bluuebunny/crossref_metadata_2025_split huggingface dataset:
0025 Circadian Dysregulation of Human DNA Repair Genes and Elevated DNA Damage in Simulated Night Shift Schedule
Authors: Van Dongen Hans , Koritala Bala , Porter Kenneth , Arshad Osama , Gajula Rajendra , Mitchell Hugh , Arman Tarana , Manjanatha Mugimane , Teeguarden Justin , McDermott Jason , Gaddameedhi Shobhan 
Published: May 2022

Abstract

Introduction
Circadian misalignment from night shift (NS) work is associated with increased risk of cancer. In a simulated NS study, we sought to investigate the potential role of circadian disruption of cancer hallmark pathway genes.

Methods
N=14 healthy adults (aged 22-34) participated in a laboratory study. Seven were assigned to a simulated day shift (DS) schedule involving 3 days of daytime wakefulness (06:00-22:00); the other seven were assigned to a simulated NS schedule involving 3 days of nighttime wakefulness (18:00-10:00). Subjects then underwent a 24-hour constant routine protocol, during which blood was collected at 3-hour intervals. Leukocytes extracted from blood were subjected to transcriptomics using the NanoString nCounter PanCancer Pathways panel augmented with canonical clock genes. Statistical analysis involved mixed-effects cosinor analysis followed by functional enrichment analysis of rhythmic genes. Leukocytes were also subjected to endogenous DNA damage assessment through alkaline comet and immunofluorescence assays. Furthermore, exogenous DNA damage from exposure to ionizing radiation was investigated for blood collected at opposite times of day (07:30 and 19:30) based on DNA damage biomarkers assessed with immunofluorescence and immunoblot assays.

Results
Transcriptomics data showed that the simulated NS schedule, as compared to the simulated DS schedule, significantly altered the endogenous circadian rhythmicity of genes involved in cancer hallmark pathways, as measured under constant routine. A DNA repair pathway showed enrichment of rhythmic genes following the DS schedule (P&lt;0.05), but not following the NS schedule. Functional assessments revealed that the NS schedule was associated with increased endogenous DNA damage, as evidenced by alkaline comet assay (P&lt;0.001) and increased BRCA1 foci (P&lt;0.01) and γH2AX foci by immunofluorescence assay (P&lt;0.001). After exposure to ionizing radiation, there were increased BRCA1 foci (P&lt;0.01) and γH2AX foci by immunofluorescence assay (P&lt;0.005) and elevated DNA damage response signaling biomarkers by immunoblot assay, especially in the samples collected at 19:30.

Conclusion
These results suggest that a NS schedule causes circadian dysregulation of DNA repair genes and increases DNA damage – a primary hallmark of carcinogenesis – which may underlie the elevated cancer risk in NS workers.

Support (If Any)
WSU, CHHE P30ES025128, USAMRDC W81XWH-18-1-0100, NIH R01ES030113 and R21CA227381, CDMRP CA171123, DOE BRAVE DE-AC05-76RL01830.
0027 Reciprocal Modulation of Cortical Excitatory and Inhibitory Synapses by Wake-Sleep Homeostatic State
Authors: Rybalchenko Volodymyr , Greene Robert 
Published: May 2022

Abstract

Introduction
A widely debated function of sleep involves a homeostatic program of down-regulation of excitatory synaptic strength following an overall increase during the preceding waking period, preserving however the previously existing synaptic weights associated with newly acquired memories. We tested this hypothesis by applying thorough statistical analysis of parameters of excitatory and inhibitory miniature postsynaptic currents (mEPSC/mIPSC) recorded ex vivo in mouse cortical pyramidal neurons at three characteristic wake/sleep stages.

Methods
Cingulate cortex coronal slices were obtained at fixed Zeitgeber time (ZT6, to control for circadian clock) from control C57BL6 (MEF2C f/f) mice subjected to 6h acute sleep deprivation (SD), recovery sleep =4hSD+2h(RS), or 6h control sleep (CS). mEPSCs and mIPSCs were recorded from functionally identified whole-cell patch-clamped pyramidal neurons in cortical layer 2/3 (L2/3). Statistical analysis of frequencies, amplitudes, and charge transfer rates of mEPSCs and mIPSCs was done using non-parametric Kruskal-Wallis multiple comparison test and K-means clustering test.

Results
mEPSC frequency (F) and charge transfer (CT) were significantly reduced for RS and CS compared to SD (F: -57%, -47%; CT: -64%, -55%). mEPSC amplitude (A) was significantly reduced for CS compared to SD (-15%). Two-centroid clustering test revealed that analyzed parameters of F, A and CT for SD condition were approximately evenly split between upper and lower range clusters, while the same parameters for RS and CS conditions revealed a pronounced redistribution (&gt;75% lower-, &lt;25% upper ranges). Wake/sleep state related changes of mIPSC parameters showed opposite pattern compared to excitatory synapses. All three parameters were increased in RS vs. SD (F: +63%, A: +7%, CT: +42%) and this difference reached significance levels in CS vs. SD (F: +88%, A: +24%, CT: +109%). Clustering analysis of mIPSC parameters revealed mostly stable distribution pattern between upper and lower ranges for all wake/sleep states.

Conclusion
Significant changes in excitatory/inhibitory balance in the frontal cortex is part of the homeostatic response upon transition from wakefulness to various phases of sleep. The excitatory component prevails during wakefulness, while the inhibitory component peaks during sleep.

Support (If Any)
NIH grant R01 NS103422 to RWG.
0029 Developing a pipeline for translating genome-wide association signals to behavioral correlates of sleep dysfunction
Authors: Zimmerman Amber , Palermo Justin , Chesi Alessandra , Sonti Shilpa , Lasconi Chiara , Brown Elizabeth , Pippin James , Wells Andrew , Doldur-Balli Fusun , Mazzotti Diego , Pack Allan , Gehrman Philip , Keene Alex , Grant Struan 
Published: May 2022

Abstract

Introduction
Insomnia is a pervasive sleep disorder affecting up to one-third of the adult U.S. population. An extensive amount of genetic association data from genome wide association studies (GWAS) has uncovered hundreds of loci associated with insomnia and other sleep traits, yet few of these targets have undergone full characterization and their contribution to sleep traits remain poorly understood. Additionally, GWAS does not necessarily determine the true effector gene(s) at a given locus, leading to frequent mischaracterization and misinterpretation of genotype-phenotype interactions.

Methods
Our group has developed a variant-to-gene mapping approach that integrates existing insomnia GWAS loci with a combination of ATAC-seq and promoter-focused Capture C-derived data in human induced pluripotent stem cell-derived neural progenitor cells. We identified candidate genes with accessible promoter regions that were contacted at high resolution by insomnia-associated SNPs residing in open chromatin. Target genes with known orthologs and available Drosophila RNAi lines were then subjected to deep phenotyping of sleep traits. Candidate genes producing greater than 20 percent change in sleep duration in Drosophila were then screened in a vertebrate zebrafish model using CRISPR/Cas9 mutagenesis in F0 larvae.

Results
This pipeline revealed fifteen genes producing robust sleep phenotypes with more than a 20 percent change in sleep duration in Drosophila. Of the candidate genes screened thus far in zebrafish, we found that disruption of pigq expression significantly (p&lt;0.05) increased sleep duration in both zebrafish and Drosophila through regulation of sleep bout length and frequency, revealing a conserved, yet novel regulator of sleep duration. Additionally, CRISPR mutations in cbx1b and meis1b in zebrafish resulted in reduced sleep duration similar to results in Drosophila.

Conclusion
This pipeline uses cutting-edge genomic and behavioral approaches to perform high-throughput screening of existing GWAS-identified insomnia loci. This genotype-to-phenotype approach emphasizes the importance of behavioral validation following large cohort studies and narrowed the candidate gene list from more than 200 to fewer than 20 providing a more tractable set of gene targets for further molecular characterization. Cross-species validation also improves our understanding of the conservation of sleep characteristics throughout evolution.

Support (If Any)
NIH grants R01 HL143790, P01 HL094307, T32 HL07953
0045 Examining the Association of Trait Sleep Reactivity with Changes in Sleep, Depression, and Anxiety in the COVID-19 Pandemic
Authors: Cirelli Abigail , Krause Adam , O'Hora Kathleen , Osorno Raquel , Sadeghi-Bahmani Dena , Lopez Mateo , Morehouse Allison , Goldstein-Piekarski Andrea 
Published: May 2022

Abstract

Introduction
Sleep Reactivity (SR), a trait-like tendency for stressful events to trigger sleep disturbances, is an established diathesis for insomnia and depression. However, no studies to date have examined SR in the context of the COVID-19 pandemic and it’s related restrictions. Thus, the goal of this analysis is to test whether SR confers a vulnerability for greater sleep and mood symptoms due to the stress of COVID-19 and it’s related restrictions. We hypothesized that (1) The onset of the pandemic will trigger greater increases in insomnia symptoms in highly sleep reactive individuals. 2) Sleep-reactive individuals would experience reduced recovery of insomnia, anxiety, and depression symptoms over the course of the pandemic.

Methods
SR, insomnia, anxiety, and depressive symptoms were assessed by the Ford Insomnia Response to Stress Test (FIRST), Insomnia Severity Index (ISI), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI II), respectively, at two time points (early-pandemic, 6-month follow-up). Additionally, participants retrospectively reported ISI prior to the pandemic. N = 253 adults from Stanford’s COVID-19 Pandemic Sleep Study (April-November 2020) provided baseline insomnia measures, and were excluded if they reported pre-pandemic clinical insomnia (ISI &gt;10). Ranked-correlation tests were used to test the current hypotheses. Paired t-tests were used to evaluate changes in mean insomnia, depression, and anxiety scores. Covariates included essential worker status, sex, and age.

Results
ISI after COVID-19 was significantly higher than retrospective, pre-pandemic ISI (t = 8.2, d = 0.55, p &lt; 0.0001). However, SR was not significantly correlated with the pandemic-related increase in ISI (ρ = 0.07, p = 0.34). Depression significantly increased after 6-months (t = 2.0, d = 0.27, p = 0.047), whereas anxiety did not (t = 1.7, d = 0.26, p = 0.10). Neither changes in depression nor anxiety were predicted by SR (Depression: ρ = 0.15, p = 0.32; Anxiety: ρ = -0.13, p = 0.40).

Conclusion
Insomnia and depression, but not anxiety, increased with the onset of the pandemic. However, trait SR was not a predisposing factor for pandemic-related sleep and mood changes. This is the first analysis examining SR as a risk factor for insomnia and mood symptoms in the pandemic.

Support (If Any)
0047 Relationship of Emotions, Social Isolation, and COVID-Related Media to Subjective Sleep Quality during the COVID-19 Pandemic
Authors: Peszka Jennifer , Mastin David , Kennedy Lindsay , Sestir Marc , Harsh John 
Published: May 2022

Abstract

Introduction
The COVID-19 pandemic safety restrictions led to changes in social interactions and information seeking about the virus. For some, these led to increased negative emotions, feelings of social isolation, and increased COVID-related media consumption. We examined the relationship of these variables to subjective sleep quality from participant daily diaries kept early in the pandemic.

Methods
From April 20th-May 12th, 2020, college (students, faculty/staff, alumni, parents) and local (churches, community centers, libraries) community members (N=94, 72 women, ages 18-77) completed a 30-minute survey for before and during social distancing (measuring: mental health, personality, social distancing, and demographics) for possible prizes. Participants then completed daily evening and morning diaries for 5-14 days describing daily affect, social isolation, emotion regulation, COVID media consumption, and subjective sleep quality.

Results
Emotions: During the pandemic, poor sleep quality was predicted by less positive mood (r(91)=.486, p&lt;.001) and more negative mood (r(91)=-.433, p&lt;.001). Participants with poorer sleep quality reported less success regulating their emotions that day (r(90)=.292, p=.005) and greater suppression of emotions (rather than cognitive reappraisals to regulate them) (r(91)=-.260, p=.012). Social Isolation: Subjective sleep quality was not predicted by social distancing behaviors (r(88)=.069, p&gt;.05); however, poorer sleep quality was significantly predicted by greater daily feelings of social isolation (r(91)=-.264, p=.005) and lower feelings of social life satisfaction (r(91)=.338, p&lt;.001). COVID-related media: Sleep quality was not significantly related to COVID-media consumption for all participants; however, moderation analyses showed that participants with low avoidance coping, low neuroticism, and high emotional well-being did experience poorer sleep quality associated with greater COVID media consumption (all p’s&lt;.05).

Conclusion
That mood and social isolation are associated with sleep quality replicates previous findings. The pandemic, however, provided a unique opportunity to observe these relationships in individuals not normally socially isolated because of confounding variables (e.g., health issues, depression, anxiety) with known relationships to sleep quality. That COVID-related media was only related to sleep quality for more well-adjusted participants (low avoidance coping, low neuroticism, high emotional well-being) was surprising, suggesting some may find COVID-19 information anxiety-relieving rather than anxiety-provoking.

Support (If Any)
Nancy and Craig Wood Odyssey Professorship and Charles L. Brewer Endowed Fund
0050 The Role of Poverty and Perceived Stress on Insomnia Symptom Severity During the COVID-19 Pandemic
Authors: Egeler Mara , Hire Veronica , Walker Jamie , Vargas Ivan 
Published: May 2022

Abstract

Introduction
In 2020, poverty in the United States increased as the COVID-19 pandemic led to the loss of work and/or income. Recent research has also shown that stress caused by the pandemic has led to increased rates of poor sleep. While insomnia rates have increased nationwide, it is not yet known if those living in poverty experienced insomnia symptoms at disproportionate rates. This study examined the effect poverty has had on insomnia symptom severity, as well as whether perceived stress mediated this association.

Methods
Survey data was collected from 3,775 U.S. adults (83.1% White, 78.6% female, age = 18 – 86 years old) during the initial months of the COVID-19 pandemic (April-June 2020). These data were used for a secondary analysis. Participants completed an online survey aimed to assess basic demographics, sleep, physical activity, social engagement, and overall stress levels. Poverty was defined using the poverty guidelines provided by the Department of Health and Human Services (i.e., based on self-reported income and family/household size). The Insomnia Severity Index (ISI) was used to assess insomnia symptoms. Perceived stress was assessed using the Perceived Stress Scale (PSS).

Results
316 participants (8.4%) met criteria to be considered living below the poverty threshold. Those below the poverty threshold had a mean ISI of 10.20 (95% CI: 9.54, 10.86), while those above the poverty threshold had a mean ISI of 8.33 (95% CI: 8.13, 8.53). Put differently, 26.6% of those below the poverty threshold met criteria for clinical insomnia (i.e., ISI &gt; 14), whereas 15.9% of those above the poverty threshold met criteria for clinical insomnia. Finally, a mediation test (with bootstrapping) confirmed that the association between poverty and insomnia was partially mediated by perceived stress (indirect effect = 1.15, 95% CI: 0.76, 1.55).

Conclusion
While poverty guidelines vary by state, these data generally support that there are notable disparities in sleep and insomnia based on family/household income, and that these differences are, in part, due to greater perceived stress. This may be due to increased stress related to loss of work or income. Future studies examining the impact of pandemic stress on insomnia should consider the role of socio-economic status.

Support (If Any)
K23HL141581 (PI: Vargas); R25HL10544 (PI: Jean-Louis); K24AG055602 (PI: Perlis)
0054 A Fear of Dying: How an Obsession with Death During the Pandemic Contributes to More Severe Insomnia
Authors: Jankowski Samantha Samantha , Wellman Camryn Camryn , Reign Deva , Grandner Michael , Dailey Natalie , Killgore William 
Published: May 2022

Abstract

Introduction
The prevalence of insomnia and other sleep disorders increased during the COVID-19 pandemic. While general anxiety, which increased during the pandemic, may account for some of the rise in sleep complaints, other factors may also contribute to insomnia. Here, we examined the potential contribution of fear of dying from the novel coronavirus on the severity of insomnia. We hypothesized that those endorsing a high fear of dying specifically from COVID-19 within 12 months of their assessment would demonstrate more severe insomnia.

Methods
From April 2020 through October 2021, 13,298 U.S. participants (18-92 years old; 57.5% female) completed a online survey (~1,000 participants per month) that included an assessment of their perceived likelihood of dying from COVID in the next year, the Generalized Anxiety Disorder scale-7 (GAD-7), and the Insomnia Severity Index (ISI). We examined insomnia over the course of the first year of the pandemic and divided the sample into those who endorsed at least a 50% or greater perceived likelihood that they would die from COVID-19 in the next year versus those who endorsed a less than 50% perceived likelihood of dying from the illness.

Results
Fear of dying (50% chance or higher) was associated with higher ISI scores (p&lt;.00001) and tended to decline over the course of the year (p&lt;.00001). A significant month x fear interaction (p=.021) suggested that individuals who believed they would die within the year showed significantly fluctuations in insomnia over the course of 13 months with peaks around June and October 2020. Even accounting for situational anxiety (GAD-7), those with a fear of dying still demonstrated higher insomnia levels than their counterparts (p&lt;.00001).

Conclusion
Self-perceived likelihood of dying from COVID-19 in the near future was associated with significantly elevated severity of insomnia, and this remained true even when controlling for a clinical assessment of generalized anxiety levels. These findings suggest that fear of succumbing to the novel coronavirus contributed significantly to the severity of sleep problems during the first year of the pandemic.

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0056 Rest-Activity Rhythms (RARs) and Cognitive Functions in Early Post-menopausal Women
Authors: Paget-Blanc Alexandra , Smagula Stephen , Thurston Rebecca , Chang Yuefang , Maki Pauline 
Published: May 2022

Abstract

Introduction
RAR disruptions are more common among individuals with dementia than healthy individuals. In healthy older women, RAR disruption predicted future diagnosis of Mild Cognitive Impairment (MCI). With no cure for Alzheimer’s Disease, it is crucial to identify modifiable risk-factors for early prevention of cognitive decline. Here we aim to determine whether RAR disruption was associated with cognitive status and cognitive performance in early post-menopausal women, thereby representing a modifiable risk factor for dementia.

Methods
The sample drawn from MsBrain study, included 229 cognitively unimpaired women and 42 women with MCI/dementia, based on score on Montreal Cognitive Assessment (MOCA) adjusted for age and race. Participants completed a 72-hour wrist actigraphy monitoring and neuropsychological assessment including: California Verbal Learning Test (CVLT), Letter Number Sequencing (LNS), Card Rotation Test, Symbol Digit Modalities Test (SDMT). Latent profile analysis (LPA) was performed using five nonparametric RAR variables (intra-daily variability (IV), inter-daily stability (IS), relative amplitude (RA), alpha and F-statistic). The association between RAR clusters and cognitive performance and the relationship between RAR clusters, cognitive status and race/ethnicity were assessed using linear regression models, controlling for age, race/ethnicity, education and body mass index (BMI); and using chi-square test respectively.

Results
LPA revealed three clusters: Robust with high F-Stat, RA and IS and low IV; Normal;Weak with low RA and high alpha. The proportion of subjects with MCI/dementia did not differ between clusters however there was a significant association between race and RAR clusters, X2 (2, N = 271)=14.18, p&lt;0[P1] .001, with non-white women more likely than white women to belong in the Weak group (p &lt; .01). In an adjusted analysis of healthy women, the Weak group performed worse than the Robust group in LNS control (p&lt;.050 ). In the unadjusted model, the Weak group performed worse than Robust group in CVLT Total Learning and Long Delay Recall and SDMT (p=.0074, p=.011and p= .0041, respectively).

Conclusion
Non-white women had weaker RAR than their white counterparts. Weaker RARs related to poorer working memory as measured by LNS; and poorer verbal memory and processing speed, measured by CVLT and SDMT however these effects were largely influenced by covariates, particularly race/ethnicity and education.

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0059 Does Discrimination Moderate the Relationship between Insomnia and Telomere Length in Older Adults from Three Racial/Ethnic Groups?
Authors: Roussett Greg , Prather Aric , Wallhagen Margaret , Weiss Sandra 
Published: May 2022

Abstract

Introduction
Both insomnia and discrimination have been associated with adverse physical and mental health outcomes. Evidence suggests that discrimination may moderate the effects of sleep on telomeres, DNA sequences at the end of chromosomes that protect them from degradation. The purpose of this study was to determine the relationship between insomnia and telomere length among older non-latinx white, black, and latinx individuals and whether discrimination moderated this relationship differently based on race or ethnicity.

Methods
This study is a secondary analysis from the Health and Retirement Study, a longitudinal project sponsored by the National Institute on Aging. Our analysis consisted of 3,205 US participants who provided information on sleep problems as well as salivary samples from which telomere data were assayed. We computed a linear regression to examine the relationship between insomnia symptoms and telomere length in each racial/ethnic group, including interaction terms to assess moderating effects of discrimination.

Results
Insomnia symptoms were associated with shortened telomere length among non-latinx white participants (β -0.046, p=0.015, [-0.06, -0.01]). Discrimination had a moderating effect between insomnia symptoms and telomere length among black participants (β -0.28, p=0.045, [-0.33, -0.00]). Analyses remained significant after adjusting for age, medical co-morbidities, smoking status, and a history of depression.

Conclusion
Our results suggest that symptoms of insomnia may contribute to telomere erosion, with potentially adverse effects on genomic integrity. For black individuals, those who experienced discrimination were at greater risk of telomere damage associated with insomnia.

Support (If Any)
Funding has been made available by the NIH, granted to UCSF School of Nursing Biobehavioral Research Training Program in Symptom Science (NIH: T32 NRO16920).