Citations

Abstract Myocardial infarction (MI) triggers a systemic neutrophil response, yet the roles of distinct neutrophil subsets in cardiac remodeling remain unclear. Studying this requires murine models that accurately mirror human neutrophil dynamics. Here, we show that a minimally invasive intact-chest MI model is more pathophysiologically relevant than the standard open-chest approach for investigating post-MI immune responses. In the open-chest model, surgical trauma disrupts bone marrow homeostasis, releases large numbers of immature neutrophils, and masks MI-specific immune mechanisms. In contrast, the intact-chest model preserves bone marrow integrity and induces only a modest rise in circulating immature neutrophils, closely reflecting MI patient profiles. We further demonstrate that accumulation of immature neutrophils in the infarcted heart exacerbates cardiac dysfunction. Beyond neutrophils, the overall cardiac immune landscape differs markedly between both models. Collectively, our findings establish the intact-chest model as superior for studying post-MI inflammation and reveal immature neutrophils as mediators of adverse cardiac remodeling.

Abstract Purpose To develop and implement an in‑house treatment‑management platform to improve communication, data accessibility, and task tracking across a radiation oncology department. Methods We developed Capsule, a custom software platform that centralizes patient data from the ARIA oncology information system (Varian Medical Systems, Palo Alto, United States), and integrates it with data from Outlook (Microsoft, Redmond, United States), spreadsheets, and manual inputs. Built using C#, SQL, and the .NET framework, it features a graphical interface in XAML with twelve modular tools to support workflows across a large multi‐modality department. A formal validation, feedback, and maintenance cycle was established. Its impact on workflow efficiency was evaluated using average CarePath task duration before and after implementation, supplemented by user interviews and surveys. Results The Department Schedule, Treatment Planning and On‐Treatment Whiteboard, Spreadsheet, and various workload tracking modules emerged as the most frequently used among dosimetrists surveyed.The Whiteboard module consolidates planning metadata for streamlined workflows. Workload and scheduling modules help distribute tasks fairly. The Department Schedule module centralizes daily role and contact information. The Spreadsheet module allows dosimetrists to identify a reference for unique plans and provides secure access to large exportable tabulated patient data and clinical trends. Other modules support proton down‐time replanning and special procedure physics assignment. One year after Capsule's implementation, most tasks in the external beam radiation therapy workflow experienced a reduction in average duration. Discussion Capsule streamlines workflows by integrating multiple tools into a single platform, supporting urgent scenarios, and improving task hand‐off. Its modular design allows customization to local workflows, but implementation must be guided by institutional oversight and formal quality management to ensure data security and compliance. Conclusion Capsule can provide a solution for improved workflow efficiency, communication, and interdisciplinary coordination. By democratizing access to routine and retrospective data, it supports treatment planning, scheduling, and quality improvement. Ongoing updates are essential as clinical practices evolve.

ABSTRACT Polyprenal reductase is an enzyme encoded by the SRD5A3 gene, which is involved in the synthesis of dolichol from polyprenol. Dolichol serves as a carrier for glycan precursors or monosaccharides in N‐linked glycosylation. Pathogenic variants in SRD5A3 can result in a congenital disorder of glycosylation (CDG), SRD5A3‐CDG, which is inherited in an autosomal recessive manner. Most plasma proteins are glycosylated and changes in the glycosylation of several glycoproteins are associated with pathological consequences. Despite the critical role of SRD5A3 in glycosylation, the impact of its deficiency on the glycosylation of serum proteins remains largely unexplored. In this study, we used tandem mass tag‐based multiplexed quantitative approach to analyze serum N‐glycoproteomics and proteomics in SRD5A3‐CDG patients and controls. We quantified 2200 serum N‐glycopeptides from 359 N‐glycosites from 204 serum proteins. Extensive hypoglycosylation of serum proteins was observed in patients, with 245 of 291 altered glycopeptides decreased in SRD5A3‐CDG. Altered glycopeptides included those derived from haptoglobin, plasma serine protease inhibitor, alpha‐1‐B glycoprotein, alpha‐2‐macroglobulin, and ceruloplasmin. Some of these proteins have previously been reported to be associated with liver dysfunction, anemia, and coagulopathy, which could underlie similar clinical features observed in SRD5A3‐CDG patients. Overall, our study provides novel insights into alterations in the glycosylation status of specific serum proteins in SRD5A3‐CDG. Some of these alterations could be further pursued to develop glycopeptide‐based biomarkers as the current diagnosis of SRD5A3‐CDG by screening assays remains challenging. In addition, knowledge of altered glycoproteins could enhance our understanding of the disease spectrum and potentially unveil additional therapeutic avenues.

ABSTRACT Imaging mass spectrometry has made significant advancements in recent years owing to its ability to study the spatial localization and abundance of proteins, peptides, lipids, glycans, metabolites, and drugs. In this study, we employed an imaging mass spectrometry‐based workflow called MALDI‐IHC, which uses antibodies conjugated with photocleavable mass‐tags, to investigate the detection of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) along with pan‐cytokeratin in formalin‐fixed paraffin‐embedded (FFPE) sections from cases with breast cancer. The expression of ER, PR, and HER2 was consistent with the clinical diagnosis based on conventional immunohistochemistry, lacking signal in triple‐negative cases and concordant signals in the cases that were classified as ER+/PR+/HER2+, ER+/PR+/HER2−, and ER−/PR−/HER2+ groups, respectively. In addition, the potential utility of a seconday antibody‐based MALDI‐IHC approach for HER2 expression was evaluated. In agreement with immunohistochemistry results, HER2 expression co‐localized within tumor regions in a HER2+ breast cancer case, while no expression was observed in a HER2− case. Collectively, these results highlight the potential of imaging mass spectrometry‐based MALDI‐IHC workflow for multiplexed detection of proteins in clinically relevant tissue sections.

ABSTRACT Objective The Minnesota Electronic Health Record Consortium (MNEHRC) was established during the early days of the COVID‐19 pandemic to provide data for public health surveillance from the eleven largest health care systems in Minnesota. Methods This is a descriptive study of the Consortium, which is a federated network that implements best practices for governance and data infrastructure to support public health surveillance and clinical research. We conducted an analysis of the Consortium members, governance structure, infrastructure, and the characteristics of the patient population. Results The Consortium health systems collect information from 105 hospitals, 773 clinics, 100 emergency departments and 29 040 providers. Information about the health systems and the demographic and clinical characteristics of its 5 471 367 patients is provided, which represents more than 90% of the patients in Minnesota. This manuscript also details the MNEHRC governance structure, working groups, data use agreements and technical infrastructure. The Consortium has produced several studies with state‐wide impact. One study, Health Trends Across Communities in Minnesota, is described in detail to illustrate aspects of this collaboration. Conclusion MNEHRC has been a successful collaboration and vital resource for public health surveillance in the state of Minnesota. Initially, the Consortium focused on surveillance related to COVID‐19 infections and vaccinations but has recently expanded into other public health and chronic disease research.

Abstract Objective To examine the impact of immunosuppressive regimens on chronic rhinosinusitis (CRS) development in kidney and liver transplant recipients. Study Design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022, were included. Patients with documented sinonasal complaints before transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic data, relevant comorbidities, CRS diagnoses, and immunosuppressive regimens were collected. Results In total, 1459 transplant recipients (986 kidney, 473 liver) with a mean age of 55.1 years and M:F ratio of 1.5:1 were included. Kidney recipients who received anti‐thymocyte globulin (ATG, Thymoglobulin®) for immunosuppressive induction had a greater risk of CRS compared to those who did not (odds ratio [OR] = 3.0, 95% CI [1.3, 6.9], P = .005). Among liver recipients, patients on cyclosporine, mycophenolate mofetil (MMF), and corticosteroids had a greater risk of CRS compared to those on tacrolimus‐based regimens (OR = 6.0, 95% CI [1.5, 24.1], P = .027). Cyclosporine use was also associated with an increased rate of endoscopic sinus surgery (ESS) compared to tacrolimus (4.2% vs 0.3%, P = .015). Conclusion Tacrolimus‐based regimens are associated with significantly decreased rates of CRS compared to cyclosporine, suggesting that immunosuppressive choice is a modifiable risk factor for sinonasal morbidity in this population.

ABSTRACT Introduction/Aims There are no established biomarkers of upper motor neuron degeneration to aid in the diagnosis of motor neuron disease (MND). This study examines the diagnostic value of the motor band sign as a marker of upper motor neuron degeneration and its relationship to clinical findings in MND. Methods Records of consecutive patients who underwent 7T magnetic resonance imaging (MRI) between October 2021 and April 2025 for evaluation of MND or other neurologic indications were retrospectively reviewed. Clinical variables and plasma neurofilament light chain (pNfL) levels were recorded. An upper motor neuron score (Mayo UMNS) was derived from reflex scores. Blinded MRI review assessed the degree of susceptibility‐weighted imaging (SWI) hypointensity in the hand, foot, and bulbar motor cortex regions. Results An MBS was observed in 100 of 117 (85.5%) MND patients and in 16 (15.5%) patients with non‐MND diagnoses, corresponding to a sensitivity of 85.5% (78.0%–90.7%) and 84.5% (76.2%–90.2%) specificity. The MBS in 78 MND patients (70.9%) preferentially involved the middle and deep cortical layers, giving a trilaminar appearance, while only one non‐MND patient had this finding. Mayo UMNS ( β = 0.89, p < 0.001), pNfL ( β = 0.63, p = 0.033), and age at evaluation ( β = 0.68, p = 0.027) were independently associated with the summed SWI score. Discussion The 7T MRI MBS is a sensitive and specific marker for MND that complements established clinical evaluation. Using 7T, a trilaminar appearance of the motor cortex, reflecting known histopathological changes, can be visualized and may be specific to MND.

ABSTRACT 162 patients with relapsed secondary central nervous system lymphoma (R‐SCNSL) (median age, 65 years; male, 59.9%) including central nervous system (CNS)‐only ( n = 120) and concomitant CNS/systemic relapse ( n = 42) were retrospectively analyzed. Overall, 21.9% of patients were classified as high risk according to the CNS International Prognostic Index (CNS‐IPI). Several biological and clinical features were significantly associated with leptomeningeal involvement, including double‐ or triple‐hit (DHL/THL) status, MYC rearrangement, negative BCL6 expression by IHC, bone marrow involvement, and concomitant R‐SCNSL. Multivariable analysis showed that leptomeningeal involvement independently predicted inferior OS and was associated with a 98% increase in the hazard of death compared with parenchymal relapse (HR = 1.98, 95% CI: 1.20–3.26, p = 0.008). Based on anatomical localization, R‐SCNSL was classified into four subtypes: parenchymal‐only involvement (parenchymal‐CNS [P‐CNS], 68/42%) and parenchymal involvement plus systemic relapse (parenchymal‐concomitant [P‐concomitant], 17/10.5%); and leptomeningeal with or without parenchymal involvement (leptomeningeal‐CNS [LM‐CNS], 52/32.1%) and leptomeningeal with systemic relapse (leptomeningeal‐concomitant [LM‐concomitant], 25/15.4%). This anatomical classification significantly impacted OS and PFS ( p < 0.001). Two‐year OS and PFS were 58.2% and 29.1% for P‐CNS, 32.4% and 17.7% for P‐concomitant, 22% and 13.9% for LM‐CNS, and 7.1% and 0% for LM‐concomitant, respectively. ASCT showed a trend toward improved survival among patients with a response (CR/PR) in a 4‐month landmark analysis. These findings support the clinical application of the anatomical classification in the management of R‐SCNSL.

ABSTRACT Cohort studies are vulnerable to confounding and time‐related biases. Recent advances emphasize the importance of emulating a hypothetical target trial to minimize several of these biases. The target trial framework is a critical tool for designing cohort studies. It requires explicit specification of protocol components: eligibility criteria, treatment strategies, outcomes, timing of follow‐up (time zero), and the causal contrast to be estimated. Critical to this framework is defining “time zero” when treatment assignment takes place and follow‐up begins, which prevents prevalent user and immortal time bias and ensures proper temporal sequencing of confounders, exposure, and outcome. By guiding design, data collection, and analysis, the target trial framework helps align observational studies with the principles of randomized trials, improving the validity and interpretability of their findings. While it cannot eliminate unmeasured confounding, this approach promotes transparent, bias‐conscious cohort design, minimizes time‐related bias, and supports more robust causal inference with observational data.