Citations

Abstract Objectives Granulomatous myositis (GM) is defined by focal collections of activated macrophages that fuse to form multinucleated cells that aggregate into granulomas within skeletal muscle. This study aimed to elucidate the pathophysiology of GM by defining its specific transcriptomic profile. Methods Bulk RNA sequencing was performed on 722 muscle biopsies, including 38 from patients with GM, other myopathies and healthy comparators. Spatial transcriptomics and immunohistochemistry assays were used to identify the location of specific transcripts and proteins within the tissue. Results We conducted a systematic analysis of the inflammatory pathways implicated in GM. This analysis revealed that GM muscle biopsies are characterized by elevated levels of IFNγ, IFNγ-inducible genes and proinflammatory cytokine genes including IL1B, TNF and TGFB1. Additionally, we identified a specific gene signature in GM, comprising 1293 genes that were significantly upregulated and 256 significantly downregulated. These genes were strongly correlated with transcriptomic markers of disease activity. Using this gene signature, support vector machine models accurately identified GM, achieving an area under the curve of 99.6% (99.0–99.9%) and an accuracy of 98.6% (98.2–98.9%). Among the identified genes, CHIT1 emerged as the most significantly upregulated gene, with its expression strongly correlating with disease severity. Furthermore, CHIT1 was detected at both the RNA and protein levels in granulomas and giant cells. Conclusion GM is transcriptomically characterized by a strong IFNγ signature and overexpression of proinflammatory cytokines, including IL1B, TNF and TGFB1. Additionally, it exhibits a unique transcriptomic profile, including CHIT1, which correlates with disease activity.

Abstract We present a high-fidelity, patient-specific computational framework for simulating cardiovascular hemodynamics in left ventricular assist device (LVAD) patients, with the ability to evaluate the impact of mitral and aortic valve repair. The method couples three-dimensional computational fluid dynamics (CFD) with a zero-dimensional lumped-parameter network representing the full cardiovascular system. Valve dynamics are governed by pressure–flow physics with patient-specific regurgitant areas, enabling the investigation of valve insufficiency and surgical repair. The model incorporates dynamic contrast-enhanced CT imaging, echocardiography, and catheter-based measurements. We demonstrate the utility of this framework using a clinical case involving a patient on long-term LVAD support with mitral regurgitation and aortic insufficiency. The coupled model resolves detailed pressure and velocity fields in the left heart, LVAD cannulae, and aortic root, while maintaining system-wide physiological consistency. Importantly, the framework also quantifies right ventricular loading and function, allowing assessment of how left-sided valve interventions propagate through the cardiopulmonary circulation. Using this pipeline, we simulate mitral and aortic valve repair by modulating valve closure mechanics and regurgitant area, revealing changes in both local and global hemodynamics. This modeling platform provides a powerful means to study the interplay between mechanical circulatory support, native valve physiology, and right heart function. It enables rigorous, patient-specific evaluation of surgical interventions in LVAD patients and delivers quantitative insight into clinically important metrics—such as aortic pulsatility, RV afterload, and chamber-level flow patterns—that are challenging to capture with current imaging modalities.

ABSTRACT Consumer health informatics is becoming increasingly important in a world where more than 5 billion people rely on the internet and social media for health information. eHealthyinfo is a physician‐initiated and reviewed artificial intelligence (AI) applied digital health information website, aiming to be essential in advancing health literacy and promoting preventive health behaviors. To assess the effectiveness of its digital content, we conducted a mixed‐methods evaluation of 13 wellness and nutrition videos randomly selected from eHealthyinfo, representing 30% of its relevant content. Two independent reviewers used the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT‐A/V) and the modified version of the CDC Clear Communication Index (CCI) to evaluate each video. Website log data were also analyzed to assess levels of user engagement. The average PEMAT scores were 89.5% for understandability and 100% for actionability, while the average CCI score was 94.4%, indicating the content was understandable, actionable, and clear. Weblog analysis revealed 16,000 active users, with an average engagement time of 41 seconds per user and a 27% average bounce rate for the examined year. eHealthyinfo demonstrates a strong potential as a digital health education tool, with high‐quality, user‐friendly content.

Objective: To systematically review the existent literature on radiosurgery for treatment of sporadic facial nerve schwannomas (FNS). Databases reviewed: PubMed, SCOPUS, EMBASE, and Web of Science databases. Methods: Systematic review was performed per PRISMA criteria of studies published from 1990 through 2024 on patients diagnosed with sporadic FNS who were treated with radiosurgery. Outcomes included change in facial nerve function, change in hearing class, and radiosurgical treatment failure defined by need for reintervention. Study quality was assessed using the LEGENDS rubric for mixed modality studies. Results: In total, 35 studies encompassing 364 patients were included for data abstraction. Gamma Knife was the most common modality reported. Longitudinal patient-level data on facial nerve function were available for 101 patients, with 8% of patients experiencing worsening facial nerve function and 92% of patients having either stable nerve function or improvement in facial nerve function following treatment over a median follow-up of 36 months. Longitudinal patient-level hearing data were available for 53 patients, including 35 patients with serviceable hearing (AAO-HNS class A or B) at baseline; only 2 patients developed nonserviceable hearing (AAO-HNS class C or D) following treatment over a median follow-up of 36 months. Clinical tumor control data were available for 295 patients, of whom 11 required salvage treatment over a mean follow-up of 49 months. Conclusions: This systematic review demonstrates a relatively low risk of worsening facial nerve function and a high rate of clinical tumor control following radiosurgery for sporadic FNS.

Latissimus dorsi (LD) and teres major (TMA) injuries are increasingly recognized as significant sources of pain in overhead athletes, particularly pitchers. These injuries are challenging to diagnose clinically, and conventional MRI often lacks sufficient detail to fully evaluate them. Musculoskeletal ultrasound (US) offers dynamic, high‐resolution evaluation and may better characterize these injuries. This pictorial review illustrates the sonographic appearance of common LD and TMA injuries, aiming to enhance diagnostic accuracy, increase clinician familiarity with this region, and support future research in injury classification using ultrasound.

Abstract Lewy pathology can form over decades in patients with Lewy body diseases, but the causal cellular mechanisms associated with this process remain unclear. This project aims to discover proteins that associate with monomeric and/or oligomeric alpha-synuclein during early stages of the aggregation process. To mimic the aggregation processes, cells expressing a synuclein-biotin ligase fusion protein were treated human recombinant pre-formed fibrils and subjected to BioSITe and mass spectrometry. Using a novel split biotin ligase fused to alpha-synuclein facilitated the identification of proteins specifically associated with multimeric alpha-synuclein. A total of 581 proteins were differentiated into potential interactors of monomeric versus multimeric alpha-synuclein in physiological versus aggregated conditions. The data reveal important phosphorylation mechanisms, connections to insulin processing, and a potential interaction with ALS-associated FUS. Interestingly, we identified that loss of specific interactions may contribute to pathology in patients with sporadic onset of Lewy body diseases. Future studies will validate both true interaction of highlighted proteins with alpha-synuclein, and the impact of such proteins on alpha-synuclein aggregation.