bluuebunny/crossref_metadata_2025 huggingface dataset:
In-depth analysis and exploration of rogue wave, lump wave, and different solitonic patterns to the Painlevé-integrable (3+1)D nonlinear evolution equations using a new extended methodology
Authors: Mann Nikita , Kumar Sachin
Published: January 2025

This paper proposes a novel extended methodology, establishing the new extended Generalized Exponential Rational Function Method (GERFM), which is known as a “new extended GERFM” for solving the Painleve-integrable [Formula: see text]D generalized nonlinear evolution equation. We enhance GERFM by incorporating additional terms that combine functions and derivatives, making it a more generalized and efficient approach for solving nonlinear partial differential equations. Moreover, the unified method is applied to thoroughly delve deeper into the equation’s properties to understand its mathematical characteristics and potential solutions. This approach aims to systematically investigate and elucidate the equation’s inherent features, providing a more complete insight into its behavior and the nature of its solutions. Utilizing these methods, we have derived new exact solutions that involve exponential, trigonometric, hyperbolic, polynomial, and rational functions with additional parameters to the model. To emphasize the physical importance of these solutions, we present three-dimensional (3D) and contour plots, investigating different parameter choices. The graphs illustrate various wave patterns such as irregular periodic solitons, rogue waves, lumps, and the interaction of solitary and lump waves based on different parameter values. This visualization method enriches our comprehension of the solutions and facilitates a thorough exploration of how they could be applied to the generation of prolonged waves with small magnitudes in plasma physics, fluid dynamics, and other media with weak dispersion.
If You Write It Better, You Will Say It Better
Authors: Yaffe Philip
Published: January 2025

Each "Communication Corner" essay is self-contained; however, they build on each other. For best results, before reading this essay and doing the exercise, go to the first essay "How an Ugly Duckling Became a Swan," then read each succeeding essay.

Today it is generally accepted that to fully achieve in most fields of endeavor you must be a competent (if not a superior) writer and public speaker. Computer science and computer programming are no exception. However, it is a mistake to believe that good expository (non-fiction) writing public speaking are distinct disciplines. They are flipsides of the same coin. Recognizing this essential dualism makes achieving competence in both faster and significantly easier.

This essay (slightly modified) originally appeared in the March 2010 edition of Toastmaster, the official monthly magazine of Toastmasters International, which has more than 14,000 clubs for members seeking to grow their public-speaking and leadership skills.
Image-guided Interventions for Core Muscle Injury and Other Disorders in the Pubic Symphysis
Authors: Flores Dyan V. , Lee Juvel , Murray Timothy
Published: January 2025

Image-guided musculoskeletal interventions at and about the pubic symphysis should be performed to address core muscle injury, with an emphasis on anatomic considerations and techniques that lead to a successful procedure.
Table 1 from Evaluating Ovarian Cancer Risk–Reducing Salpingectomy Acceptance: A Survey
Authors: Lukey Alexandra , Sowamber Ramlogan , Huntsman David , Pearce Celeste Leigh , Howard A. Fuchsia , Meza Rafael , Law Michael R. , Phung Minh Tung , Hanley Gillian E.
Published: January 2025

Sample characteristics of 211 participants
Supplementary Table 1 from Evaluating Ovarian Cancer Risk–Reducing Salpingectomy Acceptance: A Survey
Authors: Lukey Alexandra , Sowamber Ramlogan , Huntsman David , Pearce Celeste Leigh , Howard A. Fuchsia , Meza Rafael , Law Michael R. , Phung Minh Tung , Hanley Gillian E.
Published: January 2025

Supplementary Table 1. Logistic regression analysis of factors associated with accepting risk-reducing surgery (RRS) for ovarian cancer when lifetime risk is less than 4% compared to greater or equal to 4%, using complete case analysis
Data from Evaluating Ovarian Cancer Risk–Reducing Salpingectomy Acceptance: A Survey
Authors: Lukey Alexandra , Sowamber Ramlogan , Huntsman David , Pearce Celeste Leigh , Howard A. Fuchsia , Meza Rafael , Law Michael R. , Phung Minh Tung , Hanley Gillian E.
Published: January 2025

Abstract
With evidence that salpingectomy is effective in preventing high-grade serous carcinoma, it is time to consider offering this procedure to people at higher-than-average lifetime risk for ovarian cancer, despite not having a pathogenic genetic variant that increases the risk for ovarian cancer. This targeted approach has potential to be effective at reducing ovarian cancer incidence, and unlike opportunistic salpingectomy, it is focused on people with an increased lifetime risk of ovarian cancer. However, the acceptability of this approach within the population of potential patients remains unknown. We conducted an online survey of adults in British Columbia, Canada, who were defined as “at risk” for ovarian cancer (i.e., people born with ovaries). Participants completed a questionnaire on demographics, ovarian cancer risk and protective factors, concerns about risk-reducing salpingectomy (RSS), and the risk they considered high enough to warrant RRS. We included 211 participants. Among these participants, 42% (n = 88) indicated that they would consider RRS at any lifetime risk or any risk above the population average. Another 20 participants chose risks between 1.5% and 4% for a cumulative 51% of the sample choosing risks below thresholds for oophorectomy. In contrast, 6% (n = 12) indicated that they would not consider the procedure at any risk level. None of the factors collected were associated with the likelihood that a person would find RRS acceptable. Overall, our participants showed broad interest in RRS as an ovarian cancer prevention strategy. These results suggest that there would likely be uptake if RRS was offered.
Significance:
This study found that many participants were willing to consider RRS to prevent ovarian cancer. Further research on RRS should be undertaken to understand how this can be best used for ovarian cancer prevention.
Impaired Exercise Capacity in High-Risk Diabetic Cardiomyopathy: The ARISE-HF Cardiopulmonary Exercise Testing Subanalysis
Authors: Tang W.H. Wilson , Liu Yuxi , Butler Javed , Del Prato Stefano , Ezekowitz Justin A. , Ibrahim Nasrien E. , Lam Carolyn S.P. , Marwick Thomas H. , Perfetti Riccardo , Rosenstock Julio , Solomon Scott D. , Zannad Faiez , Januzzi James L. , Lewis Gregory D.
Published: January 2025

BACKGROUND:

Objective indices of functional capacity in patients with diabetic cardiomyopathy and stage B heart failure (HF) have not been comprehensively defined. We sought to characterize the cardiopulmonary exercise characteristics of individuals with diabetic cardiomyopathy at high risk for overt HF.

METHODS:

The relationships from cardiopulmonary exercise testing with clinical and laboratory characteristics of participants with diabetic cardiomyopathy were evaluated using baseline data from the ARISE-HF trial (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure). Cluster phenogroups with different comorbidities and their corresponding functional capacity profiles were identified.

RESULTS:

Among study participants (n=689), the median (Q1, Q3) peak oxygen uptake and ventilatory efficiency (slope of the ratio of minute ventilation/carbon dioxide production) were 15.7 (interquartile range, 13.0–18.0) mL/kg per minute and 31.2 (interquartile range, 27.2–34.1), respectively. Lower peak oxygen uptake was associated with older age, female sex, higher body mass index, higher N-terminal pro-B-type natriuretic peptide, and an increasing burden of noncardiac comorbid conditions but was not associated with cardiac troponin T or echocardiogram-derived strain, left atrial volume index, E/e′, or right ventricular systolic pressure. Elevated left ventricular mass index was the only echocardiographic abnormality associated with lower peak oxygen uptake. Multivariable analysis revealed that female sex, higher body mass index, and no history of dyslipidemia were independently associated with lower baseline peak oxygen uptake. Cluster analysis revealed 3 clusters with profiles of different cardiovascular/exercise parameters and health status profiles.

CONCLUSIONS:

Baseline cardiopulmonary exercise testing data from the ARISE-HF trial highlight predominant associations of extracardiac clinical and demographic variables with significant impairment in exercise capacity despite strict fulfillment of diagnostic criteria for stage B HF.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04083339.
Abstract 102: Association Between Kidney Function and Severity of White Matter Hyperintensity: The Atherosclerosis Risk in Communities Study
Authors: Littig Lauren , Krothapalli Neeharika , Wong Ka-Ho , Kim Yvonne , Smith Harper , de Havenon Adam
Published: January 2025

Background and Purpose:
Chronic kidney disease (CKD) is associated with an increased risk of stroke and worse outcomes, yet it is often asymptomatic, with an estimated 90% of individuals unaware they have CKD until its later stages. Due to the functional and anatomical similarities of the kidney and brain microvasculature, the effects of early-stage CKD on brain health warrant further investigation. This study aimed to explore the association between estimated glomerular filtration rate (eGFR), a measure of how well the kidneys filter toxins and waste from the blood, and white matter hyperintensity (WMH), an MRI biomarker of cerebral small vessel disease linked to stroke and vascular cognitive impairment.

Methods:
We performed a cross-sectional post-hoc analysis of the Atherosclerosis Risk in Communities (ARIC) cohort at study visit 7 (2018-2019), including participants with WMH measured on MRI and eGFR estimated by the CKD-EPI. While eGFR had a standard distribution and did not require transformation, WMH was right-skewed so we standardized it to total intracranial volume and created a z-score for analysis (Figure 1).

Results:
We included 661 individuals (mean age 81.1±4.7, 56.6% female, 22.1% Black) with a mean WMH burden of 20.0±16.8 mL. In a linear regression model adjusted for age, sex, race, hypertension, diabetes, prior stroke, current smoking, current alcohol use, systolic blood pressure, and APOE genotype, lower eGFR was significantly associated with higher WMH (β = -0.008; 95% CI -0.013, -0.003; p < 0.001) (Figure 2). Sensitivity analysis using the same adjustments but predicting the top tertile of WMH in a logistic regression and using a categorical approach to eGFR (<30, 30-60, 60-90, >90) confirmed the results of our primary analysis (Figure 3).

Discussion:
We found a significant independent association between impaired kidney function and increased WMH burden, even in the early stages of CKD. These findings emphasize the importance of early CKD detection and management to preserve brain health. Future research should investigate the bidirectionality of this relationship, particularly in the context of acute ischemic injury, focusing on the shared mechanisms of renal and neurovascular dysfunction to develop more effective prevention and therapeutic strategies aimed at reducing the burden of disease in our aging population.
Abstract 103: Anticoagulation versus Antiplatelets Across Subgroups of Embolic Stroke of Undetermined Source: A Meta-Analysis of Seven Randomized Controlled Trials
Authors: Ghannam Malik , Al-Qudah Abdullah , Alshaer Qasem , Kronmal Richard , Ntaios George , Longstreth W , Furie Karen , Saver Jeffrey , KASNER SCOTT , Elkind Mitchell , Tirschwell David , Poli Sven , Kamel Hooman , Yaghi Shadi
Published: January 2025

Background:
The term embolic stroke of undetermined source (ESUS) encompasses a substantial but heterogeneous population of patients with ischemic stroke, underscoring the importance of identifying personalized treatment strategies. In subgroups of patients randomized in ESUS trials, we evaluated the effectiveness of anticoagulation compared to antiplatelet therapy in secondary ischemic stroke prevention.

Methods:
A study-level meta-analysis was conducted of randomized controlled trials of patients with ESUS, comparing anticoagulation to antiplatelet therapy. The primary efficacy outcome was recurrent ischemic stroke and safety outcomes were major bleeding and death. Subgroups assessed were age, sex, presence of patent foramen ovale (PFO), left atrial enlargement (LAE), and atrial cardiopathy. Pooled relative risks (RRs) were meta-analyzed. Cochrane Risk of Bias Tool 2.0 (RoB 2) was used for risk of bias assessment.

Results:
A total of seven randomized controlled trials involving 14,804 patients were analyzed, with 7,406 patients treated with anticoagulation, and 7,398 treated with antiplatelet therapy. Compared with antiplatelet therapy, anticoagulation was associated with a similar rate of recurrent ischemic stroke (RR 0.91, 95% CI 0.80-1.05; I2 = 0%). In ESUS with PFO, anticoagulation was associated with significantly lower risk of ischemic stroke (RR 0.59, 95% CI 0.35-0.98; I2 = 0%). Heterogeneity was present in those with LAE: antiplatelet therapy was superior in trials allowing cardiac monitoring after randomization (RR 6.65, 95% CI 1.26-35.08; I2 = 0%), but anticoagulation was superior in trials prohibiting cardiac monitoring after randomization (RR 0.25 95% CI 0.07-0.89). Subgroups based on age, sex, or presence of atrial cardiopathy did not benefit from anticoagulation over antiplatelet therapy.

Conclusions:
In this meta-analysis, an empiric anticoagulation approach is not beneficial for patients with ESUS. This finding highlights the importance of an individualized treatment strategy. Such a strategy should include prolonged cardiac monitoring for atrial fibrillation, particularly in patients with moderate to severe LAE. Anticoagulation treatment showed promise in patients with medically treated PFO. Other subgroups did not benefit from anticoagulation therapy. Large prospective studies within ESUS subgroups are needed to validate our findings.
Abstract 107: Polygenic risk prediction improves clinical prediction of atrial fibrillation diagnosed after stroke.
Authors: Tack Reinier , Senff Jasper , Tan Benjamin Yong Qiang , Kimball Tamara , Prapiadou Savvina , Singh Sanjula , Rosand Jonathan , Ashburner Jeffrey , Khurshid Shaan , Jurgens Sean , Mayerhofer Ernst , Lubitz Steven , Anderson Christopher
Published: January 2025

Introduction:
Atrial fibrillation diagnosed after stroke (AFDAS) is common and differs from known atrial fibrillation (KAF), the most common cause of cardioembolic stroke. Because identification of AFDAS warrants administration of oral anticoagulants for secondary prevention, extended cardiac monitoring is often used, yet it is unclear who is most at risk for developing AFDAS. We aimed to determine whether prediction of AFDAS improves when adding genetic risk to clinical risk predictors in a real world clinical population of stroke survivors.

Methods:
We retrospectively included patients with stroke between June 2003 and April 2017. Characteristics and outcomes were obtained from a data repository at Mass General Brigham (MGB), with chart review of AF diagnosis. Genome-wide polygenic risk scores (PRS) for AF were calculated using recent GWAS summary statistics. Clinical risk was determined using ReCHARGE-AF, a clinical post-stroke AF prediction score recalibrated from the CHARGE-AF score. For a subgroup, we obtained information on rare cardiomyopathy loss-of function genetic variants associated with AF risk. We determined whether patients had KAF, AFDAS or no AF, and used descriptive statistics to compare groups. We used Cox proportional hazards models to predict AFDAS, and calculated c-statistics to determine predictive validity at 1 month, 1 year and 5 years after stroke. We compared performance of clinical and genetic risk models through the DeLong test. We used 1,000-iteration bootstrapping to determine whether the addition of PRS improves model prediction.

Results:
Of 1004 stroke patients, 900 (90%) were non-Hispanic white, with a mean age of 67. KAF was present in 239 (23.8%) patients, and 87 (8.7%) developed AFDAS. Patients with KAF and AFDAS had higher ReCHARGE-AF scores, higher rates of surface monitors and ILRs, and were more likely to have a high PRS, but did not differ in the presence of rare variants. Addition of PRS to clinical risk was associated with an increased performance at 30 days (AUC 0.784 vs 0.665, p < 0.01), 1 year (AUC 0.738 vs 0.659, p = 0.02) and 5 years (AUC 0.757 vs 0.708, p = 0.01). Addition of PRS was associated with improved discrimination, better reclassification, and a median improvement in risk score.

Conclusion:
Prediction of AFDAS can be improved by adding polygenic risk scores to clinical risk prediction tools. Future studies are necessary to determine the feasibility of incorporating polygenic risk prediction for AFDAS.
Abstract 111: Targeting Neutrophil Integrin α9 Enhances Microglial Efferocytosis and Improves Sensorimotor and Cognitive Recovery Following Subarachnoid Hemorrhage in Mice
Authors: Kaur Harpreet , Pandey Nilesh , kumar Dhananjay , Chandaluri Lakshmi , Martinez Alexa , Reece Erika , Gaddam Ravinder , Murnane Kevin , Vikram Ajit , Mohandas Rajesh , Orr Wayne , Lu Xiao-Hong , Rom Oren , Yurdagul Arif , Dhanesha Nirav
Published: January 2025

Background:
Neutrophil infiltration plays a pivotal role in exacerbating brain injury following subarachnoid hemorrhage (SAH). Integrin α9, highly expressed on activated neutrophils, facilitates their adhesion and transendothelial migration. Once infiltrated, neutrophils aggravate inflammatory response and can impair microglial efferocytosis. Defective efferocytosis may results in accumulation of apoptotic cells, persistent inflammation, and resultant poor recovery following SAH. Despite the known role of integrin α9 in promoting cerebral inflammation, the impact neutrophil integrin α9 on microglial efferocytosis and subsequent SAH outcomes remains unknown.

Hypothesis:
Integrin α9 dependent neutrophil transendothelial migration impedes microglial efferocytosis, promotes cerebral inflammation, and mediates poor SAH recovery.

Methods:
Neutrophil specific integrin α9 knockout mice (

α9
fl/fl
Mrp8Cre
+/-

) and littermate controls (

α9
fl/fl
Mrp8Cre
-/-

) were subjected to the endovascular perforation model to induce SAH. Sensorimotor tests (modified neurological severity score, corner, and cylinder test) and cognitive function tests (Y-maze and novel object recognition test) were performed up to 4-weeks. Neutrophil infiltration, inflammation, apoptosis, and blood brain barrier (BBB) disruption were quantified 24-hr post-SAH. In vitro and in vivo functional assays were carried out to assess the neutrophil integrin α9-dependent effects on microglial efferocytosis.

Results:
Mice with SAH exhibited increased integrin α9 levels on infiltrated neutrophils as compared to mice with sham-surgery.

α9
fl/fl
Mrp8Cre
+/-

mice showed improved sensorimotor and cognitive recovery (up to 4-weeks) (Fig 1), reduced neutrophil infiltration, BBB damage, neuronal apoptosis as compared to controls.

α9
fl/fl
Mrp8Cre
+/-

mice exhibited reduced brain neutrophil elastase levels along with enhanced microglial efferocytosis of apoptotic neurons. In vitro mechanistic studies revealed that reduced transendothelial migration of

α9
-/-

neutrophils directly contributed to the enhanced microglial efferocytosis of apoptotic neurons (Fig 2). Pharmacological targeting of integrin α9 with macitentan significantly improved SAH outcomes, reduced neutrophil infiltration, BBB damage, neuronal apoptosis, and showed enhanced microglial efferocytosis (Fig 3).

Conclusions:
Our study uncovered a previously unrecognized role of neutrophil integrin α9 in microglial efferocytosis and post-SAH sensorimotor and cognitive recovery.
Abstract 114: Microglial IGSF6 Promotes Post-Stroke Neuroinflammation and Worsens Ischemic Brain Injury
Authors: Liu Pinyi , Zou Xinxin , Li Huiya , Li Qi , Xu Yun
Published: January 2025

Introduction:
Post-stroke neuroinflammation is a hallmark of ischemic stroke. This study investigates the role of IGSF6 in microglia during ischemic stroke and its contribution to neuroinflammatory responses and brain injury following stroke.

Methods:
IGSF6 expression was examined in murine microglia under various inflammatory stimuli. Using a middle cerebral artery occlusion (MCAO) model, we evaluated the impact of microglial
Igsf6
knockdown (
Igsf6
-KD) on neuroinflammation and ischemic outcomes. Pro-inflammatory cytokine levels were measured using qPCR and ELISA in both
Igsf6
-KD and wild-type (WT) mice, and functional outcomes were assessed through neurological tests. Subcellular localization and cytokine trafficking studies were conducted using immunofluorescence, electron microscopy, and protein interaction assays.

Results:
IGSF6 expression was significantly upregulated in microglia following MCAO. Knockdown of Igsf6 in microglia resulted in reduced secretion of pro-inflammatory cytokines (TNF, IL-6, CCL2, CCL5) at day 1 post-stroke, despite unchanged mRNA levels. Morphological analysis of microglia from
Igsf6
-KD mice revealed a less reactive phenotype. Additionally,
Igsf6
-KD mice exhibited a reduction in infarct volume and improved functional outcomes, including enhanced performance on rotarod, grip strength, and foot-fault tests.

Mechanistically, IGSF6 was shown to localize to the trans-Golgi network (TGN) and mediate cytokine trafficking. Knockdown of
Igsf6
disrupted this process, reducing the secretion of key cytokines without affecting their transcription or translation.

Conclusions:
Microglial IGSF6 exacerbates post-stroke neuroinflammation by promoting the secretion of pro-inflammatory cytokines. Its knockdown attenuates neuroinflammatory responses, reduces ischemic brain injury, and improves functional recovery. These findings highlight the detrimental role of IGSF6 in stroke pathology and suggest that targeting IGSF6 may offer therapeutic benefits for mitigating neuroinflammation and improving outcomes after ischemic stroke.
Abstract 116: Wallerian axon degeneration is required for chronic neuroinflammation and infarct-induced neurodegeneration
Authors: Wang Jack , Song Andrew , Buckwalter Marion
Published: January 2025

Background:
Ischemic stroke triggers a chronic B-lymphocyte response in the stroke core that is required for delayed post-stroke cognitive decline in mice. Because immune cells primarily infiltrate into connected subcortical axonal tracts after stroke, we hypothesized that degenerating axons promulgate a persistent neuroinflammation that is critical for late cognitive decline. To test this, we utilized mice deficient in Sarm1 (
Sarm1-/-),
a molecular trigger of axon degeneration and the loss of which leads to axonal protection after injury.

Methods:
Wildtype and
Sarm1-/-
male mice (N=9 per condition) underwent distal MCA stroke followed by transient hypoxia, which reliably leads to infarct-induced neurodegeneration 7 weeks after injury. Innate (monocytes) and adaptive (T, B lymphocytes) immune cell infiltration were evaluated via immunohistochemistry 1&7 weeks after stroke. Cognition was assessed using the Barnes maze at both time points after stroke.

Results:
Absence of
Sarm1
resulted in robust axonal protection after ischemic stroke. In connected thalamic region, mean immunostained intensity of axons was 166 in wildtype vs. 267 in
Sarm1-/-
(p < 0.005) 1 week, and 106 vs. 201 (p < 0.005) 7 weeks after stroke. Compared to wildtype mice,
Sarm1-/-
mice had an attenuated innate immune response in connected subcortical white matter 1 week after stroke (% area of CD68+ reactivity was 35 ± 5% in WT vs. 19 ± 4% in
Sarm1-/-
(p < 0.01), while peri-infarct CD68 was not different. Moreover, loss of
Sarm1
reduced B220+ B-cell infiltration into the infarct 7 weeks after stroke. Percent area of B220+ reactivity was 30 ± 8% in WT vs 15 ± 7% in
Sarm1-/-
(p <0.05). Compared to wildtype littermates,
Sarm1-/-
mice were resistant to chronic post-stroke cognitive decline on the Barnes maze. There was no difference in cognition between cohorts 1 week after stroke but there was at 7 weeks. The mean escape latency was 97 ± 11 sec in wildtype vs 57 ± 9 sec in
Sarm1-/
- mice (P<0.05).

Conclusion:
We report that
Sarm1
-mediated axonal degeneration is critical for chronic neuroinflammation and delayed cognitive decline after ischemic stroke. Directly targeting axon degeneration by modulating Sarm1 activity provides a novel therapeutic approach to ameliorate infarct-induced neurodegeneration.
Abstract 118: Long Term Outcomes in the CHARM Trial Evaluating Intravenous Glyburide for the Treatment of Large Hemispheric Infarction
Authors: Sheth Kevin , Molyneaux Bradley , Saver Jeffrey , Albers Greg , Campbell Bruce , Steiner Thorsten , Toyoda Kazunori , Wintermark Max , Nogueira Raul , Simard J Marc , Jacobson Sven , Cordonnier Charlotte , Hinson H.E. , Kimberly W Taylor
Published: January 2025

Introduction:
The phase III CHARM trial evaluated the safety and efficacy of intravenous glyburide as a treatment for large hemispheric infarction (LHI) patients at high risk for cerebral edema.

Hypothesis:
We aimed to determine whether subjects who were treated with IV glyburide would have better 12-month outcomes than those who received placebo in the CHARM trial.

Methods:
The source population included all CHARM subjects who were enrolled and treated with IV glyburide or placebo and had a recorded 12-month outcome. For those subjects missing a 12-month outcome, multiple imputation including baseline covariates and the 90-day modified Rankin Scale (mRS) was used. Shift analysis was performed on the 12-month mRS using 5 categories, where 0-1 and 5-6 were each collapsed into a single category. Independent variables included age, sex, baseline NIHSS, world region, tPA, and thrombectomy. Based on prior analysis, we also examined subjects with a baseline stroke volume ≤125 mL.

Results:
The cohort included a total of 431 subjects (mean age 58±9 years, 33% female, baseline NIHSS 19 (16-22), 40% received thrombolysis), the median 90-day mRS was 5 (4-6) and the median 12-month mRS was 5 (3-6). A total of 90 subjects (21%) had missing 12-month outcomes (n=38 in glyburide and n=52 in placebo). The correlation between 90d and 12mo mRS was r=0.93, p<0.0001. At 12 months, IV glyburide was not associated with better functional outcome (cOR 1.09, 95% CI 0.73-1.62, p=0.68) in the primary analytic population. However, among the subgroup of subjects with a baseline stroke volume ≤125 mL (n=118), the IV glyburide treatment arm had a favorable effect, cOR 2.26, 95% CI 1.06-4.78, p=0.034 (see figure). This effect was also present among those treated with endovascular thrombectomy at baseline (n=34, cOR 5.52, 95% CI 1.05-28.9, p=0.043).

Conclusions:
Long term outcomes in the CHARM trial suggests a potential for durable improvement in functional outcome in patients treated with IV glyburide among those with a baseline stroke volume ≤125 mL. Demonstration of clinical efficacy requires a dedicated trial focusing on this patient population.
Abstract 122: Radiology Nurse-Led Training: A Game Changer for After-Hours Stroke Care
Authors: Smith Hannah , Chun Jeff
Published: January 2025

Introduction:
Standardized stroke response protocols have been shown to reduce Door to Puncture (DTP) times for Acute Ischemic Strokes (AIS), potentially improving functional outcomes and reducing mortality. However, not all institutions can staff stroke-trained nurses 24/7. After-hours, these codes may be handled by staff less familiar with the process. To address increasing after-hours DTP times, radiology staff nurses designed and implemented an institution-specific, comprehensive educational stroke training program for all night shift ED nurses. The goal was to standardize stroke response and decrease DTP times during off-hours, ultimately improving patient care and outcomes in AIS cases.

Methods:
Radiology staff nurses developed and implemented a comprehensive AIS training program for night shift ED nurses. The program consisted of a tailored PowerPoint presentation, a 3-hour small group educational in-service, and hands-on time in the angiography suite. Training focused on practical, actionable steps, including early identification of large vessel occlusion, proper patient preparation, and expedited transport from CT to angiography. One to two in-service sessions were provided monthly over a three-year period. To date, 43 ED nurses have completed the training program.

Results:
Pre and post intervention DTP times were compared using Statistical Process Control (SPC) charts generated with data from June 2019 through December 2023 and a trend-line was applied. The year prior to project initiation (6/2019-6/2020), median DTP time was 69 minutes (trend line p-value 0.006). One year after project initiation (6/2021-12/2023), median DTP time dropped to 57 minutes (trend line p-value 0.028), a 12-minute decrease. This reduction time is equivalent to 22.8 million neurons saved and meets the National Stroke Standard goal of 60 minutes for DTP. The median time from "CT Complete" to "Patient in Angio" went from 20 minutes down to 5.

Conclusion:
Standardized stroke training is paramount, particularly for hospitals facing constraints in round-the-clock stroke nursing resources or regulatory requirements. Institution-specific stroke education, including familiarization of patient transport routes and angiography suite location, is essential to reduce delays in DTP time. Harnessing the expertise of radiology staff nurses to provide standardized stroke education is a pivotal strategy for hospitals to meet quality outcomes for comprehensive stroke care.
Abstract 124: Impact of Targeted Stroke Education: Zip Codes and Last Known Well
Authors: Peiris Iranthi , Guzik Amy , Johnson Leonard , Lycan Sarah
Published: January 2025

Background and Purpose:
Certified Comprehensive Stroke Centers (CSC) provide 2+ community education events per year. In hospitals with a large geographical referral area, targeted education is impactful given fixed financial support, limited staff and time resources.

We utilized Local Get With The Guidelines (GWTG) Stroke data and population health data to identify targeted community education.

Methods:
We analyzed 2023 stroke data to identify zip codes of patients with long Last Known Well (LKW) to arrival time. We analyzed the demographic and social determinants of health (SDOH) characteristics of zip codes and compared them to state demographics. Educational events were prioritized based on content impactful to the unique needs of each community.

Results:
Two zip codes (27101, 27105) had the longest LKW to arrival times. These zip codes have larger health disparities when analyzing demographic and SDOH characteristics.

In 2023, 4 community educational events were conducted including health fairs and educational events at libraries, churches, and the North Carolina Medication Assist Mobile Pharmacy. Increased signage, brochures, and magnets were distributed from our medical practices, free health clinic, and mobile health clinics providing care to uninsured in identified zip codes. Education was provided in both Spanish and English and focused on the signs and symptoms of stroke and activating 911.

After targeted education was completed in the targeted zip codes, there was an improvement in patients presenting within 3.5 hours of last known well.

Conclusions:
Local GWTG Zip code-based data is helpful to plan community education to address disparities in stroke metrics such as LKW to arrival time. Utilizing SDOH and population data can help guide community education to better fit the community in that area. Targeted, purposeful community education can improve LKW to arrival times in communities.

References

https://data.census.gov

Local Get With The Guidelines® (GWTG) – Stroke

“This work represents the authors’ independent analysis of local or multicenter data gathered using the AHA Get With The Guidelines® (GWTG) IQVIA Registry Platform but is not an analysis of the national GWTG dataset and does not represent findings from the AHA GWTG National Program."
Abstract 126: In-bed robot-guided ankle sensory-motor rehabilitation in early subacute stroke survivors: a preliminary clinical trial
Authors: Huang Mei , Zhang Chunyang , Xu Dali , Kehs Glenn , Braun Robynne , Cole John , Zhang Li-Qun
Published: January 2025

Introduction:
The most commonly observed motor impairment associated with stroke is the weakness of ankle muscles and stiffness of the ankle joint, which severely restricts gait and balance function and limits the performance of many activities of daily living. Stroke survivors have the most potential for motor recovery in their acute and subacute stages. An intensive in-bed robot-guided ankle training may aid in promoting motor recovery in early sub-acute stroke survivors. The purpose of the study was to investigate the feasibility and efficacy of in-bed robot-guided ankle movement training in early subacute stroke survivors.

Method:
This was a controlled trial. The initial 8 patients were assigned to the study group and the rest patients were randomized to the study and control groups. In total, 44 stroke survivors at the early subacute stage were assigned to either a study group (n=26) or a control group (n=18) during their hospital stay. Individuals in the study group received 45-minutes of in-bed robot-guided ankle movement training, including passive stretching and game-based active movement training; while the control group used the same ankle robot and received passive ankle movement in the mid-range of motion and attempted active ankle movement without robotic assistance. Biomechanical and clinical outcome measures were obtained before and after the intervention.

Results:
After the training (sessions: 11.3 ± 4.2 sessions), the study group had a significantly larger increase in ankle active range of motion (p=0.002, eta
2
=0.213), maximal voluntary contraction in plantar flexion (p=0.016,eta
2
=0.131) and dorsiflexion (p=0.035,eta
2
=0.102), compared with the control group. Patients in both groups showed a significant increase in Fugl-Meyer assessment lower limb motor score (p<0.001, eta
2
=0.560), Berg Balance Scale (p<0.001, eta
2
=0.503), and a decrease in Modified Ashworth Scale in plantar flexors (p<0.001, eta
2
=0.291), without significant group differences.

Conclusions:
In-bed robot-guided ankle training is feasible in patients at the early subacute stage. The robotic training including passive stretching and active movement helped the recovery of ankle voluntary muscle contraction and active range of motion. Incorporating an early in-bed robotic ankle rehabilitation is a feasible intervention technique that may help facilitate the ankle volitional control.
Abstract 129: The evolution of focal cerebral arteriopathy (FCA) treatment and outcomes from 2010 to 2022: results of the VIPS studies
Authors: Fullerton Heather , Hills Nancy , Stence Nicholas , Wintermark Max
Published: January 2025

Background:
The most common cause of arterial ischemic stroke (AIS) in previously healthy children, focal cerebral arteriopathy (FCA) can progress rapidly over days with worsening brain injury. A 2017 retrospective study of corticosteroid treatment for FCA changed practice at many pediatric stroke centers. To assess its impact, we compared FCA treatment rates and outcomes in FCA cohorts from the two Vascular effects of Infection in Pediatric Stroke studies.

Methods:
The (VIPS II) study prospectively enrolled and centrally confirmed 205 children (29 days to 18 years) with AIS at 22 centers (North America, Australia), 12/2016-1/2022. Study neuroradiologist (M.W.) and pediatric vascular neurologist (H.J.F.) independently reviewed all baseline and follow-up brain and vascular imaging and clinical data to classify the AIS etiology using published definitions from the original VIPS I study and confirm recurrent strokes; disagreements were resolved through discussion. M.W. measured the FCA Severity Score (FCASS); higher scores reflect more severe disease. We compared the FCA patients in VIPS II to those in VIPS I (2010-2014), the prospective cohort study with similar methods.

Results:
Of 75 children with definite arteriopathy enrolled in VIPS II, 43% had FCA, compared to 32% of 127 definite arteriopathy cases in VIPS I (Table). Treatment changed dramatically between the two studies, with 56% of VIPS II FCA cases receiving IV corticosteroids, compared to only 5% of FCA cases in VIPS I. The use of anticoagulation declined in favor of antiplatelets. Compared to VIPS I, the VIPS II FCA cases were more severe at baseline (median FCASS 6 versus 4; p=0.006). Among cases with short-term follow-up imaging, the increase in FCASS was not significantly different: median + 2 points in VIPS II (n=24) and +3 in VIPS I (n=33; p=0.76). The 12-month neurological outcomes were similar.

Conclusions:
Treatment of FCA with corticosteroids increased dramatically between the VIPS I and VIPS II studies, reflecting a major shift in clinical practice on the basis of modest evidence. VIPS II cases were more severe at baseline, but we observed no significant difference in disease progression or neurological outcomes. Pediatric stroke centers should enroll FCA patients into ongoing FCA corticosteroid treatment trials—PASTA in Europe and Australia and FOCAS in North America—that will provide rigorous data regarding the effectiveness and safety of this intervention.
Abstract 132: Transcriptomic Profiling of Vein of Galen Malformations Implicates a VEGFR-Mediated Non-coding RNA Signature of Angiogenesis
Authors: Devarajan Alex , Seah Carina , Philbrick Brandon , Bazil Maximilian , Bonet Jessica , Sorscher Michelle , Richter Felix , Kellner Christopher , Berenstein Alejandro , Shigematsu Tomoyoshi , Fifi Johanna
Published: January 2025

Introduction:
Vein of Galen malformations (VOGM) are challenging congenital arteriovenous malformations (AVMs) to treat. During management, for unknown reasons, VOGM may develop fine angiogenic networks of feeding vessels within subarachnoid spaces. This is associated with increased symptom burden and complicates treatment. Here, we temporally characterized the evolution of VOGM during endovascular therapy to investigate changes in gene expression associated with onset and cessation of angiogenesis.

Methods:
Whole blood was prospectively collected from femoral access (peripheral) and catheterized intracranial feeding vessels (intralesional) during endovascular embolization of 4 angiogenic and 4 non-angiogenic patients for management of VOGM. Patients were grouped by development of extra-axial angiogenesis during treatment. If angiogenesis developed, whole blood was collected upon onset and cessation of angiogenesis as determined by serial cerebral angiograms. RNA sequencing of 15,730 genes from 23 samples after quality-control was aligned, normalized, and residualized using Rsubread, sva, and limma/voom. Differentially expressed genes were identified between actively angiogenic, formerly angiogenic, and non-angiogenic patients. Gene set enrichment analysis (GSEA) was conducted using Gene Ontology biological processes and cellular components.

Results:
677 genes (349 upregulated, 328 downregulated) were significantly associated with actively angiogenic VOGM versus formerly angiogenic VOGM. These included VEGFR and VEGFR-mediated genes associated with hypoxia-induced angiogenesis (e.g. FLT1, DAAM2), angiogenic non-coding RNAs (ncRNA) (e.g. SBF2-AS1, RP11-430C1.1, ANKRD20A4), and markers suggestive of neurological symptom burden (e.g. MT1F, FAM171B). GSEA highlighted enrichments in aerobic respiration pathways and ncRNA processing. 1349 genes (673 upregulated, 676 downregulated) were differentially expressed in actively angiogenic versus non-angiogenic VOGM with hypoxic and angiogenic roles (e.g. PDC). 274 genes (192 upregulated, 82 downregulated) were expressed in formerly angiogenic versus non-angiogenic VOGM, comprised of pro-coagulation and antiproliferative genes (e.g. PROS1, PROSER2).

Conclusion:
Angiogenesis in VOGM is mechanistically driven by local hypoxia-induced VEGFR-mediated responses. VOGMs transiently express an angiogenic ncRNA signature during active angiogenesis, which switches to a pro-coagulatory profile as the VOGM is progressively treated.
Abstract 133: Asymmetry of Arteriopathy in Pediatric Moyamoya
Authors: Xu Lori , Barry Dwight , Amlie-Lefond Catherine
Published: January 2025

Introduction:
Moyamoya is a progressive steno-occlusive cerebrovascular arteriopathy of bilateral anterior circulation. The pathophysiology is elusive, and once established, moyamoya is typically inexorably progressive.

Hypothesis:
We hypothesized that the left-sided circulation is more vulnerable to steno-occlusive arteriopathy compared to the right, which may reflect differences in mechanical stress from blood flow.

Methods:
All children with moyamoya cared for between 1/1/2009 and 7/1/2024 at a single institution were identified through an IRB-approved, retrospective study. The charts and neuroimaging at the time of diagnosis were reviewed to assess symmetry of steno-occlusion. Chi-square test was used for statistical analysis, with p-value <0.05 considered statistically significant.

Results:
A total of 67 children (35 males) with moyamoya were identified. Steno-occlusive arteriopathy at diagnosis was assessed on head and neck MRA for all 67, as well as on cerebral catheter angiogram in the 32 patients who underwent interventional neuroimaging. Arteriopathy was more severe on the left than the right in 29 (43%), and more severe on the right than the left in 15 (22%). This left-sided predilection was statistically significant (p=0.03). Twenty-three (34%) children had complete occlusion of bilateral anterior circulation without asymmetry at diagnosis. Of the 38 (57% of the total) patients with clinical stroke at the time of presentation, 21 (55%) had right hemiplegia, 10 (26%) had left hemiplegia, and 7 (18%) presented without focal weakness.

Conclusions:
Moyamoya is an important cause of childhood stroke, and a risk factor for recurrent ischemic and hemorrhagic stroke throughout life. The mechanism of arteriopathy initiation and progression is unknown, and current treatment consists of palliative revascularization. The left predominance of arteriopathy with moyamoya may provide insight into underlying causes of moyamoya arteriopathy. A better understanding of moyamoya pathophysiology may also inform interventions to halt the progression of steno-occlusive arteriopathy once it has begun.
Abstract 135: Carotid Artery Tortuosity and Incidence of Ischemic Stroke: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Jiang Chao , Caughey Melissa , Xu Ziyang , Guan Yueyi , Sun Eric , Wasserman Bruce , Qiao Ye
Published: January 2025

Introduction:
Carotid artery tortuosity, characterized by abnormal vessel twisting, has been reported to be associated with various vascular pathologies and the presence of stroke. We aimed to evaluate the association between carotid artery tortuosity and the incidence of ischemic stroke.

Methods:
We analyzed 3D contrast-enhanced MRA datasets from 2,066 participants enrolled in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study. Of these, 368 were excluded due to prevalent stroke, missing covariates, or missing/uninterpretable contrast-enhanced MRA data. Tortuosity was qualitatively evaluated using the Weibel method
1
, categorized into three types (tortuosity, kinking, and coiling), and quantitatively measured using LAVA software as distance and angle metrics (Figure 1)
2
. The association between carotid tortuosity, a time-dependent exposure variable, and incident ischemic stroke was evaluated using Cox regression models adjusted for demographic and cardiovascular risk factors.

Results:
Among the 1,698 participants (71.51±0.44 years, 51.7% women; 22.1% Black), 135 had an ischemic stroke over a median follow-up of 8.6 years. The Kaplan-Meier plot demonstrated that the coiling type was associated with an increased rate of stroke compared to other groups (Figure 2). Tortuosity metrics validated the significant difference between two groups (mean distance matrix tortuosity: 1.66 ± 0.31 for coiling vs. 1.21 ± 0.18 for non-coiling, p<0.001). Cox regression analysis showed that the presence of carotid artery coiling was associated with a 2.5-fold increased risk of ischemic stroke (95% CI, 1.08-5.61) compared to those without coiling, after adjusting for age, sex, race and cardiovascular risk factors (smoking, hypertension, diabetes mellitus, and statin use).

Conclusion:
Carotid artery tortuosity (i.e., coiling) is associated with incidence ischemic stroke, suggesting its potential as an imaging morphological marker for predicting future cerebrovascular events.

References:

1. Weibel J, et. al, . Neurology. 1965 Jan;15:7-18.

2. Zhou S, et.al,. J Magn Reson Imaging. 2024;59(5):1612-1619.
Abstract 136: Infarct Topography, Effect of Anticoagulation, and Recurrence after Cryptogenic Stroke: A Subgroup Analysis of the ARCADIA Trial
Authors: Karunamuni Nilushi , Gologorsky Rachel , Longstreth W , Tirschwell David , Elkind Mitchell , Kamel Hooman
Published: January 2025

Introduction:
The ARCADIA trial found no benefit of anticoagulation for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. The trial screened all patients with cryptogenic stroke, regardless of infarct topography. Acute brain infarction in multiple arterial territories could more strongly suggest a central embolic source. The recurrent stroke risk and role of apixaban versus aspirin in these patients is not well understood.

Hypothesis:
Cryptogenic stroke patients with multi-territory infarction are at increased risk for recurrent stroke, and this population will benefit from treatment with apixaban compared to aspirin.

Methods:
The ARCADIA trial screened patients with cryptogenic stroke for atrial cardiopathy at 185 centers in the U.S. and Canada. Among participants who met eligibility criteria for atrial cardiopathy and were randomly assigned to treatment assignment, we performed a subgroup analysis of those with multi-territory infarction, defined as acute infarction in at least two of the following territories: left anterior circulation, right anterior circulation, or posterior circulation. Cox models were used to compare stroke recurrence in patients with multi-territory versus single-territory infarction. Models were adjusted for age, sex, race, ethnicity, heart failure, coronary artery disease, peripheral artery disease, hypertension, diabetes, and tobacco use. We used tests of interaction to compare the effect of apixaban versus aspirin in patients in multi- versus single-territory infarcts.

Results:
Of 1,015 randomized patients in ARCADIA, 123 had multi-territory infarction, of whom 55 (44.7%) received apixaban and 68 (55.3%) received aspirin. Risk of recurrent stroke was higher in patients who presented with multi-territory infarcts (HR 2.5, 95% CI 1.50-4.18). When adjusting for demographics and vascular risk factors, results were similar (HR 2.5, 95% CI 1.48-4.15). There was a similar lack of benefit of apixaban in patients with multi-territory infarct (HR 1.0, 95% CI 0.62-1.71) versus single-territory infarct (HR 1.0, 95% CI 0.43-2.51) (
P
for interaction = 0.98).

Conclusion:
In patients with cryptogenic stroke and markers of atrial cardiopathy, multi-territory infarction was associated with an increased risk of recurrent stroke, but this population did not benefit from anticoagulation compared to aspirin.