bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil-derived apoptotic body membranes-fused exosomes targeting treatment for myocardial infarction
Authors: Wang Jingjing , Li Jingjing , Su Gang , Zhang Youbin , Wang Zhu , Jia Yujuan , Yu Qian , Shen Zhenya , Zhang Yanxia , Yu Yunsheng 
Published: December 2024

Abstract
Myocardial infarction (MI) poses a substantial threat to human health, prompting extensive research into effective treatment modalities. Preclinical studies have demonstrated the therapeutic potential of mesenchymal stem cell-derived exosomes for cardiac repair. Despite their promise, the inherent limitations of natural exosomes, mainly their restricted targeting capabilities, present formidable barriers to clinical transformation. To address this, it is proposed to enhance their targeting specificity and retention in infarcted myocardium by fusing exosomes with neutrophil-derived apoptotic body membranes (NAM). These NAM inherit the surface signals from neutrophils, which allow them to home in on the damaged tissues and participate in regulating inflammatory responses. In this current work, we utilized a membrane fusion technique to create NAM-fused exosomes (NAM-Exo) for MI treatment. Compared to their native counterparts, NAM-Exo demonstrated enhanced adhesion to inflammatory endothelial cells, replicating the neutrophil recruitment mechanism at sites of myocardial injury in MI. Furthermore, our findings revealed that NAM-Exo not only significantly modulated inflammation responses but also promoted angiogenesis in a mouse model of MI, ultimately leading to improved cardiac function and ventricular remodeling post-treatment. These results underscore the potential of membrane fusion as an effective strategy to enhance the therapeutic efficacy of exosome-based cardiac repair and regeneration therapies, thereby paving the way for their translation into clinical practice.
Elevated Fcy receptor expression augments pro-inflammatory macrophage phagocytosis in systemic sclerosis and associated rheumatic diseases
Authors: Hukara Amela , Bonazza Gino A , Tabib Tracy , Micheroli Raphael , Jordan Suzana , Bürki Kristina , Rudnik Michal , Ciurea Adrian , Distler Oliver , Lafyatis Robert , Błyszczuk Przemysław , Kania Gabriela 
Published: December 2024

Abstract

Objectives
To investigate the pro-phagocytic phenotype of macrophages in SSc and other rheumatic diseases by examining their activation, signalling pathways and treatment responses, with the goal of uncovering mechanisms that drive enhanced phagocytosis.

Methods
Single-cell RNA sequencing (scRNA-seq) datasets (GSE138669/GSE212109) from skin and lung macrophages of healthy controls (HC) and SSc patients were analysed. Human monocyte-derived macrophages (hMDMs) were differentiated from CD14+ monocytes from HC, SSc, RA, PsA, and axSpA patients. In selected experiments, hMDMs were pretreated with 0.1 μM nintedanib. Phagocytic activity was quantified using pHrodo bioparticles and flow cytometry. Macrophage surface markers were evaluated by flow cytometry, NF-κB signalling by Western blot and gene expression by RT-qPCR.

Results
Analysis of scRNA-seq datasets revealed a pro-phagocytic signature in SSc-affected organs. SSc macrophages, particularly the FCGR3Ahi cluster in skin, exhibited elevated expression of FCGR genes and enriched FcγR-mediated phagocytosis pathways, accompanied by pro-inflammatory markers. This phenotype extended to FCN1hi lung macrophages in SSc patients with interstitial lung disease, indicating a systemic pro-inflammatory and phagocytic profile. hMDMs from SSc, RA and PsA patients demonstrated enhanced phagocytic activity in vitro. Elevated FcγRI and FcγRII levels were identified as key drivers of increased phagocytic activity and subsequent IL-6-driven inflammation. Nintedanib showed reduction in FcγRI expression, suggesting its potential therapeutic benefit in attenuating the phagocytic process.

Conclusion
This study highlights FcγR-expressing macrophages as drivers of phagocytosis and inflammatory responses in SSc. Dysregulated activation of these macrophages could lead to persistent inflammation and fibrosis in rheumatic diseases, highlighting new potential therapeutic approaches.
The evolution of Industry 4.0 capacities across regions in EU research programmes
Authors: Ciffolilli Andrea , Lopolito Antonio , Muscio Alessandro , Reid Alasdair 
Published: December 2024

Abstract
European policy supports cutting-edge research on Industry 4.0, aiming to promote excellence and ensure a balanced distribution of regional Industry 4.0 capacities. We analyse Industry 4.0 research projects financed by the European Union’s framework programmes over a 14-year period, investigating whether less developed regions benefit from interaction with more advanced regions that have a stronger capacity to diversify their Industry 4.0 technologies. We find a strong path-dependency in technological diversification between programming periods. Moreover, while national Industry 4.0 programmes negatively affect the capacity of regions to diversify technologies, possibly generating a substitution effect, we find that regional networking does not support less diversified regions in mastering multiple technologies.
Pupillometric and perceptual approaches provide independent estimates of melanopsin activity in humans
Authors: Woelders Tom , Didikoglu Altug , Bickerstaff Lucien , Brown Timothy M , Lucas Robert J 
Published: December 2024

Abstract

Study Objectives
Melanopsin-expressing retinal ganglion cells, which provide light information to time sleep and entrain circadian clocks, also influence perceived brightness raising the possibility that psychophysical paradigms could be used to explore the origins and implications of variability in melanopic sensitivity. We aimed to develop accessible psychophysical tests of melanopic vision and relate outcomes with a pupillometric measure of melanopsin function (post-illumination pupil response) and prior light exposure.

Methods
Individually calibrated pairs of isoluminant stimuli differing in melanopic radiance from a four primary source were presented sequentially with superimposed random color offsets in a two alternative forced choice brightness preference paradigm to 41 naïve adult participants with personal light exposure data for the prior 7 days and post-illumination pupil response measures defined by comparing maintained pupil constriction for luminance matched “red” vs “blue” pulses.

Results
Across participants we observed the expected tendency to report positive melanopsin contrast stimuli as “brighter” (one-tailed t-test p &lt; 0.001), but with substantial inter-individual variability in both sensitivity (melanopsin contrast at criterion preference p = 0.75) and amplitude (preference at maximum melanopic contrast). There was little correlation between these psychophysical outcomes and post-illumination pupil response magnitude, or between either psychophysical or post-illumination pupil response measures and light history metrics (pairwise Pearson correlation coefficients -0.5&gt; &lt; 0.5). Random forest machine learning failed to satisfactorily predict outcome for either psychophysical or post-illumination pupil response measures based upon these inputs.

Conclusions
Our findings reveal that estimates of melanopic function provided by perceptual and pupillometric paradigms can be largely independent of one another and of recent history of light exposure.
O005 Age related changes in sleep quantitative EEG and longitudinal relationship to cognitive function
Authors: Stumbles E , Appleton S , Adams R , Yee B , Parker J , Vakulin A , Wittert G , Marshall N , D’Rozario A 
Published: December 2024

Abstract

Objectives
Altered sleep microarchitecture including sleep spindles and decline in cognitive function occurs with advancing age. However, the longitudinal relationship between changes in sleep neurophysiology and cognition in middle-to-late life is currently unclear. This study examined sleep micro-architecture measured by electroencephalography (EEG) and cognitive performance in middle-aged and older men over a 10-year period.

Methods
156 participants from the Florey Adelaide Male Ageing Study who reported no previous obstructive sleep apnoea diagnosis underwent home-based polysomnography and cognitive testing including mini mental state examination (MMSE) and trail-making tests A (visual attention) and B (executive function) at baseline (2010-2011) and follow up (2019-2020). Power spectral analysis of single-channel EEG (F4-M1) recordings at follow up (n=142) was performed. Baseline and follow-up sleep parameters including spindle metrics, and cognition were compared using paired t-tests, and associations examined with Pearson’s correlations.

Results
NREM (267.6 vs 299.2 minutes) and REM (57.0 vs 77.7 minutes) sleep was higher during follow up compared to baseline (p &lt;0.001). NREM sleep spindle events (257.5 vs 351.7) and spindle density (0.95 to 1.17 events/minute) was higher at follow-up (p &lt;0.001). Performance on the TMT was worse (TMT-A: 15.4 vs. 38.7 seconds, TMT-B: 74.9 vs. 93.7 seconds, p &lt;.001), indicating cognitive decline in these domains. There was no change in MMSE. The change in sleep spindles and cognition were not correlated.

Conclusions
In this community-dwelling cohort of men, no longitudinal relationship between sleep spindles and cognitive function was observed. The unexpected increase in spindle activity across the 10-year follow-up warrants further exploration.
O007 Menstrual cycle phase classification methods and the relationship with sleep, mood, and performance in elite female athletes
Authors: Mascaro L , Leota J , Sammak S , Rajaratnam S , Drummond S , Facer-Childs E 
Published: December 2024

Abstract

Introduction
Female athletes are often excluded from sports-science research due to hormonal variations across the menstrual cycle. Effects of menstrual cycle phase on outcomes are inconclusive likely due to between-study variation in phase classification. We aimed to test if the relationship between menstrual cycle phase and sleep, mood, and performance differed depending on whether a continuous, 2-phase, 3-phase, or 4-phase approach was used to classify cycle phase.

Methods
Elite Australian Rules footballers reporting a regular menstrual cycle and not on contraception (N=18, M-age=24.9±5.1) were recruited. Over two weeks, they completed continuous sleep/wake monitoring via actigraphy and sleep diaries, daily self-reported sleep quality, mood, and performance ratings, and five sessions of cognitive (vigilant attention) and physical (ecological kicking task) performance testing. Using baseline self-report data, menstrual cycle phase for each day of the study was inferred using a continuous (percentage through the cycle), 2-phase (follicular, luteal), 3-phase (menses, mid-late follicular, luteal), and 4-phase (menses, mid-late follicular, early-mid luteal, pre-menses) model.

Results
No outcome was consistently predicted by all phase-models. Objective sleep efficiency was lower in menses according to the 3- and 4-phase models. Subjective mood and performance were higher in the mid-late follicular according to the 3-phase model.

Discussion
The relationships between menstrual cycle phase and sleep, mood, and performance depend on how menstrual cycle phases are classified. Discordant findings highlight the importance of methodological differences in athlete menstrual cycle research. The effects of the menstrual cycle phase need to be further studied using consistent and standardised classifications across studies.
O011 Loss of sleep due to high ambient temperatures and its impact on healthy life years: Implications for global warming
Authors: Lechat B , Toson B , Scott H , Nguyen D , Kaambwa B , Escourrou P , Catcheside P , Eckert D 
Published: December 2024

Abstract

Introduction
The summer of 2023 in the northern hemisphere saw the highest global temperatures in over 2000 years. This study uses big data from an under-mattress sensor and global ambient temperature records to estimate the impact of high temperatures on poor sleep and associated wellbeing costs.

Methods
Data were from 219,808 consumers who used an under-mattress sensor (Withings Sleep Analyzer; 89,219) or a smartwatch (Withings ScanWatch; 130,589) regularly between January 2020 and September 2023. Generalized non-linear mixed effect models tested the effects of 24h average ambient temperature on sleep duration and poor sleep (&lt;6h) adjusting for potential confounders. Health economics models quantified wellbeing cost due to sleep loss from high temperatures.

Results
Extreme temperatures were associated with a ~30 to 300% increase in the prevalence of poor sleep and a 10-40 min average sleep duration loss compared to median temperatures, depending on the country, and this effect was stronger in older participants. The global burden (35 locations; 3.5 billion total population) associated with sleep loss due to higher than historical average temperatures in 2023 was ~2.2 million disability adjusted life years, including 82,000 years of life lost, which was 2.5-fold higher compared to 2000.

Conclusions
High ambient temperatures are associated with reduced sleep duration and a marked increase in poor sleep prevalence. Wellbeing cost associated with sleep loss due to high temperatures is substantial – equivalent to medical conditions such as bipolar disorders, chronic kidney diseases, and alcohol use disorders.
O015 Autonomic Activations in Sleep: Tachycardic responses to nocturnal swallows and arousals in people with OSA
Authors: Lung K , Bilston L , Burke P 
Published: December 2024

Abstract

Introduction
Nocturnal swallowing and cortical arousals from sleep both produce rapid transient heartrate increases driven by autonomic activation. Obstructive Sleep Apnoea (OSA) is associated with autonomic dysfunction and cardiovascular diseases, however, the underpinning mechanisms remain unclear. Here, we examine autonomic activation associated with swallowing and arousals during sleep in OSA.

Methods
Overnight sleep with epiglottic pressure data from a previous study were analyzed using custom semi-automated analysis scripts to extract variables for swallows and arousals during sleep. The following variables were extracted: average heartrate 30 seconds prior to a swallow or arousal and, peak heartrate 10 seconds afterwards, plus data on associated arousals and arousal duration, respiratory events preceding the swallow(s).

Results
53 datasets were analyzed, including 6 controls, 12 mild, 17 moderate and 18 severe OSA subjects, in total: 2794 swallows and 9147 arousals.
Across all samples, heartrate elevation was greater when swallows occurred in close succession (21.4bpm vs 14.7bpm, p&lt;0.0001). Arousals with swallows produced larger heartrate elevations (17.0bpm vs 10.7bpm, p&lt;0.0001) and prolonged duration by 6 seconds compared to arousals without swallows. Arousals during Rapid Eye Movement (REM) sleep also produced a higher heartrate increase (16.4bpm vs 12bpm, p&lt;0.0001). Notably, the severe OSA group exhibited reduced magnitude of swallow and arousal heartrate increases (18.4bpm vs 22.3bpm and 11.9bpm vs 12.9bpm, p&lt;0.0001).

Discussion
Individuals with severe OSA exhibited diminished magnitude of heartrate elevation responses to swallows and arousals. This finding potentially advances our comprehension of the underlying mechanisms of OSA with association with cardiovascular diseases.
O020 A novel method to demask non-circadian effects on core body temperature to enhance daily circadian timing and amplitude estimation
Authors: Nguyen P , Dunbar C , Scott H , Lechat B , Manners J , Micic G , Lovato N , Reynolds A , Lack L , Adams R , Eckert D , Vakulin A , Catcheside P 
Published: December 2024

Abstract

Introduction
Circadian disruption contributes to adverse effects on sleep, performance and health. One of the most practical methods to track continuous daily changes in circadian timing is to measure core body temperature (CBT) to identify the CBT minimum time (Tmin), usually via cosine-model fits to measured data in controlled studies. However, this method ignores large effects of activity, sleep and wake on CBT that confound and mask the circadian component of primary interest. This study introduces a novel physiology-grounded analytic approach to separate circadian from non-circadian effects on CBT.

Methods
The dataset comprised 33 healthy participants (mean±SD 32±13 years old) attending a 39-hour in-laboratory study with an initial overnight sleep followed by extended wake. CBT data were collected at 30-second intervals via ingestible capsules. A physiology-guided generalized additive model was constructed to model the combined circadian and non-circadian effects of sleep, wake, and activity on CBT. Model fits and estimated Tmin inferred from extended wake without sleep were compared with traditional cosine-based models fits.

Results
Compared to the traditional cosine model, the new model exhibited superior fits to CBT (Pearson R 0.90 [95%CI; [0.83,0.96] versus 0.81 [0.55-0.93]) and better estimation of Tmin (difference of 0.2 [-0.5,0.3] hours versus 1.4 [1.1 to 1.7] hours).

Conclusions
This new method provides superior demasking of non-circadian influences compared to traditional cosine fits, including the removal of a sleep related bias towards an earlier estimate of the circadian component of Tmin.
O021 Distinguishing Circadian from Sleep Effects on Cognitive Performance During a Simulated Night Work Lighting Intervention
Authors: Guyett A , Lovato N , Manner J , Stuart N , Toson B , Nguyen D , Scott H , Catcheside P 
Published: December 2024

Abstract

Introduction
We previously found that a circadian-informed lighting intervention accelerated circadian retiming, improved cognitive performance and sleep during 4-days of simulated nightwork. This study explores the independent and combined effects of circadian retiming and sleep duration on cognitive performance improvements with circadian-informed lighting.

Methods
Data were from 19 healthy sleepers (12 male; mean±SD aged 29 ±10 y) underwent two 8-day in-lab protocols with circadian and control lighting. On days 3-7, participants transitioned to day sleeps (10:00–19:00) and underwent cognitive tests simulating nightwork (00:00–08:00). Cognitive performance was measured by psychomotor vigilance task (PVT) lapses. Polysomnography measured total sleep time (TST) during each sleep. Core body temperature minimum (Tmin) was estimated via ingestible capsules. Multilevel generalized structural equation modelling tested the mediation effect of TST on the relationship between Tmin and PVT lapses, and the moderating effect of lighting intervention on all three pathways.

Results
For both mediating pathways between Tmin and TST, TST and PVT are not moderated by lighting intervention (B = 16.81, SE = 8.99, p =.062 and B = 0.00, SE = 0.97, p =.332 respectively) so we can conclude there is no moderated mediation effect. There was a moderated direct effect of lighting intervention on Tmin time and worse PVT time (B = -0.64, SE = -3.74, p&lt;.001).

Discussion
While homeostatic and circadian processes impact sleep and cognitive performance, PVT performance improvements from circadian-informed lighting appear to be dominated by circadian retiming effects rather than longer sleep under night shift work conditions.
O025 Impact of Temporal Rhythms on Blood Pressure Variability: Daily, Weekly, and Seasonal Effects
Authors: Manners J , Scott H , Lechat B , Pinilla L , Perlis M , Adams R , Escourrou P , Eckert D 
Published: December 2024

Abstract

Introduction
High blood pressure (BP) and BP variability are associated with increased risk of cardiovascular events and mortality. Despite known impacts of daily, weekly, and seasonal fluctuations on BP and BP variability, the independent temporal impacts are not well quantified, particularly in sleep research.

Methods
Participants comprised users of the Withings Sleep Analyzer and home blood pressure monitors, with ≥6 months of measurements, ≥3 times/week and at 3 unique hours of the day. Mixed models tested non-linear associations between mean-arterial pressure (MAP) and hour of the day, day of the week, and hemisphere-adjusted month of the year, adjusting for wake time, sleep duration, apnea-hypopnea index, age, and sex.

Results
Results included 40,332 participants (mean±SD 59±12 years old, 87/13% male/female) with 9.5 million BP measurements (median[IQR]=97[43,245] measurements per participant). MAP was independently associated with time since wake (range=1.14mmHg), peaking at wake and declining over the day, and the hour of the day (range=2.36mmHg), typically peaking at 6AM. Significant weekday (range=0.96mmHg) and monthly variability (range=2.14mmHg) resulted in the highest MAP on Monday, in winter months. The greatest variation, Monday morning in winter vs Friday evening in summer, accounted for a 6.69±0.08mmHg difference in MAP.

Conclusion
Measured BP varied considerably by time of day, day of week, and season, independently from sleep duration and timing. The significant variability imposed by these rhythms has important clinical implications. Without accounting for this temporal aspect, measurements of BP changes due to external factors like sleep disorders or treatment interventions could yield misleading or incorrect associations.
O026 Within-subject variation in circadian timing in shift workers repeating the same shift patternn
Authors: Ji Y , Shen L , Postnova S , Knock S , Zhong Y , Howard M , Stone J , Facer-Childs E , Rajaratnam S , Sletten T 
Published: December 2024

Abstract

Introduction
While inter-individual variation in circadian response to shift work has been demonstrated, the within-individual variation across repeated roster patterns is unknown. This study aims to examine the consistency in circadian timing during repeated occasions of the same shift pattern.

Methods
In an ongoing study, shift workers (n=24, age 36.79±8.83 years, 8 females) from multiple industries were monitored during two replications of their usual shift patterns, separated by at least 6 weeks. Shifts included consecutive night shifts, consecutive early morning shifts, and early-morning-to-night rotations. Participants completed daily sleep diaries and wore an activity monitor to measure sleep, and a light sensor to measure light exposure. Circadian phase was assessed at the end of each shift pattern via 6-sulphatoxymelatonin (aMT6s) acrophase (peak) in urine.

Results
Preliminary analyses (n=15) showed considerable within-subject variability in aMT6s acrophase at the end of each shift patterns. Mean difference in acrophase was 2.06±1.36 h (range 0.15-5.22 h). Individuals working consecutive night shifts demonstrate larger variation in acrophase (3.43±1.58 h; range 1.50-5.22 h), compared to those working consecutive morning (2.01±0.69 h, range 1.18-2.86 h) or early morning-to-night shifts (1.30±0.95 h, range 0.15-2.95 h). The mediating role of individual light exposure patterns in the variation in aMT6s acrophase will be presented.

Discussion
Preliminary findings highlight inconsistency in circadian phase within individual shift workers, possibly associated with variation in socially-driven behaviours. Further factors influencing variability in circadian timing, i.e., individual light exposure, will be examined, to support prediction of circadian timing for informing personalised interventions for shift workers.