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Background: Patients with spina bifida are living longer and more productive lives; however, many continue to experience functional limitations in adulthood. This study evaluated long-term functional progression and ambulatory status using the combined Myelomeningocele Functional Classification (MMFC) and Functional Mobility Scale (FMS), and examined factors associated with long-term changes. Methods: A retrospective review at a tertiary care rehabilitation center identified 168 patients with spina bifida. MMFC and FMS classifications were recorded at initial and final visits. A subgroup of ambulatory patients who underwent 3D-gait analysis was analyzed to assess the relationship between MMFC, body mass index (BMI), and functional speed (FS) using multiple linear regression. Results: The average follow-up was 15±10.31 years. The mean age at final follow-up was 20 years (range, 5 to 52), with 52% of patients being male. Fifty-two percent of patients were ≥18 years of age at final follow-up. Within the MMFC1 cohort, 48% used wheelchair mobility (FMS 1,1,1) at initial presentation; this increased to 80% at final follow-up. Eighty percent of the MMFC2 patients were able to complete the 50-yard walk test at initial classification, whereas only 60% were able to complete it at final follow-up. Within the MMFC3 cohort, there was a decline in patients requiring no external support (FMS 6,6,6) from 90% to 78%. All MMFC4 patients maintained an FMS of 6,6,6. A statistically significant relationship was found between functional speed (FS) and MMFC (with MMFC4 faster than MMFC3 and MMFC2) ( P =0.01414). Conclusions: Long-term follow-up demonstrates that functional classification may decline over time in MMFC1 to 3 cohorts, whereas MMFC4 remains stable. In addition, within individual cohorts (MMFC1 to 3), there was also a decline in FMS and functional walk testing. A positive and statistically significant relationship was observed between gait analysis FS and MMFC, and a negative and statistically significant relationship was observed between BMI and MMFC. The combined use of MMFC and FMS provides a structured framework for longitudinal functional assessment in patients with spina bifida. Level of evidence: Level III.

Summary Long-read nanopore sequencing enables simultaneous detection of germline variation and native DNA base modifications on individual DNA molecules, providing a unique opportunity to investigate allele-specific epigenetic regulation. Here, we performed whole-genome nanopore sequencing on normal and tumor prostate tissues to characterize differential methylation, methylation entropy, and allele-specific methylation (ASM) associated with noncoding genetic variants. Genome-wide analysis identified extensive cancer-associated differentially methylated regions (DMRs), with hypermethylated DMRs significantly enriched near transcription start sites and transcriptional regulatory regions. Integration with transcriptomic datasets revealed strong inverse relationships between promoter methylation and gene expression, while 5-hydroxymethylcytosine (5hmC) levels positively correlated with transcriptional activity across gene bodies. Using fragment-level methylation patterns enabled by long-read sequencing, we further quantified methylation entropy incorporating both 5mCG and 5hmCG states. Cancer-hypermethylated DMRs exhibited markedly reduced entropy, consistent with clonal fixation of methylation states during tumor progression. Entropy profiling across chromatin annotations demonstrated maximal epigenetic heterogeneity at partially modified enhancer-associated regions. To investigate cis-regulatory genetic effects, we developed a simple ASM framework (nanoASM) that can partition sequencing reads by allelic state and identifies allele-specific DMRs directly from long-read data. Compared with conventional population-level mQTL analysis, ASM demonstrated substantially improved statistical efficiency by leveraging within-individual contrasts and reducing sample-level heterogeneity. Although germline single nucleotide polymorphisms (SNPs) were largely shared between normal and tumor tissues, ASM patterns differed substantially, with tumor-associated ASM regions displaying significantly larger genomic span and stronger allelic methylation differences. Comparative analysis with TCGA prostate mQTL and GTEx prostate eQTL datasets demonstrated substantial concordance between ASM directionality and downstream transcriptional effects, particularly for variants located within DMRs and near transcription start sites. At the IRX4 prostate cancer risk locus, ASM identified an androgen-responsive regulatory domain overlapping AR ChIP-seq and H3K27ac peaks, nominating rs6885084 as a candidate functional variant. At the PSCA locus, ASM anchored by rs4736369 was associated with allele-specific methylation, chromatin activation, transcript abundance, and isoform usage. Together, these findings establish nanopore-based ASM analysis as a powerful approach for resolving functional noncoding variants and their regulatory domains they control in prostate cancer.

Background Long-acting injectable buprenorphine (LAI-BUP) is safe and effective, however is underutilized. Little is known regarding how buprenorphine prescribers view LAI-BUP, and which medication attributes they prioritize when selecting opioid use disorder (OUD) treatment. Methods Secondary analysis of a national, cross-sectional survey of U.S. physicians prescribing buprenorphine for OUD. Respondents reported OUD caseload, LAI-BUP use, and importance of medication attributes (eg, efficacy, safety, ease of prescribing, administrative requirements). Providers were categorized as no LAI-BUP use or, among LAI-BUP prescribers, Low vs High use by a median split. Group comparisons used chi-square (or Fisher’s exact) tests for categorical variables and Jonckheere–Terpstra tests for ordinal responses. Results Among 125 respondents, 39 (31.2%) reported no LAI-BUP use. The remaining 86 (68.8%) were split evenly into Low and High use groups (n’s = 43). LAI-BUP use did not differ meaningfully by specialty, region, or practice setting. Greater LAI-BUP use was reported by providers with larger OUD panels. Ratings of medication attributes were uniformly high. Conclusions LAI-BUP remains underused, with uptake highest among clinicians managing larger OUD caseloads. Measured attitudes toward medication attributes did not explain these differences. Future work should assess clinic workflow, staffing, reimbursement, and REMS burden, testing targeted implementation strategies using mixed-methods trials.

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type–specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced lysosomal biogenesis contributed to the observed neuroprotection. These findings reveal potentially novel roles for microglial VRAC in regulating seizure outcomes and microglia-neuron interactions.

Background: Pediatric tibial fractures are common long-bone injuries, yet uncertainty remains in the optimal immobilization strategy. The comparative effectiveness and safety of short leg versus long leg casts in achieving stable healing and functional recovery have not been clearly established. Methods: A literature search was conducted across Medline, CINAHL, Embase, and Cochrane Library, from inception to August 2025, following PRISMA guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO). Statistical analyses were performed using a random-effects model. Results: The initial search yielded 1236 studies; 6 studies with 413 pediatric patients met the inclusion criteria. A total of 163 underwent short leg casting (SLC) and 250 long leg casting (LLC). No differences were observed between SLC and LLC for coronal angulation (MD=0.12 degrees, 95% CI=−0.89 to 1.12, I 2 =58%) or sagittal angulation (MD=0.18 degrees, 95% CI=−0.71 to 1.07, I 2 =56%). Subgroup analyses showed no differences for tibial shaft fractures or Salter-Harris distal tibial fractures. Cast duration was similar between groups (MD=−0.74 wk, 95% CI=−1.49 to 0.01, I 2 =92%). Overall complication rates did not differ (OR=0.76, 95% CI=0.25 to 2.34, I 2 =0%), with no differences in Salter-Harris subgroup analysis (OR=0.67, 95% CI=0.05 to 9.91; I 2 =54%). SLC was associated with shorter time to weight-bearing (MD=−2.29, 95% CI=−4.49 to −0.08, I 2 =68%) and faster time to union (MD=−1.21, 95% CI=−2.16 to −0.25, I 2 =30%). Conclusion: SLCs may be considered as an alternative to LLCs in pediatric tibial shaft and distal tibial physeal fractures based on currently available retrospective comparative evidence. However, the evidence is limited by the retrospective design, clinical heterogeneity, and risk of confounding. Further prospective comparative studies are needed to define optimal indications for SLC use in this population. Level of Evidence: Level III, systematic review and meta-analysis of retrospective comparative studies.

Abstract Objective . The use of Feraheme (ferumoxytol) as a contrast agent in MR-guided focused ultrasound (MRgFUS) tumor ablations could enhance treatment safety and efficacy by improving vascular visualization through strong T1 and T2 shortening effects. However, Feraheme impact on MR thermometry and tissue heating is unclear. This study evaluates the feasibility of incorporating Feraheme into MRgFUS by assessing its impact on MR imaging contrast, MR thermometry, and thermal response in tissue-mimicking phantoms. Approach . Tissue-mimicking phantoms with 0 (baseline), 0.25, and 0.5 mM Feraheme concentrations were prepared using a validated recipe. Acoustic attenuation was measured with a commercial diagnostic ultrasound scanner. MR imaging at 1.5 T was performed to assess gradient-recalled-echo (GRE)-based thermometry signal-to-noise-ratio (SNR), relaxation rates, and relaxivities. MRgFUS system integrated with 1.5 T MRI was used to perform multiple sonications in the phantoms. Temperature elevations and focal heating areas were quantified from proton resonance frequency (PRF) shift thermometry. Experiments were repeated three times over the period of eight-weeks. Separately, temperature-dependent nuclear magnetic resonance (NMR) spectroscopy was performed at 3.0 T in saline-diluted Feraheme phantoms (0, 0.25, 0.5, and 1.0 mM) to assess the influence of Feraheme concentration on PRF coefficients used in MR thermometry. Main results . Phantoms showed nuclear relaxation times ( T 1: 1178.1 ± 77.8, T 2: 103.21 ± 2.45 ms) and attenuation coefficients (0.34–0.36 dB cm −1 MHz −1 ) within expected biological tissue ranges. Relaxivities demonstrated a strong linear dependence on Feraheme concentration ( r 1: 17.5 ± 0.2, r 2: 209.2 ± 2.6 s −1 mM −1 ). Relative to baseline (0 mM) phantom, the SNR of GRE-based thermometry increased by 12.6% at 0.25 mM and decreased by 27.1% at 0.5 mM. Sonications in Feraheme-containing phantoms resulted in statistically higher temperature elevations ( p < 0.001 ) although no statistically significant difference was observed between 0.25 and 0.5 mM. All NMR measurements demonstrated stable, linear PRF temperature dependence ( R 2 = 0.996–0.999), with PRF coefficients (between −0.0074 and −0.0082 ppm °C −1 ). The resulting thermometry bias was small and predictable (+0.67 and +1.73 per 20 °C at 3.0 T for 0.25 and 0.5 mM). Significance . These findings demonstrate that MR thermometry remains feasible at moderate Feraheme concentrations and support its potential use to enhance visualization of critical vasculature near targeted tissues during MRgFUS.

Importance Hypopigmented mycosis fungoides (HMF) is uncommon in adults, and data on clinicopathologic features and long-term outcomes remain sparse. Objective To investigate the clinicopathologic features and outcomes of adults with HMF in a large multicenter cohort. Design, Setting, and Participants This retrospective multicenter cohort study conducted from January 2011 to October 2023 at 6 US tertiary referral centers and included adults (18 years or older at diagnosis) with biopsy-confirmed HMF and hypopigmentation documented at diagnosis, with a median (range) follow-up of 39 (1-347) months. Data were analyzed from February to December 2025. Exposures Clinical variant, immunophenotype predominance, and polymerase chain reaction–based T-cell receptor ( TCR ) gene rearrangement in peripheral blood and/or skin. Main Outcomes and Measures Best overall response, defined as complete response, partial response, stable disease, or progressive disease, and progression to a higher stage. Results The cohort included 224 adults with HMF (median [range] age, 44 [18-74] years), of whom 164 (73%) were women (60 men [27%]), 5 (2%) were Asian individuals, 1 (0.4%) was a Hispanic/Latino individual, 1 (0.4%) was a Middle Eastern individual, 19 (8%) were White individuals, and 186 (83%) were Black individuals; 219 (98%) presented with early-stage disease. Most had hypopigmented lesions only (159 [71%]), whereas 65 (29%) exhibited mixed-variant mycosis fungoides; outcomes were similar between groups. Among 141 patients with available immunophenotyping, 88 (63%) had CD8-positive predominance. Among 207 treated patients, most (179 [90%]) received skin-directed therapy alone. Among 198 evaluable patients, the best overall response was complete response for 52 (26%), partial response for 101 (51%), stable disease for 34 (17%), and progressive disease for 11 (6%). Over a median (range) follow-up of 39 (1-347) months, 14 of 224 patients (6%) experienced progression to a higher stage, including 5 of 219 patients (2%) with early-stage disease at baseline who experienced progression to advanced-stage disease. Peripheral blood TCR monoclonality was detected in 23 of 85 tested patients (27%) and was associated with poorer treatment response but not with disease progression. Conclusions and Relevance The finding of this cohort study suggest that adult HMF demonstrated a generally indolent course, with favorable response to skin-directed therapy, irrespective of immunophenotype or mixed-variant presentation. Peripheral blood TCR monoclonality was associated with lower treatment response but not disease progression.

Introduction Guillain-Barré syndrome (GBS) is an autoimmune polyradiculopathy linked to various triggers. Recently, several case reports described GBS development following intracranial hemorrhage (ICH), posing diagnostic and therapeutic challenges. Methods PubMed and EMBASE were searched from inception till February 2023 for case reports. Two reviewers independently screened the articles and extracted data using a standardized form. The extracted data were then analyzed narratively. Quality was assessed with the JBI Checklist for Case Reports. Results Twenty-three cases from 11 countries were identified (14 males, mean age of 60.1 years). Onset of GBS occurred after a median of 9 days (range 2–24) post-ICH, with intracerebral hemorrhage being the most common antecedent (39.1%), followed by subarachnoid (26.1%) and subdural hemorrhage (21.7%). Electrophysiology showed predominantly axonal variants, while CSF consistently demonstrated albuminocytologic dissociation with positive antiganglioside antibodies in five cases. The clinical course was severe, marked by rapid progression to nadir (median 2.5 days), profound functional impairment (average Hughes Functional Grading Scale: 4.57 ± 0.66), and a high rate of respiratory failure requiring mechanical ventilation (78.3%). Axonal variants were associated with higher rates of mechanical ventilation and poorer outcomes than demyelinating forms. Among the 21 patients who received immunomodulatory treatment, 3 (14.3%) showed complete recovery, 13 (61.9%) had partial recovery, 3 (14.3%) had a poor recovery, and 2(9.5%) died at last follow up. Conclusion GBS may complicate recovery after ICH and appears to present with an aggressive course, particularly in axonal variants. Clinicians should consider GBS when patients with ICH develop progressive, symmetrical weakness unexplained by the initial brain injury, as prompt initiation of immunotherapy may improve outcomes.

Background Long-term corticosteroid (LTC) use is a known risk factor for adverse outcomes after various surgical procedures. However, the impact of LTC use on surgical complications after TSA remains underexplored. This study aims to assess the influence of LTC use on 90-day and 5-year complications following TSA. Methods A retrospective cohort study utilizing the PearlDiver database was conducted. Patients undergoing primary TSA with a minimum 5-year follow-up were included. LTC users were propensity-matched 1:10 with controls based on demographic variables and comorbidities. Postoperative complications within 90 days of surgery and long-term complications within 5 years were compared between groups. Multivariable logistic regressions were used to compare complications controlling for demographic variables and comorbidities. Results In a matched cohort of 556 LTC users to 4942 controls, corticosteroid users exhibited a 2.91-fold higher risk of pneumonia (95% CI: 1.69–4.80, p < 0.001) and a 2.19-fold higher risk of venous thromboembolism (VTE) (95% CI: 1.30–3.51, p = 0.001) within 90 days following TSA. No significant differences in 5-year surgical outcomes were observed. Discussion LTC users are at a heightened risk for 90-day medical complications, including pneumonia and VTE following TSA. However, their 5-year risk of surgical complications was comparable to patients without LTC use.

Delayed graft function (DGF) is a frequent complication after deceased donor kidney transplantation, yet its long-term impact remains understudied. Heterogeneous populations, short follow-up, and inadequate control of donor-related factors have limited prior studies. Using the Scientific Registry of Transplant Recipients (2005–2024), we evaluated the association between DGF and long-term graft outcomes, including a mate-kidney (same donor, discordant DGF status) analysis to isolate its independent effect. We identified 103,678 dialysis-dependent deceased donor kidney recipients maintained on tacrolimus and mycophenolate. Mixed-effects Cox models, adjusted for donor, recipient, immunologic, and procurement factors. DGF occurred in 30.1% of recipients and was associated with increased death-censored graft failure (HR 1.40; 95% CI 1.33–1.47) and overall graft failure (HR 1.27; 95% CI 1.23–1.31). DGF recipients had higher rejection rates at 6 (6.0% vs. 4.7%) and 12 months (8.9% vs. 7.3%), longer hospital stay, and higher 1-year rehospitalization. In the mate-kidney analysis (6,818 donors), DGF remained strongly associated with death-censored graft failure (HR 1.58; 95% CI 1.39–1.80) and overall graft failure (HR 1.35; 95% CI 1.25–1.46), confirming the independent effect of DGF. DGF is a strong predictor of adverse long-term outcomes irrespective of rejection and warrants targeted prevention strategies and intensified follow-up.