Citations

Abstract Context Menstrual irregularities have been associated with cardiovascular disease (CVD) risk, but underlying etiologies may confer distinct risk profiles. Functional hypothalamic amenorrhea (FHA) has not been evaluated as a separate risk phenotype. Objective To assess the association between FHA phenotype and incident CVD and cardiometabolic risk factors. Design Prospective cohort study with biennial follow-up from 1993 to 2019. Setting Nurses’ Health Study II cohort. Participants The sample included 52,655 premenopausal women free of CVD in 1993. FHA phenotype was defined as irregular or absent cycles without PCOS traits combined with low body mass index and/or high physical activity. Intervention None Main Outcome Measures Incident CVD (coronary heart disease [CHD; myocardial infarction or coronary revascularization] and stroke) and incident elevated cholesterol, hypertension, and type 2 diabetes (T2DM). Results During up to 26 years of follow-up, 1,007 CVD events occurred. Among women who developed CVD, the median time to the first CVD event was 17.0 years (IQR, 11.3-21.0). FHA phenotype in mid-adulthood was associated with a 62% higher risk of CVD (95% confidence interval [CI]: 1.01–2.59), driven by an almost two-fold higher risk of CHD (hazard ratio [HR] = 1.91; 95% CI: 1.11–3.27), compared with women with regular cycles. FHA was also associated with T2DM (HR = 1.86; 95% CI: 1.41–2.47), but not hypertension or elevated cholesterol. Non-FHA menstrual irregularity was associated with elevated cholesterol, hypertension, and T2DM, but not CVD. FHA in early adulthood was not associated with outcomes. Conclusions FHA phenotype in mid-adulthood was associated with increased CHD risk independent of traditional risk factors. Menstrual history may serve as an early marker of cardiometabolic risk.

Introduction: Ureteral stones are a common cause of emergency presentations. Definitive stone removal at the index encounter can reduce delays and repeat interventions. It is unknown whether fellowship-trained endourologists are more likely to perform definitive management than general/other subspecialist urologists. This multicenter retrospective cohort study evaluated the influence of endourology subspecialty training on the choice between upfront definitive stone treatment and initial ureteral decompression at first presentation. Patients managed with medical expulsive therapy alone were not included. Methods: Adults (≥18 years) presenting at 2022 to seven North American academic centers with symptomatic, noninfected, computed tomography-confirmed ureteral stones were included. Patients with infection, sepsis, positive nitrites, or intraoperative pyelonephritis were excluded from the study. Variables included demographics, stone size and location, subspecialty of the on-call urologist, and management type (definitive [ureteroscopy or shockwave lithotripsy] vs deferred [(initial stent]). Multivariate logistic regression was used to identify the predictors of definitive treatment. Results: Among the 395 patients, 190 (48.0%) underwent definitive management and 205 (52.0%) underwent deferred treatment. Distal stones were treated definitively more often than proximal stones were (51.1% vs 36.6%). An endourologist was on call for 150 encounters (38.0%); 64.7% of these patients received definitive treatment, compared with 38.0% under general/other subspecialist urologists. On multivariate analysis, endourologist on-call remained independently associated with definitive management (odds ratio [OR] 3.46, 95% confidence interval [CI] 2.19–5.47, p < 0.0001), as did distal stone location (OR: 2.46, 95% CI: 1.21–5.00, p = 0.013). Severe complications are rare, and none of the patients developed sepsis. Conclusions: Endourologists were more than three times more likely to perform definitive interventions for symptomatic, noninfected ureteral stones at initial presentation. Subspecialty expertise and timely operative access enable safe, efficient, single-stage management.

ABSTRACT Objectives Lasers are integral to contemporary endourologic stone surgery; however, reported institutional practices regarding laser access, personnel requirements, and safety protocols vary. We sought to characterize respondent‐reported laser access models, operational requirements, safety practices, and perceived barriers to care. Materials and Methods A cross‐sectional, web‐based 25‐item survey was distributed between October 2024 and March 2025 through social media, professional organizations, and departmental contacts. The survey assessed practice characteristics, laser access, physician and technician responsibilities, institutional safety requirements, and perceived barriers to care. Responses were self‐reported, collected anonymously, and summarized using descriptive statistics. Results A total of 187 respondents completed the survey; 85.6% identified as endourologists and 61.5% practiced in academic settings. Most respondents reported institution‐owned laser equipment (70.1%), while 9.6% reported contracted equipment and 20.3% combination models. Among respondents addressing contracted equipment availability ( n = 58), 55.2% reported ready access after regular business hours and 46.6% on weekends. Among 182 evaluable responses, 65.4% reported that physicians could operate lasers without a technician present. Fifty‐two respondents perceived that technician availability could affect patient care; among these, 40 reported potential delays in definitive treatment and 33 reported potential multiple or staged procedures. Staff laser safety goggles could be deferred according to 78.4% of evaluable responses, and 18.3% reported a prior institutional laser safety incident. Conclusion This survey identified substantial respondent‐reported variation in laser access, staffing requirements, and safety practices. The findings describe perceived institutional practices and barriers and do not establish effects on treatment delays, workflow efficiency, patient outcomes, or comparative safety. Future studies should directly compare institutional models using objective measures of access, workflow, treatment delays, and safety outcomes.

ABSTRACT Background Mobility functional status is inconsistently recorded in electronic health records. Recent advances in Large Language Models (LLMs) enable automated extraction of functional information from unstructured clinical notes. Leveraging a validated functional LLM with high performance in mobility extraction, we aimed to study the association between LLM‐derived mobility functional status and clinical outcomes, including emergency department (ED) visits, hospitalizations, and mortality. Methods Individuals aged 60 years and older enrolled in the Mayo Clinic Study of Aging, with documented clinical notes in 2022 were included. Individuals without any identifiable functional information were excluded. The LLM‐derived mobility functional status categorized mobility as impaired or unimpaired, across the five mobility domains as classified by International Classification of Functioning, Disability, and Health. Clinical outcomes in 2023 were extracted from the Rochester Epidemiology Project database. Logistic regression models assessed associations between mobility impairment and outcomes, adjusted for age, sex, Elixhauser comorbidity index, and education. Results Three thousand three hundred thirty‐seven individuals were screened, of whom three hundred forty‐three had no functional information. Two thousand nine hundred ninety‐four individuals were analyzed. 79.4% had at least one mobility impairment. Higher mobility impairment is associated with older age and greater Elixhauser comorbidity. Individuals with 3 or more impairments had an increased adjusted odds of ED visits (Adjusted Odds Ratio (aOR): 2.18 (1.64, 2.90)) and hospitalizations (aOR: 2.35 (1.51, 3.65)) compared to unimpaired individuals ( p < 0.001), while mortality did not demonstrate a significant association with mobility impairment. Conclusion LLM‐derived mobility functional status assessment was associated with ED visits and hospitalization, but not with all‐cause mortality after adjustment. Prospective validation and evaluation of incremental discrimination, calibration, and clinical utility are needed before clinical implementation.

Messenger RNA (mRNA) therapeutics have transformed vaccination and protein replacement strategies, yet efforts to improve their performance have focused largely on sequence engineering, nucleotide modification, and delivery vehicles. Here we show that mRNA function can be controlled by rational design of higher-order RNA architectures. We develop self-assembling mRNA origami (mRNA-OG), a class of unimolecular RNA nanostructures that encode protein-coding sequences within higher-order, programmable, and compact nucleic acid architectures. Using computational design and experimental validation, we demonstrate that mRNA-OG folds into well-defined nanostructures while remaining translationally competent in mammalian cells. Although folded mRNA-OG recruits ribosomes comparably to unfolded constructs, it produces lower protein output, indicating that RNA architecture can directly influence translational efficiency. The compact geometry of mRNA-OG also enhances encapsulation by cationic lipid delivery systems, suggesting a structural route to improved cargo packaging. Beyond its effects on translation, mRNA architecture modulates innate immune recognition. In primary human dendritic cells, folded and unfolded mRNA-OG elicit distinct cytokine programs and differential activation of stress-response pathways, including a modest induction of the integrated stress response that is not fully explained by canonical PKR signaling. Our results establish programmable structure as a new design parameter for mRNA therapeutics that can affect its functionality, delivery properties, and immune sensing.

Odontogenic myxoma (OM) is an uncommon, locally aggressive odontogenic neoplasm with characteristic histologic and clinico-radiographic features but with potential for histologic overlap with other odontogenic and non-odontogenic entities and a non-specific immunoprofile. Widespread loss of heterozygosity (LOH) has been recently described in rare cases of OM. The aim of this study was to determine whether widespread LOH represents a recurrent molecular signature that can be leveraged for clinical decision-making. Allele-specific copy number variation data from chromosomal microarray were generated from 7 OM, comprising a combined prospective and retrospective cohort. Four tumors arose in the mandible and 3 in the maxilla in patients ranging in age from 18 to 94 years (median: 44), with tumor size ranging from 2.2 to 13.0 cm. Variable amounts of fibrous stroma (odontogenic “fibromyxoma”) were present in 4/7 OM, and hypercellularity not typically appreciated in conventional OM was present in 3/7 cases. All OM (7/7) demonstrated widespread LOH, with 5 cases showing a near-haploid/low hypodiploid genomes (multiple monosomies) and 2 cases showing evidence of pseudo-hyperdiploidy due to probable endoreduplication. Both pseudo-hyperdiploid cases were ≥10 cm in size; 1 represented local recurrence. Chromosomes 1 to 3, 6, 9, 11, 13, 15, and 22 demonstrated LOH in ≥75% of cases (chromosomes 1 to 3, 6, and 9 in 100% of cases), while chromosomes 5, 12, 19, and 20 universally retained heterozygosity. Altogether, widespread LOH is a recurrent event in OM and a novel finding in odontogenic pathology, and allele-specific copy number variation analysis can serve as a diagnostic adjunct in challenging cases.

Objective To assess the effect of Moses™ 2.0 (Lumenis Be Ltd., Yokneam Illit, Israel; Boston Scientific, Marlborough, MA, USA) for lithotripsy of renal stones of 8–20 mm in diameter on operative time, surgeon workload, and retropulsion. Subjects/Patients and Methods In our multicentre, randomised, double‐blind clinical trial, patients were randomised 1:1 to standard or Moses 2.0 laser lithotripsy and stratified by stone size. Patients and surgeons were blinded to laser modality. Primary outcomes were total operative time as well as surgeon workload assessed by the National Aeronautics and Space Administration‐Task Load Index (NASA‐TLX). Secondary outcomes were stone retropulsion evaluated by blinded video review and postoperative clinical outcomes. Linear regression modelling was used for analysis. Results A total of 153 patients (79 Standard, 74 Moses 2.0) with similar clinical, stone, and operative characteristics were evaluated. There was no significant difference in operative times between the Standard and Moses 2.0 groups ( P = 0.73). Moses 2.0 was associated with lower effort, frustration, mental, physical, and temporal workload, as well as higher rated overall performance compared to the standard laser. Video review demonstrated no difference in rates of retropulsion ( P = 0.13). Complication rates (Standard: 13%; Moses 2.0: 10%) and stone‐free rates (Standard: 51%; Moses: 2.0 55%) were comparable. Conclusion Our study evaluated the impact of Moses 2.0 technology on high‐powered renal stone dusting, constituting the largest double‐blind trial of its kind to date. There was insufficient evidence to suggest any difference in operative times or clinical outcomes when using Moses 2.0 compared to standard laser lithotripsy. Moses 2.0 was associated with reduced surgeon workload, which has implicit impact on surgeon wellness.