bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease activity and erectile dysfunction in Japanese patients with ulcerative colitis
Authors: Furukawa Shinya , Takeshita Eiji , Miyake Teruki , Tange Kazuhiro , Tomida Hideomi , Yamamoto Yasunori , Ikeda Yoshio , Hiasa Yoichi 
Published: May 2023

AbstractBackgroundThe association between disease activity and erectile dysfunction (ED) in patients with inflammatory bowel disease (IBD) is inconsistent, although IBD, including ulcerative colitis (UC), is reported as a risk factor for ED.AimThe purpose of this study was to explore this association in Japanese patients with UC.MethodsIn this study, we enrolled 165 Japanese male patients with UC. Information regarding the Sexual Health Inventory for Men (SHIM) score, medication, and severity of UC was obtained from medical records, self-administered questionnaires, and reports from physicians. The definition of ED and severe ED is a SHIM score &lt;17 and &lt;8, respectively.OutcomesNo association between severity of UC and ED was found in Japanese patients. Aging is independently positively associated with ED in patients with UC.ResultsThe prevalence of severe ED and ED was 47.9% and 64.9%, respectively. In this study, mucosal healing, clinical remission, duration of UC, disease extent, and medication were not associated with the prevalence of ED. Older age (≥63 years of age) was independently positively associated with ED (adjusted odds ratio, 12.93; 95% CI: 4.51-43.00) and severe ED (adjusted odds ratio, 9.02; 95% CI: 3.66-23.91).Clinical ImplicationsDisease severity of UC might not be associated with the prevalence of ED in patients with UC.Strengths and LimitationsThis is the first study to investigate the association between several factors regarding UC activity and ED. The limitation of this study is the definition of ED based on SHIM scores.ConclusionNo association between severity of UC and ED was found in Japanese patients. As expected, aging may be independently positively associated with ED in patients with UC.
0008 The endogenous circadian system provides for enhanced coronary microvascular function in the morning
Authors: Thosar Saurabh , Hodovan James , Kheiri Babikir , McHill Andrew , Bowles Nicole , Rice Sean , Butler Matthew , Emens Jonathan , Shea Steven , Lindner Jonathan 
Published: May 2023

Abstract

Introduction
Major adverse cardiovascular events occur most commonly in the morning compared to other times of the day or night. Evaluation of coronary microvascular reserve perfusion can be used to reflect the anatomic and functional status of the coronary vascular system, both of which contribute to major adverse cardiovascular events. Prior work suggests that coronary microvascular function is attenuated in the morning, but whether the circadian system contributes to this attenuation is unknown.

Methods
To determine if the circadian system drives the morning attenuation in coronary microvascular function, we studied 13 healthy participants (8 females, 5 males; 42+/-13 years [mean+/-SD]) in a 5-day forced desynchrony protocol in dim light, where all behaviors and measurements were distributed across the 24-hour cycle. Coronary microvascular function was evaluated by vasodilator myocardial contrast echocardiography, sequentially 16 hours apart, corresponding to each participant’s morning, evening and night. We analyzed time-intensity data to calculate microvascular flux rate (beta) at rest and during hyperemia for each measurement. Circadian phases were calculated based on individual dim-light melatonin onsets. We grouped data into three ~8-hour circadian bins corresponding to each participant’s morning, evening and night. Mixed model analyses were used to determine if there were significant differences between data collected in the circadian morning compared to the other times while controlling for the measurement schedule and between-subject variability.

Results
There were no significant time-dependent differences in echocardiographic indices of ventricular function, including stroke volume, cardiac output, or myocardial work. Contrary to our hypothesis, hyperemic perfusion was lowest in the evening rather than the morning (2.49 /s vs. 2.82 /s, p=0.042) but not different between morning and night (also 2.82 /s, p=0.96).

Conclusion
In healthy people, there is no circadian-system-driven morning attenuation in coronary microvascular function: indeed, the circadian system facilitates coronary vascular flow in the morning, possibly to accommodate the anticipated behaviorally driven increases in myocardial demand after awakening.

Support (if any)
NIH KL2TR002370, R01HL163232, R35HL155681, R01HL140577, R01HL130046, R01HL078610, R01HL156948, K01HL146992, K01HL151745, ULTR00128, Sleep Research Society Foundation, Oregon Institute of Occupational Health Sciences.
0047 Mapping orexin 2 receptor pathways that improve sleepiness and cataplexy
Authors: Ishikawa Takashi , Kurimoto Emi , Joyal Adam A , Scammell Thomas E 
Published: May 2023

Abstract

Introduction
Narcolepsy type 1 is caused by selective loss of orexinergic neurons, resulting in poor maintenance of sleep and wakefulness, and emergence of cataplexy. Orexinergic neurons innervate many brain regions, and specific narcolepsy symptoms likely arise from dysfunction of distinct brain regions. Orexin 2 receptors (OX2R) are expressed in nearly all wake- and REM sleep-regulatory brain regions, and OX2R agonists improve narcolepsy symptoms in mouse models and human patients. However, the key brain regions and pathways through which OX2R signaling stabilizes wake and sleep and suppresses cataplexy are only partially understood. In this study, we restored OX2R expression in specific brain regions of mice lacking orexinergic neurons and OX2R, and assessed if an OX2R-selective agonist improves specific aspects of their narcolepsy symptoms.

Methods
We produced a murine narcolepsy model with the human diphtheria toxin receptor (DTR) knocked into the endogenous prepro-orexin locus (orexinDTR mice). After injection with diphtheria toxin (DTX), orexinDTR mice have severe and selective loss of orexinergic neurons. We crossed orexinDTR mice with OX2R transcription-disrupted (TD) mice to produce a new narcolepsy model lacking orexinergic neurons and OX2R (OX2R TD::orexinDTR mice). To induce focal expression of OX2R, we microinjected an adeno-associated viral vector coding for Cre recombinase into specific brain regions of OX2R TD::orexinDTR mice. At 6 weeks after DTX injection, we administered an OX2R-selective agonist OX-201 or vehicle orally to OX2R TD::orexinDTR mice expressing OX2R in the specific brain regions and evaluated the effects of OX-201 on narcolepsy symptoms including sleepiness and cataplexy.

Results
In mice expressing OX2R only in the tuberomammillary nucleus (TMN) or basal forebrain (BF) regions, OX-201 significantly improved maintenance of wakefulness but did not suppress cataplexy. In contrast, in mice expressing OX2R in the ventrolateral periaqueductal grey and lateral pontine tegmentum (vlPAG/LPT) regions, OX-201 significantly suppressed cataplexy without improving maintenance of wakefulness.

Conclusion
These findings demonstrate that OX2R signaling in the TMN and BF regions can stabilize wake and sleep, and OX2R signaling in the vlPAG/LPT region can suppress cataplexy.

Support (if any)
This work was funded by Takeda Pharmaceutical Company Limited.
0052 A Novel Biomarker of Alzheimer’s Disease Based on High-order Interactions of Low-density Electroencephalography
Authors: Herzog Rubén , Haghayegh Shahab , Ibáñez Agustín , Hu Kun 
Published: May 2023

Abstract

Introduction
Alzheimer’s disease (AD) causes disruptions in brain functions, which can be tracked by proper analysis of electroencephalography (EEG). Current efforts to understand the impact of AD on brain activity have leveraged the development of high-density EEG. Alternatively, we propose that AD can be discriminated from healthy controls (HC) by analyzing low-density EEG sleep recordings with nonlinear measures that capture functional interactions beyond pairwise such as the total correlation (TC), dual total correlation (DTC), O-information (O) and S-information (S).

Methods
We analyzed overnight polysomnography data with 4 EEG channels (left central, right central, left mastoid, and right mastoid) of 28 older men (14 with a self-reported history of clinical diagnosis of AD and 14 HC, matched in age and education) in the Osteoporotic Fractures in Men Study (MrOS) obtained from the National Sleep Research Resource (NSRR). Each 30-second epoch was scored as wake (W), N1, N2, N3, or rapid eye movement. Features based on low (2) and high order (3-4) interactions between electrodes (TC, DTC, O, and S) were extracted from raw and band-pass filtered data within each wake/sleep stage. Finally, a feature selection algorithm provided the optimal subset of features that maximizes the discrimination between conditions.

Results
AD was discriminated from HC with an average area under the receiver operating characteristic curve of 0.90±0.05 using just 3 features: O (triplet) measured within W stage in the high γ band (40-100 Hz), DTC (triplet) for raw N1 data, and TC (pairwise) in the δ band (0.5-4 Hz) within N stages.

Conclusion
State-of-the-art analysis of high-order interactions can maximize the discrimination of AD using a low-density sleep EEG set-up. The potential of these features to capture the physiopathology of AD and its impact on brain function should be further confirmed using larger samples.

Support (if any)
National Institutes of Health (RF1AG059867, RF1AG064312, R01AG057234); ANID/FONDECYT Regular (1210195 and 1210176 and 1220995); Alzheimer’s Association (SG-20-725707). MrOS Sleep Study was supported by R01 HL071194, R01HL070848, R01HL070847, R01HL070842, R01HL070841, R01HL070837, R01HL070838, and R01HL070839. The NSRR was supported by R24HL114473, 75N92019R002.
0090 Sleep Architecture Associations with Brain Age: A Multi-Site Model Validation
Authors: Vanasse Thomas J , Rusk Samuel , Nygate Yoav , Fernandez Chris , Shi Jiaxiao M , Arguelles Jessica , Klimper Matthew T , Wickwire Emerson , Watson Nathaniel F , Hwang Dennis 
Published: May 2023

Abstract

Introduction
Machine Learning (ML) can draw upon complex patient data to predict current and future health status, but the best performing ML models are often difficult to interpret. One such ML-defined health marker is the brain age index (BAI), the difference between ML-predicted age and chronological age (CA) using electroencephalogram (EEG) during sleep. BAI is associated with multiple disease states including increased risk for all-cause mortality. Still, validation of published models has been limited, and the underlying associations between polysomnography sleep architecture metrics and BAI estimation are not well understood.

Methods
A deep neural network (DNN) model was trained to predict the brain age (BA) of patients using raw EEG signals recorded during clinical polysomnography (PSG). The DNN was trained on N=54,000 PSGs. The model was then validated on two independent datasets: a Kaiser Permanente (KP) Historical PSG Dataset (N=10,694), and a multi-site retrospective PSG dataset (N=15,158). To test association with BAI, ordinary least squares (OLS) regression was performed on these validation datasets using basic features derived from sleep staging architecture and arousal data.

Results
In the validation datasets, we observed mean absolute error (MAE) of 6.67 (6.69/6.49 F/M, KP dataset) and 5.65 (5.56/5.44 F/M, independent dataset). In the OLS analysis, consistent, negative associations were detected between both N3 and REM sleep percentage vs. BAI. Furthermore, BAI was consistently positively associated with N1 sleep percentage. Each of these effects was significant at p&lt; 0.001.

Conclusion
This study builds upon and expands prior research by evaluating large multi-site datasets and assessing the relationship of N3/REM sleep duration with the predicted brain age. Using a DNN model, BAI was associated with significantly increased N1 and concomitant decreased N3/REM. Further research is needed to determine if BA is malleable and potentially reduced with clinical intervention and positive changes in lifestyle and wellness-related behavior.

Support (if any)
0129 Delta-9-tetrahydrocannabinol (THC) ingestion before bedtime reduces nocturnal parasympathetic control of the heart
Authors: Gonzalez Joshua , Robinson LaTroy , Clemons Noal , Ellison Jacqueline , Ordaz-Johnson Omar , Emens Jonathan , Shea Steven , Bowles Nicole 
Published: May 2023

Abstract

Introduction
The use of cannabis as a sleep aid has increased despite inadequate evidence of its efficacy or associated risks. Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive constituent of cannabis. Acute THC administration can induce CB1R mediated reductions in total peripheral resistance resulting in dose-dependent increases in heart rate and reductions in heart rate variability (HRV) in awake subjects. However, the influence of THC on vagal-cardiac modulation during sleep is unclear.

Methods
7 individuals who use cannabis (&gt;3x/week for 3 months; CUDIT-R = 8±1) and 8 cannabis-naïve participants (combined: age range 21-32 years; 9 female) were recruited to participate in this repeated measure, single blinded, placebo-controlled study. One hour before habitual sleep, participants received either a placebo pill or 10mg of THC. Polysomnography (PSG) and ECG were recorded over these 2 nights. HRV was assessed in both time and frequency domains in 2-min epochs of stable N2, N3 and REM sleep. Repeated measures ANOVA comparisons were made for PSG and HRV variables. [(*)=p&lt; 0.05]

Results
There were no significant changes in total sleep duration or sleep architecture (N2%, N3%, & REM%) between the placebo and dosing night in either group. Compared to the placebo night, both individuals who use cannabis and cannabis naïve participants exhibited significant decreases in HRV variables throughout the night when dosed with THC. R-R interval decreased by 25±10* ms [mean±SE] (2%) in the naïve group and 62±11* ms (6%) in the cannabis group. RMSSD decreased by 15±3* ms (22%) in the naïve group and 11±3* ms (23%) in the cannabis group. PNN50 decreased by 9±3* % in the naïve group and 11±3* % in the cannabis group. In naïve participants high frequency spectral power decreased by 398±76* ms^2 (32%).

Conclusion
Our results suggest that THC ingestion before bedtime did not systematically affect sleep depth or duration, but did significantly reduce vagal-cardiac modulation in individuals who use cannabis as well as in cannabis naïve participants. Acute reductions in parasympathetic control of the heart may indicate increased cardiovascular stress during sleep when THC is ingested.

Support (if any)
AASM; K01HL151745; T32HL083808; OHSU OFDIR; R35 HL155681; Oregon Institute of Occupational Health Sciences
0139 Impaired Sleep Mediates the Relationship Between Interpersonal Trauma and Subtypes of Delusional Ideation
Authors: Herms Emma , Wisner Krista 
Published: May 2023

Abstract

Introduction
Impaired sleep is an important area of intervention, as improving sleep can have beneficial effects on co-existing psychopathology. Under this framework, impaired sleep is examined as a mediator between IT (IT; i.e., trauma caused by another) and subtypes of delusional ideation (i.e., subclinical delusions). Impaired sleep may be a maintenance factor of delusional ideation following IT. Thus, this study seeks to clarify the role of impaired sleep in different types of delusional ideation, which may inform future treatment research.

Methods
Transdiagnostic-community participants (18-60 years) were utilized from the Nathan Kline Institute (N=496). An exploratory factor analysis was completed for the Peter’s Delusion Inventory (PDI) and extracted factors were used as DVs in separate mediation models. We assessed whether global sleep quality (GSQ) from the Pittsburgh Sleep Quality Index mediated the relationship between IT and subtypes of delusional ideation. GSQ is the summation of seven component scores: sleep duration, sleep disturbance, sleep latency, daytime dysfunction, sleep efficiency, subjective sleep quality, and medication use. Thus, specificity analyses examined each component of GSQ individually in mediation models to identify influential components.

Results
A three-factor solution of the PDI was identified: magical thinking, grandiosity, and paranoia. However, IT was only related to paranoia (β=0.312,p&lt; 0.01) and grandiosity (β=0.286,p&lt; 0.01). With GSQ as a mediator, the relationship between IT and paranoia was attenuated (direct effect=0.212,p=0.046; indirect effect=0.074,p&lt; 0.01; 25.9% mediated). Similarly, the relationship between IT and grandiosity was attenuated by GSQ as a mediator, but less variance was accounted for (direct effect=0.269,p=0.013; indirect effect=0.044,p=0.035; 14.1% mediated). Specificity analyses highlighted that for paranoia, the components of sleep disturbance (direct effect=0.121,p=0.220; indirect effect=0.165,p&lt; 0.01) and daytime dysfunction (ab=0.073,p=0.035; c=0.214,p=0.030) provided significant mediation of the relationship with IT. For grandiosity, only the sleep disturbance component (ab=0.092,p=0.011; c=0.221,p=0.043) mediated the relationship with IT.

Conclusion
In conclusion, impaired sleep significantly mediated the relationship between IT and paranoia, as well as grandiosity. This provides support for future research investigating impaired sleep as a target to improve specific subtypes of delusional ideation following IT, particularly paranoia. While our findings align with previous research, several limitations are considered including cross-sectional data and use of self-report measures.

Support (if any)
0155 Persistent Activation of TXNIP and NLRP3 Inflammasomes in Cortical Glia and Neurons after Mild Traumatic Brain Injury
Authors: Carey Sean , Gibbons Allison , Prabhala Rao , Kaplan Gary , Zielinski Mark 
Published: May 2023

Abstract

Introduction
Mild traumatic brain injuries (TBI) induce persistent dysregulated sleep, reactive oxygen species (ROS), and inflammation. Nucleotide-binding domain leucine rich family pyrin containing 3 (NLRP3) inflammasomes are protein complexes that stimulate caspase-1 to activate the somnogenic pro-inflammatory cytokines IL-1β and IL-18. ROS induce thioredoxin interacting protein (TXNIP) to activate NLRP3 inflammasomes by inhibiting thioredoxin which inhibits ROS. We previously found that mice lacking NLRP3 have increased non-rapid-eye movement (NREM) sleep and slow-wave activity (SWA) 24 h after mild TBI, but at 2 months post-injury theses values are reduced. Following up on this, we sought to determine the activity of NLRP3 inflammasomes in glia and neurons after mild TBI.

Methods
Two-month-old mice lacking NLRP3, and wild-type mice received a craniectomy and mild TBI via controlled cortical impact or sham. Frontal and somatosensory cortices were collected without a TBI and at 24 h and 2 months post-TBI. Microglia, astrocytes, and neurons were isolated using fluorescent-activated cell sorting, and reactive oxygen species (ROS), RNA and protein were quantified using RT-PCR and ELISAs. Significance was set at p &lt; 0.05.

Results
RNA, protein, and ROS control treatment values were similar for both genotypes in cortical microglia, astrocytes, and neurons. In wild-type mice, NLRP3, IL-1β, IL-18, caspase-1, and TXNIP expression along with ROS values were significantly greater and thioredoxin expression was significantly less in cortical microglia, astrocytes, and neurons 24 h and 2 months post-TBI. In wild-type cortical microglia, astrocytes, and neurons NLRP3, IL-1β, and TXNIP expression levels were significantly greater in these cell types 2 months vs. 24 h post-TBI. Wild-type mice caspase-1 activity and NLRP3, IL-18, IL-1β, and TXNIP protein levels, were significantly greater and thioredoxin protein levels were significantly less in both cortical areas 24 h and 2 months post-TBI. Mice lacking NLRP3 showed significant increased values of TXNIP but reduced thioredoxin expression and protein levels 24 and 2 months post-TBI but no significant differences in other measures.

Conclusion
Our findings suggest that TBI induces persistent oxidative stress, TXNIP, and NLRP3 inflammasome activation in cortical glia and neurons that likely contributes to sleep dysregulation.

Support (if any)
Merit Review Award (I01BX005379)(MRZ) and SPiRE Award (I21RX003722)(GBK) Department of Veterans Affairs
0175 Poor Association Between Subjective and Objective Sleepiness in Patients Evaluated in a Clinical Sleep Center
Authors: Schwab Allison , Staley Beth , Keenan Brendan , Basner Mathias , Bae Charles 
Published: May 2023

Abstract

Introduction
Sleepiness is a primary symptom among patients presenting at sleep clinics. Sleepiness is typically subjectively evaluated using the Epworth Sleepiness Scale (ESS), which has been associated with worse cardiovascular outcomes among sleep apnea patients. On the other hand, functional deficits due to sleepiness can be objectively quantified using a Psychomotor Vigilance Test (PVT). To better understand the presentation of “sleepiness”, we examined the relationship between subjective ESS and objective PVT among a clinical sample. We hypothesized that these two different measures of sleepiness would be correlated.

Methods
A prospective sample of patients being evaluated for sleep disorders in the Sleep Center at the University of Pennsylvania completed the ESS and PVT at the same clinical visit. Demographic data were obtained at the visit or derived from the electronic health record. Pearson’s linear correlations were utilized to examine the association between the ESS and both the transformed lapses (sum of square root of number of lapses and square root of lapses+1) and mean reciprocal response time (RRT) on the PVT.

Results
In total, 167 patients (98 [58.7%] males) were studied, with a mean (±SD) age of 54.7±16.8 years and BMI of 34.5±9.9 kg/m2. There were a similar number of White (67 [42.1%]) and Black (71 [44.7%]) participants and 129 (77.3%) had diagnosed or suspected obstructive sleep apnea (OSA). Patients had an average ESS of 8.1±5.4, and 10.5±10.6 lapses, 5.9±2.9 transformed lapses, and mean RRT of 3.4±0.7 seconds-1 on PVT. Among all patients, there was no statistically significant correlation between ESS and either transformed lapses (rho = 0.10, p=0.200) or mean RRT (rho = -0.10, p=0.201). Results were similar when comparing the two sleepiness measures restricted to patients with OSA.

Conclusion
Within patients being evaluated in a clinical sleep center, there was only a weak association between subjective sleepiness on the ESS and objective sleepiness on PVT. Thus, not all patients reporting daytime sleepiness have objective deficits, and vice versa. Results support using both assessments to fully characterize a patient’s sleepiness. Future studies should evaluate the relationship between adverse outcomes and subjective and objective sleepiness, alone and in combination.

Support (if any)