bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice
Authors: Li Jin , Wang Zhiqiang , Zhong Haijun , He Yifu , Zhang Chen , Niu Zuoxing , Yang Shujun , Zhang Tao , Zhu Liangjun , Shu Yongqian , Gao Yong , Peng Jianjun , Song Yan , Li Jian , Yuan Ying , Zhang Haibo , Yu Gengsheng , Hua Yunqi , Xiao Jianjun , Fu Jianfei , Zheng Yulong , Xue Hua , Luo Xian , Shi Ming , Su Weiguo , Qin Shukui
Published: April 2024

Introduction

Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors.

Methods

Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians’ discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose).

Results

Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities.

Conclusions

The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.
What if your paper were retracted for no credible reason?
Authors: Srholec Martin
Published: April 2024

Retractions are meant to protect the integrity of the published record against erroneous content, but retraction procedures are not infallible. This paper identifies imperfections in the regulatory framework of retractions, draws conceptual lessons from them, and derives recommendations to improve the handling of disputed retractions to better suit the needs of all stakeholders. The imperfections are illustrated by a retraction, which its authors and prominent members of the research community appealed at various levels to no avail. None of the relevant authorities in the system of retractions acknowledged any problems, although the retraction suffers from a number of flaws, both procedural and on merit. This paper concludes with reflections on how to revamp the framework for retractions in scientific journals.
Predictors of Long-Acting Injectable Antipsychotic Medication Use in Patients with Schizophrenia Spectrum, Bipolar, and Other Psychotic Disorders in a US Community-based, Integrated Health System
Authors: Alavi Mubarika , Ridout Samuel J , Lee Catherine , Harris Brooke , Ridout Kathryn K
Published: April 2024

Background and Hypothesis

Long-acting injectable (LAI) antipsychotics improve patient outcomes and are recommended by treatment guidelines for patients with limited medication adherence in schizophrenia spectrum, bipolar, and other psychotic disorders. Reports of LAI antipsychotic use in these disorders and if use aligns with treatment guidelines are lacking. This study aimed to report patient characteristics associated with LAI antipsychotic use in these disorders.

Study Design

Retrospective observational study of patients ≥18-years-old with bipolar or psychotic disorders at a large, integrated, community-based health system. Patient demographic and clinical characteristics served as exposures for the main outcome of adjusted odds ratio (aOR) for LAI versus oral antipsychotic medication use from January 1, 2017 to December 31, 2023.

Study Results

There were N = 2685 LAI and N = 31 531 oral antipsychotic users. Being non-white (aOR = 1.3-2.0; P < .0001), non-female (aOR = 1.5; P < .0001), from a high deprivation neighborhood (NDI, aOR = 1.3; P < .0007), having a higher body mass index (BMI, aOR = 1.3-1.7; P < .0009), having a schizophrenia/schizoaffective (aOR = 5.8-6.8; P < .0001), psychotic (aOR = 1.6, P < .0001), or substance use disorder (aOR = 1.4; P < .0001), and outpatient psychiatry (aOR = 2.3-7.5; P < .0001) or inpatient hospitalization (aOR = 2.4; P < .0001) utilization in the prior year with higher odds and age ≥40 (aOR = 0.4-0.7; P < .0001) or bipolar disorder (aOR = 0.9; P < .05) were associated with lower odds of LAI use. Non-white, non-female, age 18-39, and high NDI patients had higher LAI use regardless of treatment adherence markers. Smoking and cardiometabolic markers were also associated with LAI use.

Conclusions

Demographic and clinical factors are associated with increased LAI use irrespective of treatment adherence. Research on utilization variation informing equitable formulation use aligned with treatment guideline recommendations is warranted.
0004 Circadian Alignment and Body Composition in Overweight/obese Adults
Authors: Shafer Brooke , Kogan Sophia , Shea Steven , Olson Ryan , McHill Andrew
Published: April 2024

Introduction

Misalignment between behaviors (i.e., eating/sleeping) and the circadian timing system promotes increased risk of diabetes and obesity. Though circadian disruption has been shown to be associated with higher body fat percentage (BF%) and abdominal fat distribution among healthy weight males, but not females, these relationships may be altered in individuals with higher body mass index (BMI) given the complex interaction between obesity and circadian metabolic mechanisms. We therefore tested the association between circadian alignment and body composition in individuals with overweight/obesity.

Methods

BF% and android-gynoid (AG) percent fat ratio was assessed using dual energy x-ray absorptiometry in 28 participants (15 female). Dim-light melatonin onset (DLMO; 3pg/ml threshold) was used as a marker of circadian phase, as determined from saliva samples across an ~8h evening in-laboratory stay in dim-light (< 5 lux). Circadian alignment was determined via phase angle of entrainment, defined as the time difference between DLMO and diary-determined sleep onset over 7-days. Differences between females and males were assessed using independent t-tests and the relationships between phase angle of entrainment and body composition metrics were assessed using Pearson correlation analyses.

Results

There were no differences between groups in age (mean(SD), females vs. males, respectively; 34.2(8.2) y vs. 37.2(8.3) y; p=0.35), BMI (34.9(5.9) kg/m2 vs. 31.0(6.5) kg/m2; p=0.11), DLMO timing (19:35(1:15) vs. 19:37(0:57); p=0.95), or phase angle of entrainment (2.9(1.7) h vs. 3.0(1.1) h; p=0.77). Females had higher BF% than males (45(6) % vs. 34(8) %; p< 0.01) and lower AG ratios than males (1.06(0.13) vs. 1.33(0.15); p< 0.01). Phase angle of entrainment [i.e., later sleep] was negatively correlated with AG ratio only in males (r= -0.6; p=0.03) while phase angle of entrainment had a negative correlation with BF% only in females (r= -0.65; p=0.01).

Conclusion

Alignment of the circadian system (i.e., smaller phase angle of entrainment) may be a contributing factor to poorer body composition and, particularly amongst males, metabolically unhealthy body fat distribution in individuals with overweight/obesity. The mechanistic role of circadian timing on cardiometabolic disease risk may be differentially affected by sex and obesity, which could have implications for targeted interventions to improve health outcomes.

Support (if any)

NIH T32HL083808, K01HL146992, R35HL155681
0013 Impact of Circadian Misalignment on Executive Functioning and Risk Taking in Adolescents
Authors: Mills Andrew , Oldham Mary-Frances , Homer Kate , Rugh Kathleen , Jones Jolynn , Jube Eric , Kamhout Sarah , Kay Daniel , Duraccio Kara
Published: April 2024

Introduction

Circadian misalignment, the discrepancy between one’s internal circadian rhythms and one’s sleep patterns, is prevalent among adolescents. Circadian misalignment may confer risk for executive function difficulties and risky behavior in teens. This study aims to investigate the impact of experimentally-induced circadian misalignment on executive functioning and risk taking in adolescents.

Methods

Twenty-nine night owl adolescents (14-18 years) underwent a 20-day sleep manipulation protocol, which included two conditions simulating night owl (aligned group) and morning lark (misaligned group) sleep patterns. The study included a 5-night stabilization, 2-night washout, and two 5-day sleep conditions (aligned vs misaligned). Executive functioning and risk-taking were assessed using the Trail Making Task, (an objective executive functioning task), Iowa Gambling Task (an objective risk-taking task), and the Behavioral Inhibition and Behavioral Activation System (BIS/BAS; a self-report measure of both executive function and risk tasking), following each experimental condition. Normality for the dependent variables were assessed using the Shapiro-Wilk test, and statistical comparisons were run with Wilcoxon Signed Rank tests for non-normal variables and paired samples t-tests for normal variables.

Results

The Trail Making Task displayed no significant differences between the aligned and misaligned groups in completion times (p=.108). There were no significant differences between groups on the BAS-drive (p=.522), BAS-fun ( p=.273), and BAS-reward (p=.791) sub-components. In contrast, the misaligned group had significantly higher scores on the BIS component (p=.021). Additionally, the misaligned group had higher average total T-scores in risk taking on the Iowa Gambling Task (p=.022).

Conclusion

Our results indicate that those in the misaligned condition showed significantly increased risk-taking in a gambling task (compared to when in the aligned condition), which is consistent with prior findings emphasizing the impact of circadian misalignment on risky behavior. Interestingly, adolescents experiencing circadian misalignment also had elevated behavioral inhibition scores, suggesting that alongside greater behavioral observations of risk taking, they also self-reported to have heightened nervous reactions to expected punishment and increased sensitivity to aversive outcomes. This study enhances understanding of circadian alignment's impact on adolescent decision making, which may inform pre-clinical behavioral interventions aimed to improve adolescent health and well-being.

Support (if any)
0025 Circadian Phase Shifts After Transmeridian Travel in the Operational Environment
Authors: Huang Kathleen , Eldringhoff Hannah , Overman Grace , Carlsson Kajsa , Jones Rachell , Bode Victoria , Elkin-Frankston Seth , Bovard Pooja , Brown Stephanie , Burke Tina
Published: April 2024

Introduction

Circadian misalignment is detrimental to health and performance– decrements that can be exacerbated by rapid transmeridian travel. Such travel is unavoidable in military operations but can itself negatively impact the likelihood of mission success. To date, there are few studies assessing the impact of travel on the physiology and operational performance of military personnel. In the present study, salivary dim light melatonin onset (DLMO) is used to assess the extent to which circadian rhythms are impacted by transmeridian travel and round-the-clock missions.

Methods

Participants were 23 active-duty male Soldiers aged 23.2 ± 2.8 years (M ± SD). Baseline data were collected in the Hawaii Standard Time (HST) Zone. This was followed by rapid deployment to the Eastern Daylight Time Zone for one pre-mission day, followed by a 72-hour live-fire exercise, and two post-mission days. Salivary melatonin was assessed via a modified constant routine at baseline, upon arrival to the EDT zone, and again on the first post-mission day, with 12 passive drool saliva samples collected every 30 minutes from 1830 to 0000 hours under dim light (< 10 lux) and sedentary conditions. Participants abstained from food and drink (except for water) during the assessment. The circadian phase shift for the mission was calculated as the time difference between baseline and post-mission DLMO.

Results

During the pre-mission day, 19 participants displayed the anticipated melatonin suppression (no DLMO) upon arrival to the EDT zone. During the mission, 15 Soldiers had a circadian phase delay [ ~66 min (±72 min), (M ± SD)], and 8 Soldiers had a circadian phase advance [~90 min (± 96 min), (M±SD).

Conclusion

As anticipated, participants’ circadian rhythms were misaligned with the local day immediately upon arrival to the EDT. For all but 1 participant, circadian timing at post-mission was similar to circadian timing at baseline. Further analyses are underway to determine the extent of misalignment on the pre-mission day resulting from travel. Further research is needed to assess the extent to which transmeridian travel and round-the-clock operations impact circadian misalignment, rate of adaptation to the new time zone, and operationally relevant performance.

Support (if any)

DoD MOMRP; DEVCOM-SC
0026 Night Shift Sleep and Energy Management via Light Therapy: A Double-blinded, Placebo Controlled Study
Authors: Luo Biquan
Published: April 2024

Introduction

Lumos Smart Sleep Mask emits short light pulses during sleep aiming to pre-align and re-align the user’s circadian rhythms during travel, night shifts and other short-term and long-term circadian clock disruptions. In an earlier DoD-funded, counterbalanced, double-blinded, placebo-controlled lab study, the Lumos Mask was shown to induce circadian phase shifts determined by DLMO assessment. This study is a DoD-funded field study on healthy night shift workers to investigate the impact of Lumos Mask on sleep and alertness during night shifts.

Methods

The study involved 15 healthy night shift workers aged between 18 and 65 who underwent multiple rounds of night shift rotations under multiple conditions. The conditions included: 1) No intervention 2) Lumos Mask + sham program 3) Lumos Mask + active light programs. Sleep data was collected by Dreem headband, Fitbit Charge 5, as well as self-report questionnaires. Alertness through reaction time was measured by the Psychomotor Vigilance Test (PVT), Karolinska Sleepiness Score (KSS), and other self-report questionnaires.

Results

Preliminary findings demonstrated a consistent trend indicating the mitigation of adverse effects associated with night shift work on sleep and alertness. Participants demonstrated higher alertness and higher functionings during night shifts. When working on night shifts, participants demonstrated better perceived sleep quality, accompanied by longer sleep duration and less early awakening. During post-shift recovery sleep, participants experienced shorter sleep onset latency, shorter awakening, and better overall perceived sleep quality.

Conclusion

Taken together, the lab study and the field study demonstrated the effectiveness of the Lumos Mask in regulating human circadian clocks. The personalized light pulses in the Lumos Mask offer a great potential in improving the sleep and performance for individuals experiencing circadian clock disruptions.

Support (if any)

The DLMO lab study and the night shift field study were funded by the Department of Defense under Contract Number H9240521
0027 Personalized Light Therapy for Night Shift Work: A Precision Medicine Approach to Reducing Insomnia and Sleepiness
Authors: Paniccia Grace , Habash Salma , Drake Christopher , Walch Olivia , Cheng Philip
Published: April 2024

Introduction

Night shift workers experience symptoms of excessive sleepiness and insomnia due to misalignment between their circadian clock and work schedule. Circadian misalignment can be corrected using exposure to bright light delivered in accordance with a phase response curve. Our prior data indicate that a light schedule personalized to an individual’s melatonin rhythms produces greater reductions in circadian misalignment compared to a one-schedule-fits-all approach. This randomized controlled trial extends prior findings by examining the effect of personalized light therapy on symptoms of shift work disorder.

Methods

Individuals with shift work disorder (ICSD-3 diagnostic criteria) were randomized into two conditions: personalized light therapy (n = 14), or a non-personalized light therapy control (n = 7). Personalized light schedules were based on estimates of dim light melatonin onset (DLMO) derived from mathematical modeling of data collected via an Apple Watch. Light schedules were delivered through a mobile app (Arcashift) that updated in accordance with real-time estimates of DLMO. Estimates were confirmed with in-lab DLMO. Participants were provided light blocking glasses and a light box as source of bright light at night. Sleepiness (Karolinska Sleepiness Scale) and insomnia (Insomnia Severity Index) were assessed before and after treatment, and analyses evaluated change scores from pre- to post-treatment.

Results

Those in the personalized light therapy group demonstrated decreased insomnia symptoms during daytime sleep (mean = -4.64, SD = 8.03) compared to those in the non-personalized control (mean = 3.57, SD = 5.38), p < 0.05. The personalized light therapy group also achieved a decrease in peak sleepiness (mean = -0.21, SD = 0.68) compared to the control (mean = 0.77, SD = 0.76), p < .001.

Conclusion

Preliminary results suggest that personalizing light therapy according to the individual’s specific circadian phase may be more effective in improving symptoms of insomnia and sleepiness by delivering treatment. Future research should examine other occupational and health outcomes associated with a personalized approach to light therapy.

Support (if any)

Support for this study was provided from the National Institute of Health R41HL163783 and the American Academy of Sleep Medicine Foundation (245-SR-21) awarded to Drs. Philip Cheng and Olivia Walch.
0030 Gene Expression and Attention Lapses with a Countermeasure for Sleep Loss
Authors: Uyhelji Hilary , Munster Susan , White Vicky , Nicholson Scott
Published: April 2024

Introduction

Few studies have investigated the association between genetic and neurobehavioral performance changes during sleep loss, or how that relationship may be impacted by wakefulness promoting agents. We hypothesized that we could associate gene expression with impairment during sleep deprivation, both with and without use of the countermeasure modafinil.

Methods

Healthy young adults (N=19) were exposed to total sleep deprivation for ~36 hours on each of two separate study runs. On one night, each participant received 200 mg of modafinil, and during the other night, they were given a placebo. Objective performance was assayed with the Psychomotor Vigilance Test (PVT), Delayed Match to Sample, and Rapid Decision Making Test, along with self-reported fatigue on the Profile of Mood States questionnaire. Whole transcriptome sequencing data of blood samples drawn every 4 hours (N=8 times per subject) were analyzed with generalized linear modeling for associations of gene expression with neurobehavioral metrics.

Results

Performance was impaired during sleep loss, with maximum values of PVT lapses reaching over 10 attention lapses in ~90% of subjects. Modafinil served to mitigate the impairment. In models including circadian rhythms, we discovered 232 genes significantly associated with PVT lapses in the placebo run, but zero genes in the run with administration of modafinil. Limited overlap was found between biomarker genes associated with PVT, and genes related to other neurobehavioral assays.

Conclusion

Genetic findings include potential molecular biomarkers for neurobehavioral effects of sleep loss, and reproducible findings of select genes in prior work reveals strong candidate gene biomarkers for attention impairment during sleep loss. Differences in molecular associations across neurobehavioral tests suggests the potential to develop tailored genetic panels for specific types of neurobehavioral changes. However, the use of modafinil greatly diminished not only attention lapses but also the association of gene expression with attention impairment. These findings demonstrate the importance of considering background countermeasure use in development of biomarker panels.

Support (if any)

Blood draws and genetics analyses were supported by FAA awards DTFAAC-17-X-00001 and 6973GH-18-D-00110.
0033 Proteomic Profiling of Plasma Biomarkers in Men and Women with Diagnosed Insomnia
Authors: Mithani Sara , Brock Matthew , Pruiksma Kristi , Li Xueying , Gerwell Kelsi , Momin Arees , Powell Tyler , Straud Casey , Young-McCaughan Stacey , Peterson Alan , Mysliwiec Vincent
Published: April 2024

Introduction

Chronic insomnia disorder affects approximately 10% of the U.S. population and is linked to various adverse health consequences. Despite advancements in pharmacological interventions, many individuals continue to experience recurrent symptoms. A comprehensive understanding of the molecular mechanisms underlying insomnia is crucial for developing innovative and effective treatments. This study aimed to profile plasma proteins using an unbiased high-throughput assay to identify potential biomarkers for insomnia, with a specific focus on discerning any differential responses between men and women.

Methods

This prospective, observational study (n=60; 40 insomnia, 20 control; 58.3% females) was part of a larger study completed at Joint Base San Antonio-Lackland. Participants completed an overnight in-lab diagnostic polysomnogram, blood collection and clinical evaluation. We applied an unbiased high multiplexed proteomic discovery technique using DNA aptamers to target 7,000 proteins in plasma samples. Chi-square test and Mann–Whitney U-test were performed to determine the group differences. Adjusted p-values were calculated by using Benjamini–Hochberg's false discovery rate (FDR). Dysregulated proteins were uploaded into the Ingenuity Pathway Analysis software (Qiagen IPA) to explore the mechanistic networks most significantly associated with the study outcome. Significance level was set at 0.05 in all tests.

Results

We identified 54 significantly dysregulated plasma proteins (29 upregulated, 25 downregulated) when comparing individuals with diagnosed insomnia, stratified by gender. The top three upregulated proteins were T cell surface antigen CD2, Leptin (LEP), and N-terminal pro-BNP (NPPB); the top three downregulated proteins were Kunitz-type protease inhibitor 3 (SPINT3), Beta-defensin 104 (DEFB104A), and Benign Prostate-specific Antigen (KLK3). Pathway analysis revealed associations with proinflammatory cascades and metabolic signaling pathways.

Conclusion

Our findings highlight the feasibility of multiplex proteomic profiling in identifying blood-based biomarkers for understanding the pathophysiological mechanisms of insomnia disorder. Further research is warranted to ascertain the clinical utility of these candidate proteins.

Support (if any)

This research was supported by grants from the American Academy of Sleep Medicine Foundation (supported by Eisai, Inc.), the Defense Health Agency, Defense Medical Research and Development Program, Clinical Research Intramural Initiative for Military Women’s Health (DM170708; Mysliwiec), and the US Air Force Air Force Materiel Command (AFMC), Wright-Patterson Air Force Base, Ohio (FA8650-18-2-6953; Peterson).
0040 Metabolic Effects of Superimposed Sustained and Intermittent Hypoxia in Hepatocyte-Derived Spheroids
Authors: Hackbarth Megan , Olvera Kristine , Brewster Katie , Moya Esteban , Ganguly Souradipta , Dhar Debanjan , Mesarwi Omar
Published: April 2024

Introduction

Chronic obstructive pulmonary disease/obstructive sleep apnea (COPD/OSA) overlap syndrome is characterized by chronic sustained hypoxemia due to COPD and superimposed intermittent hypoxemia due to OSA, and is associated with poor clinical outcomes related to the severity of hypoxemia. Overlap hypoxia (OH) combining sustained hypoxia and intermittent hypoxia (IH) causes an elevation in serum LDL cholesterol (LDL-C) and hepatic malondialdehyde, a marker of oxidative stress. The use of liver organoids (spheroids) cultured in hypoxia preserves liver-specific variability in tissue oxygenation. We aimed to determine how malondialdehyde and LDL-C uptake were impacted by OH in liver spheroids.

Methods

HepG2 cells were seeded into wells of round-bottom ultra-low attachment microplates to encourage spheroid formation. Media was changed 1:1 every other day for a total of 8 days. The spheroids were then pipetted into microplates with gas-permeable membranes. In a subset of wells, half the media was replaced by reconstituted LDL-DyLight 550, a conjugated human LDL-C which fluoresces upon endocytosis. Then, the spheroids were placed into one of three hypoxic environments using an OxyCycler C42 Dynamic O2 and CO2 controller: normoxia (16% O2 and 5% CO2), IH (O2 cycling between 16% and 2.5% every 3 min, constant 5% CO2), or OH (O2 cycling between 11.5% and 2.5% every 3 min, constant 5% CO2). After 4 hours, media and spheroids were collected for quantification of malondialdehyde (n=4 pooled samples/group), and spheroids with LDL-DyLight 550 were examined for fluorescence (n=24 spheroids/group).

Results

There were no morphologic differences among the groups after hypoxic or normoxic exposures. Malondialdehyde was increased in both hypoxic spheroid groups, though more in OH (RA: 2.9±1.4 µM; IH: 7.4±3.7 µM, p=0.005 vs RA; OH: 9.6±4.8 µM, p< 0.001 vs RA). LDL-C uptake was reduced by 28.4% in OH relative to RA (p=0.003). No effect was noted in IH (p=0.863).

Conclusion

Culture of hepatocyte-derived spheroids in hypoxic environments is feasible. OH in spheroid culture increases an important marker of oxidative stress, and reduces LDL-C uptake. These results echo previous animal-based data. Future experiments are intended to understand underlying mechanisms.

Support (if any)

This project was supported by grants NIH K08HL143140 and UCSD RG104448.
0050 Glossopharyngeal Nerve Discharge Patterns in Neuromuscular Control of Breathing
Authors: Nakamura Eriko , Kola Gjinovefa , Dewald Denise , Dick Thomas , Dutschmann Mathias , Strohl Kingman , Curado Thomaz Fleury
Published: April 2024

Introduction

The glossopharyngeal nerve is important for gas exchange in fish, but in mammals concentration is focused on the hypoglossal nerve (Dewald et al, 2018). In the present study, we hypothesize the discharge pattern of glossopharyngeal nerve activity (GPNA) will relate to the 3-phase respiratory motor pattern apparent in the vagal, hypoglossal, and phrenic nerves in mammals.

Methods

We recorded GPNA from in situ arterially perfused brainstem preparations of juvenile rats (n=10) and compared these data to simultaneously recorded phrenic (PNA), vagal (VNA), and hypoglossal (HNA) nerve activities. We report the timing of GPNA relative to onset and duration of PNA, HNA, and VNA for at least 32 respiratory cycles in each preparation.

Results

Preparations had a eupnea-like 3-phase respiratory motor pattern (Dutschmann et al 2009). The average respiratory cycle length was 4.30s ± 0.61 (Mean±SD). The inspiratory discharge duration analyzed from PNA was 0.73s ± 0.15; the postinspiratory discharge duration analyzed from VNA, 2.85s ± 0.69; and a late expiratory phase duration, 0.87s ± 0.46. The GPNA started significantly before the onset of PNA with a pre-inspiratory discharge duration of 0.53s ± 0.23 (ANOVA p=0.0001). Overall the pre-inspiratory discharge of GPNA was similar compared to pre-inspiratory discharge of HNA (0.36s ± 0.21), postinspiratory discharge duration of GPNA (0.53s ± 0.12) was also comparable to HNA (0.59s ± 0.26), but significantly shorter compared to VNA (2.85s ± 0.69; p=0.0001).

Conclusion

Both GPNA and HNA displayed robust, characteristic pre-inspiratory/inspiratory discharge patterns in every preparation. Clinically, the activation pattern of the GPNA may be as crucial as that of the HNA, for maintaining a healthy, patent upper airway for breathing during sleep.

Support (if any)

The Japanese Respiratory Society Fellowship Grants, NIH/NHLBI
0058 Neural Differentiation of Competing Memory Representations After a Prediction Error Depends on REM Sleep
Authors: McDevitt Elizabeth , Kim Ghootae , Turk-Browne Nicholas , Norman Kenneth
Published: April 2024

Introduction

When we retrieve a memory, competing memories can come to mind. One way the brain might resolve this competition is by pushing the interfering memory representations away from one another (neural differentiation). Previous work found that, when an item predicted in a particular context (A predicts B) failed to appear and was later restudied in a different context, the A and B representations became less similar in the hippocampus. We used fMRI to test the preregistered hypothesis that rapid eye movement (REM) sleep (occurring post-prediction-error) is required to observe this effect.

Methods

In the morning, we first obtained pre-learning fMRI “snapshots” of each item’s neural representation by extracting the spatial pattern of BOLD activity corresponding to each item. Next, participants viewed a continuous stream of scenes that, unbeknownst to them, followed a pair structure. Each pair had one scene as the first item (scene A) and a different scene as the second item (scene B). Each pair was shown together three times, inserted in the stream continuously amongst the other pairs, creating the expectation that B will follow A. For a subset of pairs, this expectation was then violated on trials where B failed to follow A; the B item was subsequently restudied on its own (i.e., not preceded by its pairmate A). Participants were then randomly assigned to remain awake, take a nap containing non-REM sleep only, or take a nap with both non-REM and REM sleep. Later the same day, we obtained post-learning fMRI snapshots of each item’s neural representation.

Results

We used pattern similarity analysis to compare the pre- and post-learning snapshots and found evidence of neural differentiation of the A and B items in the right CA2/3/DG subfield of the hippocampus, but only in the group whose nap contained REM sleep.

Conclusion

This result provides the first evidence linking REM sleep to changes in the hippocampal representations of specific memories in humans, and - more generally - suggests that REM helps to restructure neural representations in response to competition that occurs during wake.

Support (if any)

R01 MH06945 (K.A.N and N.T.-B.) K99 MH126154 (E.A.M.)
0061 Pulling an All-Nighter Impairs Organic Chemistry Learning: An At-Home, Zoom-Based Sleep Deprivation Experiment
Authors: Barley Blake , Tran David , Fitzsimmons Corinne , Suarez Andrea Castillo , Pua Kay Chi , Scullin Michael
Published: April 2024

Introduction

College students often believe that cutting back on sleep is necessary to have success in rigorous gateway courses like organic chemistry. At the same time, experimental sleep deprivation is known to impair laboratory tests of cognitive functioning. We bridged these naturalistic-laboratory approaches by testing whether a single night of total sleep deprivation impacted at-home learning and retention of an ecologically-valid organic chemistry lecture.

Methods

Undergraduate students (N=36; Mage = 19.22; 68.8% female; 59.4% non-white) who had not taken organic chemistry and were not chemistry pre-majors completed a 5-day study. At baseline, participants visited the laboratory to complete questionnaires, computerized tasks, and receive wristband actigraphy and an Oura ring. The following night, participants joined an online Zoom session and were randomly assigned to go to bed at 10:30pm or to undergo a night of total sleep deprivation. Caffeine and other substances were not allowed overnight. At 7:30am, all participants completed a virtual organic chemistry lecture and a 50-item test. After a two-day washout period, participants returned to the laboratory for a second organic chemistry test to assess retention.

Results

Most participants (n=32) completed all study phases, and only one withdrew due to sleep deprivation. Actigraphy and ring monitoring confirmed that participants in the normal sleep condition slept on the experimental night (actigraphy M=7.37 hours, ring M=7.64 hours), whereas participants in the sleep deprivation condition did not sleep [actigraphy M=0.08 hours, ring M=0.08 hours; ts>35, ps<.001, cohen's ds > 12]. Sleep deprivation altered perceived stress and metacognitive outcomes [t(30) = 2.11, p = .043, d = .75 and t(30) = 3.27, p = .003, d = 1.16) and significantly impaired morning organic chemistry learning (M=47.4%) compared to normal sleep [M=60.8%; t(30) = 2.11, p = .044, d = .75]. Similar trends were observed at the two-day retention test (Sleep deprivation: 46.4%; Normal sleep: 57.1%, p>.05, d = .55).

Conclusion

Pulling an all-nighter was sufficient to compromise complex educational learning. Sleep deprivation experiments can be feasibly conducted in participants’ homes so long as they are video-monitored by research staff and wakefulness is confirmed by wearable sleep trackers.

Support (if any)

National Science Foundation (1943323) and Baylor URSA (#2412).
0070 The Effect of Post-Learning Rest on False Memory in the Deese-Roediger-McDermott Paradigm
Authors: Livingston William , Putnam Adam , Wamsley Erin
Published: April 2024

Introduction

Although sleep has long been known to benefit memory consolidation, recent studies demonstrate that even a brief period of eyes-closed waking rest can similarly benefit a wide variety of memory types, including declarative, procedural and spatial. But sleep is argued to not only quantitatively strengthen memory traces, but also qualitatively transform them over time. The present study tested whether post-encoding waking rest affects the formation of false memories in the Deese-Roediger-McDermott (DRM) false memory paradigm, which are thought to arise from a “gist extraction” transformation of memory. We hypothesized that rest would increase false memory as measured by recall, but decrease false memory as measured by recognition.

Methods

In a within-subjects, counter-balanced design, N=51 participants auditorily encoded 8 DRM word lists. Each list consisted of 15 semantically-related words, all of which were derived from a central “critical lure” not heard by participants. After encoding, participants either sat quietly with their eyes closed for 15 minutes or spent an equivalent period of time completing a distractor task. Afterwards, participants were tested on their memory via both recall and recognition. False memory was defined as the false recall or recognition of “critical lure” words that had not been included on the list. Scores on the recall test were adjusted for incorrect responses, by subtracting the number of words incorrectly recalled (not including the lure words) from the number of words correctly recalled.

Results

Paired samples t-tests revealed that there was no significant effect of rest on false memory using either recall (t(50)=.26, p = .796) or recognition (t(50)=1.20, p = .237) tests. There was also no significant effect of rest on memory for studied words (recall: t(50)=1.32, p = .194; recognition: t(50)=0.51, p = .612).

Conclusion

This study indicates the possibility that waking rest does not affect certain types of qualitative memory transformation thought to occur during sleep. This includes the gist-extraction type processes underlying false memory. Potentially, rather than acting independently of each other, waking rest and sleep may act in coordination, each with distinct roles in the consolidation process.

Support (if any)

Intramural funding from Furman University.
0075 Individual Differences in Habitual Sleep Discontinuity Predict Memory Consolidation and Supporting Neural Activity
Authors: Nyan Chuu , Chhabra Isha , Ram Sahana , Mirjalili Soroush , Duarte Audrey
Published: April 2024

Introduction

Numerous studies manipulating sleep (i.e., deprivation, intervening naps between encoding and retrieval) have shown that sleep facilitates episodic memory consolidation in young, healthy adults. The relationship in older adults is more mixed, though generally supportive of age-related attenuations in sleep-dependent memory consolidation. However, studies using manipulations of sleep or a single night of sleep architecture may omit potentially important information about individual differences in one’s habitual sleep patterns that may contribute to the episodic memory performance across age. There is great interest in determining if well-known age-related impairments in sleep quality are related to those in episodic memory consolidation and the neural activity supporting memory.

Methods

As part of an ongoing study, we recruited samples of cognitively unimpaired younger and older adults and measured their habitual sleep using a wrist-worn accelerometer for 1 week. Principle component analysis (PCA) was used to reduce data dimensionality and identify sleep components. We recorded their electroencephalography (EEG) as they performed an object-scene associative memory task with immediate and delayed (48 hours) retrieval assessments. Participants were asked during both retrieval phases if object-scene pairs were new, matched or did not match pairs that were presented during encoding. Memory retention (delayed-immediate d’) was used as the index of consolidation, correcting for each participant’s learning level.

Results

Across age groups, higher levels of habitual sleep discontinuity, which were elevated in older adults, were associated with reduced memory retention/consolidation estimates (t(11) = -2.74, p = 0.02, d = 0.81) and neural activity during delayed retrieval associated with successful recovery of retained memories (rho = 0.499, rho-value = 0.015).

Conclusion

These results support the idea that age-related increases in habitual sleep discontinuity may contribute to age-related reductions in sleep-dependent episodic memory consolidation, and the neural mechanisms supporting successful recovery of consolidated memories.

Support (if any)

This work was supported by the NIA # R21AG064309.
0077 TITLE: Test Format Influences the Effectiveness of Wakeful Rest for Memory Consolidation
Authors: Gonsalez Daniel , Knife Yordanos , Biggs-Rodriguez Omalys , Kowe Favour , Westerberg Carmen
Published: April 2024

Introduction

New memories are stabilized and strengthened during memory consolidation, which is facilitated during sleep. Recent research suggests that wakeful rest (WR), i,e., a period in which attention and other cognitive demands are reduced, May also facilitate memory consolidation. However other studies have failed to find such benefits of WR. Complicating matters, several methodological differences across successful and unsuccessful WR studies exist, including differences in learning material and test format. This experiment examined how test format may influence the effects of WR on memory consolidation.

Methods

Participants completed two consecutive sessions. In each session, they watched a 15-min video and then took an immediate memory test followed by a 15-min break while electroencephalography (EEG) was recorded. During the break, participants engaged in WR by sitting quietly in a comfortable chair in one session and completed a computer game distractor test in the other. Next, participants took a delayed memory test for the video and then completed a mind wandering questionnaire. For 16 participants, the memory test were multiple-choice and for 15 participants, the memory test were free recall.

Results

For participants who took multiple-choice test, let’s forgetting occururred from the immediate to the delayed memory test when participants engaged in WR compared to a distractor task during the break, and this difference was larger for participants who engaged in WR during the first session. For participants who took free recall test, although memory improved from the immediate to the delayed test during both sessions, there was no difference in size the improvement when participants engaged in WR compared to a distractor task during the break.

Conclusion

The efficacy of WR or memory consolidation depends on the format in which memory is tested. In the current experiment, WR during the break was more effective than a distractor task for preserving memories when tests were in multiple-choice but not free-call format. Additionally, when using a within-participants design, the order in which WR and the distractor task are completed is also relevant. EEG and mind-wandering data may be useful in understanding context in which WR may be most effective for memory consolidation.

Support (if any)
0078 The Brain Fails to Pre-activate the Low-level Stimulus-features of an Expected Stimulus
Authors: Topalidis Pavlos , Resinger Lisa , Schubert Juliane , Weisz Nathan , Schabus Manuel
Published: April 2024

Introduction

It has been suggested that the human brain is involved in actively predicting upcoming sensory inputs based on previous experience. The extent to which such a mechanism operates during sleep remains elusive. Studies utilizing mismatch negativity (MMN) paradigms report disruption of hierarchical predictive coding in sleep, while others argue for limited but preserved detection of the violation of predictions. Here, we inquire, for the first time, whether the brain actually pre-activates the features of an expected stimulus during sleep.

Methods

In a passive listening nap design (2.5 hours nap opportunity), participants (N=34) listened to sequences of four different auditory tones varying in pitch, presented at a fixed rate of 3 Hz, while we collected simultaneous Electroencephalography (EEG) and Magnetoencephalography (MEG) data. By manipulating the transition probabilities of the tones, we created random and predictable tone sequences. We analyzed the MEG data using multi-level pattern analysis (MVPA) to decode low-level tone properties and to search for evidence of stimulus pre-activations in the predictable tone sequences, when predicting the next tone from the previous one was actually possible. We performed cluster-based permutation across time, time-generalization, as well as cross-state decoding to identify significant above-chance classification time points.

Results

The results indicate that subtle changes in pitch, reflecting low-level stimulus features, are decodable in N1 and N2 sleep. This is in line with previous studies showing preserved but attenuated cortical activations related to the processing of low-level stimulus properties during sleep. Neural codes between states appear to be similar, as we observed high cross-state classification accuracies. In wakefulness, evidence of neural codes of the expected stimuli was found in the prestimulus interval, but this was not observed in N1 and N2 sleep, suggesting disrupted predictive abilities even in light sleep

Conclusion

Processing of low-level stimulus features persists in sleep, but the detection of stimulus statistics appears to be disrupted.

Support (if any)

We would like to express our gratitude to the Doctoral College 'Imaging the Mind' for their financial support (FWF, Austrian Science Fund: W 1233-B)."
0081 Sleep as a Mediator Between Housing Conditions and Cognitive Impairment
Authors: Johnson Dayna , Ward Laura
Published: April 2024

Introduction

Adverse housing conditions are associated with cognitive impairment; however, the mechanism is not fully understood. Adverse housing can affect sleep – an essential physiologic activity for cognitive function, yet this pathway is understudied. We tested associations between housing condition, sleep disturbances, and cognitive impairment.

Methods

This study utilized data from the Health and Retirement Study, a longitudinal panel study among adults (2020). Participants (n=2,346) completed questionnaires on housing, sleep disturbances, and cognition. Housing was measured by self-reported ratings of their homes physical condition (1-excellent to 5-poor), and further categorized as poor/fair vs. excellent/very good/good. Sleep disturbances were self-reported as trouble falling asleep, trouble waking up during the night, and trouble with waking up too early and not being able fall asleep again, and each item was scored from 0 (rarely/never) to 2 (most of the time). Subjective and objective cognitive impairment was defined as a participant rating of fair or poor regarding their memory at the present time and by diagnostic classification, respectively. Logistic regression models were fit to test associations between housing and sleep and cognitive impairment after adjustment for covariates. A bootstrapped, model based, causal mediation analysis was conducted to calculate the effect of sleep on housing and cognition.

Results

The sample had a mean age of 66.5 + 0.21 years, and 56% were female, 10% Black, 80% White, and 10% other racial group. There was a high prevalence of cognitive impairment (subjective: 25%, objective: 34%) and sleep disturbance (38%). Individuals living in fair/poor vs. excellent/very good/good housing conditions had higher odds of sleep disturbances [Adjusted Odds Ratio (aOR)=3.72, 95% confidence interval (1.89, 7.36)] and cognitive impairment [Subjective aOR=3.74 (1.73, 8.06) and Objective aOR=4.71 (2.07, 10.70)], respectively. Sleep disturbances were associated with higher odds of cognitive impairment [Subjective aOR=2.42(1.51, 3.88) and Objective aOR=1.72 (1.04, 2.87)]. The formal mediation results showed that sleep partially mediated the association between housing and cognitive decline (15% subjective and 9% objective).

Conclusion

Results suggest that sleep may explain a portion of the association between housing conditions and cognitive impairment. Targeting sleep and determinants of sleep (i.e., housing), may reduce cognitive impairment.

Support (if any)

NHLBI R01HL157954