Citations

Abstract Rationale Long COVID (LC) has affected approximately 400 million people worldwide, with about 20 million in the US. LC is characterized by a host of new symptoms, including neuropsychiatric disorders including cognitive impairment. Disruption of the gut microbiome has been correlated with symptoms of LC. This study examined whether gut microbiome modulation via intake of probiotic fermented foods mitigated psychiatric and cognitive impairments. Methods This was a pilot trial performed at a single academic medical center that enrolled and randomized patients with LC 1:1 into the treatment vs. control arm. Those enrolled into the treatment arm received teaching on the gut microbiome, its relationship to LC, and were encouraged to eat a diet high in probiotic fermented foods for 12 weeks. Those in the control arm did not receive the teaching and were encouraged to eat their normal diet. Diets were tracked using the Mayo Clinic Diet application on a smart phone at least three days per week, and those in the treatment arm received routine calls to discuss protocol adherence and gather subjective feedback on the trial. Neuropsychiatric questionnaires (HADS, IES-R, EQ-5D-5L, and MoCA Blind) were completed at enrollment and upon completion of the trial. Questionnaire scores were evaluated for changes using a paired t-test, with statistical significance defined as a p-value <0.05. Correlation between the fermented food intake and improvements in questionnaires was completed using the Spearman test. Results 43 patients were enrolled; 18 patients in the treatment arm and 20 patients in the control arm completed the trial. Groups did not differ by age, race, education, or baseline neuropsychiatric testing. There was a significant increase in fermented food intake in the treatment arm over the duration of the study. Those in the treatment arm had improvements in questionnaires related to anxiety, PTSD, and quality of life. Those in the control arm only had improvements in reported overall quality of life. Intra-group changes can be seen in Table 1. Correlations between fermented food intake and change in questionnaire scoring showed numerical but not statistically significant improvements in many of the questionnaires, except for the MOCA questionnaire and EQ-5D-5L Self-Care question. Conclusion Implementing a diet high in fermented foods in patients with LC appears to have some signal for improvement in neuropsychiatric symptoms. Completing a larger trial would help clarify if changes would be statistically significant. This abstract is funded by: Mayo Clinic Critical Care Research Committee

Context Women with obesity or polycystic ovary syndrome (PCOS) often require repeated ovulation induction (OI) due to ovulatory dysfunction and infertility. However, the cumulative effects of repeated stimulation on ovarian function and embryo development remain poorly understood. Aims The present study aimed to understand the consequences of repeated OI and/or repeated superovulation (SO) on preimplantation embryonic development in obese (high-fat diet-induced) and PCOS (high-fat diet and dehydroepiandrosterone-induced) mouse models. Methods Control (without any metabolic disorder), obese, and PCOS mice were divided into three experimental groups. The mice in one round of superovulation (SO1) were injected with 5 IU intraperitoneal (i.p.) injection of pregnant mare serum gonadotropin, followed by 10 IU of human chorionic gonadotropin 48 h later. In the repeated superovulation (SO3) group, mice were subjected to three rounds of superovulation with a gap of 9 days between each superovulation. Mice in the OI3 + SO3 group were administered with three doses of CC (50 mg/kg body weight, i.p., gap of 9 days between each CC injection), followed by three rounds of superovulation. Key results Both single and three rounds of superovulation resulted in decrease in primordial follicles and a moderate increase in atretic follicles in obese and PCOS mice. Reduction in the number of ovulated oocytes, increased rate of abnormal fertilization, decrease in blastocyst rate and elevated DNA damage in blastocysts were observed in in vitro fertilization-derived embryos. Conclusions These findings demonstrate compromised embryonic development following repeated ovarian stimulation. Implications The study highlights need for mild ovarian stimulation strategies in metabolically compromised patients undergoing infertility treatments.

Abstract Introduction Sleep-disordered breathing (SDB) is a potentially modifiable risk factor for the prevention of dementia, of which Alzheimer’s disease (AD) is the most common cause. However, there is a lack of longitudinal evidence relating SDB to AD pathology >20 years later. We examined the association between late-midlife SDB and late-life brain β-amyloid (Aβ) deposition—a hallmark of AD—assessed approximately 23 years later. Methods The Atherosclerosis Risk in Communities (ARIC) Study is an ongoing prospective cohort study initiated in 1987. Participants at two ARIC sites (Washington County, Maryland; Minneapolis, Minnesota) with primarily White participants also completed polysomnography (PSG) in the Sleep Heart Health Study (SHHS) in 1995-98. SDB measures included apnea-hypopnea index (AHI; number of apneas + hypopneas with ≥3% oxygen desaturation/hour of sleep), arousal index, and percentage of total sleep time in apnea, in hypopnea, and with oxygen saturation < 90%. A subset of participants completed florbetapir positron emission tomography (PET) scans through several ARIC ancillary studies (2011-2025 including the ARIC Sleep-PET study). We defined Aβ deposition as a global standardized uptake value ratio (SUVR) >1.2 (vs. SUVR ≤1.2). We used Poisson regression with robust standard errors to estimate relative risk (RR) of Aβ deposition by SDB, adjusting for demographics and vascular risk factors, and applied inverse probability attrition weighting to account for selective drop-out. Results Among 186 dementia-free participants (mean age=59 years at PSG and 82 years at PET scan, 58% female, 98% White), every 10% increase in total sleep time in hypopnea was associated with higher risk of Aβ deposition (RR=1.40, 95% confidence interval [CI]: 1.03, 1.91). When compared to no SDB (AHI < 5), moderate to severe SDB (AHI ≥15) was associated with elevated Aβ deposition (RR=2.36, 95% CI: 1.22, 4.57); mild SDB (AHI 5 to < 15) was not (RR=1.05, 95% CI: 0.53, 2.07). Conclusion SDB in late midlife was associated with greater risk of Aβ deposition approximately 23 years later. SDB may play a role in the early stages of AD pathogenesis. Future longitudinal studies are needed to optimize strategies for screening and treating SDB for dementia prevention. Support (if any) Supported in part by RF1AG050745.

Abstract INTRODUCTION Naturalistic driving provides real‐world behavioral indicators of early cognitive and functional changes. This study integrated naturalistic driving GPS trajectories collected from in‐vehicle sensors with points of interest (POIs) to quantify daily environmental engagement among older adults who were cognitively normal at enrollment. METHODS Data from 438 participants enrolled in the Driving Real‐world in‐Vehicle Evaluation System Project were used to generate daily POI share vectors and model latent engagement patterns using a logistic‐normal hidden Markov model (HMM). Thirteen latent states described distinct modes of environmental interaction. From each participant's inferred state sequence, we derived mobility features – state occupancy, dwell time, transition entropy, and self‐transition probability – and examined their differences across clinical status groups and associations with Preclinical Alzheimer's Cognitive Composite (PACC) performance. RESULTS Transition entropy and several state‐specific occupancy and dwelling metrics differed across clinical groups, but none of the mobility features were significantly associated with PACC scores. DISCUSSION Mobility‐derived behavioral features differentiate clinical status groups and may reflect early functional changes preceding cognitive decline.

Despite the increasing prevalence and median severity of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), medical education on the disease is scant, leading to a diagnostic crisis in which the majority of people with ME/CFS are undiagnosed. We created a care process algorithm in AskMayoExpert accessible to all Mayo Clinic medical providers as a source for information on diagnosis and management of ME/CFS. To evaluate whether the algorithm was associated with improved diagnostic accuracy, we compared concordance before versus after the algorithm was introduced, where concordance was defined as agreement between an appropriately coded referral to Mayo Clinic’s Chronic Fatigue Specialty Clinic and the specialty clinic with an expert diagnosis of ME/CFS. Referrals to the Chronic Fatigue Specialty Clinic increased overall and were more likely to show concordance between specialist diagnosis and referral after the introduction of the ME/CFS AskMayoExpert algorithm. Particularly in diseases that are prevalent and poorly understood, a point-of-care clinical tool may offer just-in-time opportunities to improve diagnosis and management.

ABSTRACT Background Driving supports independence and quality of life in later life but is vulnerable to age‐related and/or disease‐related decline. While cognitive impairment is a well‐recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. Methods We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in‐vehicle GPS dataloggers between 2019 and 2025. Linear mixed‐effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). Results At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (−0.050 vs. −0.037 trips/month), long‐distance trips (> 20 miles; p < 0.001), and maximum trip distance ( p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self‐reported driving behaviors showed that participants with higher SMI drove fewer days per‐week and were more likely to avoid night driving ( p < 0.01). Rates of self‐reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self‐regulatory behaviors. Conclusion Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low‐cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving.

57 Background: Cardiovascular disease (CVD) is the leading non-cancer cause of death among men with prostate cancer (PC), particularly during androgen-deprivation therapy. While CVD risk-prediction models are well established in the general population, barriers to integration within oncology workflows remain poorly defined. Guided by the PRISM and RE-AIM frameworks, this study evaluated multilevel determinants influencing adoption, feasibility, and sustainability of CVD risk-assessment tools in PC care. Methods: A national, cross-sectional survey of 45 physicians (medical oncology 49%, urology 38%, radiation oncology 13%) from 18 U.S. states was conducted. Respondents represented early- (27%), mid- (36%), and late-career (38%) clinicians across academic (87%) and community (13%) settings. Quantitative items mapped to PRISM/RE-AIM domains assessed adaptability, cost/resource feasibility, effectiveness, equity, and sustainability; open-ended responses explored contextual barriers and facilitators. Descriptive statistics summarized quantitative data. Results: Physicians reported moderate-to-high readiness to adopt a CVD risk-assessment tool, emphasizing workflow alignment and EHR integration over algorithmic complexity. Table 1 summarizes domain-specific findings. Ninety-three percent of respondents favored lab-independent models that minimize workflow disruption. Conclusions: Pre-implementation analysis highlighted that structural barriers, rather than algorithmic or statistical limitations, remain the primary obstacles to adopting CVD risk-assessment tools in prostate-cancer care. Physicians emphasized the need for EHR-integrated, non-laboratory-based, and time-efficient tools that align with routine oncology workflows and minimize cross-specialty friction. Addressing these practical and organizational determinants may be pivotal to achieving equitable, scalable, and sustainable cardio-oncology implementation across diverse practice settings. PRISM and RE-AIM constructs evaluation results. Construct Likely/Very Likely (%) Interpretation Perceived Effectiveness 87% Broad confidence in clinical utility Equity in Patient Reach 75% Strong perceived equity in reach Equity in Effectiveness 73% Expected to perform consistently across populations Adaptability to Workflow 71% High compatibility with existing clinic workflows Cost/Resource Feasibility 65% Feasible for resource-constrained settings Likelihood of Adoption 60% Moderate readiness for implementation Equity in Adoption 58% Equitable uptake possible despite resource differences Reach to Target Population 57% Moderate likelihood of reaching most patients Sustainability Over Time 51% Moderate long-term feasibility Consistency of Implementation 42% Need for standardized protocols

The fallopian tubes are critical segments of the female reproductive tract and are essential for transporting gametes and embryos. It creates a conducive environment necessary for successful fertilization, early embryo development, and embryo transport. The cellular composition and function of the fallopian tube are tightly regulated by the sex hormones estradiol and progesterone. Therefore, any pathological/ metabolic condition or exposure to exogenous agents with the potential to alter endocrine levels can have a significant impact on fallopian tube function and health. This review summarizes the effects of medications, infections, pathological conditions, lifestyle choices, and environmental factors that can significantly impact the morphology, histology, cellularity, and functionality of the fallopian tube.

Abstract Objective Despite being safe and effective, surgery for pediatric epilepsy is underutilized. Social determinants of health (SDoH) are important to consider when examining this treatment gap. This study examined the potential systemic inequities at three different stages in the journey toward epilepsy surgery across the Pediatric Epilepsy Research Consortium (PERC). Methods Any youth in the PERC prospective surgery database (≤18 years) was eligible and included if sociodemographic factors were also available. We examined if there were differences in disparity factors in: (1) referral to Phase I evaluation, (2) offering of surgery, and (3) completion of surgery. Results Of 1309 patients, the majority were male (53%, p = .04), White (82.2%, p < .001), not Hispanic or Latino (84.3%, p < .001), and privately insured (56.3%, p < .001). Of the youth who were offered surgical treatment ( n = 1103, 84.3%), there were no significant differences in race/ethnicity or sex. Those with a structural lesion were more likely to be offered surgery, and historically marginalized youth were more likely to have a lesion. Of patients who completed surgery ( n = 927, 84.0%), White patients were 1.88 times (95% confidence interval [CI]: 1.14–3.04) more likely than Black patients to complete surgery ( p = .01). Significance Youth who began surgery evaluation are not representative of the demographics of those with epilepsy in the United States, with greater representation of White, non‐Hispanic male individuals. In addition, youth who began surgery evaluation disproportionally have private insurance. At the next stage of offering surgery, there were no differences based on SDoH. However, there is evidence that underrepresented youth that were magnetic resonance negative were less likely to be referred for surgical workup and that Black youth were less likely to undergo surgery. Therefore, efforts to provide equitable opportunity for all youth with refractory epilepsy should be concentrated at the referral for surgery evaluation point of care; however, additional efforts are also needed at later stages.

Abstract Introduction Accurate detection of gene fusions is critical for the diagnosis and management of sarcomas. However, occasional false-negative results may occur due to factors such as low tumor cellularity, limited assay coverage of relevant genomic regions, or mis-annotation by bioinformatic pipelines. We recently encountered a case in which our clinical SARCP fusion detection assay failed to identify an HMGA2::NCOR2 (exon 3–exon 16) fusion. Method The SARCP assay is a targeted, amplicon-based RNA-seq next-generation sequencing (NGS) assay designed to detect gene fusions across 138 genes, including HMGA2. Although NCOR2 is not among the targeted genes, the assay is capable of detecting fusions when only one gene partner is represented. Results Suspicion of a false-negative result arose when the pathologist noted that the tumor’s histologic features—keratin-positive, giant cell-rich soft tissue—were consistent with a subtype previously associated with the HMGA2::NCOR2 fusion. This prompted a review of the bioinformatic output, which had erroneously reported an HMGA2::MAML2 fusion. The misannotation was traced to sequence homology involving a CAA/CAG repeat at the 5′ end of NCOR2 exon 16, likely resulting from DNA polymerase slippage and misalignment in low-complexity, partially complementary repetitive regions. This erroneously lead to the target genomic sequence getting mapped to MAML2 exon 2 as opposed to the NCOR2 exon 16. Discussion This case highlights how bioinformatic mis-annotation can lead to occasional false-negative fusion calls. It underscores the importance of manual review in cases with strong clinical or pathologic suspicion and calls attention to the need for fusion-calling algorithms that better handle repetitive and homopolymeric sequences. Citation Format: Ganesh P. Pujari, Mitch L. Klebig, Kurt S. Willkom, Montha Chhunn, Stefan W. Nelson, Neiladri Saha, Kevin C. Halling. Mis-Annotation of an HMGA2::NCOR2 Fusion in FFPE Sarcoma Samples: A Case Illustrating Bioinformatic Limitations in Fusion Detection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr A012.