Lessons Learned from Community Partnership During the COVID-19 Pandemic.

Underserved communities have been disproportionately affected by the COVID-19 pandemic. The Project Promoting Engagement and COVID-19 Testing for Health (PEACH) study was designed to understand the attitudes, beliefs, and infrastructure associated with COVID-19 risk, testing, and prevention behaviors in people living with, caring for, or at risk for type 2 diabetes. The purpose of this joint community-academic partnered manuscript is to share lessons learned for maintaining community partnerships through the challenging times of a pandemic. New and existing community partners were invited to share their perceptions about the facilitators and barriers of partnering with academia during the COVID-19 public health crisis. Key facilitators included those partners felt heard and their input valued. And the changing nature and demands in response to the pandemic on the partners' responsibilities were among the key challenges. Successful maintenance of the partnerships required flexibility, creativity, and a willingness to adapt engagement as community partners responded to the needs of their communities.

SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins.

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology. Within this work, we integrate a two-year genotyping window with structural biology to explore the selective pressures of SARS-CoV-2 on protein insights. Although genotype and the Spike (Surface Glycoprotein) protein continue to drift, most SARS-CoV-2 proteins have had few amino acid alterations. Within Spike, the high drift rate of amino acids involved in antibody evasion also corresponds to changes within the ACE2 binding pocket that have undergone multiple changes that maintain functional binding. The genotyping suggests selective pressure for receptor specificity that could also confer changes in viral risk. Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike.

Determinantal point process attention over grid cell code supports out of distribution generalization.

Deep neural networks have made tremendous gains in emulating human-like intelligence, and have been used increasingly as ways of understanding how the brain may solve the complex computational problems on which this relies. However, these still fall short of, and therefore fail to provide insight into how the brain supports strong forms of generalization of which humans are capable. One such case is out-of-distribution (OOD) generalization - successful performance on test examples that lie outside the distribution of the training set. Here, we identify properties of processing in the brain that may contribute to this ability. We describe a two-part algorithm that draws on specific features of neural computation to achieve OOD generalization, and provide a proof of concept by evaluating performance on two challenging cognitive tasks. First we draw on the fact that the mammalian brain represents metric spaces using grid cell code (e.g., in the entorhinal cortex): abstract representations of relational structure, organized in recurring motifs that cover the representational space. Second, we propose an attentional mechanism that operates over the grid cell code using determinantal point process (DPP), that we call DPP attention (DPP-A) - a transformation that ensures maximum sparseness in the coverage of that space. We show that a loss function that combines standard task-optimized error with DPP-A can exploit the recurring motifs in the grid cell code, and can be integrated with common architectures to achieve strong OOD generalization performance on analogy and arithmetic tasks. This provides both an interpretation of how the grid cell code in the mammalian brain may contribute to generalization performance, and at the same time a potential means for improving such capabilities in artificial neural networks.

Indicators of inequity: Exploring the complexities of operationalizing area-level structural racism.

•Examines two types of area-level indicators commonly used in structural racism and health research.•Uses choropleth maps to assess the spatial patterning of the area-level indicators.•Offers methodological considerations for using area-level indicators.•Highlights the prospects and limits of using area-level indicators as proxies of structural racism.

IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques.

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.

The Effects of Morally Reframed Messages on White Individuals' Attitudes Toward White Privilege.

Many White Americans are unaware of or tend to deny the existence of White privilege. One potential explanation for this denial is the belief that America functions as a meritocracy. Prior research suggests that morally reframed messages can change individuals' beliefs when the reframed messages align with their personal moral values. Contributing to the literature on morally reframed messages, the current pair of studies challenged individuals' beliefs about meritocracy in order to promote their awareness of White privilege. After demonstrating that morally reframed messages about America as a meritocracy can meaningful reflect five distinct moral foundations (i.e., Harm/Care, Fairness/Reciprocity, Loyalty/Betrayal, Authority/Respect, Purity/Sanctity), the current studies revealed that individuals who endorsed the moral values of Authority/Respect, Loyalty/Betrayal, and Purity/Sanctity (the binding foundations) reported stronger beliefs in meritocracy and less awareness of White privilege, whereas individuals who endorsed the moral values of Harm/Care and Fairness/Reciprocity (individualizing foundations) reported weaker beliefs in meritocracy and greater awareness of White privilege (Studies 1 and 2). Although the morally reframed messages promoted individuals' White privilege awareness compared to a control message (Study 2), the effectiveness of the messages was not enhanced when the messages aligned with individuals' moral values (Studies 1 and 2). The current pair of studies is the first to examine if individuals' endorsement of the five moral foundations can be used to change their beliefs about White privilege.

Water Versus Electrolyte Rehydration on Vocal Fold Osmotic and Oxidative Stress Gene Expression.

OBJECTIVES: Systemic dehydration may induce osmotic and oxidative stress in the vocal folds, but our knowledge of the biology and mitigation with rehydration is limited. The purpose of this experiment was to evaluate whether systemic dehydration induces vocal fold oxidative and osmotic stress and to compare the impact of rehydration by water intake versus electrolyte intake on osmotic and oxidative stress-related gene expression. METHODS: Four-month-old male Sprague-Dawley rats (N = 32) underwent water restriction. Rehydration was achieved with ad libitum access to water or electrolytes for 24 hours. Rats were divided into four groups: euhydration control, dehydration-only, dehydration followed by either water or electrolyte rehydration (n = 8/group). Gene expression was assessed via RT2 Gene Expression Profiler arrays. RESULTS: With respect to oxidative stress, 10 genes were upregulated and 2 were downregulated after vocal fold dehydration compared with the euhydrated control. Concerning osmotic stress, six genes were upregulated with dehydration only, six genes were upregulated following rehydration with water, whereas a single gene was upregulated with electrolyte rehydration. All genes with significantly different expression between the rehydration groups showed lower expression with electrolytes compared with water. CONCLUSIONS: The results support a potential role of oxidative and osmotic stresses in vocal folds related to systemic dehydration. The differences in stress-related gene expression in vocal fold tissue between rehydration with electrolytes or water, albeit modest, suggest that both rehydration options offer clinical utility to subjects experiencing vocal fold dehydration with preliminary evidence that electrolytes may be more effective than water in resolving osmotic stress. LEVELS OF EVIDENCE: NA (prospective animal study) Laryngoscope, 2024.

Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.

The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.

Governance and legal considerations supporting prehospital emergency care in low and middle-income countries-For the Special Series on Prehospital Care in LMICs.

The global imperative to expand prehospital emergency care in low and middle-income countries to reduce health disparities and improve outcomes for time-sensitive health conditions is well established in academic literature and public policy discussions. However, the governance and legal frameworks essential for the strategic development of prehospital systems remain understudied and inadequately addressed. This paper delves into the critical role of governance in prehospital systems, emphasizing its impact on equity, human rights, and the provision of timely, quality emergency care. Health system governance, defined as a complex interplay of mechanisms, processes, and institutions, is a neglected yet pivotal component of prehospital care. By highlighting previously described barriers, we underscore the opportunity to strengthen prehospital care through improved governance, particularly in leadership and legislative standards. Drawing on the World Health Organization's Health System Building Blocks and the Emergency Care System Framework, we elucidate the multifaceted nature of governance in the prehospital context, including the coordination of diverse stakeholders, the establishment of standards, and the creation of accountability mechanisms. We emphasize the importance of applying a human rights perspective to governance, ensuring non-discriminatory and timely access to emergency care. Through the application of an established governance framework of 10 principles to assess prehospital system governance, we offer policymakers and stakeholders a structured approach to identify weaknesses, propose solutions, and evaluate progress in the prehospital system. To provide practical insights, we present a contemporary case study of Ghana's National Ambulance Service Act and the Health Institutions and Facilities Act of 2011, which establish a structured approach to governance and oversight while reflecting Ghana's commitment to advancing emergency care yet faces common challenges to operationalizing the laws. We advocate for a renewed focus on governance as an essential building block for effective prehospital emergency care. By providing a comprehensive framework and case study analysis, the paper offers actionable insights to guide policymakers and stakeholders in developing and evaluating governance initiatives that improve the availability, accessibility, acceptability, and quality of prehospital care globally.