bluuebunny/crossref_metadata_2025 huggingface dataset:
NLRscape: an atlas of plant NLR proteins
Authors: Martin Eliza C , Ion Catalin F , Ifrimescu Florin , Spiridon Laurentiu , Bakker Jaap , Goverse Aska , Petrescu Andrei-J
Published: November 2022

NLRscape is a webserver that curates a collection of over 80 000 plant protein sequences identified in UniProtKB to contain NOD-like receptor signatures, and hosts in addition a number of tools aimed at the exploration of the complex sequence landscape of this class of plant proteins. Each entry gathers sequence information, domain and motif annotations from multiple third-party sources but also in-house advanced annotations aimed at addressing caveats of the existing broad-based annotations. NLRscape provides a top-down perspective of the NLR sequence landscape but also services for assisting a bottom-up approach starting from a given input sequence. Sequences are clustered by their domain organization layout, global homology and taxonomic spread—in order to allow analysis of how particular traits of an NLR family are scattered within the plant kingdom. Tools are provided for users to locate their own protein of interest in the overall NLR landscape, generate custom clusters centered around it and perform a large number of sequence and structural analyses using included interactive online instruments. Amongst these, we mention: taxonomy distribution plots, homology cluster graphs, identity matrices and interactive MSA synchronizing secondary structure and motif predictions. NLRscape can be found at: https://nlrscape.biochim.ro/.
GWAS Central: an expanding resource for finding and visualising genotype and phenotype data from genome-wide association studies
Authors: Beck Tim , Rowlands Thomas , Shorter Tom , Brookes Anthony J
Published: November 2022

The GWAS Central resource gathers and curates extensive summary-level genome-wide association study (GWAS) data and puts a range of user-friendly but powerful website tools for the comparison and visualisation of GWAS data at the fingertips of researchers. Through our continued efforts to harmonise and import data received from GWAS authors and consortia, and data sets actively collected from public sources, the database now contains over 72.5 million P-values for over 5000 studies testing over 7.4 million unique genetic markers investigating over 1700 unique phenotypes. Here, we describe an update to integrate this extensive data collection with mouse disease model data to support insights into the functional impact of human genetic variation. GWAS Central has expanded to include mouse gene–phenotype associations observed during mouse gene knockout screens. To allow similar cross-species phenotypes to be compared, terms from mammalian and human phenotype ontologies have been mapped. New interactive interfaces to find, correlate and view human and mouse genotype–phenotype associations are included in the website toolkit. Additionally, the integrated browser for interrogating multiple association data sets has been updated and a GA4GH Beacon API endpoint has been added for discovering variants tested in GWAS. The GWAS Central resource is accessible at https://www.gwascentral.org/.
Type I arginine methyltransferases are intervention points to unveil the oncogenic Epstein-Barr virus to the immune system
Authors: Angrand Gaelle , Quillévéré Alicia , Loaëc Nadège , Dinh Van-Trang , Le Sénéchal Ronan , Chennoufi Rahima , Duchambon Patricia , Keruzoré Marc , Martins Rodrigo Prado , Teulade-Fichou Marie-Paule , Fåhraeus Robin , Blondel Marc
Published: November 2022

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome maintenance but is also highly antigenic. Hence, EBV seemingly evolved a system in which the glycine–alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA to the minimal level to ensure its essential function, thereby, at the same time, minimizing immune recognition. Therefore, defining intervention points at which to interfere with GAr-based inhibition of translation is an important step to trigger an immune response against EBV-carrying cancers. The host protein nucleolin (NCL) plays a critical role in this process via a direct interaction with G-quadruplexes (G4) formed in the GAr-encoding sequence of the viral EBNA1 mRNA. Here we show that the C-terminal arginine–glycine-rich (RGG) motif of NCL is crucial for its role in GAr-based inhibition of translation by mediating interaction of NCL with G4 of EBNA1 mRNA. We also show that this interaction depends on the type I arginine methyltransferase family, notably PRMT1 and PRMT3: drugs or small interfering RNA that target these enzymes prevent efficient binding of NCL on G4 of EBNA1 mRNA and relieve GAr-based inhibition of translation and of antigen presentation. Hence, this work defines type I arginine methyltransferases as therapeutic targets to interfere with EBNA1 and EBV immune evasion.
PARP1 proximity proteomics reveals interaction partners at stressed replication forks
Authors: Mosler Thorsten , Baymaz H Irem , Gräf Justus F , Mikicic Ivan , Blattner Georges , Bartlett Edward , Ostermaier Matthias , Piccinno Rossana , Yang Jiwen , Voigt Andrea , Gatti Marco , Pellegrino Stefania , Altmeyer Matthias , Luck Katja , Ahel Ivan , Roukos Vassilis , Beli Petra
Published: November 2022

PARP1 mediates poly-ADP-ribosylation of proteins on chromatin in response to different types of DNA lesions. PARP inhibitors are used for the treatment of BRCA1/2-deficient breast, ovarian, and prostate cancer. Loss of DNA replication fork protection is proposed as one mechanism that contributes to the vulnerability of BRCA1/2-deficient cells to PARP inhibitors. However, the mechanisms that regulate PARP1 activity at stressed replication forks remain poorly understood. Here, we performed proximity proteomics of PARP1 and isolation of proteins on stressed replication forks to map putative PARP1 regulators. We identified TPX2 as a direct PARP1-binding protein that regulates the auto-ADP-ribosylation activity of PARP1. TPX2 interacts with DNA damage response proteins and promotes homology-directed repair of DNA double-strand breaks. Moreover, TPX2 mRNA levels are increased in BRCA1/2-mutated breast and prostate cancers, and high TPX2 expression levels correlate with the sensitivity of cancer cells to PARP-trapping inhibitors. We propose that TPX2 confers a mitosis-independent function in the cellular response to replication stress by interacting with PARP1.
Annotation and evaluation of base editing outcomes in multiple cell types using CRISPRbase
Authors: Fan Jibiao , Shi Leisheng , Liu Qi , Zhu Zhipeng , Wang Fan , Song Runxian , Su Jimeng , Zhou Degui , Chen Xiao , Li Kailong , Xue Lixiang , Sun Lichao , Mao Fengbiao
Published: November 2022

CRISPR-Cas base editing (BE) system is a powerful tool to expand the scope and efficiency of genome editing with single-nucleotide resolution. The editing efficiency, product purity, and off-target effect differ among various BE systems. Herein, we developed CRISPRbase (http://crisprbase.maolab.org), by integrating 1 252 935 records of base editing outcomes in more than 50 cell types from 17 species. CRISPRbase helps to evaluate the putative editing precision of different BE systems by integrating multiple annotations, functional predictions and a blasting system for single-guide RNA sequences. We systematically assessed the editing window, editing efficiency and product purity of various BE systems. Intensive efforts were focused on increasing the editing efficiency and product purity of base editors since the byproduct could be detrimental in certain applications. Remarkably, more than half of cancer-related off-target mutations were non-synonymous and extremely damaging to protein functions in most common tumor types. Luckily, most of these cancer-related mutations were passenger mutations (4840/5703, 84.87%) rather than cancer driver mutations (863/5703, 15.13%), indicating a weak effect of off-target mutations on carcinogenesis. In summary, CRISPRbase is a powerful and convenient tool to study the outcomes of different base editors and help researchers choose appropriate BE designs for functional studies.
COXPRESdb v8: an animal gene coexpression database navigating from a global view to detailed investigations
Authors: Obayashi Takeshi , Kodate Shun , Hibara Himiko , Kagaya Yuki , Kinoshita Kengo
Published: November 2022

Gene coexpression is synchronization of gene expression across many cellular and environmental conditions and is widely used to infer the biological function of genes. Gene coexpression information is complex, comprising a complete graph of all genes in the genome, and requires appropriate visualization and analysis tools. Since its initial release in 2007, the animal gene expression database COXPRESdb (https://coxpresdb.jp) has been continuously improved by adding new gene coexpression data and analysis tools. Here, we report COXPRESdb version 8, which has been enhanced with new features for an overview, summary, and individual examination of coexpression relationships: CoexMap to display coexpression on a genome scale, pathway enrichment analysis to summarize the function of coexpressed genes, and CoexPub to bridges coexpression and existing knowledge. COXPRESdb also facilitates downstream analyses such as interspecies comparisons by integrating RNAseq and microarray coexpression data in a union-type gene coexpression. COXPRESdb strongly support users with the new coexpression data and enhanced functionality.
OrthoDB v11: annotation of orthologs in the widest sampling of organismal diversity
Authors: Kuznetsov Dmitry , Tegenfeldt Fredrik , Manni Mosè , Seppey Mathieu , Berkeley Matthew , Kriventseva Evgenia V , Zdobnov Evgeny M
Published: November 2022

OrthoDB provides evolutionary and functional annotations of genes in a diverse sampling of eukaryotes, prokaryotes, and viruses. Genomics continues to accelerate our exploration of gene diversity and orthology is the most precise way of bridging gene functional knowledge with the rapidly expanding universe of genomic sequences. OrthoDB samples the most diverse organisms with the best quality genomics data to provide the leading coverage of species diversity. This update of the underlying data to over 18 000 prokaryotes and almost 2000 eukaryotes with over 100 million genes propels the coverage to another level. This achievement also demonstrates the scalability of the underlying OrthoLoger software for delineation of orthologs, freely available from https://orthologer.ezlab.org. In addition to the ab-initio computations of gene orthology used for the OrthoDB release, the OrthoLoger software allows mapping of novel gene sets to precomputed orthologs and thereby links to their annotations. The LEMMI-style benchmarking of OrthoLoger ensures its state-of-the-art performance and is available from https://lemortho.ezlab.org. The OrthoDB web interface has been further developed to include a pairwise orthology view from any gene to any other sampled species. OrthoDB-computed evolutionary annotations as well as extensively collated functional annotations can be accessed via REST API or SPARQL/RDF, downloaded or browsed online from https://www.orthodb.org.
Electroconvulsive Therapy
Authors: Fink MD Max
Published: November 2022

Electroshock therapy has long suffered from a controversial and bizarre public image, effectively removing it as a treatment option for many patients. In Electroshock, Max Fink, M.D., draws on 45 years of clinical and research experience to argue that ECT is now a safe, painless, and sometimes life-saving treatment for emotional and mental disorders. Dr. Fink traces the development of ECT from its discovery in 1934 followed by widespread use for two decades, to the 1950s when it was largely replaced by the introduction of psychotropic drugs, to its revival in the past twenty years as a viable treatment. He provides actual case studies of patients who have been treated with ECT and illustrates that many disorders--such as depression, mania, catatonia, and schizophrenia--respond well to it. As he explains the whole procedure from preparation to recovery, we see what the patient experiences. Fink also shows how anesthesia and muscle relaxation have refined ECT, minimizing discomfort and reducing risks to a level far lower than those experienced by patients using psychotropic drugs routinely prescribed for the same problems. Clarifying the many misconceptions surrounding ECT, Electroshock is an excellent sourcebook for patients, their families, and mental health professionals.
Synthetic fertilizers alter floral biophysical cues and bumblebee foraging behavior
Authors: Hunting Ellard R , England Sam J , Koh Kuang , Lawson Dave A , Brun Nadja R , Robert Daniel
Published: November 2022

The use of agrochemicals is increasingly recognized as interfering with pollination services due to its detrimental effects on pollinators. Compared to the relatively well-studied chemical toxicity of agrochemicals, little is known on how they influence various biophysical floral cues that are used by pollinating insects to identify floral rewards. Here, we show that widely used horticultural and agricultural synthetic fertilizers affect bumblebee foraging behavior by altering a complex set of interlinked biophysical properties of the flower. We provide empirical and model-based evidence that synthetic fertilizers recurrently alter the magnitude and dynamics of floral electrical cues, and that similar responses can be observed with the neonicotinoid pesticide imidacloprid. We show that biophysical responses interact in modifying floral electric fields and that such changes reduce bumblebee foraging, reflecting a perturbation in the sensory events experienced by bees during flower visitation. This unveils a previously unappreciated anthropogenic interference elicited by agrochemicals within the electric landscape that is likely relevant for a wide range of chemicals and organisms that rely on naturally occurring electric fields.
The Effect of Reactive Balance Training on Falls in Daily Life: An Updated Systematic Review and Meta-Analysis
Authors: Devasahayam Augustine Joshua , Farwell Kyle , Lim Bohyung , Morton Abigail , Fleming Natalie , Jagroop David , Aryan Raabeae , Saumur Tyler Mitchell , Mansfield Avril
Published: November 2022

Objective

Reactive balance training (RBT) is an emerging approach to reducing falls risk in people with balance impairments. The purpose of this study was to determine the effect of RBT on falls in daily life among individuals at increased risk of falls and to document associated adverse events.

Methods

Databases searched were Ovid MEDLINE (1946 to March 2022), Embase Classic and Embase (1947 to March 2022), Cochrane Central Register of Controlled Trials (2014 to March 2022), and Physiotherapy Evidence Database (PEDro; searched on 22 March 2022). Randomized controlled trials of RBT were included. The literature search was limited to the English language. Records were screened by 2 investigators separately. Outcome measures were number of participants who reported falls after training, number of falls reported after training, and the nature, frequency, and severity of adverse events. Authors of included studies were contacted to obtain additional information.

Results

Twenty-nine trials were included, of which 17 reported falls and 21 monitored adverse events. Participants assigned to RBT groups were less likely to fall compared with control groups (fall risk ratio = 0.76; 95% CI = 0.63–0.92; I2 = 32%) and reported fewer falls than control groups (rate ratio = 0.61; 95% CI = 0.45–0.83; I2 = 81%). Prevalence of adverse events was higher in RBT (29%) compared with control groups (20%).

Conclusion

RBT reduced the likelihood of falls in daily life for older adults and people with balance impairments. More adverse events were reported in RBT than control groups.

Impact

Balance training that evokes balance reactions can reduce falls among people at increased risk of falls. Older adults and individuals with balance problems were less likely to fall in daily life after participating in RBT compared with traditional balance training.

Lay summary

If you are an older adult and/or have balance problems, your physical therapist may prescribe reactive balance training rather than traditional balance training in order to reduce your likelihood of falling in daily life.
A Framework for Understanding the Contribution of Psychosocial Factors in Biopsychosocial Explanatory Models of Persistent Postconcussion Symptoms
Authors: Faulkner Josh W , Snell Deborah L
Published: November 2022

Biopsychosocial models are currently used to explain the development of persistent postconcussion symptoms (PPCS) following concussion. These models support a holistic multidisciplinary management of postconcussion symptoms. One catalyst for the development of these models is the consistently strong evidence pertaining to the role of psychological factors in the development of PPCS. However, when applying biopsychosocial models in clinical practice, understanding and addressing the influence of psychological factors in PPCS can be challenging for clinicians. Accordingly, the objective of this article is to support clinicians in this process. In this Perspective article, we discuss current understandings of the main psychological factors involved in PPCS in adults and summarize these into 5 interrelated tenets: preinjury psychosocial vulnerabilities, psychological distress following concussion, environment and contextual factors, transdiagnostic processes, and the role of learning principles. With these tenets in mind, an explanation of how PPCS develop in one person but not in another is proposed. The application of these tenets in clinical practice is then outlined. Guidance is provided on how these tenets can be used to identify psychosocial risk factors, derive predictions, and mitigate the development of PPCS after concussion from a psychological perspective within biopsychosocial conceptualizations.

Impact

This Perspective helps clinicians apply biopsychosocial explanatory models to the clinical management of concussion, providing summary tenets that can guide hypothesis testing, assessment, and treatment.
Early Rehabilitation Interventions and Physical Therapy in Adults Who Were Critically Ill With COVID-19 Pneumonia: A Retrospective Observational Study
Authors: Pecorelli Nadja , Eggmann Sabrina , Jeitziner Marie-Madlen , Que Yok-Ai , Messmer Anna S
Published: November 2022

Objective

The primary objective of this observational study was to analyze the time to the first edge-of-bed (EOB) mobilization in adults who were critically ill with severe versus non-severe COVID-19 pneumonia. Secondary objectives included the description of early rehabilitation interventions and physical therapy delivery.

Methods

All adults with laboratory-confirmed COVID-19 requiring intensive care unit admission for ≥72 hours were included and divided according to their lowest PaO2/FiO2 ratio into severe (≤100 mmHg) or non-severe (>100 mmHg) COVID-19 pneumonia. Early rehabilitation interventions consisted of in-bed activities, EOB or out-of-bed mobilizations, standing, and walking. The Kaplan–Meier estimate and logistic regression were used to investigate the primary outcome time-to-EOB and factors associated with delayed mobilization.

Results

Among the 168 patients included in the study (mean age = 63 y [SD = 12 y]; Sequential Organ Failure Assessment = 11 [interquartile range = 9–14]), 77 (46%) were classified as non-severe, and 91 (54%) were classified as severe COVID-19 pneumonia. Median time-to-EOB was 3.9 days (95% CI = 2.3–5.5) with significant differences between subgroups (non-severe = 2.5 days [95% CI = 1.8–3.5]; severe = 7.2 days [95% CI = 5.7–8.8]). Extracorporeal membrane oxygenation use and high Sequential Organ Failure Assessment scores (adjusted effect = 13.7 days [95% CI = 10.1–17.4] and 0.3 days [95% CI = 0.1–0.6]) were significantly associated with delayed EOB mobilization. Physical therapy started within a median of 1.0 days (95% CI = 0.9–1.2) without subgroup differences.

Conclusion

This study shows that early rehabilitation and physical therapy within the recommended 72 hours during the COVID-19 pandemic could be maintained regardless of disease severity. In this cohort, the median time-to-EOB was fewer than 4 days, with disease severity and advanced organ support significantly delaying the time-to-EOB.

Impact

Early rehabilitation in the intensive care unit could be sustained in adults who are critically ill with COVID-19 pneumonia and can be implemented with existing protocols. Screening based on the PaO2/FiO2 ratio might reveal patients at risk and increased need for physical therapy.
EFFECT OF PELVIC LEAD SHIELD ON ORGAN DOSES IN POSTERO-ANTERIOR CHEST RADIOGRAPHY
Authors: Kelaranta Anna , Mäkelä Teemu , Hyppänen Teemu , Toroi Paula , Kortesniemi Mika
Published: November 2022

Lead shields are commonly used in X-ray imaging to protect radiosensitive organs and to minimise patient’s radiation dose. However, they might also complicate or interfere with the examination, and even decrease the diagnostic value if they are positioned incorrectly. In this study, the radiation dose effect of waist half-apron lead shield was examined via Monte Carlo simulations of postero-anterior (PA) chest radiography examinations using a female anthropomorphic phantom. Relevant organs for dose determination were lungs, breasts, liver, kidneys and uterus. The organ dose reductions varied depending on shield position and organ but were negligible for properly positioned shields. The shield that had the largest effective dose reduction (9%) was partly positioned inside the field of view, which should not be done in practice. Dose reduction was practically 0% for properly positioned shields. Therefore, the use of lead shield in the pelvic region during chest PA examinations should be discontinued.
O006 Acute effects of combined cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) in insomnia disorder: A randomised, placebo-controlled trial using high-density EEG
Authors: Suraev A , McGregor I , Marshall N , D'Rozario A , Kao C , Gordon C , Grunstein R , Hoyos C
Published: November 2022

Introduction

Medicinal cannabis is often cited as a popular alternative to common sleep aids; however, there are limited studies using complex sleep EEG methods examining its’ effects in insomnia disorder.

Methods

Twenty patients (16 female; median [IQR] age, 47 [13.8] years) with insomnia disorder (mean ISI=20.8) completed two 24-hour in-laboratory visits during which they received a single oral dose of ‘CBD/THC’ containing 200 mg cannabidiol (CBD) and 10 mg delta9-tetrahydrocannabinol (THC) or placebo. Co-primary outcomes were total sleep time (TST) and wake after sleep onset (WASO). Secondary outcomes included next-day neurobehavioural function and sleep microarchitecture metrics determined using overnight polysomnography with 256-channel high-density EEG.

Results

Compared to placebo, CBD/THC significantly decreased TST (-24.5 min, p=0.047) with no significant change to WASO (+10.7 min, p=0.422). CBD/THC significantly decreased time spent in REM sleep (-33.9min, p<0.001) and increased REM sleep latency (+65.6 min, p=0.008). Preliminary high-density EEG analysis revealed increased alpha activity during REM sleep overlying the parietal cortex (p<0.05). CBD/THC did not impair next-day (+12 h post-treatment) cognitive performance, alertness or simulated driving performance (all p’s>0.05). Eighty-five mild, non-serious, adverse events were reported (55 during CBD/THC; most common dry mouth, drowsiness, and fatigue).

Conclusions

An acute dose of 200 mg CBD and 10 mg THC reduced TST and the time spent in REM sleep. Analysis of all high-density EEG outcomes is ongoing. CBD/THC did not affect next-day performance. Further research is required to determine the impact of chronic cannabinoid dosing on REM sleep and other objective sleep outcomes in insomnia disorder.
O007 The impact of physical activity on sleepiness among patients with obstructive sleep apnoea. A study from the Sydney Sleep Biobank
Authors: Callum J , Bin Y , Sarkissian N , Sutherland K , Piper A , Kairaitis K , Wheatley J , de Chazal P , Yee B , Cistulli P
Published: November 2022

BACKGROUND

Sleepiness is the most common symptom of obstructive sleep apnoea (OSA). Despite this the Epworth Sleepiness Score (ESS) has not been shown to predict OSA severity. We present the preliminary results of a cross-sectional analysis in OSA patients to examine the relationship between sleepiness and physical activity.

METHODS

Participants aged >18, with an AHI >5, and no other sleep disorders were included. Sleepiness was defined as an Epworth Sleepiness Score (ESS) of >10. Physical activity was defined as quartiles of Metabolic Equivalent of Task (MET) minutes derived from the International Physical Activity Questionnaire (IPAQ).

PROGRESS TO DATE

593 participants were included (mean age 53.7, SD 14.4 years; 70.7% male; mean BMI 32.7, SD 8.5 kg/m2). 24.3% had ESS>=10 in the lowest quartile of physical activity, 28.2% in the 2nd quartile, 35.3% in the 3rd quartile and 30.2% in those with most activity. Controlling for OSA severity, gender, age or BMI, logistic regression showed increased sleepiness among participants in the 3rd quartile (3,147–6,426 MET-min/week) compared to the 1st quartile (<924 MET-min/week) with an odds ratio of 1.75 (95%CI 1.04–2.97). There was no interaction between OSA severity and physical activity.

INTENDED IMPACT AND OUTCOME

Preliminary results suggest increased sleepiness among participants exerting 3,147–6,426 MET-min/week compared to <924 MET-min/week. Further analysis will consider frequency and type of physical activity (in addition to energy expenditure), additional confounding variables (e.g. sedating medication) and alternate measures of sleepiness (e.g. FOSQ-10).
O008 The effect of flow limited breathing and endotypes on night to night variability of sleep apnoea severity
Authors: Hynes D , Edwards B , Mann D , Landry S , Joosten S , Hamilton G
Published: November 2022

Background

Obstructive sleep apnoea (OSA) is a condition involving repetitive collapse of the upper airway during sleep. The diagnosis and characterisation of OSA is based primarily off the apnoea-hypopnoea index (AHI) in a single-night sleep study. Recent data have demonstrated night to night variability (NNV) in OSA severity. Knowledge of which patients have more variable OSA would improve long-term risk stratification and management. However, patient and polysomnographic characteristics associated with high NNV have not been completely explored. This study aims to determine whether the pattern of flow limited breathing (FLB) and underlying endotypes of patients with OSA are predictive of those with high NNV in OSA severity.

Methods

71 patients with OSA were identified from the placebo arm of randomized controlled trials testing novel OSA interventions. Each patient had undergone two sleep studies. Patient characteristics, medical history and data from both sleep studies were accessed. Sleep data were processed using established algorithms to quantify the degree of FLB as well as OSA endotypes. Differences between each night were analysed for agreement, and for change in the severity of OSA.

Progress to date

Ethics approval has been obtained and data has been processed for statistical analysis.

Intended outcome and impact

It is expected that NNV will be high in those with mild to moderate OSA, and the pattern of FLB and endotypes across multiple nights will help predict those with more variable compared to stable disease.
O012 Cardiovascular risk in a sleep clinic population with Obstructive Sleep Apnoea and association with symptom and polysomnographic profiles
Authors: Kemp E , Sutherland K , Bin Y , Chan A , Dissanayake H , Yee B , Kairaitis K , Wheatley J , De Chazal P , Piper A , Sarkissian N , Cistulli P
Published: November 2022

Background

Recent population level data has identified specific symptom and polysomnographic profiles associated with development of cardiovascular disease (CVD) in obstructive sleep apnoea (OSA). Our aims were to determine whether these profiles were present at diagnosis of OSA in pre-existing CVD and high cardiovascular risk.

Methods

Participants in the Sydney Sleep Biobank (SSB) database, aged 30-74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure). In those without CVD, the Framingham Risk Score (FRS) was calculated to estimate 10-year absolute CVD risk, categorised as “low” (<10%), “intermediate” (10-20%), or “high” (>20%). Groups were compared on symptom and polysomnographic variables.

Progress to Date

629 patients (68% male; mean age 54.3 years (SD 11.6); mean BMI 32.3 (SD 8.2)) were included. CVD was reported in 12.2%. Of the remainder, 27.7% had a low risk FRS, 25.4% had intermediate risk and 34.7% had high risk. Insomnia symptoms of waking too early and difficulty maintaining sleep were more prevalent in the high FRS group (p=0.003 and p=0.05, respectively). CVD and FRS groups differed on multiple polysomnographic variables, however none of these differences remained significant after adjusting for age, sex, and BMI.

Intended Outcome and Impact

CVD and high CVD risk are associated with OSA on insomnia symptoms and multiple polysomnographic variables, however these associations are most likely due to demographic differences. Our research adds to the growing body of evidence elucidating the association between OSA and CVD. Further research is needed to translate to personalised management strategies.
O014 Tolerance of polysomnography in children with neurodisability versus neurotypical peers
Authors: Lanzlinger D , Kevat A , Chawla J
Published: November 2022

Background

Diagnostic polysomnography (PSG) is the gold standard test to evaluate children for sleep-disordered breathing (SDB). Little is known about how well children with neurodisability tolerate the components of PSG compared to neurotypical children.

Methods

We conducted a retrospective cohort study of children >12 months old who underwent diagnostic PSG at our centre from 01/01/2021-30/06/2021, examining how PSG-related monitoring leads were tolerated, based primarily on sleep technician and physician reports. Data extracted included reports of how children tolerated PSG set-up and the individual leads through the night. Children with neurodisability were compared to neurotypical children and sub-analyses were conducted related to particular sub-groups (e.g. Trisomy 21).

Results

132 children with neurodisability and 139 neurotypical children underwent diagnostic PSG. Mean age was 8 years, 50% had a sleep disorder identified on PSG and 39% were female, with no significant differences between the groups. The most-poorly tolerated sensor for all children was the nasal pressure transducer (poorly tolerated in 30%), followed by thermistor (14%) and EEG leads (6%). Children with neurodisability were less likely to tolerate all PSG leads (44% did not tolerate all) compared to neurotypical children (20%) [relative risk 1.8, 95%CI 1.2-1.7, p<0.05]. Children with Trisomy 21 had an increased likelihood of PSG lead intolerance (63%) compared to neurotypical children [relative risk 2.3, 95%CI 1.4-3.8 p<0.05].

Conclusion

This retrospective study demonstrates that children with neurodisability are less likely to tolerate PSG monitoring than neurotypical children and highlights the need to develop alternative measures for evaluation of SDB in this population.
O018 A 10 year follow-up of positive Multiple Sleep Latency Tests in a tertiary centre
Authors: Berenyi F , Kyoong A
Published: November 2022

Background

There are limited robust population prevalence data and the natural history of central hypersomnolence disorders in Australia. We conducted a retrospective chart review of multiple sleep latency tests (MSLTs) conducted in an Australian Sleep unit and reviewed clinical outcomes over time, response to treatment and duration of follow-up.

Methods

517 MSLTs were extracted from a metropolitan hospital’s database between 2011 and 2021; 215 were positive. Data were extracted from overnight polysomnography (PSG), MSLTs and electronic medical records. The results were analysed using t-test and linear regression models.

Results

The mean age was 36.7 years and 58% were female. 37 patients met the criteria for type 1 or 2 narcolepsy, 157 for idiopathic hypersomnolence and 21 for an alternative sleep disorder. Of those with narcolepsy, 84.6% were commenced on medication. Modafinil was the most commonly prescribed first line medication.

At 1 year, 48% of patients in the narcolepsy group had complete or partial treatment success, compared with 24% in the idiopathic hypersomnolence group. At 3 years, 31% of narcolepsy patients and 12% of idiopathic hypersomnolence patients reported complete or partial treatment success. At 5 years, only 19% of narcolepsy patients and 6% of idiopathic hypersomnolence patients described ongoing treatment success.

Discussion

This study demonstrated a much higher prevalence of idiopathic hypersomnolence than expected. A significant number of patients were lost to follow-up, predominantly in the first 12 months, with progressive losses over the subsequent years. The reasons for these are unclear; however, would be important to explore in future studies.
O019 The Association between Later Circadian Timing and Higher Depressive Symptoms in Early Adolescence is Ameliorated by Longer Sleep Duration
Authors: Chachos E , Lu S , Hand A , Carskadon M , Klerman E , Lockley S , Wiley J , Phillips A , Rajaratnam S , Bei B , Stone J
Published: November 2022

Background

Circadian phase and sleep-wake timing delays are hallmark adolescent development features. These delays contribute to shorter sleep duration in combination with early school schedules. Both delayed circadian phase and insufficient sleep are associated with increased prevalence/severity of mood problems. This study examined associations between circadian phase, sleep duration, and mood in early adolescence.

Methods

157 Year 7 Australian students (M±SD=12.81±0.40 years, 56.7% female) wore actiwatches and completed sleep diaries for two weeks in school term. Circadian phase was measured via salivary dim light melatonin onset (DLMO) on the final Friday of sleep monitoring. PROMIS Paediatric Depression and Anxiety measured depression/anxiety symptom severity. Sleep duration/efficiency were calculated using actigraphy and self-reports. Multiple linear regression quantified the relationships between sleep duration and efficiency and circadian phase and mood (depression/anxiety) associations, adjusting for sex.

Results

DLMO occurred at the expected time for early adolescents [continuous decimal time; M±SD=20.52±1.20; range:17.52-24.03]. Sleep duration (p=.03), but not sleep efficiency (p=.89), moderated associations between DLMO and depression (but not anxiety; p-values>.08). Simple slope analyses showed that in individuals with shorter average sleep duration, a one-hour circadian phase delay was associated with 1.84 t-score increase in depressive symptom severity (p=.03). These associations were non-significant in individuals with longer average sleep duration (p=.44).

Conclusion

Although delayed circadian phase is a developmental norm, its association with increased depressive symptom severity was ameliorated in young adolescents who obtained longer sleep duration. Addressing sleep duration, a modifiable protective factor (e.g., by delaying school start times), may yield mood-related benefits for adolescents.
O020 Sleep regularity is a stronger predictor of all-cause mortality than sleep duration or sleep efficiency in ~60 000 UK Biobank participants
Authors: Windred D , Burns A , Lane J , Phillips A , Cain S
Published: November 2022

Sleep duration and sleep efficiency are observed risk factors for all-cause mortality, but the role of sleep regularity is unknown. Irregular sleep patterns are associated with ageing, cancer, depressed mood, and cardio-metabolic diseases, and may therefore increase risk of mortality. We extracted Sleep Regularity Index (SRI) scores, sleep duration, and sleep efficiency from one week of actigraphy in 60,997 UK Biobank participants (62.8±7.8 years, 55.6% female). Using Cox Proportional Hazards models, we assessed whether SRI, sleep duration, and sleep efficiency predicted all-cause mortality up to 7.6 years post-actigraphy. A one standard deviation increase in SRI score (+10.7), indicating more regular sleep patterns, predicted a 20.4±2.0% reduced hazard of all-cause mortality (p < .0001). This relationship remained robust after controlling for age, sex, ethnicity, education, income, and employment status (+1SD in SRI predicted an 18.7±2.4% hazard reduction, p < .0001). SRI was a relatively stronger predictor of mortality hazard than sleep duration (explaining 19.0±2.1% vs. 12.4±2.6% of hazard reduction) or sleep efficiency (19.0±2.1% vs. 13.1±2.6%) in two additional Cox models. Sleep regularity may play a causal role in mortality, via contribution to poor health outcomes, or it may be a marker of poor health leading to mortality. These findings suggest that sleep regularity should be monitored and/or adjusted alongside traditional sleep metrics for optimal health and longevity.
O021 Investigation of a novel LED lighting strategy designed to accelerate circadian entrainment to night shift-work in an encapsulated environment
Authors: Guyett A , Scott H , Lechat B , Manners J , Stuart N , Lack L , Kemps E , Eckert D , Micic G , Banks S , Dorrian J , Adams R , Catcheside P , Lovato N
Published: November 2022

Introduction

Shift-work results in misalignment between circadian timing and the sleep/wake schedule, negatively impacting sleep and performance. In encapsulated environments (e.g., submarines), the lack of strong daily lighting cues impairs circadian entrainment. This study tested whether circadian-informed LED lighting promotes greater circadian phase delays to adjust to night shift-work compared to standard lighting.

Method

To date, 11 healthy sleepers (7 males, mean±SD age27.6±8.5 y, N=24 anticipated) have completed two separate 8-day experimental conditions (circadian-informed lighting versus standard lighting). After a baseline sleep from 22:00 – 07:00 (day 1) and salivary dim light melatonin onset ([DLMO], day 2), participants undertook simulated night shift-work (00:00 - 08:00) and slept during the daytime (10:00 - 19:00) for days 3-7 followed by a post-DLMO assessment on day 8. Ingestible capsules collected core body temperature (CBT) continuously throughout days 2-8. The standard lighting condition mimicked current lighting on submarines (largely dim, blue-depleted light), while the circadian-informed lighting administered bright, blue-enriched and dim, blue-depleted lighting at times estimated to facilitate rapid circadian delay. Cosine curve fitting was applied to the CBT data to estimate temperature minima (CBTmin) and determine phase delay magnitude for comparison across conditions.

Results

There was a significant day-by-condition interaction on CBTmin (F4, 88=2.82, p=0.030). By day 6, the CBTmin delay was (mean±SD) 3.2±.97 hours greater in the circadian-informed lighting versus standard lighting, p=0.001.

Conclusions

These preliminary analyses support that circadian-informed lighting accelerates circadian re-adjustment to night shift-work. Such interventions could improve sleep, performance, and safety in shift-workers who work in encapsulated environments.
O024 Modifying light environments according to individual circadian light sensitivity
Authors: Stone J , Cain S , Phillips A
Published: November 2022

Introduction

Large inter-individual differences exist in how sensitive the circadian system is to light. Circadian light sensitivity can be affected by medications, such as antidepressants, and varies as a function of age and some mood disorders. Using a computational model, we investigated how differences in an individual’s light sensitivity can be offset by changes in their light environment to maintain stable circadian timing.

Methods

A previously validated computational model was used to simulate sleep and circadian timing under realistic assumptions about light and sleep schedules in day workers across two weeks. The model predicted circadian phase (dim light melatonin onset) and sleep onset/offset times for each day. Simulations were repeated varying two parameters: (i) light sensitivity, representing changes in the dose-response curve to light, and (ii) evening illuminance, representing home lighting levels after sunset.

Results

Higher light sensitivity and higher evening illuminance levels resulted in systematically later predicted sleep and circadian timing. The effects of increasing light sensitivity could be offset by reducing the level of evening illuminance, with this relationship holding over a wide range of light sensitivity values. Low light sensitivity combined with high evening illuminance produced a non-entrained (non-24) phenotype; decreasing evening illuminance from this state resulted in stable entrainment.

Discussion

We are only beginning to understand the influence of medications and health conditions on circadian light sensitivity. Our results show how modifications to evening light levels can be used to offset impacts of variable light sensitivity on sleep and circadian timing.
O029 Sleep architecture differs for individuals manifesting excessive daytime sleepiness with and without obstructive sleep apnea
Authors: Chen X , Korkalainen H , Kainulainen S , Leppänen T , Oksenberg A , Töyräs J , Terrill P
Published: November 2022

Introduction

The mechanism underlying the development of excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) remains unclear. Thus, we characterised the association between sleep architecture and EDS in individuals with and without OSA.

Methods

1876 suspected OSA patients reporting daytime sleepiness underwent in-lab polysomnography and next-day multiple sleep latency test (MSLT). We investigated sleep architecture characteristics in OSA (apnea-hypopnea index [AHI]≥5, n=1508) and non-OSA (AHI<5, n=368) patients with and without EDS (MSLT≤10-minutes and MSLT>10-minutes). Sleep architecture was quantified by N1, N2, N3, REM, total sleep time (TST), and wake after sleep onset (WASO).

Results

OSA patients with EDS had less N1 (median: 10.0 vs 12.0-minutes, p<0.05) and N3 (60.2 vs 71.5-minutes, p<0.05) sleep, less WASO (43.0 vs 51.0-minutes, p<0.05), more N2 (210.5 vs 189.0-minutes, p<0.05) sleep, and higher TST (365.0 vs 351.5-minutes, p<0.05) than non-EDS patients. No difference was observed in the amount of REM (70.0 vs 67.5-minutes, p=0.46) sleep.

Non-OSA patients with EDS had less WASO (31.5 vs 40.0-minutes, p<0.05), more N2 (188.5 vs 177.5-minutes, p<0.05) sleep, and higher TST (374.5 vs 359.0-minutes, p<0.05) and the amount of REM sleep (76.5 vs 68.5-minutes, p<0.05) than non-EDS patients.

Discussion

While EDS was associated with less WASO and greater TST and N2 in both OSA and non-OSA groups, there was also characteristic differences. Non-OSA patients with EDS have greater REM sleep duration, while OSA patients with EDS have less N3 sleep. There is likely a complex bi-directional relationship between sleep architecture and EDS reflecting acute/chronic sleep disruption and compensatory mechanisms.
O034 Autonomic control of heart rate stabilises with improvement of sleep disordered breathing in children with Down syndrome
Authors: Walter L , Varkey J , Gu C , Bassam A , Davey M , Nixon G , Horne R
Published: November 2022

Background

Sleep disordered breathing (SDB) alters autonomic function, assessed using heart rate variability (HRV) in typically developing (TD) and children with Down syndrome (DS). SDB resolution in TD children normalises HRV, but the effects in children with DS are unknown. We compared HRV in children with DS with improved SDB (decrease in obstructive apnoea hypopnoea index (OAHI) to ≤ 50% of baseline OAHI) to those with unimproved SDB 2 y following baseline study.

Methods

24 children (3-19 y at baseline) were included. Power spectral analysis of the ECG determined low frequency (LF, parasympathetic and sympathetic activity), high frequency (HF, parasympathetic activity) power and LF/HF (sympathovagal balance). Children were grouped into Improved (n=12; 7 treated between studies) and Unimproved (n=12; 2 treated between studies).

Results

OAHI decreased between studies in the Improved group (baseline, 29.5 (1.6,154.0) [mean (min,max)] events/h; follow-up, 8.4 (0,77.0); p<0.05), and worsened in the Unimproved group (baseline 6.1 (0,22.9); follow-up 14.4 (0.3, 54.6); p<0.05). LF power was lower at follow-up in the Unimproved group compared to baseline during Total Sleep (p<0.05), N3 (p<0.05) and REM (p<0.01). HF power was also lower at follow-up in the Unimproved group during REM (p<0.05). HRV remained unchanged between baseline and follow-up for the Improved group.

Conclusion

Autonomic control worsened as indicated by lower sympathetic and parasympathetic activity in children whose SDB was not improved. In contrast, in those children with improved SDB autonomic control remained the same, suggesting improvement in SDB severity prevents further worsening of autonomic control in children with DS.
O051 Insomnia predicts persistent symptoms of anxiety and depression during the COVID-19 pandemic: A 12-month longitudinal cohort study
Authors: Saunders W , Meaklim H , Byrne M , Junge M , Varma P , Finck W , Jackson M
Published: November 2022

Introduction

Insomnia increases risk of affective disorders. This study assessed whether individuals with insomnia symptoms at the beginning of the pandemic, either new-onset or pre-existing, were at increased vulnerability to anxiety and depressive symptoms longitudinally compared to those who continued sleeping normally. Sleep-related factors (e.g., pre-sleep arousal) were also examined for their influence on risk of clinically significant anxiety and depression.

Method

Between April 2020 and May 2021, 2069 participants (M=46.16 years, SD=13.42; 75.3% female) with new-onset, pre-existing, or no insomnia symptoms responded to a global online survey with 3-, 6-, and 12-month follow-ups. Data were analysed using mixed-effects and logistic regression models.

Results

New-onset and pre-existing insomnia were stronger predictors of anxiety and depressive symptoms over time (p’s <.001) than other established risk factors such as, age, sex, and past psychiatric diagnoses. Although depressive symptoms in both insomnia groups declined from acutely elevated baseline levels, they remained clinically significant at the majority of timepoints whereas normal sleepers remained below threshold. Pre-sleep arousal was identified as a risk factor for clinically significant symptoms of anxiety (OR=1.05) and depression (OR=1.09) at 12-months. Sleep effort predicted anxiety (OR=1.06), whereas dysfunctional sleep-related attitudes and beliefs contributed to clinically significant depression (OR=1.22).

Discussion

Insomnia and associated sleep-related factors are key modifiable risks for persistent symptoms of anxiety and depression. This study highlights sleep as an opportunity for intervention into the enduring mental health ramifications of the COVID-19 pandemic and underlines the need to integrate insomnia treatment into routine mental health care.