Citations

Background: Accurate preoperative characterization of axillary lymph nodes (ALNs) is important in breast cancer, but conventional ultrasound has variable diagnostic performance. We evaluated quantitative shear wave elastography (SWE) for distinguishing reactive from metastatic ALNs, and we explored associations between nodal SWE parameters, breast cancer subtypes, and histological grades. Methods: We prospectively enrolled women with suspicious breast lesions and ALNs identified by clinical ultrasound who were scheduled for biopsy. After exclusions, 141 patients (57 reactive and 84 metastatic ALNs) were included. ElasticNet-regularized logistic regression with nested cross-validation compared clinical ultrasound alone with ultrasound plus SWE. Among 70 patients with metastatic ALNs and immunohistochemical characterization, SWE parameters were compared across surrogate subtypes and histological grades using Kruskal–Wallis tests with Holm adjustments. Results: The combined ultrasound–SWE model achieved an area under the receiver operating characteristic curve of 0.911 (95% CI, 0.859–0.961) compared to 0.798 (95% CI, 0.723–0.873) for ultrasound alone. At the Youden-derived threshold, the combined model achieved 88.1% sensitivity, 82.5% specificity, and 85.8% accuracy. Among metastatic ALNs, SWE parameters, namely Vmean, Vsd, and Vmax, differed significantly across surrogate subtypes, with the most pronounced differences observed between Luminal A and Luminal B tumors, (p = 0.0250, p = 0.0069, and p = 0.0065). No statistically significant differences were detected with histological grades in the five SWE parameters. Conclusions: Quantitative SWE complemented conventional ultrasound for assessing axillary nodal metastasis, with higher cross-validated discrimination for the combined model. Exploratory analyses identified differences in several SWE stiffness metrics between Luminal A and Luminal B tumors; these subtype-associated biomechanical differences require validation in larger cohorts.

Aims Periacetabular osteotomy (PAO) is performed in young, opioid-naive patients and is associated with postoperative pain. Optimizing perioperative analgesia while limiting opioid exposure remains a priority. This study evaluated postoperative pain trajectories, hospital length of stay (LOS), and opioid-prescribing patterns associated with an institutional transition from epidural-based to periarticular injection (PAI)-based analgesia after PAO. Secondary aims were to assess the influence of preoperative opioid exposure and compare outcomes between ropivacaine-based and bupivacaine PAI formulations. Methods The study included 724 patients who underwent PAO between January 2010 and December 2022 at a single academic institution, with epidural use replaced by PAI in 2016. Patients were stratified by postoperative analgesia strategy: epidural catheter (n = 333) or PAI (n = 391). Outcomes included daily postoperative pain scores, LOS, discharge opioid prescriptions (morphine milligram equivalents (MMEs)), total opioid exposure, and 30-day refill rates. Statistical comparisons were performed using chi-squared, Fisher’s exact, and Kruskal–Wallis tests. Results Baseline characteristics were similar between groups. Epidural analgesia was associated with lower pain scores during the first 48 hours (last pain postoperative day 0 to 1: mean 2.9 (SD 2.0) vs 4.7 (SD 2.1); p < 0.001), whereas the PAI group had a shorter LOS (mean 2.2 days (SD 1.0) vs 3.4 days (SD 0.9); p < 0.001) and higher pain scores at discharge (mean 4.8 (SD 1.9) vs 4.0 (SD 1.9); p < 0.001). Median discharge opioid prescriptions (313 (IQR 225 to 388) vs 825 (IQR 600 to 1,000) MMEs) and total 30-day opioid exposure (360 (IQR 275 to 575) vs 900 (IQR 638 to 1,100) MMEs) were lower in the PAI group (both p < 0.001), while refill rates were higher (34.0% vs 19.2%; p < 0.001). Within the PAI cohort, ropivacaine-based and bupivacaine injections showed similar pain trajectories and refill rates. Conclusion Epidural analgesia provided superior early postoperative pain control, whereas PAI-based pathways enabled earlier discharge and lower overall opioid prescribing but with higher refill rates. These findings highlight trade-offs in contemporary perioperative pathways and support individualized analgesic strategies after PAO. Cite this article: Bone Jt Open 2026;7(11):1410–1418.

Background: Developing students' ability to transfer physiological principles across contexts remains challenging in physiology education. Comparative framing (CF), in which physiological principles are presented through nonhuman examples, may facilitate transfer by organizing reasoning around variation in environmental challenges and physiological function. However, whether benefits arises from CF itself or engagement with physiologically rich examples remains unclear. Methods: A between-semester controlled design was conducted across undergraduate (n = 99) and graduate (n = 43) exercise physiology courses. Semesters were randomly assigned to CF or human-centered framing (HF), with instructional content and structure held constant. Primary outcomes were parallel, non-identical transfer assessments administered before instruction, immediately afterward, and at delayed follow-up. Secondary outcomes included a content equivalence assessment, a two-tier conceptual reasoning measure, and mental effort ratings. Reflective writing was analyzed using inductive thematic analysis. Results: Both conditions demonstrated comparable content acquisition. Significant Framing x Time interactions were observed for Systems and Adaptive Integration and Translational Application, but not Mechanistic Reasoning. The benefits of CF were concentrated in reasoning tasks requiring context-dependent interpretation and integration of physiological principles and became more pronounced at delayed follow-up. Reflective writing analyses converged with the quantitative findings, with the largest thematic differences observed in adaptive versus pathological reasoning. Conclusion: CF produced more durable physiological reasoning despite comparable content learning, suggesting that its educational value extends beyond engaging students with physiologically rich examples alone. Organizing physiology around context, function, and physiological trade-offs may provide a framework for promoting transfer and context-dependent physiological reasoning.

BACKGROUND. Dementia is a rapidly expanding public health problem with major socio-economic burden. Insulin resistance (IR) is a prevalent but modifiable risk factor for dementia, yet its effects on brain structure, functional connectivity, and metabolism remain incompletely understood. METHODS. Regional brain glucose uptake (PET), volumes (MRI), functional connectivity (fMRI), and cognition (NIH Toolbox) was measured in 72 adults with or without markers of IR. To evaluate reversibility of IR-associated brain deficits, forty older adults with IR were randomized to forty weeks of metformin or placebo, and brain measures were repeated. As a proof-of-concept experiment, we developed a conditional brain-specific insulin receptor knockout mouse and assessed brain mitochondrial function and cognition. RESULTS. In older adults with markers of IR is associated with diminished total and regional brain volumes in areas critical for neuronal connectivity, memory, and learning, including cerebral white matter and the hippocampus. Reduced functional connectivity between brain regions detrimental for cognition was also noted. Further, we demonstrated that ATP production, essential for neuronal connectivity, was diminished in neuron-specific insulin receptor knockout mice accompanied by deficits in hippocampal- and prefrontal-dependent tasks. Forty weeks of metformin improved systemic insulin sensitivity concurrent to preserved brain glucose uptake, volume, and functional connectivity within specific regions central to decision-making and learning. Metformin was also associated with an improved composite measure of processing speed and working memory. CONCLUSION. These findings highlight IR as a key regulator of brain metabolism and support the concept that insulin sensitization can prevent neurobiological deficits in older people with IR.

Abstract Objective In 2024, the US News and World Report (USNWR)'s Best Hospitals began reporting complications following elective outpatient otolaryngology procedures in its ears, nose, and throat (ENT) ranking. However, this methodology has not been clinically adjudicated in a peer‐reviewed domain. We aimed to conduct manual health record adjudication to assess whether the USNWR methodology accurately attributes complications following elective outpatient otolaryngology procedures. Study Design Case‐cohort. Setting A case‐cohort of n = 80 elective, outpatient otolaryngology procedure/complication pairings from January 2019 to October 2023 across four academic medical centers using the 2024 USNWR otolaryngology procedure subgroups and Solventum Ambulatory Potentially Preventable Complications (AM‐PPC) software. Methods We used the AM‐PPC‐defined complication types as our standard of comparison for our clinical adjudication. Using the electronic health record, we adjudicated: (1) Was there agreement (yes/no) on complication type between our clinical adjudication and the Solventum AM‐PPC software? (2) Was the complication clinically related to, or a sequela of, the index otolaryngology procedure (yes/no)? Results The clinical adjudication agreed on complication type in 59/80 (74%) of patients, and 63/80 (79%) were judged to be clinically related to the index otolaryngology procedure. In total, 50/80 (63%) complications were adjudicated to be in agreement on both the complication type and clinical relatedness to the index procedure, while 9/80 (11%) complications did not agree with the complication type nor were clinically related to the index procedure. Conclusion Outpatient complications reported in the USNWR ENT rating lack the specificity to exclude patients whose complications are sequelae of chronic underlying conditions or related to concurrent, non‐otolaryngology procedures.

Environmental conditions experienced early in life have profound consequences for vertebrate health, yet the molecular pathways linking developmental stress to aging and reduced lifespan remain poorly understood. Through a novel highly accurate epigenetic clock, developed from RRBS-based blood DNA methylation profiles, we show that experimental lifespan-reducing early-life stress rapidly accelerates epigenetic age in zebra finch chicks (Taeniopygia guttata). Corticosterone-treated 29-day-old chicks share differentially methylated loci with non-treated aged birds and cluster with 6-month-old birds. The transcriptional repressor ZBTB16 emerges as an epigenetically top age-correlated gene and is strongest affected by corticosterone. Elevated developmental corticosterone causes rapid epigenetic remodelling of metabolic pathways well-established in aging and longevity. Our results demonstrate epigenetic rewiring of the aging trajectory through conserved stress-survival mechanisms immediately following elevated early-life stress exposure.

Abstract Cellular senescence is a central hallmark of aging, yet its measurement in humans remains invasive, low-throughput and tissue-specific, precluding population-scale study. We developed Methylation-associated Gene Expression (MaGE) predictors: whole-blood DNA methylation proxies of p14 ARF , p16 INK4A and p21 CIP1 expression, plus a composite score, providing the first scalable measure of senescence-marker expression. Deployed across Generation Scotland (n=18,859), MaGE yielded 45 Bonferroni-significant associations spanning 18 incident diseases and all-cause mortality. The two strongest associations recapitulated the established tissue specificity of p21 CIP1 and p16 INK4A activation, with MaGE-p21 associating with incident alcoholic liver disease and MaGE-p16 with pulmonary fibrosis. In a separate study, MaGE tracked disease severity and treatment response in Crohn’s disease. MaGE is a scalable, interpretable biomarker of senescence that enables its study at population scale and offers a route to patient stratification in senolytic trials.