Automated analysis of the AASM Inter-Scorer Reliability gold standard polysomnogram dataset.

Study Objectives: To compare the performance of a comprehensive automated polysomnogram (PSG) analysis algorithm-CAISR (Complete Artificial Intelligence Sleep Report)-to a multi-expert gold standard panel, crowdsourced scorers, and experienced technicians for sleep staging and detecting arousals, respiratory events, and limb movements.

Methods: A benchmark dataset of 57 PSG records (Inter-Scorer Reliability dataset) with 200 30-second epochs scored per AASM guidelines was used. Annotations were obtained from (1) the AASM multi-expert gold standard panel, (2) AASM Inter-Scorer Reliability (ISR) platform users ("crowd," averaging 6,818 raters per epoch), (3) three experienced technicians, and (4) CAISR.

Brain atrophy patterns in anti-IgLON5 disease.

Anti-IgLON5 disease is an autoimmune encephalitis that presents with a heterogenous clinical phenotype, including sleep disorders, movement abnormalities and bulbar involvement. It is characterised by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:∼ and a brainstem-dominant tauopathy. Cellular and murine models report pathogenic effects of the autoantibodies, and neurodegenerative factors suggest progressive atrophy as a common sequela.

HLA-DQB1*03:01 strongly affects age of onset of type 1 narcolepsy independently of DQA1 and ethnicity.

In this study, we investigated the effects of HLA-DQB1*03:01 on the onset age of type-1 narcolepsy. We pooled data from 5,339 cases from China, Europe, Korea, Japan, and the United States to conduct the first transethnic study on age of onset (OA). GWAS was used to detect the associated genes.

Characteristics of Maintenance of Wakefulness Test (MWT) in drug-naïve patients with narcolepsy type 1 and type 2, and relationship with other measures of sleepiness.

Study Objectives: We aimed to describe the characteristics of standard maintenance of wakefulness test (MWT), outside of clinical trials, in a sample of drug-naïve patients with narcolepsy type 1 (NT1) and type 2 (NT2).

Methods: Consecutive drug-naïve patients with narcolepsy underwent two days of continuous PSG recording, the multiple sleep latency test (MSLT), then night-PSG and, on the following day, MWT. MWT results were correlated with MSLT and Epworth Sleepiness Scale (ESS).

CAISR: achieving human-level performance in automated sleep analysis across all clinical sleep metrics.

Study Objectives: To develop and validate a Complete Artificial Intelligence Sleep Report system (CAISR), a system for comprehensive automated sleep analysis, including sleep staging, arousal detection, apnea identification, and limb movement analysis.

Methods: We utilized a large diverse dataset from four cohorts (MGH, MESA, MrOS, SHHS) comprising 25,749 participants to develop CAISR. Following American Academy of Sleep Medicine (AASM) guidelines, CAISR performs four tasks: it stages sleep into five categories (Wake, NREM 1, NREM 2, NREM 3, REM), detects arousals, detects and classifies breathing events (Obstructive Apnea, Central Apnea, Mixed Apnea, Hypopnea, and RERA), and detects limb movements and categorizes them as periodic or isolated.

Probability estimation of narcolepsy type 1 in DTA mice using unlabeled EEG and EMG data.

The manual evaluation of mouse sleep studies is labor-intensive and time-consuming. Although several approaches for automatic sleep stage classification have been proposed, no automatic pipeline for detecting a specific mouse phenotype has yet been developed. Here, we present a fully automated pipeline for estimating the probability of Narcolepsy Type 1 (NT1) in the hypocretin-tTA;TetO-Diphteria toxin A (DTA) mouse model using unlabeled electroencephalographic (EEG) and electromyographic (EMG) data.

High-resolution lifestyle profiling and metabolic subphenotypes of type 2 diabetes.

Distinct metabolic susceptibilities (beta-cell dysfunction, insulin resistance (IR), and impaired incretin response) underlie type 2 diabetes (T2D). However, their relationships with habitual lifestyle behaviors are underexplored. This study integrated high-resolution lifestyle data from wearable devices, continuous glucose monitoring, and smartphone-based food logs with gold-standard physiological tests in 36 individuals at risk for T2D (ClinicalTrials.

Comprehensive Evaluation of Odds Ratio Product and Spectral Slope as Continuous Sleep Depth Measures: Advancing Sleep Staging and Clinical Applications.

Study Objectives: This study aims to validate two innovative continuous sleep depth measures, Odds Ratio Product (ORP) and Spectral Slope (SS), using large-scale datasets, including MESA, SHHS, CHAT, and WSC, as alternatives to the traditional discrete gold-standard hypnogram.

Methods: The relationship between ORP, SS, and the gold-standard hypnogram was evaluated through Pearson correlation analysis. Feature distributions across sleep stages and transitions, the Arousability Index, and sleep cycles were systematically analyzed.

Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1.

Background: Narcolepsy type 1 is a disorder of hypersomnolence caused by a loss of orexin neurons, which results in low orexin levels in the brain.

Methods: In this phase 2, randomized, placebo-controlled trial, participants with narcolepsy type 1 received once- or twice-daily oveporexton (TAK-861), an oral orexin receptor 2-selective agonist, or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (MWT) (range, 0 to 40 minutes; normal, ≥20).

Elevated circulating cell-free mitochondrial DNA level in cerebrospinal fluid of narcolepsy type 1.

Narcolepsy type 1 (NT1) is a rare neurological disorder characterized by excessive daytime sleepiness and cataplexy, thought to result from an autoimmune process targeting the hypothalamic hypocretin-producing neurons. Aiming to add clues to the latter hypothesis, we investigated circulating cell-free mitochondrial DNA (ccf-mtDNA) levels in cerebrospinal fluid (CSF), a possible biomarker for neurodegeneration, neuroinflammation or immune activation, from 46 NT1 patients with low CSF hypocretin-1, compared with 32 controls. We found significantly increased ccf-mtDNA levels in NT1 patients compared with controls, which negatively correlated with CSF hypocretin-1 concentrations.

Automated phenotyping of mild cognitive impairment and Alzheimer's disease and related dementias using electronic health records.

Objectives: Unstructured and structured data in electronic health records (EHR) are a rich source of information for research and quality improvement studies. However, extracting accurate information from EHR is labor-intensive. Timely and accurate identification of patients with Alzheimer's Disease, related dementias (ADRD), or mild cognitive impairment (MCI) is critical for improving patient outcomes through early intervention, optimizing care plans, and reducing healthcare system burdens.

Identification of Patients With Congestive Heart Failure From the Electronic Health Records of Two Hospitals: Retrospective Study.

Background: Congestive heart failure (CHF) is a common cause of hospital admissions. Medical records contain valuable information about CHF, but manual chart review is time-consuming. Claims databases (using International Classification of Diseases [ICD] codes) provide a scalable alternative but are less accurate.

Use of Portable 24-Hour Polysomnography as Alternative Diagnostic Tool for Narcolepsy Type 1 in Adults and Children.

Background And Objectives: The diagnosis of narcolepsy type 1 (NT1) currently requires the multiple sleep latency test (MSLT), or a nocturnal sleep-onset REM period (SOREMP) combined with typical cataplexy, or alternatively the determination of CSF hypocretin-1 (CSF-hcrt-1) deficiency. We evaluated the 24-hour polysomnography (PSG) recordings in adult and pediatric patients as an alternative diagnostic tool.

Methods: Patients of any age, referred to the narcolepsy center of a university hospital for suspected central disorder of hypersomnolence (CDH), were consecutively recruited between 2013 and 2022.

A Multimodal Sleep Foundation Model Developed with 500K Hours of Sleep Recordings for Disease Predictions.

Sleep is a fundamental biological process with profound implications for physical and mental health, yet our understanding of its complex patterns and their relationships to a broad spectrum of diseases remains limited. While polysomnography (PSG), the gold standard for sleep analysis, captures rich multimodal physiological data, analyzing these measurements has been challenging due to limited flexibility across recording environments, poor generalizability across cohorts, and difficulty in leveraging information from multiple signals simultaneously. To address this gap, we curated over 585,000 hours of high-quality sleep recordings from approximately 65,000 participants across multiple cohorts and developed SleepFM, a multimodal sleep foundation model trained with a novel contrastive learning approach, designed to accommodate any PSG montage.

Associations of Cerebrospinal Fluid Orexin-A, Alzheimer Disease Biomarkers, and Cognitive Performance.

Objective: Cerebrospinal fluid (CSF) orexin-A has been suggested to be a biomarker of Alzheimer disease (AD). In both cognitively unimpaired healthy older adults and individuals with symptomatic AD, CSF orexin-A is positively associated with CSF Aβ42, p-tau181, and total tau (t-tau) concentrations. However, a recent systematic review and meta-analysis did not support differences in orexin-A between AD and controls.

Quantitative study of microplastic degradation in urban hydrosystems: Comparing in situ environmentally aged microplastics vs. artificially aged materials generated via accelerated photo-oxidation.

The degradation of plastic waste is a major research challenge due to the adverse impacts of microplastic weathering on the environment and ecosystems. As a major source of plastic contamination comes from urban hydrosystems, studying MP degradation prior to their environmental dissemination is crucial. Through a combination of field sampling and laboratory experiments, this study provides a thorough statistical degradation comparison analysis between polyethylene in situ environmentally aged microplastics and artificially aged films.

Automated Detection of Isolated REM Sleep Behavior Disorder Using Computer Vision.

Objective: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is, in most cases, an early stage of Parkinson's disease or related disorders. Diagnosis requires an overnight video-polysomnogram (vPSG), however, even for sleep experts, interpreting vPSG data is challenging. Using a 3D camera, automated analysis of movements has yielded high accuracy.

Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts.

Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leukocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls.

Mortality risk assessment using deep learning-based frequency analysis of electroencephalography and electrooculography in sleep.

Study Objectives: To assess whether the frequency content of electroencephalography (EEG) and electrooculography (EOG) during nocturnal polysomnography (PSG) can predict all-cause mortality.

Methods: Power spectra from PSGs of 8716 participants, including from the MrOS Sleep Study and the Sleep Heart Health Study, were analyzed in deep learning-based survival models. The best-performing model was further examined using SHapley Additive Explanation (SHAP) for data-driven sleep-stage specific definitions of power bands, which were evaluated in predicting mortality using Cox Proportional Hazards models.

Lifestyle Profiling Using Wearables and Prediction of Glucose Metabolism in Individuals with Normoglycemia or Prediabetes.

This study examined the relationship between lifestyles (diet, sleep, and physical activity) and glucose responses at a personal level. 36 healthy adults in the Bay Area were monitored for their lifestyles and glucose levels using wearables and continuous glucose monitoring (NCT03919877). Gold-standard metabolic tests were conducted to phenotype metabolic characteristics.

RESTORE: Once-nightly oxybate dosing preference and nocturnal experience with twice-nightly oxybates.

Objective/background: Preference for extended-release, once-nightly sodium oxybate (ON-SXB, FT218) vs twice-nightly immediate-release (IR) oxybate was assessed in participants switching from IR oxybate to ON-SXB in an open-label/switch study, RESTORE (NCT04451668).

Patients/methods: Participants aged ≥16 years with narcolepsy who completed the phase 3 REST-ON trial, were oxybate-naive, or were on a stable IR oxybate dose (≥1 month) were eligible for RESTORE. For participants who switched from twice-nightly dosing to ON-SXB, initial doses were closest or equivalent to their previous nightly IR oxybate dose.