bluuebunny/crossref_metadata_2025_split huggingface dataset:
0016 Genetic Basis of Daytime Napping and Consequence on Cardiometabolic Health
Authors: Dashti H S , Daghlas I , Lane J , Udler M , Garaulet M , Saxena R 
Published: May 2020

Abstract

Introduction
Although daytime napping is a common, evolutionarily conserved behavior, its genetic basis is unknown. Elucidating its genetic basis may clarify relevant underlying biological pathways and determine causal links with cardiometabolic health.

Methods
We performed a genome-wide association study of self-reported daytime napping using linear regression in adults of European ancestry in the UK Biobank (n=452,633) and assessed robustness of signals with accelerometer-derived daytime inactivity duration (n=84,671). Next, we conducted a phenome-wide association study in a hospital-based clinical biobank (n=30,683) using napping genome-wide polygenic score (GPS), and Mendelian randomization (MR) with cardiometabolic traits. To deconstruct the napping genetic variants, we applied a novel “soft clustering” Bayesian nonnegative matrix factorization method and generated partitioned cluster-specific polygenic risk scores (PRS).

Results
We identified 121 distinct genome-wide significant loci for daytime napping, with lead signals at or near genes KSR2 (kinase-suppressor of ras 2), HCRTR1/HCRTR2 (hypocretin-receptor 1/2), SKOR2 (SKI family transcriptional-corepressor 2), and MAPT (microtubule-associated protein tau), among others. The loci associated with accelerometer-derived daytime inactivity duration. Gene enrichment analyses pointed to pathways involved in neurogenesis and others including nervous system development and opioid signaling. Genetic overlaps were evident in a clinical biobank where highest, compared to lowest, decile of napping GPS associated with 30%, 40%, and 50% higher odds for essential hypertension, obesity, and nonalcoholic liver disease, respectively (P&lt;0.0001). In MR, potential causal links were identified with higher diastolic blood pressure (2.67 mmHg per napping category-increase, 95% CI 1.62–3.23, P=6.80e-07), systolic blood pressure (3.65mmHg, 1.86–5.44, P=6.40e-05), and waist circumference (0.28 SD-units, 0.11–0.45, P=0.0015). The clustering of variants identified 3 robust clusters (cluster-1: “higher sleep propensity”; cluster-2: “more fragmented/inefficient night sleep”; cluster-3: “early sleep timing”). Only clusters 2 and 3 PRSs were associated with worse cardiometabolic health outcomes, including higher BMI, waist circumference, CRP, and triglycerides (all P&lt;0.05).

Conclusion
These findings expand our understanding of the genetic architecture of napping implicating multiple biological pathways, indicating possible genetic overlap and causal links to cardiometabolic traits, and suggesting distinct nap-promoting mechanisms with differential associations with health outcomes.

Support
This work is supported by grants NIH-F32DK102323, NIH-4T32HL007901, NIH-R01DK107859, NIH-R35HL135818, and MGH Research Scholar Fund.
0027 Alternations in Contractility, Calcium Signaling and Nuclear Factor Kappa B Activation in Stem Cells Derived Cardiomyocytes Following Exposure to Obstructive Sleep Apnea Children’s Serum, and Intermittent Hypoxia
Authors: Goldbart A , Haddad H , Etzion S , Gopas J 
Published: May 2020

Abstract

Introduction
There are cardiovascular morbid effects of OSA in adults and children. We have previously reported over-expression of Nuclear-Factor-κappa B in tonsils of children with OSA, and NF-κB activation after exposure to sera of children with OSA. In order to investigate NF-kB activation and the physiology of cardiomyocytes of human origin (CM’s), we have established an ex-vivo model where CM’s derived from human embryonic stem cells H-9.1 clone (hES) and from Induced pluripotent stem cells (iPSC) are either incubated with human sera, or exposed to intermittent hypoxia(IH) or room air (RA).

Methods
Serum samples were drawn following overnight polysomnography (PSG) from children with OSA (AHI&gt;5) or control (AHI&lt;1). Differentiated human cardiomyocytes were incubated with 5% OSA sera or control. Average cell beating/min was determined and NF-kB p50 and p65 cytoplasmic or nuclear localization were detected by immunofluorescence (operetta). CM’s were exposed to either RA or to IH (21% alternating with 1% O2, 6 cycles/h, 24 h) in a chamber (BioSpherix Instruments, Redfield, NY)Intracellular calcium transient signal (ionoptix) and mechanical contraction of CM (Musclemotion) were assessed.

Results
1. Cell beating/min was reduced in cells incubated with OSA (n=10) as compared to control (n=10);(p&lt;0.01), and following IH exposure vs RA (p&lt;0.01),). 2. There is an over-expression of NF-κB p50, p65 subunits as a result of exposing CMs to OSA sera, and following IH exposure 3. a rapid decrease (up to 100%) was measured in calcium transient amplitude as well as contraction amplitude (p&lt;0.05) after adding OSA sera, that was completely restored after washing.

Conclusion
We revealed human cardiomyocytes NF-kB activation and decreased contractility following exposure to OSA sera and to IH. The rapid decrease in calcium signaling and contractility infer the presence of factors that reversibly affects CMs contraction. This ex-vivo model enables the study of functional and molecular alterations in human CM

Support
Israel science Foundation (ISF) 1344/15
0039 The Clinical Utility of Dim Light Melatonin Onset in Treatment of Delayed Sleep-Wake Phase Disorder: Preliminary Findings
Authors: Swanson L , Arnedt J , DuBuc K , de Sibour T , Burgess H 
Published: May 2020

Abstract

Introduction
Delayed sleep-wake phase disorder (DSWPD) is common, debilitating, and challenging to treat. In an ongoing randomized trial, we are comparing exogenous melatonin treatment outcomes in DSWPD participants for whom dim light melatonin onset (DLMO) is measured objectively vs. estimated.

Methods
Thus far, 13 participants (27±6 years old, 67% female) have completed a randomized, controlled, double-blind 4-week trial of 0.5 mg of exogenous melatonin timed to either 3 h before measured DLMO (M-DLMO, n = 6) or 3 h before DLMO estimated at 2 h before average sleep onset time based on at least 7 days of wrist actigraphy and sleep diary (E-DLMO, n = 7). All participants met International Classification of Sleep Disorders-3 diagnostic criteria for DSWPD and were otherwise healthy. Participants completed 4 weekly treatment sessions with a blinded psychologist; time of melatonin administration and bed-rise schedule were advanced up to 1 h/week. A validated home saliva collection kit measured DLMO in all participants. Between-group t-tests and Hedges’ g effect sizes (ES) were calculated at post-treatment for the following outcomes: DLMO; Pittsburgh Sleep Quality Index (PSQI) global score; Morningness-Eveningness Questionnaire (MEQ); and the actigraphy parameters sleep efficiency (SE) and clock time of sleep onset and offset. A paired-sample t-test compared the measured vs. estimated DLMO at baseline.

Results
The M-DLMO group had a 65±88 mins DLMO advance vs. 27±30 mins in the E-DLMO group (ES=0.51 p=.381). PSQI scores were similar between groups (M-DLMO=6.67±2.06, E-DLMO=7.1± 1.57, ES=-0.24, p=.646), as were MEQ scores (M-DLMO=43±4.98, E-DLMO=48±12.72, ES=-0.47, p=.387). Sleep onset time (M-DLMO=0:32±1:02, E-DLMO=0:31±1:38, ES=0.01, p=.98) and offset time (M-DLMO=8:05±1:03, E-DLMO=8:08±2:14, ES=-0.02, p=.968) were similar between the groups, although sleep was more efficient in M-DLMO vs. E-DLMO (84%±3% vs. 76%±10%, ES=0.94, p=.096). On average, baseline measured DLMO occurred 123±83 mins earlier than estimated DLMO (p=.001).

Conclusion
We are continuing to enroll participants in this trial. Preliminary results suggest some potential benefit of measuring the DLMO, but results will need to be clarified in a larger sample.

Support
American Sleep Medicine Foundation Strategic Research Award
0053 Effect of Changes in Intracellular Adhesion Molecule-1 on Measures of Sleepiness and 24-hour Ambulatory Blood Pressure After 4 Months of Continuous Positive Airway Pressure
Authors: Pak V M , Maislin D , Keenan B T , Townsend R , Dunbar S B , Pack A I , Gislason T , Kuna S T 
Published: May 2020

Abstract

Introduction
Previous studies have shown that continuous positive airway pressure (CPAP) therapy of adults with obstructive sleep apnea (OSA) reduces circulating levels of intercellular adhesion molecule 1 (ICAM-1). ICAM-1 levels may affect daytime sleepiness and elevated blood pressure associated with OSA. Our goals were to explore associations between changes in ICAM-1 and objective and subjective measures of sleepiness, as well as 24-hour ambulatory blood pressure monitor (ABPM) parameters in adults with OSA following 4 months of CPAP treatment.

Methods
We identified 140 adults with newly diagnosed OSA in the Penn Icelandic Sleep Apnea (PISA) Study, with a mean (±SD) body mass index (BMI) of 31.5±4.2 kg/m2 and apnea-hypopnea index (AHI) of 36.8±15.3 events/hour; 83.3% were males. Plasma ICAM-1 levels, 24-hour ABPM, Epworth Sleepiness Scale (ESS), and Psychomotor Vigilance Task (PVT) measures were obtained at baseline and after 4 months of CPAP treatment. Associations between changes in natural log ICAM-1 and both sleepiness and 24-hour mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, use of anti-hypertensive medications, AHI and hours/night of CPAP usage.

Results
Overall, there was no significant change in ICAM-1 from baseline to follow-up among all participants after 4 months (0.027 ng/ml, p=0.52). There were no statistically significant associations between the change in ICAM-1 and change in sleepiness measures (all p&gt;0.05) or 24-hour MAP (1.124 mm Hg, p=0.07). A nominal association between increased ICAM-1 and increased daytime MAP after 4 months was observed (1.39 mm Hg, p=0.033), although this result was not significant after correction for multiple comparisons.

Conclusion
Our results do not support changes in ICAM-1 as the biological pathway linking changes in sleepiness or ABPM following CPAP treatment of adults with OSA.

Support
P01-HL094307 (NHLBI, PI: Pack AI)
0054 Metabolite Profiles of Obstructive Sleep Apnea Distinguishes Cases from Controls and Improve With CPAP
Authors: Sengupta A , Lim D C , Keenan B T , Keele L , Pack A , Weljie A 
Published: May 2020

Abstract

Introduction
Obstructive sleep apnea (OSA) is a common sleep breathing disorder with significant public health consequences. Despite this, no clinically available objective molecular biomarkers to diagnose, risk stratify and quantify treatment efficiency exist. To this end, high-throughput metabolomics data could serve as a valuable quantitative tool.

Methods
We designed a pilot study to investigate the metabolomic effects of OSA and CPAP treatment. Blood serum samples were collected from OSA patients and healthy controls matched with respect to age (±5 years), BMI (±2.5 kg/m2) and gender (N = 20/group). Samples from OSA patients were obtained before and after continuous positive airway pressure (CPAP) treatment. Polar metabolites were analyzed using a targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics technique.

Results
Supervised multivariate analysis using serum metabolic values of OSA patients and healthy controls showed a significantly different overall metabolic profile between the two groups (orthogonal partial least squares discriminant analysis [OPLS-DA] Q2=0.25, p=0.04). Acetylornithine, choline, cytidine, dodecenoylcarnitine, methionine sulfoxide and 3-indoxylsulfate were among the most perturbed metabolites. Major metabolic pathways altered in the OSA patients were methionine and phospholipid metabolism, as well as gut microbial co-metabolism. Lysophosphatidylcholine (16:0), a phospholipid metabolite, demonstrated significant linear association with improved oxygen saturation nadir post CPAP treatment (R2 = 0.57), suggesting the metabolic features may be used as prognostic clinical biomarkers.

Conclusion
These results suggest that OSA significantly impacts blood metabolites, which could potentially be used to establish OSA biomarkers. Moreover, specific metabolic features are associated with post CPAP improvement, such as phospholipids, suggesting a functional association of these metabolites that may help us understand the heterogeneity of OSA. Overall, these results demonstrate the potential of metabolic profiling to develop quantitative molecular markers of OSA. Further studies are underway to validate these findings and investigate the utility of metabolic profiles to objectively measure CPAP efficacy.

Support
The work was supported by the program project grant P01 HL094307.
0064 Heightened Neural Responses to Negative Words in Shift Workers Using the Stroop Task
Authors: Lee K , Lee H , Jeon J , Jeon S , Kim N , Oh S , Lee M , Kim S , Lee Y 
Published: May 2020

Abstract

Introduction
Shift work is known to have a negative impact on a wide range of health problems such as sleep disturbance, cognitive impairment, and emotional disorders (e.g., anxiety and depression). It is important to understand underlying mechanisms for negative impact of shift work on health problems. This study aimed to investigate psychological and neural mechanisms associated with shift work.

Methods
Thirty six shift workers (28 females, age = 29.9 ± 7.4) and 35 non-shift workers (20 females, age = 30.5 ± 5.5) participated in this study. They were performing the word Stroop task during fMRI scanning. This task included sleep-related words and negative words to investigate neural substrates associated with sleep-related information and emotional information processing. Neutral words were included as control stimuli. The participants also completed questionnaires assessing sleep-related problems such as Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale, and emotion-related problems such as Beck Depression Inventory and Beck Anxiety Inventory. Two-sample t-tests were conducted to find group differences in self-report measures and neural response to sleep-related words and negative words compared to neutral words.

Results
Relative to non-shift workers, shift workers showed greater sleep disturbance (i.e., higher PSQI), but they did not show any evidence of emotion-related problems. Shift workers also demonstrated greater neural response to negative words (vs. neutral words) in several prefrontal regions (e.g., dorsal anterior cingulate cortex and dorsolateral prefrontal cortex), anterior insula and caudate compared to non-shift workers. However, shift workers did not show significantly different neural response to sleep-related words (vs. neutral words) compared to non-shift workers.

Conclusion
The result from this study provides supporting evidence that shift work is associated with subjective sleep disturbance. Shift workers’ heightened neural response to negative information may reflect their increased sensitivity to negative information, that may contribute to sleep disturbance.

Support
Brain Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (Study No.: 2016M3C7A1904338 and NRF-2018R1D1A1B07049704).
0081 Habitual Sleep Duration is Negatively Correlated with Emotional Reactivity within the Rostral Anterior Cingulate Cortex in Individuals with PTSD
Authors: King R , Jecmen D , Mitchell J , Ralston K , Gould J , Burns A , Bullock A , Grandner M A , Alkozei A , Killgore W D 
Published: May 2020

Abstract

Introduction
Sleep difficulties, such as insomnia, are highly prevalent in individuals with Post-Traumatic Stress Disorder (PTSD). However, sleep deprivation can also increase emotional reactivity to positive (as well as negative) stimuli. While the effects of sleep loss on emotional perception healthy individuals has been documented, it remains unclear how lack of sleep in individuals with PTSD may affect their emotional reactivity to positive stimuli. We hypothesized that lower habitual sleep duration would be associated with greater functional brain activation changes in response to subliminally presented happy faces in brain areas of the reward network, such as the rostral anterior cingulate cortex (rACC).

Methods
Thirty-nine individuals with DSM-5 confirmed PTSD were administered the Pittsburgh Sleep Quality Index (PSQI) as a measure of their average nightly sleep duration over the past month. Participants then underwent fMRI imagining while viewing subliminal presentations of faces displaying happiness, using a backward masked facial affect paradigm to minimize conscious awareness of the expressed emotion. Brain activation to masked happy expressions was regressed against sleep duration in SPM12.

Results
There was a negative correlation between habitual sleep duration and activation within the rACC in response to the masked happy faces (x=14,y=40,z=0; k=102, pFWE-corr= 0.008).

Conclusion
Individuals with PTSD who average less sleep at night showed greater emotional reactivity, as indexed by greater functional brain activation changes within an area of the reward network, than individuals who obtained more sleep per night. Future research involving actual sleep duration manipulation will be necessary to determine whether this finding reflects the well-known antidepressant effect of sleep deprivation or a form of greater emotional expression error monitoring among traumatized patients when lacking sleep. Regardless, these findings suggest that insufficient sleep could affect unconsciously perceived emotion in faces and potentially affect social and emotional responses among individuals with PTSD.

Support
US Army Medical Research and Materiel Command: W81XWH-14-1-0570
0085 Vulnerability to Sleep Restriction is Associated with Decreased Working Memory Performance
Authors: Mathew G M , Strayer S M , Ness K , Buxton O M , Chang A 
Published: May 2020

Abstract

Introduction
We investigated whether individuals with more lapses on the psychomotor vigilance task (PVT) after sleep restriction (SR) demonstrated poorer working memory compared to those with fewer PVT lapses.

Methods
Fifteen healthy men (22.3±2.8 years) participated in a 10-night inpatient protocol with three nights of 10-hour baseline time in bed (TIB), five nights of SR (5-hour TIB), then two recovery (10-hour TIB) nights. Participants completed the Visual Object Learning Task (VOLT) and Fractal 2-Back (F2B; visual n-back) measuring working memory and the PVT (Joggle Research® battery) approximately every two hours during wake. During the VOLT, participants indicated whether presented images had been shown previously. Outcomes included number of misses and false alarms. During the F2B, participants tapped the screen when an image appeared that had been shown 2 images previously. Outcomes included sensitivity and specificity. Median split of mean PVT lapses after the last night of SR was used to categorize participants into “vulnerable” (n=8) versus “resistant” (n=7) groups. Outcomes were analyzed in mixed models with the predictor day*vulnerability, excluding the first three baseline days to preclude practice effects.

Results
There was a significant interaction between day and attentional vulnerability for VOLT misses (p&lt;.001); misses increased linearly across days in vulnerable (b=.18, p&lt;.001) but not resistant (p=.956) participants. There was no interaction between day and vulnerability for VOLT false alarms, which did not change across days. There was a significant interaction between day and attentional vulnerability for F2B sensitivity (p=.002); sensitivity increased linearly across days in resistant (b=.02, p&lt;.001) but not in vulnerable (p=.273) participants. There was no interaction between day and vulnerability for F2B specificity, which did not change across days.

Conclusion
Performance on the VOLT decreased in vulnerable participants only; performance on the F2B improved in resistant participants likely due to practice effects not seen in vulnerable participants. Findings indicate vulnerability to attentional lapses after SR is a marker of vulnerability to working memory decrements.

Support
This study was funded by grant UL1TR000127 from the Clinical and Translational Science Institute (Chang PI) and the College of Health and Human Development at the Pennsylvania State University.
0086 Daytime Napping and Memory Consolidation of Novel Word Learning in Children and Adults
Authors: van Rijn E , Walker S A , Knowland V C , Cairney S A , Gouws A D , Gaskell M , Henderson L 
Published: May 2020

Abstract

Introduction
Memory for novel words benefits from sleep, particularly non-rapid eye movement (NREM) sleep and its features, such as sleep spindles and slow oscillations. This is consistent with systems consolidation models, in which sleep supports transfer from hippocampal to neocortical memory networks. Larger amounts of slow wave sleep in children has been proposed to account for enhanced consolidation effects, but such studies have typically focused on nocturnal sleep. We examined whether daytime naps benefit word retention in adults and children aged 10–12 years, and whether this relationship in children is affected by differences in white matter pathway microstructure. We hypothesized that the link between memory consolidation and structural brain connectivity will be mediated by the degree of sleep spindles during the nap.

Methods
Adults (N = 31; mean age = 20.91, SD = 1.55) and children (N = 38; mean age = 11.95, SD = 0.88) learned spoken novel words, followed by a 90-minute nap opportunity monitored with polysomnography. Memory for the words was tested pre- and post-nap. Children’s structural brain connectivity was measured using diffusion tensor imaging (DTI).

Results
Word memory was preserved following sleep in adults, while an adult wake control condition showed deterioration. Similarly, in children memory performance was stable over the nap, with wake control data currently being collected. Analyses relating behavioral changes over the nap to NREM sleep features and structural brain connectivity will be presented.

Conclusion
In line with sleep-dependent memory consolidation models, daytime naps protect novel words from forgetting in adults and children. Examining potential relationships between nap-based consolidation and structural integrity has important theoretical implications, given the increase in brain connectivity in language areas during childhood, as well as white matter alterations in developmental populations.

Support
This research was supported by the UK Economic and Social Research Council, grant no. ES/N009924/1.