Citations

Abstract Geroscience research benefits from interdisciplinary approaches, team science, and collaborations, which collectively facilitate the discovery of aging mechanisms and their translation into tangible, clinical interventions. Since its inception in 2019, the Midwest Aging Consortium (MAC) has provided an engaging platform for aging researchers in the United States’ Midwest to connect, collaborate, and exchange ideas. The Sixth Annual Research Symposium of the MAC held at the Mayo Clinic in Rochester, Minnesota, in April 2025 highlighted the continued impact of the MAC in bringing together aging researchers, including many trainees and early career investigators, into a collaborative environment. This record-setting event featured interdisciplinary research on key aging mechanisms, including lipid metabolism, mitochondrial dysfunction, stress response, cellular senescence, and immune adaptations across organ systems. New therapeutic concepts and clinical trial approaches were presented. Cutting-edge methodologies including single-cell and spatial transcriptomics, metabolomics, and organoid cultures, to dissect aging process in tissue-specific and systemic contexts also were presented. Overall, the MAC symposium underscored the translational potential of geroscience and reinforced the MAC’s mission to accelerate aging research through regional collaborations and innovation.

Understanding the evolution of clinical tools and models of care is fundamental to advancing the field of epilepsy. The 2025 American Epilepsy Society Annual Course examined the expanding spectrum of epilepsy care through the integration of multispecialty collaboration, innovative diagnostic modalities, and surgical and nonsurgical therapeutic interventions. The course underscored significant global advancements in epilepsy research and practice. This comprehensive review synthesizes key educational insights from the program, offering a critical perspective on the ongoing transformation of epilepsy care.

Abstract Introduction Periacetabular osteotomy (PAO) is performed in the setting of hip dysplasia to increase acetabular coverage of the femoral head and improve joint biomechanics and longevity. PAO fixation is generally achieved with two or three 4.5 mm screws, as compared to the generally more substantial plate and screw constructs used in the setting of acetabular fractures or pelvic ring injuries. The purpose of this study was to evaluate postoperative changes in hip joint center medialization and lateral acetabular coverage following PAO, understanding that these radiographic measures are generally used to guide intra-operative assessment of correction. Methods A retrospective chart review of 100 consecutive PAOs during 2021-2023 at a single academic institution by four surgeons was performed. Perioperative radiographs and fluoroscopy images were evaluated to measure lateral center edge angle (LCEA), Tönnis angle, and medialization of the hip joint center. The hip joint center was measured at one-third of the diameter of the femoral head from inferior to superior, to the ilioischial line, as previously validated by Fowler and colleagues. Results One hundred PAOs in 87 patients (87% female, mean age: 23.0 years) were included. Average preoperative radiographic parameters were 19.9° for LCEA, 12.5° for Tönnis angle, and 12.6 mm for distance from the femoral head to ilioischial line. Ninety-four cases (94%) used three screws, and 6 cases (6%) used two screws for unstable fragment fixation. On immediate postoperative films, average correction was to 28.3° for LCEA, 4.9° for Tönnis angle, and 1.9 mm of pre- to postoperative femoral head medialization (p≤0.001). Patients were radiographically followed for an average of 13.3 months, with an average time to radiographic union of 7.1 months. During the course of follow-up, LCEA increased to 29.3°, Tönnis angle remained to 5.0° (p=0.47), and medialization increased to 2.7 mm (p≤0.02), suggesting further significant but clinically modest increases in lateral coverage and femoral head medialization. Conclusion While the majority of lateral acetabular coverage and femoral head medialization occurs intra-operatively at the time of PAO, patients undergo modest but statistically significant postoperative increases in lateral coverage and medialization prior to radiographic union.

Abstract Background Femoral version plays a critical role in pre-arthritic hip pain, particularly in femoroacetabular impingement (FAI). Variations in femoral version may contribute to hip instability or impingement. This study examines the outcomes of hip arthroscopy for FAI across different femoral version groups. Methods A prospective multicenter cohort of 677 FAI patients undergoing primary hip arthroscopy was collected, with 603 patients in this study based on recorded femoral version. Inclusion criteria were patients aged 14-45 years with idiopathic FAI, while previous ipsilateral hip procedures, associated disorders, or Tönnis 2 or greater osteoarthritis were excluded. Femoral version was measured on low-dose computed tomography (CT) utilizing the Yoshioka oblique method and categorized into five subgroups: <5°, 6°-15°, 16°-25°, 26°-35°, 35°+. Patient-reported outcomes (PROs) were obtained at minimum one-year follow-up. The modified Harris hip score (mHHS) was assessed relative to minimal clinically important difference (MCID) of 8 and patient acceptable symptom state (PASS) of 74. Additional PROs included HOOS Pain and Sports/Recreation subscores and iHOT-12 score. Composite failure was defined as reoperation for persistent symptoms or failure to achieve either the mHHS MCID or PASS. Results Males had statistically lower femoral version than females (14.0 vs 18.0; p<0.001). In females, 38.0% had a femoral version of 16°-25°, 17.9% between 26°-35°, and 3.6% greater than 35°, compared to 27.6%, 9.2%, and 1.8% in males, respectively (all p<0.001). Increased or decreased femoral versions appear to have similar outcomes to normal version. The mildly increased femoral anteversion groups of 16°-25° and 26°-35° demonstrated the best outcomes with changes in HOOS pain and sports subscores being significantly higher. Severely increased femoral anteversion, >35°, only present in 2.8% of patients, demonstrated a higher composite failure rate (15.4%) compared to moderately increased, 26°-35°, femoral version (3.1%). The decreased femoral version group, ≤5°, had a composite failure of 10.4% compared to normal femoral version, 16°-25° (10.2%). Conclusions The general anatomy differences between males and females lends males to be more in retroversion while females tend to be more anteverted. Overall, outcomes did not seem to differ between increased or decreased femoral versions but were superior at mildly increased femoral versions.

Abstract Objective Memory impairments are common in neurological disorders, especially drug‐resistant epilepsy, where cognitive deficits such as accelerated long‐term forgetting may occur before surgery due to interictal/ictal discharges, antiseizure medications, and disease progression. Postsurgical memory decline affects 40%–60% of patients. Understanding the neural mechanisms of memory encoding is essential for identifying critical network hubs and guiding surgical interventions that preserve cognitive function. Methods We analyzed intracranial electroencephalographic recordings from epilepsy patients ( n = 15) performing a verbal memory encoding task to identify key structures involved in successful memory formation. Functional connectivity was computed using multiple features across several frequency bands. Temporal dynamics of connectivity were examined to characterize pre‐encoding and encoding phases. Results The middle temporal gyrus (MTG) consistently emerged as a verbal memory hub across features and frequency bands. The inferior frontal gyrus (IFG) was identified as a beta‐band‐specific hub via phase synchrony. Temporal analyses revealed that MTG exhibited stable and widespread connectivity differences across all encoding phases, suggesting a role in pre‐encoding network priming. In contrast, IFG displayed a transient decrease in connectivity and spatial extent during early encoding, indicating a more focal and dynamic contribution. Significance These findings suggest that successful memory encoding relies on widespread, frequency‐specific connectivity patterns centered on MTG, complemented by transient, localized IFG activity. Identifying such hubs may inform surgical planning by highlighting regions critical for cognitive outcomes, ultimately supporting strategies to preserve memory in epilepsy surgery.

Traumatic brain injury (TBI) is one of the leading causes of death and neurological disability worldwide. The search for biomarkers that indicate TBI severity and prognosis with greater accuracy is ongoing. This study aimed to evaluate the significance of several neuroinflammatory cytokines and chemokines, assessing their potential as biomarkers in pediatric TBI (pTBI). This was an exploratory analysis of inflammatory cytokines and chemokines measured in a subset of 26 children aged 0–18 years with TBI and 21 controls. TBI severity was determined by GCS. The functional outcome was measured via the GOS-E score at 6 weeks and 3, 6, 9, and 12 months post-injury. Serum samples were analyzed for ICAM-1, VCAM-1, SAA, CRP, IFN-g, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4, IL-6, IL-8, TNF-a, TNF-b, eotaxin, eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1a, MIP-1b and TARC. Levels of IL-6, IL-10, IL-13, IL-16, MDC, and GM-CSF were increased, and IFN-γ, IL-5, IL-8, and eotaxin-3 were decreased at enrollment when compared with controls. Elevated IL-6 and IL-10 at enrollment were associated with severe TBI (AUC of 1, p = 0.0002 and p = <0.0001, respectively). IL-6, IL-10, IL-16, and TNF-β at enrollment and IL-5 at 24 h were elevated in children with unfavorable outcomes, with an AUC > 0.8, suggesting biomarker potential. Our data indicate that several cytokines and chemokines measured after TBI may aid in the assessment of pTBI severity and prognosis. IL-6, IL-10, and IL-16 may show potential as biomarkers for pTBI severity and outcomes.

This economic evaluation estimates the implementation costs and cost per additional patient receiving the vaccine associated with each of the intervention strategies for increasing rates of human papillomavirus (HPV) vaccination in primary care practices.

Introduction Despite the identification of multiple susceptibility loci by genome-wide association studies (GWAS), considerable chronic obstructive pulmonary disease (COPD) heritability remains unexplained. Aim To identify interaction networks of airway epithelial cell DNA methylation in COPD and further explore potential correlations with airway bacterial composition, as potentially collective regulators of biological pathways influencing COPD severity. Methods Using DNA isolated from bronchial airway brushings of 67 ever-smokers (>20 pack-years) from the SubPopulations and InteRmediate Outcomes Measures in COPD Study (SPIROMICS), we assessed proportion of DNA methylation (β) by epigenome-wide association study (EWAS) and examined associations of differentially methylated CpG probes (DMPs) with risk for moderate-to-severe COPD (N=34) versus absent or mild COPD (N=33). We tested co-methylation modules generated by Weighted Correlation Network Analyses (WGCNA) for associations with moderate-to-severe COPD and with bacterial genus-level relative abundances (16S rRNA sequencing). Results EWAS-identified nominally significant DMPs enriched for lung function GWAS loci. Eigengenes in six WGCNA modules were associated with moderate-to-severe COPD (false discovery rate <0.05). Four of those modules were enriched for forced expiratory volume in 1 s/forced vital capacity GWAS loci, and five overlapped with DMPs from EWAS. Overlapping CpG loci in three COPD-associated modules were adjacent to mucin genes; one had 10 genes highly ranked by connectivity with MUC5B, including important pathway genes: B3GNT6 , DGKI and ITGA8 . CpGs in an independent COPD-associated module showed the most correlations with Rothia , with directionality suggestive of negative associations with moderate-severe COPD. Conclusions Bronchial epithelial DNA methylation modules enriched for lung function GWAS loci associate with COPD severity in SPIROMICS. Potential module relationships to bronchial bacterial composition require further validation.

Abstract Pain medicine triage plays a crucial role in ensuring patients receive timely and appropriate care by scheduling them to the most suitable treatment path. However, the absence of standardized triage protocols in pain medicine often leads to inefficiencies, including delay of care and wastage of healthcare resources. This study aims to develop a rule-based automated referral triage system leveraging information from patients' medical notes for scheduling patients to specific procedures in the pain medicine department. The proposed triage system, grounded in the knowledge and expertise of clinical providers, processed referral order comments and referring provider notes by iteratively refining the Natural Language Processing (NLP) rules and post-processing rules through intensively reviewing 76 patients. A post-processing regression model was incorporated to further enhance the accuracy. To ensure alignment with real-world practices, the system was integrated into an electronic health record (EHR) platform for real-time application, streamlining scheduling workflows and enhancing usability in daily clinical settings. After three iterations, the proposed NLP and post-processing rules improved accuracy from 76.3 to 80.3% compared to machine learning (ML) approaches in the preliminary study. The post-processing model further increased accuracy to 84.2%. The implementation accuracy of 200 cases for the first 3 months was consistent with our prediction at 83.5%, which concluded that the improvement over ML models (p-value = 0.018) was statistically significant at 95% significance level. This study demonstrates the feasibility and benefits of a knowledge-driven approach to referral triage in specialized medical fields. It lays a foundation for others in building similar triaging solutions to other specialties.