Citations

Abstract Motivation: Epilepsy is a diverse group of neurological disorders affecting over 50 million people worldwide. While common epilepsy types are well studied, rare epilepsies—often severe and genetically complex—pose significant challenges in diagnosis, research, and treatment. Accurate and interoperable etiology and disease classifications are critical for improving data sharing, supporting clinical decision-making, and advancing rare disease research. Results: To enhance the accuracy of epilepsy-related disease concept representation within the Mondo Disease Ontology (Mondo), we conducted a series of expert-driven workshops in collaboration with the team from the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP). Specialists in epileptology, genetics, neurodevelopment, biomedical ontology, and patient community advocates systematically reviewed and revised the epilepsy hierarchy in Mondo, aligning it with the International League Against Epilepsy (ILAE) classification system. These updates include reclassification of epilepsy subtypes, including syndromes, age-related epilepsies, and developmental epileptic encephalopathies, resulting in a more granular, standardized, and clinically relevant structure. Mondo now offers an enhanced framework for integrating epilepsy data across resources, enabling improved interoperability and facilitating rare disease research and data curation, with continued efforts underway to further refine and expand this integration.

Abstract Patent foramen ovale (PFO) has a prevalence of approximately 25%. Its association with pyogenic brain abscess (PBA) is unclear. We reviewed adults with PBA and known PFO status from 1 January 2009 through 31 December 2021 at Mayo Clinic. High PFO prevalence (40.5%) was seen. PBA patients with PFO had distinct abscess characteristics but unchanged 1-year, all-cause mortality.

Sharing research code in an open access version-controlled repository offers significant benefits for both science as a whole and for individual researchers. In this article, we focus on this practice, which is fully aligned with the NIH’s Gold Standard Science (GSS) program as well as FAIR (findable, accessible, interoperable, reusable) and TRUST (transparency, responsibility, user focus, sustainability, technology) principles. Gold Standard Science supports open science by emphasizing transparency, reproducibility, and the use of best practices that enable others to verify and extend research. Pairing a research article’s cited data snapshot with a versioned, environment-specific code release, deposited in a companion code repository, ensures that, upon submission to a medical journal, readers and reviewers can directly verify results. An executable and updatable companion code repository complements, rather than replaces, established research data repositories. When code underlying medical research results is made openly available, then other scientists can inspect, run, and validate analyses. These activities enhance reproducibility, which is a core aim of GSS. Shared code also facilitates collaborative innovation by allowing researchers to extend the utility of the code to new datasets and applications. For researchers, code sharing can increase visibility, credibility, and citation impact. Demonstrating transparency through shared executable and updatable code builds trust with journal readers, peer reviewers, funders, and peers. Shared code in an open access repository signals adherence to high standards of scientific integrity and attracts opportunities for collaboration. A researcher who shares code receives recognition as a leader in reproducible, trustworthy research consistent with NIH’s GSS principles.

Background/Objectives: Dizziness is a symptom of many disorders across a wide range of etiologies. If dizzy patients are seen for vestibular evaluation with an audiologist and no vestibular reason for the patient’s dizziness is found, the medical referral pathway can become convoluted. This can leave patients feeling discouraged and unable to manage their symptoms. Clinically symptomatic chronic respiratory alkalosis (CSCRA) is an acid–base disorder that typically presents with dizziness but is unfamiliar to practitioners in vestibular and balance care settings. Methods: In a retrospective chart review deemed exempt by the Mayo Clinic Institutional Review Board, 74 patients at Mayo Clinic Arizona were included. All had consultations with both Audiology and Aerospace Medicine to assess their dizzy symptoms. Results: After completing vestibular testing, arterial blood gas (ABG) testing, and a functional test developed at Mayo Clinic Arizona called the Capnic Challenge test, 40% of patients were found to have CSCRA contributing to their dizzy symptoms. Many of these patients also had common comorbidities of CSCRA, like postural orthostatic tachycardia syndrome (POTS), migraines, and sleep apnea. Fewer than one-fourth of these patients had measurable vestibulopathies causing their dizziness. Half of the patients referred by the vestibular audiologist to Aerospace Medicine had a diagnosis of CSCRA. Conclusions: Assessment for CSCRA should be considered as a next step for patients presenting with dizziness without a vestibular component. Being aware of the prevalence of CSCRA and its comorbidities may help balance providers offer quality interprofessional referrals and improve patient quality of life.

Background: ALG13-CDG is an X-linked N-linked glycosylation disorder caused by pathogenic variants in the glycosyltransferase ALG13, leading to severe neurological manifestations. Despite the clear CNS involvement, the impact of ALG13 dysfunction on human brain glycosylation and neurodevelopment remains unknown. We hypothesize that ALG13-CDG causes brain-specific hypoglycosylation that disrupts neurodevelopmental pathways and contributes directly to cortical network dysfunction. Methods: We generated iPSC-derived human cortical organoids (hCOs) from individuals with ALG13-CDG to define the impact of hypoglycosylation on cortical development and function. Electrophysiological activity was assessed using MEA recordings and integrated with multiomic profiling, including scRNA-seq, proteomics, glycoproteomics, N-glycan imaging, lipidomics, and metabolomics. X-inactivation status was evaluated in both iPSCs and hCOs. Results: ALG13-CDG hCOs showed reduced glycosylation of proteins involved in ECM organization, neuronal migration, lipid metabolism, calcium homeostasis, and neuronal excitability. These pathway disruptions were supported by proteomic and scRNA-seq data and included altered intercellular communication. Trajectory analyses revealed mistimed neuronal maturation with early inhibitory and delayed excitatory development, indicating an E/I imbalance. MEA recordings demonstrated early network hypoactivity with reduced firing rates, immature burst structure, and shortened axonal projections, while transcriptomic and proteomic signatures suggested emerging hyperexcitability. Altered lipid and GlcNAc metabolism, along with skewed X-inactivation, were also observed. Conclusions: Our study reveals that ALG13-CDG is a disorder of brain-specific hypoglycosylation that disrupts key neurodevelopmental pathways and destabilizes cortical network function. Through integrated multiomic and functional analyses, we identify early network hypoactivity, mistimed neuronal maturation, and evolving E/I imbalance that progresses to compensatory hyperexcitability, providing a mechanistic basis for seizure vulnerability. These findings redefine ALG13-CDG as disorders of cortical network instability, offering a new framework for targeted therapeutic intervention.

Death or dysfunction of retinal pigment epithelium (RPE) cells occurs in age-related macular degeneration (AMD) and certain inherited retinal dystrophies (IRDs). Induced-pluripotent stem cell (iPSC) derived-RPE have been used in early-stage clinical trials to treat AMD and IRDs by injecting them as a cell suspension or monolayers. While RPE transplant shows therapeutic potential, issues ranging from failure to repopulate the entire treatment area, clumping and monolayer folding, and a foreign body response to the support have been reported. We’ve shown that RPE can be grown on high concentration (>30 mg/mL) degradable fibrin hydrogels, and that cell free fibrin hydrogels implanted in the subretinal space degrade without causing inflammation. Here we describe manufacture and surgical implantation of degradable fibrin hydrogels carrying iPSC-RPE into a porcine model of geographic atrophy (GA). Large (15.25 × 58.42 × 0.2 mm) fibrin gel blanks were produced by injection molding, and iPSC-RPE were grown on their surface. Using a mechanical punch, the blank was subdivided into 1.5 × 5.0 × 0.2 mm doses, which fit a custom tool used for storage and surgical placement. Following aseptic packaging, RPE and gels were stable at 37 °C for at least 7 weeks. When transplanted into a pig model of GA, the fibrin scaffold degraded in <1 month and the iPSC-RPE provided partial rescue from GA as assessed by preservation of photoreceptors and blood flow in the choriocapillaris. We conclude that iPSC-RPE delivered on degradable fibrin hydrogels represent a potentially safe and effective approach to RPE transplantation.

ABSTRACT Background Individuals with oral cavity cancer (OCC) have negatively impacted functional status and quality of life. Little is known regarding patients' perspectives of their speech impairments. This study compared self‐reported speech function between patients surgically treated for OCC and healthy controls using the Speech Handicap Index (SHI) and identified factors associated with worse scores. Methods This is a multiinstitutional cross‐sectional study of OCC patients and healthy controls recruited between July 2024 and March 2025. Participants completed the SHI and self‐reported speech quality. Demographics, tumor, and treatment details were abstracted from the electronic health record for OCC. Group differences were assessed with t ‐tests, χ 2 , and Fisher's exact tests. Results Among 69 OCC and 90 controls, OCC patients had significantly higher mean SHI scores (50.2 vs. 34.7, p < 0.01) and were less likely to rate their speech as “good” or “excellent” (47.8% vs. 85.6%, p < 0.01). Both speech and psychosocial domain scores were significantly worse among OCC. Free flap reconstruction was associated with worse scores (29.6 vs. 15.5, p = 0.02) and worse self‐rated speech quality. Conclusions Patients with surgically treated oral cavity cancer have significantly impaired self‐perceived speech and psychosocial functioning compared with healthy individuals. Greater deficits were observed in patients who required free flap reconstruction. Despite the functional deficit, nearly half of OCC patients reported satisfaction with their speech quality. These findings highlight the importance of using validated measures for speech function and support the need for early, multidisciplinary rehabilitation including speech therapy in this population, particularly for those undergoing free flap reconstruction.

ABSTRACT The RenOx platform integrates lung and kidney support within a single extracorporeal device designed to reflect the clinical realities of multiorgan failure. Early preclinical work demonstrates the feasibility of combined gas exchange and renal support, suggesting that a unified lung–kidney device could reduce the burden of multi‐device management, streamline intensive care workflows, and potentially improve outcomes in patients with combined organ failure.

Complement-mediated hemolytic uremic syndrome (CM-HUS), commonly referred to as atypical HUS, is a rare thrombotic microangiopathy caused by uncontrolled activation of the alternative complement pathway, typically triggered by a “two-hit” mechanism. It is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ damage, most commonly affecting the kidneys. While our understanding of the complement system has advanced significantly, CM-HUS remains a complex, heterogeneous disorder influenced by a spectrum of genetic variants, risk haplotypes, and acquired factors such as anti-factor H autoantibodies. This review highlights the current knowledge of CM-HUS pathogenesis, focusing on genetic variants in regulatory and activating proteins of the complement system. We also discuss the diagnostic complexity posed by incomplete penetrance, overlapping phenotypes, and limitations of genetic and functional assays. Emerging ex-vivo assays and complement biomarkers are explored as tools for refining diagnosis and risk stratification. The use of complement inhibitors such as eculizumab and ravulizumab has significantly improved renal outcomes and survival. This review provides a comprehensive, clinically grounded update on the genetics, pathophysiology, diagnostics, and therapeutic considerations in CM-HUS, aiming to provide clinicians and researchers with a deeper understanding of this complex, complement-driven disease.

Background: Pretibial dermopathy (PTD) is a rare, disfiguring manifestation of Graves’ disease. The shared pathophysiology with thyroid eye disease (TED), centered on fibroblast activation via a thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor (IGF-1R) complex, provides a strong rationale for using the IGF-1R inhibitor, teprotumumab. Methods: We present a case series of five patients with severe PTD and concomitant TED who were treated with teprotumumab. A review of reported cases in the literature was also conducted. Results: All patients experienced significant clinical improvement, including regression of skin thickening as well as enhanced functional capacity. Side effects included mild hearing loss, muscle cramps, and fatigue. One patient experienced a severe gastrointestinal event requiring treatment discontinuation, while those experiencing a recurrence of PTD, responded to a second course of therapy. Conclusions: Teprotumumab showed promising efficacy in the treatment of PTD. Further studies are needed to confirm its durability and safety.