bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary and Specialty Palliative Care Utilization at a Regional Burn Center
Authors: Tao Zoe , Hoffman Alexandra , Stecher Anna , Eshraghi Niknam
Published: April 2024

There is little research informing appropriate specialty palliative care consultation over primary palliative care practice, or the ability of the burn surgeon to perform skills such as effective goals of care discussions. We sought to characterize patterns of palliative care utilization and hypothesized that greater modified Baux (mBaux) and systemic organ failure assessment (SOFA) scores would correlate with increased specialty palliative involvement but have no relationship with primary palliative involvement. A retrospective chart review was conducted at a regional burn center between 2020 and 2021 including patients admitted with burns or inhalation injury and a mBaux score over 60, detailing circumstances of palliative consultation and goals of care discussions. A total of 163 patients met the criteria. The odds of specialty palliative consultation increased by 3.9% for each additional mBaux score point and 23.3% for every SOFA score point. The odds of goals of care discussion by a burn surgeon increased by 3.5% for each mBaux score point and 23.9% for each SOFA score point. Those receiving palliative consultation tended to have greater burn surface area, graft complications, code status changes, and more goals of care discussions by any provider at admission; there was no difference in symptom control or hospital length of stay. Higher mBaux and SOFA scores correlate with increased odds of both specialty and primary palliative involvement in our cohort. There is bias in diverting both primary and specialty palliative care resources toward acutely ill patients and those with less immediate projected mortality may need additional attention.
Equivariant neural operators for gradient-consistent topology optimization
Authors: Erzmann David , Dittmer Sören
Published: April 2024

Most traditional methods for solving partial differential equations (PDEs) require the costly solving of large linear systems. Neural operators (NOs) offer remarkable speed-ups over classical numerical PDE solvers. Here, we conduct the first exploration and comparison of NOs for three-dimensional topology optimization. Specifically, we propose replacing the PDE solver within the popular Solid Isotropic Material with Penalization (SIMP) algorithm, which is its main computational bottleneck. For this, the NO not only needs to solve the PDE with sufficient accuracy but also has the additional challenge of providing accurate gradients which are necessary for SIMP’s density updates. To realize this, we do three things: (i) We introduce a novel loss term to promote gradient-consistency. (ii) We guarantee equivariance in our NOs to increase the physical correctness of predictions. (iii) We introduce a novel NO architecture called U-Net Fourier neural operator (U-Net FNO), which combines the multi-resolution properties of U-Nets with the Fourier neural operator (FNO)’s focus on local features in frequency space. In our experiments we demonstrate that the inclusion of the novel gradient loss term is necessary to obtain good results. Furthermore, enforcing group equivariance greatly improves the quality of predictions, especially on small training datasets. Finally, we show that in our experiments the U-Net FNO outperforms both a standard U-Net, as well as other FNO methods.
An ‘elementary’ perspective on reasoning about probability spaces
Authors: Speranski Stanislav O
Published: April 2024

This paper is concerned with a two-sorted probabilistic language, denoted by $\textsf{QPL}$, which contains quantifiers over events and over reals, and can be viewed as an elementary language for reasoning about probability spaces. The fragment of $\textsf{QPL}$ containing only quantifiers over reals is a variant of the well-known ‘polynomial’ language from Fagin et al. (1990, Inform. Comput., 87, 78–128). We shall prove that the $\textsf{QPL}$-theory of the Lebesgue measure on $\left [ 0, 1 \right ]$ is decidable, and moreover, all atomless spaces have the same $\textsf{QPL}$-theory. Also, we shall introduce the notion of elementary invariant for $\textsf{QPL}$ and use it to translate the semantics for $\textsf{QPL}$ into the setting of elementary analysis. This will allow us to obtain further decidability results as well as to provide exact complexity upper bounds for a range of interesting undecidable theories.
From tofu to T-bones: how vegan and ketogenic diets shape our immune defenses
Authors: Morowitz Michael J
Published: April 2024

Link et al. conducted a controlled study comparing the impacts of ketogenic and vegan diets on energy intake and immune function in humans. Deep omics analyses revealed distinct effects of each diet on the immune system, including changes in cell populations and blood transcriptomes indicative of diet-induced shifts between adaptive and innate immunity. The study highlights the potentially significant, rapid impact of diet on immune function and health.
Forbs, graminoids, and lepidopterans: breadth and seasonal variation in the diet of the New Mexico jumping mouse (Zapus luteus)
Authors: Sanchez Daniel E , Dikeman Austin L , Lyman Jacque A , Zahratka Jennifer , Fofanov Viacheslav , Walker Faith M , Chambers Carol L
Published: April 2024

The New Mexico Jumping Mouse (Zapus luteus) is a federally endangered granivore active for only 3 to 5 months annually. Knowledge of diet can help guide habitat recovery and yet despite calls for restoration of its riparian habitat, the diet of Z. luteus remains largely unknown. To date, only 8 plant species have been described in the diet—whereas insectivory, mycophagy, and dietary shifts have only been hypothesized. In the late summer, Z. luteus rapidly accumulates fat for a 9-month hibernation and restoration may fail if seasonal variation in the diet is overlooked. We used DNA metabarcoding on fecal DNA (n = 165) to resolve dietary taxa within multiple trophic levels of the diet and investigate monthly patterns of consumption. Seldom studied in metabarcoding frameworks, we also investigated exogenous contamination in Sherman live-capture traps. Potential contamination among feces, pelage, and trap surfaces was detectable but low (median = 0% to 2%), with fecal communities distinct from exogenous sources. The diet of Z. luteus was varied and most frequently (frequency of occurrence) of graminoids, forbs, lepidopterans, dipterids, and false-truffles. For plant foods, dietary diversity increased throughout their season of activity, shifting from sedges and woody vegetation in the early season (June to July) to forbs and grasses in the late season (August to September). Insect consumption was consistently detected throughout the season, whereas mycophagy was more frequently detected in August, when hypogeous fungi are typically more abundant. The breadth of dietary taxa suggests plasticity in resource use, potentially accommodating diverse patterns of seed availability throughout their active period. Shifts in plant consumption may reflect a dietary adaptation to the phenological patterns of their plant communities, a synchrony that might benefit both pre- and post-hibernation survival. Our work substantially improves our understanding of the diet of Z. luteus (241 dietary taxa) and will be useful for guiding habitat recovery. It also offers scalable methods to further investigate the diet under disturbance contexts (e.g., grazing, wildfire, drought).
OsRH52A, a DEAD-box protein, regulates functional megaspore specification and is required for embryo sac development in rice
Authors: Huang Jinghua , Qiao Zhengping , Yu Hang , Lu Zijun , Chen Weibin , Lu Junming , Wu Jinwen , Bao Yueming , Shahid Muhammad Qasim , Liu Xiangdong
Published: April 2024

The development of the embryo sac is an important factor that affects seed setting in rice. Numerous genes associated with embryo sac (ES) development have been identified in plants; however, the function of the DEAD-box RNA helicase family genes is poorly known in rice. Here, we characterized a rice DEAD-box protein, RH52A, which is localized in the nucleus and cytoplasm and highly expressed in the floral organs. The knockout mutant rh52a displayed partial ES sterility, including degeneration of the ES (21%) and the presence of a double-female-gametophyte (DFG) structure (11.8%). The DFG developed from two functional megaspores near the chalazal end in one ovule, and 3.4% of DFGs were able to fertilize via the sac near the micropylar pole in rh52a. RH52A was found to interact with MFS1 and ZIP4, both of which play a role in homologous recombination in rice meiosis. RNA-sequencing identified 234 down-regulated differentially expressed genes associated with reproductive development, including two, MSP1 and HSA1b, required for female germline cell specification. Taken together, our study demonstrates that RH52A is essential for the development of the rice embryo sac and provides cytological details regarding the formation of DFGs.
Plasmoid identification and statistics in two-dimensional Harris sheet and GRMHD simulations
Authors: Vos J T , Olivares H , Cerutti B , Mościbrodzka M
Published: April 2024

Magnetic reconnection is a ubiquitous phenomenon for magnetized plasma and leads to the rapid reconfiguration of magnetic field lines. During reconnection events, plasma is heated and accelerated until the magnetic field lines enclose and capture the plasma within a circular configuration. These so-called plasmoids could therefore observationally manifest themselves as hotspots, which are associated with flaring behaviour in supermassive black hole systems, such as Sagittarius A*. We have developed a novel algorithm for identifying plasmoid structures, which incorporates watershed and custom closed contouring steps. From the identified structures, we determine the plasmoids’ plasma characteristics and energetics in magnetohydrodynamical simulations. The algorithm’s performance is showcased for a high-resolution suite of axisymmetric ideal and resistive magnetohydrodynamical simulations of turbulent accretion discs surrounding a supermassive black hole. For validation purposes, we also evaluate several Harris current sheets that are well-investigated in the literature. We recover the characteristic power-law distribution of plasmoid sizes for both the black hole and Harris sheet simulations. This indicates that while the dynamics are vastly different, with different dominant plasma instabilities, the plasmoid creation characteristics are similar. Plasmoid formation rates for resistive general relativistic magnetohydrodynamical simulations are significantly higher than for their ideal counterpart. Moreover, the largest identified plasmoids are consistent with sizes typically assumed for semi-analytical interpretation of observations. We recover a positive correlation between the plasmoid formation rate and decreases in black-hole-horizon-penetrating magnetic flux, during which the accretion flow is temporarily halted. These results demonstrate the efficacy of the newly developed algorithm which has enabled an extensive quantitative analysis of plasmoid formation in black hole accretion simulations.
ΛCDM not dead yet: massive high-z Balmer break galaxies are less common than previously reported
Authors: Desprez Guillaume , Martis Nicholas S , Asada Yoshihisa , Sawicki Marcin , Willott Chris J , Muzzin Adam , Abraham Roberto G , Bradač Maruša , Brammer Gabe , Estrada-Carpenter Vicente , Iyer Kartheik G , Matharu Jasleen , Mowla Lamiya , Noirot Gaël , Sarrouh Ghassan T E , Strait Victoria , Gledhill Rachel , Rihtaršič Gregor
Published: April 2024

Early JWST observations that targeted so-called double-break sources (attributed to Lyman and Balmer breaks at z > 7), reported a previously unknown population of very massive, evolved high-redshift galaxies. This surprising discovery led to a flurry of attempts to explain these objects’ unexpected existence including invoking alternatives to the standard Λ cold dark matter (ΛCDM) cosmological paradigm. To test these early results, we adopted the same double-break candidate galaxy selection criteria to search for such objects in the JWST images of the CAnadian Near Infrared Imager and Slitless Spectrograph (NIRISS) Unbiased Cluster Survey (CANUCS), and found a sample of 19 sources over five independent CANUCS fields that cover a total effective area of ∼60 arcmin2 at z ∼ 8. However, (1) our spectral energy distribution fits do not yield exceptionally high-stellar masses for our candidates, while (2) spectroscopy of five of the candidates shows that while all five are at high redshifts, their red colours are due to high-equivalent width emission lines in star-forming galaxies rather than Balmer breaks in massive, evolved systems. Additionally, (3) field-to-field variance leads to differences of ∼1.5 dex in the maximum stellar masses measured in the different fields, suggesting that the early single-field JWST observations may have suffered from cosmic variance and/or sample bias. Finally, (4) we show that the presence of even a single massive outlier can dominate conclusions from small samples such as those in early JWST observations. In conclusion, we find that the double-break sources in CANUCS are not sufficiently massive or numerous to warrant questioning the standard ΛCDM paradigm.
Matrix metalloproteinase 9: An emerging biomarker for classification of adherent vestibular schwannoma
Authors: Nguyen Han T N , Duhon Bailey H , Kuo Hsuan-Chih , Fisher Melanie , Brickey Olivia M , Zhang Lisa , Otero Jose J , Prevedello Daniel M , Adunka Oliver F , Ren Yin
Published: April 2024

Background

The progression of vestibular schwannoma (VS) is intricately linked with interactions between schwannoma cells and the extracellular matrix. Surgical resection of VS is associated with substantial risks as tumors are adherent to the brainstem and cranial nerves. We evaluate the role of matrix metalloproteinase 9 (MMP9) in VS and explore its potential as a biomarker to classify adherent VS.

Methods

Transcriptomic analysis of a murine schwannoma allograft model and immunohistochemical analysis of 17 human VS were performed. MMP9 abundance was assessed in mouse and human schwannoma cell lines. Transwell studies were performed to evaluate the effect of MMP9 on schwannoma invasion in vitro. Plasma biomarkers were identified from a multiplexed proteomic analysis in 45 prospective VS patients and validated in primary culture. The therapeutic efficacy of MMP9 inhibition was evaluated in a mouse schwannoma model.

Results

MMP9 was the most highly upregulated protease in mouse schwannomas and was significantly enriched in adherent VS, particularly around tumor vasculature. High levels of MMP9 were found in plasma of patients with adherent VS. MMP9 outperformed clinical and radiographic variables to classify adherent VS with outstanding discriminatory ability. Human schwannoma cells secreted MMP9 in response to TNF-α which promoted cellular invasion and adhesion protein expression in vitro. Lastly, MMP9 inhibition decreased mouse schwannoma growth in vivo.

Conclusions

We identify MMP9 as a preoperative biomarker to classify adherent VS. MMP9 may represent a new therapeutic target in adherent VS associated with poor surgical outcomes that lack other viable treatment options.
Adapting a Financial Incentives Intervention for Smoking Cessation With Alaska Native Families: Phase 1 Qualitative Research to Inform the Aniqsaaq (To Breathe) Study
Authors: Sinicrope Pamela S , Tranby Brianna N , Young Antonia M , Koller Kathryn R , King Diane K , Lee Flora R , Sabaque Corinna V , Prochaska Judith J , Borah Bijan J , Decker Paul A , McDonell Michael G , Stillwater Barbara , Thomas Timothy K , Patten Christi A
Published: April 2024

Introduction

Alaska Native and American Indian (ANAI) peoples in Alaska currently experience a disproportionate burden of morbidity and mortality from tobacco cigarette use. Financial incentives for smoking cessation are evidence-based, but a family-level incentive structure has not been evaluated. We used a community-based participatory research and qualitative approach to culturally adapt a smoking cessation intervention with ANAI families.

Aims and Methods

We conducted individual, semistructured telephone interviews with 12 ANAI adults who smoke, 12 adult family members, and 13 Alaska Tribal Health System stakeholders statewide between November 2022 and March 2023. Through content analysis, we explored intervention receptivity, incentive preferences, culturally aligned recruitment and intervention messaging, and future implementation needs.

Results

Participants were receptive to the intervention. Involving a family member was viewed as novel and aligned with ANAI cultural values of commitment to community and familial interdependence. Major themes included choosing a family member who is supportive and understanding, keeping materials positive and encouraging, and offering cash and noncash incentives for family members to choose (eg, fuel, groceries, activities). Participants indicated that messaging should emphasize family collaboration and that cessation resources and support tips should be provided. Stakeholders also reinforced that program materials should encourage the use of other existing evidence-based cessation therapies (eg, nicotine replacement, counseling).

Conclusions

Adaptations, grounded in ANAI cultural strengths, were made to the intervention and recruitment materials based on participant feedback. Next steps include a beta-test for feasibility and a randomized controlled trial for efficacy.

Implications

This is the first study to design and adapt a financial incentives intervention promoting smoking cessation among ANAI peoples and the first to involve the family system. Feedback from this formative work was used to develop a meaningful family-level incentive structure with ANAI people who smoke and family members and ensure intervention messaging is supportive and culturally aligned. The results provide qualitative knowledge that can inform future family-based interventions with ANAI communities, including our planned randomized controlled trial of the intervention.
The Pluralities of Property
Authors: Rostill Luke
Published: April 2024

In Property Rights: A Re-Examination, James Penner returns to and develops a project that he has been engaged in for nearly three decades: to replace the influential ‘bundle of rights’ picture of property, which he regards as irredeemably flawed, with an alternative account—one that regards property as a unified entitlement. In this review article, I expound and analyse the central features of Penner’s theory. I defend the view that, in its original iteration, Penner’s account was trebly monistic: it regarded property as a single entitlement justified by a single human interest and protected by a single duty of non-interference. I go on to critically examine one of Penner’s central ideas—that to understand property it is necessary to understand its justification. Along the way, I trace how Penner’s account has evolved and explain how certain alterations have put some problems to bed while generating others.
Systemic cellular migration: The forces driving the directed locomotion movement of cells
Authors: De la Fuente Ildefonso M , Carrasco-Pujante Jose , Camino-Pontes Borja , Fedetz Maria , Bringas Carlos , Pérez-Samartín Alberto , Pérez-Yarza Gorka , López José I , Malaina Iker , Cortes Jesus M
Published: April 2024

Directional motility is an essential property of cells. Despite its enormous relevance in many fundamental physiological and pathological processes, how cells control their locomotion movements remains an unresolved question. Here, we have addressed the systemic processes driving the directed locomotion of cells. Specifically, we have performed an exhaustive study analyzing the trajectories of 700 individual cells belonging to three different species (Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis) in four different scenarios: in absence of stimuli, under an electric field (galvanotaxis), in a chemotactic gradient (chemotaxis), and under simultaneous galvanotactic and chemotactic stimuli. All movements were analyzed using advanced quantitative tools. The results show that the trajectories are mainly characterized by coherent integrative responses that operate at the global cellular scale. These systemic migratory movements depend on the cooperative nonlinear interaction of most, if not all, molecular components of cells.
0006 Circadian Cyclic Gene Expression in Human Airway Epithelial Cells in Asthma and Viral Infections
Authors: Powell Weston , Clark Lindsay , White Maria , Rich Lucille , Gates Camille , Vanderwall Elizabeth , Debley Jason
Published: April 2024

Introduction

Cellular circadian rhythms regulate gene expression and innate immune pathways related to airway diseases in animal models of disease. However, circadian regulation of gene expression remains uninvestigated in human airway epithelial cells. Primary human airway epithelial cells can be grown at an air-liquid interface as an ex vivo organotypic model to characterize molecular circadian rhythms in the human airway. Using cells from healthy and donors with disease, we hypothesized that circadian cyclic gene expression would be altered in asthma and would display altered viral responses.

Methods

Cells were synchronized with temperature cycled incubators and RNA isolated every 4 hours over a 48 hour period for RNA-sequencing from primary human airway epithelial cells from healthy and asthmatic children. CompareRhythms in R was used to identify differential rhythmicity using the cosinor method. EnrichR pathway analysis for Reactome, Panther, GO molecular functions, and GO biological processes was used to identify relevant biological pathways with altered circadian rhythmic expression. Human rhinovirus 16 was applied to the apical surface at a multiplicity of infection of 0.5 and RNA isolated 96 hours later for genome copy number assessment with PCR.

Results

Circadain clock genes were rhythmic in airway epithelial cells from health and donors with asthma with preserved phase relationships indicating an intact core circadian clock. Analysis of circadian cyclic gene expression identified 4% of genes with circadian cyclic gene expression following temperature synchronization. Approximately 100 genes demonstrated altered circadian rhythmicity in airway epithelial cells from donors with asthma. Circadian rhythm and nuclear receptors had common rhythmicity in healthy and asthma. IL-17 signalling, cytokine receptor, and neutrophil chemotaxis pathways had altered circadian rhythmicity in asthma. Infection at time zero (end of temperature cycling) was associated with a two-fold lower viral replication than infection 12 hours later in healthy airway epithelial cells.

Conclusion

The core circadian clock genes maintain rhythmicity in healthy and asthma airway epithelia. Circadian regulation in immune and cytokine signaling pathways is altered in asthma.

Support (if any)

Sleep Research Society Foundation Career Development Award (WTP), ATS ASPIRE (WTP), Parker B Francis Fellowship (WTP), NIH R01AI163160 (JSD); NIH K24AI150991 (JSD)
0009 Circadian Proteins and Circadian Phase Estimation in Healthy Adults
Authors: Specht Adrien , Saha Puja , Cederberg Katie , Bueno Flavia , Arrona-Palacios Arturo , Pardilla-Delgado Enmanuelle , Ruiz-Herrera Noelia , Zitting Kirsi-Marja , Kramer Achim , Zeitzer Jamie , Czeisler Charles , Duffy Jeanne , Mignot Emmanuel
Published: April 2024

Introduction

Circadian rhythms, which control sleep-wake cycles and metabolism, are fundamental to human health. Our study aimed to understand how these rhythms affect proteins in the body throughout the day, and to develop a tool that predicts the body's internal clock phase based on protein expression.

Methods

Plasma samples from 17 healthy adults were collected hourly under controlled conditions designed to unmask endogenous circadian rhythmicity; in a subset of 8 participants, we also collected samples across a day on a typical sleep-wake schedule. Using the SomaScan aptamer-based multiplexed platform, we analyzed a total of 6916 proteins were analyzed. We used differential rhythmicity analysis based on a cosinor model with mixed effects to identify a subset of proteins that demonstrates circadian rhythmicity. Finally, we trained a machine learning model to predict the Dim Light Melatonin Onset (DLMO) for a given protein sample.

Results

Four hundred and thirty-one (6.2%) proteins displayed consistent endogenous circadian rhythms on both a sleep-wake schedule and under controlled conditions. This subset not only aligns with the proteins selected by the elastic-net model but also maintains performance without diminishing it in comparison to using the complete set of available proteins. Overall, our circadian phase predictor reached a median absolute error (MdAE) of 1.2 hours when performing a leave-one-cross-out cross-validation subject-wise.

Conclusion

This research demonstrates that a considerable number of plasma proteins follow natural circadian rhythms within the human body. Furthermore, it establishes that the DLMO can be accurately predicted with a MdAE slightly over one hour using a single blood sample. More research with larger and more diverse datasets is essential to confirm our method, promising better treatments for circadian disorders and advancing personalized circadian health care.

Support (if any)

Collection, processing, and analysis of the samples were supported by National Institutes of Health (NIH) grant R01 HL148704 and unrestricted gifts. Collection of additional samples was supported by US Office of Naval Research grant N00014-15-1-2408. The BWH CCI is supported by Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH Award UL1 TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers.
0011 Using Polygenic Scores for Circadian Rhythm to Predict Wellbeing, Depressive Symptoms, Chronotype, and Health
Authors: Landvreugd Anne , Pool René , Nivard Michel , Bartels Meike
Published: April 2024

Introduction

The association between the circadian rhythm and diseases has been well-established, while the association with mental health is less explored. Given the heritable nature of the circadian rhythm, this study aimed to investigate the relationship between genes underlying the circadian rhythm and mental health outcomes, as well as a possible gene-environment correlation for circadian rhythm.

Methods

In a sample from the Netherlands Twin Register (N = 14,021), polygenic scores (PGSs) were calculated for two circadian rhythm measures: Morningess and Relative Amplitude. The PGSs were used to predict mental health outcomes such as subjective happiness, quality of life, and depressive symptoms In addition, we performed the same prediction analysis in a within-family design in a subset of dizygotic twins.

Results

The PGS for Morningness significantly predicted Morningness (R2 = 1.55%,) and Depressive Symptoms (R2= 0.22%,). The PGS for Relative Amplitude significantly predicted General Health (R2 = 0.12%,) and Depressive Symptoms (R2 = 0.20%,). Item analysis of the depressive symptoms showed that 4/14 items were significantly associated with the PGSs. The within-family results hinted at a gene-environment correlation for Morningness.

Conclusion

Overall, the results showed that people with a genetic predisposition of being a morning person or a high relative amplitude are likely to have fewer depressive symptoms. Contrarily to our hypotheses, the four associated depressive symptoms described symptoms related to decision-making, energy, and feeling worthless, rather than sleep. Our findings plead for a substantial role for the circadian rhythm in depression research, and to further explore the gene-environment correlation in the circadian rhythm

Support (if any)
0016 In Search of Vitamin Sleep: Vitamin and Mineral Intake and Multimodal Sleep Outcomes in Adolescents
Authors: Broadbent Mary , Kamhout Sarah , Zhang Victoria , Martin McKenna , Homer Kate , Fisher Morgan , Reese Matthew , Duraccio Kara
Published: April 2024

Introduction

Previous studies suggest that under 15% of adolescents regularly consume vitamin- and mineral-rich foods such as leafy greens and legumes. In addition to experiencing poor dietary intake, this developmental group is also subject to high rates of insufficient sleep duration (~70%). Thus, adolescents may be especially susceptible to the influence on micronutrient deficiencies on poor sleep. This study seeks to generalize previous adult findings to an adolescent population who may especially benefit from multimodal therapies targeting poor sleep and diet in tandem.

Methods

Seventy-four adolescents (43 females) ages 14-18 submitted 2-3 dietary recalls on randomized weekends and weekdays. Additionally, participants completed a Dim-Light Melatonin Onset (DLMO) appointment, the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the Pittsburgh Sleep Quality Index (PSQI). Possible associations between vitamin (Folate, Folic Acid, Niacin, Retinol, Riboflavin, Thiamin, Vitamins A, B-6, B12, C, D, E, and K) and mineral (Calcium, Copper, Iron, Magnesium, Phosphorus, Potassium, Selenium, and Zinc) intake and melatonin onset time (DLMO, threshold 4 pg/mL), daytime sleepiness (ESS-CHAD total), and self-reported sleep duration (PSQI Item 4) were evaluated using multiple bivariate regression models.

Results

Following correction for multiple comparisons, no vitamins or minerals were found to be significant predictors of sleep quality outcomes. B12 approached significance for predicting DLMO time (beta=.337, t(64)=2.367, p=.021; R2 = .073, F(3,61)=2.684, p=.054) and daytime sleepiness (beta=.334, t(72)=2.517, p=.014; R2 = .065, F(3,69)= 2.662, p=.055), as did Magnesium for daytime sleepiness (beta=-.284, t(73)=-2.349, p=.022; R2 = .057, F(3,70)=2.481,p=.068) and Zinc for DLMO time (beta=.369, t(65)=2.562, p=.013; R2 = .083, F(3,62)=2.961, p=.039).

Conclusion

Vitamin and mineral intake was not significantly related to self-reported sleep outcomes and DLMO in adolescents. Future studies can examine dietary intake in conjunction with more objective physiological measures of sleep health. Failure to meet RDA in this age group presents limitations when studying the effects of increased consumption. Other study designs could incorporate B12, magnesium, and zinc measurement given potential signal.

Support (if any)
0019 Body Weight Reduction Following 8-weeks of Time-restricted Eating in Peri- and Postmenopausal Women with Obesity
Authors: Grant Leilah , Webb Jennifer , Bates Hailey , Carter Megan , Dressel Madeline , Williams Jonathan , Manson JoAnn , Mora Samia , Joffe Hadine , Rahman Shadab
Published: April 2024

Introduction

Many women experience weight gain due to hormonal changes during menopause. Time-restricted eating (TRE) has been proposed as a dietary intervention to reduce body weight but has not been studied extensively during the menopause transition. We aimed to test the effect of TRE on body weight and composition in peri- and recently (< 5 yrs) postmenopausal women with obesity.

Methods

Participants were recruited from the New England area. To date, 23 women (mean age±SD: 51.9±4.1 yrs; mean BMI±SD: 34.9±3.2 kg/m2) have been randomized to 8-weeks of unrestricted eating (URE; n=11) or TRE (n=12), where participants were instructed to consume calories only during a self-selected 8-hour eating window each day (e.g., 10 am-6 pm). Outcomes included body weight, body composition [fat, fat-free and visceral adipose tissue (VAT) mass, measured via dual x-ray absorptiometry], and 7-day caloric intake [kCal/day; per MealloggerTM app with time-stamp]. Change from baseline to post-intervention was compared between the groups using t-tests.

Results

On average, the TRE eating window was 4.1±0.7 (95%CI 2.7 to 5.6) hours shorter than the URE group (p< 0.001; 7.1±0.2 vs. 11.2±0.7 hours, respectively). Compliance with the daily 8-hour TRE eating window (average compliance 93±6.9% of days) and acceptability (11/12 planned to continue TRE after study completion) were high. Despite no statistically significant between-group difference in calorie intake (1515.8±561.7 vs 1430.0±419.6 kCal/day), the TRE group lost an average of 2.4±0.6 kg (SD), significantly more than the URE group who gained an average of 0.46±0.4 kg (p< 0.01; mean difference=2.8±0.7, 95%CI -4.4 to -1.3). Furthermore, there was a trend toward a greater reduction in fat mass in the TRE (-0.7±0.4 kg) compared to URE group (0.65±0.6 kg) (p=0.059; mean difference=1.4±0.7 kg, 95%CI -2.8 to 0.06). Change in fat-free and VAT mass did not differ.

Conclusion

In this interim analysis of an ongoing trial, 8 weeks of TRE led to a reduction in body weight and possibly fat mass in peri- and postmenopausal women with obesity. Importantly, compliance and acceptability of the diet were high, suggesting that the intervention is feasible and sustainable in this population.

Support (if any)

BWH and Bayer Pharmaceuticals supporting U54AG062322; BWH Pollin Research Award; WHAM Edge Award
0021 Effects of Pharmacological Estradiol Suppression on Urinary 6-sulfatoxymelatonin Output in Premenopausal Women
Authors: Rahman Shadab , Lockley Steven , Cohn Aviva , Kim Hannah , Wiley Aleta , Joffe Hadine , Grant Leilah
Published: April 2024

Introduction

The relationship between the female sex steroid estradiol and the pineal hormone melatonin has been hypothesized to be reciprocal, whereby estradiol is low when melatonin is high and vice versa. Results from human studies have been mixed, however, which may be attributable to the large inter-individual differences in overall levels of melatonin secretion between individuals. Furthermore, menopause, characterized by declining levels of estradiol, has been associated with decreased levels of melatonin, although the contributions of ovarian aging versus chronological aging on melatonin levels is not clear. In the current within-subject experimental study of premenopausal women, we aimed to examine the effects of pharmacologically-induced estradiol suppression on the 24-hour output and circadian rhythm characteristics of the urinary melatonin metabolite, 6-sulfatoxymelatonin (aMT6s), thereby isolating estradiol-related effects from those if chronological aging.

Methods

Urine was collected every 3-4 hours during the daytime and 8-10 hours overnight over ~24 hours during a laboratory study from 12 premenopausal women (mean age±SD= 27.9±5.6 yrs) during their mid-to-late follicular phase when estradiol levels were high (i.e., estrogenized state), and again ~6 weeks later following pharmacologically-induced estradiol suppression (i.e., hypo-estrogenized state) due to administration of the gonadotrophin releasing hormone agonist, leuprolide (3.75mg intramuscular injection). Morning single-timepoint serum estradiol levels, 24-hour aMT6s output, and the cosinor analysis-derived mesor, amplitude and acrophase of the aMT6s rhythm were compared between the estradiol states using paired t-tests or non-parametric alternative.

Results

As expected, leuprolide suppressed estradiol levels by ~90% on average compared to levels in the mid-to-late follicular phase (p< 0.001; 120.7±43.4 vs. 5.6±0.6 pg/mL, respectively, Cohen’s d= 1.1). On average, 24-h aMT6s output was 5.3% higher following estradiol suppression but this was not significantly different from the estrogenized state (p=0.4; 16.1±5.7 vs. 15.4±1.6 µg/24-h, respectively, Cohen’s d= 0.12). Similarly, there were no differences in any of the aMT6s rhythm characteristics between estradiol states.

Conclusion

In a within-subject analysis, pharmacologically-induced estradiol suppression did not influence the overall 24-h output or rhythm characteristics of urinary 6-sulphatoxmelatonin, suggesting that that melatonin and estradiol may not be reciprocal. Furthermore, these results suggest that the decline in melatonin observed across menopause may not be due to ovarian aging.

Support (if any)

R01AG053838
0022 Daily Rhythms of Fractal Motor Activity Regulation in Older Adults: Relevance to Prediction of Alzheimer’s Dementia
Authors: Sun Haoqi , Li Peng , Gao Lei , Yang Jingyun , Yu Lei , Buchman Aron , Bennett David , Westover M Brandon , Hu Kun
Published: April 2024

Introduction

Fractal motor activity regulation (FMAR), characterized by self-similar temporal correlations in activity fluctuations across different timescales, is robust in healthy young but degrades in patients with Alzheimer’s disease (AD). We recently discovered that disrupted FMAR predicted increased risk for AD dementia. It is unknown whether FMAR and its predictability for incident AD vary across the 24-h cycle.

Methods

We studied 1,077 participants in the Rush Memory and Aging Project who were cognitively normal at baseline, had baseline actigraphy, and had at least one follow-up clinical assessment until 2020. To assess the daily rhythm of FMAR, we obtained a scaling exponent α in each 1-h actigraphy data that estimates the temporal correlations in activity fluctuations across timescales of 1.5-10 min, using detrended fluctuation analysis (DFA). For each 1-hour bin across the 24-h cycle, we used a Cox regression model to examine the association of scaling exponent α with incident AD while adjusting for age at baseline, sex, and years of education. The p-values were corrected using Bonferroni correction for the 24 hourly comparisons.

Results

The scaling exponential α from DFA showed a daily rhythm with a trough at 3am (α=0.71) and a peak at 3pm (α=0.84). The hazard ratio (HR) for incident AD (per 1-SD increase in α) also showed a daily rhythm. Specifically, smaller α (indicating more random activity fluctuations) between 7am to 10pm was associated with an increased risk of incident AD (HR ranging from 0.59 [95% CI 0.50-0.70, p < 0.001] to 0.79 [95%CI 0.69-0.91, p = 0.0013], lowest at 3pm); α between 11pm-6am was not significantly correlated with incident AD.

Conclusion

Fractal motor activity regulation in older adults exhibited a daily rhythm and more random activity fluctuations between 7am-10pm were predictive of higher risk for AD dementia.

Support (if any)

NIH RF1AG064312 and BrightFocus Foundation Alzheimer’s Research A2020886S.
0024 Measuring Melanopsin-driven Retinal Responses in Sleep and Circadian Health: Performance of the Pupil Light Reflex
Authors: Klevens Alison , Wescott Delainey , Taylor Maddison , Gamlin Paul , Franzen Peter , Hasler Brant , Siegle Greg , Roecklein Kathryn
Published: April 2024

Introduction

Alterations in the melanopsin-driven post-illumination pupil response (PIPR) may reflect a physiological vulnerability for circadian mood disruptions. However, the PIPR is confounded by other factors affecting retinal irradiance, like how much light reaches the retina. The pupil light reflex (PLR) measures effects on pupil responses that are nonspecific to melanopsin. Controlling for nonspecific factors related to retinal irradiance (i.e., age, entrance pupil diameter, iris pigmentation) is necessary to isolate melanopsin-driven retinal response in PIPR studies. The present study re-analyzed data using group, season, and a group-by-season interaction to predict the PIPR with different covariates testing nonspecific effects on the PIPR. We hypothesized that the PLR alone would explain more variance in the PIPR then the above set of indirect measures of nonspecific effects.

Methods

Participants ages 19-65 (M=34.9, SD=10.6) with seasonal depression (n=25) and non-depressed controls (n=22) completed assessments in the winter and summer months. The PLR was measured as the difference between baseline pupil diameter and the acute minimum constriction in millimeters and expressed as a percent of baseline. The Net PIPR was calculated as the difference between the red and blue trials averaged 10-40 seconds post-light stimulus. Iris pigmentation was rated using the Franssen (2008) scale. Model performance for different covariate sets was assessed using Akaike Information Criteria (AIC). All models included time of the PIPR relative to midsleep.

Results

Significant associations between group, season, and a group*season interaction in predicting the PIPR were found in every model. Model fit varied based on covariates included. The PLR following red light performed best in models predicting the PIPR (AIC=-161.63) compared to a model including age, entrance pupil diameter, and iris pigmentation (AIC=-144.98). The next best fit model included the PLR in response to blue light (AIC=-157.57).

Conclusion

Studies aiming to isolate melanopsin-driven retinal responsivity should adopt the PLR as an individually specific, objective, and contemporaneous measure of nonspecific influences of light on pupil responsivity. Methodology separating the effects of light incident on the retina (e.g., PLR) from melanopsin-driven retinal responses (e.g., PIPR) can inform treatments like bright light therapy, allowing titration of light intensity to account for individual differences in retinal irradiance.

Support (if any)
0031 Shared Genetic Mechanisms Underlying Association Between Sleep Disturbances and Depressive Symptoms
Authors: Moyses-Oliveira Mariana , Zamariolli Malú , Tempaku Priscila , Galduróz José , Andersen Monica , Tufik Sergio
Published: April 2024

Introduction

Although associations between insomnia and major depression disorder have been reported, little is known about the shared genetic mechanisms underlying their comorbidity. Polygenic scores (PGS) for sleep disturbances and depressive symptoms in an epidemiological cohort were calculated and correlated. Genes assigned to variants that compose the best-fit PGS predictions were overlapped to explore the shared genetic bases of sleep problems and depressive symptoms.

Methods

Human OmniExpress BeadChip genotyping was performed on the São Paulo Epidemiologic Sleep Study (EPISONO, N=1042), an adult epidemiological sample subjected to a sleep-based survey. PGS analysis was performed on 900 individuals with PRSice2. Summary statistics from a genome wide association study (GWAS) for depression (N=500,199, United Kingdom Biobank (UKBB) and Psychiatry Genetics Consortium) grounded the PGS calculations for Beck Depression Index (BDI), while insomnia GWAS (N=386,988, UKBB) based the PGS for Insomnia Severity Index (ISI) and Pittsburg Sleep Quality Index (PSQI) in EPISONO. Pearson’s correlation was applied to contrast PGS and clinical scores. Genes were assigned to SNPs using Ensembl Variant Effect Predictor and Fisher’s Exact test was used to test the overlap between gene lists. Pathway enrichment analysis was performed on sets of interest genes using Benjamin-Hochberg test.

Results

All PGS models were significant when individuals were divided as cases or controls according to BDI, PSQI and ISI scales. When clinical scales were used as continuous variables, the best-fit PGS models for BDI (p=0.0004, R2=1.56%) and PSQI scores (p=0.0058, R2=0.87%) reached statistical significance, but PGS calculations were unable to significantly predict ISI scores. PSQI and BDI scores were highly correlated, and the same observation was applied to PGS for sleep quality and depressive symptoms. Genes associated with the variants which compose the best-fit PGS predictions for sleep quality and depressive symptoms were significantly overlapped. Pathways enriched among the intersect genes are related to synapse function and formation.

Conclusion

The genetic bases of sleep quality and depressive symptoms are correlated; their implicated genes are significantly overlapped and converge on neural pathways. This data suggests that sleep complaints accompanying depressive symptoms are not secondary issues, but part of the core mental illness.

Support (if any)

AFIP, FAPESP, CNPq.
0032 Metabolomic Profile of Excessive Daytime Sleepiness in the Hispanic Community Health Study/Study of Latinos
Authors: Faquih Tariq , Yu Bing , Kaplan Robert , Isasi Carmen , Redline Susan , Sofer Tamar , Wang Heming
Published: April 2024

Introduction

Excessive daytime sleepiness (EDS) is a prevalent condition estimated to affect up to 33% of the United States population. EDS is a heterogeneous and complex symptom of various sleep disorders, insufficient sleep, and other chronic conditions and medications. EDS has also been associated with increased risk of cardiovascular and neuropsychiatric diseases, potentially through bidirectional causal pathways. In this study, we used metabolomic measurements in 6071 individuals from the Hispanic Community Health Study/Study of Latinos to elucidate the metabolomic factors associated with EDS.

Methods

EDS was assessed using the Epworth Sleepiness Score (a 24-point scale) at baseline (2008), continuously modeled. Metabolomics (877 metabolites) were quantified using the Metabolon platform—from blood assayed at baseline—and were log scaled. Our primary and sex stratified models adjusted for age, body mass index, ethnicity, recruitment center, alcohol, smoking, and physical activity. Secondary analysis further adjusted for insomnia, sleep duration, and sleep apnea. Significance threshold was set to 0.00013 to account for multiple testing. Finally, the interplay between metabolites, pathways, and genes was investigated through network and pathway enrichment analyses.

Results

Levels of seven metabolite were each associated with a decrease of the sleepiness score by approximately 0.4 points per one log unit increase in metabolite levels. Those metabolites were primarily categorized as fatty acids (Eicosadienoic acid, Docosadienoate), steroids (Pregnenolone sulphate, Tetrahydrocortisol-glucuronide), along with a sphingomyelin and two uncharacterized metabolites. Sex stratified analysis identified three additional metabolites associated with EDS in men: Tyramine O-sulfate and two phosphatidylcholines. Tyramine O-sulfate was particularly associated with an increased sleepiness score by 0.5 per log unit; with attenuation after adjusting for sleep traits. Network and pathway enrichment analysis indicated that changes in pathways related to cortisol metabolism, hormonal steroid metabolism, and melatonin metabolism were linked to EDS.

Conclusion

These results suggest that a combination of metabolomic factors, representing diet and steroid hormonal pathways dietary related metabolites, and some genetic factors contributes to the metabolic profile of EDS. Some associations appeared independent of common sleep disorders while a male-specific association was driven by sleep disturbances (insomnia).

Support (if any)

NIH R01HL153814 (to H.W.), R01HL161012 (to T.S.), and R35HL135818 (to SR).