Publications by Year: 2026

The host genetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have previously been studied based on cases from the earlier waves of the pandemic in 2020 and 2021, identifying 51 genomic loci associated with infection and/or severity. SARS-CoV-2 has shown rapid sequence evolution, increasing transmissibility, particularly for Omicron variants, which raises the question of whether this affected the host genetic factors. We performed a genome-wide association study of SARS-CoV-2 infection with Omicron variants, including more than 150,000 cases from four cohorts. We identified 13 genome-wide significant loci, of which only five were previously described as associated with SARS-CoV-2 infection. The strongest signal was a single nucleotide polymorphism in an intron of ST6GAL1, a gene affecting immune development and function, connected to three other associated loci (harboring MUC1, MUC5AC and MUC16) through O-glycan biosynthesis. Our study provides robust evidence for individual genetic variation related to glycosylation, translating into susceptibility to SARS-CoV-2 infections with Omicron variants.

Extracellular nanocarriers, such as extracellular vesicles (EVs), lipoproteins, supermeres, and exomeres are diverse lipid-protein-nucleic acid assemblies. Among them, supermeres hold significant diagnostic potential but are challenging to characterize due to limited surface biomarker information and labor-intensive isolation methods. This study introduces an isolation-free Ion Exchange Membrane Sensing method for the detection of supermeres within 30 min using 50 µL of sample, with a sensitivity of 10⁶-10⁷ supermeres/mL. Validation through ultracentrifugation (UC) and surface plasmon resonance (SPR) confirms the detection accuracy and specificity. Supermeres carry key proteins such as HSPA13, ENO2, and DDR1 analogous to tetraspanin in EV. Supermeres outperform small EVs (sEVs) and exomeres across multiple shared and unique surface proteins critical to colorectal cancer diagnosis, highlighting their superior clinical utility and potential as next-generation biomarkers in precision medicine.

BACKGROUND: Nursing professional governance (NPG) promotes shared decision-making and is a Magnet® expectation, yet inconsistent tools and fragmented education can decrease council effectiveness.

PURPOSE: The purpose of this project was to standardize tools and education to improve role clarity, engagement, and council health across a large academic medical center.

METHODS: This quality improvement project used iterative Plan-Do-Study-Act cycles from June 2023-July 2024. Interventions included redesigned council charters and agendas, slides created for enhanced communication, a centralized SharePoint site, a formal NPG orientation, an electronic feedback form, and a governance-specific email inbox. Council health was measured using the Hess Council Health Survey (CHS) at baseline and two post-intervention time points.

RESULTS: Baseline CHS results identified gaps in education, role expectations, time-dedication strategies, and pathways for non-member input. Postintervention improvements were observed in: agreement that new members received formal education (40.9% to 57.3%), availability of strategies to dedicate time (50% to 76.1%), clarity of expectations (63.6% to 83.3%), and opportunities for non-member input (46.3% to 61.1%). Although some gains declined at later follow-up, most remained above baseline.

CONCLUSIONS: Standardizing governance tools and providing structured education improved engagement and role clarity; ongoing reinforcement is needed to sustain gains.

In this issue of Neuron, Sun, Peng, et al.1 identify two separate mechanisms that together provide a brain-wide noradrenergic control of cerebral blood flow in larval zebrafish.

BACKGROUND: Hypertension affects nearly half of U.S. adults. The 2025 American College of Cardiology/American Heart Association guideline adopts the Predicting Risk of Cardiovascular Disease Events (PREVENT) risk equations and updates treatment recommendations for stage 1 hypertension, potentially altering eligibility for antihypertensive therapy.

OBJECTIVES: The primary objective was to quantify changes in antihypertensive treatment eligibility under the 2025 vs 2017 guidelines. Secondary objectives were to characterize adults newly meeting treatment thresholds, assess concordance and discordance in eligibility, and evaluate robustness across PREVENT model variants.

METHODS: We conducted a simulation-based analysis using nationally representative National Health and Nutrition Examination Survey data (2017-2020) among adults aged 30 to 79 years. Treatment eligibility was assigned using 2017 and 2025 guideline criteria. Survey-weighted estimates quantified population-level eligibility, newly eligible adults, and concordance patterns. Analyses were repeated using PREVENT Base, Full, hemoglobin A1c, and albumin-to-creatinine ratio variants, and multivariable models identified predictors of eligibility.

RESULTS: Among 5,578 adults (weighted population 160 million), 36.4% were eligible for treatment under the 2017 guideline and 36.6% under the 2025 guideline, representing a minimal net increase of 0.7% (approximately 400,000 adults). Most adults were consistently ineligible (63.3%), whereas one-third were consistently eligible (36.3%). Newly eligible adults were predominantly older women with higher body mass index and borderline glycemic measures but without established cardiovascular disease. Eligibility patterns were stable across racial and ethnic groups. Analyses were repeated across all PREVENT risk equation variants, and multivariable models identified predictors of eligibility.

CONCLUSIONS: Adoption of the 2025 American College of Cardiology/American Heart Association guideline results in a minimal expansion of antihypertensive treatment eligibility. Results were robust across PREVENT model variants, supporting risk-based guideline implementation.

BACKGROUND: Patients with pulmonary hypertension (PHTN) (i.e., chronic PHTN) have right ventricular hypertrophy, elevated right-sided heart pressures, and frequently have pericardial effusions. When evaluating these patients for cardiac tamponade, the hypertrophy and elevated pressure in right heart may be protective from tamponade by counteracting the pressure from the pericardial effusion. However, these patients may be harmed if echocardiographic signs of tamponade (e.g., right ventricular diastolic collapse) are obscured.

STUDY OBJECTIVE: The effect of PHTN on patients with cardiac tamponade remains unclear. We aimed (1) to evaluate whether PHTN influences the echocardiographic findings of tamponade, and (2) to examine whether PHTN is associated with in-hospital mortality among patients undergoing pericardial drainage primarily for cardiac tamponade.

METHODS: We conducted a retrospective observational study of adult patients who underwent pericardial drainage within 48 h of emergency department presentation at two academic centers. PHTN probability was classified using the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. We classified patients in four categories: no PHTN, low probability, intermediate probability, and high probability of PHTN. PHTN parameters were manually extracted from cardiologist-interpreted echocardiography reports. The primary outcome was in-hospital mortality. Secondary outcomes included the prevalence of echocardiographic findings of cardiac tamponade and their associations with mortality.

RESULTS: A total of 249 patients met the inclusion criteria. In-hospital mortality did not significantly differ across PHTN probability categories: no PHTN (63.8%), low probability (9.3%), intermediate probability (20.9%), and high probability (5.3%) (p-values all >0.2). Among patients who died, 50.0% were in the no PHTN group compared to 7.1% in the high probability group (p = 0.222). The echocardiographic impression of cardiac tamponade was significantly lower among patients with high PHTN probability compared to those with no PHTN (64.3% vs. 85.4%, p = 0.041), with a weak negative correlation (r = -0.493) between increasing PHTN probability and tamponade impression.

CONCLUSIONS: In this cohort of patients undergoing pericardial drainage primarily for cardiac tamponade, PHTN was not significantly associated with in-hospital mortality. However, patients with a high probability of PHTN showed fewer echocardiographic signs of tamponade, suggesting that PHTN may obscure typical sonographic findings of tamponade.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) constitutes the second most common cause of chronic kidney disease (CKD) in children. A monogenic cause can be identified in approximately 25% of SRNS cases. In contrast, steroid-sensitive or steroid-dependent nephrotic syndrome (SSNS/SDNS) is typically attributed to multifactorial or immunological causes and rarely linked to monogenic etiology.

METHODS: We performed exome sequencing (ES) in 237 families, including 183 with SRNS and 54 with SSNS/SDNS.

RESULTS: A (likely) pathogenic variant in a known SRNS gene was identified in 29/183 individuals with SRNS (15.8%). Additionally, 6/183 (3.3%) individuals with SRNS carried pathogenic variants in phenocopy genes-genes associated with diseases that clinically mimic SRNS. The diagnostic yield was significantly higher in individuals with ≥ 50 Mb homozygosity-by-descent (HBD) (44.7% vs. 8.5%) and in those with SRNS disease onset before 1 year of age (41.9%). In individuals with SSNS/SDNS, we found a likely causative variant in only 1 of 54 probands.

CONCLUSIONS: A genetic cause was established in 19.1% of SRNS patients (15.8% in known SRNS genes and 3.3% in phenocopy genes), but only 1.9% of non-steroid-resistant cases.