Citations

Among the transcriptional dependencies that sustain leukemic identity in acute myeloid leukemia (AML), the menin–KMT2A chromatin complex has emerged as a central regulatory node. The scaffold protein menin, encoded by MEN1, facilitates transcriptional activation of HOX and MEIS family genes during normal hematopoietic development. In AML, this physiologic and developmentally regulated role is co-opted to sustain constitutive HOX/MEIS-driven programs that block differentiation and maintain leukemic potential. Although dependency on menin is most clearly established in KMT2A-rearranged and NPM1-mutated AML, this vulnerability appears to arise from a shared transcriptional state characterized by persistent HOX activation rather than from any single genetic alteration. Pharmacologic disruption of the menin-KMT2A interaction collapses stemness-associated transcriptional networks, promotes myeloid differentiation, and attenuates leukemic self-renewal. Clinical activity observed with menin inhibitors provides translational validation of this dependency and establishes menin inhibition as a differentiation-based therapeutic strategy. In this review, we examine the molecular basis of menin-dependent transcriptional regulation in AML and its implications for therapeutic targeting with menin inhibitors and resistance to therapy.

ABSTRACT Objective Odontogenic sinusitis (ODS) ranges from isolated maxillary disease to pansinusitis. We compared patient characteristics, microbial and histopathological features, and symptom outcomes following endoscopic sinus surgery (ESS) between low and high radiographic burden ODS patients. Methods ODS patients undergoing ESS between 01/2013 and 08/2024 were reviewed. Preoperative CT scans were used to classify patients into high radiographic burden [with ostiomeatal complex (OMC) opacification] and low radiographic burden ODS [clear OMC]. Demographic, microbiological, and histopathological data were analyzed. Symptom improvement was assessed using pre‐ and post‐operative SNOT‐22 scores. Results Eighty‐seven patients were identified (high CT burden: 70; low CT burden: 17). High CT burden ODS was associated with older age ( p = 0.014), higher overall degree of inflammation ( p = 0.002), hyperplastic/papillary epithelial changes ( p = 0.034), and neutrophil infiltration ( p = 0.003). Culture of classic ODS bacteria ( Fusobacterium spp., Prevotella spp., mixed anaerobes, Streptococcus anginosus group) did not correlate with CT disease burden ( p = 0.110). No independent predictors of radiographic high‐burden disease were identified. Post‐ESS, significant reduction in total and rhinologic SNOT‐22 scores was only observed in the radiographic high‐burden ODS group ( n = 39; median reductions: 23 and 12 respectively; p < 0.001). Conclusion High radiographic burden was associated with older patients and with tissue inflammation level. Classic ODS bacterial profile did not associate with increased CT burden. While these findings remain exploratory, the observed differences in inflammatory and symptomatic profiles between groups suggest that radiographic burden warrants further study as a potential factor in ODS clinical decision‐making. Level of Evidence 3.

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of advanced spinal cord imaging techniques. Finally, we discuss spinal cord–specific processing pipelines and reproducibility challenges. Collectively, these insights underscore the need to integrate advanced and quantitative spinal cord imaging into clinical trials, research studies, and—when feasible—clinical care, to fully capture the extent of MS pathology, and ultimately improve patient outcomes.

Abstract Darier disease (DD) is a rare autosomal dominant genodermatosis. This comprehensive review, developed by the Darier Disease International Task Force (DDITF), consolidates current knowledge on the genetic basis, molecular pathophysiology, clinical presentation, diagnosis and management of DD, offering a global perspective that unites shared expertise. The disease arises from pathogenic variants in the ATP2A2 gene, which encodes sarco/endoplasmic reticulum Ca 2+ ‐ATPase isoform 2 (SERCA2), leading to disrupted calcium homeostasis and impaired desmosomal integrity. Clinically, DD is classified based on lesion type (classic vs. non‐classic) and is often accompanied by significant extracutaneous manifestations. Management remains challenging and requires a multifaceted approach, including topical therapies, systemic retinoids and lifestyle modifications. Emerging treatments that target the underlying molecular mechanisms offer promise for improved outcomes. This review aims to provide an updated reference and practical guidance for clinicians involved in the care and study of DD.

Background: Conflicts of interest pose a risk to the integrity of clinical research. As part of the Sunshine Act, the Open Payments Program was established to provide transparency in financial relationships between commercial entities and physicians. Previous research indicates disparities between industry payments self-reported by plastic surgeon authors and those disclosed by commercial entities. This study sought to revisit the accuracy of conflict-of-interest disclosures, comparing current trends with previously published data, and introduce a novel automated search tool designed to facilitate future reviews of self-disclosures. Methods: Articles from the Aesthetic Surgery Journal and Plastic and Reconstructive Surgery published between 2017 and 2022 were reviewed. Self-reported disclosures for plastic surgeon authors were aggregated and compared against the Open Payments database using Python. Results: A total of 8040 articles were reviewed. After filtering and applying inclusion criteria, 961 unique authors and 4226 authorships were identified. A total of 5802 discrepancies were found, with 78.6% of eligible authors having at least 1 discrepancy. Four percent of the included publications were estimated to contain undisclosed relationships that qualified as conflicts of interest. The median total payments for authors with discrepancies were greater than for authors without discrepancies ($9600 vs. $2500; P <0.001). A discrepancy in self-reporting was more likely to be identified among senior authors ( P <0.001). Conclusions: Plastic surgeon authors continue to underreport their financial relationships. Automated screening may help identify disclosure discrepancies and support more complete author self-reporting.

Introduction Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are progressive neurodegenerative disorders characterized by alpha-synuclein pathology. As current therapies largely target symptoms, there is a clear need for disease-modifying treatments. Emerging evidence links these disorders to glucose metabolism dysregulation, suggesting antidiabetic agents may hold therapeutic potential. Methods This was a prospective, randomized, double-blind pilot study involving 12 subjects with PD or DLB to evaluate the tolerability and preliminary effects of a dipeptidyl peptidase 4 (DPP4) inhibitor (sitagliptin 100 mg) vs. sodium glucose like transporter 2 (SGLT2) inhibitor (dapagliflozin 10 mg) over a 4-week period, compared to a placebo. We assessed changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, cognitive function, and autonomic biomarkers. Both sitagliptin and dapagliflozin were well-tolerated, with no adverse events. While no significant changes were observed in cognitive scores, a significant difference was found in the change from baseline for MDS-UPDRS part 1 ( P = 0.008), part 2 ( P = 0.020), and total scores ( P = 0.047) when comparing the three groups. Discussion The dapagliflozin group showed more favorable trends in MDS-UPDRS scores. Limitations include small study size and duration as well as all participants had PD except one subject in the DPP4 inhibitor group with DLB. This pilot study suggests that these inhibitors are safe in PD and DLB patients. The preliminary findings, particularly the trends in the dapagliflozin group, provide a basis for larger-scale, long-term studies to confirm these potential symptomatic benefits and explore disease-modifying effects. Clinical trial registration https://clinicaltrials.gov/study/NCT06263673 , identifier: NCT06263673.

Background: Perianal Crohn’s disease (PCD) is a severe and disabling phenotype of Crohn’s disease that often requires multidisciplinary medical and surgical management. Although ustekinumab (UST) and vedolizumab (VDZ) are widely used after antitumor necrosis factor (anti-TNF) failure, direct comparative data specifically in PCD remain limited. Methods: We conducted a multicenter, retrospective cohort study using the TriNetX US Collaborative Network to compare the effectiveness of UST versus VDZ in adults (18 y or older) with PCD between January 2017 and May 2023. Outcomes were perianal-specific clinical events, including definitive fistula surgery, incision and drainage, diversion procedures, and antibiotic use (metronidazole or ciprofloxacin), assessed at 1 and 2 years after biological initiation. Propensity score matching (PSM) (1:1) was performed to balance baseline variables. Time-to-event analyses were conducted in the matched population using Kaplan–Meier methods, and hazard ratios (HRs) were estimated using Cox proportional hazards models within the matched cohorts. Results: A total of 2936 patients were identified before PSM: 1997 patients in the UST group and 939 patients in the VDZ group. After PSM, 936 patients were included in each cohort. In the matched cohorts, UST was associated with significantly lower risk of definitive perianal fistula surgery (HR: 0.66, 95% CI: 0.50-0.89; P <0.01), and composite surgical events (HR: 0.70, 95% CI: 0.54-0.87; P <0.01) compared with VDZ at 1 year. Rates of antibiotic use, incision and drainage of perianal abscess, and diversion procedures were numerically lower but not statistically significant. At 2 years, these findings persisted, with significantly lower cumulative incidence of definitive perianal fistula surgery (HR: 0.78, 95% CI: 0.61-0.90; P =0.03), composite surgical events (HR: 0.81, 95% CI: 0.69-0.90; P <0.01), and antibiotic use (HR: 0.86, 95% CI: 0.75-0.93; P =0.04) in the UST cohort compared with VDZ. Rates of incision and drainage and diversion procedures remained similar between groups. Conclusion: In this large real-world cohort, UST was associated with lower risks of perianal surgical interventions at one and two years and reduced antibiotic utilization at two years compared with VDZ in patients with PCD. These findings highlight meaningful differences in real-world effectiveness between therapies and support the need for prospective studies to further evaluate comparative effectiveness in this population.

Abstract Travelling waves are a prominent feature of hippocampal activity, but the mechanisms determining their propagation and influence on the cerebral cortex remain unclear. Using a biophysically-grounded model of neural activity evolving across hippocampal and cortical surfaces, we show that spatial gradients in external in-put or neural excitability are a sufficient mechanism for the emergence of travelling waves along the long axis of the hippocampus. These waves emerge only above a critical gradient threshold, propagate with biologically-plausible velocities and exhibit frequency-dependent reversals in direction across slow and fast theta regimes. When coupled to the cerebral cortex, anterior-to-posterior hippocampal waves selectively reorganise globally synchronous cortical activity into metastable travelling waves, whereas posterior-to-anterior hippocampal waves do not, revealing a directional asymmetry in hippocampal–cortical communication. Conversely, cortical waves aligned with large-scale functional gradients induce structured hippocampal waves, revealing complementary direction specific effects across the two systems. These analyses identify structured excitability gradients as a principle governing wave propagation in the hippocampus and suggest how wave-to-wave interactions may coordinate complex cortical and hippocampal interactions during mnemonic and perceptual processes.

Background: Epstein–Barr virus (EBV) is a key environmental risk factor for multiple sclerosis (MS), and tonsils and adenoids serve as a primary viral reservoir. This study investigates the potential role of adenotonsillectomy in pediatric-onset multiple sclerosis (POMS) risk and relapse rate. Objectives: POMS participants and controls were recruited from 16 pediatric MS clinics between 1 November 2011 and 1 July 2017. Clinical and demographic information, including history of adenotonsillectomy, EBV serostatus, and HLA-DRB1*15:01:01 status, were collected. Multivariable logistic regression assessed the association between adenotonsillectomy and MS risk. In addition, negative binomial regression offset by follow-up time was used to assess the relationship between adenotonsillectomy and relapse rate in POMS participants with available follow-up data. Results: The case-control analysis included 359 POMS participants and 560 pediatric controls. Individuals with a history of adenotonsillectomy had a 63% increased odds of MS (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.01–2.64, p = 0.046). Among the 239 POMS participants with available follow-up data, adenotonsillectomy was associated with a twofold increase in annualized relapse rate (adjusted incidence rate ratio (IRR) = 2.00, 95% CI = 1.15–3.48, p = 0.013). Conclusions: Prior adenotonsillectomy was associated with increased risk of MS and greater relapse rate in pediatric patients, suggesting a potential interplay between EBV, immune regulation, and MS pathogenesis.