bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of canakinumab in a patient with adult-onset glucocorticoid-resistant periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome
Authors: Sopeña Bernardo , Araújo Olga , Freire Mayka , Barrera-López Lucía , Hernández-Rodríguez José
Published: May 2022

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, a polygenic or multifactorial condition, is the most frequent autoinflammatory disease in children. There is increasing evidence that some patients may have a disease onset during adulthood. With regard to PFAPA syndrome treatment, single medium-to-high doses of glucocorticoids during flares constitute the therapy of choice in children and adults, colchicine may be useful in some patients, and tonsillectomy has been reported of utility mainly in paediatric patients. Interleukin-1 (IL-1) blockers have been sporadically used with good response in glucocorticoid-resistant cases. We report a patient with an adult onset of glucocorticoid-resistant PFAPA syndrome and inconsistent response to colchicine and anakinra, who later achieved a complete and sustained response to canakinumab. Although canakinumab seems to be a good therapeutic option in paediatric and adult patients with refractory PFAPA syndrome, the best anti-IL-1 agent and the sequence of administration have to be still determined in well-designed clinical trials.
A case of septic arthritis of the elbow joint in rheumatoid arthritis diagnosed by arthroscopic synovectomy
Authors: Hayashibara Masako , Hagino Hiroshi , Hayashi Ikuta , Nagira Keita , Takasu Yuta , Mukunoki Daichi , Nagashima Hideki
Published: May 2022

We report a case of methicillin-resistant Staphylococcus aureus (MRSA) septic arthritis of the elbow detected by arthroscopic synovectomy in an 81-year-old woman with rheumatoid arthritis (RA) who was initially diagnosed with a rheumatoid arthritis flare-up. The patient was administered abatacept, an antirheumatic biological agent, as the synovial fluid culture was negative. Destruction of the joint progressed despite medication, and the patient underwent arthroscopic synovectomy. MRSA was detected in the culture of the synovium that was collected intraoperatively, and septic arthritis was diagnosed. The infection subsided with anti-MRSA antibiotics, but the patient continued to experience moderate pain and limited motion. In RA patients, it might be difficult to differentiate minor findings from infection. Arthroscopic synovectomy is one of the selectable procedures that should be actively considered when infection is suspected.
EHF is a novel regulator of cellular redox metabolism and predicts patient prognosis in HNSCC
Authors: Oyelakin Akinsola , Nayak Kasturi Bala , Glathar Alexandra Ruth , Gluck Christian , Wrynn Theresa , Tugores Antonio , Romano Rose-Anne , Sinha Satrajit
Published: May 2022

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous disease with relatively high morbidity and mortality rates. The lack of effective therapies, high recurrence rates and drug resistance driven in part, by tumor heterogeneity, contribute to the poor prognosis for patients diagnosed with this cancer. This problem is further exacerbated by the fact that key regulatory factors contributing to the disease diversity remains largely elusive. Here, we have identified EHF as an important member of the ETS family of transcription factors that is highly expressed in normal oral tissues, but lost during HNSCC progression. Interestingly, HNSCC tumors and cell lines exhibited a dichotomy of high and low EHF expression, and patients whose tumors retained EHF expression showed significantly better prognosis, suggesting a potential tumor suppressive role for EHF. To address this, we have performed gain and loss of function studies and leveraged bulk and single-cell cancer genomic datasets to identify global EHF targets by RNA-sequencing (RNA-seq) and Chromatin Immunoprecipitation and next generation sequencing (ChIP-seq) experiments of HNSCC cell lines. These mechanistic studies have revealed that EHF, acts as a regulator of a broad spectrum of metabolic processes, specifically targeting regulators of redox homeostasis such as NRF2 and SOX2. Our immunostaining results confirm the mutually exclusive expression patterns of EHF and SOX2 in HNSCC tumors and suggest a possible role for these two factors in establishing discrete metabolic states within the tumor microenvironment. Taken together, EHF may serve as a novel prognostic marker for classifying HNSCC patients for actionable and targeted therapeutic intervention.
ePeak: from replicated chromatin profiling data to epigenomic dynamics
Authors: Daunesse Maëlle , Legendre Rachel , Varet Hugo , Pain Adrien , Chica Claudia
Published: May 2022

We present ePeak, a Snakemake-based pipeline for the identification and quantification of reproducible peaks from raw ChIP-seq, CUT&RUN and CUT&Tag epigenomic profiling techniques. It also includes a statistical module to perform tailored differential marking and binding analysis with state of the art methods. ePeak streamlines critical steps like the quality assessment of the immunoprecipitation, spike-in calibration and the selection of reproducible peaks between replicates for both narrow and broad peaks. It generates complete reports for data quality control assessment and optimal interpretation of the results. We advocate for a differential analysis that accounts for the biological dynamics of each chromatin factor. Thus, ePeak provides linear and nonlinear methods for normalisation as well as conservative and stringent models for variance estimation and significance testing of the observed marking/binding differences. Using a published ChIP-seq dataset, we show that distinct populations of differentially marked/bound peaks can be identified. We study their dynamics in terms of read coverage and summit position, as well as the expression of the neighbouring genes. We propose that ePeak can be used to measure the richness of the epigenomic landscape underlying a biological process by identifying diverse regulatory regimes.
Automated brain tumor identification using magnetic resonance imaging: A systematic review and meta-analysis
Authors: Kouli Omar , Hassane Ahmed , Badran Dania , Kouli Tasnim , Hossain-Ibrahim Kismet , Steele J Douglas
Published: May 2022

Background

Automated brain tumor identification facilitates diagnosis and treatment planning. We evaluate the performance of traditional machine learning (TML) and deep learning (DL) in brain tumor detection and segmentation, using MRI.

Methods

A systematic literature search from January 2000 to May 8, 2021 was conducted. Study quality was assessed using the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Detection meta-analysis was performed using a unified hierarchical model. Segmentation studies were evaluated using a random effects model. Sensitivity analysis was performed for externally validated studies.

Results

Of 224 studies included in the systematic review, 46 segmentation and 38 detection studies were eligible for meta-analysis. In detection, DL achieved a lower false positive rate compared to TML; 0.018 (95% CI, 0.011 to 0.028) and 0.048 (0.032 to 0.072) (P < .001), respectively. In segmentation, DL had a higher dice similarity coefficient (DSC), particularly for tumor core (TC); 0.80 (0.77 to 0.83) and 0.63 (0.56 to 0.71) (P < .001), persisting on sensitivity analysis. Both manual and automated whole tumor (WT) segmentation had “good” (DSC ≥ 0.70) performance. Manual TC segmentation was superior to automated; 0.78 (0.69 to 0.86) and 0.64 (0.53 to 0.74) (P = .014), respectively. Only 30% of studies reported external validation.

Conclusions

The comparable performance of automated to manual WT segmentation supports its integration into clinical practice. However, manual outperformance for sub-compartmental segmentation highlights the need for further development of automated methods in this area. Compared to TML, DL provided superior performance for detection and sub-compartmental segmentation. Improvements in the quality and design of studies, including external validation, are required for the interpretability and generalizability of automated models.
Radiomics and radiogenomics in pediatric neuro-oncology: A review
Authors: Madhogarhia Rachel , Haldar Debanjan , Bagheri Sina , Familiar Ariana , Anderson Hannah , Arif Sherjeel , Vossough Arastoo , Storm Phillip , Resnick Adam , Davatzikos Christos , Fathi Kazerooni Anahita , Nabavizadeh Ali
Published: May 2022

The current era of advanced computing has allowed for the development and implementation of the field of radiomics. In pediatric neuro-oncology, radiomics has been applied in determination of tumor histology, identification of disseminated disease, prognostication, and molecular classification of tumors (ie, radiogenomics). The field also comes with many challenges, such as limitations in study sample sizes, class imbalance, generalizability of the methods, and data harmonization across imaging centers. The aim of this review paper is twofold: first, to summarize existing literature in radiomics of pediatric neuro-oncology; second, to distill the themes and challenges of the field and discuss future directions in both a clinical and technical context.
Genomic Surveillance of SARS-CoV-2 in a University Community: Insights Into Tracking Variants, Transmission, and Spread of Gamma (P.1) Variant
Authors: Ciubotariu Ilinca I , Dorman Jack , Perry Nicole M , Gorenstein Lev , Kattoor Jobin J , Fola Abebe A , Zine Amy , Hendrix G Kenitra , Wilkes Rebecca P , Kitchen Andrew , Carpi Giovanna
Published: May 2022

Background

Using a combination of data from routine surveillance, genomic sequencing, and phylogeographic analysis, we tracked the spread and introduction events of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focusing on a large university community.

Methods

Here, we sequenced and analyzed 677 high-quality SARS-CoV-2 genomes from positive RNA samples collected from Purdue University students, faculty, and staff who tested positive for the virus between January 2021 and May 2021, comprising an average of 32% of weekly cases across the time frame.

Results

Our analysis of circulating SARS-CoV-2 variants over time revealed periods when variants of concern (VOC) Alpha (B.1.1.7) and Iota (B.1.526) reached rapid dominance and documented that VOC Gamma (P.1) was increasing in frequency as campus surveillance was ending. Phylodynamic analysis of Gamma genomes from campus alongside a subsampling of >20 000 previously published P.1 genomes revealed 10 independent introductions of this variant into the Purdue community, predominantly from elsewhere in the United States, with introductions from within the state of Indiana and from Illinois, and possibly Washington and New York, suggesting a degree of domestic spread.

Conclusions

We conclude that a robust and sustained active and passive surveillance program coupled with genomic sequencing during a pandemic offers important insights into the dynamics of pathogen arrival and spread in a campus community and can help guide mitigation measures.
Piercing the Parliamentary Veil against Judicial Review: The Case against Parliamentary Privilege
Authors: Lui Edward
Published: May 2022

For centuries, parliamentary privilege has stood as a bar against judicial review over the internal affairs of Parliament. The literature surrounding parliamentary privilege has mostly been about the scope of the privilege; few have discussed if the existence of the privilege itself is justified. This article undertakes that task, by examining parliamentary privilege as a defence against judicial review. Three propositions will be made. First, in the context of judicial review, parliamentary privilege is defined by the outer limits of the principle of exclusive cognisance. Article 9 of the Bill of Rights 1689 adds nothing. Second, parliamentary privilege as it relates to judicial review is incompatible with the two prevailing models of the separation of powers. Third, six arguments that may be made in favour of parliamentary privilege will be refuted. Accordingly, parliamentary privilege should no longer provide a defence towards judicial review.
Naive and memory T cells TCR–HLA-binding prediction
Authors: Glazer Neta , Akerman Ofek , Louzoun Yoram
Published: May 2022

T cells recognize antigens through the interaction of their T cell receptor (TCR) with a peptide-major histocompatibility complex (pMHC) molecule. Following thymic-positive selection, TCRs in peripheral naive T cells are expected to bind MHC alleles of the host. Peripheral clonal selection is expected to further increase the frequency of antigen-specific TCRs that bind to the host MHC alleles. To check for a systematic preference for MHC-binding T cells in TCR repertoires, we developed Natural Language Processing-based methods to predict TCR–MHC binding independently of the peptide presented for Class I MHC alleles. We trained a classifier on published TCR–pMHC binding pairs and obtained a high area under curve (AUC) of over 0.90 on the test set. However, when applied to TCR repertoires, the accuracy of the classifier dropped. We thus developed a two-stage prediction model, based on large-scale naive and memory TCR repertoires, denoted TCR HLA-binding predictor (CLAIRE). Since each host carries multiple human leukocyte antigen (HLA) alleles, we first computed whether a TCR on a CD8 T cell binds an MHC from any of the host Class-I HLA alleles. We then performed an iteration, where we predict the binding with the most probable allele from the first round. We show that this classifier is more precise for memory than for naïve cells. Moreover, it can be transferred between datasets. Finally, we developed a CD4–CD8 T cell classifier to apply CLAIRE to unsorted bulk sequencing datasets and showed a high AUC of 0.96 and 0.90 on large datasets. CLAIRE is available through a GitHub at: https://github.com/louzounlab/CLAIRE, and as a server at: https://claire.math.biu.ac.il/Home.
T-LOC: A comprehensive tool to localize and characterize T-DNA integration sites
Authors: Li Shaofang , Wang Chenyang , You Chenjiang , Zhou Xueping , Zhou Huanbin
Published: May 2022

Scientists have developed many approaches based on PCR or next-generation sequencing to localize and characterize integrated T-DNAs in transgenic plants generated by Agrobacterium tumefaciens-mediated T-DNA transfer. However, none of these methods has the robust ability to handle all transgenic plants with diversified T-DNA patterns. Utilizing the valuable information in the whole-genome sequencing data of transgenic plants, we have developed a comprehensive approach (T-LOC) to localize and characterize T-DNA integration sites (TISs). We evaluated the performance of T-LOC on genome sequencing data from 48 transgenic rice (Oryza sativa) plants that provide real and unbiased resources of T-DNA integration patterns. T-LOC discovered 75 full TISs and reported a diversified pattern of T-DNA integration: the ideal single-copy T-DNA between two borders, multiple-copy of T-DNAs in tandem or inverted repeats, truncated partial T-DNAs with or without the selection hygromycin gene, the inclusion of T-DNA backbone, the integration at the genome repeat region, and the concatenation of multiple ideal or partial T-DNAs. In addition, we reported that DNA fragments from the two A. tumefaciens plasmids can be fused with T-DNA and integrated into the plant genome. Besides, T-LOC characterizes the genomic changes at TISs, including deletion, duplication, accurate repair, and chromosomal rearrangement. Moreover, we validated the robustness of T-LOC using PCR, Sanger sequencing, and Nanopore sequencing. In summary, T-LOC is a robust approach to studying the TISs independent of the integration pattern and can recover all types of TISs in transgenic plants.
Three-dimensional-printed polycaprolactone scaffolds with interconnected hollow-pipe structures for enhanced bone regeneration
Authors: Duan Jiahua , Lei Dong , Ling Chen , Wang Yufeng , Cao Zhicheng , Zhang Ming , Zhang Huikang , You Zhengwei , Yao Qingqiang
Published: May 2022

Three-dimensional (3D)-printed scaffolds are widely used in tissue engineering to help regenerate critical-sized bone defects. However, conventional scaffolds possess relatively simple porous structures that limit the delivery of oxygen and nutrients to cells, leading to insufficient bone regeneration. Accordingly, in the present study, perfusable and permeable polycaprolactone scaffolds with highly interconnected hollow-pipe structures that mimic natural micro-vascular networks are prepared by an indirect one-pot 3D-printing method. In vitro experiments demonstrate that hollow-pipe-structured (HPS) scaffolds promote cell attachment, proliferation, osteogenesis and angiogenesis compared to the normal non-hollow-pipe-structured scaffolds. Furthermore, in vivo studies reveal that HPS scaffolds enhance bone regeneration and vascularization in rabbit bone defects, as observed at 8 and 12 weeks, respectively. Thus, the fabricated HPS scaffolds are promising candidates for the repair of critical-sized bone defects.
0049 Screen time and sleep in young adolescents before and across the first year of the COVID-19 pandemic
Authors: Kiss Orsolya , de Zambotti Massimiliano , Schaefer Emil , Durley Ingrid , Kerr Erin , Dulai Teji , Arra Nicole , Obilor Todd , Camacho Leticia , Hsu Carrie , Baker Fiona
Published: May 2022

Introduction

The COVID-19 pandemic has been associated with profound biopsychosocial changes for children, potentially affecting their health and wellbeing. Among these changes are altered sleep patterns and screen time use, however, no work has examined interactions between these two behaviors in the context of the pandemic. Here, we used longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study® to investigate changes in both sleep and screen time, and their relationship, from before and across the first year of the COVID-19 pandemic in young adolescents.

Methods

More than 5000 adolescents (11-14 years; 48% girls) completed digital surveys about their sleep and daily screen time use before the pandemic and across six timepoints during 2020-2021, as part of the ongoing ABCD Study®. Random intercept linear mixed effect models (LMMs) were used to examine longitudinal associations between bedtime, wake-up time, and daily screen time use (social media, gaming), considering age, sex, and school effects.

Results

Adolescents’ wake up time was delayed (R2 = 0.51; ~1.5 hour) during May-August 2020 relative to the pre-pandemic assessment (p<0.01), which was partially related to the summer break (p<0.01), before advancing to earlier times in October 2020. Bedtimes also delayed at all pandemic assessments (R2=0.62; ~1 hour), even after starting the new school year (p<0.01), particularly in older adolescents (p<0.01) and girls (p<0.01). Recreational screen time was dramatically higher across the first year of the pandemic, relative to pre-pandemic (p<0.01; ~45min social media, ~20min video gaming). More time spent with screen related activities was associated with later bedtimes and wake up times (p<0.01), across the pandemic, with effects being evident in male and female adolescents.

Conclusion

Our findings show profound changes in sleep timing and screen time use across the pandemic in young adolescents, and critically, that excessive screen time negatively impacts sleep. As adolescents increasingly turn to more screen usage, these data highlight the need to promote their balanced and informed use of social media platforms, video games, and other digital technology to ensure adequate opportunity to sleep and maintain other healthy behaviors during this critical period of developmental change.

Support (If Any)

NIH U01DA041022
0075 Food Insecurity is Associated with Sleep Duration and Sleep Disorders Symptoms in a Community Adult Sample
Authors: Craig Chloe , Martinez Suzanna , Hale Lauren , Branas Charles , Killgore William , Wills Chloe , Grandner Michael
Published: May 2022

Introduction

Food insecurity is an issue of socioeconomic disadvantage and is increasingly recognized as a key risk factor psychosocial stress and metabolic health. This study examined relationships with aspects of sleep health including sleep duration, quality, continuity, and control, and sleep disorders symptoms.

Methods

This cross-sectional study used data from the Sleep and Healthy Activity, Diet, Environment, and Socialization (SHADES) study of working-age adults ages 22-60 (N=1003). Food insecurity was assessed using items regarding: worry that food would run out, food would not last, and inability to afford healthy meals. Each item was scored 0-2 and total scores ranged from 0-6. Sleep-related variables included habitual sleep duration, Insomnia Severity Index, Brief Index of Sleep Control, Epworth Sleepiness Scale, self-reported habitual sleep latency and wake after sleep onset (WASO), nightmares, restless legs symptoms, STOP-BANG, and statements indicating that medical health and/or stress interfere with sleep. Covariates included age, sex, race/ethnicity, education, insomnia, and shiftwork.

Results

Greater food insecurity was associated with an increased likelihood of being a very short (<5h) sleeper (RRR=1.23, 95%CI[1.08,1.04) or short (5-6h) sleeper (RRR=1.15, 95%CI[1.05.1.25]), as well as having mild (RRR=1.28, 95%CI[1.16,1.41]) or moderate/severe insomnia (RRR=1.38, 95%CI[1.24,1.54]). Those with higher food insecurity perceived less control over sleep (B=-0.11, 95%CI[-0.14,-0.07]), more sleepiness (B=0.40, 95%CI[0.23,0.57]), longer sleep latency (B=2.24, 95%CI[1.09,3.38]), more WASO (B=1.80, 95%CI[0.09,3.51]), and more nightmares sometimes (RRR=1.13, 95%CI[1.04,1.23]) or often (RRR=1.23, 95%CI[1.07,1.40]). Participants were more likely to report uncomfortable sensations in their legs at night and needing to move legs to alleviate discomfort >3 times/week (RRR=1.33, 95%CI[1.17,1.51] and RRR=1.27, 95%CI[1.11,1.45], respectively). They also experienced a higher STOP-BANG score (B=0.09, 95%CI[0.05,0.13]) and were more likely to either agree or strongly agree that medical symptoms (RRR=1.30, 95%CI[1.15,2.47]l and RRR=1.34, 95%CI[1.15,1.57], respectively) and stress (RRR=1.88, 95%CI[1.31,2.69]l and RRR=2.16, 95%CI[1.51,3.10], respectively). Post-hoc analyses showed that most of these relationships were consistent across all 3 components of food insecurity.

Conclusion

Food insecurity was associated with worse sleep health, including risk for insufficient sleep, insomnia, sleep apnea, restless legs, and nightmares. Future research should investigate if efforts to reduce food insecurity can help improve sleep health and other associated outcomes.

Support (If Any)
0085 SleepInceptionNet: A Deep Learning Algorithm for Real-Time Sleep Stages Scoring Using Single-channel EEG
Authors: Haghayegh Shahab , Hu Kun , Stone Katie , Redline Susan , Schernhammer Eva
Published: May 2022

Introduction

Most of the current automatic polysomnography sleep staging methods use multi-signal data and require a sequence of preceding and following epochs to score the stage of a specific epoch, which may not be desirable for analysis in real-time and/or in free-living conditions. We developed a deep learning-based sleep staging algorithm, namely SleepInceptionNet, that is designed to score each epoch using only single-channel electroencephalogram (EEG) data within that specific epoch.

Methods

Polysomnography data of 883 participants (937,975 thirty-second epochs) in the Multi-Ethnic Study of Atherosclerosis (MESA) obtained from the National Sleep Research Resource (NSRR) were randomly divided into a separate training/validation set of 194 participants and a test set of 689 participants. Each 30-second raw central EEG channel signal was transformed to time-frequency domain images using continuous wavelet transform method. Sleep stage in each epoch was obtained using SleepInceptionNet, in which the InceptionV3 convolutional neural network structure was trained and tuned on the time-frequency images of the training set to classify each epoch into one of the five stages of Wake, N1, N2, N3, or rapid eye movement (REM) sleep.

Results

Compared to the ground truth manually scored polysomnography sleep stages, SleepInceptionNet achieved an overall kappa agreement of 0.690 and overall weighted accuracy of 0.897. The model showed accuracy (mean±SD across the test set participants) of 0.940±0.067 in detecting Wake, 0.883±0.047 in detecting N1, 0.845±0.055 in detecting N2, 0.939±0.038 in detecting N3, and 0.930±0.038 in detecting REM epochs, in reference to manually scored polysomnography.

Conclusion

SleepInceptionNet showed a high agreement with manually scored polysomnography in epoch-by-epoch classification of sleep stages. This study demonstrates the viability of real-time, accurate sleep staging using a single-channel EEG, which could have a variety of applications such as delivery of on-demand interventions during specific sleep stages in free-living conditions.

Support (If Any)

MESA Sleep Ancillary study was funded by NIH-NHLBI Association of Sleep Disorders with Cardiovascular Health Across Ethnic Groups (RO1 HL098433). MESA is supported by NHLBI (HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01- HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169) and NCATS (UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420). NSRR was supported by NHLBI (R24 HL114473, 75N92019R002).
0088 Remote clinical research operations during COVID-19: Lessons learned and recommendations
Authors: Adornetti Julianna , Wade Christine , Deeley Maura , Eldringhoff Hannah , Jones Rachell , Mantua Janna , Collen Jacob , Wickwire Emerson
Published: May 2022

Introduction

As a result of the global COVID-19 pandemic, there have been significant challenges conducting clinical sleep research. Participant recruitment has been a particular challenge due to federal safety guidelines and institutional directives. The purpose of this project is to describe the adaptation of an in-person study protocol (of sleep problems among military service members and their families) to an entirely remote approach.

Methods

Prior to COVID-19, planned research methods included in-person recruitment, enrollment, and study support; approved by the Institutional Review Board (IRB) of Walter Reed National Military Medical Center (WRNMMC), Fort Belvoir Community Hospital (FBCH), and the University of Maryland, Baltimore (UMB). As COVID-19 restrictions increased, the research team adapted to a fully remote approach (via phone/email) and developed a “research call center” to replace in-clinic recruitment/enrollment. Detailed operating procedures were standardized, including shipping study materials (wearable device) via FedEx. Following enrollment, participants completed multiple assessments, sleep diaries 2x/day over 10 days, and a post-monitoring satisfaction survey.

Results

Thirty-five participants between the ages of 18-75 years (M= 46 years, SD= 15.8) were successfully recruited from the Internal Medicine clinic and Sleep Disorders Center at WRNMMC. Following data collection, the research team debriefed and developed recommendations to execute a successful remote study protocol. Three key operational domains were identified: research team, remote procedures, and data management. Recommendations included 1) prioritizing consistent communication, mutual support, and personal wellbeing among the research team, 2) advancing recruitment by establishing and refining preferred recruitment pathways, and 3) providing critical attention to remote data management—allocating responsibilities to regulate the evolving changes of multiple data sources. In addition, partnering closely with IRB personnel was invaluable to refine procedures and maintain regulatory compliance.

Conclusion

Despite challenges associated with the on-going pandemic, researchers can conduct high-quality clinical research by transitioning to a fully remote study approach. These recommendations can help guide investigative teams to transition from in-person protocols to remote approaches, thus advancing the perpetuation of research activities through a pandemic.

Support (If Any)

This research was supported by an investigator-initiated research award from the Department of Defense (via the Medical Technology Enterprise Consortium) to the University of Maryland, Baltimore (PI: EMW).
0090 Performance of a Multisensor Ring to Evaluate Sleep: In-Lab Evaluation Relative to PSG and Actigraphy: Importance of Generalized Versus Personalized Scoring
Authors: Grandner Michael , Hutchison Stephen , Bromberg Zohar , Morrell Zoe , Graf Arnulf , Freckleton Dustin
Published: May 2022

Introduction

Multisensor sleep wearable devices have demonstrated utility for research and relative accuracy for discerning sleep-wake patterns at home and in the laboratory. Additional sensors and more complex scoring algorithms may improve the ability of wearables to assess sleep health.

Methods

Thirty-six healthy adults completed assessment while wearing the experimental device (Happy Ring), as well as Philips Actiwatch, Fitbit, Oura, and Whoop devices. Evaluations occurred in the laboratory (Alice 6 polysomnogram). The Happy Ring includes sensors for accelerometry, photoplethysmography, electrodermal activity, and skin temperature. Epoch-by-epoch analyses compared the Happy Ring to lab polysomnography, as well as other sleep-tracking devices. Scoring was accomplished using two machine-learning-derived algorithms: a “generalized” algorithm which was static and applied to all users (like those used for other devices) and a “personalized” algorithm where parameters are personalized, dynamic, and change based on data collected across different parts of the night of sleep.

Results

Compared to in-lab polysomnography, the generalized algorithm using data from the Happy Ring demonstrated good sensitivity (94%) and specificity (70%). The personalized algorithm also performed well with good sensitivity (93%) and specificity (83%). Other devices also demonstrated good sensitivity, ranging from 89% (Fitbit) to 94% (Actiwatch); specificity however, was more variable, ranging from 19% (Actiwatch) to 54% (Whoop). Overall accuracy was 91% for generalized and 92% for personalized, compared to 88% for Oura, 86% for Whoop, 84% for Fitbit, and 85% for Actiwatch. Measurement of sleep stage accuracy was 67%, 85%, and 85% for light, deep, and REM sleep, respectively, for the Happy generalized algorithm. For the Happy personalized algorithm, accuracy for sleep stages were 81%, 95%, and 92%, for light, deep and REM sleep, respectively. Post-hoc analyses showed that the Happy personalized algorithm demonstrated better specificity than all other modalities (p<0.001). Kappa scores were 0.45 for generalized and 0.68 for personalized, compared to 0.32 for the Oura Ring, 0.32 for Whoop Strap, and 0.37 for Fitbit wristband.

Conclusion

The multisensory Happy ring demonstrated good sensitivity and specificity for the detection of sleep in the laboratory. The personalized approach outperformed all others, representing a potential innovation for improving detection accuracy.

Support (If Any)

Dr. Grandner is supported by R01DA051321 and R01MD011600. This work was supported by Happy Health, Inc.
0095 Sleep Enhancement Technology in 2021: An Updated Survey of Apps
Authors: Stekl Emily , Klosterman Grace , Simonelli Guido , Collen Jacob , Doty Tracy
Published: May 2022

Introduction

Commercially available smartphone apps that claim to improve sleep quantity and/or quality represent an ever-evolving and fast-growing market. Although a large body of work has validated the performance of sleep tracking technologies, there is little information regarding potential sleep enhancement technologies. Our study systematically surveyed currently available commercial sleep enhancement smartphone apps to provide details to inform both providers and patients alike, in addition to the healthy consumer market.

Methods

We systematically searched the Google Play Store (Android) on 30 JUN 2021 and the App Store (Apple) on 30 JUN 2021 and 26 JUL 2021 in the US using the keyword “sleep.” The Android search was conducted via the Google Play Store website. The Apple search was conducted via third-party websites linked to the App Store due to restrictions on searching the App Store online. This survey was conducted using Google Chrome web browsers and is inclusive of all smartphone applications found.

Results

We identified 550 apps: 59.5% on Android (N=327) and 40.5% on Apple (N=223). Ninety-four percent of apps offered a free version. The majority of sleep apps were intended for use during wake (72.7% exclusively during wake; 25.1% during both wake and sleep), with only 2.2% intended to be used during sleep alone. Most apps purport to enhance rather than measure sleep (87.8% versus 0.5%). The vast majority of apps claim to enhance sleep via reductions in sleep latency (92.9%). Reduced sleep latency is primarily achieved using auditory stimuli (74.5%).

Conclusion

Most current sleep apps are designed to be used while awake, prior to sleep, and focus on the enhancement of sleep, rather than measurement, by targeting sleep latency. Given the evidence that supports sleep latency as an important target for sleep promoting interventions and the multitude of available sleep enhancement apps across both Android and Apple platforms, sleep apps could be considered a possible strategy for patients and consumers to improve their sleep, although validation of these apps is required.

Support (If Any)

Department of Defense Military Operational Medicine Research Program (MOMRP)
0140 Operationalizing Sleep for the Military: Advancing an Infrastructure for Fatigue Risk Management with Wearable Technology
Authors: Markwald Rachel , Jameson Jason , Chinoy Evan , Kubala Andrew , Roma Pete , Casachahua John , Russell Dale
Published: May 2022

Introduction

A recent investigation on fatigue within United States (US) Naval Surface Force by the Government Accountability Office recommended that the US Navy incorporate methods to empirically monitor and manage fatigue-related threats. In response, a feasibility effort was undertaken to assess two commercial wearable devices previously evaluated against polysomnography by our group for potential use within a novel fatigue monitoring system onboard US warships.

Methods

501 Sailors from three warships (415 men, 85 women, 1 response missing; 29.1±7.4 years, mean±SD) were included in analyses. During multi-day missions at sea, participants were instructed to continuously wear a wrist-worn Fatigue Science Readiband and an Oura Ring. Participants met with the research team daily to sync wearable devices and complete self-ratings of sleep and fatigue on a tablet. While returning to port, participants completed a user experience questionnaire that included 5-point scales for device comfort and interference with daily activities (larger values indicate greater comfort or interference).

Results

There were no overall differences in total sleep time (TST) and sleep efficiency (SE) between devices (TST: Ring=352.23±87.1, Readiband=353.89±97.79; p=0.45, d=-0.01; SE: Ring=84.59±7.08, Readiband=84.20±10.24; p=0.06, d=0.04). There were 9 days for TST and 4 days for SE (of 66 total days) that resulted in effect sizes >0.50 between devices (for >0.20: TST, 39/66; SE, 29/66). Preliminary analyses between TST and self-reported exhaustion and inability to function suggest predictive relationships with the wearables (Ring: r=-0.20; Readiband: r=-0.21), with no relationship with SE across devices (both r<0.01). Average comfort ratings for Ring (3.74) exceeded Readiband (3.59), but this difference was small (p=0.04, d=0.12). Interference with daily activities was also similar between devices (Ring=2.10, Readiband=2.20; p=0.14, d=0.08).

Conclusion

Both commercial wearables performed similarly for their TST and SE assessments, and TST was associated with self-rated fatigue within this operational environment. While the ring form factor was selected more for comfort than the wrist form factor, the difference was small. Collectively, findings indicate that both devices show promise for operational use within fatigue monitoring systems. Further testing is being conducted to better understand the strengths and limitations of wearable devices for monitoring sleep in warship environments.

Support (If Any)

Military Operational Medicine Research Program
0148 Associations Between Subjective and Objective Sleep Outcomes and Nightly Pain Changes in a Chronic Pain Sample
Authors: McGovney Kevin , Curtis Ashley , McCrae Christina
Published: May 2022

Introduction

Patients with chronic pain often experience poor sleep. Research demonstrating the bidirectional nature of the pain/sleep association has focused on interindividual patterns based on between person averages, leaving acute, intraindividual patterns based on night-to-night fluctuations understudied. Because both pain and sleep fluctuate considerably, better understanding of those fluctuations may provide important insight into the pain/sleep relationship. Here we examine inter- and intraindividual associations between subjective and objective sleep outcomes and nightly pain changes in individuals with chronic pain and sleep complaints.

Methods

Adults with chronic pain and sleep complaints (n=169, Mage=52, SD= 12, 95% female) completed 14 days of actigraphy and sleep diaries each morning and evening. Evening diaries recorded pain and sleep medication use (yes/no), and evening pain intensity (0-none, 100-most intense). Actigraphy and morning diaries recorded sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and morning pain intensity (0-none, 100-most intense). A nightly pain difference score (morning – evening) was calculated, where positive values indicate worse morning pain relative to previous evening pain. Multi-level models examined the inter- and intraindividual associations between sleep (subjective and objective SOL, WASO, TST) and nightly pain difference scores. Analyses controlled for age, sleep, and pain medication use.

Results

Greater interindividual subjective WASO was associated (B=0.06, SE=0.03, p=0.02) with greater interindividual pain difference scores. Other interindividual sleep outcomes (subjective and objective) were not significantly associated with interindividual pain difference scores. There were no associations between sleep outcomes (subjective and objective) and pain difference scores at the intraindividual level.

Conclusion

Findings show sleep and pain were not linked at the daily, intraindividual level. However, on average, greater WASO was linked with worse morning relative to evening pain. Thus, although a single night of poor sleep may not impact pain, the buildup of fragmented sleep over time may interfere with restorative properties of sleep and exacerbate morning pain. Future work should investigate mechanisms underlying sleep fragmentation (e.g., sleep architecture, physiological arousal) and how such factors relate to nightly pain changes.

Support (If Any)

NIH/NIAMS R01AR055160, ClinicalTrials-NCT02001077, PI McCrae.
0174 The Odds Ratio Product as a Marker of Sleep Homeostasis
Authors: Toutant Darion , Younes Magdy , Ng Marcus
Published: May 2022

Introduction

Classic EEG markers of sleep homeostasis (process S) usually study the level and amount of slow wave activity (SWA). In recent years, the odds ratio product (ORP) has been described as a novel quantitative measure of sleep depth (and conversely, arousability), which is derived from a four-digit permutation of the power in four respective frequency bands. Therefore, we sought to determine whether the ORP can also be used as a novel quantitative marker of process S.

Methods

Utilizing C3/C4 electrodes with TP9/TP10 reference, ORP was calculated from 25 nights in 15 patients. We used ORP from REM and NREM1-3 segments/bouts in each person’s night(s) with varying number of data points per REM segment(s) in each night(s). Artifacts and wake segments were discarded from analysis. Average ORP is calculated for an individual bout per night per patient. Generalized Estimating Equation (GEE) modelling used GEEQBOX MATLAB toolbox to identify change in sleep depth over bouts. Resultant beta (β) values represented change in nightly sleep depth over sequential NREM/REM segments per patient. Significance was p≤0.000833.

Results

From 15 people in the epilepsy monitoring unit, 3 did not have epilepsy. In NREM, the average ORP for C3/C4 is 1.26/1.19 (n=146307/125709). Average number of nightly NREM segments for C3/C4 are 4.64/4.9 (n=1261.27/1282.74 average ORP values per nightly segment). In REM, the average ORP for C3/C4 is 1.44/1.44 (n=47629/43528). Average number of nightly REM segments for C3/C4 are 4.36/4.38 (n=418.68/453.33 average ORP values per nightly segment). Signifying the change in sleep depth the beta values from C3/C4 were consistently positive: REM (epilepsy 0.033/0.018, non-epilepsy 0.096/0.053), NREM (epilepsy 0.047/0.053, non-epilepsy 0.026/0.064).

Conclusion

As a marker of sleep homeostasis, SWA decreases across a period of sleep. Consistently positive beta values derived from ORP in both REM and NREM are comparable because they demonstrate shallower sleep depth (i.e. greater arousability) across segments over nights as sleep debt is repaid. Also as expected, REM has a higher ORP than NREM. Furthermore, our findings of positive beta values are robust against sleep stage and pathology (i.e. epilepsy). Therefore, these findings may represent a novel quantitative marker of sleep homeostasis that includes REM.

Support (If Any)
0204 Sleep Irregularity Is Associated with Increased Risk of Hypertension: Data From Over Two Million Nights
Authors: Scott Hannah , Lechat Bastien , Reynolds Amy , Lovato Nicole , Escourrou Pierre , Catcheside Peter , Eckert Danny
Published: May 2022

Introduction

Sleep irregularity has been associated with worse cardio-metabolic health compared to regular sleep, but prior studies have been limited in sample size and have assessed sleep irregularity by actigraphy or questionnaires over a relatively short duration (~ 14 days). The current study investigated associations between sleep regularity and hypertension in a large, global sample over multiple months.

Methods

Data from 12,300 participants (aged 18-90 years) who used an under-mattress sleep device and a portable blood pressure monitor between July 2020 and March 2021 were included in this study. Sleep duration regularity was assessed as the standard deviation via device-assessed total sleep time. Sleep timing regularity was assessed as the standard deviation in sleep onset time and in sleep midpoint. Logistic regressions controlling for age, sex, BMI, and mean total sleep time were conducted to investigate potential associations between sleep regularity and hypertension.

Results

Participants were typically middle-aged (Mean ± SD; 50 ± 12 years) and predominantly male (12% females). Each participant had ~180 nights of recordings and ~70 blood pressure entries. There were 2,499 cases of hypertension defined as SBP>140 and/or DBP >90mmHg (20% of the sample). Across total sleep time quartiles, high sleep duration irregularity was consistently associated with a 9 to 15% increase in hypertension risk. A 38-minute increase in sleep midpoint irregularity was associated with an 11% (1.11 [1.03, 1.20]) increase in hypertension risk, independent of mean total sleep time and mean sleep midpoint. Similarly, a ~31-minute increase in sleep onset time irregularity was associated with a 29% increased risk of hypertension (1.29 [1.18, 1.42]).

Conclusion

These novel findings provide insight into the potential important impact of sleep irregularity on cardiovascular health. Further assessment of day-to-day fluctuations in sleep duration and timing for potential effects on next-day blood pressure and other cardiovascular health outcomes are warranted.

Support (If Any)

This was an unfunded investigator-initiated study. De-identified data were provided by Withings for unrestricted investigator-led analysis. PE serves as a consultant for Withings.
0214 Effects of Simulated Night-Shiftwork Induced Circadian Misalignment on the Human Plasma Metabolome
Authors: Kubicki Michelle , McHill Andrew , Melanson Edward , Reisdorph Nichole , Wright Kenneth , Depner Christopher
Published: May 2022

Introduction

Circadian misalignment occurs when behaviors such as food intake and sleep happen at inappropriate endogenous circadian times, is common among shift-workers, and is a risk factor for cardiometabolic disease. Identifying mechanisms underlying adverse cardiometabolic risk linked to circadian misalignment could help develop new countermeasure strategies to mitigate health consequences of shiftwork. Thus, we analyzed 24-hour profiles of plasma metabolites during circadian alignment and misalignment in a night-shiftwork protocol.

Methods

14 healthy adults (6M/8F), aged 26.4±1.2y (mean±SD), completed a 6 day in-laboratory simulated night-shiftwork study. The protocol comprised 2 baseline days (circadian alignment) followed by a transition day to shiftwork, and then 2 simulated night-shiftwork days (circadian misalignment). Participants consumed energy-balanced diets throughout the protocol, starting 3 days prior to laboratory admission. Plasma was collected every 4h during circadian alignment and misalignment conditions and was analyzed via untargeted metabolomics (liquid chromatography/mass-spectrometry). A model selection approach (best fit) with circadian and behavioral cosine models identified metabolites influenced by circadian (central circadian clock measured via dim-light melatonin onset) versus behavioral cycles (food intake/sleep).

Results

5,171 metabolites were detected with average abundance of 424 (~8%) changing between conditions (false discovery rate (FDR)<0.05). 380 metabolites had significant (FDR<0.05) 24-h time-of-day patterns. Of these 380 metabolites, 248 had 24-h time-of-day patterns during circadian alignment, 283 had 24-h time-of-day patterns during misalignment, and 141 had 24-h time-of-day patterns during both conditions. Of the metabolites with 24-h time-of-day patterns in both conditions, 50 were circadian-influenced (e.g., arachidinoyl-serine) and 91 were behaviorally-influenced (e.g., propionylcarnitine).

Conclusion

Almost twice as many metabolites were influenced by the behavioral versus circadian cycle suggesting altered timing of behaviors like food intake and sleep have a significant impact on 24-h time-of-patterns in the human plasma metabolome. For example, propionylcarnitine is involved in energy metabolism and likely reflects 24h time-of-day patterns altered by food intake. Alternatively, arachidinoyl-serine was circadian influenced, is involved in vasodilation, and thus may contribute to circadian regulation of blood pressure. Further understanding circadian and behavioral regulation of the metabolome could have application in identifying mechanisms of physiological dysregulation and targets for intervention to mitigate health consequences of circadian misalignment.

Support (If Any)

NIH-DK092624, NIH-TR001082, NIH-DK048520, NIH-HL132150, NIH-HL145099, NIH-DK111161