) facilitates extensive fork reversal, on one hand through resolving the topological stress generated by the initial reversal, on the other hand via its role in recruiting the SUMO-targeted DNA translocase PICH to stalled forks in a manner that is dependent on its SUMOylation by the SUMO E3 ligase ZATT. However, how TOP2A activities at stalled forks are precisely regulated remains poorly understood. Here we show that, upon replication stress, the SUMO-targeted ubiquitin E3 ligase RNF4 accumulates at stalled forks and targets SUMOylated TOP2A for ubiquitination and degradation. Downregulation of RNF4 resulted in aberrant activation of the ZATT–TOP2A–PICH complex at stalled forks, which in turn led to excessive reversal and elevated frequencies of fork collapse. These results uncover a previously unidentified regulatory mechanism that regulates TOP2A activities at stalled forks and thus the extent of fork reversal.
Critical roles of mitochondrial fatty acid synthesis in tomato development and environmental response
Authors: Zhou Yuhong , Yu Huiyang , Tang Yaping , Chen Rong , Luo Jinying , Shi Chunmei , Tang Shan , Li Xin , Shen Xinyan , Chen Rongfeng , Zhang Yuyang , Lu Yongen , Ye Zhibiao , Guo Liang , Ouyang Bo
Published: May 2022

Plant mitochondrial fatty acid synthesis (mtFAS) appears to be important in photorespiration based on the reverse genetics research from Arabidopsis (Arabidopsis thaliana) in recent years, but its roles in plant development have not been completely explored. Here, we identified a tomato (Solanum lycopersicum) mutant, fern-like, which displays pleiotropic phenotypes including dwarfism, yellowing, curly leaves, and increased axillary buds. Positional cloning and genetic and heterozygous complementation tests revealed that the underlying gene FERN encodes a 3-hydroxyl-ACP dehydratase enzyme involved in mtFAS. FERN was causally involved in tomato morphogenesis by affecting photorespiration, energy supply, and the homeostasis of reactive oxygen species. Based on lipidome data, FERN and the mtFAS pathway may modulate tomato development by influencing mitochondrial membrane lipid composition and other lipid metabolic pathways. These findings provide important insights into the roles and importance of mtFAS in tomato development.
Perceived Pain and Smoking Interrelations Among Veterans with Chronic Pain Enrolled in a Smoking Cessation Trial
Authors: Lee Megan , Bastian Lori A , LaRowe Lisa , DeRycke Eric C , Relyea Mark , Becker William C , Ditre Joseph W
Published: May 2022

Introduction

The Pain and Smoking Inventory (PSI) measures patients’ perceived interrelations of their pain and smoking behavior, and it comprises three conceptually distinct domains: smoking to cope with pain (PSI-Cope), pain as a motivator of smoking (PSI-Motivate), and pain as a barrier to cessation (PSI-Barrier). Associations between PSI scores and pain interference and self-efficacy to quit smoking, two measures that can affect cessation outcomes, remain unclear.

Methods

We conducted a secondary analysis of baseline data from 371 veterans with chronic pain (88% male, Medianage =60) enrolled in a randomized smoking cessation trial. We used sequential multivariate regression models to examine associations between the three PSI domains and pain interference / self-efficacy.

Results

Of 371 veterans who completed baseline surveys, 88% were male, with a median age of 60 years. PSI-Motivate scores were positively associated with pain interference (beta [B]: 0.18, 95% confidence interval [CI]: 0.02 to 0.34). PSI-Barrier subscores were negatively associated with self-efficacy (B: –0.23, 95% CI: –0.36 to –0.10).

Conclusion

Findings suggest that individuals who hold maladaptive perceptions of pain–smoking interrelations could be more likely to endorse higher pain interference and lower self-efficacy—two established predictors of cessation outcomes. Moreover, each PSI subscale demonstrated unique relationships with the dependent variables, and our results provided support for a three-factor structure. These findings further demonstrate that the PSI comprises three conceptually and empirically distinct domains; future research should evaluate the clinical utility of assessing each domain in relation to cessation outcomes.
Mosaic variants in TNFRSF1A: an emerging cause of tumour necrosis factor receptor-associated periodic syndrome
Authors: Assrawi Eman , Louvrier Camille , El Khouri Elma , Delaleu Jérémie , Copin Bruno , Dastot-Le Moal Florence , Piterboth William , Legendre Marie , Karabina Sonia A , Grateau Gilles , Amselem Serge , Giurgea Irina
Published: May 2022

Objective

To identify the molecular basis of a systemic autoinflammatory disorder (SAID) evocative of TNF receptor-associated periodic syndrome (TRAPS).

Methods

(i) Deep next generation sequencing (NGS) through a SAID gene panel; (ii) variant allele distribution in peripheral blood subpopulations; (iii) in silico analyses of mosaic variants using TNF receptor superfamily 1A (TNFRSF1A) crystal structure; (iv) review of the very rare TNFRSF1A mosaic variants reported previously.

Results

In a 36-year-old man suffering from recurrent fever for 12 years, high-depth NGS revealed a TNFRSF1A mosaic variant, c.176G>A p.(Cys59Tyr), which Sanger sequencing failed to detect. This mosaic variant displayed a variant allele fraction of 14% in whole blood; it affects both myeloid and lymphoid lineages. p.(Cys59Tyr), a recurrent germline pathogenic variant, affects a crucial cysteine located in the first cysteine-rich domain (CRD1) and involved in a disulphide bridge. Introduction of a tyrosine at this position is expected to disrupt the CRD1 structure. Review of the three previously reported TNFRSF1A mosaic variants revealed that they are all located in a small region of CRD2 and that germinal cells can be affected.

Conclusion

This study expands the localization of TNFRSF1A mosaic variants to the CRD1 domain. Noticeably, residues involved in germline TNFRSF1A mutational hot spots can also be involved in post-zygotic mutational events. Including our study, only four patients have been thus far reported with TNFRSF1A mosaicism, highlighting the need for a high-depth NGS-based approach to avoid the misdiagnosis of TRAPS. Genetic counselling has to consider the potential occurrence of TNFRSF1A mosaic variants in germinal cells.
0032 Objective and Subjective Measures of Sleep Initiation are Differentially Associated with DNA Methylation in Adolescents
Authors: Larsen Michael , He Fan , Imamura Yuka , Berg Arthur , Vgontzas Alexandros , Liao Duanping , Bixler Edward , Fernandez-Mendoza Julio
Published: May 2022

Introduction

The onset of puberty is associated with a shift in the circadian timing of sleep leading to delayed sleep initiation [i.e., later sleep onset time (SOT)] driven by later bedtimes and/or longer sleep onset latency (SOL). Subjective sleep initiation, as per self-reports, and objective sleep initiation, as per actigraphy (ACT) or polysomnography (PSG), assess equally relevant but different domains of the same physiological process. Several GWAS have identified genes associated with sleep and circadian phenotypes; however, little is known regarding the epigenetic basis and significance of delayed sleep initiation in adolescence, a critical developmental period.

Methods

We analyzed data from 263 adolescents from the Penn State Child Cohort follow-up study who had complete subjective (self-reported questionnaires), at-home 7-night ACT, and in-lab 9-hour PSG data for bedtime, SOL and SOT. Epigenome-wide single-nucleotide resolution of DNA methylation in cytosine-phosphate-guanine (CpG) sites and surrounding regions were obtained from peripheral leukocytes. Linear regression assessed the association between bedtime, SOL and SOT with site-specific methylation levels, adjusting for sex, age, race/ethnicity, body mass index, and psychotropic medication use. P-values were adjusted using the Benjamini & Hochberg method to correct for false discovery rate and, thus, q-values are reported.

Results

Exome-wide analysis showed differential methylation in 1450 unique genes across the 9 sleep measurements, while GWAS-informed analysis yielded 57 genes. Gene hits were identified for bedtime (PSG), SOL (subjective, ACT and PSG) and SOT (subjective and PSG): 14 genes were associated with both subjective and PSG-measured SOL, 34 with both ACT- and PSG-measured SOL, and one (TBC1D22A) with subjective, ACT- and PSG-measured SOL. One gene (ABTB2) was associated with subjective and PSG-measured SOT.

Conclusion

Objective and subjective sleep initiation in adolescents is associated with altered DNA methylation in genes previously identified in adult GWAS of sleep and circadian phenotypes. Our data provides evidence for a potential epigenetic link between habitual (subjective and ACT) SOL and in-lab SOT and DNAm in genes involved in circadian regulation (i.e., RASD1, RAI1), metabolism (i.e., FADS1, WNK1, SLC5A6), and neuropsychiatric disorders (i.e., PRR7, SDK1, FAM172A).

Support (If Any)

National Institutes of Health (R01HL136587, R01MH118308, UL1TR000127)
0082 External Validation of an Enhanced Machine Learning Algorithm: Polysomnography-Based Narcolepsy-Like Feature Assessment and Clinician Notification in Routine Sleep Medicine Clinics
Authors: Moore Hyatt , Zheng Alex , Cairns Alyssa , Lillaney Prasheel , Black Jed
Published: May 2022

Introduction

Polysomnography (PSG) contains quantitative information that, using machine learning (ML) algorithms, may aid the identification of type 1 narcolepsy. This study aimed to evaluate the utility of a previously developed quantitative tool (ML evaluation of PSG data) for detecting narcolepsy (types 1 and 2) in a “real-world” sleep clinic population.

Methods

Nocturnal PSG studies from a random sample of sleep clinic patients (narcolepsy, n=302; controls, n=21,535) were randomly split (1:1) into a training set and a validation set for algorithm testing. A separate, external PSG dataset was used for additional testing of the final model. Sleep stage probability graphs (hypnodensities) were estimated from PSGs on 15-second epochs using a previously developed convolutional neural network. Feature engineering was applied to hypnodensities to create a feature vector that was used to train a Gaussian process (GP) model to identify patients with a high probability of having narcolepsy. Features could be scaled to the 85th percentile, zero-mean and unit-variance, or unscaled. A recursive feature-elimination scheme was compared with training the GP kernel’s length scale for determining the subset of features that best discriminate narcolepsy and controls. A synthetic minority oversampling technique was applied in combination with random undersampling to balance the distribution of cases and controls in the training set. Several kernels and relevant hyperparameters were evaluated. Model performance (specificity and sensitivity) was examined using receiver operating characteristics with the goal of achieving an area under the curve (AUC) ≥0.80.

Results

The final GP model used a Matérn 5/2 covariance kernel with the length scale hyperparameter trained to determine the feature subset selection. Input features were normalized to zero-mean and unit-variance. The model had AUC=0.9960 and AUC=0.8014 for classifying narcolepsy in the training and validation sets, respectively. Sensitivity ranged from 73% to 65% when specificity was between 75% and 80%. Final performance evaluation of the model for classifying narcolepsy in an external PSG dataset is ongoing; results will be presented at the congress.

Conclusion

An ML-based algorithm can offer an objective, sensitive, and specific tool for alerting sleep clinicians about patients at risk for narcolepsy, using nocturnal PSG in general sleep medicine clinics.

Support (If Any)

Jazz Pharmaceuticals.
0114 Evolution of brain circuits supporting spatial navigational memory across sleep
Authors: Parekh Ankit , Kam Korey , Valencia Daphne , Fleysher Lazar , Fakhoury Ahmad , Castillo Bresne , Rapoport David , Ayappa Indu , Varga Andrew
Published: May 2022

Introduction

Systems consolidation is one of the major theories of sleep’s function in memory. Sleep is thought to be important in integrating and distributing hippocampal information to cortical structures such that there is less hippocampal activation, while at the same time increasing striatal activation, upon subsequent experience in the same environment that co-occurs with improved performance. Here we sought to examine the evidence supporting systems consolidation across sleep in spatial navigational memory.

Methods

15 subjects (28±5 yrs., 8 female) with no prior videogame experience and no sleep disorders were recruited to undergo spatial navigational memory testing before and after a night of sleep. Spatial navigational memory was tested across two functional MR (fMRI) sessions (approx. 7PM and 8AM) separated by in-lab nocturnal polysomnography (NPSG) measured sleep using a virtual 3D Maze. Each fMRI session consisted of six runs: three maze trials interleaved with three control trials. During maze trials participants were instructed to reach a prespecified goal as quickly as possible, whereas during the control trials, participants were instructed to navigate a Z-shaped corridor with no prespecified goal. fMRI data was analyzed in 2-step procedure using Analysis of Functional Neuroimages (AFNI) software package. To estimate hippocampal activity during fMRI, parameter estimates of the %change in blood-oxygen-level-dependent (BOLD) signal using the contrast maze-control were used as the primary metric. Regions of interest were limited to the bilateral hippocampus, parahippocampal gyrus, caudate, and putamen using the Eickhoff-Zilles macro labels from the MNI-N27 template.

Results

During in-lab NPSG, participants experienced a total sleep time of 6.1±1.1 hrs (8.7±2.9%stage1, 51.2±7.6%stage2, 21.8±8.5%stage3, 18.1±6%REM). Within subjects, compared to pre-sleep, a significantly lower activation of the bilateral hippocampus and parahippocampal gyrus was observed post-sleep (evening-morning %change=0.26±0.11, p<0.05). Compared to pre-sleep, caudate and putamen activity was not significantly different post-sleep (evening-morning %change=-0.02±0.04,p=0.5). Greater evening hippocampal activity was associated with greater change in maze completion times across sleep (rho=0.54, p=0.04).

Conclusion

In young healthy adults, a night of uninterrupted sleep supports redistribution of hippocampal contribution toward spatial navigation. Greater initial pre-sleep hippocampal contribution was associated with improved recall of spatial navigational memory after a night of sleep.

Support (If Any)

NIH R21AG059179, R01AG056682, K25HL151912
0143 Firefighters' Sleepiness and Total Sleep Time Varies Throughout Their Shift Schedule
Authors: Billings Joel
Published: May 2022

Introduction

Most career firefighters in the US are allowed to rest and sleep, yet at the same time must be ready to respond to emergencies. We recently found that inter-daily rhythms in firefighter total sleep time (TST) and that the rhythms are related to their shift schedule. Considering the relationship between sleep duration and health outcomes, the purpose of this research is to assess the daily relationship between preceding TST and sleepiness throughout two popular fire department shift schedules.

Methods

Firefighters participated in a pre-experimental, longitudinal sleep study that assessed sleep over 18 days on the 24-hours on and 48-hours off (24/48) (n=22) and again 18 days, six-months after firefighters transitioned to the 48-hours on and 96-hours off (48/96) shift schedules (n=20). Daily TST was assessed using actigraphy and the Emergency Services Sleep Diary and daily sleepiness was assessed using the Epworth Sleepiness Scale (ESS), completed every afternoon at 1:00 PM.

Results

The results of the one-way repeated measures ANOVA for each schedule indicated a statistically significant difference in ESS scores among days within the 24/48 (F(2,42) = 8.56, p<0.01) and 48/49 shift schedule (F(5,95) = 7.40, p<0.05). Using pre-shift as baseline, differences of preceding TST and afternoon sleepiness were related in the 24/48 (r(64)= -.62, p ≤.001) and 48/96 (r(118)= -.54, p ≤.001) shift schedule. The greatest mean levels of sleepiness occurred on days in which firefighters commuted to and from the fire station. During non-workdays, mean afternoon sleepiness decreased as firefighters returned to baseline TST.

Conclusion

Firefighters experienced an inverse relationship between preceding TST and afternoon sleepiness. The least TST occurred on commute days; firefighters begin shift with insufficient sleep and drove home with insufficient sleep. Subsequently, firefighters experienced greatest levels of sleepiness during those afternoons. The findings of daily variation in TST and sleepiness highlight the importance for firefighters to prioritize sleep so that they begin shift well rested and commute home well rested. In addition, the implication of the results questions whether other acute health outcomes also vary within fire department shift schedules.

Support (If Any)
0226 Circadian influence on food intake among adolescents with overweight and healthy weight
Authors: Barker David , Carskadon Mary , Gredvig-Ardito Caroline , Hart Chantelle , Raynor Hollie , Scheer Frank
Published: May 2022

Introduction

Meal timing has been linked to obesity in adults and children; however, evidence for an endogenous influence of the circadian system on food intake is unknown. We measured food intake during forced desynchrony (FD) in adolescents with healthy weight (HW) or overweight (OW), hypothesizing that circadian timing would affect food intake independent of the environmental cycle and that the food intake rhythm would be delayed in adolescents with OW compared to HW.

Methods

Participants were 51 (29m) adolescents (12-15yr); 24 were HW and 27 OW determined by CDC norms. Participants completed seven, 28h-FD cycles; 6 meals occurred at fixed times each cycle with foods selected ~1h before meals and weighed before and after. Each meal’s energy intake was computed relative to total energy consumed in that FD cycle. Endogenous circadian period was determined using salivary dim-light melatonin onset (DLMO) phases (DLMO=0°). Time awake effect was assessed using mixed effect models and circadian phase with multilevel cosinor that included time awake as a categorical covariate.

Results

Circadian period was not significantly different between OW and HW (mean, StDev; HW =24.19h,0.22; OW=24.22h,0.14). Overall, participants consumed more calories on the cycles’ first meals (22.0% [21.3;22.6]) compared to the last meal (12.4% [11.8;13.0]). Adolescents with OW vs. HW consumed a higher proportion of calories later in the wake episode (F(5,2081)=2.63,p=.02). As hypothesized, circadian phase influenced caloric intake with an amplitude of 2.66% [2.19;3.14] percent daily calories and an acrophase of 301°[291;310], equivalent to ~17:52 in this population. The circadian influence differed by weight category (likelihood ratio test of both amplitude and acrophase; χ2(2)=10.7,p<.01), with those with OW showing a lower amplitude (OW = 2.11%[1.40;2.82], HW=3.53%[2.94;4.12] and later acrophase (OW=301° [287;314], HW=290° [278;302]).

Conclusion

Results show for the first time an independent influence of the endogenous circadian timing system on caloric intake of humans that differed as a function of body weight: caloric intake for adolescents with OW had a circadian rhythm with blunted amplitude and delayed peak phase. These observations show circadian control of food intake that may be stronger in HW than OW adolescents.

Support (If Any)

P20GM139743; R01DK101046; R01HL153969
0232 An Intraindividual Variability of Sleep Health and Perceived Stress in College Students During the COVID-19 Pandemic
Authors: Kwon Misol , Wang Jia , Dean Grace , Dickerson Suzanne
Published: May 2022

Introduction

Pandemic-related societal response and uncertainty have generated marked changes in sleep-wake patterns and psycho-social well-being especially among first year college students. The current study sough to describe the changes in the sleep health domains determined from Actigraph and self-report, and examine the associations between the repeated-measure and intraindividual variability (IIV) of these domains and perceived stress in young college students over the course of a semester in the midst of an on-going COVID-19 pandemic (i.e., Fall, 2020).

Methods

A repeated measure design at 1-month interval across a 3-month period was conducted among a group of diverse racial and ethnic groups of college students (N=23, 78.3% female, age range 17-18). Participants completed a 7-days of wrist Actigraph, daily sleep diaries, and other surveys at each interval. A multidimensional sleep health was determined using Actigraph and daily sleep diary measures of sleep duration, efficiency, timing and regularity, and self-reported surveys of sleep satisfaction and alertness during daytime. Participants also completed the Perceived Stress Scale. Non-parametric tests were used to assess the changes in sleep health across 3 intervals, and a series of linear mixed effects model and regression analysis were conducted to assess associations between stress and subjective sleep health, adjusting for sex.

Results

Actigraph-determined sleep timing and regularity, and sleep diary-determined sleep timing and alertness during daytime demonstrated statistically significant changes between given timepoints. Among the sleep diary-determined sleep health domains, greater perceived stress was associated with more irregular (B=2.25 [.87–3.62], p<.001), more dissatisfied (B=.04 [.02–.19], p<.01), and sleepier during daytime (B=.18 [.05–.31], p<.001), across 3 timepoints. Moreover, greater perceived stress was associated with greater IIV (i.e., fluctuations) in sleep satisfaction, but no significance was found among IIV of other domains.

Conclusion

This study aids understanding of the relationship between stress and sleep health in this population, and offers insight to future research questions that can facilitate intervention development to promote both mental and sleep health among young college students.

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0249 Sleeping In to Avoid Acting Out: The Association Between Sleep Regularity and Emotion Regulation
Authors: Perez Elliottnell , Sabet Sahar , Soto Pablo , Dzierzewski Joseph
Published: May 2022

Introduction

Sleep and emotions are closely intertwined facets of individuals’ mental health and well-being. Previous studies have consistently shown that sleep is critical in the maintenance of emotion regulation; however, few research studies have examined the association between sleep regularity and emotion regulation skills. The current study seeks to answer this question by examining whether sleep regularity is associated with individual facets of emotion regulation, as well as overall emotion regulation ability.

Methods

Secondary analysis was performed on data obtained from 999 individuals (M age=44.17, SD=16.23; 47.7% female) who participated in the Investigating Sleep Longitudinally Across Normal Development (ISLAND) online study. The Sleep Regularity Questionnaire was used to measure the degree to which individuals engage in consistent sleep behavior. The Difficulties in Emotion Regulation Scale was used to measure perceived overall emotion regulation ability, as well as individual facets of emotion regulation. Regression analyses were used to determine whether sleep regularity predicted difficulties in emotion regulation while controlling for age, race, gender, sleep quality, and total sleep time. Total sleep time and sleep quality information were obtained from item #4 and item #6 of the Pittsburgh Sleep Quality Index, respectively.

Results

Less sleep regularity significantly predicted greater overall emotion regulation difficulties (p=.021, B=-.13). Less sleep regularity was associated with greater difficulty in individual facets of emotion regulation including emotional clarity (p<.001, B=-.05), impulse control (p<.001, B=-.05), nonacceptance of emotional responses (p=.009, B=-.04), and access to emotion regulation strategies (p<.001, B=-.06). Surprisingly, greater sleep regularity was associated with more difficulties with emotional awareness (p<.001, B=.09). Sleep regularity was not associated with difficulty engaging in goal-direct behavior (p=.103, B=-.02).

Conclusion

Poorer sleep regularity significantly predicted greater overall emotion regulation difficulties. Findings from the current study add to the literature supporting the close links between sleep and emotion regulation, and suggest that the promotion and enhancement of consistent, regular sleep may be an important factor that leads to improved emotion regulatory skills beyond the sleep experience (i.e., sleep quality and duration). Additional research is needed to disentangle this association and identify additional factors or mechanisms that may further elucidate this association.

Support (If Any)

Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number K23AG049955 (PI: Dzierzewski).
0267 The Influence of Antidepressants on Non-REM Hypertonia
Authors: Levendowski Daniel , Boeve Bradley , Walsh Christine , Lee-Iannotti Joyce , Salat David , Hamilton Joanne , Tsuang Debby , Berka Chris , Shprecher David , Westbrook Philip , Mazeika Gandis , Neylan Thomas , Louis Erik St
Published: May 2022

Introduction

The severity of REM sleep without atonia, a prodromal biomarker for synucleinopathy-related neurodegenerative disorders, is influenced by selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine retake inhibitor (SNRI) use. This study investigates whether SSRI/SNRIs similarly impacts the severity of Non-REM hypertonia (NRH), a biomarker independently associated with patients broadly characterized with presumed Parkinsonian-spectrum disorders (PSD).

Methods

In this multi-center study, the relationship between NRH and SSRI/SNRIs was evaluated in PSD patients [Lewy Body/Parkinson Disease Dementia (DLB/PDD=16), Parkinson Disease (PD=16), isolated REM sleep behavior disorder (iRBD=19), and progressive supranuclear palsy (PSP=12)], and non-PSD subjects [Alzheimer Disease (AD=22), mild cognitive impairment (MCI=35), and normal cognition (NC=61)]. Studies were conducted with the Sleep Profiler in all participants. NRH was auto-detected based on persistently elevated electromyographic (EMG) power relative to delta, theta, and sigma bands. Abnormal-NRH was based on a threshold of >5% of sleep time, and weight-averaged by sleep time, in the 75% of studies with two-nights of data. Statistical analyses included multiple logistic regression, Fisher Exact, and Mann-Whitney U tests.

Results

Across all 181 records, 38% had abnormal-NRH and 24% used SSRI/SNRIs (P<0.005). No differences were observed in the distributions of NRH for those with NRH-only vs. those with combined NRH and SSRI/SNRI use (n=45, 14.5+/-7.7% versus n=24, 18.6+/-11.6%, respectively; P=0.19). Abnormal-NRH was associated with the PSD versus non-PSD groups (P<0.0001, odds-ratio=14.0) and SSRI/SNRI use (P<0.05, odds-ratio=2.4), but not age and sex. Within the PSD and non-PSD groups, the frequency of abnormal-NRH was 75% vs. 19% (P<0.0001), and SSRI/SNRI use was 32% vs. 19% (P=0.07), respectively. The distributions of abnormal-NRH in the PSD and non-PSD subgroups ranged from PSP=92%, DLB/PDD=81%, PD=56% ,and RBD=74% versus MCI=26%, and NC=16%, AD=14%, respectively. By comparison, distributions of SSRI/SNRI use were DLB/PDD=50%, RBD=42%, PSP=33%, and PD=0% in the PSD subgroups, compared to MCI=34%, AD=23%, and NC=10% in the non-PSD subgroups.

Conclusion

Abnormal non-REM hypertonia exhibited a very strong association with Parkinsonian-spectrum disorder diagnoses (odds-ratio=14.0) and a relatively weaker association with selective serotonin reuptake inhibitor or serotonin-norepinephrine retake inhibitor use (odds-ratio=2.4), suggesting a finding that reflects an interactive, rather than causal inference.

Support (If Any)

NIA grants R44AG050326, R44AG054256, P30AG62677 and R34AG56639.
0314 Oral Contraceptives and Sleep Duration and Timing, Daytime Sleepiness, and Snoring in NHANES 2015-2018
Authors: Kennedy Kathryn , Tubbs Andrew , Nowakowski Sara , Wills Chloe , Grandner Michael
Published: May 2022

Introduction

Oral contraceptives have been associated with psychiatric disorders including depression and anxiety, but few studies have looked at the relationships with sleep health.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 and 2017-2018 waves were examined. Of 6,335 females aged 44 and under, 308 had used hormonal contraceptives within 30 days of survey completion. These women also self-reported sleep and wake times and usual sleep duration on weekdays. They also reported snoring frequency, with answer choices ranging from “never” to “1-2 nights per week”, “3-4 nights/week”, or “>5 nights/week”. Lastly, they reported how often they felt overly sleepy during the day, with answer choices ranging from “never”, to “once/month”, “2-4 times/month”, “5-15 times a month”, or “16-30 times/month”. Linear and logistic regression analyses were adjusted for age, race/ethnicity, education, employment status, marital status, and income.

Results

Contraceptive users were more likely to be white, more highly educated, with higher income, employed, and never married. There were no differences by severity of depression symptoms between users and non-users according to PHQ-9 score. Contraceptive use was not associated with self-reported sleep duration in unadjusted or adjusted linear models (p=0.502 and p=0.146, respectively). Contraceptive use was also not a significant correlate of time to bed, time out of bed, time in bed, or midpoint of sleep in either unadjusted and adjusted linear models. In unadjusted logistic regression models, individuals who reported sleepiness “sometimes” or “often” were about twice as likely to be contraceptive users (OR=1.98, p=0.0023; and OR=1.87, p=0.0084, respectively). These associations were no longer significant after adjusting for covariates. In unadjusted logistic regression models, individuals with frequent snoring had 50% lower odds of contraceptive use (OR=0.50, p=0.0023), but similarly, there were no associations after adjusting for covariates.

Conclusion

Oral contraceptive use did not appear to be related to habitual sleep parameters, after adjusting for sociodemographic covariates in these analyses. However, further investigation must look at both objective measures and larger samples.

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0319 Age Estimation from Sleep using Deep Learning Predicts Life Expectancy
Authors: Brink-Kjaer Andreas , Leary Eileen , Sun Haoqi , Westover M Brandon , Stone Katie , Peppard Paul , Lane Nancy , Cawthon Peggy , Redline Susan , Jennum Poul , Mignot Emmanuel , Sorensen Helge
Published: May 2022

Introduction

Sleep disturbances increase with age and are predictors of mortality. However, summary metrics typically derived in sleep clinics from gold standard clinical analysis of polysomnograms (PSGs) only represent a very small fraction of data collected. In this study, we designed deep neural networks that estimate age as a proxy for overall health using full PSG signals. Age estimation was next used to evaluate association to mortality risk.

Methods

Aging was modeled using 2,500 PSGs and tested in 10,808 PSGs from men and women in 7 different cohorts aged between 20 and 90. The deep neural network was trained using as a regression model of age in the 2,500 PSGs roughly uniformly distributed across 6 to 90 years. The estimates of the network were interpreted using Gradient SHAP, which attributes relevance scores to the input in terms of the age estimate. The association between age estimate error (AEE), which is the residual of the estimate, and mortality risk was investigated with Cox proportional hazards models that adjusted for demographics, sleep, and health covariates.

Results

Ages were estimated with a mean absolute error of 5.81 ± 1.18 years, while a linear regression model using basic sleep scoring measures had an error of 15.10 ± 6.48 years. Interpretation of the network revealed that patterns such as arousal, sleep apnea, and sleep stage transitions contribute to the age estimate. Each 10-year increment in AEE was associated with increased all-cause mortality rate of 28 % (95% confidence interval: 19–38 %) and cardiovascular mortality rate of 38 % (95% confidence interval: 19 – 59 %). An increase from -10 to +10 years in AEE translates to an estimated decreased life expectancy of 6.21 years (95% confidence interval: 4.31–8.21 years).

Conclusion

Greater AEE was mostly reflected in increased sleep fragmentation, suggesting this is an important biomarker of future health independent of sleep apnea.

Support (If Any)

The Klarman Family Foundation and grants HL46380, M01 RR00080-39, T32-HL07567, RO1-46380, U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL64360, U01HL53938, U01HL53940, U01HL53941, U01HL63463, 38-PM-07, R01HL62252, R01AG036838, R01AG058680, 1UL1RR025011, U01AG027810, U01AG042124, U01AG042139, U01AG042140, U01AG042143, U01AG042145, U01AG042168, U01AR066160, UL1TR000128, R01HL071194, R01HL070848, R01HL070847, R01HL070842, R01HL070841, R01HL070837, R01HL070838, R01HL070839, R24HL114473, and 75N92019R002.
0347 Sleep health education and a personalized smartphone application improve sleep and productivity and reduce healthcare utilization among employees: Results of a randomized clinical trial
Authors: Robbins Rebecca , Weaver Matthew , Quan Stuart , Sullivan Jason , Cohen-Zion Mairav , Glasner Laura , Czeisler Charles , Barger Laura
Published: May 2022

Introduction

Sleep deficiency and undiagnosed or untreated sleep disorders are pervasive among employed adults, yet are often ignored in the context of workplace health promotion. Smartphone applications (apps) are a promising, scalable approach to improving sleep among employees. We evaluated an online sleep education program followed by access to a mobile sleep training program, the dayzz app, that promotes healthy sleep, sleep disorders awareness and intervention.

Methods

In a sample of daytime employees affiliated with a large healthcare organization, we evaluated the intervention (sleep education at baseline plus access to the personalized app for up to 9 months) in a parallel group, randomized controlled trial. Participants were randomly assigned to either the experimental condition that received the intervention in months 1 through 9 or the control group that was assigned to receive the intervention in month 10. In a prespecified data analysis plan, the experimental and control groups were compared in months 1 through 9; no outcome data was collected thereafter. We collected data on employee sleep, workplace outcomes, and healthcare utilization, monthly throughout the study.

Results

The final cohort was comprised of 794 participants assigned to the experimental and 561 to the control condition. Those assigned to the experimental condition were more likely to maintain consistent sleep schedules (OR:1.40;95%CI:1.12-1.75) and less likely to experience fatigue and sleepiness (OR:1.30;95%CI:1.08-1.57). At the 9-month follow-up assessment, the experimental group reported significantly longer sleep duration than the control group on work (experimental: 7.20hrs; control: 6.99hrs, p=0.01) and free (experimental: 8.26hrs; control: 8.04hrs, p=0.03) nights. The odds of poor sleep quality at follow-up were lower in the experimental condition (OR:0.79,95%CI:0.63-0.98) as compared to control. Mean total dollars lost due to presenteeism was less among experimental compared to control participants (p=0.0001), corresponding to an average of $274 saved per person per month. Finally, participants in the experimental group were less likely to report mental health visits (p=0.01) and had a lower rate of overall healthcare utilization (p=0.03), compared to the control group.

Conclusion

Results from this randomized clinical trial demonstrate that a digital workplace sleep wellness program can be beneficial to both employees and employers, by improving employee sleep and fatigue, increasing work productivity, and reducing direct healthcare costs.

Support (If Any)

This study was funded by dayzz Live Well Ltd.
0381 High levels of patient engagement with a novel sleep telehealth platform in the US military
Authors: Thomas Mary
Published: May 2022

Introduction

Despite very high prevalence and documented adverse consequences of insufficient and disturbed sleep in the US military, there are well-recognized barriers limiting access to evidence-based sleep interventions within the military health system (MHS). Chief among these is an insufficient number of trained sleep specialists and sleep centers. As part of a larger implementation effort, the purpose of this pilot study was to evaluate patient engagement with a novel sleep telehealth platform at a busy military treatment facility.

Methods

The sleep telehealth platform consists of an online web portal for patients and providers, a secure mobile app, and integrated wearable sensors using an off the shelf commercial solution (COTS; in this study, Fitbit). The purposes of this platform are to 1) help primary care managers (PCMs) assess sleep complaints, 2) empower patients and PCMs to make evidence-based sleep treatment decisions, 3) deliver evidence-based behavioral sleep treatments via mobile devices, and 4) connect patients with sleep specialists in virtual or physical sleep centers. Participants were recruited from the Internal Medicine clinic and the Sleep Disorders Center at Walter Reed National Military Medical Center (WRNMMC). Inclusion criteria included ages of 18-75 years and self or provider referral for sleep problems, including insufficient sleep duration. In addition to wearing the COTS sleep tracker, participants completed a baseline assessment and 2x/daily diaries for ten days, and a brief satisfaction survey.

Results

Participants included 35 patients (57% female, mean age=44.7 years). One hundred percent of participants wore the COTS sleep tracker and completed the post-monitoring assessment. Satisfaction survey results indicated that 96.7% of participants found completing the 10-day continuous sleep monitoring assessments to be “easy” or “very easy,” and 96.7% of those who completed the monitoring expressed a preference for app-based sleep treatment either alone or in conjunction with virtual or in person care. Finally, participants offered suggestions to optimize the app and platform for pending clinical implementation.

Conclusion

Results of this pilot study demonstrate high levels of patient engagement with the sleep telehealth platform. Given the large number of patients seeking treatment and the shortage of trained specialist providers, sleep telehealth is a promising pathway to increase access to evidence-based care.

Support (If Any)

This research was supported by an investigator-initiated research award from the Department of Defense (via the Medical Technology Enterprise Consortium) to the University of Maryland, Baltimore (PI: EMW).
0411 Once-Nightly Sodium Oxybate Dose Titration and Tolerability: Interim Data From RESTORE
Authors: Roy Asim , Abaluck Brian , Stern Thomas , Kushida Clete , Seiden David , Dubow Jordan , Gudeman Jennifer
Published: May 2022

Introduction

Extended-release, once-nightly sodium oxybate (ON-SXB; FT218) is under FDA review for the treatment of adults with narcolepsy. RESTORE, an ongoing, open-label extension/switch study (NCT04451668), evaluates long-term ON-SXB safety and tolerability. This interim analysis assessed dosing titration, tolerability, and study continuation.

Methods

RESTORE enrolls adults with narcolepsy in 1 of 3 groups: those with prior REST-ON participation but no current oxybate use (Group A), those who switched from twice-nightly oxybates (Group B), and oxybate-naïve patients (Group C). No patients rolled directly from REST-ON to RESTORE. Initial dose for Groups A/C was 4.5 g/night. Group B switched to ON-SXB from stable doses of twice-nightly oxybate to the nearest equivalent single dose. Investigators could increase or decrease dose by 1.5-g increments weekly as needed. Descriptive statistics were used to analyze dose titration and discontinuations.

Results

At an interim data cutoff date of November 14, 2021, 99 participants were enrolled and had received ≥1 dose of ON-SXB (not currently taking oxybate, n=24; switch, n=75). For Groups A/C, 5 (21%) participants continued the 4.5-g dose, 8 (33%) increased to 6 g, 8 (33%) increased to 7.5 g, and 3 (13%) increased to 9 g by this data cutoff. Most Group B participants received initial ON-SXB doses of either 9 g (n=27) or 7.5 g (n=24). For Group B participants with >1 visit, 41 maintained their initial dose, 20 increased the dose, and 8 increased the dose but then later decreased it. All but 2 Group B participants with initial 9-g doses of ON-SXB maintained this dose. Twenty participants (20%) discontinued study treatment since the first patient enrolled in July 2020; the primary reason was withdrawal of consent (n=3; 3%). Two (2%) discontinued due to adverse reactions: vivid dreams/anxiety/lightheadedness and lack of efficacy (7.5 g); and difficulty breathing (6 g). Two discontinued due to taste/texture (2%); the remainder for miscellaneous reasons (eg, withdrew consent, could not adhere to schedule, left the country, caring for sick parent/child, wanted to get pregnant, using cannabis).

Conclusion

These interim data indicate that the majority of participants in all groups titrated to therapeutic and tolerable doses of ON-SXB.

Support (If Any)

Avadel Pharmaceuticals
0441 Treating Insomnia Disorder in Black Women: Results from an Internet-Based, Randomized Clinical Trial of a Culturally Tailored Intervention
Authors: Zhou Eric , Ritterband Lee , Bethea Traci , Robles Yvonne , Heeren Timothy , Rosenberg Lynn
Published: May 2022

Introduction

Black women are at high risk for insomnia. Despite considerable interest in addressing sleep health disparities, there is very limited research investigating the efficacy of gold standard treatment (cognitive-behavioral therapy for insomnia; CBT-I) among this minority population. Further, we are not aware of any data studying whether a culturally tailored intervention would improve treatment efficacy and/or engagement among Black women.

Methods

We conducted a randomized clinical trial within a national, longitudinal cohort study (Black Women’s Health Study; BWHS). BWHS participants with elevated insomnia symptoms were randomized to receive: (1) automated Internet-delivered CBT-I (Sleep Healthy Using the Internet; SHUTi); (2) a stakeholder-informed, tailored version of SHUTi for Black women (SHUTi-BWHS); or (3) patient education about sleep (PE). Primary outcomes were insomnia severity (Insomnia Severity Index; ISI) and treatment engagement (completion of the intervention). We hypothesized that both SHUTi and SHUTi-BWHS would lead to significantly decreased insomnia severity compared to PE, and that SHUTi-BWHS participants would be more likely to complete the intervention.

Results

Three-hundred and thirty-three Black women (mean age=59.3 years) were enrolled in the trial. Those randomized to receive either SHUTi or SHUTi-BWHS had greater reductions in ISI scores at 6-month follow-up (-10.0 and -9.3 points, respectively) compared to PE (-3.6 points). More participants randomized to SHUTi-BWHS completed the intervention compared to those randomized to SHUTi (78.2% vs 64.8%; p<.01). Participants who completed either SHUTi or SHUTi-BWHS showed greater reductions in insomnia severity compared to non-completers (-10.4 vs -6.2 points; p<.01).

Conclusion

Both SHUTi and SHUTi-BWHS improved sleep outcomes more than an active control. The culturally tailored SHUTi-BWHS program was more effective at engaging participants with the program as a greater proportion completed the full intervention, which was associated with greater improvements in sleep outcomes. These compelling data demonstrate that offering a culturally adapted program is a possible path in efforts to address the sleep health disparities facing Black Americans.

Support (If Any)

This trial was funded by Patient-Centered Outcomes Research Institute grant AD-2017C1-6314. National Cancer Institute grant U01 CA164974 supports the BWHS infrastructure.