Introduction: Innate immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection activates multiple interferon stimulated genes (ISGs), including ADAR1 p150 isoform, which edits adenosine (A) residues within double stranded RNAs in both the virus and the host. In addition to its immune role, ADAR editing also serves as a mechanism of dynamic regulation of transcriptome and proteome diversity. While evidence points to changes in ADAR editing during infection, we do not know whether editing targets change over the course of the infection.

Methods: Here, we explored temporal changes in ADAR expression and editing patterns, across three distinct stages of SARS-CoV-2 infection. Furthermore, we examined whether infection-triggered dysregulation in ADAR editing persists or returns to pre-infection states post-viral clearance using publicly available whole blood RNA sequencing samples from forty-five, age-matched individuals. The individuals selected had no documented comorbidities, developed mild COVID-19, and were sampled across three distinct stages of SARS-CoV-2 infection: pre-, mid-, and post-infection.

Results and discussion: Our results demonstrate dynamic changes in ADAR expression and editing across the three stages. We further identified editing sites that were edited only in one of the three stages of infection within genes involved in immune response pathways, specifically, within neutrophil degranulation pathway genes. Our results demonstrate a consistent trend of elevated ADAR expression and reduced overall ADAR editing within each individual mid-infection. Subsequently, post-infection, though ADAR expression returns to pre-infection levels, ADAR editing remains dysregulated in some individuals. Given that dysregulated ADAR editing could be a mechanistic link between viral infections and sequalae, it is possible that persistent dysregulation of ADAR editing in a subset of recovered individuals contributes to the heterogeneity in disease outcomes seen in individuals post-SARS-CoV-2 infection.

Enhanced signaling of dopamine and/or serotonin during highly arousing situations can be reduced in part by monoamine transporters, such as plasma membrane monoamine transporter (PMAT, Slc29a4). An absence of selective pharmacological inhibitors means genetically modified mice constitutively deficient in PMAT remain the best tool for studying PMAT’s organism-level functional effects. Fear conditioning is a high arousal process. Generalization of fear is evolutionarily advantageous, whereby information learned from one experience is applied to other new but similar encounters. Pathological fear generalization, in contrast, is a core feature of most anxiety disorders. Given our previous findings indicating PMAT function reduces male mice’s context fear and enhances extinction of female mice’s cued fear, we hypothesized PMAT would similarly reduce generalization (i.e., enhance discrimination) of context and cued fear in male and female mice, respectively. Our context and cued fear conditioning experiments in adult PMAT wildtype (+/+) and heterozygous (+/−) male and female mice partially supported our hypotheses. We discovered PMAT facilitates extinction of contextually generalized fear, plus subsequent extinction of context-specific fear, selectively in females. Moreover, when specific fear cues or contexts were temporally presented before cues or contexts that were similar enough to make generalization possible, PMAT enhanced biological sex differences. Growing evidence reports common PMAT polymorphisms elicit measurable effects when PMAT function is reduced. Thus, we suspect future experiments may reveal positive associations between PMAT polymorphisms and risk for anxiety disorder symptoms, particularly in people assigned female at birth. Inclusion of these genetic variations in pharmacogenomic analyses may prove therapeutically beneficial.

Background: 
The next generation of PhD-prepared nurses must be forward-thinking and equipped to solve existing and emerging health care problems requiring educators to reimagine curricula to surpass conventional scientific methods.

Problem: 
Limited guidance exists on effectively integrating human-centered design (HCD) with scientific methods in doctoral education.

Approach: 
Grounded in a learner-centered paradigm, faculty developed a doctoral-level innovation and intervention course that blended HCD with traditional research methodologies. This article explores the course’s philosophical approach, design and implementation, highlighting challenges as well as areas of convergence and divergence between the 2 approaches. Emphasis is placed on how these dynamics shaped teaching strategies and student learning.

Outcome: 
A pedagogical model emerged structured around the 3 integrated domains of the course: design thinking, philosophical and theoretical frameworks, and complementary research methods.

Conclusions: 
The model supports the development of adaptive nurse scientists equipped to engage with complex health care problems through iterative, stakeholder-informed inquiry.

Objective: The present study examines the relationships between different forms of stigma related to one’s weight and gender identity on health care utilization within a gender diverse sample. Method: Gender diverse individuals across the weight spectrum were recruited from an online panel via Prolific. Participants completed questionnaires regarding health care experiences, health behaviors, health beliefs, and gender identity. Data were collected between September and November 2023. Results: The final sample was 343 transgender and nonbinary participants. Adding weight stigma (enacted, internalized), transgender stigma, and intersectional stigma to the models accounted for 49.8% of the variance in weight-based health care avoidance, ΔR² = .217, ΔF(4, 331) = 35.80, p < .001, and 13.1% of the variance in general avoidance of health care, ΔR² = .071, ΔF(4, 331) = 6.72, p < .001. Adding the stigma variables to the model predicting health care delay accounted for 13% of the variance, ΔR² = .08, ΔF(4, 331) = 7.60, p < .001. However, adding stigma did not uniquely contribute to the variance in hormonal gender affirming care interest, ΔR² = .014, ΔF(4, 331) = 1.68, p = .155, gender affirming care typical for those assigned male at birth, ΔR² = .050, ΔF(4, 76) = 1.18, p = .325, and gender affirming care typical for those assigned female at birth, ΔR² = .029, ΔF(4, 197) = 1.80, p = .131. Conclusions: Results partially supported our hypotheses, suggesting both enacted weight/transgender stigma and internalized weight stigma are significantly associated with utilization of health care services in a gender diverse sample. Future research is needed to understand the relationships between coping strategies and health care utilization.

Background
Grief among neuro-oncology healthcare providers (NOPs) affects emotional resilience, professional performance, and patient care. This study adapted and validated the 30-item Neuro-Oncology Grief Index (NOGI) to assess grief experiences and coping strategies in NOPs after patient loss.

Methods
A cross-sectional design was used to adapt the NOGI through item generation, expert review, and field testing. Psychometric properties were evaluated via exploratory factor analysis, internal consistency using Cronbach’s alpha, and stepwise regression was performed using variables that were significantly associated with provider grief to determine their predictive value and the amount of variance.

Results
The sample comprised 80 NOPs (68% female, 75% white, 62% with >5 years’ experience). An exploratory factor analysis identified a single factor for the grief scale. Internal consistency was acceptable with Cronbach’s alpha = .92. High grief was linked to frequent patient deaths, burnout, and compassion fatigue. Adverse coping behaviors, like staying overly busy or isolating, were common; 58% of NOPs avoided emotional support due to workplace norms. Regression analysis identified past-year risk factors, provider protective factors, and adverse behavioral risks as significant predictors of grief.

Conclusions
The NOGI is a reliable, valid tool for assessing NOP grief, highlighting emotional grief, burnout, compassion fatigue, and coping strategies. Interventions addressing emotional support, burnout, and workplace norms are needed to enhance provider well-being and patient care. Future research should further validate the NOGI and address compassion fatigue and emotional support access.

Background: Multiple sclerosis (MS) is a debilitating neurological disease with physical, cognitive, and emotional symptoms that is characterised by recurrent, unpredictable symptom exacerbations. Despite treatment advancements, patients with relapsing-remitting MS remain at high risk for psychopathology. While prior studies have investigated the influence of physical symptoms on psychological well-being, psychological factors are often overlooked.

Methods: This study investigated the association between baseline reports of perceived functioning and one year of weekly reports of psychological well-being (i.e. positive affect), while considering physical disability and weekly reports of symptom intrusiveness and fatigue symptom exacerbations in adult patients with MS (N = 25). A linear mixed-effects model examined these associations over 12 months, across 858 diary time points.

Results: Results indicated greater perceived functioning reported at baseline was associated with higher weekly positive affect, even when considering weekly fatigue symptom exacerbations.

Conclusions: These results suggest a potential novel target for psychological interventions, as perceived functioning can be targeted in treatments focusing on patient self-management and/or self-efficacy.