bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP289: Cytochrome P450 2C19 genotypes and the efficacy of clopidogrel in non-diabetic patients with ischemic stroke
Authors: Jung Yo Han , sung minsoo , Lee Kyung-Yul
Published: January 2025

Background:
The ABCD-GENE score, incorporating age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genotypes, is a validated risk score that integrates clinical risk factors with genetic information to predict clopidogrel response. However, to enhance the accuracy of risk identification, it is essential to assess the individual impact of each clinical risk factor. Notably, diabetes has been linked to the modulation of clopidogrel’s antiplatelet efficacy by CYP2C19 genotypes. Therefore, excluding the confounding effect of diabetes may refine the precision of identifying at-risk patients by isolating the interaction between CYP2C19 genotypes and clinical outcomes.

Method:
This study is a post-hoc analysis of the PLATELET trial (A Multicenter Prospective Observational Study to Evaluate the Effect of Clopidogrel on the Prevention of Major Vascular Events According to the Genotype of Cytochrome P450 2C19 in Ischemic Stroke Patients, NCT04072705). Patients were stratified based on CYP2C19 genotyping into carriers and non-carriers of the loss-of-function CYP2C19 allele. Clopidogrel therapy was continued throughout the study period. The primary efficacy endpoint was the incidence of cardiovascular events (including ischemic or hemorrhagic stroke, myocardial infarction, or cardiovascular death) within six months following an ischemic stroke in carriers versus non-carriers of the loss-of-function CYP2C19 allele. The primary safety endpoints were all-cause mortality and the incidence of major bleeding events.

Results:
Out of the 2,925 patients enrolled in the PLATELET trial across 37 clinical sites, 2,001 non-diabetic patients were included in this analysis. The mean age of the participants was 64.4 years, with 65.0% being male. Among these patients, 61.5% were identified as carriers and 38.5% as non-carriers of the loss-of-function CYP2C19 allele. The primary efficacy outcome occurred more frequently in carriers than in non-carriers (2.5% [31 of 1,230] vs 1.2% [9 of 771], log-rank p-value = 0.038). There were no significant differences between the two groups in terms of major bleeding or all-cause mortality (p = 0.760 and p = 0.667, respectively).

Conclusions:
In non-diabetic patients with acute ischemic stroke treated with clopidogrel, those carrying the loss-of-function CYP2C19 genotype exhibited a higher risk of cardiovascular events compared to non-carriers.
Abstract WP294: Racial Disparities among the risk of Stroke and other clinical outcomes post Infective Endocarditis: A Propensity Matched Analysis
Authors: Jaiswal Vikash , Hanif Muhammad , Latif Fakhar , Jaiswal Akash , Zomkowska Edyta , Sundas FNU , Rajak Kripa , Patel Nirmit , Iqbal Rabia , Shah Viraj , Biswas Monodeep , Daggubati Ramesh
Published: January 2025

Background:
Racial disparities have been well described in cardiovascular disease. However, the impact of race on the risk of stroke among infective endocarditis (IE) patients is not well understood.

Objective:
This study aims to investigate the racial disparities in the risk of stroke and clinical outcomes among IE patients.

Method:
The TriNeTX Global Collaborative Network database was used to identify patients aged ≥18 years of age from January 2000 to May 2023 which included IE patients. Patients were categorized into two groups, one with Black or African American and another with White race patients. Both groups were followed for 12 months. Propensity score-matched analysis (PSM) (1:1) was performed on age, gender, BMI, hypertension, diabetes mellitus, chronic kidney disease, hemoglobin level, LDL level, left ventricular ejection fraction and various drugs including beta blockers, ACEi and ARBi. Primary outcome was ischemic stroke, while secondary outcomes were all-cause mortality, heart failure, cardiogenic shock, MACE (composite of all-cause mortality, heart failure, and ischemic stroke), and acute kidney injury (AKI).

Result:
After 1:1 propensity score matching, the study cohort comprised 9, 814 Black patients and 9, 814 White patients. The mean age of patients was comparable between both groups (59.8 and 63.1 years). IE patients were having a comparable risk of ischemic stroke among both the races after 1 month (RR, 1.17 (95% CI: 0.96-1.42), P = 0.11), however, the risk of ischemic stroke was significantly higher among Black patients after 1 year (RR, 1.18 (95% CI:1.02-1.36), P = 0.024) when compared with White patients. Black patients were having a significantly higher risk of all-cause mortality after one month (RR, 0.818 (95% CI: 0.74-0.89), P<0.001), and after 1 year (RR, 0.91 (95% CI: 0.86-0.96), P = 0.001) when compared with White patients. However, the risk of heart failure, cardiogenic shock, MACE, and AKI was found to be comparable between Black and White patients of IE after 1 month and 1 year follow up.

Conclusion:
These findings suggest that Black patients with infective endocarditis were having a higher a long term risk of stroke and mortality.
Abstract WP305: Childhood Trauma Exposure, Loneliness, Mental Health, and Stroke Recovery: Findings From The STRONG Study
Authors: Holman Alison , Shahbaba Ryan , Cai Hengrui , Poe Jaeden , Egharevba Faithful , Cramer Steven
Published: January 2025

Introduction:
Childhood trauma exposure (CTE) is a known risk factor for poor adult mental&physical health, higher mortality, and disability. Understanding the psychosocial mechanisms by which CTE affects functional outcomes could help identify intervention targets to improve outcomes after stroke. We examine post-stroke mental health and loneliness as potential mediators of the association between CTE and functional/cognitive disability at 1-year post-stroke.

Methods:
Adults with a new stroke enrolled in the STRONG (
S
troke, s
T
ress,
R
ehabilitati
ON
, and
G
enetics) study at 28 US sites and were assessed 4 times over 1 year. Assessments included CTE, mental health (depression, anxiety, PTSD), and loneliness 90 days post-stroke, and Stroke Impact Scale (SIS), modified Rankin Scale (mRS),&Telephone Montreal Cognitive Assessment (tMoCA) 1-year post-stroke. Analyses examined 90-d mental health and loneliness as mediators of the link between CTE and 1-year outcomes.

Results:
The 763 enrollees had age 63.1±14.9 years; initial NIHSS score 4 [2-9]; 41.2% Female; 69.4% White. Complete case (N=332) analysis revealed that controlling for age, gender, race, and acute NIHSS score, CTE was not directly associated with any 1-year functional outcome but was significantly associated with loneliness and mental health symptoms 3-months post-stroke. However, greater CTE was indirectly and significantly linked to worse 1-year mRS and SIS scores through 3-mo loneliness, and to worse 1-year mRS, SIS, and tMOCA scores through 3-mo mental health symptoms.

Conclusions:
Mental health and loneliness are pathways through which CTE is linked to post-stroke functional outcomes. Addressing mental health symptoms and loneliness early post-stroke may support improved functional outcome 1-year post-stroke in patients who have experienced CTE.
Abstract WP313: Associations of Extreme Precipitation and Cerebrovascular Disease Mortality Events Among Older Adults in California
Authors: Majeed Haris , Zuberi Daniyal
Published: January 2025

Introduction:
In mid- to high-latitude regions, cerebrovascular diseases (CBVD) are known to peak during the winter. Aside from traditional clinical risk factors, emerging research has documented the associations between extreme seasonal climate conditions and CBVD, especially among older male and females who are vulnerable to such environments. Despite the growing climate-cerebrovascular literature, there is still a need to understand seasonal- and sex-specific associations between extreme precipitation and CBVD events among older adults. We hypothesize that extreme precipitation will increase the risk of cerebrovascular events in winter and summer for both older and male and females.

Methods:
This population-based study utilizes CDC county data for CBVD deaths [ICD-10 (I60-69)] among older (≥65 years) male and females in California (N=28 counties) from January 2016 to December 2020. Covariates of diabetes, smoking, obesity, excessive drinking, uninsured prevalence, household income, and college education attainment were also obtained. Precipitation was classified as; extreme (>90
th
percentile: >4.9 inches), moderate (10-90
th
percentile: 1-4 inches), and low (≤10
th
percentile: ≤1 inch). With population estimates, CBVD mortality rates were associated with precipitation categories by sex and season [winter (December-May) and summer (June-November)] using negative binomial regression with autocorrelation upon adjusting for covariates. Model estimated parameters were interpreted as a rate ratio (RR).

Results:
From 2016-2020; 59,360 (61.8% females; 52.6% in winter) CBVD deaths were recorded. Extreme (compared to low) precipitation was associated with increased risk of CBVD mortality rates for males only during the summer [adjusted RR 1.45 (95% CI 1.08-1.95)], not winter (Figure). Whereas extreme precipitation was associated with increased risk of CBVD mortality rates for females only during the winter [1.08 (95% CI 1.01-1.15)]. Significant interactions were observed between precipitation and maximum temperatures.

Conclusion:
Extreme precipitation was associated with increased risk of CBVD deaths among older males and females, where the effects differed by season. Seasonality and climate factors can be considered predisposing risk factors for cerebrovascular disease. Further studies are needed to assess such risks for other areas in the United States.
Abstract WP315: Effects of Alcohol Use on Cerebral Small Vessel Disease and Intracerebral Hemorrhage
Authors: Hindsholm Mette , Das Alvin , Rotschild Ofer , Gokcal Elif , Steven greenberg , Rosand Jonathan , Goldstein Joshua , Gurol Edip
Published: January 2025

Objective:
We sought to investigate the consequences of alcohol intake on intracerebral hemorrhage (ICH) and cerebral small vessel disease (cSVD) in patients with spontaneous ICH.

Methods:
We compared markers of cSVD [Figure 1], features of ICH, and outcomes among consecutive spontaneous ICH patients with different alcohol use strata admitted to a tertiary care center between 2003-2019. Alcohol intake was categorized as none/mild (<5 drinks/week), moderate/severe (5 drinks/week-5 drinks/day), and heavy (>5 drinks/day). We performed descriptive statistics and bivariate/multivariate analyses based on demographic and radiologic data.

Results:
We included 1590 patients (53% male, median age 74 years [IQR 64-82]). Among them, 82.6% had none/mild alcohol intake, 14.2% moderate/severe, and 3.3% heavy alcohol intake. Heavy alcohol users were 13 years younger at time of ICH than none/mild users (median [IQR], 62 [57-70] vs 75 [65-83], p<0.0001). Heavy alcohol users were more likely to have deep ICHs (60% vs 45%, p=0.037), larger median ICH volumes (30 vs 15mL, p=0.025), and lower platelet counts (195/µL vs 225/µL, p=0.049). MRI analysis showed that heavy alcohol users had similar degree of cSVD as none/mild users, even though they were much younger. In separate regression models heavy alcohol use was independently associated with younger age at the time of ICH (p=0.004) and higher ICH volume (p=0.007). There was no significant difference in in-hospital mortality between the two groups (31% vs 42%, p=0.1).

The moderate/severe users were 5 years younger at the time of ICH compared to none/mild alcohol users (p<0.0001). There was no significant difference in ICH location, volume, or platelet counts between the groups. In-hospital mortality was lower in the moderate/severe group (23% vs 42%, p<0.0001). None/mild alcohol use was independently associated with more severe leukoaraiosis (p<0.0001) and higher case fatality (p<0.0001) compared to moderate/severe use in separate multivariable models.

Conclusion:
Heavy alcohol use is strongly associated with an earlier ICH risk (median age difference of 13 years) and larger ICH volumes compared to none/mild alcohol use, relationships that might be explained by alcohol-related hypocoagulable state. Despite being much younger, heavy drinkers have similar cSVD burden compared to none/mild users. Moderate/severe alcohol consumption did not display clear negative effects on ICH- or cSVD-related characteristics or short-term outcomes.
Abstract WP350: Microglial-derived Ifi27l2a acts as a novel cytokine and contributes to brain inflammation
Authors: Kim Sodam , Burrous Haven , Vance Lauren , Jung Joo Eun , Blixt Frank , McCullough Louise , Marrelli Sean , Kim Gab Seok
Published: January 2025

Proinflammatory cytokines significantly contribute to the initiation and propagation of inflammation and to impaired functional recovery in neuroinflammatory diseases. We identified that microglia express and secrete interferon alpha-inducible protein 27 like 2A (Ifi27l2a) in response to inflammatory signals. However, the functional role of Ifi27l2a in inflammation has not been well defined. Through a combination of cell culture and
in vivo
mouse models, we now demonstrate that Ifi27l2a acts as a novel hub protein that regulates proinflammatory responses in microglia.

Methods:
Endotoxemia was induced by LPS administration in aged mice to determine the subsequent circulating Ifi27l2a protein levels in the plasma. Sim-A9 cells and primary microglia were stimulated with recombinant Ifi27l2a (rIfi27l2a) at concentrations of 10 and 100 ng/ml to investigate whether Ifi27l2a promotes mitochondrial dysfunction and conversion of microglial phenotype. RNA-seq was performed on primary microglia to define transcriptional changes induced by Ifi27l2a as well as alterations in cellular signaling associated with proinflammatory microglia.

Results:
Systemic injection of LPS increased circulating Ifi27l2a protein levels in the plasma of aged mice (
Veh:
38.1,
LPS:
122.1 pg/ml, n=4-5, p<0.05). To investigate how exogenous Ifi27l2a modulates microglial phenotypic changes, we treated microglia to rIfi27l2a. Reactive oxygen species (ROS) levels were elevated by rIfi27l2a treatment in both Sim-A9 and primary microglia (n=6-8, p<0.05). Notably, treatment with rIfi27l2a increased the ATP production, which LPS did not, as assessed by Seahorse cell analysis (n=10-21, p<0.05). In addition, inflammation marker genes (
Il1b
,
Tnfa
, and
Mmp9
) were significantly elevated in rIfi27l2a-treated microglia compared to the control. Transcriptional analysis of rIfi27l2a treatment with RNA-seq (n=5) revealed that a set of proinflammatory genes, including
Mmps
, were highly upregulated. The data also showed that microglial phagocytosis-related genes and disease-associated microglia (DAM)-related genes were suppressed by rIfi27l2a.

Conclusions:
These data suggest a novel role for Ifi27l2a in brain inflammation through the shifting of microglia toward a proinflammatory phenotype and away from the reparative DAM phenotype. We propose that selective disruption of Ifi27l2a signaling may provide a new therapeutic strategy to reduce harmful inflammation and improve functional outcome following stroke.
Abstract WP355: Long wavelength light exposure reduces ischemic stroke brain injury through reduced platelet function
Authors: Denorme Frederik , Andraska Elizabeth , Kaltenmeier Christof , Arivudainambi Aishwarrya , Dyer Mitchell , Rosengart Matthew , Neal Matthew , Campbell Robert
Published: January 2025

Introduction:
Variations in light exposure are associated with changes in inflammation. The risk of thrombotic events such as ischemic stroke have been found to oscillate with the day-light cycle.

Aim:
To investigate the impact of altering the light spectrum on ischemic stroke brain injury.

Methods:
Mice were exposed to ambient (mice-white, 300lux), red light (mice-red, 617nm) or blue light (mice-blue, 442 nm) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, male and female mice were subjected to transient middle cerebral artery occlusion. Stroke outcomes were assessed at 24 hours.

Results:
Exposure to long wavelength red light resulted in a significant reduction in infarct volume following stroke (mice-red 38.8±17.6 mm3 vs. mice-white 73.3±15.0 mm3; p<0.01 vs mice-blue 72.9±27.9 mm3; p<0.001). Red light exposure significantly improved neurological function compared to white and blue light exposure based on a modified Neurological Score (p<0.05). Furthermore, red light significantly improved motor function as measured by a reduced latency to turn and fall on a rotarod (p<0.05). The change in thrombosis only occurred when mice were pre-exposed to red light. Furthermore, red light had no effect on thrombosis in blind Vsx2
orJ
/J mice. Red light exposure reduced platelet deposition in the brain while neutrophil levels were similar between light exposure groups. However, neutrophil extracellular traps (NETs) were significantly reduced (p<0.05) after ischemic stroke brain injury in mice exposued to red light. As platelets are known to activate neutrophils during ischemic stroke, we assessed the effect of red light on platelet function. Red light exposure reduced platelet aggregation (p=.02) and activation (p=.02). RNA-seq analysis demonstrated little transcriptomic changes between light exposed mice. However, red light exposure altered the platelet metabolome, suggesting red light altered platelet metabolism to effect platelet function. To examine if red light reduced platelet-dependent NET formation, releasate from activated platelets were incubated with neutrophils. Releasate from red light exposure platelets resulted in reduced NET formation (p=.03).

Conclusion:
Exposure to long wavelength red light reduced ischemic stroke burden through a reduction in platelet-dependent NET formation. Light exposure modulation is a promising alternative for prophylaxis and treatment from ischemic stroke brain injury.
Abstract WP356: Use of MicroRNA as a Prospective Biomarker for Post-Stroke Socially Isolated Patients
Authors: Baskin Lynae , Couture Lucy , Banerjee Anik , Delevati Colpo Gabriela , Lee Juneyoung
Published: January 2025

Introduction:
Blood-based biomarker investigations for neurological diseases such as ischemic stroke are commonly used in clinical practice and traditionally have focused on measuring alterations in cytokine quantity and composition. An emerging area has been the use of microRNA studying the effects of gene expression after ischemic stroke. There has been extensive evidence that gene expression changes after ischemic injury, especially in gene pathways related to inflammatory response, vascular injury, and cellular degeneration. Establishing a reliable blood-based biomarker used to quantify clinical indications is necessary for emergent treatment. With a blood-based assessment that utilizes transcriptomics, healthcare providers can better understand post-stroke molecular changes more rapidly, which is crucial during this acute phase.

Methods:
Peripheral blood samples were collected from ischemic stroke patients (N=100) during the acute onset of disease, 24 hours after the last known well. In this study, we investigated possible differences among the stroke population based on risk factors including age, sex, race, social isolation status, and presence of cognitive impairment. For this analysis, overall social isolation status was defined by a mixed model matrix comprised of Lubben Social Network score and UCLA Loneliness score. We used whole transcriptomic sequencing to assess these variables.

Results:
Overall, there were 8 miRNA sequences significantly upregulated in socially isolated patients. There were no significant differences found among patients based on sex or age variability. Interestingly, we found that circulatory miR-24-3p (FDR adjusted p-value <0.05) was significantly upregulated in post-stroke socially isolated patients and post-stroke socially isolated mice. Other candidates such as miR-143-3p, miR-629-5p, miR-223-5p, and miR-331-3p showed significantly different expressions among this cohort.

Conclusion:
Our results show there is a significant difference in circulatory miRNA signature among SI and non-SI patients. The clinical translation of this identified upregulation among this vulnerable population must be explored further to characterize the nature of these changes in gene expression. These results can be utilized in the future as a reliable biomarker of SI status. Future studies using these results should be translated into mice models to understand the biomolecular mechanisms behind SI-induced changes within microRNA signatures.
Abstract WP367: Attenuating Post-stroke Ischemia Reperfusion Injury: Establishing the Efficacy of Disodium Malonate in a Clinically Relevant Sheep Model
Authors: Sorby-Adams Annabel , Sharkey Jessica , Prag Hiran , Turner Renee , Skein Keziah , Guglietti Bianca , Pullan Caitlin , Williams Georgia , Krieg Thomas , Murphy Mike
Published: January 2025

Introduction:
Ischemia reperfusion injury (IRI) is a paradoxical and deleterious consequence of current interventions for acute ischemic stroke (AIS). Rapid restoration of oxygen to brain tissue upon reperfusion initiates mitochondrial reverse electron transport (RET) and production of reactive oxygen species (ROS), which exacerbate cell death. A pivotal role of the citric acid cycle intermediate succinate has been identified in driving RET post-reperfusion, whereby succinate accumulated during ischemia is rapidly reoxidized following reperfusion leading to a burst of ROS. Disodium malonate (DSM), a competitive inhibitor of succinate dehydrogenase, has been shown to attenuate RET ROS production following reperfusion and reduce infarct volume in rodent models. Here, we sought to evaluate the effect of DSM on infarct evolution post-reperfusion in a clinically-relevant sheep model of AIS for enhanced clinical translation.

Methods:
Male Merino sheep (N=13, 24-36 months, 62±6 kgs) underwent right pterional craniotomy and middle cerebral artery occlusion (MCAo) via aneurysm clip application for 4 hrs followed by reperfusion. Animals were pre-operatively randomized into vehicle (0.9% saline, N=5), medium dose DSM (0.5 mmole/min; N=4) and high dose DSM (1.0 mmole/min; N=4). Treatment was administered via right common carotid catheter at a rate of 15 mL/min for 10 min, starting 5 min prior to reperfusion. MCAo and reperfusion were confirmed on digital subtraction angiography (DSA). One hour following reperfusion, animals underwent magnetic resonance imaging (MRI) with a follow-up MRI performed 6 hours later. Infarct volume was calculated on diffusion weighted imaging (DWI) at each time-point to assess ischemic evolution.

Results:
All animals displayed evidence of MCAo and successful reperfusion following aneurysm clip removal (Figure 1). Infarct volume between groups was comparable at 1 hr post reperfusion (P>0.05), however, by 6 hrs infarct expansion was attenuated in animals receiving DSM compared with vehicles (P=0.0037). This was apparent in both the medium (P=0.006) and high (P=0.011) DSM groups.

Conclusions:
Intraarterial DSM administration reduces infarct expansion following reperfusion in a sheep model of MCAo. Evaluation of treatment efficacy in a larger cohort of animals is essential to address stroke therapeutic and industry roundtable (STAIR) guidelines and provide evidence to progress DSM to clinical trial for the treatment of IRI in AIS.
Abstract WP371: Cranial bone marrow-derived polymorphonuclear neutrophils comprise a small fraction of infiltrating leukocytes within the ischemic cortex following ischemia/reperfusion injury.
Authors: Batra Ayush , Arias Erika , Lipfert Zoie , Muller William , Sullivan David
Published: January 2025

Introduction:
The cranial bone marrow has been recognized as a potential reservoir for myeloid cells, capable of entering the cerebral cortex through direct channels connecting the skull and cortical surface of the brain. The significance of cranial bone marrow-derived leukocytes following ischemic stroke in the setting of ischemia/reperfusion remains uncertain. We sought to characterize the fraction of cranial bone marrow-derived leukocytes entering the ischemic cortex following ischemia/reperfusion injury using a murine transient middle cerebral artery occlusion (tMCAO) model.

Methods:
C57BL/6 LysM-GFP (green neutrophils and monocytes) mice underwent gamma irradiation with and without head shielding prior to adoptive transfer of bone marrow harvested from heterozygous
CatchUp
mice (Ly6G-tdTomato, red neutrophils). As a result, the exact percentages of cranial- and peripheral-derived neutrophils could easily be quantified and tracked, both in circulation and in the post-mortem brain. Mice underwent 90 min tMCAO with peripheral blood collection prior to and at 24 hours following ischemia/reperfusion. The relative fractions of green and red fluorescent Lys6G+ neutrophils post tMCAO in the brain were compared to the blood using flow cytometry and wide field fluorescence microscopy.

Results:
The ratio of red and green Ly6G+ neutrophils in the brain most closely matched the ratio of circulating red and green neutrophils and was not particularly enriched in GFP+ neutrophils. The distribution of red and green cells in brain tissue was nearly identical and did not show an enrichment of either blood-derived or cranial bone marrow-derived cells in any particular region following tMCAO at 24 hours.

Conclusions:
Together these data suggest that the majority of neutrophils entering the brain at 24 hours following stroke come from circulation with only a small contribution of neutrophils arriving directly from the cranial bone marrow. Furthermore, the distribution of red and green cells in tissue suggests that the neutrophils intermix regardless of origin. Further studies evaluating the subset of cranial bone marrow-derived neutrophils are needed to understand their significance specific to ischemia/reperfusion injury.
Abstract WP57: The Effects of Atrial Fibrillation Burden on Cognitive Function and Brain Structure
Authors: Rotschild Ofer , Le Brian , Gokcal Elif , Abramovitz Fouks Avia , Das Alvin , Greenberg Steven , Helmer Karl , Gurol Edip
Published: January 2025

Introduction:
Atrial fibrillation (AF) has been linked to cognitive impairment and dementia (CID) even among patients without clinically obvious stroke, but the mechanism is not established. In this study, we aim to clarify the relationship between the burden of AF and CID in a cohort of AF patients without any history of stroke. We hypothesized that a higher AF burden would be associated with CID, possibly through more pronounced cerebral hypoperfusion and covert infarcts.

Methods:
We included 843 patients with AF and without a history of clinical stroke or neurodegenerative disease, who underwent brain MRI at a tertiary center. Clinical data were collected through chart review, assisted with natural language processing algorithms to improve accuracy. Patients with a diagnosis of mild cognitive impairment or dementia were classified as having CID. AF load was categorized as low-burden (paroxysmal/persistent AF) or high-burden (longstanding persistent/permanent AF). A vascular neurologist extracted data on the brain atrophy score, Fazekas score, the presence of embolic and lacunar infarcts, cerebral microbleeds (CMB), and cortical superficial siderosis (cSS) from brain MRIs (FIGURE).

Results:
In total, 114 patients (13.7%) had CID, and they were older (78.4±7.6 vs 72.4±9.5 years, p < 0.001), and more likely to have a higher AF burden (44.7% vs 15.3%, p<0.001), Fazekas score, atrophy score, CHA
2
DS
2-
VASC score, presence of embolic infarct on imaging, lacunar infarct, and anticoagulant use. In multivariate analysis, higher AF burden (OR=3.33, C.I=2.08-5.36, p<0.001), brain atrophy score (p=0.005), Fazekas score (p=0.001), and presence of embolic infarct (p=0.045) remained associated with CID, while age, sex, CHA
2
DS
2-
VASC score, and lacunar infarct were not. AF burden was independently associated with higher brain atrophy scores (p=0.022) in a separate multivariate model, adjusted for age, CHA
2
DS
2-
VASC and Fazekas scores, anticoagulant use, and embolic and lacunar infarcts.

Conclusion:
A higher AF burden is a contributing factor to the development of CID and brain atrophy. Brain atrophy and embolic infarcts are likely mechanisms for the effects of AF burden on cognition. White matter hyperintensities, which are mainly related to cerebral small vessel diseases, also contribute to CID in this population. Whether early and rigorous rhythm control can decrease the risk of cognitive impairment in patients with AF should be tested in randomized controlled trials.
Abstract WP9: IV Thrombolysis in Acute Stroke Management Secondary to Extracranial Artery Dissections: Systematic Review and Metanalysis
Authors: Mahmoud Noor , Mansour Pearla , El Ahdab Jad , Lee Elizabeth , Shu Liqi , Ghannam Malik , Yaghi Shadi
Published: January 2025

Background:
Acute ischemic stroke can result from extracranial arterial dissection. The effectiveness and safety of intravenous thrombolysis (IVT) for acute ischemic stroke in these cases, particularly those involving large vessel occlusions, are debated. We conducted a systematic review and metanalysis to assess the efficacy and safety of IVT in patients with acute ischemic stroke attributed to extracranial arterial dissection.

Methods:
This systematic review was registered in PROSPERO (CRD42024499774). We searched MEDLINE (OVID), EMBASE, web of Science, and SCOPUS from inception to 03/03/2024. Search terms included a combination of keywords and controlled vocabulary terms for carotid or vertebral artery dissection and fibrinolysis or alteplase or tenecteplase. We included randomized controlled trials, observational studies, case series that compared IV thrombolysis and standard management with at least 10 patients in each group in patients with cervical or vertebral artery dissection. Where studies were sufficiently similar, we performed metanalyses for benefits (excellent (0-1) and good (0-2) modified Rankin scale at 90 days), safety (symptomatic intracerebral hemorrhage (sICH)), and mortality outcomes, using relative risks (RR). Given the impact of NIHSS on 90-day modified Rankin Scale, we pooled adjusted ORs (adjusting for NIHSS) when exploring 90-day functional outcomes.

Results:
Our search identified 418 records, we screened 12 studies as potentially eligible. Four studies (all retrospective cohort, 3 studies adjusted for NIHSS variable, one study addressed LVO cohort) met our inclusion criteria. The risk of bias was assessed using the Risk of Bias in Nonrandomized Studies of Interventions tool. Two studies had serious risk of bias while the other two had a moderate bias risk. When compared no IVT, IVT was associated with comparable risk of sICH (RR, 0.91 [95% CI, 0.11-7.94]) and mortality (RR, 0.63 [95% CI, 0.29-1.37]). However, IVT was associated with a significantly higher odds of good functional outcome at 90-days (aOR, 1.53 [95% CI, 1.14-2.05]) and a non-significantly lower chance of excellent functional outcome at 90-days (aOR 2.16 [95% CI 0.72-6.51]).

Conclusion:
Our metanalysis suggests that in patients with acute ischemic stroke secondary to extracranial artery dissection, IVT may have improved efficacy but comparable safety and mortality. Our findings should be interpreted with caution until supported by randomized controlled trials.
Ultra-Early Hematoma Expansion Is Associated With Ongoing Hematoma Growth and Poor Functional Outcome
Authors: Mutimer Chloe A , Wu Teddy Y , Zhao Henry , Churilov Leonid , Campbell Bruce C V , Cheung Andrew , Meretoja Atte , Kleinig Timothy , Choi Philip M.C. , Ma Henry , Cloud Geoffrey C , Grimley Rohan S , Shah Darshan , Ranta Anna , Mahawish Karim M , Yogendrakumar Vignan , Sharma Gagan , Donnan Geoffrey A. , Davis Stephen M , Yassi Nawaf
Published: January 2025

Background:
There is limited data on ultra-early hematoma growth dynamics and its clinical relevance in primary intracerebral hemorrhage (ICH). We aimed to estimate the incidence of hematoma expansion (HE) within the hyperacute period of ICH, describe hematoma dynamics over time, investigate the associations between ultra-early HE and clinical outcomes after ICH, and assess the effect of tranexamic acid on ultra-early HE.

Methods:
We performed a planned secondary analysis of the STOP-MSU international multicenter randomized controlled trial. Repeat CT imaging ~1 hour after treatment commencement was encouraged. Patients who underwent re-imaging up to 3 hours from baseline imaging were included in this descriptive study. Hematoma expansion was defined as either a ≥33% or ≥6 ml increase from baseline hematoma volume.

Results:
We included 105 patients who had 1-hour imaging (median age 66years, 40% female, 53% tranexamic acid). Median time from onset to baseline imaging was 74min (IQR 56-87min), and between baseline and 1-hour imaging was 95min (IQR 74-132min). Forty-one patients (39%) had ultra-early HE. These patients had larger baseline hematoma volumes (15.9ml vs 9.1ml, p=0.03) compared to those with no early HE. Hematoma growth rate significantly reduced over time compared to the onset-to-baseline imaging period (clustered median regression p<0.01). In 92 patients with both 1-hour and 24-hour re-imaging, further HE between the 1-hour and 24-hour imaging was more common in those with ultra-early HE (29%) compared to those without (29% vs 6.6%, p<0.01). Ultra-early HE was associated with poor functional outcomes (mRS 3-6; aOR3.87 [1.21-12.40], p=0.02) and mortality (aOR6.16 [95% CI 2.15-17.68], p<0.01), adjusted for treatment group. There was no observed effect of tranexamic acid treatment on ultra-early hematoma expansion (41% vs. 37%, p=0.65).

Conclusion:
Most hematoma growth occurs in the ultra-early period. The presence of hyperacute hematoma expansion is associated with ongoing hematoma growth, and poor clinical outcomes, and represents a target for therapeutic intervention.
Validation of a Novel MRI Biomarker of Infarct Severity to Predict Functional Outcome After Endovascular Thrombectomy
Authors: Favilla Christopher G. , Regenhardt Robert W , Denny Braden , Shakibajahromi Banafsheh , Patel Aman B , Mullen Michael T , Leslie-Mazwi Thabele M. , Dmytriw Adam A , Bonkhoff Anna K. , Schirmer Markus D. , Rost Natalia S. , Simonsen Claus Z , Messé Steven R.
Published: January 2025

Background:
Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the final infarct volume (FIV) on MRI only accounts for a minority of the treatment effect. An imaging biomarker that more strongly correlates with post-EVT functional outcome would be helpful for clinical prognosis and serve as a surrogate outcome measure in trials of EVT-adjuvant therapies. Here, we aimed to validate a novel MRI-based metric, infarct density, which leverages post-EVT apparent diffusion coefficient (ADC) as a marker of infarct severity.

Methods:
A retrospective cohort was derived from a single-center prospective EVT registry. Consecutive anterior circulation EVT patients were included from 2018-2019 who achieved successful reperfusion (mTICI ≥2b). MRI was performed 12-48 hours post-EVT and processed via RAPID to quantify FIV using the ADC <620 threshold. Lesion volume was also collected using ADC <470 threshold, and infarct density was calculated as: (volume <470/volume <620)x100%. Good outcome was defined as ≤2 on the 90-day modified Rankin Scale. Multivariable logistic regression models quantified the association between clinical/imaging variables and outcome. ROC analysis quantified model classification performance.

Results:
Of 319 EVT patients, 272 met inclusion criteria. The mean age was 69 ±13 years, 41% were female, and 62% achieved a good outcome. After adjusting for clinical and radiographic factors, FIV (aOR 0.99 per 1mL; 95%CI: 0.98-1.00; p=0.03) and infarct density (aOR 0.95 per 1%; 95%CI: 0.94-0.97; p<0.001) were both independently inversely associated with good outcome. The final model incorporating both FIV and infarct density achieved excellent classification performance (AUC 0.87; 95%CI: 0.83-0.91). Removing infarct density from the model diminished its performance (AUC 0.83; 95%CI: 0.78-0.88; p=0.01).

Conclusion:
ADC-based infarct density after EVT is independently associated with long‐term outcome and provides greater prognostic information than FIV alone. Post-EVT infarct density may be useful in clinical care and as a surrogate outcome measure in trials of EVT-adjuvant therapies.
Characterizing the spatial patterns and determinants of cerebrospinal fluid pseudorandom flow in the human brain with low b-value diffusion MRI
Authors: Nazeri Arash , Hosseini Helia , Dehkharghanian Taher , Lindsay Kevin E. , LaMontagne Pamela , Shimony Joshua S. , Benzinger Tammie L.S. , Sotiras Aristeidis
Published: January 2025

The circulation of cerebrospinal fluid (CSF) is essential for maintaining brain homeostasis and clearance, and impairments in its flow can lead to various brain disorders. Recent studies have shown that CSF effective motility can be interrogated using low b-value diffusion magnetic resonance imaging (low-b dMRI). Nevertheless, the spatial organization of intracranial CSF flow dynamics remains largely elusive. Here, we developed a whole-brain voxel-based analysis framework, termed CSF pseudo-diffusion spatial statistics (CΨSS), to examine CSF mean pseudo-diffusivity (MΨ), a measure of CSF flow magnitude derived from low-b dMRI. We showed that intracranial CSF MΨ demonstrates characteristic covariance patterns by employing seed-based correlation analysis. Next, we applied non-negative matrix factorization analysis to further elucidate the covariance patterns of CSF MΨ in a hypothesis-free, data-driven way. We identified 10 distinct CSF compartments with high reproducibility and reliability, reflected by a high mean adjusted Rand index with a low standard deviation (0.82 [SD: 0.018]) in split-half analyses of the discovery multimodal aging dataset (n = 187). The identified patterns displayed similar MΨ across three replication datasets. In discovery and replication multimodal aging cohorts (unique n = 264), our study revealed that age, sex, brain atrophy, ventricular anatomy, and cerebral perfusion differentially influence MΨ across these CSF spaces. Notably, of the 35 individuals exhibiting anomalous CSF flow patterns, five displayed clinically consequential incidental findings on multimodal neuroradiological examinations, which were not observed in other participants (p = 3.04 × 10-5). Our work sets forth a new paradigm to study CSF flow, with potential applications in clinical settings.
Understanding “World Literature” in China Today
Authors: Liu Yan
Published: January 2025

This essay will analyse how Goethe’s “Weltliteratur” is interpreted and re-invented in China in the twenty-first century mainly by reviewing selective essays published in the Chinese journal Comparative Literature in China. The analysis reveals how Chinese scholars strive to engage actively in the international discussions of the concept and to chart a map of world literature by offering Chinese perspectives. One such attempt is to trace a parallel development line of similar ideas in Chinese literary history whereas another is to emphasize the position of Chinese literature in the picture of world literature, especially by incorporating overseas Chinese literature into comparative literary studies with the intention to enlarge the scope of reference of Chineseness. These attempts reflect the growing confidence of Chinese scholars to secure our position in the global development of world literature and world literature studies.
Are Loan Sales Really Off-Balance Sheet?
Authors: GORTON GARY , PENNACCHI GEORGE
Published: January 2025

A commercial loan sale or secondary loan participation is a contract under which a bank sells the cash stream from a loan to a third party, usually without recourse. In accordance with accepted accounting procedures, this no-recourse contract allows removal of the underlying loan from the balance sheet of the bank, so that the funding of the loan is not subject to capital or reserve requirements. Since commercial banks are thought to specialize in the origination of nonmarketable claims on borrowing firms, the apparent ability of banks to sell these assets seems paradoxical. The paradox could be explained if loan sales contracts contained implicit guarantees in the form of options by loan buyers to sell the loans back to the bank if the underlying borrower performs worse than anticipated. If such guarantees exist, then loans that are sold represent contingent liabilities, and a rationale for increasing capital requirements may exist. As an indirect test of the existence of this guarantee, we investigate whether loan sales and commercial paper prices contain a risk premium for the default of the selling bank. The empirical evidence supports the hypothesis of implicit guarantees.
Money Demand and Off-Balance Sheet Liquidity: Empirical Analysis and Implications for Monetary Policy
Authors: GLICK REUVEN , PLAUT STEVEN E.
Published: January 2025

In recent years, off-balance sheet credit facilities have grown dramatically and now represent the most prevalent contractual framework within which commercial and industrial borrowing from banks occurs. One important role of these facilities is to provide liquidity to bank customers that acts as a substitute for on-balance sheet liquidity or "money.”

This paper discusses empirical evidence of the substitutability between on- and off-balance sheet liquidity for the business sector. It also discusses the implications of this relationship for interest rate determination and monetary policy. In particular, it is argued that monetary policy should pay more attention to off-balance sheet liquidity when choosing targets and operating procedures.
On Bankruptcy Indicators From Analysts’ Earnings Forecasts
Authors: MOSES O. DOUGLAS
Published: January 2025

Research has documented that forecasts of future earnings made by financial analysts capture aspects of risk and expected return for firms, and reflect information not reflected in firms’ accounting reports. This study investigates the usefulness of measures developed from analysts’ earnings forecasts as indicators of impending bankruptcy. Results indicate that healthy and failing firms differ significantly with respect to four properties of earnings forecasts: forecast level, forecast error, forecast bias, and forecast dispersion. When combined in a model, measures related to these four forecast properties are able to predict bankruptcy in the year prior to failure as accurately as more traditional approaches using accounting ratios.
The Information Content of Funds Statement Ratios
Authors: BARLEV BENZION , LIVNAT JOSHUA
Published: January 2025

This study examines the incremental information content of funds statement ratios. The funds statement ratios are presumed to have incremental information content when the association with security returns is stronger than when only balance sheet and income statement ratios are used.

The empirical results indicate that funds statement ratios possess incremental information content. Moreover, funds statement ratios seem to be more highly correlated with security returns than traditional ratios that are based on the balance sheet and income statement. These results are robust to various specifications of the variables.
Factors Influencing Help-seeking Behavior for Mental Health Among Distressed Young Adults: A Path Analysis Model
Authors: Sanghvi Prachi , Chandrashekhar Priyesh , Mehrotra Seema , Sharma Manoj Kumar
Published: January 2025

Background:

There seems to be a relationship between barriers of distress-perception and stigma to consult a mental health professional (MHP), help-seeking inclination from MHP, help negation, and encouragement from significant others (SO) to consult MHP in bringing about a change in help-seeking behavior. However, these have not been studied in tandem. This study aimed to explore the relationship between factors influencing help-seeking behavior among distressed, non-treatment-seeking young adults (D-NTS) for common mental health concerns following the ReachOut intervention.

Methods:

A total of 109 D-NTS aged 20–35 engaged with ReachOut were recruited online using purposive and snowball sampling. ReachOut was aimed at enhancing professional help-seeking. Participants were assessed at baseline and one month post-intervention for help-seeking barriers, inclination, and encouragement from SO. Help-seeking behavior from MHP was evaluated at a two-month follow-up. Inferential statistics in the form of Spearman’s rho correlation, logistic regression, and path analysis were computed.

Results:

Regression analysis revealed a significant model (χ2 = 34.53, P < .001) with an R2 value of 0.52. Help-seeking inclination from MHP (B = 0.711, P = .037), help negation (B = −0.452, P = .039), and encouragement from SO to consult MHP (B = 1.942, P = .008) at post-assessment were significant predictors of help-seeking behavior, assessed at follow-up. The SEM hypothesized for path analysis with help-seeking behavior as the outcome was a good fit.

Conclusion:

Help-seeking decisions are complex processes influenced by an intricate interplay of internal and external factors. A comprehensive examination of these elements simultaneously provides valuable insights for tailoring interventions and strategies aimed at enhancing help-seeking behavior in D-NTS young adults.

Trial registration:

The intervention trial was registered in the ISRCTN registry (ISRCTN14504454).
Virtual diversity and the value-ladenness of science
Authors: Thorpe Charles
Published: January 2025

Collins, Evans, and Reyes-Galindo develop the concept of interactional expertise into the idea of virtual diversity. They thereby provide a strong case against the epistemic barriers established by identity politics. This commentary questions, however, whether virtual diversity can incorporate the critique of institutional power that Wynne has argued is at the center of tensions between lay publics and scientific establishments. The commentary argues for a critical theory of science, as suggested by Doppelt on the basis of his normative interpretation of Kuhnian incommensurability.
Recent Legal Developments: Criminal Justice Decisions of the United States Supreme Court, 2023 Term
Authors: Hemmens Craig , McGlynn Ciara , Shaw Keilah
Published: January 2025

In this paper, we review and analyze the criminal justice-related decisions of the 2023 term of the United States Supreme Court. We also provide a summary of the Court's voting patterns and opinion authorship. Sixteen of the Court's 59 decisions touched on criminal justice. There were significant decisions involving the Second Amendment, the Sixth Amendment, and federal criminal statutes. Each of these is discussed in turn.
Sleep Patterns and Human Brain Health
Authors: Fjell Anders M. , Walhovd Kristine B.
Published: January 2025

It is a widely held opinion that sleep is important for human brain health. Here we examine the evidence for this view, focusing on normal variations in sleep patterns. We discuss the functions of sleep and highlight the paradoxical implications of theories seeing sleep as an adaptive capacity versus the theory that sleep benefits clearance of metabolic waste from the brain. We also evaluate the proposition that sleep plays an active role in consolidation of memories. Finally, we review research on possible effects of chronic sleep deprivation on brain health. We find that the evidence for a causal role of sleep in human brain health is surprisingly weak relative to the amount of attention to sleep in science and society. While there are well-established associations between sleep parameters and aspects of brain health, results are generally not consistent across studies and measures, and it is not clear to what extent alterations in sleep patterns represent symptoms or causes. Especially, the proposition that long sleep (>8 hours) in general is beneficial for long-term brain health in humans seems to lack empirical support. We suggest directions for future research to establish a solid foundation of knowledge about a role of sleep in brain health based on longitudinal studies with frequent sampling, attention to individual differences, and more ecologically valid intervention studies.