bluuebunny/crossref_metadata_2025_split huggingface dataset:
0159 Sleep-wake stability and variability in the middle-aged adult population: a UK Biobank study
Authors: Lok Renske , Weed Lara , Chawra Dwijen , Winer Joe , Zeitzer Jamie 
Published: May 2022

Abstract

Introduction
Given the increasing use of consumer, wrist-worn devices with triaxial accelerometry (actigraphy), understanding whether 24-hr activity patterns are associated with specific mental and physical health deficits is of paramount importance. The UK Biobank, a community-based sample of adults in the United Kingdom, provides an opportunity to examine this question given its size (more than 100,000 actigraphy records) and scope (association health records). As a first step in understanding these relationships, understanding the impact of missing data, ways to interpolate missing data, and the general characteristics of 24-hr patterns is necessary.

Methods
A subset (n=70) of complete (i.e., no missing data) actigraphy records from individuals participating in the UK Biobank were used to examine the impact of missing data on intradaily variability (IV; rhythm fragmentation) and interdaily stability (IS; rhythm regularity). Data were intentionally removed and imputed and the impact of the manipulations was examined with Bland-Altman statistics. After determining the best imputation method and the limits of the method, it was applied to missing data in the full cohort, resulting in 82,840 actigraphy records. These were examined for IV and IS, as well as relative amplitude and the timing of L5 and M10. Data were categorized by age, gender, ethnicity, BMI and material deprivation. ANOVA with eta² effect sizes were used for comparisons. Data shown as median (interquartile range).

Results
Relative to IV and IS, median and mean imputation methods corrected for missing data of up to 24 hours. Linear imputation of long (&gt;3 hours) missing data worsened IV and IS scores. Non-parametric patterns in the general population were within expected range, with IV=0.89(0.74-1.05), IS=0.55(0.46-0.63), RA=0.90(0.85-0.99), L5-timing=00:52 (00:07-01:37), and M10-timing=08:25(07:40-09:20). Stratifying by gender, age, ethnicity, BMI and material deprivation resulted in significant differences within all groups (p&lt;0.0001), but small effect sizes (0.0019-0.00052).

Conclusion
Median imputation is useful for correcting for missing data (&lt;24 hours) when examining IV and IS. Non-parametric analysis of the general population indicated values within the expected range. Even though there were significant differences in non-parametric outcomes between genders, age groups, ethnicities, body-mass index and material deprivation, none of these had significant effect sizes.

Support (If Any)
This research has been conducted using the UK Biobank Resource
0164 Overnight Oximetry in Generationally Un-Adapted Residents of High-Altitude
Authors: Stothard Ellen , Hickey Mark , Ebert-Santos Christine 
Published: May 2022

Abstract

Introduction
A recent population shift has increased residents of high-altitude locations. Additionally, travel infrastructure has created the opportunity for rapid displacement to high altitudes without adaptation. Residing at high-altitude is a physiological challenge, which increases the risk of overnight hypoxia from sleep disordered breathing. Sleep disordered breathing, including sleep apnea, is a risk factor for a variety of additional negative health outcomes. Additional information is needed to understand the physiology of high-altitude adaptation in generationally un-adapted residents and prevent negative health outcomes.

Methods
Healthy residents of high altitude participated in this community-supported observational study. Health and altitude history were gathered. Participants completed one night of overnight oxygen monitoring with finger pulse oximetry. Participants with BMI &gt;30 kg/m2, sleep time &lt;4 or &gt;10 hours were excluded.

Results
Total of 41 participants included, 68.3% female, 44.9±13.0 years (SD), BMI 23.7±2.5 kg/m2. Participants resided at altitudes between 2500–3048 m. Participants were also characterized by their years at altitude and percent of life spent at altitude, average 15.9±12.2 years (median 13) and average 33.0±21.7% of life at altitude. Neither years or percent of life at altitude were predicted percent of time below 88% O2 on overnight pulse oximetry (R2 = 0.04 and 0.03, both p&gt;0.12). Multiple Linear Regression indicated BMI was the only factor that explained a signification portion of the variance in adaptation (p&lt;0.01).

Conclusion
In a generationally un-adapted population of high-altitude residents, years at altitude and percent of life at altitude do not explain the variance of adaptation to altitude as measured by percent of night spent hypoxic with less than 88% SpO2. While these data do not provide support for an adaptation response based on time at altitude, they indicate future directions in human altitude adaptation should focus on other covariates, potentially including genetic differences.

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0170 Slow Oscillation Power and Heart Rate Variability During Sleep Predicts Next-day Subjective Sleepiness in Healthy, Young Adults
Authors: Subramoniam Anjana , Chen Pin-Chun , Mednick Sara , Whitehurst Lauren 
Published: May 2022

Abstract

Introduction
High amplitude, slow oscillations in the electroencephalogram (EEG) often characterize the central nervous system’s homeostatic drive for sleep. Slow oscillations dominate the first part of the night and often dissipate as sleep need is satiated. These physiological changes are also reflected in next day subjective measures of sleepiness. Fluctuations in the autonomic nervous system, particularly parasympathetic activity, also coincide with slow wave sleep and are understood to represent bodily homeostasis. However, it is unclear if autonomic indicators effectively predict next-day sleepiness. Here, we investigated whether slow oscillatory (SO) power and cardiac autonomic activity during a night of sleep can predict next day subjective sleepiness.

Methods
88 young (aged 18-35), healthy participants spent the night in a University sleep lab. Before and after sleep, participants completed the Karolinska Sleepiness Scale (KSS) to measure subjective sleepiness. Each participant slept with polysomnography, including electroencephalography and electrocardiography. From these measures, we assessed slow oscillation power (0.5-1Hz) and high frequency heart rate variability (HRV; 0.15-0.45 Hz) --an indicator of parasympathetic, vagally-mediated cardiac tone-- during the first quartile of slow wave sleep. Paired T-tests compared the differences in KSS scores pre- and post-sleep. Pearson’s correlations assessed bivariate associations between slow oscillatory power, high frequency HRV, and KSS scores. Mixed linear models assessed the ability of SO power and high frequency HRV to predict next day subjective sleepiness.

Results
No significant differences were found in KSS ratings pre- (M±SD = 4.23±1.92) and post-sleep (4.38±1.80). No bivariate correlations were present between pre-sleep KSS, SO, or high frequency HRV. A significant correlation between KSS-post sleep and SO power emerged (r=0.286, p=0.001). In Model 1, we found that SO power was a predictor of subjective sleepiness (p&lt;0.001; AIC: 777.469). In Model 2, we included high frequency HRV and reduced the AIC to 515.588. Both slow oscillatory power (p&lt;0.001) and high frequency HRV (p&lt;0.001) were significant predictors of KSS after sleep in Model 2.

Conclusion
We found evidence that both central and autonomic indicators of sleep predict psychological measures of sleepiness. Using autonomic indicators to characterize physiological sleepiness, compared to in-lab polysomnography, may be a more generalizable and cost-effective approach.

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0173 Kynurenine aminotransferase II inhibition improves sleep architecture in adult male and female rats exposed to kynurenic acid elevation during development
Authors: Milosavljevic Snezana , Rentschler Katherine , Wright Courtney , Pocivavsek Ana 
Published: May 2022

Abstract

Introduction
Dysregulated sleep and cognitive impairments are commonly reported in individuals with psychotic disorders, including schizophrenia (SZ) and bipolar disorder (BPD). Emerging evidence implicates the kynurenine pathway (KP) of tryptophan catabolism in the pathophysiology of psychotic disorders. Kynurenic acid (KYNA), a KP metabolite synthetized by kynurenine aminotransferases (KATs) from its biological precursor kynurenine, is elevated in brain tissue and the cerebrospinal fluid of patients with SZ and BPD. KYNA is hypothesized to play a key role in sleep disturbances, thus, we presently investigate if pharmacological inhibition of KAT II to reduce brain KYNA formation may overcome sleep.

Methods
We employed the embryonic kynurenine (EKyn) paradigm to induce KYNA elevation in the fetal brain (Pocivavsek et al 2014 Psychopharm). Wistar dams were fed either kynurenine (100 mg/day) (EKyn) or control wet mash (ECon) from embryonic day (ED) 15 to ED 22. Adult (postnatal day 56-85) male and female offspring were used in sleep studies (EEG/EMG telemetry) to evaluate the effectiveness of PF-04859989 (30 mg/kg, s.c.), an irreversible KAT II inhibitor. Each subject was treated at zeitgeber time (ZT) 0 with either vehicle or PF-04859989 and rapid-eye movement (REM) sleep, non-REM (NREM) sleep, and wakefulness parameters were assessed.

Results
KAT II inhibition significantly increased REM duration during the second half of the light phase in both male (P&lt;0.01) and female (P&lt;0.05) EKyn compared to vehicle treatment. PF-04859989 increased NREM duration and reduced wakefulness during the latter part of the dark phase in both ECon and EKyn male rats, accompanied with significant decrease in relative cage activity, but no differences were determined in female rats across 24 hr. Light phase analysis of spectral power during NREM sleep in EKyn rats revealed significant frequency by treatment interaction (P&lt;0.0001) in males only, with enhanced delta power (0-4 Hz) after PF-04859989 treatment.

Conclusion
Acute decrease in brain KYNA mitigates sleep deficits and elicits higher quality sleep in male EKyn offspring, suggesting KAT II inhibition as a novel mechanistic approach to treating sleep deficiencies in a translationally-relevant preclinical paradigm.

Support (If Any)
This work was funded by National Institutes of Health Grant Nos. NIH R01 NS102209 & P50 MH103222.
0187 Brain Connectivity and Parenting: Association between Familial Factors and Sleep EEG Coherence in Infancy
Authors: Markovic Andjela , Schoch Sarah , Huber Reto , Kohler Malcolm , Kurth Salome 
Published: May 2022

Abstract

Introduction
Brain connectivity is tied to cognitive development and behavior. Previous work suggests that interactions with the environment tune the maturing patterns of brain connectivity. As the relevant environmental factors remain largely unknown, we examined whether the sleep-related familial context is associated with infant brain functional connectivity measured through sleep EEG coherence.

Methods
At-home 124-channel sleep EEG was recorded in 31 healthy infants aged 5.5 to 7.4 months (mean age=5.9±0.5mo; 15 females). Coherence was calculated for the first 80 20-second epochs of NREM sleep in delta (0.75–4.25Hz) and sigma (9.75–14.75Hz) bands, frequencies undergoing pronounced maturational dynamics. We averaged coherence within three regions over the frontal lobe (left, central, right) identified as regions with the strongest connectivity through data-driven clustering. For these regions and bands, linear regression models quantified the association between coherence and familial context, i.e., scores from the Brief Infant Sleep Questionnaire (i.e., sleeping arrangement and bedtime routine), Baby Care Questionnaire (i.e., Structure and Attunement subscales reflecting parental principles regarding infant sleep regularity), Maternal Cognitions about Infant’s Sleep (i.e., total score), age and sex. The best-fitting model was selected through backward selection (Akaike information criterion).

Results
Surprisingly, sex was the most consistent contributor across regions and bands, with girls exhibiting greater coherence than boys (FDR-corrected 0.004≤p≤0.038). Furthermore, older infants showed lower sigma coherence over the right frontal lobe (FDR-corrected 0.002≤p≤0.004). Additionally, infants co-sleeping with parents or siblings demonstrated lower delta and sigma coherence over the right frontal lobe than infants sleeping in their own bed (FDR-corrected 0.001&lt;p≤0.025). Similarly, fewer maternal worries regarding the infant’s sleep were associated with lower sigma coherence in the right frontal region (FDR-corrected p=0.014). Finally, more regular bedtime routines were linked to increased delta coherence over the left frontal lobe (FDR-corrected p=0.014).

Conclusion
Based on previous observations indicating that in healthy children the right hemisphere develops first with a subsequent shift in asymmetry to the left, we propose that environmental factors such as co-sleeping, fewer parental worries, and more structured sleeping routines in infancy may serve as targets for early interventions to support this process and thereby healthy brain development.

Support (If Any)
This work was supported by the Swiss National Science Foundation (PCEFP1 181279) and the University of Zurich (Medical Faculty; Forschungskredit FK 18 047; Stiftung für wissenschaftliche Forschung STWF 17 008).
0192 Effects of emerging alcohol use on developmental trajectories of functional sleep measures in adolescents
Authors: Kiss Orsolya , de Zambotti Massimiliano , Yuksel Dilara , Goldstone Aimée , Colrain Ian , Schaefer Emil , Hasler Brant , Franzen Peter , Clark Duncan , Baker Fiona 
Published: May 2022

Abstract

Introduction
Adolescence is characterized by developmental changes in sleep timing and architecture as well as alcohol use initiation. While the effects of acute and chronic alcohol use on sleep in adults are well-documented, much less is known in adolescents. We used longitudinal data from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) to examine how emerging alcohol use affected sleep architecture in adolescents.

Methods
Overnight polysomnographic recordings were made each year, for 4 years, in 94 adolescents (12–21 years at baseline, 43% female) from the NCANDA cohort. All participants were no or low (youth adjusted Cahalan score of zero) alcohol users at baseline. These data were used to examine developmental trajectories of sleep macro-architecture and sleep electroencephalographic (EEG) measures using linear mixed effect models (LMMs), considering age, sex, family history of alcohol use, body mass index, ethnicity, and alcohol use class (i.e., no-to-low, moderate or heavy) at each annual assessment.

Results
There were strong developmental changes in sleep macro-structure and EEG, most notably, a decrease in slow wave sleep percentage and slow wave (delta) EEG activity with advancing age (p=0.02)​. Compared to those who remained no-to-low drinkers, participants who became moderate/heavy drinkers during the follow-up period, had different sleep trajectories, especially those older at baseline at baseline, including higher slow wave activity (p = 0.04), higher REM sleep percentage (p = 0.03), poorer sleep efficiency​ (p=0.003), and longer latency to sustained sleep (p = 0.03). The effects of alcohol use depended on sex, with male heavy drinkers having more REM sleep than female heavy drinkers (p = 0.04). Overall, a positive family history of alcohol use was associated with less NREM sleep and shorter sleep duration.

Conclusion
Our results present novel findings showing that emerging alcohol use during adolescence exerts complex effects on sleep macro- and micro-structure, over and above normal developmental changes in sleep. These effects could, in part, be alcohol effects on brain maturation processes underlying sleep regulation.

Support (If Any)
AA021696, AA021690
0201 Sleep duration and timing is prospectively linked with increases in insulin resistance over late adolescence
Authors: Jansen Erica , Burgess Helen , Chervin Ronald , O'Brien Louise , Dolinoy Dana , Tellez-Rojo Martha Maria , Cantoral Alejandra , Olascoaga-Torres Libni , Lee Joyce , Dunietz Galit , Peterson Karen 
Published: May 2022

Abstract

Introduction
During puberty, adolescents experience a period of transient insulin resistance (IR) that normalizes upon full maturation. Yet, IR continues to rise for some adolescents, increasing metabolic disease and type 2 diabetes risk in adulthood. Whether short sleep duration and/or later sleep timing are risk factors for persistently increasing IR in late adolescence has not been explored.

Methods
The study population includes 362 adolescents from Mexico City enrolled in a longitudinal birth cohort (ELEMENT study). Beginning in 2015, when participants were between the ages of 9 and 17, there were 2 clinic visits that occurred approximately 2 years apart. During the visit, a fasting blood sample and anthropometric measurements were taken. Insulin resistance was assessed with glucose and insulin via HOMA-IR. Four groups were defined using puberty-specific cutpoints for IR: normal HOMA-IR over the follow-up period (reference), transition from normal to IR, transition from IR to normal, and IR at both time points. Baseline sleep assessments (sleep duration, timing, and variability of both duration and timing) were measured with 7-day actigraphy. Multinomial logistic regression models were used to evaluate associations between sleep duration and timing with HOMA-IR categories, adjusting for age, sex, and baseline pubertal status

Results
Seventeen percent of the sample developed insulin resistance over the follow-up period. Adolescents ≥1 hour below the sleep duration recommendations-for-age were over twice as likely to be in the group that developed IR compared to the normal group (95% CI 1.1, .9; P for trend=0.03). Similarly, adolescents who had a sleep midpoint later than 4:36 AM were 2.77 times as likely to be in the increasing HOMA-IR category (95% CI 1.0, 7.5; P for trend=0.05). Interestingly, there was no evidence that changes in adiposity over follow-up mediated associations between sleep and insulin resistance.

Conclusion
Insufficient sleep duration and late sleep timing were independently associated with development of IR over a 2-year period in peri-puberty. Adequate sleep during the pubertal period may promote metabolic health into young adulthood, independent of any changes in adiposity.

Support (If Any)
Dr. Jansen is supported by K01HL151673. The study is supported by P01 ES02284401.
0209 The Effect of Time of Day of COVID-19 Vaccination and other Covariates on Side Effects
Authors: Abbaspour Sara , Wang Wei , Robbins Gregory , Klerman Elizabeth 
Published: May 2022

Abstract

Introduction
Circadian rhythms have critical roles in human health. We quantified the effect of time-of-day of COVID-19 vaccination and other covariates on self-reported side effects post vaccination.

Methods
The dataset was created from MassGeneralBrigham (MGB) electronic health records and REDCap survey that collected self-reported symptoms for 1-3 days after each immunization. Variables are demographics (age, sex, race, and ethnicity), vaccine manufacturer, clock time of vaccine administration/appointment, any COVID-19 diagnosis/positive test prior to vaccination, any history of allergy, and any note of epinephrine self-injection (e.g., EpiPen) medication. Time of day groupings were morning (6 am–10 am), midday (10 am–2 pm), late afternoon (2 pm–6 pm) or evening (6 pm–10 pm). Side effects were classified as Allergic (Rash; Hives; Swollen lips, tongue, eyes, or face; Wheezing) and Non-Allergic (New Headache, New Fatigue, Arthralgias, Myalgias, Fever) symptoms. The study was approved by the MGB IRB.Machine learning (ML) techniques (e.g., extreme gradient boosting) were applied to the variables to predict the occurrence of side effects. Stratified k-fold cross validation was used to validate the performance of the ML models. Shapley Additive Explanation values were computed to explain the contribution of each of the variables to the prediction of the occurrence of side effects.

Results
Data were from 54,844 individuals. On day 1 after the first vaccination, (i) females, people who received the Moderna vaccine, and those with any allergy history were more likely to report Allergic side effects; and (ii) females, people who received the Janssen vaccine, those who had prior COVID-19 diagnosis ,and those who received their vaccine in the morning or midday and were more likely to report Non-Allergic symptoms. Older persons had fewer side effects of any type.

Conclusion
ML techniques identified demographic and time-of-day-of-vaccination effects on side effects reported on the first day after the first dose of a COVID-19 vaccination. We will use these techniques to test for changes on days 2 and 3 after the first dose, and the first 3 days after the second dose and for the influence of recent night or shiftwork. Future work should target underlying physiological reasons.

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0211 A 10-week observational research study in individuals with delayed sleep-wake phase disorder (DSWPD) symptoms
Authors: Smieszek Sandra 
Published: May 2022

Abstract

Introduction
We conducted an observational research study in suspected delayed sleep-wake phase disorder (DSWPD) participants. The objective was to measure sleep-wake patterns and to conduct exploratory genetic analyses to delineate the landscape of DSWPD.

Methods
We measured the sleep-wake patterns of participants by daily post-sleep diaries for 10 weeks. Participants also completed questionnaires on demographics, medical/surgical history, sleep history, and concomitant medications. Altogether, 119 participants were consented and 76 participants provided samples for whole genome sequencing.

Results
Sleep diary analysis confirmed delayed sleeping patterns in the study population. Midpoint of sleep was 4:50 AM (SD = 2:06) versus 3:06 AM (SD = 0:59) in controls, a statistically significant difference (t (df) = 6.57 (72.063); p ≤ 0.0001). Mean total sleep time (TST) was 6.88 h (SD = 1.35) versus 7.79 h (SD = 0.56) in controls, a statistically significant difference (t (df) = -5.38 (70.863); p ≤ 0.0001). This effect was driven by shorter participant-reported TST on work nights (6.33 h) versus free nights (7.22 h). Sleep latency was significantly later on work nights than free nights. Altogether 17% of participants reported at least one psychiatric condition.We observed an enrichment of the minisatellite 54bp (1: 7829913-7829966 (GRCh38)) variable number of tandem repeat (VNTR) PER3 rs57875989 4 allele. Significantly higher frequencies of the 4/4 and 4/5 variants were observed when compared to controls (n = 1937; recessive: OR 3.3, CI 2.1177 to 5.4304, p &lt; 0.0001).We analyzed the putative loss-of-function and missense variants. We report on presence of cases with PER3 rs144178755 (NM_001289862:p.T1049), PER3 rs228696 (NM_001289861:p.L835P), and PER2 rs76355956 (NM_022817:p.V197M), among other rare nonsynonymous variants. We observed higher frequency of missense variants in core clock genes when compared to controls.

Conclusion
Sleep diary data confirmed significantly delayed sleep patterns, with more pronounced results during work nights and larger SDs across all sleep parameters, suggesting more variable sleep patterns. Genetic analysis confirmed these individuals are more likely to harbor variants within their core clock genes with enrichment of the VNTR variant, potentially leading to a pronounced delay in sleep period.

Support (If Any)
Vanda Pharmaceuticals Inc.