bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication-related hospitalisations in patients with SLE
Authors: Stanciu Michèle , Lee Joo-Young Esther , McDonald Emily G , Clark Gregory , Pineau Christian A , Kalache Fares , Grenier Louis-Pierre , Vinet Évelyne , Bernatsky Sasha , Mendel Arielle
Published: January 2025

Objectives

Patients with SLE take multiple medications. Within a large prospective longitudinal SLE cohort, we characterised medication-related hospitalisations and their preventability.

Methods

We identified consecutive admissions to our tertiary hospitals between 2015 and 2020. Two independent adjudicators evaluated if medication-related events contributed to the hospitalisation, considering (1) adverse drug events (ADEs) and (2) events from medication non-adherence, using the Leape and Bates method. We classified ADEs as potentially preventable/ameliorable if we identified modifiable factors. Logistic regressions with generalised estimating equations evaluated associations between participant characteristics and medication-related hospitalisations, accounting for repeat hospitalisations within the same participant.

Results

We studied 68 hospitalisations among 45 participants (91% female). At first hospitalisation, the median age was 38 years (IQR 26.5–53.0) and median SLE duration was 12 years (IQR 5.5–19.5). One or more ADEs contributed to 20 (29%) hospitalisations (11/23 (48%) ADEs being preventable/ameliorable), and SLE flares associated with medication non-adherence contributed to 7 (10%) hospitalisations. Adjusting for age and sex, current prednisone use (adjusted OR (aOR) 3.7, 95% CI 1.1 to 13.0) or ≥1 current immunosuppressant (aOR 11.5, 95% CI 2.7 to 50.0), renal involvement at SLE diagnosis (aOR 6.5, 95% CI 2.7 to 15.7) and polypharmacy (≥5 medications; aOR 11.3, 95% CI 1.2 to 103.8) were associated with having an ADE-related (vs non-ADE) hospitalisation. Age at SLE diagnosis<18 years (OR 5.9, 95% CI 1.3 to 26.6) was associated with hospitalisation for a flare related to non-adherence.

Conclusion

Forty per cent of SLE hospitalisations were medication-related, while half were potentially preventable/ameliorable. Renal involvement, polypharmacy, prednisone and immunosuppressant use were associated with hospitalisation related to an ADE, highlighting a vulnerable group.
Effectiveness of syndecan-1 as an adjunct diagnostic marker in small bowel injury: a report of two cases
Authors: Yamaji Fuminori , Fukuta Tetsuya , Ichihashi Masahiro , Mizuno Yosuke , Suzuki Keiko , Miyake Takahito , Kanda Norihide , Okada Hideshi
Published: January 2025

Background

Small bowel injuries are rare in trauma. Diagnosing these injuries is difficult owing to the lack of clear signs, and delays in diagnosis might increase complications and mortality. Trauma can damage the vascular endothelial glycocalyx, with syndecan-1 emerging as a marker of injury. Here, we describe two cases of small bowel injury due to traffic motor vehicle crash trauma.

Case presentation

The patients, one in their 40s and one teenaged, were transported to our hospital after a traffic motor vehicle crash. Both patients were wearing seat belts at the time of the motor vehicle crash, and the car’s airbags deployed properly. Their vital signs were stable at admission, and non-operative treatment was selected. However, their abdominal pain did not improve, and based on posthospitalization CT reconstructive imaging, intra-abdominal hemorrhage was suspected. Surgery was performed, revealing small intestinal injuries. In both patients, a high serum syndecan-1 level in the blood test at admission was a common characteristic.

Conclusion

Increased serum syndecan-1 level was observed in blood tests during the initial treatment of small intestinal injuries in these patients, suggesting its potential utility in early diagnosis. However, further accumulation of cases and detailed studies are required to substantiate these results.
Spruce budworm defoliation patterns during outbreak rise are influenced by tree species, insecticide spraying, and spatial autocorrelation
Authors: Donovan Shawn David , MacLean David A. , Hennigar Chris , Johns Rob , Zhang Yun
Published: January 2025

Spruce budworm (SBW; Choristoneura fumiferana Clem.) outbreaks are an important natural disturbance in North America, killing trees over millions of hectares. We related 11 years of SBW defoliation in 87 plots in Gaspé Peninsula, Québec, to 23 stand, site, and climate variables. Defoliation was consistently ordered among host species: balsam fir > white spruce > black spruce. Within the relatively small 200 km2 study area, cluster analyses resulted in four and 10 clusters for balsam fir cumulative and current defoliation, respectively; variation in cumulative defoliation converged over 11 years. Current defoliation was significantly spatially autocorrelated among plots within stands, but autocorrelation weakened at distances >2500m. Cumulative defoliation was significantly related to insecticide spraying, minimum and maximum summer temperature, and interactions between SBW larvae per branch versus hardwood and white spruce basal area. Tree species, insecticide spraying, and number of defoliating SBW larvae were the main determinants of defoliation. Results showed much higher local spatial variability in current defoliation patterns than previous studies, but over the course of an outbreak, cumulative defoliation patterns converged. Cumulative defoliation patterns similar to these, assigned based on local defoliation severity, can be input into defoliation-based growth models to predict impacts on growth and survival.
Karyotype Evolution of Suliformes and Description of a ♂Z1Z1Z2Z2/♀Z1Z2W Multiple Sex Chromosome System in boobies (Sula spp.)
Authors: Pozzobon Luciano , Toma Gustavo Akira , Cioffi Marcelo Bello , Herculano Correa de Oliveira Edivaldo , Kretschmer Rafael , de Freitas Thales Renato Ochotorena
Published: January 2025

Our comprehension of avian karyotypes still needs to be improved, especially for Suliform birds. To enhance understanding of chromosomal evolution in this order, we conducted conventional and molecular cytogenetic analysis in five species, named Sula dactylatra, S. leucogaster, S. sula (Sulidae), Fregata magnificens (Fregatidae), and Nannopterum brasilianum (Phalacrocoracidae). The diploid chromosome number for S. dactylatra and S. leucogaster was established as 2n = 76 in males, and 2n = 75 in females, but S. sula displayed a karyotype of 2n = 76 chromosomes in males. The disparity in diploid chromosome numbers between male and female Sula is due to a multiple sex chromosome system of the Z1Z1Z2Z2/Z1Z2W type. We propose that the emergence of this multiple-sex chromosome system resulted from a Robertsonian translocation involving the W chromosome and the smallest microchromosome. F. magnificens exhibited a diploid number 76 (2n = 76), while N. brasilianum displayed a diploid number of 74 (2n = 74) in both sexes. The ribosomal cluster was located in one microchromosome pair in S. dactylatra, S. leucogaster, S. sula, and F. magnificens and in four pairs in N. brasilianum. Our findings provide evidence of a conserved multiple-sex chromosome system within the Sula genus, shedding light on the high karyotype diversity in Suliformes.
Analytical investigation of the mass spectrum of tetraquarks with a relativistic approach
Authors: Ghasempour A. , Tazimi N. , Monemzadeh M.
Published: January 2025

In this paper, we study four-body systems and consider them as diquark–antidiquark. We use the Bethe–Salpeter equation (Schrödinger equation with relativistic kinematics) to calculate the binding energies and the mass of heavy tetraquarks with hidden charm and bottom structures. To solve the Bethe–Salpeter equation, we use the Hellmann potential and the Ansatz method and calculate the mass of tetraquarks X(3.872),  Y(3.940), 

$$Z_{cs}(3.985),$$

Z

cs

(
3.985
)

,

X(4.140), 

$$Z_{b}(10.610),$$

Z
b

(
10.610
)

,

and

$$Z_{b}(10.650).$$

Z
b

(
10.650
)

.

Our results are in good agreement with theoretical and experimental data.
Positive energy density in topologically charged exponential wormholes and Regge–Wheeler potential
Authors: Ahmed Faizuddin , Goswami Jaydeep , Bouzenada Abdelmalek
Published: January 2025

In this paper, we investigate a series of topologically charged exponential traversable wormhole models described by the standard metric form:

$$\begin{aligned}ds^2=-\mathcal {A}^2(r)\,dt^2+\mathcal {B}^2(r)\,\left[ \frac{dr^2}{\alpha ^2}+r^2\,(d\theta ^2+\sin ^2\theta \,d\phi ^2)\right] ,\end{aligned}$$

d

s
2

=
-

A

2

(
r
)

d

t
2

+

B

2

(
r
)

d

r
2

α
2

+

r
2

(
d

θ
2

+

sin
2

θ

d

ϕ
2

)

,

where

$$0< \alpha < 1$$

0
<
α
<
1

is the global monopole chare parameter. We focus on the positivity of the energy density across these models, defined by the following functions: (i)

$$\mathcal {A}(r)=\exp \left( -\frac{M}{r}\right) $$

A

(
r
)

=
exp

-

M
r

and

$$\mathcal {B}(r)=\exp \left( \frac{M}{r}+\beta \,r\right) $$

B

(
r
)

=
exp

M
r

+
β

r

, (ii)

$$\mathcal {A}(r)=\exp \left( -\frac{M}{r}-\gamma \,r\right) $$

A

(
r
)

=
exp

-

M
r

-
γ

r

and

$$\mathcal {B}(r)=\exp \left( \frac{M}{r}\right) $$

B

(
r
)

=
exp

M
r

, and (iii)

$$\mathcal {A}(r)=\exp \left( -\frac{M}{r}-\gamma \,r\right) $$

A

(
r
)

=
exp

-

M
r

-
γ

r

and

$$\mathcal {B}(r)=\exp \left( \frac{M}{r}+\beta \,r\right) $$

B

(
r
)

=
exp

M
r

+
β

r

, where

$$M, \beta $$

M
,
β

and

$$\gamma $$

γ

are constants. For each model, we evaluate key properties such as the wormhole throat radius, geometric stability, and energy conditions. Additionally, we analyze geodesic motions of test particle around a generalized wormhole, highlighting how the presence of the global monopole parameter affects trajectories of test particles within this topologically charged wormhole. Our results demonstrate that the radius of the wormhole throat is consistent with established characteristics of traversable wormholes and is free from singularities. subsequently, we study the Regge–Wheeler (RW) potential in the context of our chosen wormhole background, providing a detail analysis of its implications for spin zero scalar s-waves with multipole number

$$\ell =0$$

ℓ
=
0

. our analysis shows that the RW potential for spin zero scalar field is influence by the global monopole parameter and the coupling constant, which possesses dimensions inverse to that of length present in the wormhole space-time geometry. This modification has profound implications for the stability and dynamics of scalar perturbations in the vicinity of the wormhole, potentially affecting the stability of the wormhole itself.
Notes on integrating out M2 branes
Authors: Hattab Jarod , Palti Eran
Published: January 2025

Integrating out supersymmetric M2 branes wrapped on two-cycles in Calabi–Yau manifolds is an important calculation: it allows the determination of, and in some ways defines, the free energy of topological strings. In these notes, based on a short course aimed at graduate students, we go through various aspects of this calculation in detail. The end result is a recently proposed new formula for the topological string free energy.
Polarized $$W^+W^-$$ pairs at the LHC: Effects from bottom-quark induced processes at NLO QCD + EW
Authors: Dao Thi Nhung , Le Duc Ninh
Published: January 2025

We investigate the effects of the bottom-quark induced processes on the doubly polarized cross sections of

$$W^+W^-$$

W
+

W
-

pair production at the LHC. The method to extract the on-shell single-top contribution is provided. Results for phenomenological and experimental analyses are given at next-to-leading order (NLO) QCD + EW accuracy, with the leading contribution from the gluon–gluon and photon–photon fusion included. We found that the contribution of the bottom-quark induced processes, after the subtraction of the on-shell tW channel, is largest for the doubly longitudinal polarization. At the integrated cross section level, using a fiducial ATLAS cut with a jet veto, the effect is

$$9\%$$

9
%

compared to the NLO value of the light-quark contribution. It increases to

$$13\%$$

13
%

after removing the jet veto. A bound of the tW interference is calculated for various kinematic distributions, showing that this interference effect is, in general, smaller for the no jet veto case. Relevant scale uncertainties are calculated to help us decide on the importance of this interference.
Breaking Barriers with Data Equity: The Essential Role of Data Disaggregation in Achieving Health Equity
Authors: Ponce Ninez A. , Becker Tara , Shimkhada Riti
Published: January 2025

Achieving health equity necessitates high-quality data to address disparities that have remained stagnant or even worsened over time despite public health interventions. Data disaggregation, the breakdown of data into detailed subcategories, is crucial in health disparities research. It reveals and contextualizes hidden trends and patterns about marginalized populations and guides resource allocation and program development for specific needs in these populations. Data disaggregation underpins data equity, which uses community engagement to democratize data and develop better solutions for communities. Years of research on disaggregation show that researchers must collaborate closely with communities for adequate representation. However, despite generally positive support for this approach in health disparities research, data disaggregation faces methodological and political challenges. This review offers a framework for understanding data disaggregation in the context of data equity and highlights critical aspects of implementation, including challenges, opportunities, and recent policy and community-based efforts to address hurdles.
Predictive Value of Left Atrial Strain for Thrombotic Events in Hypertrophic Cardiomyopathy without Atrial Fibrillation
Authors: Pu Lutong , Jie Wang , Li Jialin , Qi Weitang , Xu Yuanwei , Wan Ke , Kang Yu , Zhang Qing , Han Yuchi , Chen Yucheng
Published: January 2025

Left atrial fast long-axis strain derived from cardiac MRI independently predicted the occurrence of thrombotic events in individuals with hypertrophic cardiomyopathy without atrial fibrillation.
Modified CT Technique Improves Image Quality for Assessment of Cardiac Conduction Device Lead Perforation
Authors: Huang Ryan S. , Karur Gauri Rani , Soares Torres Felipe , Cadour Farah , Du Plessis Jacques , Hanneman Kate , Karasfi Behruz , Nguyen Elsie T.
Published: January 2025

Adapting patient positioning and adjusting CT gantry angle significantly reduced the impact of metallic artifacts and enhanced image quality in identifying cardiac conduction device lead perforations.
Abstract 117: Comparison of Three Computational Algorithms for Determining Personalized Blood Pressure Targets after Thrombectomy
Authors: Thinzar Pwint , Jayasundara Sithmi , Vargas David , Stoehr Kaitlyn , Gilmore Emily , Kim Jennifer , Beekman Rachel , Matouk Charles , Smielewski Peter , Miller Eliza , Ortega-Gutierrez Santiago , Petersen Nils
Published: January 2025

Introduction:
Autoregulation-guided blood pressure (BP) management offers a promising alternative to targeting fixed BP thresholds after acute ischemic stroke. However, the time required to compute personalized BP goals has hindered its broad application at the bedside for post-thrombectomy patients. To address this gap, our study compared the ability of three computational algorithms to rapidly determine a personalized BP target without compromising reliability.

Methods:
From our prospectively maintained stroke database, we identified 206 patients who underwent thrombectomy for an anterior circulation large-vessel occlusion and had continuous physiologic data recordings for 24 hours post-thrombectomy. The cerebral autoregulatory index was used to calculate and trend the mean arterial pressure (MAP) at which autoregulation was most preserved (MAPopt) using three distinct algorithms (Yale, modified COGiTATE phase II, and Beqiri et al. 2024). Personalized BP targets were compared for the initial hour following the computation of MAPopt with each algorithm and throughout the 24-hour post-thrombectomy period. We analyzed the time to compute the first personalized MAPopt target and the reliability of MAPopt values over 24 hours using Bland-Altman analysis and intraclass correlation coefficient (ICC) analysis. One-way repeated measures ANOVA was conducted to examine differences in MAPopt values.

Results:
The first personalized BP target value could be calculated using the Yale algorithm after a median of 86 minutes, compared to 121 and 184 minutes for the Beqiri et al. and COGiTATE algorithms (p < .05). The Yale algorithm also significantly increased the number of patients for whom a personalized BP target could be calculated and provided more continuous MAPopt values (Table 1). The mean and standard deviations of MAPopt were similar across the algorithms over both the 1-hour and 24-hour periods (p > .05, Table 1). MAPopt values calculated by the Yale algorithm were consistent with those calculated by the other two algorithms, with a slight bias in the Bland-Altman analysis (0.05 mmHg for Yale vs. COGiTATE and 0.61 mmHg for Yale vs. Beqiri et al.) and an ICC of 0.89 (95% CI 0.86 - 0.91), p < .05.

Conclusions:
Our results demonstrate that the Yale algorithm computes a more continuous MAPopt and achieves target values faster without compromising reliability, making it a viable option for early and reliable personalized BP management in post-thrombectomy patients.
Abstract 119: Mediation of Time-Related Blood Pressure Variability on Intensive Blood Pressure Lowering and Functional Outcomes Post-Endovascular Therapy
Authors: Chang Jun
Published: January 2025

Background:
The deleterious effects of intensive blood pressure (BP) lowering in patients who achieved successful reperfusion may result from high BP variability (BPV). However, there is still uncertainty regarding whether the association between high BPV and poor outcomes indicates a causal relationship or if high BPV is merely a bystander or consequence of various factors associated with poor outcomes. We investigated whether the association between intensive BP management after endovascular therapy (EVT) and unfavorable functional outcomes is mediated by BPV.

Methods:
This is a secondary analysis of OPTIMAL-BP (The Outcome in Patients Treated with Intra-Arterial Thrombectomy-Optimal Blood Pressure Control), comparing intensive and conventional systolic BP (SBP) management for functional outcomes in patients with successful reperfusion post-EVT. Multivariable logistic regression analysis was conducted for the association between BPV and outcomes including 90-day modified Rankin Scale (mRS), symptomatic intracranial hemorrhage (sICH), and final infarction volume. Mediation analysis was performed to evaluate the causal inference whether the relationship between intensive BP management and the 90-day mRS is mediated by BPV.

Results:
The 24-hour time rate (TR) of SBP was significantly higher in the intensive BP management group. Higher TR was significantly associated with an unfavorable ordinal shift of the 90-day mRS (adjusted OR [aOR] 1.19, 95% CI 1.06–1.33, P=0.003). High TR significantly increased the final infarction volume (coefficient 24.03, 95% CI 6.50–41.56, P=0.007), but did not increase the risk of sICH. TR fully mediated the association between intensive BP management and functional outcomes. The proportions of the association explained by TR was 32.15%.

Conclusions:
TR mediated the association of intensive BP management for 24 hours and poor functional outcome in successfully reperfused ischemic stroke patients. Efforts to modulate BPV after EVT may be helpful in improving clinical outcomes.
Abstract 130: Recent Infection is Associated with Pediatric Stroke: A Population-Based Study Using Linked Administrative Data
Authors: Dalli Lachlan , Olaiya Muideen , Morgan Hannah , Kilkenny Monique , Fahey Michael , Mackay Mark , Cadilhac Dominique , Gall Seana , Boyle Jacqueline , Clothier Hazel , Buttery Jim
Published: January 2025

Introduction:
Pediatric stroke is a rare event associated with high morbidity and reduced quality of life. While the causes of pediatric stroke are often unclear, recent infection is thought to be a significant factor. We sought to determine the incidence of pediatric stroke in Australia and whether recent infections and vaccinations are associated with pediatric stroke.

Methods:
A population-based observational study was undertaken using routinely collected and linked data from the Vaccine Safety Health Link. The cohort comprised all children, aged 28 days to 18 years, admitted to hospital between 1 Jan 2017 and 31 December 2023 in the state of Victoria, Australia. Pediatric stroke was determined using state-wide hospital admissions and death registration datasets. To examine associations with pediatric stroke, each case of pediatric stroke was matched with up to five controls based on age (within 5-year bands), sex, and month and year of admission. Using national immunization and notifiable infection registers, we examined vaccines and notifiable infections in the 60-day period before admission. Associations with pediatric stroke were examined using logistic regression, adjusted for age, sex and country of birth (Australia vs other).

Results:
Among 430,368 admitted children (46% female; median age 9.1 years [interquartile range: 4.5-14.4]), 411 had a pediatric stroke (45% female; median age 7.3 years [interquartile range: 1.2-14.4 years]), corresponding to an incidence rate of 13.6 events (95% CI 12.4–15.0) per 100,000 person-years. COVID-19 and influenza were the most common notifiable infections in the previous 60 days (Figure 1). After matching, there were 411 stroke cases and 2,055 controls. Children with pediatric stroke (vs matched controls) were more likely to have had a notifiable infection in the previous 60 days (6.6% vs 3.3%; adjusted odds ratio: 2.09; [95% CI: 1.32–3.32]). There was no significant association between vaccination in the previous 60 days and pediatric stroke (6.1% vs 4.9%; adjusted odds ratio: 1.23 [95% CI: 0.77–1.94]).

Conclusions:
We provide contemporary data on the incidence of pediatric stroke and show that having a recent infection doubles the odds of pediatric stroke. Vaccination was not associated with an increased risk of stroke and should be encouraged more widely to prevent infections and any downstream effect on the risk of stroke.
Abstract 14: A distinct clot transcriptomic signature is associated with atrial fibrillation-derived ischemic stroke in the INSIGHT Registry
Authors: Seah Carina , Devarajan Alex , Vicari James , Dabney Alan , Baltan Selva , Sohrabji Farida , Pennypacker Keith , Nanda Ashish , Woodward Britton , Rivet Dennis , Fraser Justin , Kellner Christopher
Published: January 2025

Funding:
The INSIGHT Registry is funded by Penumbra.

Introduction:
Rapid and precise determination of the etiology of acute ischemic stroke is crucial in long-term management and prevention of recurrence. Identification of etiology-associated molecular biomarkers following thrombectomy may allow for personalized intervention. Here, we examine the transcriptomics of cardioembolic thrombi as a result of atrial fibrillation, identifying a distinct transcriptomic signature relative to other causes of ischemic stroke.

Methods:
The INSIGHT registry is a prospective, multicenter, multi-omic registry focused on elucidating the molecular underpinnings of stroke from analysis of clot and interarterial blood. RNA sequencing of 10,990 genes from 292 thrombi from patients undergoing thrombectomy was analyzed using edgeR, sva, and limma/voom. 111 patients had a determined etiology of atrial fibrillation. Controls had unknown, atheroembolic, or coagulopathy stroke etiology. Significant association of thrombus gene expression with atrial fibrillation was conducted using the Wilcoxon Rank Sum test using Benjamini-Hochberg multiple testing correction (FDR <5%). Gene set enrichment was performed using FGSEA using Gene Ontology biological processes gene sets. Co-expression modules were detected using WGCNA and analyzed using cytoscape.

Results:
33 genes (27 upregulated, 6 downregulated) within thrombi were significantly associated with atrial fibrillation etiology. These included upregulated endothelial cell markers associated with cardiac endothelial cells (e.g.
KDR
,
AMDHD2
,
IL18BP
) compared to thrombi of other etiologies. In addition, upregulated genes were associated with oxidative stress (FDR= 8.46x10
-8
) and metabolism (1.04x10
-6
), while adaptive T-cell immunity was downregulated (FDR= 7.52x10
-3
). Co-expressed gene networks upregulated by atrial fibrillation-associated thrombi included a module implicated in innate immune signaling and cytotoxic granule release (p=0.02), which included key hub genes
GZMH
and
TBX21.

Conclusion:
Cardioembolic thrombi possess a distinct transcriptomic signature consistent with collection and retainment of cardiac endothelial tissue at origin, and display immunomodulatory activity associated with innate vs adaptive immune balance. This signature suggests the active role thrombi likely play in the vascular microenvironment and may ultimately be used to identify atrial fibrillation as an etiology in strokes of unknown origin.
Abstract 140: Risk of Recurrent Ischemic Stroke Among Patients with Cryptogenic Stroke and Left Ventricular Ejection Fraction <50%: A Secondary Analysis of the ARCADIA Trial
Authors: Jillella Dinesh , Sharma Richa , Zhang Cenai , Elkind Mitchell , Kamel Hooman , Kronmal Richard , Longstreth W , Tirschwell David , Di Tullio Marco , Merkler Alexander , Nahab Fadi
Published: January 2025

Background:
Nearly one-quarter of ischemic strokes (IS) in the U.S. are recurrent. We aimed to determine the risk of recurrent IS associated with reduced left ventricular ejection fraction (LVEF) in patients enrolled in the ARCADIA trial.

Methods:
We performed a post-hoc exploratory analysis in the ARCADIA trial, a phase III RCT of 1,015 cryptogenic stroke patients with atrial cardiopathy from February 2018 to February 2023. Those with LVEF <30% were not eligible. We dichotomized patients with LVEF into <50% and
>
50% and built adjusted Cox proportional hazard models to estimate the hazard ratio (HR) of recurrent IS within each LVEF strata by treatment strategy of apixaban versus aspirin. Significance of the interaction was assessed after adjustment for imbalanced covariates found among these groups.

Results:
The analytic cohort comprised 963 participants, with LVEF <50% in 74 (7.7%) and ≥50% in 889 (92.3%). Participants with LVEF<50% compared to
>
50% were younger (65 vs 68 years, p=0.006), more likely male (63.5% vs 44.4%, p=0.002) and of non-White race (45.9% vs 23.8%, p<0.001), and to have coronary artery disease (25.7% vs 8.9%, p<0.001) and CHF (33.8% vs 4.7%, p<0.001), higher N-terminal pro-BNP (median 487 vs 292 pg/mL, p<0.001), larger left atrial diameter index (median 2.1 vs 1.9 cm, p<0.001), and lower LVEF (median 43% vs 62%, p<0.001); P-wave terminal force in V1 was similar. Recurrent IS occurred in 10 (13.5%) patients with LVEF <50% and 61 (6.9%) with LVEF ≥ 50%. The incidence rates of recurrent stroke per 100 person-years were 7.1 (95% CI, 3.8-13.3) with LVEF <50% and 3.9 (95% CI, 3.0-5.0) with LVEF ≥ 50%. In the adjusted analysis, the risk of recurrent stroke was significantly higher with LVEF <50% vs ≥50% (HR 2.23, 95% CI 1.03-4.83). There was no significant interaction between LVEF stratum and the treatment effect (p=0.35; Figure). The risk of recurrent stroke was nominally lower among patients randomized to apixaban than aspirin with LVEF <50% (HR 0.11, 95% C.I. 0.01-1.12), and EF
>
50% (HR 0.87, 95% C.I. 0.52-1.45) but did not reach statistical significance.

Conclusion:
Recurrent stroke risk was higher among patients with LVEF <50% vs ≥50%. The risk of recurrent stroke was not different among patients randomized to apixaban compared to aspirin. Further study is needed to identify the optimal anti-thrombotic treatment for patients with cryptogenic stroke and left ventricular dysfunction.
Abstract 15: Integrated Genomic and Proteomic Drug Target Discovery for Ischemic Stroke
Authors: Huo Shufan , Clocchiatti-Tuozzo Santiago , Magid-Bernstein Jessica , Sharma Richa , RANGARAJU Srikant , Sansing Lauren , Sheth Kevin , Rivier Cyprien , Falcone Guido
Published: January 2025

Background:
Ischemic stroke (IS) is a multifactorial disease with a significant genetic component contributing about 40% of the risk. Current prevention strategies focus on risk factor control, but integrating genomic and proteomic data could uncover key molecular targets for more effective treatments based on genetic insights.

Objective:
To utilize a comprehensive multi-omic approach to identify novel drug targets that mediate the genetic risk of IS.

Methods:
We analyzed genomic and proteomic data from 53,014 UK Biobank participants. Using a polygenic risk score (PRS) for IS from 43 independent risk variants, we deployed four analytical steps (Fig. 1, all steps corrected for multiple testing): (1) linear regression between PRS and 2,923 standardized protein levels measured at baseline, adjusted for age, sex, and genetic principal components; (2) association between selected proteins and IS; (3) Mendelian Randomization to assess causality for the proteins from (1+2), and (4) mediation to quantify the intermediary role of causal proteins in the PRS-stroke relationship. To provide clinical context, we conducted a proof-of-concept analysis using Alzheimer's disease (AD) given APOE's established role in AD risk.

Results:
We found 15 proteins that causally mediate the association between polygenic risk and IS (Fig. 2). The identified proteins are involved in cell adhesion (e.g. CD34, CD48, PODXL), inflammatory pathways (e.g. CD28, CD300A, NCR1), angiogenesis (FGF5, MET), and protein glycosylation (GALNT10, GCNT1), influencing vascular integrity, immune response, and blood vessel formation. Mediated effects range from 1-5% per protein and two proteins served as targets for existing or developing drugs (Tab. 1). As proof-of-concept, we discovered five proteins with significant mediation in AD, the strongest effect seen in APOE (10% mediated effect) and MENT (5%), confirming their known roles in neurodegenerative processes.

Conclusion:
This multi-omic strategy successfully identified 15 proteins mediating polygenic risk of IS, highlighting crucial pathways such as cell adhesion, inflammation, angiogenesis, and glycosylation. These findings can advance targeted therapies for stroke risk in primary prevention. Our proof-of-concept study illustrates the clinical meaning of the proteins in comparison with the known impact of APOE on AD. Future work should focus on validating these targets in clinical settings and exploring drug repurposing opportunities.
Abstract 151: Presenting Signs and Symptoms of Maternal Stroke by Stroke Type: a Multicenter, Retrospective Case Series
Authors: shang catherine , Haghighi Noora , Bourscheid Raeann , Romo Elida , Seitz Alison , Shapouran Sara , Mamer Lauren , Meurer William , Liberman Ava , Shields Andrea , Holl Jane , Prabhakaran Shyam , Miller Eliza
Published: January 2025

Introduction:
Stroke is a leading cause of maternal morbidity and mortality, and the incidence of maternal stroke is triple that of age-matched, non-pregnant counterparts. Mechanisms of pregnancy-related stroke differ compared to those of the non-pregnant population, but few data exist regarding presenting signs and symptoms of maternal stroke, which is often missed at initial presentation. We characterized presenting signs and symptoms by stroke subtype in a large retrospective multicenter case series.

Methods:
We reviewed cases of pregnant and postpartum stroke patients at 5 stroke centers. Eligible patients were between ages 18-50 years, with a confirmed diagnosis of arterial ischemic stroke (AIS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) or cerebral venous thrombosis (CVT) between 01/01/2012 and 12/31/2021. Presenting signs and symptoms were reviewed and aggregated into 6 categories: altered mental status (AMS), seizure, headache, focal neurological deficits, systemic symptoms, and dizziness/imbalance. We show the distribution of presenting symptoms for each stroke subtype and for all strokes.

Results:
A total of 121 cases of maternal stroke were reviewed, of which 37% had AIS, 17% had SAH, 31% had ICH, and 15% had CVT. Characteristics of the study population are shown in the Table. Focal neurological deficits were the most common presenting sign/symptom, overall (59%), followed by headache (51%), systemic symptoms (26%), AMS (16%), and dizziness (16%). The distribution of symptoms varied by stroke subtype (p<0.000001; Figure): AIS had the highest proportion of focal neurological deficits (91%) whereas headache was the most common presenting symptom in all other stroke subtypes. Systemic symptoms were present in 42% of ICH cases, 33% of SAH, and 25% of CVT, compared with 11% of AIS.

Conclusions:
This is the largest case series to date of maternal stroke in the United States. The characteristics of strokes in the cohort are consistent with those observed in previous studies, in which up to half of maternal strokes were hemorrhagic and most occurred postpartum. Given the high proportion of non-focal symptoms observed in non-AIS subtypes, stroke should be considered in the differential diagnosis for pregnant and postpartum women presenting acutely with headache, particularly if accompanying systemic symptoms or focal neurological deficits are present.
Abstract 153: Thrombectomy Versus Medical Therapy In Patients With Acute Ischemic Stroke Irrespective of The Alberta Stroke Program Early Computed Tomography Score. A Systematic Review And Meta-Analysis.
Authors: OBI OGECHUKWU , Cavalcante Deivyd , Nweze Uchenna , Asonye Patricia , Lee Timothy
Published: January 2025

Background:
The efficacy and safety of thrombectomy compared to medical therapy in patients with acute ischemic stroke irrespective of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) has been debated.

Method:
We systematically searched EMBASE, PubMed and Scopus for randomized controlled trials (RCTs) and observational studies evaluating the efficacy and safety of thrombectomy compared to medical therapy in patients with acute ischemic stroke irrespective of the ASPECTS score with primary outcomes of modified rankin scale (mRS) score 0-3 at 90 days, functional independence mRS score 0-2 at 90 days and symptomatic intracranial hemorrhage (sICH).

Results:
We included 20 RCTs and 6 observational studies containing 6580 patients comparing thrombectomy with medical therapy in patients with acute ischemic stroke irrespective of the ASPECTS scores. The pooled results showed that mRS score 0-3 at 90days (RR = 2.10; 95% CI [1.59; 2.77]; I
2
= 71%; p < 0.001; Figure 1A) and mRS score 0-2 at 90 days (OR = 2.48; 95% CI [1.97; 3.12]; I
2
= 64%; p < 0.001; Figure 1B) were significantly improved by thrombectomy compared to the medical therapy. Early neurologic worsening (RR = 0.93; 95% CI [0.57; 1.51]; I
2
= 63%; p = 0.770; Figure 1C) was not significantly different between groups. The safety outcome, sICH within 48hrs (RR = 1.82; 95% CI [1.25; 2.64]; I
2
= 50%; p = 0.002; Figure 2A) was significantly higher in thrombectomy group. The National Institutes of Health Stroke Scale (NIHSS) score at 24hrs (MD = -2.84; 95% CI [-4.11; -1.58]; I
2
= 65%; p < 0.001; Figure 2B) and mean change in infarct volume from baseline at 24hrs (MD = -26.10; 95% CI [-40.18; -12.02]; I
2
= 97%; p < 0.001; Figure 2C) were significantly reduced by thrombectomy. However, decompressive craniotomy (RR = 1.17; 95% CI [0.78; 1.75]; I
2
= 20%; p = 0.453; Figure 2D) did not show any difference between groups. Death within 90 days (OR = 0.71; 95% CI [0.61; 0.81]; I
2
= 22%; p < 0.001; Figure 3A) was significantly reduced by thrombectomy. The early neurologic improvement (SMD = 3.43; 95% CI [2.39; 4.93]; I
2
= 37%; p < 0.001) and median EuroQol Group 5 Dimension (EQ-5D) index at 90days (MD = 0.15; 95% CI [0.07; 0.23]; I
2
= 84%; p < 0.001; Figure 3C) were also improved by thrombectomy.

Conclusion:
Compared with medical therapy, thrombectomy may improve functional outcomes in patients with acute ischemic stroke irrespective of the ASPECTS scores, despite associated with an increased risk of sICH.
Abstract 157: Bio-orthogonal Amino Acid Tagging Identifies Nascent
in vivo
Astrocyte-specific Proteomic Alterations following Transient Global Ischemia
Authors: Malepati Sneha , kumar prateek , Srivastava Upasna , Cheng Lihong , Rayaprolu Sruti , Xiao Hailian , Duong Duc , Seyfried Nicolas , RANGARAJU Srikant
Published: January 2025

Introduction:
Ischemic injury to the brain results in both acute and long-lasting effects that may trigger progressive neurodegenerative cascades mediated by glial cells such as astrocytes, the most common glial cell in the brain. However, a comprehensive understanding of proteomic changes occurring in astrocytes following ischemic injury, while retaining their native state
in vivo
, is lacking.

Methods:
We applied cell type-specific
in vivo
bio-orthogonal non-canonical amino acid tagging (ciBONCAT) to label newly-synthesized (nascent) proteins, specifically in astrocytes. BONCAT uses Cre-mediated recombination to express mutant Methionyl-tRNA synthetase (MetRS) that tags nascent proteins with the Methionine analog Azidonorleucine (Anl) for purification using Click-chemistry, along with GFP reporter expression. Experimental diffuse cortical ischemia was induced in Aldh1l1-Cre-ert2/MetRS-floxed mice via a 20-minute bilateral common carotid artery occlusion (BCCAO), followed by 3-week Anl water supplementation. Azide-tagged proteins from cortices were Click-labeled with biotin-alkyne, then enriched and analyzed by label-free Mass Spectrometry (LFQ-MS).

Results:
Immunofluorescence (IF) microscopy confirmed astrocyte-specific GFP expression in the brains of astrocyte-BONCAT mice (A). Western blot confirmed proteomic labeling in astrocyte-BONCAT mice as compared to controls (B). After enrichment of azide-tagged proteins, LFQ-MS identified an astrocyte-specific nascent proteome of over 1,200 proteins, including canonical astrocyte markers (eg. GFAP, Aqp4, Aldh1l1). BCCAO resulted in reactive astrocytosis in the cortex and hippocampus as verified by IF. LFQ-MS identified distinct proteomic changes occurring specifically in astrocytes, including 84 upregulated (eg. Fus, Adrbk1) and 100 downregulated (eg. Ndufs8, Necap1) proteins (C). Gene set enrichment analyses revealed increased translation and mitochondrial metabolic changes in astrocytes in response to BCCAO.

Conclusions:
We used ciBONCAT to obtain native-state astrocyte-specific nascent proteomes from the adult mouse brain. This novel approach identified unique astrocyte-specific proteomic alterations related to mitochondria, metabolism, and translation following BCCAO. These astrocytic proteomic changes are likely indicative of long-lasting progressive changes several weeks following transient global ischemic injury, representing potential targets for drug therapy to facilitate and improve stroke recovery.
Abstract 16: Short and long term efficacy of Colchicine for prevention of stroke and major adverse cardiovascular events: A Meta-analysis with CHANCE 3, and CONVINCE randomized controlled trials.
Authors: Jaiswal Vikash , Deb Novonil , Hanif Muhammad , Iqbal Rabia , Naz Sidra , Shrestha Abhigan , Jaiswal Akash
Published: January 2025

Background:
Colchicine has shown to reduce major adverse cardiovascular events and stroke among patients with coronary artery disease. However, its efficacy with short and long use and risk of stroke has not been well studied with conflicting results till date.

Objective:
We sought to evaluate the short and long term efficacy of Colchicine for prevention of stroke and major adverse cardiovascular events (MACE).

Methods:
We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until July 20th, 2024. Odds ratios (OR) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant. Studies were categorized based on followup duration of < 6 months vs ≥ 6 months.

Results:
A total of 16 randomized controlled trials with 24967 patients were included (12538 in Colchicine and 12429 in the control group) in the analysis. The mean age of the colchicine intervention group was 61.69 years, and 62 years in the placebo group. Polled analysis of primary outcome shows that colchicine with longer followup (i.e; ≥ 6 months) significantly reduced the risk of stroke by 39% (OR, 0.61(95%CI: 0.39-0.96), however colchicine with shorter followup (i.e;< 6 months) shows comparable risk of stroke compared with placebo (OR, 0.98 (95%CI: 0.82-1.16). Similarly, colchicine reduced the risk of MACE by 34% among patients with long term followup (OR, 0.66(95%CI: 0.53-0.82), but not in short term groups of patients (OR, 0.91(95%CI: 0.05-15.54). However, risk of cardiovascular mortality at long term followup (OR, 0.81 (95%CI: 0.47, 1.39), short term followup (OR, 0.71 (95%CI: 0.40-1.27), and risk of all cause mortality at long term followup (OR, 1.04 (95%CI: 0.67-1.63), and short term followup (0R, 0.74(95%CI:0.50-1.12) was comparable between colchicine and placebo group.

Conclusion:
These findings suggest that Colchicine reduced the risk of stroke and MACE at long term followup (≥ 6 months), but not among patients with shorter followup duration. These key findings for the first time shows colchince can be more effictive if used for longer duration among high risk patients .
Abstract 160: Offspring From Preeclamptic Pregnancy Have Worse Stroke Outcome in Adult Males but Not Females
Authors: Hunt Ryan , Tremble Sarah , Anderson Jennifer , McGreer Jayden , Cipolla Marilyn
Published: January 2025

Introduction:
Offspring from preeclamptic women are at increased risk of neurologic disorders later in life and have an increased risk of death from stroke. We hypothesized that the unfavorable intrauterine environment during preeclampsia (PE) causes cerebrovascular dysfunction and inflammation in offspring that worsens stroke outcome.

Methods:
Adult male and female offspring (n=6-8/group) from Sprague Dawley rats that had normal pregnancies (NormP-F1) or experimental PE (ePE-F1) underwent transient MCA occlusion (tMCAO) for 3 hours with 1 hour of reperfusion. Blood gases were kept within normal ranges. Multisite laser Doppler was used to measure changes in pial collateral flow and MCA cerebral blood flow (CBF) simultaneously. Infarct and edema were measured by TTC staining. After tMCAO, plasma was obtained to measure circulating inflammatory factors using Multiplex and ELISA. Data are reported as mean±SEM.

Results:
Offspring from ePE dams had elevated blood glucose, and sex-specific increases in infarct and edema—only ePE-F1 males had significantly larger infarcts compared to all other groups (48.0±5.7% vs. 9.0±1.3% ePE-F1 female, 10.9±3.9% NormP-F1 male, and 4.9±1.9% NormP-F1 female). The rate of hemorrhagic transformation (HT) was increased in both ePE-F1 males (100%) and females (62.5%) vs. NormP-F1s (male: 37.5%, female: 0%). The increased infarct in ePE-F1 males was associated with poor collateral flow, decreasing -59.8±3.3% which remained low during the ischemic period. In contrast collateral flow decreased -43.9±17.8% in ePE-F1 females that was not sustained and increased to baseline after 40 min of tMCAO. Both female and male NormP-F1’s had robust collateral flow, decreasing only -14.8±25.5% and -17.5±22.1%, respectively. There was an increase in circulating VEGF in ePE-F1 males vs NormP-F1 males (188.8±69.3 vs 39.2±7.5 pg/ml; p<0.05) but not between females. The concentration of the proinflammatory cytokine IL-1β and the anti-inflammatory cytokine IL-10 were increased in ePE-F1 males vs. NormP-F1 males (119.3±17.8 vs 35.3±7.7 and 765.4±83.8 vs 356.4±62.6 pg/ml; p<0.05) indicating an inflammatory mechanism not present in other groups.

Conclusion:
These data demonstrate the far-reaching effects of adverse pregnancy in PE that worsens stroke outcome in offspring. The mechanisms by which PE negatively impacts offspring in a sexually dimorphic manner is unclear but may be related to (epi)-genetic programming in utero on cerebrovascular development.
Abstract 17: The Effectiveness of a Community Health Worker-Led Intensive Blood Pressure Intervention on Stroke
Authors: Allouch Farah , Sun Guozhe , Guo Xiaofan , Liu Songyue , Wang Chang , xing liying , Qiao Lixia , Ye Ning , Xie Ziyi , Yin Yangzhi , Miao Wei , li zhi , Yu Yao , He Jiang , Sun Yingxian
Published: January 2025

Background:
Hypertension is the most important modifiable risk factor for stroke, a leading cause of death in China. Despite national efforts, stroke incidence and mortality rates remain high in China, with significant urban-rural disparities.

Objectives:
We aimed to examine the effectiveness of non-physician health worker-led antihypertensive interventions on the risk of stroke in rural China.

Methods:
We included 33,995 hypertensive participants from 326 villages in rural China using 48-month follow-up data from the China Rural Hypertension Control Project (CRHCP). In the CRHCP trial, non-physician healthcare workers initiated and titrated antihypertensive medications using a simple stepped-care protocol recommended by clinical guidelines. The primary outcome was total stroke during the 48-month follow-up period. Secondary outcomes included fatal and nonfatal strokes. We conducted a secondary analysis adjusted for pre-defined baseline covariates to examine the robustness of the intervention effect on stroke. Safety outcomes were also assessed at 48 months.

Results:
During a median of 48.2 months of follow-up, 1,151 strokes (1.7% yearly rate) occurred in participants in intervention villages compared to 1,484 strokes (2.4% yearly rate) in participants in usual care villages. The non-physician health worker-led intervention reduced stroke by 28% (hazard ratio = 0.72; 95% CI: 0.67, 0.77) in intervention compared to usual care participants. Similar reductions were also observed for fatal (hazard ratio = 0.74; 95% CI 0.63, 0.87) and nonfatal stroke (hazard ratio = 0.71; 95% CI 0.66, 0.78). Participants in intervention villages had a significantly lower rate of hospitalizations and deaths compared to usual care participants (risk ratio = 0.94; 95% CI 0.91, 0.98). There were no significant differences in rates of injurious falls, symptomatic hypotension, or syncope between the intervention and usual care villages.

Conclusion:
This study shows that a nonphysician health worker-led intensive BP control was effective at reducing stroke among rural residents in China. The non-physician community health worker-led intervention should be scaled up in China and other low- and middle-income countries to reduce the burden of stroke.