Targeting Ras-, Rho-, and Rab-family GTPases via a conserved cryptic pocket.

The family of Ras-like GTPases consists of over 150 different members, regulated by an even larger number of guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) that comprise cellular switch networks that govern cell motility, growth, polarity, protein trafficking, and gene expression. Efforts to develop selective small molecule probes and drugs for these proteins have been hampered by the high affinity of guanosine triphosphate (GTP) and lack of allosteric regulatory sites. This paradigm was recently challenged by the discovery of a cryptic allosteric pocket in the switch II region of K-Ras. Here, we ask whether similar pockets are present in GTPases beyond K-Ras. We systematically surveyed members of the Ras, Rho, and Rab family of GTPases and found that many GTPases exhibit targetable switch II pockets. Notable differences in the composition and conservation of key residues offer potential for the development of optimized inhibitors for many members of this previously undruggable family.

Effect of Choose-Your-Own-Adventure (CYOA) Activities on Pharmacy Student Knowledge.

OBJECTIVE: Many strategies are used in pharmacy education to maintain student engagement through active learning. Gamification, such as the choose-your-own-adventure activity (CYOAA), is one such method. The purpose of this study was to assess improvement in clinical knowledge and retention after the implementation of CYOAA. METHODS: Two CYOAAs were designed and implemented within second-year pharmacy courses. One activity was on venous thromboembolism (VTE) and the other on chronic obstructive pulmonary disease (COPD). Students completed a six question prequiz and postquiz for both activities mapped to core learning objectives and four similar but more difficult questions on corresponding exams. After the CYOAAs, the students completed a reflection and perceptions survey. RESULTS: Seventy-five students completed the VTE CYOAA and 77 completed COPD CYOAA. Over the three time points, there was a significant decrease in the mean assessment scores on the VTE activity (68% to 65% to 40%) versus a significant and sustained increase in mean assessment scores on COPD (62% to 83% to 85%). Of the 36 and 33 students who completed the postsurvey, the majority agreed or strongly agreed that they preferred CYOAA to traditional cases and that the activities improved their knowledge, critical thinking skills, and confidence in clinical decision-making. CONCLUSION: There was a mixed result in the mean assessment scores, with an increase seen with the COPD CYOAA and a decrease with VTE, as well as positive perceptions for VTE and COPD, indicating that this classroom innovation is well-liked and may improve knowledge outcomes.

Planetary health learning objectives: foundational knowledge for global health education in an era of climate change.

Planetary health is an emerging field that emphasises that humans depend on a healthy Earth for survival and, conversely, that the sustainability of Earth systems is dependent on human behaviours. In response to member demands for resources to support teaching and learning related to planetary health, the Consortium of Universities for Global Health (CUGH) convened a working group to develop a set of planetary health learning objectives (PHLOs) that would complement the existing ten CUGH global health learning objectives. The eight PHLOs feature Earth system changes, planetary boundaries, and climate change science; ecological systems and One Health; human health outcomes; risk assessment, vulnerability, and resilience; policy, governance, and laws (including the UN Framework Convention on Climate Change and the Paris Agreement); roles and responsibilities of governments, businesses, civil society organisations, other institutions, communities, and individuals for mitigation, adaptation, conservation, restoration, and sustainability; environmental ethics, human rights, and climate justice; and environmental literacy and communication. Educators who use the PHLOs as a foundation for teaching, curriculum design, and programme development related to the health-environment nexus will equip learners with a knowledge of planetary health science, interventions, and communication that is essential for future global health professionals.

Impact of the South African Child Support Grant on memory decline and dementia probability in rural and low-income mothers, 2014-2021.

INTRODUCTION: Aging populations across sub-Saharan Africa are rapidly expanding, leading to an increase in the burden of Alzheimer's disease and related dementias (ADRD). Cash transfer interventions are one plausible mechanism to combat ADRD at a population-level in low-income settings. We exploited exogenous variation in eligibility for South Africa's Child Support Grant (CSG) to estimate the longitudinal association between potential CSG benefit and cognitive trajectories in rural mothers with <10 children (n = 1090). METHODS: South Africa's CSG delivers monthly cash payments to primary caregivers, predominantly mothers, to offset the costs associated with child rearing. This study implemented a quasi-experimental design using data (2014-2022) from a rural, low-income cohort in the Agincourt research area, South Africa. We fit linear mixed effects models and generalized linear models to estimate the association of potential CSG benefit per eligible child with memory decline and dementia probability, respectively. We stratified all models by the mother's total number of children (1-4 and 5-9) and examined effect modification by household wealth and the mother's education level. RESULTS: Having above median CSG per eligible child was associated with higher baseline memory scores (ß = 0.12 SD units, 95% CI = 0.02, 0.22) but steeper memory decline (ß = -0.02 SD units, 95% CI = -0.04, -0.00) compared to below median CSG. Within stratified analyses, this effect was primarily observed among mothers with 5-9 children. No associations were observed between potential CSG per eligible child and dementia probability. CONCLUSIONS: Our findings support the use of large-scale cash transfers as a promising intervention to promote healthy cognitive aging in mid-life women within rural, low-income settings. However, we found evidence that the CSG in its current structure may not be sufficient support for women to sustain measurable cognitive benefits over the long-term.

Exploring the role of pain on physical activity among youth with acute lymphoblastic leukemia using the biopsychosocial model.

BACKGROUND: Engaging in physical activity (PA) throughout cancer treatment offers many benefits, but may be challenging due to cancer-related pain. Pain research in pediatric cancer has primarily focused on procedural pain, with fewer studies exploring how pain affects PA. The current study qualitatively investigated the impact of pain on PA in youth with acute lymphoblastic leukemia (ALL) using a biopsychosocial framework. PROCEDURE: As part of a larger study, caregivers (N = 17) of a child diagnosed with ALL and on treatment for less than 1 year completed a semi-structured interview about perceptions of their child's health behaviors during ALL treatment. This secondary analysis focused specifically on discussions about pain and its impact on PA. We followed Braun and Clarke's (2006) six-step thematic analysis framework to identify themes of pain-related barriers to PA. RESULTS: Key pain-related barriers endorsed by caregivers included: interactions among pain and treatment effects, caregiver distress around seeing their child in pain, and fear of interfering with medical equipment. Despite these barriers, caregivers found creative solutions to adapt activities for their child. Caregivers were reassured by PA advice from their medical team; however, advice varied between teams. CONCLUSION: The relationship between pain and PA during ALL treatment is influenced by an intricate system of biological (e.g., treatment effects), psychological (e.g., parental distress), and social (e.g., communication among families and medical teams) factors. Future directions include identifying evidence-based PA recommendations and exploring family-team communication dynamics. This study also highlights a need to prioritize ALL pain management and involve caregivers in behavioral treatment protocols to improve PA.

Structure of calcineurin bound to PI4KA reveals dual interface in both PI4KA and FAM126A.

Phosphatidylinositol 4-kinase alpha (PI4KA) maintains the phosphatidylinositol 4-phosphate (PI4P) and phosphatidylserine pools of the plasma membrane. A key regulator of PI4KA is its association into a complex with TTC7 and FAM126 proteins. This complex can be regulated by the CNAß1 isoform of the phosphatase calcineurin. We previously identified that CNAß1 directly binds to FAM126A. Here, we report a cryoelectron microscopic (cryo-EM) structure of a truncated PI4KA complex bound to calcineurin, revealing a unique direct interaction between PI4KA and calcineurin. Hydrogen deuterium exchange mass spectrometry (HDX-MS) and computational analysis show that calcineurin forms a complex with an evolutionarily conserved IKISVT sequence in PI4KA's horn domain. We also characterized conserved LTLT and PSISIT calcineurin binding sequences in the C terminus of FAM126A. These dual sites in PI4KA and FAM126A are both in close proximity to phosphorylation sites in the PI4KA complex, suggesting key roles of calcineurin-regulated phosphosites in PI4KA regulation. This work reveals novel insight into how calcineurin can regulate PI4KA activity.

The role of parents' ability mindsets in parent-child interactions during math and reading activities.

Parents can be instrumental in promoting young children's early mathematics and literacy skills. However, differences in parents' beliefs can influence their behavior during parent-child interactions. We examined how parental beliefs about the fixedness of children's math and reading abilities shape their interactions with their 4- and 5-year-old children during an educational activity. Parental beliefs about children's abilities were manipulated using "articles" indicating that academic ability is fixed in one domain (e.g., math) but malleable in another (e.g., reading). We then investigated differences in parental unconstructive (performance-oriented and controlling) and constructive (mastery-oriented and autonomy-supportive) involvement across conditions. We also examined whether parent behavior differed depending on the type of educational material parents were told the activity tapped into. The results showed that parents who were induced to have a fixed mindset about reading took full control of the reading activity more often than those who were induced to have a growth mindset about reading, but not math. Parents did not differ in constructive involvement between mindset induction conditions in either domain. We also found that parent autonomy behavior in math differed depending on parents' general theory of intelligence beliefs. Overall, we found some evidence that parents' beliefs about the malleability of their children's ability in a specific domain affected their behaviors in that domain.

Medication development for AUD: A systematic review of clinical trial methodology.

Refining clinical trial methodology has become increasingly important as study design is shown to influence treatment efficacy. To maximize the efficiency of randomized clinical trials (RCTs), researchers aim to establish standardized practices. The goal of this systematic review is to describe methodological practices of clinical trials for alcohol use disorder (AUD) over the past 40 years. To achieve this goal, a PubMed search was conducted in April 2023 for RCTs on AUD medications published between July 2018 through April 2023. Resulting studies were combined with a previous search from 1985 through 2018. Inclusion criteria for the RCT studies were: (1) a randomized controlled trial, (2) double or single blinded, (3) placebo or active control condition, (4) alcohol use as the primary endpoint, (5) 4 or more weeks of treatment, and (6) 12 or more weeks of follow-up. In total, methodological data from 139 RCTs representing 19 medications and spanning the past four decades were summarized. Results indicated that the most common medications tested were naltrexone (k = 42), acamprosate (k = 24), and baclofen (k = 11). On average, participants were 74% male and consumed 226 drinks per month pre-randomization. The median length of treatment was 12 weeks (IQR = 12-16; min = 4 max = 52) and the median follow-up duration was 12.5 weeks (IQR: 12-26; min = 7 max = 104). There were two broad domains of outcomes (i.e., abstinence and heavy drinking), with most studies featuring outcomes from both domains (k = 87; 63%). Reporting practices were summarized by decade, revealing an increased enrollment of females, better reporting of race and ethnicity data, and less studies requiring pre-trial abstinence. This review summarizes the current state of the literature on randomized clinical trials for AUD including effect sizes for individual studies and summaries of key methodological features across this representative set of clinical trials.

SARS-CoV-2 correlates of protection from infection against variants of concern.

Serum neutralizing antibodies (nAbs) induced by vaccination have been linked to protection against symptomatic and severe coronavirus disease 2019. However, much less is known about the efficacy of nAbs in preventing the acquisition of infection, especially in the context of natural immunity and against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune-escape variants. Here we conducted mediation analysis to assess serum nAbs induced by prior SARS-CoV-2 infections as potential correlates of protection against Delta and Omicron infections, in rural and urban household cohorts in South Africa. We find that, in the Delta wave, D614G nAbs mediate 37% (95% confidence interval: 34-40%) of the total protection against infection conferred by prior exposure to SARS-CoV-2, and that protection decreases with waning immunity. In contrast, Omicron BA.1 nAbs mediate 11% (95% confidence interval: 9-12%) of the total protection against Omicron BA.1 or BA.2 infections, due to Omicron's neutralization escape. These findings underscore that correlates of protection mediated through nAbs are variant specific, and that boosting of nAbs against circulating variants might restore or confer immune protection lost due to nAb waning and/or immune escape. However, the majority of immune protection against SARS-CoV-2 conferred by natural infection cannot be fully explained by serum nAbs alone. Measuring these and other immune markers including T cell responses, both in the serum and in other compartments such as the nasal mucosa, may be required to comprehensively understand and predict immune protection against SARS-CoV-2.

Pediatric sport and nonsport concussions presenting to emergency departments: injury circumstances, characteristics, and clinical management.

OBJECTIVE: The aim of this study was to compare injury circumstances, characteristics, and clinical management of emergency department (ED) presentations for sports-related concussion (SRC) and non-SRC. METHODS: This multicenter prospective observational study identified patients 5-17 years old who presented to EDs within 24 hours of head injury, with one or more signs or symptoms of concussion. Participants had a Glasgow Coma Scale score of 13-15 and no abnormalities on CT (if performed). Data were stratified by age: young children (5-8 years), older children (9-12 years), and adolescents (13-17 years). RESULTS: Of 4709 patients meeting the concussion criteria, non-SRC accounted for 56.3% of overall concussions, including 80.9% of younger child, 51.1% of older child, and 37.0% of adolescent concussions. The most common mechanism of non-SRC was falls for all ages. The most common activity accounting for SRC was bike riding for younger children, and rugby for older children and adolescents. Concussions occurring in sports areas, home, and educational settings accounted for 26.2%, 21.8%, and 19.0% of overall concussions. Concussions occurring in a sports area increased with age, while occurrences in home and educational settings decreased with age. The presence of amnesia significantly differed for SRC and non-SRC for all age groups, while vomiting and disorientation differed for older children and adolescents. Adolescents with non-SRC were admitted to a ward and underwent CT at higher proportions than those with SRC. CONCLUSIONS: Non-SRC more commonly presented to EDs overall, with SRC more common with increasing age. These data provide important information to inform public health policies, guidelines, and prevention efforts.

Special considerations for the child with obesity: An Obesity Medicine Association (OMA) clinical practice statement (CPS) 2024.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details assessment and management of the child with overweight or obesity. The term "child" is defined as the child between 2 and 12 years of age. Because children are in a continual state of development during this age range, we will specify when our discussion applies to subsets within this age range. For the purposes of this CPS, we will use the following definitions: overweight in the child is a body mass index (BMI) ≥ 85th and <95th percentile, obesity in the child is a BMI ≥95th percentile, and severe obesity is a BMI ≥120% of the 95th percentile. Methods: The information and clinical guidance in this OMA Clinical Practice Statement are based on scientific evidence, supported by medical literature, and derived from the clinical perspectives of the authors. Results: This OMA Clinical Practice Statement provides an overview of prevalence of disease in this population, reviews precocious puberty in the child with obesity, discusses the current and evolving landscape of the use of anti-obesity medications in children in this age range, discusses the child with obesity and special health care needs, and reviews hypothalamic obesity in the child. Conclusions: This OMA Clinical Practice Statement on the child with obesity is an evidence based review of the literature and an overview of current recommendations. This CPS is intended to provide a roadmap to the improvement of the health of children with obesity, especially those with metabolic, physiological, psychological complications and/or special healthcare needs. This CPS addresses treatment recommendations and is designed to help the clinician with clinical decision making.

Respiratory neuropathology in Spinocerebellar ataxia type 7.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurological disorder caused by a deleterious CAG repeat expansion in the coding region of the ataxin-7 gene. Infantile onset SCA7 leads to severe clinical manifestation of respiratory distress, but the exact cause of respiratory impairment remains unclear. Using the infantile SCA7 mouse model, the SCA7266Q/5Q mouse, we examined the impact of pathological poly-Q-ataxin-7 mutant ataxin-7 on hypoglossal (XII) and phrenic motor units. We identified the transcript profile of the medulla and cervical spinal cord and, investigated the XII and phrenic nerve and the neuromuscular junctions in the diaphragm and tongue. SCA-7 astrocytes showed significant intranuclear inclusions of ataxin-7 in the XII and putative phrenic motor nuclei. Transcriptomic analysis revealed dysregulation of genes involved in amino acid and neurotransmitter transportation and myelination. Additionally, SCA7 mice demonstrated blunted efferent output of the XII nerve and demyelination in both XII and phrenic nerves. Finally, there was an increased number of NMJ clusters with higher expression of synaptic markers in SCA7 mice compared to WT controls. These pre-clinical findings elucidate the underlying pathophysiology responsible for impaired glial cell function and death leading to dysphagia, aspiration and respiratory failure in infantile SCA7.

Tailored approach to participant recruitment and retention to maximize health equity in pediatric cancer research.

BACKGROUND: Lack of diversity in participants throughout the research process limits the generalizability of findings and may contribute to health disparities. There are unique challenges to recruitment of families to pediatric cancer research studies, especially for those from disadvantaged backgrounds. Thus, there is a need to evaluate the most effective recruitment and retention strategies to optimize equitable recruitment of diverse participants. METHODS: The present study adapted and implemented methods outlined previously in the literature. These previous efforts were developed to address barriers to pediatric research, behavioral health intervention research and research with Black adolescents. Recruitment and retention strategies are described across four different time points: pre-approach, initial connection, building connection and follow-up. Eligible families of children with a pediatric cancer diagnosis were approached during a routine oncology visit. Once consented, enrollment and retention rates over three timepoints of data collection were recorded and evaluated. RESULTS: Results indicated high rates of enrollment (86%) and retention (95%) for eligible participants. There were no trends in heightened attrition for any specific subgroup. CONCLUSIONS: The findings of this study are promising and suggest these recruitment and retention strategies may be useful in recruiting individuals from disadvantaged backgrounds.

Study of pediatric appendicitis scores and management strategies: A prospective observational feasibility study.

OBJECTIVE: The objective was to investigate the feasibility of prospectively validating multiple clinical prediction scores (CPSs) for pediatric appendicitis in an Australian pediatric emergency department (ED). METHODS: A literature search was conducted to identify potential CPSs and a single-center prospective observational feasibility study was performed between November 2022 and May 2023 to evaluate the performance of identified CPSs. Children 5-15 years presenting with acute right-sided or generalized abdominal pain and clinician suspicion of appendicitis were included. CPSs were calculated by the study team from prospectively clinician-collected data and/or review of medical records. Accuracy of CPSs were assessed by area under the receiver operating characteristic curve (AUC) and proportions correctly identifiable as either low-risk or high-risk with the best performing CPS compared to clinician gestalt. Final diagnosis of appendicitis was confirmed on histopathology or by telephone/email follow-up for those discharged directly from ED. RESULTS: Thirty CPSs were identified in the literature search and 481 patients were enrolled in the study. A total of 150 (31.2%) patients underwent appendectomy with three (2.0%) having a normal appendix on histopathology. All identified CPSs were calculable for at least 50% of the patient cohort. The pediatric Appendicitis Risk Calculator for pediatric EDs (pARC-ED; n = 317) was the best performing CPS with AUC 0.90 (95% confidence interval [CI] 0.86-0.94) and specificity 99.0% (95% CI 96.4%-99.7%) in diagnosing high-risk cases and a misclassification rate of 4.5% for low-risk cases. CONCLUSIONS: The study identified 30 CPSs that could be validated in a majority of patients to compare their ability to assess risk of pediatric appendicitis. The pARC-ED had the highest predictive accuracy and can potentially assist in risk stratification of children with suspected appendicitis in pediatric EDs. A multicenter study is now under way to evaluate the potential of these CPSs in a broader range of EDs to aid clinical decision making in more varied settings.

Multilevel Interventions Targeting Obesity: State of the Science and Future Directions.

A seminal report, released in 2001 by the Institute of Medicine, spurred research on the design, implementation, and evaluation of multilevel interventions targeting obesity and related behaviors. By addressing social and environmental factors that support positive health behavior change, interventions that include multiple levels of influence (e.g., individual, social, structural) aim to bolster effectiveness and, ultimately, public health impact. With more than 20 years of multilevel obesity intervention research to draw from, this review was informed by published reviews (n = 51) and identified intervention trials (n = 103), inclusive of all ages and countries, to elucidate key learnings about the state of the science. This review provides a critical appraisal of the scientific literature related to multilevel obesity interventions and includes a description of their effectiveness on adiposity outcomes and prominent characteristics (e.g., population, setting, levels). Key objectives for future research are recommended to advance innovations to improve population health and reduce obesity.

Respiratory Syncytial Virus-Associated Hospitalizations in Children <5 Years: 2016-2022.

BACKGROUND: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities. METHODS: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses. We estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 prepandemic seasons (2016-2020) to those hospitalized in 2021 or 2022. RESULTS: There was no difference in median age or age distribution between prepandemic and 2021 seasons. Median age of children hospitalized with RSV was higher in 2022 (9.6 months vs 6.0 months, P < .001). RSV-associated hospitalization rates were higher in 2021 and 2022 than the prepandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37-2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in prepandemic seasons (P < .001 and P = .003, respectively), but there was no difference in the proportion hypoxemic, mechanically ventilated, or admitted to intensive care. CONCLUSIONS: The atypical 2021 and 2022 RSV seasons resulted in higher hospitalization rates with similar disease severity to prepandemic seasons.

Correction: The cross-sectional association of parental psychosocial status with children's Body Mass Index z-score and the mediating role of children's energy balance behaviors-the ABCD Study.

[This corrects the article DOI: 10.1371/journal.pone.0302147.].

Does the Paraphilia Scale Work for Everyone? Confirmatory Factor Analysis and Measurement Invariance Across Gender and Sexual Orientation Groups.

We conducted three studies to examine the factor structure and measurement invariance of the Paraphilia Scale, a measure of paraphilic interests used in multiple studies. In the first study, we conducted a confirmatory factor analysis (CFA) testing different a priori models with a community sample of 1,040 adults previously reported by Seto et al. (2021), and found support for a hierarchical four-factor model: An agonistic continuum involving coercion or physical pain (biastophilia, sexual sadism, masochism), chronophilias (pedophilia, hebephilia), courtship disorders (voyeurism, exhibitionism, and frotteurism), and fetishism (object fetishism, transvestic fetishism, urophilia-coprophilia). This factor structure was replicated in a second study comprising a combined sample of 400 mTurk participants and 870 university students. The third study analyzed the community sample and found evidence of configural invariance but not scalar or metric invariance across gender (man or woman) and sexual orientation for gender (heterosexual or other sexual orientation). This indicates that the factor structure of the Paraphilia Scale is robust for gender and sexual orientation for gender, but factor loadings differ across these groups, as do the loadings of individual items on the four factors. Implications for research on gender and sexual orientation differences in paraphilic interests are discussed.

Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

Pioneering a multi-phase framework to harmonize self-reported sleep data across cohorts.

STUDY OBJECTIVES: Harmonizing and aggregating data across studies enables pooled analyses that support external validation and enhance replicability and generalizability. However, the multidimensional nature of sleep poses challenges for data harmonization and aggregation. Here we describe and implement our process for harmonizing self-reported sleep data. METHODS: We established a multi-phase framework to harmonize self-reported sleep data: (1) compile items, (2) group items into domains, (3) harmonize items, and (4) evaluate harmonizability. We applied this process to produce a pooled multi-cohort sample of five US cohorts plus a separate yet fully harmonized sample from Rotterdam, Netherlands. Sleep and sociodemographic data are described and compared to demonstrate the utility of harmonization and aggregation. RESULTS: We collected 190 unique self-reported sleep items and grouped them into 15 conceptual domains. Using these domains as guiderails, we developed 14 harmonized items measuring aspects of satisfaction, alertness/sleepiness, timing, efficiency, duration, insomnia, and sleep apnea. External raters determined that 13 of these 14 items had moderate-to-high harmonizability. Alertness/Sleepiness items had lower harmonizability, while continuous, quantitative items (e.g. timing, total sleep time, and efficiency) had higher harmonizability. Descriptive statistics identified features that are more consistent (e.g. wake-up time and duration) and more heterogeneous (e.g. time in bed and bedtime) across samples. CONCLUSIONS: Our process can guide researchers and cohort stewards toward effective sleep harmonization and provide a foundation for further methodological development in this expanding field. Broader national and international initiatives promoting common data elements across cohorts are needed to enhance future harmonization and aggregation efforts.