bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP395: Mapping the Spatial Distribution of Neutrophils in a Murine Model of Ischemia/Reperfusion Injury
Authors: Schappell Laurel , Madeira Miguel , Tang Meiyi , Tsirka Stella , Nadkarni Neil
Published: January 2025

Introduction:
Polymorphonuclear Neutrophils (PMNs) are the first blood-derived immune cells to respond in ischemia/reperfusion injury (I/RI). PMNs exhibit spatial heterogeneity and play complex roles in injury progression and resolution. However, preclinical studies investigating the immune response have been limited to studying the area of maximal infarction or highly representative images throughout the stroke hemisphere. As a result, the spatial relationships of PMNs in the acute stages of I/RI throughout the whole brain remain largely unknown. To address this gap in knowledge, we applied light sheet microscopy (LSM) to fully map the spatial patterns of PMNs in relation to neuronal injury throughout the murine brain in I/RI.

Methods:
The transient middle cerebral artery occlusion (tMCAO) model was used to recapitulate I/RI in a Ly6G-tdTomato transgenic mouse line expressing an endogenous fluorescent marker for PMNs. Mice were subject to 60 min or 90 min of ischemia to model strokes of varying severity. Whole brains were collected 72h post-tMCAO, (the point of maximal PMN infiltration), cleared, and then imaged using LSM. Brains were co-labeled with NeuN (neurons), registered, and parcellated according to the Allen Brain Atlas. Relationships of PMNs to the M1 segment of the MCA were then mapped.

Results:
Following 60 min tMCAO, PMNs infiltrated predominantly in infarcted regions of the cerebral cortex (NeuN Negative). Further, the density of PMNs was higher in anatomic regions supplied by the middle cerebral artery (MCA) and negatively correlated with the distance from the M1. In the 90 min tMCAO, PMN infiltration followed a similar pattern with PMN accumulation predominantly in the ischemic cortex and increased with proximity to the M1. However, PMN densities in the 90 min tMCAO were significantly higher than in the 60 min tMCAO. Additionally, PMN-rich regions in the 90 min tMCAO were more concentrated than in the 60 min tMCAO.

Conclusions:
Our data demonstrate that PMNs exhibit spatial heterogeneity following experimental stroke and cluster in regions corresponding to increased neuronal death and proximity to the MCA. PMN distribution was also influenced by the duration of ischemia, suggesting that PMNs are highly responsive to both stroke topology and severity. These data enable a more in-depth understanding of neutrophil dynamics in I/RI that can be leveraged to inform future stroke therapies directed at limiting the immune response.
Abstract WP397: Targeting miR-200 Family miRNAs Protects BV2 Microglia Cells Against OGD/Reoxygenation Injury by Restoring the Tgfβ2/Zeb1 Signaling Pathway
Authors: Yadav Sanjeev , Gamiotea Turro Daylin , Verma Rajkumar
Published: January 2025

Backgrounds:
Our prior work demonstrated the upregulation of miR-200 family miRNAs specifically miR-141&miR-200c after stroke in mice models. Moreover, we found a significant upregulation of miR-141 in stroke patient's blood samples and validated the potential of targeting miR-141 to mitigate ischemic stroke damage. In this study, we aimed to validate the upregulation of miR-200c in stroke patients plasma samples and evaluate the potential of inhibiting miR-200c alone or in combination with miR-141 to mitigate stroke damage in oxygen-glucose deprivation (OGD) in microglial BV2 cells.

Methods:
Total RNA (including miRNAs) was isolated from plasma samples of stroke patients and healthy controls and miR-200c expression was assessed by qPCR.
In vitro
, an oxygen-glucose deprivation (OGD) model in BV2 cells was used to assess the potential of inhibition using antagomiRs of miR-200c alone and in combination with miR-141 on cell viability, cytotoxicity, apoptosis and inflammation via MTT, LDH assays, and qPCR for gene expression. TargetScan web portal was used to obtain the potential targets of miR-200c/141 and explored the molecular mechanism behind this neuroprotection.

Results:
miR-200c was significantly upregulated in stroke patients compared to healthy individuals, confirming the current study's translational potential. We found a gradual increase in miR-200c expression after 1h, 2h, 3h, and 4h (>5 folds) OGD followed by 24h reperfusion (R). Inhibition of miR-200c or miR-141/200c cluster after 4h OGD/24h R showed a synergistic effect on cell viability and cytotoxicity. Inhibition of the miR-141/200c increased anti-apoptotic gene
Bcl2
and reduced the pro-apoptotic (
Bax
) and pro-inflammatory genes (
Il-1β, Il-6,
and
Tnf-α
) in BV2 cells following OGD/R. According to TargetScan analysis,
Smad2
is a direct target of miR-200c,
Tgfb2
is targeted by miR-141, and
Zeb1
is commonly targeted by both miR-200c and miR-141-3p; the expression of these genes significantly decreases following OGD/R. The inhibition of miR-141/200c restored the levels of
Tgfβ2, Smad2
&
Zeb1
.

Conclusion:
Cluster miR-141/200c can act as a biomarker and a prominent therapeutic target for stroke treatment.
In vitro
, inhibition of miR-200c alone or together with miR-141-3p protects from OGD-induced injury in microglial BV2 cells by reducing neuroinflammation and apoptosis. Overall, the Tgfβ2/Zeb1 pathway is involved in the cluster miR-141/200c mediated neuroprotection.
Abstract WP402: Hypertension-linked oxidative stress and inflammatory transcriptomic pathways in the brain cortical regions of a rat model following ischemic stroke
Authors: Wesley Umadevi , Nelson Dylan , Sennholz Ian , Walton Brandon , Kpegeol Confidence , Dempsey Robert
Published: January 2025

Background:
Patients with hypertension (HTN) are almost 3 times more likely to have a stroke than non-hypertensive individuals. HTN is associated with oxidative stress (OS), exacerbated inflammation, and vascular remodeling. In experimental models, normotensive Sprague-Dawley (SD) and Spontaneously Hypertensive Rats (SHR) show different susceptibilities and outcomes to ischemic stroke. We propose that better understanding of the modulation in gene expression profile in HTN brains may provide critical insight into this complex process.

Methods:
We focused on transcriptomic characterization of OS, inflammatory, and apoptosis pathway specific genes in SD and SHR brains before and after ischemic stroke. Middle Cerebral Artery Occlusion was used to induce focal ischemia/reperfusion injury (I/R). Using pathway specific arrays containing 84 selected genes, we performed a transcriptome analysis in the brain cortical regions. Fold-changes in gene expression were determined using the 2
−ΔΔCt
method.

Results:
In no-stroke SHR brain, HTN was associated with increased levels of pro-inflammatory genes including chemokine ligand (CCL)5 (3.0-fold), IL-6 (3.3-fold), and TNF superfamily member 7 (14-fold) as compared to normotensive SD rats without stroke. On the other hand, Mitogen-activated protein kinase 13, involved in tissue remodeling and cell proliferation was significantly decreased in SHR brains. However, following I/R, expression of redox signaling genes including aldehyde
oxidase
1 (3.4 fold), dual oxidase 1 (2.5-fold), and lactoperoxidase (3.3-fold) were upregulated in SHR brains as compared to SD rat brains. This was linked to a dysregulation in inflammatory response genes including SELE (2.8-fold), IL-1β (2-fold), and CCL21 (3.2-fold). The downstream effects of OS and inflammation on apoptotic process was supported by an upregulated expression of pro-apoptotic genes, including caspases-3,6,12 (2.1,1.7, 3.4-fold), CIDEA (1.7-fold), FAS (1.7-fold), and PYCARD (2-fold). These data indicate that OS and inflammatory pathways are further over-activated in hypertensive rat brains.

Conclusion:
Our data show that the expression of genes involved in OS and inflammation are coordinately upregulated as a function of HTN, which may worsen the outcome of ischemic stroke by likely regulating vascular remodeling, neuronal apoptosis, and blood brain barrier functions. Further studies focusing on these key genes may open up new ways to mitigate HTN-linked post-stroke brain damage.
Abstract WP47: Atrial Fibrillation Burden and Enlarged Perivascular Spaces in Basal Ganglia
Authors: Rotschild Ofer , Le Brian , Gokcal Elif , Abramovitz Fouks Avia , Das Alvin , Greenberg Steven , Helmer Karl , Gurol Edip
Published: January 2025

Introduction:
The brain's glymphatic system is crucial for clearing metabolic waste and maintaining balanced fluid circulation within the brain. Enlarged perivascular spaces in the basal ganglia (EPVS-BG) are markers of hypertensive cerebral small vessel disease (HTN-cSVD) due to glymphatic system dysfunction. Atrial fibrillation (AF) has been proposed to increase the wall shear stress and blood pressure in the lenticulostriate arteries (LSA), both potentially contributing to glymphatic dysfunction and cSVD development. We hypothesized that a higher AF burden is related to the presence of a severe degree EPVS-BG, potentially through the hemodynamic effects of AF on LSAs.

Methods:
We analyzed data from 641 AF patients who had no clinical history of stroke or neurodegenerative disease and received brain MRIs with appropriate sequences at a tertiary care center. Neuroimaging data were collected by a stroke neurologist blinded to the clinical data. AF load was classified as lower-burden (paroxysmal/persistent AF) or higher-burden (longstanding persistent/permanent AF). The imaging outcome variables were the presence of severe EPVS-BG (>20 on one side of the brain), Fazekas score, atrophy score, lacunes and microbleeds (MB) in deep/lobar locations (FIGURE). The multivariable model was adjusted for all variables with p<0.1 in univariate analysis.

Results:
The mean age of the 641 AF patients was 74
+
10 years, 242 (37.8%) were female, and 123 (19.2%) had a higher AF burden. Severe EPVS-BG were found in 15.9%, deep lacunes in 24.5%, and deep MBs in 8.3%. In univariate analyses, the presence of severe EPVS-BG was associated with a higher AF burden (31.4% vs 16.9%, p<0.001), Fazekas score (p<0.001), atrophy score (p<0.001), higher counts of deep lacunes (p<0.001), and deep MBs (p=0.002). In multivariable analyses, higher AF burden remained an independent predictor of EPVS-BG (OR=2, 95% CI 1.14-3.5, p=0.015), together with Fazekas score, deep lacunes, and deep MBs, after adjusting for age, sex, serum creatinine, sleep apnea, hypertension, smoking status, lobar lacunes and MBs.

Conclusion:
Our results show that AF burden is independently associated with severe EPVS-BG, even after adjusting for important imaging markers of HTN-cSVD (leukoaraiosis, deep lacunes and deep MB). Higher AF burden can independently contribute to glymphatic dysfunction around the LSAs resulting in parenchymal brain injury, in addition to the known harmful effects of hypertension on these vessels.
Abstract WP48: Potential Role of Diabetes-Associated Hyperamylinemia in Stroke
Authors: Verma Nirmal , ly han , Lee Kin Sing Stephen , Hammock Bruce , Despa Florin
Published: January 2025

Introduction:
Type-2 diabetes increases the risk of stroke; however, the mechanisms remain incompletely understood. Using a rat model of type-2 diabetes that expresses amyloid-forming human amylin in the pancreas (the HIP rat), we previously reported that human amylin deposits in the brain microvasculature causing brain microhemorrhages and neurological deficits. Here, we tested the hypotheses: 1, mechanisms of amylin-mediated cerebral microvascular injury involve damage of the endothelial cell tight junctions; 2, an increase in epoxyeicosatrienoic acids (EETs), protective proteins secreted by the endothelial cells, reduces brain microvasculature and microvascular injury in HIP rats.

Methods:
To delineate amylin-mediated neurological deficits and brain microvascular injury, we used HIP rats expressing amyloidogenic human amylin in the pancreas and amylin knockout (AKO) rats intravenously infused with aggregated human amylin. To upregulate EETS, HIP rats were treated for 10 weeks with a soluble epoxide inhibitor, APAU (UC1153) which was added in the drinking water (1 ml drug/L). Biochemical analyses were carried out for investigating the formation of adducts of amylin aggreagtes with tight junction proteins and the peroxidative injury of the endothelial cells.

Results:
HIP rats and AKO rats infused with aggregated amylin have increased brain microhemorrhages (HIP 14.86 ± 6.619; p=0.04, and AKO-inj 8.500 ± 5.137; p=0.17), white matter injury (HIP 170.5 ± 43.90; p=0.0022), and neurologic deficits (neurological Z-score -0.5337 ± 0.3505; p>0.01). Vascular amylin deposition provokes peroxidative injury (HIP 4HNE 166.4 ± 44.28; p=0.0027, MDA 45.04 ± 13.15; p=0.005, and AKO-inj 4HNE 182.2 ± 56.54; p=0.012, MDA 44.17 ± 21.84; p=0.07)), loss of endothelial cell coverage (HIP p=0.0002, and AKO-inj p=0.42) and tight junctions in HIP and AKO rats infused with aggregated amylin. Treatment with sEHI reduced vascular amylin deposition (198.6 ± 96.75; p=0.11), prevented loss of tight-junction proteins, and improved cognitive and motor function in HIP rats (neurological Z-score for cognitive function 0.2063 ± 0.4635; p=0.71, and motor function 0.8858 ± 0.1931; p<0.01).

Conclusions:
Systemic amylin dyshomeostasis is a mediator of microvascular injury to the brain by damaging the endothelial cell tight junctions. Reducing amylin dyshomeostasis by upregulating EETs reduces amylin-mediated cerebrovascular injury and neurological deficits in the setting of diabetes.
Abstract WP49: Diagnostic performance of plasma pTau217 for the detection of Cognitive Impairment in a Vascular Disease-Enriched Population
Authors: Gunda Rashmika , Chatterjee Roopsha , Windon Charles , Hinman Jason
Published: January 2025

Cerebral small vessel disease, particularly characterized by white matter hyperintensities (WMHs), is a prominent contributor to cognitive impairment. The concurrent role of Alzheimer's disease (AD) pathology, as measured by hyperphosphorylated tau species (pTau), in vascular cognitive impairment remains unclear. While plasma pTau217 is an established biomarker for AD, its relevance in vascular disease-enriched populations has not been extensively studied. This study investigates plasma pTau217 as a biomarker for distinguishing cognitive impairment and dementia in a cohort de-enriched for AD but enriched for vascular disease, focusing on its relationship with cognitive status and Fazekas scores. A cohort of 72 participants (mean age: 70.4, SD 7.9, 58% female) from the MarkVCID Consortium study were selected with 75% having a Fazekas score ≥ 2. pTau217 levels were quantified using the Meso Scale Discovery S Plex assay. Individuals were classified based on their cognitive status into cognitively normal, mild cognitive impairment (MCI), or dementia. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pTau217 to distinguish between these groups. Linear regression models were used to examine the association between pTau217 levels and Clinical Dementia Rating (CDR) global scores. Plasma pTau217 levels were found to be elevated in individuals with MCI and dementia. The ROC curve analysis showed pTau217 could distinguish between patients with MCI (AUC: 0.74) and dementia (AUC: 0.72), suggesting moderate diagnostic accuracy in this vascular disease-enriched cohort. No significant relationship was observed between pTau217 levels and Fazekas scores. Regression analysis revealed plasma pTau217 levels were significantly associated with CDR global scores (β=0.337; p=0.0007), a correlation that remained significant after adjusting for sex, age, and education, underscoring pTau217 as an independent predictor of cognitive decline. Additionally, 75% of participants with an AD diagnosis (6/8) had pTau217 levels >10 pg/mL (consistent with prior studies) ranging from 12.2 to 35.3 pg/mL. In conclusion, for this cohort enriched for vascular disease and de-enriched for AD, plasma pTau217 exhibited accuracy in distinguishing patients with MCI and dementia, independent of Fazekas scores. These findings support the utility of plasma pTau217 as a biomarker for cognitive impairment, even in populations with a significant vascular pathology.
Abstract WP5: Age-Dependent Effect Of Thrombolytics On Likelihood Of Stroke Scale Improvement In Minor Strokes
Authors: Thomas Tarun , Dubinski Michael , Patel Karan , Penckofer Mary , Khalife Jane , Thon Jesse , Schumacher Hermann , Hanafy Khalid , Patel Pratit , Tonetti Daniel , Shaikh Hamza , Jovin Tudor , Koneru Manisha
Published: January 2025

Introduction:
Thrombolytic therapy has been a standard part of treatment of large vessel occlusion acute ischemic strokes. There is, however, insufficient evidence in literature to draw significant conclusions as to the efficacy of different thrombolytic agents with extremes of age (elderly or young) in minor stroke patients. The objective is to describe rates of clinical improvement of patients with minor stroke with various thrombolytic agents across ages.

Methods:
A registry of acute ischemic stroke patients between 1/2017 - 9/2023 was retrospectively reviewed. Patients with National Institutes of Health Stroke Scale (NIHSS) score less than or equal to 5 were included. Multivariable age-adjusted logistic regression for the effect of thrombolysis, and the type of thrombolytic agent used, on the likelihood of improvement in NIHSS by 24 hours was performed. Margins plots were derived from regression analyses.

Results:
Of 1257 patients with minor stroke, median age was 67 years (IQR 58-76). Median NIHSS on admission was 2 (IQR 0-3), with 29.0% (365/1257) of patients experiencing improvement by 24 hours. Thrombolytics were administered in 9.5% (119/1257). In a multivariable regression, there was a significant interaction effect between age and thrombolytics (p=0.01). Thrombolytics were associated with significantly higher odds of NIHSS improvement (p=0.004). Between the types of thrombolytic agents used, there was a significant interaction effect between age and tenecteplase (p=0.02). In contrast, there was not a significant interaction between age and tissue plasminogen activator (p=0.08). In prediction models, the odds of NIHSS improvement in thrombolytic-treated patients were above 50% for patients less than 70 years. Odds of NIHSS improvement in tenecteplase-treated patients were above 50% for patients less than 60 years old.

Conclusion:
There is an age-dependent effect on the benefit of thrombolytics, specifically tenecteplase, administration for stroke symptom improvement. Although recent studies show neutral or mixed outcomes using thrombolytics in minor strokes, certain subpopulations, such as young patients, may benefit from this intervention. Future studies may elucidate minor stroke subpopulations potentially benefiting from acute thrombolytic treatment.
Abstract WP51: Non-Traumatic Intracranial Hemorrhage and Risk of Incident Dementia
Authors: Zhang Cenai , Young Kym , Bruce Samuel , Merkler Alexander , Kamel Hooman , Murthy Santosh
Published: January 2025

Introduction:
To study the risk of incident dementia after a non-traumatic intracranial hemorrhage in a diverse US population, and evaluate if this risk is different among the subtypes of intracranial hemorrhage.

Methods:
We performed a retrospective cohort study using both inpatient and outpatient claims data on Medicare beneficiaries between 2008 and 2018. The exposure was an incident diagnosis of non-traumatic intracranial hemorrhage, defined as a composite of intracerebral hemorrhage, subarachnoid hemorrhage, or subdural hemorrhage. The outcome was an incident diagnosis of dementia. The exposure and outcomes were identified using previously validated
ICD-9
and
ICD-10-CM
diagnosis codes. In the primary analysis, we used Cox regression to study the risk of dementia after any intracranial hemorrhage, after adjusting for demographics and comorbidities. In secondary analyses, the risks of dementia in different subtypes of intracranial hemorrhage were studied.

Results:
Among 2.1 million patients, 14,775 had a diagnosis of intracranial hemorrhage. During a median follow up of 5.6 years (IQR, 3.0-9.1), incident dementia was diagnosed in 2527 (17.1%) patients with an intracranial hemorrhage and 260,691 (12.8%) patients without. In adjusted Cox regression analysis, intracranial hemorrhage was associated with an increased risk of incident dementia (HR, 2.0; CI, 1.9-2.2). In secondary analyses, a higher risk of incident dementia was observed with intracerebral hemorrhage (HR, 2.4; CI, 2.2-2.5), subarachnoid hemorrhage (HR, 2.0; CI, 1.7-2.2), and subdural hemorrhage (HR, 1.6; CI, 1.4-1.7).

Conclusion:
In a large, heterogeneous cohort of elderly US patients, we found that intracranial hemorrhage was independently associated with a 2-fold increased risk of incident dementia. This elevated risk was consistently observed across subtypes of intracranial hemorrhage.
Abstract WP64: Microglia LILRB4 Upregulation Reduces Brain Damage after Acute Ischemic Stroke by Limiting CD8
+
T Cell Recruitment
Authors: Yilin Ma , Zheng Kai , Zhao Chengcheng , chen jieli , Chen Lin , Zhang Yue , Chen Tao , Xiuhua Yao , Ying Cai , WU JIALING
Published: January 2025

Introduction:
Leukocyte immunoglobulin-like receptor B4 (LILRB4) is a crucial regulator of immune responses, particularly within microglia, where it may influence the infiltration of peripheral T cells into the brain. However, the specific role of LILRB4 in modulating brain damage after acute ischemic stroke remains unclear. This study aims to investigate the role of LILRB4 in modulating the immune response and its potential protective effects against ischemic brain injury in mice.

Methods:
Microglia-specific LILRB4 conditional knockout (LILRB4-KO) and overexpression transgenic (LILRB4-TG) mice were constructed using a Cre-loxP system. A transient MCAO model was employed to induce ischemic stroke. Single-cell RNA sequencing (scRNA-seq), RT-PCR, Flow cytometry (FACS), and immunofluorescence, TTC staining, laser speckle imaging, and neurological behavioral tests were employed.

Results:
Spatial transcriptomics analysis revealed increased LILRB4 expression in the ischemic hemisphere. ScRNA-seq identified microglia-cluster3, an ischemia-associated microglia subcluster with elevated LILRB4 expression in the ischemic brain. FACS and immunofluorescence staining showed increased CD8
+
T cell infiltration into the brain in LILRB4-KO-tMCAO mice. Behavioral tests, cortical perfusion maps, and infarct size measurements indicated that LILRB4-KO-tMCAO mice had more severe functional deficits and larger infarct sizes compared to Control-tMCAO and LILRB4-TG-tMCAO mice. LILRB4-KD microglia promoted CD8
+
T cell recruitment and activation in vitro and in vivo, which was mitigated by CCL2 inhibition and recombinant Arginase-1 addition. ScRNA-seq and spatial transcriptomics identified that CCL2 was predominantly secreted from activated microglia/macrophage and that increased CCL2 expression in LILRB4-KD microglia.

Conclusion:
LILRB4 in microglia plays a crucial role in modulating the post-stroke immune response by regulating CD8
+
T cell infiltration and activation. Knockout of LILRB4 exacerbates ischemic brain injury by promoting CD8
+
T cell recruitment. Overexpression of LILRB4, conversely, offers neuroprotection. These findings highlight the therapeutic potential of targeting LILRB4 and its downstream pathways to mitigate immune-mediated damage in ischemic stroke.

Keywords:
Ischemic stroke, LILRB4, Microglia, Neuroinflammation, CD8
+
T cells
Abstract WP65: Inflammatory Biomarkers and Progression of MRI-Visible Perivascular Spaces: Findings from The Framingham Heart Study
Authors: Araujo Contreras Robert , Pinheiro Adlin , Kang Matthew , Sisto Joseph , Ekenze Oluchi , Aparicio Hugo , Beiser Alexa , Himali Jayandra , Lioutas Vasileios , Benjamin Emelia , DeCarli Charles , Seshadri Sudha , Demissie Serkalem , Romero Jose
Published: January 2025

Introduction:
Perivascular Spaces (PVS) visible on brain magnetic resonance imaging (MRI) are markers of Cerebral Small Vessel Disease (CSVD). Recent evidence suggests a potential role of inflammatory biomarkers in the pathogenesis of PVS. This study aimed to examine the relation between inflammation markers and progression of PVS burden in community-dwelling individuals.

Methods:
Offspring Framingham Heart Study participants with available inflammatory biomarkers at exam 7 and MRI-PVS assessments at exams 7 and 8 were included. Sixteen components of the inflammatory cascade were analyzed at baseline. PVS were rated as low PVS burden (grade I-II) and high PVS burden (grade III-IV) separately in the Basal Ganglia (BG) and Centrum Semiovale (CSO), using a validated method. Progression in PVS burden between exams 7 and 8 were categorized as change (low to high burden) vs no change. Multivariable logistic regression models were used to assess the association between individual inflammatory biomarkers and changes in MRI-PVS burden. Model 1 was adjusted for age and sex, and Model 2 was additionally adjusted for smoking (SMK), diabetes (DM), hypertension (HTN), prevalent cardiovascular disease (CVD), body mass index and apoE4.

Results:
Among 561 participants (mean age 61.12 ± 8.85 years, 48% male) with an overall low prevalence of vascular risk factors (HTN 37 %, DM 11,15%, SMK 10,87%, CVD 10.34%) we observed that Osteoprotegerin (OPG) levels (mean 5.40 pmol/L ± 1.62) were associated with increase in PVS burden in BG (OR 1.43 [1.08, 1.88] p = 0.01) and CSO (OR 1.32 [1.07, 1.62] p = 0.008). Further adjustment for vascular risk factors did not change this association. No other significant associations were observed.

Conclusion:
In community dwelling individuals free of stroke and dementia with a low prevalence of vascular risk factors, the inflammatory marker OPG was associated with progression of PVS burden in BG and CSO. Further research is needed to elucidate the specific mechanism behind this association and the potential role of OPG as treatment target to mitigate the inflammatory processes contributing to PVS and its adverse consequences.
Abstract WP77: Escape Room Stroke Challenge: Improving Stroke Code Competency and Comfort Levels among Nurses Using an Innovative Educational Tool
Authors: Pancoska Eric , Tenoso Roche , Spokoyny Ilana
Published: January 2025

Background:
Strokes can occur anywhere in the hospital and stroke codes are not limited to dedicated stroke units. Despite this, most educational resources are focused on stroke-specific units rather than on all inpatient nursing areas. For our 2024 stroke educational initiative we assessed the nurses' competency and comfort level serving as the primary nurse in a stroke code by designing an interactive Escape Room for nurses working in both stroke and non-stroke units. We measured the its success using a pre- and post-activity survey of the nurses as well as their ability to successfully complete the Escape Room challenges.

Purpose:
The purpose of this project was to implement an educational activity and assessment for nurses on both stroke and non-stroke units, and to measure the success of this intervention.

Methods:
The intervention consistent of a stroke competency, conducted over four days, that included over 200 nurses from non critical care units. The Escape Room consisted of three puzzles for non-stroke units and an additional puzzle for stroke units. Participants were asked to complete a pre-intervention survey self-reporting their comfort level in managing a stroke code using a Likert scale of 1 (very uncomfortable) to 5 (very comfortable). The puzzles included identifying the components of the BEFAST stroke mnemonic, preparing necessary equipment and utilizing appropriate communication for a stroke code, and recognizing potential post-stroke complications. Stroke unit nurses also completed a fourth puzzle focused on patient education. A post-intervention survey allowed nurses to self-report their comfort level after completing the training and interactive Escape Room activity.

Results:
After completing the stroke Escape Room there was a significant increase in nurses' comfort levels serving as the primary nurse in a stroke code across both stroke and non-stroke units. On stroke units the comfort level increased from 3.73 to 4.75 and 3.01 to 4.24 on non-stroke units. All nurses as a group were able to complete the Escape Room.

Conclusion:
As an adjunct to standard stroke education, Escape Rooms are an innovative and interactive way to increase nurses' comfort levels serving in a lead role during a stroke code on both stroke and non-stroke units. Further studies are warranted to assess the benefits of Escape Room challenges as a tool for assessing stroke knowledge, with the implication of potential integration into larger stroke training programs.
Abstract WP79: Medication Safety in the Digital Age: Leveraging Technology to Increase Right Route Medication Orders for Patients with Feeding Tubes
Authors: Reagin Richard , Burnham Nicole , Serber Stacy , Antonio Darvin , Carlton Sean , Schenone Brian
Published: January 2025

Background:
To maximize patient safety in our academic The Joint Commission-designated Comprehensive Stroke Center, dysphagia screening is essential in preventing aspiration. Feeding tubes (FT) allow safe medication administration to patients with identified swallow dysfunction. Thorough review of our dysphagia fallouts revealed oral (PO) route medications ordered and documented as administered PO for patients with “nothing by mouth” (NPO) orders who also had FTs.

Purpose:
We developed and implemented a safety alert using the electronic health record (EHR) to ensure right route medication orders. Right route is one of the Five Rights of Medication Administration. Patients NPO with FT require a non-oral route for medication administrations.

Methods:
Our team retrospectively analyzed one year of dysphagia fallouts, noting a trend of PO medication administrations documented for stroke patients who had both NPO orders and FT. Review with unit leadership and clinical staff revealed these medications were being appropriately given via FT, indicating the fallouts were documentation, rather than administration, errors. The etiologies of wrong route medication documentations were incorrect medication ordering (providers), EHR medication administration record (MAR) entry (pharmacists), and administration (nurses). An interdisciplinary team partnered with clinical informatics to develop an EHR best practice alert (BPA) for patients NPO with FT, alerting providers to the ordering discrepancy. Evaluation included new PO medication orders entered for Neurology patients NPO with FT before and after BPA implementation.

Results:
Our 10-week pre-intervention sample contained 306 new PO medication orders, with 153 (50%) PO MAR entries, and 47 (15.4%) nursing PO administration documentations. The 10-week post-BPA activation sample had 406 new PO medication orders, with 74 (18.2%) PO MAR entries, and 19 (4.7%) nursing PO administration documentations. After dysphagia BPA alert implementation, Χ
2
comparisons (α=.05) revealed significant reductions in wrong-route PO MAR entries (63.6%, P<.001, Fig.1) and nursing PO administration documentation errors (69.5%, P<.001, Fig.2).

Conclusions:
This project suggests a multidisciplinary approach to leverage the EHR to improve right route medication orders and nursing documentation in patients NPO with FT. Other centers may replicate this approach utilizing the EHR to reduce medication documentation errors and improve patient safety.
Abstract WP81: Stroke Coordinator Onboarding – Developing a Pathway for Success and Longevity of the Stroke Coordinator
Authors: Allen Leigh , McAlpine Candace , Sinkey Shanda , McCabe Penelope
Published: January 2025

Introduction:
Factors contributing to stroke coordinator turnover include not understanding the role of the coordinator, not enough time to do all the things of a stroke coordinator, sufficient resources, and stroke coordinator peer support (1). In 2023, the role of the stroke coordinator was given a much-needed definition with regard to roles and responsibilities (2). This information can help the new stroke coordinator understand the roles and responsibilities of the stroke coordinator. In our system we looked to explore how we can formalize a process to support the onboarding of new stroke coordinators. We first turned to our existing coordinator group to help use gather information on what would have been helpful to their onboarding.

Methods:
The system stroke coordinator group was surveyed via a Microsoft Forms questionnaire. All responses were anonymous.

Results:
14 responses were received out of 19 stroke coordinators/program managers.

Question 1: 12 of 14 responses said that having time with the former stroke coordinator or the system stroke coordinator group was most helpful when they were starting their stroke coordinator role

Question 2: 14 of 14 responses said a mentor, time with a stroke coordinator, knowing their roles and responsibilities, and orientation to the GWTG -Stroke tool would have made the transition into their new role easier.

Question 3: Top items for stroke coordinator orientation: regulatory elements, GWTG-Stroke, data management, patient tracers, and daily stroke coordinator expectations.

Question 4: 13 out of 14 responses said “yes” a mentorship would have helped with their onboarding.

Conclusions:
Formalizing and standardizing stroke coordinator onboarding would be helpful when starting the role as a stroke coordinator. Initial steps for our system include development of a stroke coordinator competency tool, partnering new stroke coordinators with a regional stroke program manager for mentorship, training with our local AHA representative, and meeting with our system data abstraction team to understand the data abstraction process. Further data will need to be collected to see if these strategies improve stroke coordinator stability and decrease stroke coordinator turnover.

1. Abstract WP396: Barriers to Stroke Coordinator Practice | Stroke (ahajournals.org)

2. Ideal Foundational Requirements for Stroke Program Development and Growth: A Scientific Statement From the American Heart Association (ahajournals.org)
Abstract WP82: Time to Anticoagulation Reversal in Hemorrhagic Stroke (ICH) Patients Not Equal Among Arrival Mode
Authors: Abelt Susan , Luciano Jeanie , Serdynski Lynn , Congdon Michelle , Sheth Kevin
Published: January 2025

Background:
ICH accounts for 10% of all strokes and is deadliest and most disabling stroke subtype. Patients with anticoagulant-related hemorrhage require rapid reversal to mitigate risk of hematoma expansion. Measuring time to reversal (TTR) data can facilitate critical quality improvement efforts towards improving outcome. Increased compilation of TTR data will help inform process improvement strategies for this time sensitive metric.

Methods:
Twenty Comprehensive Stroke Centers participated in a learning collaborative from 2020-2022. Expanded ICH data elements were added to the American Heart Association Get With The Guidelines® (GWTG)-Stroke registries to identify gaps and facilitate quality improvement, coding definitions were reviewed to ensure data rigor. ICH data was reviewed quarterly.
TTR
was one of fourteen measures analyzed;
TTR
documentation revealed varied compliance.

Findings:
Over three years, 6,648 ICH patients were abstracted, of which 37.6% were reversed in < 90 minutes from arrival,
TTR
metric was further delineated by patient arrival mode. Percent of patients reversed in < 90 minutes when transferred from another hospital=55.6%, EMS=41.1%, and private transport=16.1%.

Conclusions:
Patients transferred from referring to receiving hospitals had the greatest percentage of patients reversed < 90 minutes whereas those arriving from home had the least. We identified the following factors which may be barriers to timely reversal: symptom presentation, unknown date time of last anticoagulation dose, last known well not documented, delays in imaging due to symptom presentation, administration approval, and interfacility transport delays. Consideration to adopt a quality initiative similar to door to needle in ischemic stroke may prove beneficial.
Abstract WP83: Improving Care Delivery Times in a Prehospital Mobile Stroke Unit Setting
Authors: Kilani Kayla , Morgan-Downing Curtis , Yu Agnes , Villareal Bryan , Mall Lubna , Steiner Nili , De Sisto Travis , Nour May
Published: January 2025

Background:
Stroke centers across the country followadhere to established best practice timeframes for stroke care delivery, such as door-to-doctor, door-to-CT, and door-to-needle times. Mobile Stroke Units (MSUs) represent offer a novel approach to stroke care, and there are currently no established, agreed upon, standards for time metric goals. This study is aimedaims at to establishing MSU time metrics and implementing strategies to improve the efficiency of prehospital stroke care.

Methods:
We analyzed data from 289 patients admitted to the MSU between the years of 2017-2023. Key metrics were identified and analyzed, including alarm-to-dispatch time, on-scene-to-MSU evaluation time, admission-to-lab time, admission-to-CT non-contrast start time, CT non-contrast end-to-interpretation time, admission-to-thrombolysis/hemorrhage reversal/antihypertensive treatment time, and on-scene duration.

From these metrics, goal times were established for the MSU program. These goals were shared with the MSU staff, who identified modifiable and non-modifiable factors affecting each metric. The team implemented action items to improve the metrics. A debriefing form was introduced, enabling staff to review metrics post-care, document whether goal times were met, and identify barriers and successes. Monthly reviews were conducted to monitor progress and refine practices.

Results:
Between January-July 2024, 31 MSU patients were treated, and the established metrics were analyzed and evaluated. Notable improvements were observed in five key areas: Alarm-to-dispatch time improved by 54% (.45 mins), on-scene-to-evaluation time improved by 48% (1.54 mins), admission-to-lab time improved by 23% (2.84 mins), admission-to-CT non-contrast start time improved by 44% (3.94 mins), on-scene duration improved by 13% (6.16 mins).

These improvements highlight the potential for significant enhancement in time-sensitive stroke care delivery through the active implementation of quality improvement action plans by the MSU team.

Conclusions:
Setting and adhering to goal time metrics similar to those practiced in hospital-based stroke centers can greatly enhance the performance and care delivery of MSUs. These goal times offer measurable benchmarks to evaluate team performance, allowing for modifications in practice that can further reduce care delivery times. Implementing such improvements is crucial for optimizing patient outcomes in the prehospital stroke care setting.
Non-Traumatic Intracranial Hemorrhage and Risk of Incident Dementia in U.S. Medicare Beneficiaries
Authors: Bruce Samuel S , Pawar Anokhi , Liao Vanessa , Merkler Alexander E. , Liberman Ava L. , Navi Babak Benjamin , Iadecola Costantino , Kamel Hooman , Zhang Cenai , Murthy Santosh B.
Published: January 2025

Background:
To study the risk of incident dementia after a non-traumatic intracranial hemorrhage in a diverse US population, and evaluate if this risk is different for the subtypes of intracranial hemorrhage.

Methods:
We performed a retrospective cohort study using both inpatient and outpatient claims data on Medicare beneficiaries between January 1, 2008 and December 31, 2018. The exposure was a new diagnosis of non-traumatic intracranial hemorrhage, defined as a composite of intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and subdural hemorrhage (SDH). The outcome was a first-ever diagnosis of dementia. The exposure and outcomes were identified using validated ICD-9 and ICD-10-CM diagnosis codes. We excluded patients who had prevalent intracranial hemorrhage or dementia, to ensure that only incident cases were counted in our analyses. In the primary analysis, we used Cox regression to study the risk of dementia after intracranial hemorrhage, after adjusting for demographics and comorbidities. In secondary analyses, the risks of dementia in different subtypes of intracranial hemorrhage were studied.

Results:
Among 2.1 million patients, 14,775 had a diagnosis of intracranial hemorrhage. During a median follow up of 5.6 years (IQR, 3.0-9.1), incident dementia was diagnosed in 2527 (17.1%) patients with an intracranial hemorrhage and 260,691 (12.8%) in those without intracranial hemorrhage. The cumulative incidence rate of dementia was 8.6% (IQR, 8.1-8.9) among patients with an intracranial hemorrhage, and 2.2% (2.0-2.4) in patients without intracranial hemorrhage. In adjusted Cox regression analysis, intracranial hemorrhage was associated with an increased risk of incident dementia (HR, 2.0; CI, 1.9-2.2). In secondary analyses, a higher risk of incident dementia was observed with ICH (HR, 2.4; CI, 2.2-2.5), SAH (HR, 1.99; CI, 1.7-2.2), and SDH (HR, 1.6; CI, 1.4-1.7).

Conclusion:
In a large heterogeneous cohort of elderly US participants, intracranial hemorrhage was independently associated with a 2-fold increased risk of incident dementia. This elevated risk was consistently observed across subtypes of intracranial hemorrhage.
Heat and Hate: Climate Security and Farmer-Herder Conflicts in Africa
Authors: Eberle Ulrich J. , Rohner Dominic , Thoenig Mathias
Published: January 2025

We investigate the impact of climate shocks on farmer-herder violence, using geolocalized data on conflict events for Africa, 1997-2014. We find that a one degree temperature increase yields a 54% increase in conflict probability in mixed areas populated by both farmers and herders (versus 17% in non-mixed areas). Quantifying the impact of projected climate change in 2040, we find that -when factoring in the magnifying effect of mixed settlements- annual conflicts are predicted to rise by a third. Drawing on a fine-grained analysis of groups' mobility patterns, we show that resource competition is a major driver of farmer-herder violence.
Startups, Unicorns, and the Local Influx of Inventors
Authors: Balsmeier Benjamin , Fleming Lee , Marx Matt , Shin Seungryul Ryan
Published: January 2025

We provide evidence that an influx of technical human capital improves regional entrepreneurship, both by increasing firm entry and reducing entrepreneurial failure. The results also indicate negative externalities upon lowtech and competing industries: an influx of inventors in a county shifts the locus of venture capital investment away from low-tech startups to high-tech startups and moreover towards new ventures in the same sector as those inventors' skills. We strengthen causal inference with a shift-share instrument which combines the spatial distribution of surnames in the LM>= U.S. Census with thousands of surnamespecific shifts based on modern inventor mobility.
Individualized Benefits and Access to Active Labor Market Programs Boost Refugee Women's Economic Integration
Authors: Bratu Cristina , Martén Linna , Ottosson Lillit
Published: January 2025

The economic and social integration of refugees is a key policy concern and the situation of refugee women is particularly challenging, as many never enter the labor force. We study a reform of the Swedish integration program designed to tackle this issue by increasing women's participation in and access to active labor market programs. Using administrative data and a regression discontinuity design, we show that the reform resulted in lasting improvements in women's earnings and employment. We find no effects for men. Additional analyses suggest that individualizing financial benefits and early registration with the Public Employment Service are key mechanisms.
Persistent Stigma in Space: 100 Years of Japan's Invisible Race and Their Neighborhoods
Authors: Yamagishi Atsushi , Sato Yasuhiro
Published: January 2025

We provide evidence of a large and persistent land price discount in neighborhoods historically inhabited by the outcaste group (buraku) in Japan. Our border design shows that this price discount declined from 53% in 1912 to 11% in 2006 but remained constant thereafter. Furthermore, we provide evidence that the vestiges of territorial stigma of buraku areas is the primary cause of these persistently lower land prices. Living in the stigmatized buraku area increases the risk of being identified as buraku and experiencing discrimination. Therefore, the lower land prices reflect the higher discrimination risk in the spatial equilibrium of our model.
Sticky Prices or Sticky Wages? An Equivalence Result
Authors: Bilbiie Florin , Trabandt Mathias
Published: January 2025

We show an equivalence result in the representative-agent New-Keynesian model after demand, wage-markup and correlated price-markup and TFP shocks: assuming sticky prices and flexible wages yields identical allocations for GDP, consumption, labor, inflation and interest rates to the opposite case—flexible prices and sticky wages. This equivalence arises with identical price and wage Phillips-curve slopes and generalizes to any slopes' pair whose sum and product are identical. Equilibrium profits and wages are, however, substantially different; equivalence breaks when these factor-distributional implications matter for aggregate allocations, e.g. in New-Keynesian models with heterogeneous agents, endogenous firm entry, and non-constant returns to scale.
Soft Texts
Authors: Orsini Francesca
Published: January 2025

David Damrosch’s formulation of world literature has energized the field but struggles to include texts that circulate but are not “read as literature.” This essay takes up the case of songs, and particularly Bhojpuri songs, and follows their trajectory of circulation and of linguistic adaptation to prise open this formulation and make space for songs and oral literature.
Facing Challenges and Opportunities
Authors: Zhang Longxi
Published: January 2025

Chinese-Western comparative literature is a difficult area of study that requires a high level of competence in languages, cultures, and histories across the huge differences between China and the West. It also has the remarkable potential to make contributions to comparative literature and comparative poetics. This essay discusses the exemplary works of Zhu Guangqian and Qian Zhongshu as our predecessors and continues to explore the different relationship between parallelism and end rhyme as an example of making contributions to comparative poetics from the perspective of Chinese literature and criticism.
Some Under Heaven
Authors: Saussy Haun
Published: January 2025

The extension of World Literature, a profoundly valuable concept, implies a degree of homogeneity among its objects which undermines the promise of this disciplinary field. Enlarging the scope of World Literature to include the vast corpus of Chinese writing only raises the stakes, for this corpus is internally heterogeneous, temporally differentiated, and does not always answer to the generic labels most commonly assumed in the constitution of comparables by investigators in World Literature. The present article pleads for a deeper temporal range and a greater categorical flexibility in the theory of World Literature, and above all for a suspension of the privilege tacitly granted to European neoclassical ideas of genre and style.
A new species of Neosilba (Diptera, Lonchaeidae) associated with fig orchards in Mexico
Authors: MACGOWAN IAIN , NAVARRO-DE-LA-FUENTE LAURA , WILLIAMS TREVOR , LASA RODRIGO
Published: January 2025

A distinctive species of Neosilba Waddill & Weems, namely Neosilba flavitarsis sp. nov is described from specimens reared from cultivated figs in Mexico. DNA sequencing confirms that the species belongs in the genus Neosilba and it is placed in a phylogenetic tree with other close relatives.