Citations

Abstract Provided herein are novel compounds as TREM2 agonists, pharmaceutical compositions, use of such compounds in treating Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Nasu-Hakola disease and stroke, and processes for preparing such compounds.

Abstract Reliable extraction of trial characteristics and outcomes is essential for systematic reviews, yet incorrect values can alter evidence synthesis and are difficult to detect without clear source evidence. We evaluate EviSearch, a clinical evidence-curation system that links extracted values to source passages, independently verifies cited evidence, and prioritizes higher-risk cells for review. Using ten trial publications, a 133-column schema, reference annotations, and consistent scoring across model families, we assess answer quality, inter-reading agreement, evidence reproduction, targeted review, and evidence modality. In the Qwen evaluation, EviSearch achieved 91.70% accuracy, cited 100.0% of admitted values, and reproduced 98.9% independently. Reviewing 15.6% of cells increased accuracy to 95.22%.

ABSTRACT Persistent gaps in anatomical knowledge among incoming residents have raised concerns about clinical preparedness, especially in surgical and interventional disciplines. Conventional anatomy instruction and limited cadaveric exposure and learning opportunities in medical curricula have prompted calls for innovative, clinically focused anatomical curricular integration in clinical training. This article describes the development, implementation, and impact of a tailored Year 4 Clinical Anatomy Elective in the Department of Clinical Anatomy at Mayo Clinic, designed to reinforce competency in clinically relevant anatomical understanding and support learners' perceived preparedness during transitions to residency. A 4‐week elective was designed for fourth‐year medical students interested in pursuing a specific residency program. The course was personalized for students' clinical interests and incorporated fresh tissue dissection, simulation, procedural skills training, and imaging using an immersive learning platform. The elective was structured within the experiential learning model using a guided, self‐directed format within a multicapability laboratory and instructional environment, grounded in constructivist theory. A 5‐year review of elective records and informal thematic analysis of student feedback were conducted. Most participants pursued surgically related specialties, with orthopedic surgery being the most common. Exploratory thematic analysis identified six core themes: Professional Identity Formation, Educational Benefits, Learning Challenges, Connection to Clinical Practice, Patient Care Implications, and Future Preparation and Transferability. These students perceived gains in areas aligned with ACGME milestones: increased confidence, greater preparedness for residency, and improvement in their ability to apply anatomical knowledge in clinical settings. This perception may be indicative of lifelong learning and early educator identity formation. A specialty‐specific, clinically integrated anatomy elective may support learners' perceived preparedness for residency, reinforce clinically relevant anatomical understanding, and support the development of educational and professional competencies. Such targeted interventions may help address perceived gaps in anatomical preparedness during the transition to residency and contribute to postgraduate training within a competency‐based medical education framework.

Background & Aims: We examined treatment patterns and clinical outcomes in a contemporary cohort of children with newly diagnosed inflammatory bowel disease (IBD) in a large, commercially insured U.S. population. Methods: Using the OptumLabs® Data Warehouse, we created an inception cohort of physician-diagnosed IBD in children aged 6–17 years between 2007–23. We examined cumulative incidence of hospitalization, surgery, safety events, and medication use in patients with Crohn's disease (CD) and ulcerative colitis (UC), overall and stratified by diagnostic era, race and ethnicity, sex, and age at diagnosis. Results: Among 787 children with newly diagnosed CD (age at diagnosis, 13.4±2.9y; 57% male; 82% White, 5% Black, 7% Hispanic) followed over mean 4.6±3.0y, 5-year risk of IBD-related hospitalization and major surgery was 30% and 10%, respectively. In children diagnosed in 2019–23, 1-year cumulative use of corticosteroids and advanced therapy was 46% and 75%, respectively; advanced therapy use increased significantly over time (aHR, 3.43 [95% CI, 2.71–4.32] for 2019–23 vs. 2007–12), while corticosteroid use declined (0.67 [0.53–0.84]). Risk of IBD-related hospitalization was lower in children diagnosed between 2019–23 (0.65 [0.43–0.97]) compared with those diagnosed between 2007-12; surgical risk did not decline significantly, with confidence intervals compatible with a clinically meaningful reduction. Among 399 children with newly diagnosed UC (age at diagnosis, 14.0±3.0y; 53% male; 78% White, 5% Black, 7% Hispanic) followed over 4.5±3.0y, 5-year risk of IBD-related hospitalization and colectomy was 36% and 8%, respectively. Advanced therapy use increased significantly over time (4.46 [2.85–6.98] for 2019–23 vs. 2007–12), with no significant change in hospitalization or surgical risk across eras. No consistent racial and ethnic, age, or sex differences in advanced therapy use or clinical outcomes were identified in either CD or UC. Conclusions: In a contemporary cohort of commercially insured children with newly diagnosed IBD, early advanced therapy use has increased markedly over time. Surgical risk did not decline significantly in either disease; however, the study was not powered to exclude a clinically meaningful reduction, and these findings are hypothesis-generating rather than conclusive.

Background African American adults experience a disproportionate burden of dementia, shaped by structural and clinical factors that remain unclear. Objective To quantify associations between multimorbidity, polypharmacy, and cognition in the context of neighborhood disadvantage. Methods This study is a cross-sectional analysis of 348 African American adults aged 45–92 years (mean 64.3 years; 73.6% female) from the Aging Research Characterizing Health Exposome via Social drivers (ARCHES) cohort. Comorbidity burden was assessed using a modified Charlson Comorbidity Index (CCI), polypharmacy as ≥5 medications, and neighborhood disadvantage using the Area Deprivation Index (ADI). Linear regression estimated associations with a Preclinical Alzheimer’s Cognitive Composite (PACC). The polypharmacy model included modified CCI as a covariate, and effect modification by ADI was assessed using an interaction term between polypharmacy and ADI. Results Higher modified CCI was associated with lower cognitive performance (B = −0.071; 95% CI: −0.130, −0.012). Polypharmacy was not independently associated with cognition after modified CCI adjustment (B = −0.081; β = −0.057; p = 0.257). No significant ADI interaction was found (p = 0.064).

Background: This qualitative study sought to understand factors related to low rates of screening mammography among transgender and gender-diverse (TGD) individuals and how these rates might be improved. Methods: Individuals who self-reported as TGD were recruited from multiple sites and national patient advocates. Consenting participants completed an individual interview using a semistructured guide informed by the Health Belief Model (HBM). Interview data were analyzed using thematic analysis. Results: A total of 44 individuals completed the interview (median age, 44.9 years; range, 19–77 years); 11% were a racial/ethnic minority; and 52%, 20%, and 25%, respectively, self-identified as a transgender woman, transgender man, or nonbinary. Three themes emerged around constructs in the HBM. First, individuals voiced a hope to be treated equally (“I just want to go to work, pay my taxes, love my family, and go along my day and be a good human”) and described how such equitable treatment during screening guarded against gender dysphoria and favored gender affirmation (“it is affirming…being treated as any other woman”). Second, barriers and facilitators related to mammography were identified, including the need to address cost/low cost (“screenings are a luxury”); prior negative/positive experiences (“they would call my name and look at me but dismiss me”); absence/presence of education (“none of the doctors…ever told me what that process looks like”); and perceived low/high cancer risk (“my mom died pretty young from breast cancer”). Finally, practical recommendations were offered, including individual changing/waiting rooms, hiring gender-diverse staff, and engaging clinicians who provide whole-person, trauma-informed care. Conclusions: Mammographic screening among TGD individuals could be improved by proactively creating safe, affirming spaces; working to lower costs; providing educational materials tailored to the TGD community about cancer risk and the practical aspects of screening; and hiring gender-diverse staff. These recommendations from TGD participants merit implementation as well as further study.

ABSTRACT Background Pectus excavatum (PE), the most common congenital chest wall deformity, has known associations with connective tissue disorders and may lead to cardiopulmonary impairment; however, its relationship with atrial fibrillation (AF) remains underexplored. Objectives This study aimed to describe the frequency, clinical characteristics, and management of AF within an institutional cohort of patients with PE, and to determine whether the outcomes observed in clinically distinct subgroups persisted after adjustment for baseline risk. Methods This was a retrospective cohort study design. Patients with both PE and documented AF between January 1, 1990, and November 10, 2024, were included. Clinical, echocardiographic, and therapeutic data were collected. Bleeding and thromboembolic outcomes were evaluated using multivariable logistic regression adjusted for age, sex, CHA 2 DS 2 ‐VASc score, and anticoagulant class, and the surgically treated subgroup was additionally compared using propensity score matching. Results Among 11,578 patients with PE, 1309 (11.3%) had AF. Of those who had AF, mean age was 66.9 years; 54% were female, and 83% had paroxysmal AF. The mean CHA 2 DS 2 ‐VASc and HAS‐BLED scores were 2.8 and 1.9, respectively. Thromboembolic events occurred in 196 (15%) patients, most commonly stroke (11%), followed by pulmonary embolism (4%) and deep venous thrombosis (4%). Bleeding events occurred in 313 patients (24%), most commonly hematuria (12%), gastrointestinal bleed (11%), epistaxis (5%), and intracranial hemorrhage (1%). Seventy‐two patients (6%) underwent the Nuss procedure and were younger (45.3 vs. 68.2 years, p < 0.001), predominantly male (65%), and had lower risk scores compared to the non‐Nuss cohort. Patients who underwent the Nuss procedure had significantly fewer bleeding events (5.6% vs. 25%, p < 0.001) with similar thromboembolic rates. The pectus severity index, available in the 370 patients who underwent dedicated radiologic review, was not associated with bleeding (adjusted OR 0.89, 95% CI 0.75–1.05). The difference in bleeding by surgical status persisted after multivariable adjustment (adjusted OR 0.28, 95% CI 0.10–0.79) and after propensity score matching (5.6% vs. 16.7%, p = 0.030). Conclusions AF was identified in approximately one in nine patients within this single‐institution cohort of adults with PE, with paroxysmal AF representing the predominant subtype. Patients who had undergone surgical repair demonstrated a lower incidence of bleeding events than anticipated based on their baseline risk profile; however, given the limited number of events observed, this finding should be interpreted with caution and requires validation in larger studies. In the absence of a non–PE comparator group, these data are insufficient to determine whether PE independently confers an elevated risk of AF, and prospective, controlled investigations are necessary to elucidate this relationship.

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a promising therapeutic option for women with polycystic ovary syndrome (PCOS). Clinical trials and data demonstrate significant improvements in body weight, insulin resistance, hyperandrogenism, and, in some studies, menstrual regularity and reproductive outcomes. However, the current evidence base remains disproportionately focused on short-term metabolic and anthropometric endpoints, while outcomes most relevant to patients—including treatment satisfaction, gastrointestinal tolerability, psychological well-being, body image, fertility planning, financial burden, and long-term adherence—remain inadequately characterized. Methods: We searched PubMed and Google Scholar for English-language literature published between 2021 and 2026, using structured keyword searches. This narrative review evaluates the literature on GLP-1RA use in PCOS beyond weight-focused outcomes, examining mechanisms of action, comparative tolerability across agents, and patient-centered domains including quality of life, eating behavior, and reproductive planning. Results: The published literature reveals a substantial gap between trial-reported completion rates and treatment success, and actual persistence and patient satisfaction. This discrepancy is particularly consequential in PCOS, where treatment decisions intersect with high baseline rates of depression, anxiety, and body image disturbance, and where ovulatory benefits must be weighed against mandatory discontinuation before conception. Conclusions: We identify a systematic absence of validated patient-reported outcome measures, standardized core outcome sets, and long-term follow-up data after treatment withdrawal. This review proposes a research agenda prioritizing patient-centered endpoints as co-primary outcomes, structured assessment of acceptability and persistence, qualitative and mixed-methods approaches, and a dedicated study of fertility planning and treatment interruption.

Purpose To evaluate the agreement between a simple magnetic resonance imaging‐based measurement method for determining the patellar tendon‐to‐lateral trochlear ridge (PT‐LTR) distance using an external adhesive marker and a previously validated conventional measurement technique. Methods Patients diagnosed with patellofemoral instability before undergoing primary patellar stabilization surgery at a single institution between 2020 and 2024 were eligible for inclusion. PT‐LTR distances were measured in a blinded fashion by 2 musculoskeletal‐trained radiologists using the conventional technique and by an orthopaedic group using the simple technique. Interrater reliability between the musculoskeletal‐trained radiologists and between the orthopaedic groups was calculated using intraclass correlation coefficients (ICCs) and concordance correlation coefficients (CCCs) and subsequently intermethod reliability between the 2 groups. The measurements were plotted on concordance correlation graphs. Results One hundred knees (38 right, 62 left) from 97 patients (37 men, 60 women; mean age 22 ± 9 years) were included. The average distance for PT‐LTR measured by the radiologists using the conventional technique was 10.9 ± 7.5 mm and by the orthopaedic group using the simple technique was 9.3 ± 6.8 mm. Excellent interobserver agreement was noted for the radiologist group (ICC 0.941, 95% confidence interval [CI], 0.914‐0.960; CCC 0.941, 95% CI, 0.915‐0.959) and orthopaedic group (ICC 0.976, 95% CI, 0.964‐0.985; CCC 0.976, 95% CI, 0.965‐0.984). Excellent intermethod agreement was noted between the 2 techniques (ICC 0.903, 95% CI, 0.775‐0.942; CCC 0.902, 95% CI, 0.861‐0.932). Conclusions There was excellent interobserver reliability for measuring PT‐LTR distance using both the conventional radiologist‐based technique and the external adhesive marker technique. Excellent intermethod agreement was also shown between the 2 techniques, with comparable mean measurements between groups; thus, the simple technique can be used as a reproducible alternative for PT‐LTR distance. Level of Evidence Level III, retrospective comparative study.