Citations

ABSTRACT Objective Identifying and addressing pediatric hearing loss is critical to supporting a child's development. School‐based hearing screening is a mainstay of timely identification of hearing loss. The objectives of this study were to characterize the current hearing screening practices in public, charter, and private elementary schools in Minnesota. Methods This was a cross‐sectional survey with data collected between March and June 2023. Surveys assessed the presence of standardized hearing screening processes and compliance with American Academy of Audiology (AAA) or Minnesota Department of Health (MDH) guidelines. Results About 146 public schools, 43 charter schools, and 60 private schools met inclusion criteria and responded to the survey. There was a statistically significant difference in the rate of standardized screening between school types ( χ 2 = 18.06; p < 0.001). Only 10.44% ( n = 26) of schools completed hearing screenings per AAA guidelines, and even fewer, 4.82% ( n = 12), completed hearing screenings according to MDH guidelines. The odds of screening per AAA or MDH guidelines were 3.50 times higher in charter schools compared to public schools (95% CI: 1.14, 10.73) and 4.61 times higher in private schools compared to public schools (95% CI: 1.73, 12.26). Conclusion There is a lack of standardization in hearing screening processes in Minnesota elementary schools. Adherence to screening per AAA or MDH recommendations is low in all types of elementary schools. Charter and private schools were more likely than public schools to screen per AAA or MDH guidelines. Overall, our data demonstrate an opportunity for improvement in school‐based hearing screening. Level of Evidence N/A.

Abstract We present chromosome-level, phased diploid genome assemblies of two widely used human fibroblast cell lines: BJ (46,XY) and IMR-90 (46,XX). Using Oxford Nanopore, PacBio HiFi, and Hi-C sequencing data, we generated assemblies spanning 5.9 and 6.0 Gbp with diploid quality values exceeding QV 60. To validate structural integrity, we developed KaryoScope, an alignment-free tool for generating computational karyograms from k-mer feature databases. We identify &gt;50 000 structural variants relative to T2T-CHM13v2.0, the majority of which are heterozygous and cell-line-specific. Combining reference-based and de novo gene annotation, we uncover a previously unreported 1 Mbp homozygous duplication at the 16p11.2 locus in BJ, demonstrating that even karyotypically normal cell lines can harbor clinically relevant submicroscopic rearrangements. We show that mapping publicly available short-read, RNA-seq, and ChIP-seq data to sample-matched diploid assemblies substantially improves read alignment and enables haplotype phasing of 23%–28% of short reads. The BJ and IMR-90 assemblies and associated variant calls are publicly available as a resource for the research community.

Cognitive impairment in sepsis survivors is a growing clinical challenge as the number of sepsis cases rise and acute mortality rates fall. It is estimated that up to 70% of sepsis patients experience cognitive dysfunction and many report persistent dysfunction post‐sepsis. Cognitive impairment is a broad term that refers to sepsis‐associated brain dysfunction or encephalopathy (SABD or SAE, respectively). While many contributors, such as inflammation, blood–brain barrier dysfunction, and extended microglial activation are implicated in SABD/SAE development, much is still unknown regarding the underlying mechanistic causes of persistent cognitive defects in sepsis survivors. Here, we employed cecal ligation and puncture (CLP) to model surgical sepsis in mice, after which mice were subjected to multiple memory function assays for up to 2 months post‐sepsis. Furthermore, single‐cell RNA sequencing and validation studies were performed with murine hippocampi to query alterations in the brain microenvironment. Our study shows that CLP mice exhibited decreased spontaneous alternation at 4 weeks and decreases in both short‐ and long‐term recognition (at 6 weeks and 2 weeks, respectively) accompanied by substantially altered cell type makeup of the hippocampus, including hippocampal neuron and pericyte loss. Finally, transcriptional alterations in the macrophage populations implicate aberrant activation in CLP survivors. In conclusion, post‐sepsis mice exhibit reduced memory capacity and altered hippocampal cell composition and transcriptional profiles. This study and associated data set will be valuable for further investigation of the underlying pathophysiology of SABD/SAE and elucidation of potential therapeutic candidates.

Morel-Lavallee lesions (MLLs) are traumatic closed degloving injuries with operative intervention (OI), especially excisional debridement, remaining the mainstay of treatment. However, high-quality evidence describing operative techniques and outcomes remains limited. This study aimed to characterize current OI practices and associated outcomes, especially among patients undergoing excisional debridement, hypothesizing an increased risk of wound complications with this approach for MLLs. Methods This prospective (2021-2024), multicenter, observational study was conducted across 15 trauma centers and included patients diagnosed with MLL who underwent OI. The association between operative technique (eg, excisional debridement) and the primary outcome of wound complications was evaluated. Wound complications were defined as cellulitis, deep wound infection, skin necrosis, necrotizing soft tissue infection (NSTI), and/or organized hematoma. Results Of 88 MLL patients undergoing OI, 36 (40.9%) had excisional debridement, with 4 (11.1%) limited excision to skin, 20 (55.6%) extended to subcutaneous tissue, and 12 (33.3%) down to muscle. Excisional debridement had higher rates of skin necrosis (22.2% vs. 1.9%, P = .002). Although overall rates of wound complications were statistically similar between cohorts (33.3% vs. 17.3%, P = .098), univariate analysis demonstrated excisional debridement had increased risk of wound complications (OR 2.52, CI 1.07-5.97, P = .035). Conclusion This prospective multicenter study over three years demonstrated that a fifth of MLLs undergoing excisional debridement developed postoperative skin necrosis. Excisional debridement also had a more than two-fold increased risk of wound complications compared to other OIs. These findings underscore the importance of investigating alternative operative techniques, such as incision and drainage or minimally invasive debridement methods.

Abstract Early pregnancy loss can have a profound impact on the lives of women and their families, but the experience is often underacknowledged, with the diverse and complex needs of these women not always being met. Health care providers are in a unique position to provide support, helping each woman navigate through what is often a significant event in her lifetime. In response to these gaps, a large academic medical center in the upper Midwest established the Early Pregnancy Care (EPC) Clinic in 2019 as a subclinic of the Department of Obstetrics and Gynecology. The goal of the EPC Clinic is to standardize the management of early pregnancy loss and related concerns to ensure each woman receives timely, holistic, and patient‐centered care that fully encompasses the physical and emotional needs of the patient and her family. The EPC Clinic is run by a small, dedicated team of certified nurse‐midwives and registered nurses in collaboration with a multidisciplinary team, providing comprehensive care to women with a confirmed early pregnancy loss, first trimester bleeding, pregnancy of unknown location, inconclusive viability, or a history of a prior early pregnancy loss, including ectopic and molar pregnancies. Team members coordinate timely visits and evaluation, offer comprehensive management options, and provide bereavement care and resources. Follow‐up care is arranged to monitor each woman's physical and emotional recovery following a loss, including check‐ins with consistent members of the team to maintain continuity of care. Anecdotal evidence as well as Press‐Ganey surveys obtained from patients and their families have demonstrated the exceptional value of the EPC Clinic. In this article, we outline our EPC Clinic's components and processes and discuss strategies that may benefit other health care systems aspiring to develop similar programs to improve early pregnancy loss care and the patient experience.

Diagnosing rare genetic diseases remains a major challenge despite widespread clinical testing. Long-read RNA sequencing (RNA-seq) offers a powerful approach to capturing the effects of genetic variants on the transcriptome, yet challenges with sequencing coverage, cost, tissue selection, and scalability have limited its clinical adoption. To address this, we developed STRIPE (Sequencing Targeted RNAs Identifies Pathogenic Events), a targeted long-read RNA-seq–based strategy for rare disease diagnosis and variant interpretation. STRIPE enables deep sequencing of full-length transcripts for any customized disease-specific gene panel such that a wide range of clinically informative readouts, including transcript aberrations and sequence variants, can be detected at haplotype-level resolution. Applying STRIPE to 88 individuals spanning two major rare disease groups, we accurately reidentified known pathogenic variants and revealed their transcript consequences, including many unexpected ones. For 8 of 15 splice site region variants, we observed more complex RNA processing defects beyond single exon skipping or cryptic splice site activation. Notably, we find that donor splice site variants frequently activate cryptic intronic polyadenylation sites, leading to premature transcript termination. Leveraging unique strengths of long-read RNA-seq, STRIPE also resolved variants of uncertain significance and uncovered disease-causing variants in five previously undiagnosed individuals. Overall, STRIPE is a powerful, adaptable, and scalable strategy with broad potential to improve clinical variant interpretation and advance genetic diagnosis of rare diseases.

BACKGROUND: The metabolic mechanisms underlying right ventricular (RV) dysfunction are poorly understood, particularly outside of group 1 pulmonary hypertension (PH). We aimed to identify metabolites and pathways associated with RV systolic function and explored whether associations differed by pulmonary vascular resistance, PH group 1 status, and sex. METHODS: We analyzed data from the multicenter PVDOMICS (Pulmonary Vascular Disease Phenomics) cohort. RV systolic function metrics included fractional area change (echo), global longitudinal strain (echo), and ejection fraction (cardiac magnetic resonance). We used linear regression adjusted for age, sex, body mass index, and PH group to assess associations between metabolites and RV function. Pathway enrichment analyses were used to identify pathways significantly associated with RV function. Interaction terms were assessed to determine whether metabolite associations were modified by pulmonary vascular resistance, group 1 PH status, or sex. Least absolute shrinkage and selection operator regression was used to develop metabolite-based scores for RV function, and prognostic performance was assessed. RESULTS: There were 979 participants with plasma metabolomics and RV function data. Linear regression identified 170 metabolites that were significantly associated with all 3 RV metrics. Androgenic steroid, gamma-glutamyl amino acid, polyamine, vitamin A, fatty acid, and sterol pathways are most strongly associated with RV systolic function. Two metabolites interacted with group 1 PH status, and 6 interacted with pulmonary vascular resistance. Four androgenic steroids are associated more strongly with RV systolic function in women compared with men. Metabolite-based scores were prognostically equivalent to RV systolic function metrics and less accurate than REVEAL Lite 2 scores. CONCLUSIONS: We provide a blueprint of metabolites and metabolic pathways associated with RV systolic function across the spectrum of PH. Novel links to vitamin A and glutathione metabolites were observed. We detected few metabolites that associated with RV systolic function differentially by group 1 PH status or degree of pulmonary vascular resistance elevation. Androgenic steroids may associate more strongly with RV systolic function in women compared with men.

Importance Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. Objective To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. Design, Setting, and Population Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. Exposure Device-enabled TTVR. Main Outcomes and Measures Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. Results Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P &amp;lt; .001) and mean KCCQ-OS score (22.4 points; P &amp;lt; .001) from baseline to 30 days. There were no significant differences in 30-day mortality ( P = .47), heart failure hospitalization ( P &amp;gt; .99), and functional outcomes ( P = .55) when patients were stratified by baseline CIED status. Conclusions and Relevance Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.

Effective translation relies on high performance teams integrating diverse disciplines to bring new drugs, medical devices, diagnostics or behavioral interventions into improved health. Despite substantial advancements informed by the Science of Team Science (SciTS), challenges remain in effective translational team (TT) operations, while limited institutional, scholarly, and practitioner legitimacy of team science expertise constrains efforts to address them. Here, we describe an essential member of the TT, the Team Science Professional (TSP). Serving as a team educator and facilitator of team interventions, the TSP plays a pivotal role in facilitating effective team performance. Current challenges faced by this nascent profession are defining career pathways and establishing competencies needed for expert performance. To address these challenges, the authors, representing a spectrum of academic universities organized as a special interest group (SIG) of the Association of Clinical and Translational Science (ACTS), propose a suite of individualized, standardized and pathway-selective micro-credentials (digital badges). Digital badges in “Team Science (TS) Fundamentals,” “TS Practitioner,” “TT Trainer” and “TT Intervention Expert” are described, along with preliminary feasibility and usability evaluations of the submission process. These stackable credentials provide a customizable, portable recognition of skills and help advance career pathways for TSPs. In so doing, the Digital Badge Initiative will enhance the capacity of translational science “Hubs” such as those supported by Clinical and Translational Science Awards to conduct effective and rigorous translation. Moving forward, the ACTS TSP SIG will be examining the impact of digital badging on standardization and its effect on career recognition and retention.

Objective We investigated potential racial disparities in the effects of audiometric hearing loss and its treatment on dementia and mortality among 3,602 older adults aged 68–89 years, 22% of whom were self-identified Black race. Methods Adjudicated all-cause dementia was determined using neurocognitive test data, proxy reports, and surveillance of hospital records and death certificates. Audiometric hearing loss, defined as the better-ear averaged pure-tone threshold (0.5–4 kHz), was categorized using clinical cutpoints. Multivariable-adjusted Cox proportional hazards models included hearing loss–race interaction terms. Results Dementia risk associated with moderate-to-severe hearing loss did not differ by race [Black participants: hazard ratio (HR): 1.66; 95% confidence interval (CI): 1.05, 2.61; White participants: HR: 1.71; 95% CI: 1.16, 2.51; P -interaction = 0.92]. However, moderate-to-severe hearing loss was associated with a 2.3-fold increase in mortality among Black participants only (95% CI: 1.17, 4.60). Conclusions Our findings emphasize the importance of including minoritized populations in hearing treatment research to build an evidence base for policy development and clinical decision-making. Hearing loss affects the health of both Black and White Americans. Racial disparities in hearing healthcare should be addressed to advance health equity for all older adults.