University of South Dakota

Abstract Background Non-ischemic cardiomyopathy (NICM) represents a major cause of heart failure with limited tools for early risk stratification. Atrial fibrillation (AF) is a well-established contributor to cardiomyopathy but is often clinically silent in its early stages. The atrial fibrillation polygenic risk score (AF-PRS) reflects genetic susceptibility to AF and may identify individuals at risk for AF-related cardiomyopathy. We hypothesized that higher AF-PRS is associated with greater risk of NICM. Methods This was a retrospective cohort study of 16,801 individuals of European ancestry from the Sanford Biobank and Imagenetics program with genetic sequencing and longitudinal electronic health record data. AF-PRS was calculated using 315 genome-wide significant single-nucleotide polymorphisms with standard quality control. NICM was defined by International Classification of Diseases, 10th Revision, Clinical Modification codes, excluding ischemic etiologies. Cox regression models evaluated the association between AF-PRS and incident NICM, adjusting for age, sex, smoking status, body mass index (BMI), hypertension, and diabetes. AF-PRS was analyzed both as a quasi-continuous variable (15% quartile increments) and dichotomized at the 85th percentile. Sensitivity analyses assessed associations with all-cause cardiomyopathy and ischemic cardiomyopathy. Survival analysis was used to model time-to-event outcomes. Results Among all participants, 418 (2.5%) had NICM. 99% were Caucasian. NICM cases were older and more often male (both p<0.001) than those without a diagnosis. After multivariable adjustment for sex, smoking status, BMI, and hypertension, a linear AF-PRS (15% increments) was specifically predictive of increased hazard risk of NICM (HR = 1.09 [1.03, 1.15], p < 0.001). Conclusion These findings complement recent evidence of bidirectional genetic relationships between cardiomyopathy and AF, supporting comprehensive genetic risk assessment in cardiovascular disease prevention. Clinical implementation requires validation in diverse populations and prospective evaluation. Future research should investigate the mechanistic pathways linking AF-associated genetic variants to cardiomyopathy development and evaluate whether AF-PRS-guided screening improves clinical outcomes. Visual abstract: Summary of study design, exposure, outcome, key findings, and clinical implications. This graphical abstract provides a comprehensive overview of the study investigating the association between atrial fibrillation polygenic risk score (AF-PRS) and non-ischemic cardiomyopathy (NICM). Abbreviations: AF, atrial fibrillation; AF-PRS, atrial fibrillation polygenic risk score; CI, confidence interval; HR, hazard ratio; ICD-10, International Classification of Diseases, 10th Revision; ICM, ischemic cardiomyopathy; NICM, non-ischemic cardiomyopathy; PPV, positive predictive value; PRS, polygenic risk score; SNP, single nucleotide polymorphism. Created in BioRender. https://BioRender.com/ k3t1w68

Background/Objectives: Evidence indicates that aberrant glutamate transporter function and expression are linked to the pathophysiology of comorbid major depressive disorder (MDD) and pain. We have previously reported that cefepime (CFP) attenuates lipopolysaccharide (LPS)-evoked pain and depression by regulating hyperglutamatergic activity in male mice. However, the effects of CFP on LPS-evoked pain, depression-related anxiety, and cognitive impairment in female mice regarding sex-specific glial mechanisms remain unknown. Methods: Using behavioral paradigms, we evaluated the therapeutic potential of CFP in mitigating LPS-evoked pain, depression-related anxiety, and cognitive impairment in female mice. Furthermore, we used Western blot analysis to examine the effects of CFP on ionized calcium-binding adaptor molecule 1 (Iba-1) and glutamate transporter 1 (GLT-1) protein levels in the prefrontal cortex (PFC) and hippocampus (HPC). We also measured tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations in the HPC and PFC after CFP treatment using ELISA. Results: Pretreatment with CFP significantly increased the mechanical threshold and withdrawal latency in female mice. Additionally, systemic treatment with CFP markedly reduced immobility during the forced swim and tail suspension tests. Moreover, pretreatment with CFP remarkably augmented the open arm time during elevated plus maze test and spontaneous alternation between arms during Y-maze test. Western blot analysis indicated that systemic administration of CFP significantly reversed the downregulation of astroglial GLT-1 expression and reduced the microglial Iba-1 protein levels in the HPC and PFC. Furthermore, pretreatment with CFP significantly attenuated the LPS-evoked increase in the production of pro-inflammatory cytokines in the HPC and PFC. Conclusions: These results represent the novel inaugural report of a combined pain-MDD phenotype in female mice. The findings imply that positive glutamate transporter modulator CFP could be a novel treatment for comorbid pain and MDD in female patient population.

The Takini/Survivor project examined factors promoting healing and resilience among women survivors of domestic violence in primarily South Dakota, with particular attention to American Indian/Native American (Native hereinafter) and rural experiences through the resilience portfolio model. Using a phenomenological design, this study explored the narratives of 31 Native women using semistructured qualitative interviews. When appropriate, the study also delineated between narratives of Native rural (10) and nonrural women (21). Participants described "poly-strengths" sequences in which environmental strengths (such as housing and transportation) enabled them to draw on their other strengths across resilience portfolio model domains. Rural participants emphasized how geographic isolation, limited mobility, and safety concerns in small communities constrained access to additional resources such as interpersonal supportive relationships. Survivors contextualized abuse within intergenerational trauma, drew on cultural identity and spirituality as distinct meaning-making pathways, and cited children/grandchildren and helping others as central purposes. Healing occurs through reinforcing poly-strengths rather than isolated protective factors. Our findings contribute to resilience portfolio model by building on the importance of environmental strengths and how cultural identities create distinct resilience pathways. Implications include culturally responsive and supportive services, innovative service delivery in rural areas, and reforms to transportation policies. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

To demonstrate the utility of applying demographic and epidemiological models to assess the potential effects of sociopolitical status and childhood stress on survivorship, mortality, and morbidity to shed new light on life during the Maya Classic period. Elite and commoner burials (n = 63) from the Lower Dover polity, Belize dating to the Early (CE 250/300-600) and Late/Terminal Classic (CE 600-900/1000) periods were analyzed for lesions associated with developmental stress. Kaplan-Meier and Cox regression hazards analyses were applied to assess survivorship and mortality trends across ages, sociopolitical statuses, and for individuals displaying macroscopic indicators of cribra orbitalia and linear enamel hypoplasia. Kaplan-Meier and Cox regression showed that there are no significant differences in mortality and morbidity between sociopolitical status groups when nonadults (<15 years) are excluded. However, among commoners, those with cribra orbitalia had higher survival than those without it (p = 0.02). Findings show that despite small sample sizes, paleodemographic models have the potential to elucidate the effects of early life stressors and that despite inferred status differences in Maya archaeology, elites and commoners experienced similar survivorship rates at Classic period Lower Dover. This study exemplifies how integrating paleopathological data with demographic modeling provides insights even when sample sizes are limited, and it clarifies some of the complexities inherent in understanding ancient Maya. Poor preservation impacted the analysis of pathological conditions. Paleopathology-broadly and in Mesoamerica more regionally-needs to engage in more rigorous model approaches and reconsider long-held narratives to make substantial headway in understanding the societal and biological impact of childhood stressors.

Introduction: Acute eosinophilic pneumonia (AEP) is a rare, rapidly progressive pulmonary disorder that can lead to acute respiratory failure requiring ICU-level support and invasive mechanical ventilation (IMV). Although case reports and small series have described its clinical course, national-level data on hospitalization patterns, illness severity, and resource utilization remain limited. We aimed to fill this research gap. Methods: We analyzed adult hospitalizations with a primary diagnosis of AEP(ICD-10 codes) from the 2022 Nationwide Readmissions Database. Survey weights were applied to generate nationally representative estimates. Illness severity was categorized into three mutually exclusive groups: floor admission, ICU admission without intubation, and ICU admission with intubation. Primary outcomes included in-hospital mortality, length of stay (LOS), and total hospital charges. Seasonal variation and the prevalence of comorbid asthma and gastroesophageal reflux disease (GERD) were also assessed. Descriptive statistics and survey-weighted subgroup comparisons were performed. Results: A total of 10,035 weighted hospitalizations (n = 3,912 unweighted) were identified. The median age was 60 years (IQR: 45–72), and 61.2% of the participants were female. Asthma and GERD were significantly more prevalent in AEP hospitalizations compared to non-AEP hospitalizations (58.9% vs. 7.0% and 30.8% vs. 16.2%, respectively; p < 0.001). AEP discharges peaked in November (18.5%), with seasonal clustering from June to October and less frequent from January to March. ICU admission occurred in 42%, and 14.1% required IMV. LOS ranged from 4.8 to 8.0 days, and charges from $59,198 to $170,057, increasing with severity. Mortality was 0.24% (floor), 0.26% (ICU without IMV), and 4.18% (ICU with IMV). Conclusions: In our study, AEP hospitalizations show a clear severity-outcome gradient, with higher ICU use, ventilation need, mortality, and cost as illness advances. These findings highlight AEP as a resource-intensive condition with a substantial impact on survival in severe cases. Although asthma and GERD were common, their impact on outcomes was not assessed, and treatment data were not available. Early recognition and triage based on severity may reduce resource burden and improve outcomes.

Myeloid-derived suppressor cells (MDSCs) are a diverse group of immature myeloid cells critically involved in establishing an immunosuppressive environment within tumors. They impede effective anti-tumor immune responses through multiple mechanisms, including metabolic reprogramming, cytokine secretion, and immune checkpoint ligand expression. This immunosuppressive activity enables tumor progression and resistance to therapies, including immunotherapy. Recent advances reveal that targeting the metabolic pathways of MDSCs can impair their suppressive functions, offering promising strategies to enhance anti-cancer immunity. Approaches such as metabolic inhibition, direct depletion, blockade of recruitment and expansion, and promotion of differentiation into mature immune cells are under active investigation. Combining these strategies with immune checkpoint inhibitors and cell-based therapies, such as cancer vaccines and adoptive T-cell or NK-cell therapies, holds significant potential for overcoming immune resistance. Nonetheless, challenges including MDSC heterogeneity, toxicity, and biomarker validation must be addressed to optimize clinical translation. This review comprehensively covers current insights into the immune-metabolic mechanisms underpinning MDSC-mediated immunosuppression in the tumor microenvironment. It explores emerging therapeutic strategies aimed at targeting MDSCs through metabolic interventions, depletion, and modulation of their recruitment and differentiation. Furthermore, it discusses the integration of MDSC-targeted approaches with existing immunotherapies, highlights ongoing clinical trials, and assesses future directions, such as personalized, biomarker-driven treatments. Ultimately, this review underscores the potential of MDSC-focused therapies to significantly improve the efficacy of cancer immunotherapy and overcome mechanisms of tumor immune evasion.

This paper presents an integrated framework that combines Kernel Principal Component Analysis (KPCA) with trajectory normalization for robust classification of hand gestures in non-contact remote control systems. The approach supports both mouse-tracked and visionbased gesture data, enabling source-agnostic recognition. Trajectory normalization is employed to standardize input variations caused by gesture speed, orientation, and sampling inconsistencies, while KPCA effectively captures non-linear gesture patterns in reduced dimensions. The framework incorporates and evaluates various interpolation techniques to refine temporal alignment across input sequences. Experimental results demonstrate improved accuracy in recognizing complex and degenerate gesture patterns, particularly in scenarios involving user inconsistency and noisy input. Furthermore, the paper provides a comprehensive analysis of the trade-offs involved in different normalization schemes and their impact on classifier performance. This work contributes to the development of intuitive and reliable human-computer interaction systems, suitable for smart environments and assistive technologies. Experimental results show over 99.9% accuracy for non-degenerate gestures and over 98% for degenerate gestures using distance-based normalization with uniform scaling. The system demonstrates strong generalization across input modalities. This work paves the way for real-world contactless control in assistive and industrial domains.

This study investigates the psychological factors that influence how a hearer interprets a speaker's intention in response to a question. The analysis focuses on wh-questions and the extent of exhaustivity required to fulfill the speaker's communicative goal. While previous research suggests that such questions typically elicit exhaustive answers, the findings presented here indicate that exhaustivity is not an inherent property of the question itself. Question paraphrase ratings were collected across varied linguistic contexts to support this conclusion. The results highlight the significance of both linguistic and discourse-level considerations-particularly the hearer's assessment of the speaker's intent-in shaping the interpretation of meaning in question-answer exchanges.

Background:Pregnancy requires finely tuned immune changes that support implantation, placental development, maternal–fetal tolerance, and preparation for labor, yet the normative trajectories of circulating inflammatory proteins across gestation remain poorly defined. This cross-sectional study investigates how circulating inflammatory proteins vary with gestational age in pregnancy and examines the impacts of fundamental biological characteristics, such as gravidity and fetal sex.Methods:Data were drawn from 1154 pregnant individuals from six study sites of the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Cohort. We used Olink high-throughput proteomic profiling to map cross-sectional associations between protein expression levels and gestational age at blood draw using linear, spline-based, and generalized additive modeling approaches.Results:Generalized additive models provided the best fit, revealing that immune changes across pregnancy were predominantly nonlinear. Sixty-one proteins showed significant associations with gestational age, with many exhibiting shared inflection points that aligned with major physiological transitions. A small subset of proteins also showed evidence of modification by fetal and maternal characteristics. CD244 displayed different gestational patterns by fetal sex, while CST5 and SIRT2 showed varied gestational associations by maternal gravidity.Conclusion:The findings highlight pregnancy as a sequence of coordinated immune transitions rather than a simple linear shift and provide one of the most detailed characterizations to date of circulating inflammatory protein dynamics across human gestation. Establishing these normative trajectories offers a crucial reference for detecting early deviations that may signal risk for pregnancy complications and for identifying biomarkers in maternal and fetal health research.