bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental Age and Childhood Lymphoma and Solid Tumor Risk: A Literature Review and Meta-Analysis
Authors: Domingues Allison , Moore Kristin J , Sample Jeannette , Kharoud Harmeet , Marcotte Erin L , Spector Logan G
Published: May 2022

Background

Although advanced parental age has been definitively linked to pediatric acute lymphoblastic leukemia, studies of parental age and pediatric solid tumors have not reached firm conclusions. This analysis aimed to elucidate the relationship between parental age and pediatric solid tumors through meta-analysis of existing studies based in population registries.

Methods

We searched Medline (PubMed) and Embase for registry-based studies of parental age and solid tumors through March 2022. We performed random-effects meta-analysis to estimate pooled effects and 95% confidence intervals (CIs). All statistical tests were 2-sided.

Results

A total of 15 studies covering 10 childhood solid tumor types (30 323 cases and 3 499 934 controls) were included in this analysis. A 5-year increase in maternal age was associated with an increased risk of combined central nervous system tumors (odds ratio [OR] = 1.07, 95% CI = 1.04 to 1.10), ependymoma (OR = 1.19, 95% CI = 1.09 to 1.31), astrocytoma (OR = 1.10, 95% CI = 1.05 to 1.15), rhabdomyosarcoma (OR = 1.14, 95% CI = 1.03 to 1.25), and germ cell tumors (OR = 1.06, 95% CI = 1.00 to 1.12). A 5-year increase in paternal age was associated with an increased risk of non-Hodgkin lymphoma (OR = 1.06, 95% CI = 1.00 to 1.12).

Conclusions

This meta-analysis of registry-based analyses of parental age and childhood cancer supports the association between older maternal age and certain childhood solid cancers. There is also some evidence that paternal age may be associated with certain cancers such as non-Hodgkin lymphoma. However, as maternal and paternal age are highly correlated, disentangling potential independent causal effects of either factor will require large studies with extensive data on potential confounders.
Current situation survey for establishing personally acceptable radiation dose limits for nuclear disaster responders
Authors: Iyama Keita , Kakamu Takeyasu , Yamashita Kazunori , Shimada Jiro , Tasaki Osamu , Hasegawa Arifumi
Published: May 2022

When responding to disasters, emergency preparedness is essential to ensure that disaster activities are performed smoothly, safely and efficiently. Investigations on the Fukushima accident revealed that lack of preparedness, poor communication and unsuitable emergency measures contributed to an inadequate emergency response to the nuclear disaster. In this study, we conducted a questionnaire survey on the establishment of a personal radiation exposure dose among Disaster Medical Assistance Team (DMAT) members in Japan who might be involved in the initial response to a nuclear disaster. Establishing personal exposure doses for personnel can encourage emergency preparedness and inform decisions on appropriate role assignments during nuclear response activities. Valid responses were obtained from 178 participants, and the response distribution was as follows: ‘Already have own acceptable dose standard,’ 16 (9%); ‘Follow own institution’s standard (and know its value),’ 30 (17%); ‘Follow own institution’s standard (but do not know its value),’ 59 (33%); ‘Haven’t decided,’ 63 (35%) and ‘Don’t understand question meaning,’ 10 (6%). We also assessed intention to engage in nuclear disaster activities among respondents via engagement intent scores (EIS) and found that participants who had established personal exposure standards had significantly higher EIS scores than those who had not decided or who did not understand the question. Thus, educating potential nuclear disaster responders on personal exposure doses may contribute to a higher intention to engage in emergency responses and improve preparedness and response efficiency.
Am I Prepared? The Fears of a Military Resident
Authors: Stewart J Alex
Published: May 2022

The stress of residency has led to continued emphasis on developing resiliency in residents, but what does that mean? When the heartbreak of medicine tries to keep us from moving forward, sometimes all we can do is take a pause.
Ancestral Sequence Reconstruction of a Cytochrome P450 Family Involved in Chemical Defense Reveals the Functional Evolution of a Promiscuous, Xenobiotic-Metabolizing Enzyme in Vertebrates
Authors: Harris Kurt L. , Thomson Raine E.S. , Gumulya Yosephine , Foley Gabriel , Carrera-Pacheco Saskya E. , Syed Parnayan , Janosik Tomasz , Sandinge Ann-Sofie , Andersson Shalini , Jurva Ulrik , Bodén Mikael , Gillam Elizabeth M.J.
Published: May 2022

The cytochrome P450 family 1 enzymes (CYP1s) are a diverse family of hemoprotein monooxygenases, which metabolize many xenobiotics including numerous environmental carcinogens. However, their historical function and evolution remain largely unstudied. Here we investigate CYP1 evolution via the reconstruction and characterization of the vertebrate CYP1 ancestors. Younger ancestors and extant forms generally demonstrated higher activity toward typical CYP1 xenobiotic and steroid substrates than older ancestors, suggesting significant diversification away from the original CYP1 function. Caffeine metabolism appears to be a recently evolved trait of the CYP1A subfamily, observed in the mammalian CYP1A lineage, and may parallel the recent evolution of caffeine synthesis in multiple separate plant species. Likewise, the aryl hydrocarbon receptor agonist, 6-formylindolo[3,2-b]carbazole (FICZ) was metabolized to a greater extent by certain younger ancestors and extant forms, suggesting that activity toward FICZ increased in specific CYP1 evolutionary branches, a process that may have occurred in parallel to the exploitation of land where UV-exposure was higher than in aquatic environments. As observed with previous reconstructions of P450 enzymes, thermostability correlated with evolutionary age; the oldest ancestor was up to 35 °C more thermostable than the extant forms, with a 10T50 (temperature at which 50% of the hemoprotein remains intact after 10 min) of 71 °C. This robustness may have facilitated evolutionary diversification of the CYP1s by buffering the destabilizing effects of mutations that conferred novel functions, a phenomenon which may also be useful in exploiting the catalytic versatility of these ancestral enzymes for commercial application as biocatalysts.
Detecting critical transition signals from single-cell transcriptomes to infer lineage-determining transcription factors
Authors: Yang Xinan H , Goldstein Andrew , Sun Yuxi , Wang Zhezhen , Wei Megan , Moskowitz Ivan P , Cunningham John M
Published: May 2022

Analyzing single-cell transcriptomes promises to decipher the plasticity, heterogeneity, and rapid switches in developmental cellular state transitions. Such analyses require the identification of gene markers for semi-stable transition states. However, there are nontrivial challenges such as unexplainable stochasticity, variable population sizes, and alternative trajectory constructions. By advancing current tipping-point theory-based models with feature selection, network decomposition, accurate estimation of correlations, and optimization, we developed BioTIP to overcome these challenges. BioTIP identifies a small group of genes, called critical transition signal (CTS), to characterize regulated stochasticity during semi-stable transitions. Although methods rooted in different theories converged at the same transition events in two benchmark datasets, BioTIP is unique in inferring lineage-determining transcription factors governing critical transition. Applying BioTIP to mouse gastrulation data, we identify multiple CTSs from one dataset and validated their significance in another independent dataset. We detect the established regulator Etv2 whose expression change drives the haemato-endothelial bifurcation, and its targets together in CTS across three datasets. After comparing to three current methods using six datasets, we show that BioTIP is accurate, user-friendly, independent of pseudo-temporal trajectory, and captures significantly interconnected and reproducible CTSs. We expect BioTIP to provide great insight into dynamic regulations of lineage-determining factors.
Molecular Regulation and Evolution of Cytokinin Signaling in Plant Abiotic Stresses
Authors: Li Lijun , Zheng Qingfeng , Jiang Wei , Xiao Nayun , Zeng Fanrong , Chen Guang , Mak Michelle , Chen Zhong-Hua , Deng Fenglin
Published: May 2022

The sustainable production of crops faces increasing challenges from global climate change and human activities, which leads to increasing instances of many abiotic stressors to plants. Among the abiotic stressors, drought, salinity and excessive levels of toxic metals cause reductions in global agricultural productivity and serious health risks for humans. Cytokinins (CKs) are key phytohormones functioning in both normal development and stress responses in plants. Here, we summarize the molecular mechanisms on the biosynthesis, metabolism, transport and signaling transduction pathways of CKs. CKs act as negative regulators of both root system architecture plasticity and root sodium exclusion in response to salt stress. The functions of CKs in mineral-toxicity tolerance and their detoxification in plants are reviewed. Comparative genomic analyses were performed to trace the origin, evolution and diversification of the critical regulatory networks linking CK signaling and abiotic stress. We found that the production of CKs and their derivatives, pathways of signal transduction and drought-response root growth regulation are evolutionarily conserved in land plants. In addition, the mechanisms of CK-mediated sodium exclusion under salt stress are suggested for further investigations. In summary, we propose that the manipulation of CK levels and their signaling pathways is important for plant abiotic stress and is, therefore, a potential strategy for meeting the increasing demand for global food production under changing climatic conditions.
Prospects of Feral Crop De Novo Redomestication
Authors: Pisias Michael T , Bakala Harmeet Singh , McAlvay Alex C , Mabry Makenzie E , Birchler James A , Yang Bing , Pires J Chris
Published: May 2022

Modern agriculture depends on a narrow variety of crop species, leaving global food and nutritional security highly vulnerable to the adverse effects of climate change and population expansion. Crop improvement using conventional and molecular breeding approaches leveraging plant genetic diversity using crop wild relatives (CWRs) has been one approach to address these issues. However, the rapid pace of the global change requires additional innovative solutions to adapt agriculture to meet global needs. Neodomestication—the rapid and targeted introduction of domestication traits using introgression or genome editing of CWRs—is being explored as a supplementary approach. These methods show promise; however, they have so far been limited in efficiency and applicability. We propose expanding the scope of neodomestication beyond truly wild CWRs to include feral crops as a source of genetic diversity for novel crop development, in this case ‘redomestication’. Feral crops are plants that have escaped cultivation and evolved independently, typically adapting to their local environments. Thus, feral crops potentially contain valuable adaptive features while retaining some domestication traits. Due to their genetic proximity to crop species, feral crops may be easier targets for de novo domestication (i.e. neodomestication via genome editing techniques). In this review, we explore the potential of de novo redomestication as an application for novel crop development by genome editing of feral crops. This approach to efficiently exploit plant genetic diversity would access an underutilized reservoir of genetic diversity that could prove important in support of global food insecurity in the face of the climate change.
Alternative splicing of REGULATOR OF LEAF INCLINATION 1 modulates phosphate starvation signaling and growth in plants
Authors: Guo Meina , Zhang Yuxin , Jia Xianqing , Wang Xueqing , Zhang Yibo , Liu Jifeng , Yang Qingshen , Ruan Wenyuan , Yi Keke
Published: May 2022

Phosphate (Pi) limitation represents a primary constraint on crop production. To better cope with Pi deficiency stress, plants have evolved multiple adaptive mechanisms for phosphorus acquisition and utilization, including the alteration of growth and the activation of Pi starvation signaling. However, how these strategies are coordinated remains largely unknown. Here, we found that the alternative splicing (AS) of REGULATOR OF LEAF INCLINATION 1 (RLI1) in rice (Oryza sativa) produces two protein isoforms: RLI1a, containing MYB DNA binding domain and RLI1b, containing both MYB and coiled-coil (CC) domains. The absence of a CC domain in RLI1a enables it to activate broader target genes than RLI1b. RLI1a, but not RLI1b, regulates both brassinolide (BL) biosynthesis and signaling by directly activating BL-biosynthesis and signaling genes. Both RLI1a and RLI1b modulate Pi starvation signaling. RLI1 and PHOSPHATE STARVATION RESPONSE 2 function redundantly to regulate Pi starvation signaling and growth in response to Pi deficiency. Furthermore, the AS of RLI1-related genes to produce two isoforms for growth and Pi signaling is widely present in both dicots and monocots. Together, these findings indicate that the AS of RLI1 is an important and functionally conserved strategy to orchestrate Pi starvation signaling and growth to help plants adapt to Pi-limitation stress.
Spatially specific mechanisms and functions of the plant circadian clock
Authors: Davis William , Endo Motomu , Locke James C W
Published: May 2022

Like many organisms, plants have evolved a genetic network, the circadian clock, to coordinate processes with day/night cycles. In plants, the clock is a pervasive regulator of development and modulates many aspects of physiology. Clock-regulated processes range from the correct timing of growth and cell division to interactions with the root microbiome. Recently developed techniques, such as single-cell time-lapse microscopy and single-cell RNA-seq, are beginning to revolutionize our understanding of this clock regulation, revealing a surprising degree of organ, tissue, and cell-type specificity. In this review, we highlight recent advances in our spatial view of the clock across the plant, both in terms of how it is regulated and how it regulates a diversity of output processes. We outline how understanding these spatially specific functions will help reveal the range of ways that the clock provides a fitness benefit for the plant.
Phosphate transporter PHT1;1 is a key determinant of phosphorus acquisition in Arabidopsis natural accessions
Authors: Chien Pei-Shan , Chao Ya-Ting , Chou Chia-Hui , Hsu Yu-Ying , Chiang Su-Fen , Tung Chih-Wei , Chiou Tzyy-Jen
Published: May 2022

Phosphorus (P) is a mineral nutrient essential for plant growth and development, but most P in the soil is unavailable for plants. To understand the genetic basis of P acquisition regulation, we performed genome-wide association studies (GWASs) on a diversity panel of Arabidopsis (Arabidopsis thaliana). Two primary determinants of P acquisition were considered, namely, phosphate (Pi)-uptake activity and PHOSPHATE TRANSPORTER 1 (PHT1) protein abundance. Association mapping revealed a shared significant peak on chromosome 5 (Chr5) where the PHT1;1/2/3 genes reside, suggesting a connection between the regulation of Pi-uptake activity and PHT1 protein abundance. Genes encoding transcription factors, kinases, and a metalloprotease associated with both traits were also identified. Conditional GWAS followed by statistical analysis of genotype-dependent PHT1;1 expression and transcriptional activity assays revealed an epistatic interaction between PHT1;1 and MYB DOMAIN PROTEIN 52 (MYB52) on Chr1. Further, analyses of F1 hybrids generated by crossing two subgroups of natural accessions carrying specific PHT1;1- and MYB52-associated single nucleotide polymorphisms (SNPs) revealed strong effects of these variants on PHT1;1 expression and Pi uptake activity. Notably, the soil P contents in Arabidopsis habitats coincided with PHT1;1 haplotype, emphasizing how fine-tuned P acquisition activity through natural variants allows environmental adaptation. This study sheds light on the complex regulation of P acquisition and offers a framework to systematically assess the effectiveness of GWAS approaches in the study of quantitative traits.
Liquid flow in scaffold derived from natural source: experimental observations and biological outcome
Authors: Salerno Elisabetta , Orlandi Giulia , Ongaro Claudio , d’Adamo Alessandro , Ruffini Andrea , Carnevale Gianluca , Zardin Barbara , Bertacchini Jessika , Angeli Diego
Published: May 2022

This study investigates the biological effects on a 3D scaffold based on hydroxyapatite cultured with MC3T3 osteoblasts in response to flow-induced shear stress (FSS). The scaffold adopted here (B-HA) derives from the biomorphic transformation of natural wood and its peculiar channel geometry mimics the porous structure of the bone. From the point of view of fluid dynamics, B-HA can be considered a network of micro-channels, intrinsically offering the advantages of a microfluidic system. This work, for the first time, offers a description of the fluid dynamic properties of the B-HA scaffold, which are strongly connected to its morphology. These features are necessary to determine the FSS ranges to be applied during in vitro studies to get physiologically relevant conditions. The selected ranges of FSS promoted the elongation of the attached cells along the flow direction and early osteogenic cell differentiation. These data confirmed the ability of B-HA to promote the differentiation process along osteogenic lineage. Hence, such a bioactive and naturally derived scaffold can be considered as a promising tool for bone regeneration applications.
Development and psychometric evaluation of the PMR-Impact Scale: a new patient reported outcome measure for polymyalgia rheumatica
Authors: Twohig Helen , Mitchell Caroline , Mallen Christian D , Muller Sara
Published: May 2022

Objectives

PMR causes pain, stiffness and disability in older adults. Measuring the impact of the condition from the patient’s perspective is vital to high-quality research and patient-centred care, yet there are no validated patient-reported outcome measures (PROMs) for PMR. We set out to develop and psychometrically evaluate a PMR-specific PROM.

Methods

Two cross-sectional postal surveys of people with a confirmed diagnosis of PMR were used to provide data for field testing and psychometric evaluation. A total of 256 participants completed the draft PROM. Distribution of item responses was examined, and exploratory factor analysis and Rasch analysis were used to inform item reduction, formation of dimension structure and scoring system development. Some 179 participants completed the PROM at two time points, along with comparator questionnaires and anchor questions. Test–retest reliability, construct validity and responsiveness were evaluated.

Results

Results from the field-testing study led to the formation of the PMR-Impact Scale (PMR-IS), comprising four domains (symptoms, function, psychological and emotional well-being, and steroid side effects). Construct validity and test–retest reliability met accepted quality criteria for each domain. There was insufficient evidence from this study to determine its ability to detect flares/deterioration, but the PMR-IS was responsive to improvements in the condition.

Conclusion

The PMR-IS offers researchers a new way to assess patient-reported outcomes in clinical studies of PMR. It has been developed robustly, with patient input at every stage. It has good construct validity and test–retest reliability. Further work is needed to fully establish its responsiveness and interpretability parameters, and to assess its real-world clinical utility.
Low incidence and transient elevation of autoantibodies post mRNA COVID-19 vaccination in inflammatory arthritis
Authors: Blank Rebecca B , Haberman Rebecca H , Qian Kun , Samanovic Marie , Castillo Rochelle , Jimenez Hernandez Anthony , Vasudevapillai Girija Parvathy , Catron Sydney , Uddin Zakwan , Rackoff Paula , Solomon Gary , Azar Natalie , Rosenthal Pamela , Izmirly Peter , Samuels Jonathan , Golden Brian , Reddy Soumya , Mulligan Mark J , Hu Jiyuan , Scher Jose U
Published: May 2022

Objectives

Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls.

Methods

Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization.

Results

Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, P = 0.014). Incidence of de novo anti-CCP seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titre, transient, and not associated with increase in IA flares.

Conclusions

In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population.
0007 Temporal Associations Between Actigraphy-Measured Daytime Movement Behaviors and Daytime Sleep in Early Childhood
Authors: Laurent Christine St , Holmes Jennifer , Spencer Rebecca
Published: May 2022

Introduction

Although napping in early childhood is associated with some cognitive and behavioral outcomes, less is known about relations with physical health measures. Lower levels of sedentary behavior and higher levels of physical activity have been beneficially associated with sleep measures in adults. Studies exploring sleep and daytime movement behaviors (sedentary time and physical activity) in young children have had inconsistent results and primarily focused on overnight sleep. The purpose of this micro-longitudinal analysis was to determine if: 1) daytime movement behaviors predicted the likelihood of napping the next day, 2) daytime movement behaviors predicted next-day nap duration, and 3) the occurrence of a nap predicted next-day movement behaviors.

Methods

In 240 children (age=50.8±9.8 months, 49.2% female) sedentary time (% of wake time), total physical activity (counts/min), and nap duration (min) were derived from wrist-based actigraphy (mean = 9.7 days), and occurrence of a nap was recorded daily. Multilevel logistic and linear models with lagged effects were used to examine temporal within-person relations between wake behaviors and nap sleep, and adjusted for night’s sleep duration of nights between days of interest (min), age (months), sex (male or female), and socioeconomic status (index). Preliminary models included interactions with nap habituality (rarely, sometimes, or frequent).

Results

Occurrence of a nap was not associated with next-day wake behaviors and previous-day wake behaviors did not predict nap duration. However, on days children napped, they were less sedentary (B=-2.09, p<0.001) and more active (B=25.8, p<0.001) the following day. Nap habituality did not moderate these associations.

Conclusion

Bidirectional associations between nap sleep and daytime wake behaviors were not evident. While daytime movement behaviors were not predictive of nap sleep, napping was beneficially associated with subsequent-day movement behaviors in preschool children. Further studies could explore specific nap sleep metrics in samples with more diverse sleep health, as well as consider the reason for daytime napping.

Support (If Any)

NIH R01 HL111695
0031 Sleep Regularity is Associated with DNA Methylation in Cognitive, Cardiovascular and Mood-related Genes: A GWAS-informed Study in Adolescents
Authors: Larsen Michael , Morales-Ghinaglia Natasha , He Fan , Imamura Yuka , Berg Arthur , Vgontzas Alexandros , Liao Duanping , Bixler Edward , Fernandez-Mendoza Julio
Published: May 2022

Introduction

Adolescence is associated with a delay in the circadian timing of sleep. However, social factors prevent adolescents from adapting to a later sleep-wake pattern, leading to different forms of circadian misalignment that may increase the risk of cardiovascular and mental health disorders. Several GWAS have identified genes associated with sleep and circadian phenotypes, however, little is known regarding the epigenetic basis and significance of sleep timing and its regularity in adolescence.

Methods

We analyzed data from 230 adolescents from the Penn State Child Cohort follow-up study who provided a blood sample for DNA extraction and had complete at-home 7-night (at least 3) actigraphy (ACT) data. ACT-measured sleep midpoint was calculated as the intra-individual mean of the 7-night midpoint (zeroed to midnight) of the sleep period. ACT-measured sleep regularity was calculated as the intra-individual standard deviation of the 7-night sleep midpoint. Epigenome-wide single nucleotide resolution of DNA methylation in cytosine-phosphate-guanine (CpG) sites and surrounding regions were obtained from peripheral leukocytes. This study focuses on methylation sites in GWAS-informed genes previously associated with sleep and circadian phenotypes. Linear regression assessed the association between sleep midpoint and sleep regularity with site-specific methylation levels, adjusting for sex, age, race/ethnicity, body mass index, and psychotropic medication use. Using the Benjamini & Hochberg method to adjust for a false discovery rate. Adjusted p-values are reported as q-values.

Results

Sleep midpoint was not associated with a significant change in methylation at any of the measured intragenic sites. Sleep regularity was significantly associated with differential methylation at 238 intragenic sites in 147 genes with an adjusted p<0.05, of which, three sites were within GWAS-informed sleep/circadian-related genes. Higher sleep irregularity was associated with hypermethylation in MAD1L1 (q=2.4x10-2) and with hypomethylation in CALN1 (q=3.8 x 10-4) and ZNF618 (q=3.8 x 10-2).

Conclusion

Sleep irregularity is associated with altered DNA methylation in genes previously identified in GWAS of sleep/circadian phenotypes. Our data provides evidence for a potential epigenetic link between sleep irregularity and genes involved in neurocognitive functioning (CALN1), internalizing disorders (MAD1L1) and blood pressure (ZNF618).

Support (If Any)

National Institutes of Health (R01HL136587, R01MH118308, UL1TR000127)
0040 Sleeping during the Pandemic: COVID-19-related stressors and their influence on parental sleep, parenting, and children’s psychosocial health
Authors: Peltz Jack , Daks Jennifer , Rogge Ronald
Published: May 2022

Introduction

The COVID-19 pandemic has affected millions of parent in the United States by creating physical health-related stress, changes to work and parenting demands, and the possibility of losing a job or not being able to pay bills (Brooks et al., 2020). Such stressors have the potential to disrupt parents’ basic, essential needs, such as sleep (e.g., Sadeh et al., 2004). Although ample research suggests that disturbances to parents’ sleep can have diverse, negative repercussions on their own behavior and functioning (e.g., Grandner et al., 2020), there remains relatively little evidence linking parents’ sleep problems to potentially disrupt parenting processes and children’s behaviors. Given the emerging and established links between these diverse constructs, the proposed study will examine the potential for COVID-19-related stressors to prospectively influence children’s behavior via parents’ sleep quality and subsequent parenting practices.

Methods

The sample is comprised of 1003 parents of school-aged (5-18 years old) children who completed an initial online survey (from March 27th to April 30th of 2020) followed by up to 8 weekly online diary assessments. During the initial survey, parents reported on three forms of COVID-related stress: health-related stress, stress associated with work/parenting demands, and finance-related stress. In the follow-ups, parents completed measures of sleep (i.e., PROMIS sleep disturbance questionnaire), parenting (e.g., Alabama Parenting Questionnaire), and child behavioral problems (i.e., CBCL).

Results

Multi-level modeling results, at the between-person level, suggested that the influence of COVID-related financial stress on children’s behavioral problems was mediated by parental sleep disturbance and angry/hostile parenting behaviors. At the within-person level, weekly spikes in parental sleep disturbance were associated with corresponding spikes in angry/hostile parenting, which, in turn, were associated with subsequent spikes in children’s behavior problems.

Conclusion

Our results highlight the longitudinal impact of parental sleep disturbance as a mechanism linking COVID-19-related stressors, parenting, and child functioning.

Support (If Any)
0044 Pre-Pandemic Circadian Phase Predicts Pandemic Sleep, Depression, and Alcohol Use Among Adolescents
Authors: Hasler Brant , Wallace Meredith , Graves Jessica , Buysse Daniel , Siegle Greg , Clark Duncan
Published: May 2022

Introduction

Growing evidence links later circadian timing during adolescence to worse sleep, more severe depression, and greater alcohol involvement, perhaps due to circadian misalignment and sleep restriction imposed by early school start times. School schedules initially shifted later during the COVID-19 pandemic, which hypothetically should reduce circadian misalignment and sleep restriction for adolescents with later circadian timing, and thus may mitigate any problems with sleep, depression, and alcohol. Here we used the pandemic as a natural experiment to test whether adolescent drinkers with later circadian timing, relative to those with earlier circadian timing, showed improved sleep, depressive symptoms, and alcohol involvement.

Methods

We studied 42 high school students reporting alcohol use (aged 16-18; 27 female participants), assessing circadian phase via the dim light melatonin onset (DLMO) during pre-pandemic conditions, and then following them over four remote assessments every 3 months during the pandemic. Sleep characteristics were assessed via the Munich Chronotype Questionnaire, depressive symptoms were assessed via the Quick Inventory of Depressive Symptomatology, and alcohol use was assessed via a 90-day Timeline Followback. Mixed-effect models focused on the pre-pandemic baseline, COVID baseline (Apr/May 2020), and COVID-9-mo (Jan/Feb 2021) timepoints, and covaried for age, time between pre-pandemic and COVID baselines, and current school/work status.

Results

In the pre-pandemic period, compared to those with earlier circadian timing, individuals with later circadian timing (later DLMO) got relatively less sleep (shorter total sleep time) on school nights. During the pandemic, earlier and later groups no longer differed on school night sleep. Over the course of the pandemic, compared to the earlier group, individuals with later circadian timing also reported larger increases in alcohol use (number of drinks, drinking days, and maximum drinks). Individuals with later circadian timing reported relatively greater depressive symptoms both pre-pandemic and 9-months into the pandemic.

Conclusion

While individuals with later circadian timing benefitted in terms of more school night sleep during the pandemic, this did not translate to mitigating depression or alcohol use. These findings suggest that later circadian timing may contribute to risk for depression and alcohol use over and above effects due to insufficient sleep.

Support (If Any)

Supported by grants from NIH (R01AA025626; P50DA046346).
0052 A mixed-methods examination of perceived challenges during the COVID-19 pandemic: Associations with sleep health and nightmares among healthcare workers
Authors: Franzen Ronald , Kahlon Ramandeep , Jones Melissa , Agrawal Ritwick , Crew Earl
Published: May 2022

Introduction

The emergence of CoVID-19 has created an immense burden on healthcare systems across the world, placing healthcare workers (HCWs) under significant, additional stress while they also confront multiple personal, family and sociopolitical challenges during the pandemic. Many studies have reported the negative impact of pandemic-related stress on sleep of HCWs. Our mixed-methods investigation sought to extend existing research by characterizing the themes of HCWs’ primary concerns during the early pandemic and identifying the most salient concerns which might be impacting sleep.

Methods

North American HCWs (n = 1331) were surveyed during the “second wave” of CoVID-19 case increases (6/9/2020 – 8/17/2020), which included a questionnaire with measures of sleep health (RU-SATED) and nightmare frequency (PSQI). Additionally, each HCW was asked to openly-describe their most salient concern with regard to the pandemic. Each response was categorized by topic. T-tests were conducted to compare frequencies of each response category with sleep health and nightmare frequency.

Results

The study sample comprised 1331 HCWs (91.7% female; 74.5% non-Hispanic white; 64.31% with exposure to CoVID-19 patients; 85.1% working in-person). Primary concerns were grouped into 8 categories including combinations of personal/familial-level concerns (e.g. concern about CoVID-19 infection/spread), and work-related stressors (e.g. increased workload). Concerns about lack of PPE/equipment was significantly associated with lower scores on RU-SATED (t = -2.69; p = .007) and increased nightmare frequency (t = 2.70; p = .007). Additionally, concerns about increased workload were significantly associated with lower scores on both RU-SATED (t = -2.79; p = .005) and increased nightmare frequency (t = 5.24; p = .000). Individually, primary concerns for CoVID-19 infection/spread was significantly associated with more-frequent nightmares (t = 2.01; p = .045). Neither sleep measure was associated with categories involving societal-level concerns (e.g. sociopolitical concerns) among the sample.

Conclusion

Our results indicate that the HCWs most concerned about workplace stressors during the pandemic indicated poorer sleep health and more frequent nightmares. Further analyses could help guide proper stratification of therapeutic approaches to improve sleep health and related distress for HCWs.

Support (If Any)
0055 Bidirectional Associations Between Sleep and Daily Behaviors in Urban American Indian/Alaska Native (AI/AN) Youth
Authors: Dong Lu , D'Amico Elizabeth , Dickerson Daniel , Brown Ryan , Palimaru Alina , Johnson Carrie , Troxel Wendy
Published: May 2022

Introduction

American Indian/Alaska Native (AI/AN) individuals experience health disparities that emerge early in life. This is the first study to prospectively examine associations between sleep and daily behaviors in urban AI/AN adolescents.

Methods

Participants were 142 urban AI/AN adolescents (mean age = 14 years, 58% female). Sleep health characteristics were measured with actigraphy (total sleep time [TST], sleep efficiency [SE]) and daily diary (bedtime, wakeup time, sleep quality, alertness) over 7 days. Daily behaviors (caffeine consumption, physical activities, participation in traditional cultural activities, electronic use after 8PM, and mood) were measured via daily diary. Multilevel models examined the degree to which nightly sleep predicted next day’s behaviors and, reversely, daily behaviors predicted nightly sleep, controlling for age, gender, and weekday/weekends. Weekday/weekend was tested as a moderator.

Results

Earlier bedtime (b = -0.11, p = 0.03) and wakeup time (b = -0.18, p < 0.001) were associated with more physical activity the following day. Earlier wakeup time (b = -0.17, p = 0.048) and shorter TST (b = -0.004, p = 0.03) were associated with greater participation in cultural activities. Later wakeup time (b = 0.96, p = 0.004), better sleep quality (b = 0.38, p < 0.001), longer TST (b = 0.02, p = 0.001), and higher alertness (b = 0.28, p < 0.001) were associated with higher mood rating.When examining the reverse direction, greater daytime caffeine consumption was associated with later wakeup time (b = 0.17, p = 0.01). More physical activity was associated with earlier bedtime (b = -0.12, p = 0.002) and wakeup time (b = -0.12, p = 0.01), but only during weekdays. Participation in cultural activities was associated with later bedtimes (b = 0.14, p = 0.02). More electronic use after 8 PM was associated with later bedtime (b = 0.38, p < 0.001) and wakeup time (b = 0.32, p < 0.001), shorter TST (b = -8.24, p = 0.001) and lower SE (b = -0.94, p = 0.002), with stronger effects on the weekdays than weekends.

Conclusion

Findings highlight dynamic associations between sleep and daily behaviors in AI/AN adolescents and may elucidate novel pathways for intervention and future research.

Support (If Any)

This work was supported by NIMHD R01MD012190 (WMT, EJD, DLD).
0063 Biopsychosocial Predictors of Sleep Health in Black, Asian, and Hispanic/Latinx Samples
Authors: Nielson Spencer , Dautovich Natalie , Dzierzewski Joseph
Published: May 2022

Introduction

Sleep health is an important aspect of sleep and is associated with biopsychosocial factors such as physical health, mental health, and social functioning. Disparities in sleep health are widely prevalent in individuals who identify as Black, Asian, and Hispanic/Latinx. Investigating unique associations between general sleep health and biopsychosocial factors may elucidate underlying associations and lead to innovative approaches to promote sleep health in these historically marginalized populations.

Methods

3,284 adults participated in an online study investigating sleep longitudinally across normal development (ISLAND). These analyses were conducted in the samples of individuals who self-identified as Black (n = 263, Mage = 40.6 years, 52.1% female), Asian (n = 208, Mage = 34.8 years, 39.9% female), and Hispanic/Latinx (n = 216, Mage = 35.8 years, 44.4% female). Participants were stratified across the lifespan, with equal numbers of men and women recruited. Participants completed several questionnaires including demographics, the RU-SATED, Patient Health Questionnaire-15 (PHQ-15), Patient Health Questionnaire-2 (PHQ-2), Generalized Anxiety Disorder-2 (GAD-2), and the De Jong Gierveld Loneliness Scale. Multiple regression analyses were conducted within each group to determine whether biological (PHQ-15 without the sleep item), psychological (composite score of PHQ-2 and GAD-2), and social (social loneliness factor of the De Jon Gierveld Loneliness Scale) predictors of sleep health while controlling for demographic variables (i.e., age, sex, education).

Results

Within the Black sample, lower mental health functioning was associated with poorer sleep health (p=0.008). Within the Asian sample lower physical functioning and lower mental health functioning were significantly associated with poorer sleep health (p’s<.001). Within the Hispanic/Latinx sample, lower physical functioning was significantly associated with poorer sleep health (p<.001).

Conclusion

Sleep health was observed to be associated with biopsychosocial factors within Black, Asian, and Hispanic/Latinx samples. Unique patterns of associations were observed within each sample. Future research would benefit from employing longitudinal designs or using more objective measurements to further elucidate these associations.

Support (If Any)

National Institute on Aging of the National Institutes of Health under Award Number K23AG049955 (PI: Dzierzewski).
0068 Impact of OSA Therapy on Healthcare Economics: Actuarial Analysis of OSA Prevalence, Therapy Adherence, Co-morbidity, and Costs in a Large CMS Population Cohort
Authors: Fernandez Chris , Rusk Sam , Glattard Nick , Turkington Fred , Nygate Yoav , Kaiser Mark , McClurg Jen , Richard Maggie , Duncan Ian , Watson Nathaniel
Published: May 2022

Introduction

Research studying the economics of OSA therapy faces confounds including the prevalence of undiagnosed OSA, rate of diagnosed patients declining therapy, spectrum of treatment adherence, and effects of concurrent co-morbidity. We provide an actuarial analysis to study the economic impact of OSA therapy, accounting for these confounds, using the 2016-2018 Medicare 5% LDS Analytical File, a random sample of Medicare Claims containing approximately 2.9 million patients/year, resulting in N=2,001,538 eligible Fee-For-Service patients excluding managed care patients and incomplete data.

Methods

We segmented the study population into three cohorts and three 12-month time-periods. The cohorts analyzed were A) patients with OSA diagnosis and >12 months treatment, B) patients with OSA and <12 months treatment, and C) patients with OSA diagnosis who never received treatment, resulting in 1,351,838 patient-months. We analyzed the healthcare costs in each cohort in the year before treatment, the first year of treatment, and following treatment year. We applied actuarial risk adjustment within each cohort and time-period to provide a risk-adjusted cost comparison. Results were analyzed cross-sectionally given zero-to-seven co-morbidities among obesity, hypertension, type-II diabetes, depression, COPD, CHF, and/or prior stroke, facility-vs-home testing, and with-or-without surgical procedures.

Results

The average per-patient-per-month (PPPM) total medical spending was highest in the diagnosed-but-never-treated cohort-C ($1,375), second highest in <12-months treatment cohort-B ($1,005), and lowest in >12-months treatment cohort-A ($983). In both cohorts that started therapy, average/quantile costs decreased from pre-treatment year to post-treatment year, and from the first-to-second year on therapy. Compared to no-therapy cohort-C, costs were 29% lower in cohort-A and 27% lower in cohort-B. Among co-morbid, 75th quartile of cost members, we observed similar differences (18% and 16%) but larger absolute dollars. Patients undergoing surgical procedures had higher costs but lower spend reduction in initial and following year of therapy (22% and 5%).

Conclusion

We observed significant differences in cost between OSA patients that started treatment versus those that did not, and those differences further increased the year following therapy onset. These findings imply that receiving treatment for OSA reduces a patients overall medical spend. In terms of mean cost, the >12-month and <12-month cohorts costs fell in both follow-up treatment years.

Support (If Any)
0071 A Mexican Spanish Version of the Circadian Energy Scale
Authors: Valencia Dora , Begay Tommy , Granados Karla , Delgadillo Marcos , Ghani Sadia , Molina Patricia , Alfonso-Miller Pamela , Fernandez Fabian-Xosé , Wills Chloe , Grandner Michael
Published: May 2022

Introduction

Circadian health is increasingly recognized for the contributions it makes to general health. Few instruments assessing circadian rhythms have been translated into Spanish, however. The present study describes a Spanish translation of the Circadian Energy Scale (CIRENS). The instrument was designed according to the language norms of those living along the US-Mexico border by a bilingual research team. The CIRENS was completed by both English and Spanish speaking border residents, in their preferred language.

Methods

Data were collected from a sample of N=100 individuals of Mexican descent living in Nogales, Arizona. CIRENS is a 2-item scale that assesses chronotype by examining overall energy level in the morning and evening. Translation of the instrument into Spanish was done according to the following process: (1) a bilingual study team member attempted an initial translation; (2) a bilingual community member edited the translation; (3) a certified medical translator edited the revision; (4) a focus group of N=5 bilingual community members made further contextual edits; (5) a back-translation was performed; (6) an additional bilingual focus group examined the final version for compatibility; and (7) the medical translator certified the accuracy of the final version. T-tests examined differences between those who completed the measure in Spanish vs English.

Results

Of the N=100 survey respondents, N=42 completed the CIRENS in Spanish. No significant differences were observed in overall chronotype determination between those who took the Spanish versus English version (p=0.22) of the instrument. As a continuous score, the respondents in Spanish demonstrated slightly more morningness (p=0.01). Per the individual items, no differences were seen for evening energy levels (p=0.22), but Spanish respondents reported slightly higher morning energy scores (2.76 vs 2.17, p=0.008).

Conclusion

The individuals that completed the CIRENS in Spanish reported higher morning energy scores but no significant differences in chronotype. Future studies can use the Spanish CIRENS to evaluate circadian factors across cultural/linguistic groups.

Support (If Any)
0080 Influence of neighborhood safety on stress and sleep
Authors: Corona Frida , Mednick Sara
Published: May 2022

Introduction

Our health is influenced by the environment in which we live. Due to socioeconomic differences, disparities exist across neighborhoods, with certain groups experiencing higher detriments to their health compared to others. Emotional distressing experiences due to the neighborhood in which we live cause stress levels to rise. Given the psychological and physiological impact of stress, high levels of stress can be a contributing factor for poor sleep. We investigated the influence of feelings of neighborhood safety on stress and sleep and the ethnic differences found in each of these outcomes. In addition, we ask whether feelings of neighborhood safety mediate the association between stress and sleep.

Methods

1,606 participants were recruited online through Amazon Mechanical Turk to participate in a questionnaire. Components of this survey included demographic data, the Pittsburgh Sleep Quality Index (PSQI), Perceived Stress Scale (PSS), and the Neighborhood Questionnaire Neighborhood Safety Subscale.

Results

We found that as neighborhood safety levels rise, stress levels lower. Further, ethnic differences were found for feelings of neighborhood safety, stress, and sleep: Latino participants had the lowest feelings of neighborhood safety, highest stress levels, and worst sleep. We also found that stress mediates the association between neighborhood safety and sleep.

Conclusion

Our results highlight the contribution of feeling safe in one's own neighborhood on stress and sleep outcomes. Given the ethnic differences present in each of our outcomes, future work should investigate neighborhood characteristics influencing neighborhood safety as possible areas of intervention benefitting sleep.

Support (If Any)