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Abstract Background Despite the many benefits of school meals, not all students participate. One reason students may not participate in school meals is because they instead purchase breakfast or lunch from food outlets located around schools that mostly carry unhealthy items. This study examined whether school participation in the Community Eligibility Provision (CEP), which allows qualifying schools to serve free meals to all students, moderated the association between the community food environment around schools and student meal participation. Methods This study employed a longitudinal repeated-measures design using school-level data collected between 2014 and 2020 within four low-income school districts (n = 126 schools) in the US. We obtained meal participation data from state records and created a measure characterizing the community food environment within 0.25 miles of schools (characterized as low-density of unhealthy food outlets vs. high-density of unhealthy food outlets) through a latent class analysis. Regression analysis estimated associations between community food environments, CEP participation, and participation rates in school breakfast and school lunch, assessed in separate models. Results While no moderating effect of school CEP status was observed for breakfast or lunch participation, school breakfast participation was predicted to be 4% lower in high-density food environments than in low-density environments (P-value = .049) among non-CEP schools, and there was no difference in participation by the community food environment among CEP-participating schools. Differences in breakfast participation by the community food environment among non-CEP schools were mostly attributable to middle/high schools, with participation predicted to be 10% lower in high-density environments than in low-density environments among non-CEP middle/high schools (P-value

Abstract The advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery. We report key genetic pathways, including changes in erythrocyte regulation, stress induction, and immune changes affected by spaceflight. We also present the first m6A methylation profiles for a human space mission, suggesting a significant spike in m6A levels immediately post-flight. These data and results represent the first longitudinal long-read RNA profiles and RNA modification maps for each gene for astronauts, improving our understanding of the human transcriptome’s dynamic response to spaceflight.

Abstract Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a “spaceflight signature” of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

Abstract Background Mobile upright PET devices have the potential to enable previously impossible neuroimaging studies. Currently available options are imagers with deep brain coverage that severely limit head/body movements or imagers with upright/motion enabling properties that are limited to only covering the brain surface. Methods In this study, we test the feasibility of an upright, motion-compatible brain imager, our Ambulatory Motion-enabling Positron Emission Tomography (AMPET) helmet prototype, for use as a neuroscience tool by replicating a variant of a published PET/fMRI study of the neurocorrelates of human walking. We validate our AMPET prototype by conducting a walking movement paradigm to determine motion tolerance and assess for appropriate task related activity in motor-related brain regions. Human participants (n = 11 patients) performed a walking-in-place task with simultaneous AMPET imaging, receiving a bolus delivery of F18-Fluorodeoxyglucose. Results Here we validate three pre-determined measure criteria, including brain alignment motion artifact of less than

Objective: To describe differences in the frequency of small-for-gestational age (SGA) and large-for-gestational age (LGA) driven by different birth weight curves in assisted reproductive technology (ART)–conceived pregnancies. Design: Retrospective cohort study. Setting: Single academic medical center. Patients: Singleton live births between the gestational ages of 36 weeks and 0 days and 42 weeks and 6 days from fresh or frozen embryo transfer (ET). Intervention(s): None. Main Outcome Measure(s): SGA (90th percentile) classified by Fenton, INTERGROWTH-21, World Health Organization, Duryea, and Oken curves. Results: The median birth weight and gestational age at birth among fresh ET pregnancies were 3,289g (interquartile range [IQR], 2,977–3,600g) and 39.4 (IQR, 38.6–40.3) weeks, respectively, and those among frozen ET pregnancies were 3,399g (IQR, 3,065–3,685g) and 39.4 (IQR, 38.7–40.1) weeks, respectively. The frequencies of SGA neonates using each birth weight standard ranged from 5.8% to 13.4% for fresh ET and from 3.5% to 8.7% for frozen ET. Those of LGA neonates ranged from 5.3% to 14.3% for fresh ET and from 6.6% to 21.2% for frozen ET. Conclusion: The frequency of SGA and LGA neonates among ART-conceived gestations is partially driven by the birth weight standard. Selecting an appropriate standard that best reflects the patient population is critical to quantifying the risk of ART-conceived pregnancies.

Objective: To evaluate whether access to buprenorphine to treat opioid use disorder (OUD) was associated with the coronavirus disease pandemic, the relaxation of training requirements to obtain an X-Waiver to prescribe buprenorphine (April 2021), and the removal of the X-Waiver (December 2022). Patients and Methods: The OptumLabs Data Warehouse, which includes claims from Commercial and Medicare Advantage enrollees, was used to evaluate trends in prescription fills from January 1, 2019, to June 30, 2023. We compared fill patterns of buprenorphine for OUD with acamprosate to treat alcohol use disorder and naltrexone to treat alcohol use disorder or OUD. We evaluated trends in the rate ratio (RR) of overall fills; RR by days supply; distribution of fills by daily dose; and distribution of fills by prescriber type. Results: Coronavirus disease (RR, 1.06; 95% CI, 1.01-1.11) was associated with a slightly increased rate of fills for Commercial enrollees but not overall or for Medicare Advantage enrollees. There were also no significant increases (P>0.05) associated with the change in training requirements or removal of the X-Waiver. Over the study period, there was an increasing share of fills for 16+ mg for Commercial enrollees, and buprenorphine prescribers were more likely to be advanced practice nurses or physician assistants. Conclusion: We did not find meaningful improvement in access in response to coronavirus disease or the changes in the X-Waiver. These findings suggest that interventions beyond removing the X-Waiver may be needed to improve buprenorphine access.

The COVID-19 pandemic has been a major disruption in higher education, challenging universities to engage with community partners in unprecedented ways. Among them was an accelerated challenge to ways of engaging with surrounding communities and the resulting importance this holds for social change. A common approach has been for the university to offer mutually beneficial help to communities through top-down directives and strategies. Another approach prioritizes democratic engagement, including co-constructed knowledge generation and political action where the university is part of a larger ecosystem engaged in public problem solving and deeply sustained ways of collaborating. Moments of economic and social crises put into stark view higher education's intentions: are we playing at community involvement, or are we committed partners, leveraging our unique missions to join our communities in solving the problems facing us? This article discusses how a university's response to the pandemic illustrates democratic community engagement, including how the university partnered with community organizations to alleviate the dire impacts of the pandemic on peoples' basic needs and equity. Lessons learned for university-community engagement during normal times and times of crisis are shared, including ways to foster social change that addresses the inequities illuminated by the pandemic.

Multicellular life requires altruistic cooperation between cells. The adaptive immune system is a notable exception, wherein germinal center B cells compete vigorously for limiting positive selection signals. Studying primary human lymphomas and developing new mouse models, we found that mutations affecting BTG1 disrupt a critical immune gatekeeper mechanism that strictly limits B cell fitness during antibody affinity maturation. This mechanism converted germinal center B cells into supercompetitors that rapidly outstrip their normal counterparts. This effect was conferred by a small shift in MYC protein induction kinetics but resulted in aggressive invasive lymphomas, which in humans are linked to dire clinical outcomes. Our findings reveal a delicate evolutionary trade-off between natural selection of B cells to provide immunity and potentially dangerous features that recall the more competitive nature of unicellular organisms.

Abstract Cell motility plays an essential role in many biological processes as cells move and interact within their local microenvironments. Current methods for quantifying cell motility typically involve tracking individual cells over time, but the results are often presented as averaged values across cell populations. While informative, these ensemble approaches have limitations in assessing cellular heterogeneity and identifying generalizable patterns of single‐cell behaviors, at baseline and in response to perturbations. In this study, CaMI is introduced, a computational framework designed to leverage the single‐cell nature of motility data. CaMI identifies and classifies distinct spatio‐temporal behaviors of individual cells, enabling robust classification of single‐cell motility patterns in a large dataset (n = 74 253 cells). This framework allows quantification of spatial and temporal heterogeneities, determination of single‐cell motility behaviors across various biological conditions and provides a visualization scheme for direct interpretation of dynamic cell behaviors. Importantly, CaMI reveals insights that conventional cell motility analyses may overlook, showcasing its utility in uncovering robust biological insights. Together, a multivariate framework is presented to classify emergent patterns of single‐cell motility, emphasizing the critical role of cellular heterogeneity in shaping cell behaviors across populations.

AS K-12 SCHOOL OFFICIALS struggle to address a post-Covid surge of student misbehavior and violence, they must also navigate rapid swings in civil rights directives from the U.S. Department of [...]

ObjectivesThis double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19.MethodsCOVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory).ResultsIn all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment.ConclusionERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.

Abstract Despite regulating overlapping gene enhancers and pathways, CREBBP and KMT2D mutations recurrently co-occur in germinal center (GC) B cell-derived lymphomas, suggesting potential oncogenic cooperation. Herein, we report that combined haploinsufficiency of Crebbp and Kmt2d induces a more severe mouse lymphoma phenotype (vs either allele alone) and unexpectedly confers an immune evasive microenvironment manifesting as CD8+ T-cell exhaustion and reduced infiltration. This is linked to profound repression of immune synapse genes that mediate crosstalk with T-cells, resulting in aberrant GC B cell fate decisions. From the epigenetic perspective, we observe interaction and mutually dependent binding and function of CREBBP and KMT2D on chromatin. Their combined deficiency preferentially impairs activation of immune synapse-responsive super-enhancers, pointing to a particular dependency for both co-activators at these specialized regulatory elements. Together, our data provide an example where chromatin modifier mutations cooperatively shape and induce an immune-evasive microenvironment to facilitate lymphomagenesis.

INTRODUCTION: Given the challenges health systems face in providing effective nonpharmacologic treatment for pain and psychological distress, clinical effectiveness studies of evidence-based strategies such as music therapy (MT) are needed. OBJECTIVES: This study examined changes in patient-reported outcomes (PROs) after MT and explored variables associated with pain reduction of ≥2 units on a 0 to 10 numeric rating scale (NRS). METHODS: A retrospective review was conducted on initial MT interventions provided to adults receiving community hospital care between January 2017 and July 2020. Sessions were included if participants reported pre-session pain, anxiety, and/or stress scores of ≥4 on the NRS. Data analysis included a bootstrap analysis of single-session changes in PROs and a logistic regression exploring variables associated with pain reduction (ie, ≥2 units vs

Abstract To date, the most complete paleolake‐level reconstructions for the late Pleistocene water bodies that once occupied the Dead Sea depression have been based on the combination of dating of lake sediments and terrestrial materials. However, despite these major accomplishments, there is still limited spatial control regarding the water levels, suggesting some degree of uncertainty concerning the magnitude and rate of lake‐level changes. Here, we re‐examine the late Pleistocene lake‐level changes in the Dead Sea during the transition from paleolake Lisan to the present‐day Dead Sea. We rely on systematic dating of fossil stromatolites including 84 radiocarbon and 15 U‐series ages, stable‐isotope measurements, paleobiology, high‐resolution topography, and numerical modeling to assess lake‐level changes. Our results indicate that the highstand of paleolake Lisan was of shorter duration and the transition between Lake Lisan and the Dead Sea occurred at least 5 Kyrs earlier than previously indicated. By refining the timeline and accuracy of lake‐level positions during the transition paleolake Lisan—Dead Sea, our study offers new insights into the regional and local paleo‐climatic conditions during the last glacial period in this region.

Abstract Examining kidney fibrosis is crucial for mechanistic understanding and developing targeted strategies against chronic kidney disease (CKD). Persistent fibroblast activation and tubular epithelial cell (TEC) injury are key CKD contributors. However, cellular and transcriptional landscapes of CKD and specific activated kidney fibroblast clusters remain elusive. Here, we analyzed single cell transcriptomic profiles of two clinically relevant kidney fibrosis models which induced robust kidney parenchymal remodeling. We dissected the molecular and cellular landscapes of kidney stroma and newly identified three distinctive fibroblast clusters with “secretory”, “contractile” and “vascular” transcriptional enrichments. Also, both injuries generated failed repair TECs (frTECs) characterized by decline of mature epithelial markers and elevation of stromal and injury markers. Notably, frTECs shared transcriptional identity with distal nephron segments of the embryonic kidney. Moreover, we identified that both models exhibited robust and previously unrecognized distal spatial pattern of TEC injury, outlined by persistent elevation of renal TEC injury markers including Krt8 and Vcam1, while the surviving proximal tubules (PTs) showed restored transcriptional signature. We also found that long-term kidney injuries activated a prominent nephrogenic signature, including Sox4 and Hox gene elevation, which prevailed in the distal tubular segments. Our findings might advance understanding of and targeted intervention in fibrotic kidney disease.

Samuel N Rodgers-Melnick,1,2 Robert J Trager,1 Thomas E Love,2– 4 Jeffery A Dusek5 1Connor Whole Health, University Hospitals of Cleveland, Cleveland, OH, USA; 2Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 4Population Health and Equity Research Institute, The MetroHealth System, Cleveland, OH, USA; 5Department of Family Medicine and Community Health, Case Western Reserve University School of Medicine, Cleveland, OH, USACorrespondence: Samuel N Rodgers-Melnick, University Hospitals Connor Whole Health, 11100 Euclid Avenue, Wearn 548A, Cleveland, OH, 44106, USA, Tel +1 216 844 7727, Fax +1 216 201 6220, Email Samuel.RodgersMelnick@UHhospitals.orgObjective: To examine variables associated with engagement in (1) integrative health and medicine (IHM) and (2) nonpharmacologic modalities rather than opioids among United States adults with chronic pain.Methods: Using the 2019 National Health Interview Survey, we examined sociodemographic, pain, and mental health predictors of (1) the sum of IHM modalities (ie, chiropractic care, yoga/Tai Chi, massage, or meditation/guided imagery) used to manage pain and (2) exclusive engagement in nonpharmacologic pain management modalities (ie, IHM, a chronic pain self-management program, support groups, or physical, rehabilitative, occupational, or talk therapy) or opioids in the past 3 months.Results: Metropolitan residency, higher family income, higher education levels, increased number of pain locations, and increased frequency of pain limiting life/work activities were associated with increased odds of IHM engagement. Older age, male sex, non-Hispanic Black/African American race/ethnicity, and daily opioid use were associated with decreased odds of IHM engagement. Older age, male sex, and increased depressive symptoms were associated with decreases in the count of IHM modalities used to manage pain. Metropolitan residency, higher family income, and higher education levels were associated with increased odds of exclusive nonpharmacologic modality engagement. Older age and increasing frequency of pain limiting life/work activities were associated with decreased odds of exclusive nonpharmacologic modality engagement.Conclusions: We identified several contrasts between factors prevalent among individuals with chronic pain and factors associated with engagement in nonpharmacologic and IHM modalities. These results support efforts to address barriers to accessing these modalities among subpopulations of adults with chronic pain (eg, older adults, individuals identifying as Black/African American, rural residents, and those with lower levels of education and income).Plain Language Summary: This study examined factors influencing the use of integrative health and non-drug treatments for chronic pain in the United States. Results revealed that metropolitan residence, higher income, and education were associated with increased use of these treatments, while older age, male sex, daily opioid use, and non-Hispanic Black/African American ethnicity were associated with decreased use. The findings emphasize the importance of addressing barriers to these forms of care, especially among older adults, Black/African American individuals, and those with higher depressive symptoms and lower education and income levels, who are more likely to have chronic pain.Keywords: integrative medicine, chronic pain, nonpharmacologic, opioids

Purpose: The goal of this study is to examine how shyness affects a child's performance on language assessments that vary in sociability. We hypothesized that accuracy on language tasks would be driven by shyness such that shyer children would perform better on nonsociable tasks compared to sociable tasks. Method: The procedures followed a quasi-experimental design. One hundred twenty-two participants, ages 17-42 months and varying in their temperament, each underwent a series of three language tasks. The order of tasks was randomized, and each task varied in the social interaction required: a looking task, a pointing task, and a production task. Data were collected via Zoom, and parents reported their child's shyness level via the Early Child Behavior Questionnaire. Results: Shyness was compared with participants' accuracy across the three tests while controlling for age and vocabulary percentile. There were significant differences in children's performance across the tasks, with respect to shyness. Shyer children performed worse on the production task compared to less shy children. All children did well on the pointing task regardless of shyness level, but performance was more nuanced on the looking task such that shyer children were at times more accurate but also less likely to respond in general. Conclusions: As shown by these results, shyer and less shy children respond differentially to methods of language assessment that vary in sociability. It is important for clinicians to acknowledge shyness when choosing an appropriate assessment of children's language. Future direction includes assessing performance on standardized assessments.

Purpose: This study aims to explore barriers and pathways to a whole-institution governance of sustainability within the working structures of universities. Design/methodology/approach: This paper draws on multi-year interviews and hierarchical structure analysis of ten universities in Canada, the USA, Australia, Hong Kong, South Africa, Brazil, the UK and The Netherlands. The paper addresses existing literature that championed further integration between the two organizational sides of universities (academic and operations) and suggests approaches for better embedding sustainability into four primary domains of activity (education, research, campus operations and community engagement). Findings: This research found that effective sustainability governance needs to recognise and reconcile distinct cultures, diverging accountability structures and contrasting manifestations of central-coordination and distributed-agency approaches characteristic of the university's operational and academic activities. The positionality of actors appointed to lead institution-wide embedding influenced which domain received most attention. The paper concludes that a whole-institution approach would require significant tailoring and adjustments on both the operational and academic sides to be successful. Originality/value: Based on a review of sustainability activities at ten universities around the world, this paper provides a detailed analysis of the governance implications of integrating sustainability into the four domains of university activity. It discusses how best to work across the operational/academic divide and suggests principles for adopting a whole institution approach to sustainability.