bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel design for sampling benthic zooplankton communities in disparate Gulf of Alaska habitats using an autonomous deep-water plankton pump
Authors: Wilborn Rachel E , Rooper Christopher N , Goddard Pam , Williams Kresimir , Towler Rick 
Published: May 2020

Abstract
Deep-water larval fish and zooplankton utilize structurally complex, cold-water coral and sponge (CWCS) habitats as refuges, nurseries and feeding grounds. Fine-scale sampling of these habitats for larval fish and zooplankton has proven difficult. This study implemented a newly designed, autonomous, noninvasive plankton pump sampler that collected large mesozooplankton within 1 m of the seafloor. It was successfully deployed in the western Gulf of Alaska between the Shumagin Islands (~158°W) and Samalga Pass (−170°W), and collected in situ zooplankton from diverse benthic communities (coral, sponge and bare substrates) at depths in excess of 100 m. Key design parameters of the plankton pump were its ability to be deployed from ships of opportunity, be untethered from the vessel during sampling and be deployed and retrieved in high-relief, rocky areas where CWCS are typically present. The plankton pump remains stationary while collecting from the water column, rests within 1 m of the seafloor and captures images of the surrounding habitat and substrate. This plankton pump design is a low-cost, highly portable solution for assessing the role of benthic habitat in the life cycle of mesozooplankton, a linkage that has been relatively underexplored due to the difficulty in obtaining near-bottom samples.
0005 Cataplexy Triggered by Social Cues: A Role for Oxytocin in the Amygdala
Authors: Mahoney C E , Zhao W , Coffey A , Woods C , Kroeger D , Scammell T 
Published: May 2020

Abstract

Introduction
People with narcolepsy type 1 report that cataplexy is triggered most often by positive social experiences such as laughing with friends, yet the mechanisms through which social interaction promotes cataplexy are unknown. We hypothesize a subpopulation of central amygdala neurons that are sensitive to the prosocial neuropeptide, oxytocin (CeAOTR), respond to positive valence and trigger cataplexy.

Methods
We have used in vivo calcium imaging, chemogenetic and optogenetic approaches to characterize the activity pattern of these neurons and to manipulate their activity state.

Results
Cre-dependent anterograde tracing of the CeAOTR neurons of the central amygdala indicate a moderate to dense projection to the REM sleep-regulatory region of the ventral lateral periaqueductal gray (vlPAG). Additionally, Channel Rhodopsin Assisted Circuit Mapping (CRACM) experiments show that CeAOTR neurons inhibit vlPAG neurons that innervate the REM atonia-promoting region, the sublaterodorsal nucleus. Targeted photostimulation (15Hz (10ms) for 20sec every hour) of the CeAOTR fibers in the vlPAG doubled the amount of cataplexy. Preliminary in vivo calcium imaging indicates that the CeAOTR are active just prior to the onset of cataplexy. Chemogenetic and optogenetic activation of CeAOTR neurons increased cataplexy.

Conclusion
We conclude that the CeAOTR subpopulation is sufficient to promote cataplexy. Our future directions include determining the necessity of these oxytocin sensitive neurons in cataplexy under different conditions of positive valence.

Support
R01 NS106032 and WakeUp Narcolepsy.
0007 Daytime Sleep in Night Shift Workers: Quantifying the Role of Circadian Misalignment
Authors: Mann E , Sagong C , Cuamatzi Castelan A , Singh M , Roth T , Drake C L , Cheng P 
Published: May 2020

Abstract

Introduction
Circadian misalignment is commonly cited as a culprit of daytime sleep disturbances in night shift workers; however, the specific impact and magnitude that circadian misalignment has on daytime sleep has not been well-characterized in larger samples of night shift workers.

Methods
Participants included fixed-night shift workers (n=52, ages 18–50) who completed an 8-hour daytime polysomnography (PSG) in the lab following a night shift. Measures of sleep disturbances included: difficulty falling asleep (sleep onset latency [SOL], latency to persistent sleep [LPS]), difficulty staying asleep (sleep efficiency [SE], wake after sleep onset [WASO]), and sleep duration (total sleep time [TST]). Melatonin samples were collected hourly for 24 hours under dim light (&lt;10 lux) and used to determine dim light melatonin offset (DLMOff). Circadian misalignment (CM) was calculated as the time difference between bedtime and DLMOff (higher values represented sleeping after DLMOff), and correlated with PSG sleep variables.

Results
CM was significantly associated with difficulty staying asleep (WASO: r=0.48, p&lt;0.001; SE: r=-0.45, p&lt;0.001), and sleep duration (TST: r=-0.38, p&lt;0.01). Specifically, every 3 hours of CM on average added 19.2 minutes of WASO and reduced TST by 15 minutes. In contrast, CM was not significantly correlated with sleep onset difficulties (SOL: r=-0.27; LPS: r=-0.02).

Conclusion
These data suggest that circadian misalignment in shift workers may be a better predictor of difficulties staying asleep and sleep duration during the day relative to difficulties falling asleep. Because longer work hours (10–12 hours) are common in night shift worker, it may be that sleep initiation difficulties associated with circadian misalignment is masked by elevated fatigue or an increased homeostatic drive from prolonged wakefulness. These results may help guide decisions about the magnitude of phase shifts required (e.g., with light therapy) for the desired improvement in daytime sleep.

Support
Support for this study was provided to PC by the NHLBI (K23HL138166)
0014 Reduced Cortical Thickness as a Biomarker of Daytime Sleepiness in Mild Traumatic Brain Injury
Authors: Dailey N S , Raikes A C , Alkozei A , Grandner M A , Killgore W D 
Published: May 2020

Abstract

Introduction
Sleep disruptions, including the increase of daytime sleepiness, are reported in roughly 70% of all individuals who have suffered a mild traumatic brain injury (mTBI). Prior research using magnetic resonance imaging (MRI) has identified associations between functional brain changes and daytime sleepiness following mTBI. In the present study, we aimed to identify whether structural differences in cortical thickness are associated with increased daytime sleepiness in adults with mTBI.

Methods
A total of 58 adults between 18 and 45 years of age (M=23.58±5.31) participated in the study, including 19 healthy controls and 39 individuals with a documented mTBI. Individuals with mTBI were further divided based on time-since-injury into a sub-acute (n=22) or chronic (n=17) group. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS) and cortical thickness was measured using high-resolution T1-weighted structural MRI. Whole-brain vertex-wise estimations of cortical thickness were calculated using FreeSurfer (v.6.0) and entered into a GLM to identify between-group differences in cortical thickness and the association with ESS.

Results
Significant differences in cortical thickness were found between the two mTBI groups (cluster-forming threshold p&lt;.01; cluster-wise threshold p&lt;.05; two-tailed; FWE-corrected). Specifically, lower cortical thickness in the left hemisphere was found in the inferior parietal lobule (p=.01), precuneus (p=.03), and pars triangularis (p=.04) for the sub-acute, compared to chronic group. Furthermore, a significant negative correlation was found between ESS and cortical thickness in the inferior parietal lobule (r=-.55, p=.009) for the sub-acute mTBI group.

Conclusion
More daytime sleepiness was associated with reduced inferior parietal cortical thickness in those 2 to 12-weeks post-injury, an association not observed in those 6 to 12-months post-injury or healthy controls. The inferior parietal lobule is part of the frontoparietal attention network and has been associated with vulnerability to sleep loss. Our findings suggest structural damage to the attention network following mTBI may be one factor affecting daytime sleepiness in mTBI. These findings may reflect a potential biomarker of sleep disturbances in mTBI.

Support
USAMRMC grant (W81XWH-12–0386).
0031 Photoperiodic Effects on Diurnal Rhythms in the Immune System, Rest-Activity Behavior, and Cortisol Revealed in a Diurnally Active Large Animal Model - The Domestic Pig
Authors: Engert L C , Weiler U , Pfaffinger B , Stefanski V , Schmucker S S 
Published: May 2020

Abstract

Introduction
Diurnal variations in immune cell number and function are regarded important for immune competence and are thought to be mediated by rest-activity rhythms and hormones. Moreover, the photoperiod is also known to modulate the immune system and considered to affect seasonal disease susceptibility. Whereas few studies investigated seasonal effects, the present study is the first investigating the specific effect of the photoperiod on diurnal rhythms in cell numbers of peripheral leukocyte types in any species.

Methods
Domestic pigs were held either under long day (LD, 16L:8D, lights-on 07:00-23:00, n=9) or short day conditions (SD, 8L:16D, lights-on 07:00-15:00, n=11) and fed concentrate at 07:30 + 14:00 (ad libitum hay/water). Blood samples were taken every 2 h over periods of 50 h via indwelling vein catheters. Rest-activity behavior of the pigs was analyzed using continuous camera recordings.

Results
Cosinor analyses (p&lt;.05) revealed photoperiodic differences in diurnal rhythms of cell numbers of various peripheral leukocyte subtypes, rest-activity behavior, and cortisol concentration. Cell numbers of total leukocytes, NK cells, T cells, and eosinophils in blood, rest-activity behavior, and cortisol concentration peaked earlier relative to lights-on under SD (p&lt;.05). Relative amplitudes in rest-activity behavior and cell counts of total leukocytes, NK cells, T cells, and monocytes were higher under SD (p&lt;.05). However, there was no photoperiodic effect on diurnal rhythms in neutrophil counts and mesor in any leukocyte type. Generalized linear mixed models revealed associations of leukocyte counts with rest-activity behavior and cortisol concentration in most cell types (p&lt;.05). Moreover, the found photoperiodic effects on diurnal rhythms in rest-activity behavior and cortisol concentration are in agreement with research in humans and primates.

Conclusion
The present study revealed photoperiodic effects on diurnal rhythms in the immune system, rest-activity behavior, and cortisol concentration in pigs and strengthens the importance of the domestic pig as suitable model for chronoimmunology.

Support
German Research Foundation DFG (grant provided to SS, grant number SCHM3162/1-1), Federal Ministry of Education and Research, Germany (grant number 01PL16003), Faculty of Agricultural Sciences, University of Hohenheim (scholarship provided to LE).
0038 The Effects of Morning Blue Light Therapy on Insomnia Severity and PTSD Symptoms in a Clinical Sample
Authors: Jecmen D , King R , Gould J , Mitchell J , Ralston K , Burns A I , Bullock A , Grandner M A , Alkozei A , Killgore W D 
Published: May 2020

Abstract

Introduction
Individuals with Post Traumatic Stress Disorder (PTSD) often present with insomnia, which may exacerbate other symptoms of the disorder. Morning Blue Light Therapy (BLT) can regulate circadian rhythms and may even improve sleep and mood in individuals with major depressive disorder. However, it is unclear whether morning BLT could also be an effective treatment for the insomnia associated with PTSD. We investigated whether 6 weeks of daily morning BLT would improve insomnia severity and symptom presentation in individuals with PTSD in comparison to a placebo condition of amber light (ALT). We hypothesized that changes in insomnia severity would correlate with improvement in PSTD symptom severity.

Methods
Forty-one participants with a clinical diagnosis of PTSD were randomized to receive 6 weeks of either daily morning BLT (n=22) or ALT (n=19). Insomnia and PTSD symptom severity were evaluated at pre- and post-treatment using the Insomnia Severity Index (ISI) and the Clinician-Administered PTSD Scale (CAPS) for DSM-5, respectively.

Results
Both groups showed a significant decrease in their PTSD symptom severity (p&lt;0.001) and insomnia severity (p&lt;0.001) over the 6-week treatment period. However, improvement in insomnia severity significantly predicted improvements in PTSD symptom severity for the BLT group only (BLT: r =0.542, p=0.009; ALT: r=-0.095, p=0.699). The difference between the two correlation coefficients was significant (Z=-2.07, p=0.039).

Conclusion
The results suggest that morning BLT may be effective in improving PTSD symptoms by regulating the circadian rhythm and improving sleep. While ALT also led to improved PTSD symptom severity, it appears that those changes cannot be explained by improved sleep and may have other underlying mechanisms (e.g., placebo effect). Morning BLT may be a promising adjunctive method to bolster current treatment approaches for PTSD. Because of its ease of administration, it could be easily added to ongoing treatment as usual. This approach warrants further research.

Support
US Army Medical Research and Materiel Command: W81XWH-14-1-0570
0042 Stroke Volume and Cardiac Index are Differentially Altered by Total Sleep Deprivation and Psychological Stress in Resilient vs. Vulnerable Individuals and Predict Cognitive Performance
Authors: Yamazaki E M , Rosendahl-Garcia K M , MacMullen L E , Ecker A J , Kirkpatrick J N , Goel N 
Published: May 2020

Abstract

Introduction
Individuals show robust resilience and vulnerability in neurobehavioral performance to sleep loss and stress. For the first time, we investigated the time course of two cardiovascular measurements, stroke volume (SV) and cardiac index (CI), both derived from echocardiography, across baseline, total sleep deprivation (TSD), the combination of TSD+psychological stress, and recovery. We also determined whether these variables differ in resilient vs. vulnerable individuals and whether they predict differential vulnerability in cognitive performance.

Methods
Thirty-one healthy adults (ages 27–53; mean±SD, 35.4±7.1y; 14 females) participated in a five-day experiment consisting of two 8h time-in-bed (TIB) baseline nights, 39h TSD, and two 8h-10h TIB recovery nights. A modified Trier Social Stress Test (TSST) was conducted on the TSD day to induce psychological stress. Echocardiographic measures of SV and CI were obtained at six time points (pre-study, baseline, during TSD, during TSD after the TSST, after recovery, and post-study). A median split of TSD performance [total lapses (&gt;500 ms response time) and errors] on the 10-minute Psychomotor Vigilance Test (PVT), defined cognitively resilient (n=15) and vulnerable (n=16) groups. Repeated measures ANOVA and post-hoc comparisons corrected for multiple testing, examined SV and CI across time points between groups.

Results
There was a significant time*group interaction for SV: cognitively resilient individuals had greater SV during the five-day experiment. In addition, in both resilient and vulnerable individuals, SV increased with TSD and with TSD+psychological stress compared with baseline. Like SV, there was a significant time*group interaction for CI: resilient individuals had greater CI at all points of the experiment.

Conclusion
SV and CI differed between resilient and vulnerable individuals across TSD, psychological stress and recovery sleep. Greater SV and greater CI at baseline predicted resilience to TSD and TSD+psychological stress. CI and SV are novel physiological biomarkers of sleep loss, stress, and individual differences in cognitive performance.

Support
NASA NNX14AN49G.
0062 Improved Circadian Data Ordering in the Presence of Biological and Technical Confounds
Authors: Hammarlund J , Anafi R 
Published: May 2020

Abstract

Introduction
We recently used unsupervised machine learning to order genome scale data along a circadian cycle. CYCLOPS (Anafi et al PNAS 2017) encodes high dimensional genomic data onto an ellipse and offers the potential to identify circadian patterns in large data-sets. This approach requires many samples from a wide range of circadian phases. Individual data-sets often lack sufficient samples. Composite expression repositories vastly increase the available data. However, these agglomerated datasets also introduce technical (e.g. processing site) and biological (e.g. age or disease) confounders that may hamper circadian ordering.

Methods
Using the FLUX machine learning library we expanded the CYCLOPS network. We incorporated additional encoding and decoding layers that model the influence of labeled confounding variables. These layers feed into a fully connected autoencoder with a circular bottleneck, encoding the estimated phase of each sample. The expanded network simultaneously estimates the influence of confounding variables along with circadian phase.
We compared the performance of the original and expanded networks using both real and simulated expression data. In a first test, we used time-labeled data from a single-center describing human cortical samples obtained at autopsy. To generate a second, idealized processing center, we introduced gene specific biases in expression along with a bias in sample collection time. In a second test, we combined human lung biopsy data from two medical centers.

Results
The performance of the original CYCLOPS network degraded with the introduction of increasing, non-circadian confounds. The expanded network was able to more accurately assess circadian phase over a wider range of confounding influences.

Conclusion
The addition of labeled confounding variables into the network architecture improves circadian data ordering. The use of the expanded network should facilitate the application of CYCLOPS to multi-center data and expand the data available for circadian analysis.

Support
This work was supported by the National Cancer Institute (1R01CA227485-01)
0063 Age Related Changes in Central Autonomic Couplings During Sleep
Authors: Chen P , Naji M , Sattari N , Whitehurst L N , Mednick S C 
Published: May 2020

Abstract

Introduction
Studies show coupling between central nervous system (CNS) and autonomic nervous system (ANS) activity during sleep. We reported on a novel central/autonomic coupling event (ACE) during non-rapid eye movement (NREM) sleep, in which bursts in heart rate (HRBs) coincide with increased slow-wave activity (SWA) 5 seconds prior to the HRB, followed by a surge in vagal high-frequency activity in the RR signal (HFRR) 5 seconds after the HRB. ACEs predicted sleep-related explicit memory improvement. Aging is characterized with impaired sleep and autonomic loss. We, therefore, investigated ACE activity in older adults.

Methods
We compared ACEs during a daytime nap between youngers (18-25yrs, N=49) and olders (60-75yrs, N=32). Subjects took an EEG-monitored, 90-minute nap. We measured SWA and HFRR in a 20-sec window around the HRB peak separately for Stage 2 and slow-wave sleep (SWS). EEG were binned into 5-sec intervals around the HRB: -10, -5, +5, +10 bins. For Stage 2 and SWS, repeated-measure ANOVAs with two factors (age and windows) were performed on SWA and HFRR. Corrections used Greenhouse-Geisser and Bonferroni methods.

Results
For SWA, we found an interaction between age and windows during Stage 2 (p&lt;.001), and SWS (p=.001). SWA during the -5bin was greater in youngers than olders during both Stage 2 and SWS (ps &lt; .001). The ACE profile in youngers showed highest SWA in the -5bin in Stage 2 and SWS (ps &lt; .001) and highest HFRR in the +5bin in Stage 2 (ps &lt; .001) The ACE profile in olders, however, showed no clear pattern for SWA in either sleep stage. Olders showed greater HFRR during the +5bin compared to the -10bin (p=.041) during Stage 2 but no HFRR modulations were found during SWS.

Conclusion
Our results replicated the ACE profile in daytime naps first reported by Naji et al (2018). In youngers, heart rate bursts were coupled with increased SWA and vagal activity. In contrast, olders demonstrated a lack of boost in SWA and HFRR, which provides implications in cognitive aging. Future research is needed to further understand the impact of decreased coupling between ANS/CNS activity on cognitive decline.

Support
0072 Preclinical Characterization of SUVN-G3031, a Histamine H3 Receptor Inverse Agonist for the Treatment of Narcolepsy
Authors: Jayarajan P , Subramanian R , Kamuju V , Muddana N , Palacharla R , Mekala V , Abraham R , Reballi V , Achanta P , Nirogi R 
Published: May 2020

Abstract

Introduction
Narcolepsy is a chronic sleep disorder characterized by overwhelming daytime drowsiness, sudden attacks of sleep and sometimes accompanied by cataplexy. Although the orexin deficiency is considered to be the primary cause of this disorder, lot of attention has been focused recently on targeting histaminergic neurotransmission by blockade of histamine H3 receptor (H3R). SUVN-G3031 is one of the potent and selective H3R inverse agonist currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380).

Methods
Binding of SUVN-G3031 in human and rat histamine H3R was evaluated in in vitro radioligand binding assay and functionality was assessed in GTPγS assay. Pharmacokinetic properties were evaluated after oral administration in rat and dog. Neurotransmitters like histamine, dopamine and norepinephrine were estimated in rat cortex using microdialysis.

Results
SUVN-G3031 is an inverse agonist at histamine H3R with hKi of 8.7 nM and showed minimal binding against over 70 target sites. SUVN-G3031 exhibited desired pharmacokinetic properties in rat and dog with excellent brain penetration in rats. SUVN-G3031 produced significant increase in histamine, dopamine and norepinephrine levels in cortex. SUVN-G3031 produced no change in the striatal and accumbal dopamine levels in rats, suggesting no propensity to induce abuse liability. SUVN-G3031 blocked R-α-methylhistamine induced water intake and produced dose dependent increase in tele-methylhistamine levels in various brain regions and in cerebrospinal fluid of male Wistar rats.

Conclusion
SUVN-G3031 is an inverse agonist at histamine H3 receptor and results from the preclinical studies presented here provide a strong evidence for the potential utility of SUVN-G3031 in the treatment of narcolepsy with and without cataplexy.

Support
None