Citations

ABSTRACT Introduction/Aims Scapular winging occurs as an abnormal protrusion of the scapula due to nerve injury, muscle weakness, bone, or joint pathology. The main muscular stabilizers of the scapula include the serratus anterior, trapezius, rhomboid major and minor, levator scapulae, and pectoralis minor. Needle electromyography (EMG) has historically been used as one of the primary diagnostic tests for evaluating this finding. However, sampling of these muscles can be technically difficult and carries risks for complications. Muscle ultrasound (MUS) can also reliably identify abnormalities in the muscles involved in scapular stabilization while offering the benefit of rapid side‐to‐side comparison and improved patient comfort. This study aims to highlight the concordance of ultrasound and EMG findings using our published MUS protocol in patients with scapular winging. Methods A retrospective analysis was performed of 13 patients who presented to an electrodiagnostic (EDX) laboratory with the referral diagnosis of “scapular winging” or “scapular dyskinesis.” All patients underwent MUS testing of scapular muscles according to a previously published protocol followed by EMG of muscles deemed relevant by the clinician. Results Seven patients were found to have a neurogenic cause of their scapular winging and in those patients, all had both EMG and MUS abnormalities. MUS was found to have a sensitivity of 87.5%, specificity of 95.7%, and individual muscle concordance with EMG of 90.6%. Discussion There is high concordance between EMG and MUS in patients with scapular winging. This combined with potential advantages of the MUS modality supports their concurrent use in patients with scapular winging.

Introduction Placental inflammation is a major contributor to preterm birth (PTB), and there are currently few targeted strategies to prevent PTB and its associated adverse neonatal outcomes. Serum amyloid A (SAA), particularly the isoforms SAA1 and SAA2, are well-recognized inflammatory markers, but their functional roles in placental inflammation remain poorly defined. Methods Using a translational mouse model of sub-chronic maternal inflammation, we investigated the immune mechanisms and therapeutic potential of siRNA-mediated targeting of Saa2 (siSaa2). Placental expression patterns of SAA2 were examined in vivo , and macrophage responses to extracellular SAA2 were modeled in vitro using RAW264.7 cells to assess downstream P2X7R-dependent signaling and functional outcomes. Results SAA2 is primarily induced in placental trophoblast and endothelial compartments during inflammation, where it acts as an extracellular inflammatory mediator. In vitro , we model macrophage responses to extracellular SAA2 using RAW264.7 cells to examine downstream P2X7R-dependent signaling and functional outcomes. Maternal administration of siSaa2 improved PTB rates, placental morphology and fetal brain development. Additionally, SAA1 and SAA2 exhibited distinct expression patterns in the mouse and human placenta. Discussion These findings identify placental SAA2 as a key inflammatory mediator in inflammation-associated PTB and demonstrate that targeted silencing of Saa2 represents a potential therapeutic strategy to mitigate placental injury and adverse fetal outcomes.

Abstract Here, we examine immune signaling pathways affecting the duration of primary nasopharyngeal colonization by Streptococcus pneumoniae ( Spn ), the first step in its pathogenesis. Spn colonization which lasts days to weeks in WT mice was persistent ( > 6 months) in the absence of IL-17RA-signaling. RNA-seq analysis confirmed the role of IL-17RA signaling in neutrophil-associated pathways. Rather than driving neutrophil specific chemokine expression, IL-17RA-signaling was required to replenish neutrophils in nasal tissue that were otherwise depleted during infection. Enhanced neutrophil trafficking correlated with IL-17RA-dependent expression of endothelial cell adhesion molecules that promote neutrophil trafficking from the circulation into nasal tissue. Persistent colonization was also observed in mice lacking IL-1R-signaling. Recognition of IL-1-family cytokines, however, was not necessary for the expression of IL-17A or neutrophil recruitment. Instead, IL-1R-signaling was associated with the activation of neutrophils in nasal tissue that displayed increased levels of the surface marker CD11b, an important receptor for the complement-opsonized phagocytosis of Spn . Our findings provide insight into the requirement for sustained neutrophil presence and activity to prevent persistent mucosal infection by a leading opportunistic mucosal pathogen. Author Summary Colonization of the upper airway by Streptococcus pneumoniae ( Spn ) is common and often asymptomatic, particularly in early life, yet prolonged colonization increases the risk of transmission and invasive disease. Despite its importance, the immune mechanisms that prevent long-term persistence of Spn in the upper airway are not fully understood. In this study, we investigated how two immune signaling pathways, the IL-17RA and IL-1R pathways, contribute to preventing persistent Spn colonization. Using a mouse model, we found that the IL-17RA pathway supports continued replenishment of neutrophils into nasal tissue by promoting expression of molecules that allow these cells to exit the bloodstream and enter the nasal tissue. In contrast, the IL-1R pathway activates neutrophils in a way that makes them more effective at clearing Spn . Loss of either pathway resulted in persistent Spn colonization, with an additive effect seen when both pathways were removed. Collectively, our results highlight how two distinct immune pathways cooperate to control pneumococcal colonization by sustaining neutrophil recruitment and function.

Abstract Radiation therapy (RT) has long been included in the treatment of glioblastoma (GBM). However, radioresistance in cancer cells as well as toxicity in normal tissues are major obstacles to clinical efficacy. Improved understanding of the mechanisms of tumor microenvironment-induced radioresistance during and after radiation therapy can provide fundamental insights to improve clinical outcomes in GBM. Here, using three-dimensional engineered hydrogel models in vitro, we report the influence of extracellular matrix, hypoxia, and adjacent neuronal cells in radiotherapeutic sensitivity. We find that mechanical cues and oxygen availability regulate cellular response to radiation, with softer matrices allowing for more DNA damage. Hyaluronan fragments from the extracellular matrix also modulate rapid metabolic response to radiation, especially in hypoxic environments. We show that neuronal networks influence tumor metabolic activity and the inflammatory response. Overall, we demonstrate here that alternative radiation strategies, such as low dose rate radiation therapy and microenvironmental regulation, have the potential to be more effective in a specific subset of radiosensitive GBM tumors.

ABSTRACT Background Systemic infections are a leading cause of hospitalization and death among patients with cirrhosis. Timely and accurate infection identification is essential for both clinical care and the development of predictive models. However, existing methods such as ICD-10 coding are unreliable, and manual chart review is resource-intensive and difficult to scale. This study aimed to develop and validate an automated large language model (LLM)-based approach for infection classification and subtyping in patients with cirrhosis presenting to the emergency department (ED). Method We developed INFEHR (INfection identification and subtyping using Free-text EHR analysis), an LLM-powered pipeline utilizing Claude 3.5 Sonnet to analyze clinical notes from the first 72 hours of admission. Model outputs were compared against a physician-adjudicated gold standard in a cohort of 1,000 encounters from patients with cirrhosis who presented to the ED. Performance was benchmarked against ICD-10 code–based labeling and CDC Adult Sepsis Event criteria. Results INFEHR achieved 94.7% overall accuracy, with 99.5% sensitivity and 92.8% positive predictive value for identifying infection presence, outperforming ICD-10–based classification across all metrics ( p < 0.0001). The model also demonstrated strong performance in classifying pathogen type and infection site. This pipeline processed notes within seconds, offering improvements in efficiency and scalability over manual review. Conclusion INFEHR offers a scalable, reproducible, and accurate method for infection phenotyping in cirrhosis. By overcoming limitations of traditional coding and manual review, it supports high-throughput infection surveillance, improves cohort construction for clinical research, and enables future integration into real-time decision-support tools in hepatology.

Immunotherapy has been effective in many cancer types but has failed in multiple clinical trials in prostate cancers, with the underlying mechanisms remaining largely unclear. Here, we demonstrate that androgen receptor pathway inhibitor (ARPI) plus irradiation (IR) triggered robust anticancer immunity in prostate cancers in both patients and mice. We show that androgen-activated AR suppressed innate immune signaling by inducing inhibitor of nuclear factor kappa-B kinase subunit epsilon ( IKBKE ) gene repression through HDAC2 interaction with an IKBKE enhancer RNA ( IKBKE eRNA, or IKBKE-e ). ARPI treatment caused IKBKE derepression and enhanced an IR-induced innate immune response via action of RIG-I and MDA5 dsRNA sensors. IKBKE-e ablation largely enhanced innate immunity in prostate cancer cells in culture and anticancer immunity in mice. Our results revealed AR, HDAC2, and IKBKE eRNA as critical intrinsic immune suppressors in prostate cancer cells, suggesting that rejuvenating inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKε) signaling by targeting IKBKE-e is an actionable strategy to elicit synthetic anticancer immunity in immunologically “cold” cancers such as prostate cancer.

Bone scintigraphy is a valuable adjunct to cross-sectional imaging and can be used to evaluate disease extent in multifocal processes such as blastic osseous metastatic disease, provide diagnostic information to aid in problem solving in challenging cases, and serve as the primary diagnostic modality for diseases that manifest with pathognomonic scintigraphic appearances.

Abstract Background The accuracy and safety of generating medication orders by large language models (LLMs) must be demonstrated. Without standardization, performance evaluation is limited to time and resource-intensive clinician grading. This evaluation aimed to develop a standardized medication format that supports automated performance evaluation (MedMatch). Methods First, a survey of 40 medication prompts was given to clinicians to assess agreement in medication order communication. Second, a clinician panel developed a standardized medication format (MedMatch) for oral and intravenous medications. Third, a clinician-annotated dataset of medication prompts and standardized answers in the MedMatch format was developed for LLM testing. Finally, LLMs were retested with the same dataset, adjusted to exclude route information, to evaluate the appropriate categorization of medication route. Results The formal medication orders consistently showed low omission rates and high overlap for all entities, compared to the verbal and brief written communication types. Lexical overlap results demonstrated pattern norms amongst clinicians with entities appearing most commonly in positions 1-5 in the order of drug name, dose, unit, route, and frequency. In the second survey, the formal written group performed the highest with 78.3% of prompts considered appropriate as a computer-generated response. LLM accuracy on MedMatch order standardization was highest in oral solid (64.2-72.5%), intravenous intermittent (72.5-84.3%), and intravenous push (62.7-74.5%) categories. LLMs performed the worst at categorizing medication orders accurately into intravenous push (18-61%) and intravenous intermittent (51-100%) routes. Conclusions Standardized format for computer-based outputs may support automated performance analysis and enhance the clarity of medication communication.

Background: This systematic review examined differences in learner outcomes between traditional learning models (TLMs) and dedicated education units (DEUs) in undergraduate nursing programs. Method: Six databases were searched to identify peer-reviewed literature published between 2000 and 2025. Fifteen articles informed this review. Results: Included studies focused on various student outcomes including evaluation of students' perceptions and student performance. Themes around student perception included learning environment, learning opportunities, and learning performance. Themes around performance included standardized exams, course exams, competency exams, and preceptor evaluation of competency development. Conclusion: Main findings indicate the DEU model for clinical education enhances student satisfaction with the learning environment, increases learning opportunities, and improves self-perceived learning performance. The effects of DEUs on student performance outcomes require additional research, but preliminary research suggests a positive relationship between the DEU and competency development.