Citations

Ring-closing carbonyl-olefin metathesis (COM) reactions provide a straightforward method for producing cyclic alkenes from precursors containing carbonyl functional groups tethered to nucleophilic alkenes. Within the last decade, many methods for carrying out Lewis acid- or organocatalyzed COM reactions were reported; however, Brønsted–Lowry acid-catalyzed COM reactions are less developed. Herein, we report that phosphoric acid derivatives and N-triflylphosphoramides mediate COM reactions, although the substrate scope is limited to biaryl compounds that cyclize to produce phenanthrene products. We also disclose the synthesis and characterization of a previously non-fully characterized phosphoric acid derivative and a novel phosphoramide.

Background Evidence to guide the optimal timing of antiplatelet and oral anticoagulants (OACs) therapy after hemorrhagic infarction (HI) versus parenchymal hematoma (PH) is limited and inconsistent, leading to substantial variation in practice. This study's goal was to study the practice pattern and compare clinical outcomes associated with early‐versus‐delayed initiation of antiplatelet/OACs after hemorrhagic transformation (HT). Methods This multicenter, retrospective, cross‐sectional study included patients with acute ischemic stroke and HT. Patients with an HI or PH were categorized by HT to antithrombotic initiation time, and their outcomes—30‐day HT exacerbation, composite outcomes of recurrent stroke/systemic emboli, 90‐day vascular death, and functional outcomes—were compared. Results Of 748 patients, 496 received antiplatelets, and 252 received OACs after HT. The median HT‐to‐antiplatelet time was significantly shorter after HI than PH (1 [interquartile range, 0–2] versus 3 [interquartile range, 1–5] days; P <0.001). There were no statistically significant differences in HT exacerbation and composite outcomes (30‐day), as well as vascular death and unfavorable functional outcomes (90‐day), between patients who received same‐day, early (HI, <1 day; PH, <3 days), or late (HI, >1 day; PH, >3 days) antiplatelets after either HI or PH. Among patients on OACs, those with HI had shorter median HT‐to‐OAC time than PH (7 [interquartile range, 2–15] versus 15 [interquartile range, 7–32] days; P <0.001). Although HT exacerbation rates (30‐day) were comparable between early (HI, <7 days; PH, <15 days) and late (HI, >7 days; PH, >15 days) OAC initiation after either HI or PH, late initiation after PH was accompanied by higher rates of composite outcomes (30‐day) than early initiation (20.7% versus 3%; P =0.044). Regression models adjusted for demographics, National Institutes of Health Stroke Scale, and stroke severity showed no statistically significant association between early initiation of antiplatelets or OACs with HT exacerbation risk. Conclusions Our study found no statistically significant difference in HT exacerbation between early and late initiation of antiplatelets or OACs among patients with HI/PH, while prolonged delay among patients with PH were accompanied by increased systemic thromboembolic events. Although these findings offer preliminary clinical insight, prospective studies are needed.

Abstract Despite growing interest in AI for pancreatic cyst management, no prior study has systematically investigated how lesion characteristics influence model behavior or provided a comprehensive explainability analysis in IPMN malignancy risk stratification. We present the first multi-center study integrating explainable AI with uncertainty quantification to evaluate how cyst type, size, and location affect deep learning performance in IPMN malignancy prediction. Our retrospective study analyzed 170 IPMNs from seven centers using a radiomics-deep learning fusion model. Cases were stratified by dysplasia grade, IPMN type, size, and location; with model interpretability assessed using SHAP, LIME, Grad-CAM, and uncertainty quantification. Overall accuracy was 67.1%, with model uncertainty lower for correct versus incorrect predictions (0.72 vs 0.78, p < 0.001). On subgroup analysis: Low-Risk lesion accuracy exceeded High-Risk (81.3% vs. 42.9%, p < 0.001), BD accuracy was inversely correlated with cyst size while MD remained stable, and body and whole-pancreas cysts stratified more accurately than tail cysts (77.8%, 76.6% vs. 47.8%). AI models face significant, previously uncharacterized performance drops when evaluating complex high-risk IPMNs. Our study shows that integrating uncertainty quantification can successfully flag unreliable predictions, enabling a selective-prediction framework where clinicians can confidently rely on AI for low-risk, low-uncertainty lesions while deferring high-uncertainty cases to expert review.

Abstract Current assessments of brain permeability rely predominantly on drug delivery to contrast-enhancing tumor regions. However, substantial portions of central nervous system (CNS) tumors reside within non-enhancing brain (NEB), where drug concentrations frequently remain subtherapeutic. This collaborative Adult Brain Tumor Consortium and Food and Drug Administration workshop aimed to identify criteria for defining NEB permeability to accomplish 2 critical objectives: (1) allocate clinical trial resources toward agents achieving therapeutic NEB concentrations and (2) minimize systemic toxicity when CNS benefit is improbable. The workshop systematically evaluated permeability assessment modalities, including drug physicochemical properties, in vitro blood-brain barrier models, and penetration into cerebrospinal fluid and normal rodent brain. Methodological approaches to determine requisite NEB drug concentrations and approaches to measuring NEB pharmacokinetics and pharmacodynamics were examined. This culminated in developing the Non-Enhancing Brain Permeability Index (NEBPI), which assigns therapeutic agents to 3 categories: sufficiently permeable, insufficiently permeable, or impermeable. The NEBPI provides a standardized framework to assist investigators and regulatory agencies to evaluate NEB penetration before human efficacy studies are initiated for agents that require direct tumor contact. Assessing NEB drug penetration is critical to improving outcomes in CNS tumors and reducing the incidence of brain metastases in systemic malignancies.

Abstract Introduction Combat casualty care requires standardized proficiency criteria to ensure readiness in austere environments, yet gaps persist in defining performance thresholds for critical trauma skills. The Combat Medical Skills Sustainment Consortium (CMSSC), a novel military-civilian collaboration, aimed to validate competency thresholds for 21 Department of Defense-identified trauma skills. Materials and Methods A prospective cohort study (2022-2025) enrolled 1,495 military and civilian personnel across five academic centers, stratified by experience (novice, intermediate, expert). Skills, including cricothyroidotomy, whole blood transfusion, and ultrasound-guided vascular access, were assessed using validated checklists in Role 2-congruent simulations. Statistical analysis compared checklist performance against participant experience with a priori checklist scores estimated at 40% (novices) and 90% (experts). Results Competency thresholds were established, ranging from 77% (mechanical ventilation) to 100% (handoff). Experts achieved 85%-98% proficiency across most skills, with novices at 34%-97%. A ceiling effect was observed for less complex skills consistent with the power law of practice. Conclusion The Combat Medical Skills Sustainment Consortium validated standardized assessment tools, with potential to address readiness gaps through military-civilian synergy. Findings support consortium-guided curriculum development and highlight the need for longitudinal skill decay studies. Impact This study sets a benchmark for trauma care skills assessment, facilitating rapid adoption across military and civilian settings.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate are intended to serve as a resource for health care providers to identify individuals who may benefit from cancer risk assessment and genetic counseling and testing; help guide decisions related to genetic testing; and facilitate a multidisciplinary approach in the comprehensive care of individuals at increased risk for hereditary breast, ovarian, pancreatic, and prostate cancer. The current guidelines focus primarily on assessment of pathogenic and likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants associated with increased risk of these cancers. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding screening for prostate cancer and pancreas cancer, as well as testing criteria for nonepithelial ovarian cancer.

Background: Studies have suggested that administering antithrombotics—oral anticoagulants (OACs) and antiplatelets (APLT)—after acute ischemic stroke(AIS) with hemorrhagic transformation (HT) is safe and can reduce ischemic recurrence. However, the safety of their early initiation after HT remains unclear. Method: This study utilized data from nine centers across several countries. The study population included patients with AIS who subsequently experienced HT. Patients with a specific HT type—hemorrhagic infarction(HI) or parenchymal hematoma(PH)—were categorized based on the time between HT and antithrombotic initiation, and their outcomes were compared. Outcomes included 30-day HT exacerbation and composite outcomes of recurrent stroke and systemic emboli, as well as 90-day vascular death and functional outcome. Results: Of 748 patients,496 received APLT, and 252 were prescribed OACs after HT. The median HT-to-APLT time was significantly shorter among HI patients than PH patients(1[IQR:0-2] vs. 3[IQR:1-5] days,p<0.001). The rates of 30-day HT exacerbation and composite outcomes, as well as 90-day vascular death and unfavorable functional outcomes, did not significantly differ between patients who received same-day, early (HI:<1day;PH:<3days), or late (HI:>1day;PH:>3days) APLTs after either HI or PH. Among patients who received OACs, those with HI had a significantly shorter median HT-to-OAC time than PH (7[IQR:2-15] vs. 15[IQR:7-32] days,p<0.001). However, 30-day HT exacerbation rates were comparable between early (HI:<7days;PH:<15days) and late (HI:>7days;PH:>15days) OAC initiation among patients with either HI or PH, late initiation among patients with PH was associated with higher rates of 30-day composite outcomes than early initiation(20.7% vs. 3%,p=0.044). Based on regression models adjusted for NIHSS and stroke severity, early initiation of APLTs or OACs was not associated with increased risk of HT exacerbation. Conclusion: Findings suggest that the same-day initiation of APLTs after HI or PH-1, and within 1-3days following PH-2, might not be associated with HT exacerbation or worsening outcomes. Similarly, OACs initiated 2-7days after HI and 7-15days after PH may not be associated with worsened patients' outcomes, whereas delays beyond these timeframes can be associated with higher thromboembolic risk.

Introduction Post‐market and multicenter studies report low complete occlusion rates (41‐49%) and higher retreatment rates (13%) following WEB deployment, compared to 3.8% with microsurgical clipping. While retreatment after WEB has been shown to be technically feasible, data on final angiographic outcomes remain limited. We performed a retrospective analysis of prospective databases from 14 cerebrovascular centers in the US to compare the safety and efficacy of retreatment versus continued observation for residual and recurrent aneurysms after initial WEB deployment. Materials/Methods Multinomial logistic regression was used to identify baseline characteristics of untreated and residual/recurrent aneurysms that may act as confounders, which then underwent propensity scored matching (PSM). Results Among 211 patients (125 observed, 86 retreated), retreatment was more common in initially ruptured aneurysms (p<0.001), which showed higher recurrence (p=0.036) and sac‐dominant residuals (p=0.004). These were primarily due to WEB compression on follow‐up (p=0.001), rather than incomplete occlusion with an appropriately sized device (p<0.001). Retreatment was associated with significantly higher rates of complete angiographic occlusion at last follow‐up compared to observation alone (p<0.001), a finding that remained consistent across subgroups defined by initial unruptured status, residual type, and recurrence patterns (all p<0.05). Clipping demonstrated higher, though statistically insignificant, rates of complete occlusion; flow diversion and stent‐assisted coil embolization yielded comparable complete occlusion rates at follow‐up. After propensity score matching, retreatment remained significantly associated with higher rates of complete angiographic occlusion (all p<0.05), with comparable outcomes observed between clipping and various endovascular approaches as above. Conclusion Retreatment improved complete occlusion rates; however, no aneurysmal hemorrhages occurred in either group. Further intervention may be unnecessary when the WEB device—whether compressed or intact (BOSS 0/1)—adequately protects the dome. In cases where WEB compression significantly exposes the aneurysm wall, stent‐assisted coiling or flow diversion can be performed safely and successfully, depending on vascular anatomy and surgeon preference. image image

ABSTRACT Solid tissue‐derived extracellular vesicles (ST‐EVs) are extracellular vesicles (EVs) separated directly from solid tissues of both vertebrates and invertebrates. ST‐EVs provide a physiologically relevant snapshot of tissue‐specific molecular dynamics and can be enriched directly in situ, from tissues in their natural state, preserving the native characteristics of ST‐EVs. However, their enrichment presents unique technical challenges compared to EVs derived from biofluids or cell culture media. The need for transparent reporting in ST‐EV research is crucial to enhance the reproducibility, comparability, and reliability of research findings. The Solid Tissue Task Force, part of the Scientific Reproducibility Subcommittee of International Society for Extracellular Vesicles, aims to recommend reporting parameters and identify outstanding questions related to the pre‐analytical and analytical handling of solid tissues, as well as ST‐EV separation and characterization. These steps are essential for advancing the understanding of the biological roles of ST‐EVs and their potential clinical applications.