bluuebunny/crossref_metadata_2025 huggingface dataset:
Tight Complexity Bounds for Counting Generalized Dominating Sets in Bounded-Treewidth Graphs Part II: Hardness Results
Authors: Focke Jacob , Marx Dániel , Mc Inerney Fionn , Neuen Daniel , Sankar Govind S. , Schepper Philipp , Wellnitz Philip
Published: January 2025

For a well-studied family of domination-type problems, in bounded-treewidth graphs, we investigate whether it is possible to find faster algorithms. For sets
σ
,
ρ
of non-negative integers, a (
σ
,
ρ
)-set of a graph
G
is a set
S
of vertices such that |
N
(
u
)∩
S
| ∈
σ
for every
u
∈
S
, and |
N
(
v
)∩
S
| ∈
ρ
for every

\(v\not\in S \)

. The problem of finding a (
σ
,
ρ
)-set (of a certain size) unifies common problems like
Independent Set
,
Dominating Set
,
Independent Dominating Set
, and many others.

In an accompanying paper, it is proven that, for all pairs of finite or cofinite sets (
σ
,
ρ
), there is an algorithm that counts (
σ
,
ρ
)-sets in time

\((c_{\sigma,\rho })^{\sf tw}\cdot n^{{\rm O}(1)} \)

(if a tree decomposition of width

\({\sf tw} \)

is given in the input). Here,
c

σ
,
ρ

is a constant with an intricate dependency on
σ
and
ρ
. Despite this intricacy, we show that the algorithms in the accompanying paper are most likely optimal, i.e., for any pair (
σ
,
ρ
) of finite or cofinite sets where the problem is non-trivial, and any ε > 0, a

\((c_{\sigma,\rho }-\varepsilon)^{\sf tw}\cdot n^{{\rm O}(1)} \)

-algorithm counting the number of (
σ
,
ρ
)-sets would violate the Counting Strong Exponential-Time Hypothesis (#SETH). For finite sets
σ
and
ρ
, our lower bounds also extend to the decision version, showing that those algorithms are optimal in this setting as well.
Knowledge Distillation on Graphs: A Survey
Authors: Tian Yijun , Pei Shichao , Zhang Xiangliang , Zhang Chuxu , Chawla Nitesh
Published: January 2025

Graph Neural Networks (GNNs) have received significant attention for demonstrating their capability to handle graph data. However, they are difficult to be deployed in resource-limited devices because of model sizes and scalability constraints imposed by the multi-hop data dependency. In addition, real-world graphs usually possess complex structural information and features. Therefore, to improve the applicability of GNNs and fully encode the complicated topological information, Knowledge Distillation on Graphs (KDG) has been introduced to build a smaller but effective model, leading to model compression and performance improvement. Recently, KDG has achieved considerable progress, with many studies proposed. In this survey, we systematically review these works. Specifically, we first introduce the challenges and bases of KDG, then categorize and summarize the existing work of KDG by answering the following three questions: 1) what to distillate, 2) who to whom, and 3) how to distillate. We offer in-depth comparisons and elucidate the strengths and weaknesses of each design. Finally, we share our thoughts on future research directions.
QPredict: Using low quality volunteered geospatial data to evaluate high quality authority data
Authors: Homburg Timo , Staab Steffen , Boochs Frank
Published: January 2025

High-quality, typically administrative, geospatial data should adhere to established measurement and representation practices and be protected from malicious attacks. However, this kind of geospatial data may only be infrequently updated due to its often prolonged production process compared to a data source of volunteered geographic information such as OpenStreetMap. Existing approaches typically try to quality-assure geospatial data by comparing it to another reference dataset of perceived higher quality - often another administrative dataset facing a similar update cycle. In contrast, this article tries to determine whether actual changes present in volunteered geographic information data such as OpenStreetMap, which also need to be applied in an administrative dataset (i.e., consists of actual changes in the real world), can be identified automatically. To that end, we present QPredict, a machine learning approach observing changes in volunteered geospatial data such as OpenStreetMap to predict issues with a target (administrative) dataset. The algorithm is trained by exploiting geospatial object characteristics, intrinsic and extrinsic quality metrics and their respective changes over time. We evaluate the effectiveness of our approach on two datasets representing two mid-size cities in Germany and discuss our findings in terms of their applicability in use cases.
Shilajit Mitigates Diabetes‐Induced Testicular Dysfunction in Mice: A Modulation in Insulin Sensitivity, Germ Cell‐Junctional Dynamics, and Oxido‐Apoptotic Status
Authors: Rajpoot Arti , Pandey Ajai Kumar , Roy Vikas Kumar , Mishra Raghav Kumar
Published: January 2025

Diabetes is a chronic metabolic condition that causes testicular damage by high oxidative stress, rendering 35% of afflicted people infertile. Shilajit is a traditional Indian medicine known for its antioxidant, antidiabetic, and aphrodisiac properties. However, its effectiveness on diabetes‐induced testicular dysfunction remains unclear. Therefore, the current investigation aimed to determine whether Shilajit could restore testicular functions in diabetic mice. Two days postpartum male Parkes mice received a single intraperitoneal injection of streptozotocin (STZ) (90 mg/kg BW) to induce diabetes. Three months postinjection, the effects of daily Shilajit (100 and 200 mg/kg BW) treatment were evaluated for one spermatogenic cycle in adult diabetic mice, using Empagliflozin (10 mg/kg BW) as a positive control. In STZ‐induced diabetic mice, testicular functions were compromised due to disruptions in testosterone biosynthesis, changes in germ‐cell ratios, and increased oxidative stress and apoptosis. Shilajit restored glycemic status in diabetic mice by significantly decreasing serum glucose, insulin level, and homeostasis model assessment of insulin resistance (HOMA‐IR) value while increasing insulin sensitivity. These effects were comparable to those observed with conventional antidiabetic medication Empagliflozin. Further, Shilajit stimulates steroidogenesis and germ cell dynamics of diabetic mice by increasing the activity of StAR, 3β‐HSD, and 17β‐HSD enzymes and 1C:2C, 4C:S‐Ph, and 1C:4C germ cell ratios, respectively. Shilajit also improves blood–testis barrier (BTB) functioning by increasing expression of ZO‐1, Connexin‐43, N‐Cadherin, and β‐catenin as well as oxidative status and apoptosis by modulating NF‐E2–related factor 2 (Nrf‐2)/heme oxygenase 1 (HO‐1) signaling and Bax/Bcl‐2 ratio. Subsequently, Shilajit improved the histoarchitecture of testis and epididymis in diabetic mice and recovered both qualitative and quantitative sperm parameters, as seen by higher percentages of sperm motility, viability, and normal sperm morphology as well as increased sperm numbers in cauda epididymis. In summary, Shilajit restores glycemic status, increases insulin sensitivity, stimulates steroidogenesis, and improves testicular functions through Sertoli cell and Nrf‐2/HO‐1 signaling in STZ‐induced diabetic mice.
Rurality and Outcomes of Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Lavin Cassidy , Epstein Jacob , Chen Alvin Huanwen , Cheema Minahil , Yang Jerry , Aquino Alexa , Chan Angie , Le Nancy , Cooper Gillian , Palushi Ambra , Schrier Chad , Gandhi Dheeraj , Chaturvedi Seemant , Downing Jessica , Tran Quincy K.
Published: January 2025

Objective: To investigate differences in outcomes among patients with acute ischemic stroke from large vessel occlusion (AIS‐LVO) transferred from rural and urban hospitals to University of Maryland Medical Center (UMMC) for mechanical thrombectomy (MT).

Methods: We identified patients with AIS‐LVO transferred to UMMC for MT from July 2016 to June 2023. Primary outcome was good neurologic outcome, defined as 90‐day modified Rankin score 0–2. Multivariable logistic regression was used to identify predictors for the primary outcome.

Results: We analyzed 526 patients, 233 (44%) transferred from rural hospitals in Maryland. Median NIHSS was 17 [IQR 14–20] and was similar between groups. Patients from state‐designated rural hospitals were transferred from a longer distance (difference of 57.8 km, p = 0.001), but had shorter intervals from last known well time to recanalization (difference 19 min, p = 0.24). They had similar odds of good neurologic outcome (OR 0.88, 95% CI 0.43–1.78, p = 0.72).

Conclusions: Patients transferred from rural areas for MT for AIS‐LVO, at our institution, had a similar likelihood of achieving 90‐day mRS 0–2 as those transferred from urban areas.
Uniportal Robotic‐Assisted Tracheal Resection and Reconstruction Under Spontaneous Ventilation
Authors: Guido Guerra Ricardo Eli , Bolaños Morales Francina Valezka , Silva Gómez Oscar Francisco , Olvera Prado Hector , Ibáñez Barzalobre Sarahí , Bosinceanu Mugurel , Gonzalez-Rivas Diego
Published: January 2025

Background: Tracheal resection and reconstruction for airway tumors are traditionally performed using general anesthesia, tracheal intubation, and thoracotomy. Modern techniques, such as tubeless tracheal surgery and robotic uniportal approaches, offer several advantages including better surgical conditions, reduced postoperative complications, and faster recovery.

Case Report: A 42‐year‐old woman with a tracheal neuroendocrine tumor underwent nonintubated uniportal robotically assisted tracheal resection and reconstruction. Thoracic epidural anesthesia, airway topicalization, and intravenous anesthesia with laryngeal mask airway allowed the procedure to be performed under nonintubated spontaneous ventilation, through a single 3‐cm incision. Postoperative recovery was uneventful, with the patient experiencing minimal pain and no nausea or vomiting.

Conclusions: Nonintubated uniportal robotically assisted tracheal resection and reconstruction is a feasible, less invasive technique that offers significant benefits in terms of recovery and patient comfort when performed by experienced surgeons.
The Effect of a Video‐Based Game Exercise Program on Motor Skills, Proprioception, and Cognitive Functions in Individuals With Intellectual Disabilities
Authors: Diril Elif , Menek Burak , Emir Ahmet , Tarakci Devrim , Tarakci Ela
Published: January 2025

Background: Individuals with intellectual disability (ID) exhibit various problems, such as attention, learning, and physical–motor difficulties. The study is aimed at investigating the effects of video game–based therapy programs on cognitive and physical functions in individuals with ID.

Methods: The study, conducted through a three‐arm randomized trial, involved 45 adults aged 18–30 with mild to moderate ID. Participants were divided into three groups: Group 1 received home‐based video game–based therapy, supervised video game–based therapy, and occupational therapy–based activity training. Group 2 received video game–based therapy supervised by a therapist and an occupational therapy–based activity training program. Group 3 received occupational therapy–based activity training only. MOXO d‐CPT was used to evaluate attention; sit‐to‐stand test, joint position sense, and nine‐hole peg test were used to assess physical–motor functionality.

Results: Results showed significant improvements in attention, functional performance, proprioception, and fine motor skills in all groups (p < 0.05). Group 1 was superior to Group 3 in nondominant JPS‐flexion, sit‐to‐stand test, and nondominant JPS‐abduction parameters (p < 0.017). When comparing Group 1 and Group 2, Group 1 was found to be more effective in the sit‐to‐stand test parameter compared to Group 2 (p < 0.017), while the other parameters of the two groups were similar to each other (p > 0.017). There were no significant differences between groups for different outcome measures (p > 0.017).

Conclusion: The study suggests that video‐based game exercises combined with occupational therapy interventions can effectively enhance cognitive functions, functional performance, proprioception, and fine motor skills in adults with ID.

Trial Registration: ClinicalTrials.gov identifier: NCT06097819
The Road Less Traveled: Ciliary Sulcus Implantation of the Preserflo MicroShunt
Authors: Meisel Meishar , Berkowitz Eran , Schwalb Avi , Tiosano Beatrice
Published: January 2025

Introduction: Herein, we report on the option and clinical advantage of the Preserflo MicroShunt insertion into the posterior chamber ciliary sulcus in a patient with advanced pseudoexfoliation glaucoma at a high risk of corneal decompensation. Case Presentation: We describe a 64-year-old advanced pseudoexfoliation glaucoma patient who despite maximal tolerated medical therapy and two failed glaucoma surgeries, still suffered from uncontrolled intraocular pressure (IOP) of 36 mm Hg in his left eye. The patient underwent the implantation of the Preserflo MicroShunt. The shunt was placed nasally into an area of unscarred conjunctiva, with the anterior part of the shunt inserted into the ciliary sulcus. Postoperatively, the patient’s IOP dropped to 6 mm Hg on the first day and stabilized at 11 mm Hg at the 6-month mark. An elevated, posteriorly located bleb was observed, and the patient no longer required additional topical medications. Endothelial cell (EC) count remained stable with no signs of corneal edema. The patient did not experience any serious postoperative complications. Conclusion: Implantation of the Preserflo MicroShunt into the ciliary sulcus appears to be a viable option for patients at high risk of corneal decompensation, hence, offering effective IOP control while minimizing EC loss. Further studies with larger patient groups are warranted to better evaluate the safety and efficacy of this technique.
XOR-Derived ROS in Tie2-Lineage Cells Including Endothelial Cells Promotes Aortic Aneurysm Progression in Marfan Syndrome
Authors: Yagi Hiroki , Akazawa Hiroshi , Liu Qing , Yamamoto Kimiko , Nawata Kan , Saga-Kamo Akiko , Umei Masahiko , Kadowaki Hiroshi , Matsuoka Ryo , Shindo Akito , Okamura Shun , Toko Haruhiro , Takeda Norifumi , Ando Masahiko , Yamauchi Haruo , Takeda Norihiko , Fini Mehdi A. , Ono Minoru , Komuro Issei
Published: January 2025

BACKGROUND:

Marfan syndrome (MFS) is an inherited disorder caused by mutations in the
FBN1
gene encoding fibrillin-1, a matrix component of extracellular microfibrils. The main cause of morbidity and mortality in MFS is thoracic aortic aneurysm and dissection, but the underlying mechanisms remain undetermined.

METHODS:

To elucidate the role of endothelial XOR (xanthine oxidoreductase)–derived reactive oxygen species in aortic aneurysm progression, we inhibited in vivo function of XOR either by endothelial cell (EC)–specific disruption of the
Xdh
gene or by systemic administration of an XOR inhibitor febuxostat in MFS mice harboring the
Fbn1
missense mutation p.(Cys1041Gly). We assessed the aberrant activation of mechanosensitive signaling in the ascending aorta of
Fbn1
C1041G/+
mice. Further analysis of human aortic ECs investigated the mechanisms by which mechanical stress upregulates XOR expression.

RESULTS:

We found a significant increase in reactive oxygen species generation in the ascending aorta of patients with MFS and
Fbn1
C1041G/+
mice, which was associated with a significant increase in protein expression and enzymatic activity of XOR protein in aortic ECs. Genetic disruption of
Xdh
in ECs or treatment with febuxostat significantly suppressed aortic aneurysm progression and improved perivascular infiltration of macrophages. Mechanistically, mechanosensitive signaling involving FAK (focal adhesion kinase)–p38 MAPK (p38 mitogen-activated protein kinase) and Egr-1 (early growth response-1) was aberrantly activated in the ascending aorta of
Fbn1
C1041G/+
mice, and mechanical stress on human aortic ECs upregulated XOR expression through Egr-1 upregulation. Consistently, EC-specific knockout of XOR or systemic administration of febuxostat in
Fbn1
C1041G/+
mice suppressed reactive oxygen species generation, FAK–p38 MAPK activation, and Egr-1 upregulation.

CONCLUSIONS:

Aberrant activation of mechanosensitive signaling in vascular ECs triggered endothelial XOR activation and reactive oxygen species generation, which contributes to the progression of aortic aneurysms in MFS. These findings highlight a drug repositioning approach using a uric acid–lowering drug febuxostat as a potential therapy for MFS.
Abstract 12: High HDL Cholesterol Is Associated With Reduced Reperfusion Injury And Favorable Functional Outcome Following Thrombectomy For Ischemic Stroke
Authors: Sedghi Annahita , Schreckenbauer Sonja , Kaiser Daniel , Cuberi Ani , Arndt Martin , Barlinn Kristian , Puetz Volker , Siepmann Timo
Published: January 2025

Introduction:
Animal research suggests that HDL cholesterol (HDL-C) ameliorates reperfusion injury, a phenomenon that worsens clinical outcome following recanalization therapy for ischemic stroke.

Hypothesis:
We hypothesized that higher HDL-C levels have a guarding effect against cerebral reperfusion injury in human stroke survivors treated with thrombectomy.

Methods:
We included patients with anterior circulation large vessel occlusion (acLVO) stroke who underwent thrombectomy from 01/2017 to 01/2023 at a tertiary stroke center in Germany into a prospective registry study with retrospective analysis. We assessed the association of HDL-C serum levels and imaging indices of post interventional reperfusion injury (any intracerebral or subarachnoid bleeding involving the ischemic brain region on CT or MRT), functional outcome quantified via modified Rankin scale (mRS) at 90 days and neurological outcome via National Institutes of Health Stroke Scale (NIHSS) score at discharge using multivariable lasso logistic and linear regression adjusted for demographic, clinical and imaging characteristics. We performed sensitivity analysis applying propensity score matching and shift analysis using ordered logistic regression.

Results:
In our study population of 811 acLVO patients treated with thrombectomy (420 females, median age 77 years [66-84, interquartile range]) reperfusion injury was associated with detrimental functional outcome (adjusted OR 2.87; 95% CI [1.86;4.41]; p=0.000). Higher HDL-C was associated with lower odds of reperfusion injury (adjusted OR 0.57; 95% CI [0.35;0.95]; p=0.03) and emerged as predictor of favorable functional outcome defined as 90-day mRS 0-2 (adjusted OR 0.57; 95% CI [0.34;0.99]; p=0.04) and alleviated neurological deficits with lower NIHSS score at discharge (ß=-2.51; 95CI% [-4.88; -1.30]; p=0.04). On propensity score analysis an HDL-C level exceeding the median (1.15 mmol/L) was associated with a 13.8 % decrease in the probability of reperfusion injury (ß=-0.14; 95CI% [-0.23; -0.05]; p=0.003). A significant shift of 90-day mRS distribution favoring high HDL is shown in the figure.

Conclusions:
In patients undergoing thrombectomy for acLVO a higher level of HDL-C reduced the odds of reperfusion injury, which translated into improved functional and neurological outcome, hence constituting a possible target of adjunctive neuroprotective treatment.
Abstract 22: Implementation of increased physical therapy intensity for improving walking across inpatient stroke rehabilitation units: Primary results of the Walk ‘n Watch multi-site stepped-wedge cluster randomized controlled trial
Authors: Peters Sue , Hung Stanley , Bayley Mark , Best Krista , Connell Louise , Corriveau Helene , Donkers Sarah , Dukelow Sean , Ezeugwu Victor , Milot Marie-Helene , Sakakibara Brodie , Sheehy Lisa , Wong Hubert , Yang Yuwei , Yao Jennifer , Eng Janice
Published: January 2025

Introduction:
Though clinical practice guidelines support high repetitions of walking after stroke, practice is slow to change with low levels of walking activity in stroke rehabilitation units. We undertook an implementation trial to change practice; we enabled entire stroke units to use the Walk ‘n Watch protocol and determined the effect of implementation on the 6 Minute Walk Test (6MWT) at hospital discharge.

Methods:
This 12-site clinical trial across 7 Canadian provinces used a stepped-wedge cluster design to randomize when each site switched from Usual Care to the Walk ‘n Watch protocol. At the start of the Walk ‘n Watch phase, we trained all front-line physical therapists on the unit with training workshops, manuals, hands-on practice, and videos. Each site was provided onboarding materials to address staff changes so therapists who did not attend the initial training could adopt the protocol. Each site also identified a ‘protocol champion’ to facilitate initial weekly huddles with therapists to discuss barriers to implementation. Therapists were trained to complete safety screening and to determine eligibility. The Walk ‘n Watch protocol focused on completing a minimum of 30-minutes of daily weight-bearing, walking-related activities that progressively increased in intensity informed by activity trackers measuring heart rate and step number. Blinded assessors completed the outcomes at baseline and 4-weeks later (near discharge). Primary analysis used a linear mixed-effects model adjusted for stratum, date of enrollment, age, sex and baseline 6MWT.

Results:
The total number of participants was 306 (162 Usual Care, 144 Walk ‘n Watch, 188 males/118 females) with a mean(SD) age of 68(13), 29(17) days since stroke, and a baseline 6MWT of 152(106) m. The improvement on the 6MWT was 43.6m (95%CI 12.7, 76.1) greater in the Walk ‘n Watch group compared to the Usual Care group. Further, the Walk ‘n Watch group improved quality of life (EQ5D), balance and mobility (Short Physical Performance Battery) and gait speed.

Conclusions:
The implementation trial design enabled the protocol to be tested under real-world conditions, involving all therapists on each unit to deliver the protocol. The trial had a deliberate aim to facilitate changes in practice that resulted in clinically meaningful improvements in walking and quality of life.
Abstract 25: Discovery of Serum Biomarkers to Inform Early Rehabilitation after Acute Ischemic Stroke
Authors: Ifejika Nneka , Ray Bappaditya , Mastorakos Panagiotis , Simmonds Kent , Chavez Audrie , Venkatachalam Aardhra , Olson Daiwai
Published: January 2025

Background:
Rehabilitation therapy is an important component of acute ischemic stroke (AIS) recovery. A major hinderance is the inability to predict which patients benefit from mobilization during the first 24 hours (ERehab). We hypothesize serum biomarker analyses during the hyperacute phase can bridge the gap.

Methods:
This is a single center study of 20 AIS patients&14 age/sex matched controls enrolled from 3/2022-6/2023. Serum samples were collected at 4 time points – angiography suite before cerebral reperfusion or Neuro ICU at hospital admission, 12, 24&72 hours. Biomarker candidates were identified using a DisGeNET search for AIS associated proteins; 70% achieved an Evidence Index cutoff score of 1, indicating all publications support human gene-disease or variant-disease associations. Time course of serum proteome changes was evaluated using aptamer-based SomaScan assay, measuring 1500 proteins. NIH Database for Annotation, Visualization&Integrated Discovery (DAVID) Gene Functional Classification Tool compared shared genes and biomarkers for stroke (vs healthy controls)&unfavorable (vs favorable) outcome, characterized by modified Rankin Scale (mRS) score of 3-6 (vs 0-2), at hospital discharge&90 days (90d).

Results:
The mean age of AIS patients was 59 years, 65% were male. Median NIHSS score was 11, Charlson Comorbidity Index score was 5.5 and the median last known well to hospital admission was 6.6 hrs. The average time to first mobilization was 39 hrs, 25% received ERehab. The mean rehab duration during AIS hospitalization was 438 min; median length of stay was 8.4 days, 40% received post-acute rehabilitation. Median AIS volume was 36mL, 65% of patients had ICA or M1/MCA involvement. Approximately 65% received IV thrombolysis, 80% underwent cerebral reperfusion therapy, 94% achieved modified thrombolysis in Cerebral Infarction score ≥ 2b. The median mRS was 4 at hospital discharge, 3 at 90d. Mortality rate was 10%. DAVID analyses resulted in 22 biomarkers at hospital discharge&35 biomarkers at 90d associated with favorable outcome. Gene expression differences were present at each time point (Figure).

Conclusions:
We identified multiple serum biomarkers and gene clusters associated with favorable outcomes at hospital discharge and 90d in AIS patients, indicating a need for several biologic targets to predict ERehab response during the hyperacute phase. These findings provide an early framework for tailored stroke recovery interventions.
Abstract 30: Association between Time and Severe Hypoperfusion with Risk of Hemorrhagic Transformation in Thrombectomy Stroke Patients
Authors: Pensato Umberto , Goyal Mayank , Demchuk Andrew , Hill Michael , Ospel Johanna
Published: January 2025

Background and objective:
Perfusion imaging studies consistently show a substantially increased risk of hemorrhagic transformation (HT) in severely hypoperfused tissue. Pathophysiological evidence indicates that ischemic damage is influenced not only by the degree of hypoperfusion but also by the duration of exposure to that hypoperfused state. We aim to investigate the association of time and severe hypoperfusion with parenchymal hematoma (PH) in ischemic stroke and explore whether there is a combined effect of the two variables on PH.

Methods:
Data are from the ESCAPE-NA1 trial, which evaluated the effect of nerinetide in large vessel occlusion patients treated with thrombectomy. For this study, we included patients with some degree of recanalization (expanded Thrombolysis in Cerebral Infarct [eTICI] >0) and available baseline CT perfusion. Severe hypoperfusion was defined as at least 1mL volume of relative cerebral blood flow (rCBF)<20%. The primary and secondary outcomes were the presence of PH and of any HT, respectively, assessed on 24-hour imaging, according to Heidelberg criteria. The effect of time and severe hypoperfusion on outcomes was assessed with univariable and multivariable logistic regression analyses, including interaction terms to assess treatment effect modification.

Results:
Out of 1105 patients from ESCAPE-NA1, 396 (35.8%) were included. The median age was 70 years (IQR=59.8-79.2), 202 (51%) were females, and 50 (12.6%) experienced PH. Onset-to-imaging time (adjusted OR 1.04 [95%CI=1.01-1.06] per 15-minute increase) and the presence of severe hypoperfusion (adjusted OR 2.63 [95%CI=1.21-5.72]) were the only variables associated with PH in multivariable analysis. No significant interaction effect of time and severe hypoperfusion on PH was found. The presence of severe hypoperfusion has a negative predictive value of 98% and a positive predictive value of 39.4% for predicting PH in patients presenting within three hours and after six hours from symptom onset, respectively.

Conclusion:
Both severe hypoperfusion and time affect the risk of hemorrhagic transformation in ischemic cerebral tissue. Analyzing these variables may help identify patients with a leaky, severely compromised blood-brain barrier in the ischemic core—a “leaky core.”
Abstract 32: Ischemic and hemorrhagic risks of patients with Basal Ganglia Perivascular Spaces on Antithrombotic Therapy
Authors: Iwamoto Soya , Miwa Kaori , Koga Masatoshi , Tanaka Kanta , Yoshimura Sohei , Yakushiji Yusuke , Sasaki Makoto , Hoshino Haruhiko , Shiozawa Masayuki , Yagita Yoshiki , Kudo Kohsuke , Nagakane Yoshinari , Ihara Masafumi , Hirano Teruyuki , Toyoda Kazunori
Published: January 2025

Background:
Enlarged perivascular spaces (PVS), a marker of cerebral small vessel disease (SVD), are considered to increase the risk of stroke. However, there is limited data on the benfits and harms of antithrombotic agents in patients with PVS. We assessed the association of PVS with the risk of hemorrhagic or ischemic events in patients receiving antithrombotic agents.

Methods:
This is an investigator-initiated, prospective, multicenter observational study that enrolled patients with cerebrovascular or cardiovascular diseases who were taking oral antithrombotic agents from 52 hospitals across Japan between 2016 and 2019. All participants underwent baseline multimodal MRI. The MRI scans were centrally evaluated for radiologic indicators related to SVD, including white matter hyperintensities (WMH), cerebral microbleeds (CMBs), lacunes, basal ganglia enlarged-perivascular spaces (BGPVS), cortical superficial siderosis, using a visual scale. The outcomes included major bleeding, intracranial hemorrhage, ischemic events, ischemic stroke, and mortality.

Results:
Of the analyzed 5,250 patients (1,736 women; median age 73 [IQR 66–79] years), antiplatelets and anticoagulants were administered at baseline in 3,948 (75.2%) and 1,565 (29.8%), respectively. During a median 2 (IQR1.8–2.0) years, 278 ischemic events, 197 ischemic strokes, 93 major bleeding, 55 intracranial hemorrhage, and 217 deaths were observed. The distribution of BGPVS was as follows: 0 BGPVS in 475 patients (9.4%), 1-10 BGPVS in 2615 patients (51.6%), and 11+ BGPVS in 1975 patients (39.9%). A higher BGPVS burden was associated with older age, a lower proportion of women, higher rates of hypertension and smoking, lower eGFR values, and a higher prevalence of lacunes, CMBs, and WMH. A higher burden of BGPVS was associated with a higher risk of major bleeding (1–10 BGPVS: adjusted hazard ratio (aHR) 1.49, [95% confidence interval CI 0.76–7.92], 11+ BGPVS: aHR 3.27 [1.09–11.57] versus 0 BGPVS; p
trend
= 0.035) and ischemic stroke (1–10 BGPVS: aHR 1.79 [0.90–3.57], 11+ BGPVS: aHR 2.39 [1.19–4.81]; p
trend
= 0.014). In contrast, higher BGPVS burden was not significantly associated with an increased risk of ischemic events, intracranial hemorrhage, or mortality.

Conclusions:
A higher burden of BGPVS was associated with an increased risk of ischemic stroke and major bleeding in patients taking antithrombotic medication and might be useful in clinical decision making.
Abstract 33: A Novel Imaging Biomarker to Make Precise Outcome Predictions for Patients with Acute Ischemic Stroke
Authors: Mallavarapu Monica , Kim Hyun Woo , Iyyangar Ananya , Salazar-Marioni Sergio , Yoo Albert , Giancardo Luca , Sheth Sunil , Jeevarajan Jerome
Published: January 2025

Introduction:
Net water uptake (NWU) is a novel biomarker which measures edema and tissue injury from the degree of hypoattenuation on non-contrast CT and may serve as a precision tool for predicting outcomes after acute ischemic stroke (AIS). Using our recently developed algorithm, this study aimed to evaluate the relationship between NWU and post-stroke neurologic outcomes, including language impairment and motor weakness.

Methods:
Consecutive patients treated for AIS at certified stroke centers in Houston, TX were included. Patients’ precise functional outcomes at hospital discharge were recorded including decreased level of consciousness, presence of language impairment, visual deficit, arm and leg weakness, need for walking assistance, and gastrostomy placement. The primary outcome for this study was the performance of calculated NWU and clinical variables to predict language impairment at discharge. Baseline characteristics were compared, and then univariate and multivariate logistic regression were used to evaluate the association between clinical variables, imaging data, and the precise neurological outcomes.

Results:
Among 776 patients with AIS, average age was 67.0 +/- 14.8, 47.8% were female, median NIHSS was 10 [5,18], median ASPECTS was 9 [7,10], 42.6% received tPA, and 67.1% had a large vessel occlusion (see Table 1). In univariate logistic regression, higher NWU (OR 1.45, CI 1.30-1.63) and lower ASPECTS (OR 0.68, CI 0.63-0.74) were both significantly associated with higher likelihood of language impairment and other deficits at discharge (see Table 2). Additionally, higher NWU in all ten regions was significantly associated with deficit at discharge. In multivariate logistic regression, certain clinical and imaging variables remained significantly associated as described in Table 3. The ASPECTS and NWU-based regression models were directly compared when predicting language impairment using ROC curve analysis, and areas under the curve were 0.838 vs. 0.851 respectively (p = 0.152 with Delong test, see Figure 1).

Conclusion:
The novel NWU biomarker was significantly associated with precise post-AIS outcomes at discharge. When controlling for confounders, NWU was non-inferior to ASPECTS. Moving forward, region-based and overall NWU will need to be studied with long-term patient outcomes. Ultimately, this novel and open-access imaging biomarker could be used in the emergency setting to guide treatment decision-making and patient counseling.
Abstract 34: White Matter Alteration after Stroke Is Correlated with Neuroinflammation: A Combined Fixel-based Diffusion MRI Analysis and 18F-THK-5351 PET Study
Authors: Chang Ting-Yu , Huang Kuo-Lun , Hsiao Ing-Tsung , Yeh Chun-Hung
Published: January 2025

Introduction:
Neuroinflammation plays a major role in post-stroke neuronal injury. Previous studies applied 18F-THK-5351 tau PET to identify the existence of neuroinflammation after infarction. Meanwhile, post-stroke microstructural degradation of white matter (WM) fibers can be observed using fixel-based analysis (FBA) of diffusion MRI (dMRI). We integrate 18F-THK-5351 tau PET and FBA-dMRI in ischemic stroke patients to investigate the relationship between poststroke neuroinflammation process and WM fiber alterations.

Methods:
33 patients with lacunar infarcts received 18F-THK-5351 PET and dMRI (Siemens Biograph mMR PET-MR 3 Tesla scanner) at 3 months poststroke. 27 age-matched healthy controls were recruited. The reference region of 18F-THK-5351 PET was set at cerebellar cortex. FBA-dMRI metrics included microstructural fiber density (FD), fiber cross-section (FC, macrostructural morphometry), and combined-FD/FC (FDC, the overall fiber bundle connectivity). Clinical severity assessments included infarction volume, NIHSS, BI, and mRS.

The whole-brain fixel-wise statistical analysis used the general linear model. Correlation anlaysis was for FBA metrics and clinical severity. Non-parametric testing >5000 permutations was used for multiple comparisons,
p
<0.05 using a strong family-wise error control as statistical significance.

Results:
All patients had lacunar infarcts at internal capsule, including 19 left and 14 right lacunes. The mean age was 64.9±7.7 in patients v.s. 61.3±9.4 in controls (
p
=0.47). FBA-dMRI showed significant reductions in FD, FC, and FDC at corticospinal tract in patients compared to the controls. Tau PET demonstrated the highest uptake of 18F-THK-5351 at ischemia core. The spatial patterns of 18F-THK-5351 retention were highly consistent with the fixel metrics reduction distributions (Figure 1).

Infarct volumes and clinical severity significantly negatively correlated with the fixel measures in patients. Larger infarct volume or more severity corresponds to lower FBA value (Figure 2).

Conclusions:
Integrating 18F-THK-5351 PET and FBA-dMRI demonstrates fiber-specific WM reductions associated with the neuroinflammation process, showing consistent spatial patterns between neuroinflammation and WM degeneration in stroke patients. Tract-specific WM reductions correlated with infarct volume and functional outcomes 3 month poststroke. Our findings have implications for understanding the mechanisms underlying functional impairment after ischemic stroke.
Abstract TMP100: Associations between Food Insecurity and All-Cause Mortality in Stroke Survivors and the General NHANES Study Population
Authors: Senff Jasper , Tack Reinier , Yq Tan Benjamin , Prapiadou Savvina , Kimball Tamara , Ng Sharon , Duskin Jonathan , Brouwers H , Chemali Zeina , Fricchione Gregory , Tanzi Rudolph , Towfighi Amytis , Rosand Jonathan , Yechoor Nirupama , Anderson Christopher , Singh Sanjula
Published: January 2025

Introduction:
Food insecurity, defined as limited access to nutritious food due to financial challenges, has grown substantially over the past two decades in the United States. Stroke survivors are more likely to experience food insecurity compared to the general population. However, the impact of food insecurity on long-term survival post-stroke remains unclear. Hence, we aimed to determine associations between food insecurity post-stroke and all-cause mortality.

Methods:
The National Health and Nutrition Examination Survey (NHANES) is an iterative cross-sectional study representative of the US population. Using data from 1999-2018, we assessed associations between food insecurity and all-cause mortality among stroke survivors and the general NHANES population, using linkage to death certificates from the National Death Index. Food security was assessed using ten NHANES questions and dichotomized into food security and food insecurity. A Cox proportional hazards model was used to evaluate associations between food insecurity and mortality adjusting for NHANES weighting, sex, age, race/ethnicity, education, marital status, poverty income ratio, BMI, diabetes, stroke, myocardial infarction, and cancer.

Results:
Among 101,316 NHANES participants, 2,197 (2.2%) self-reported as stroke survivors (mean age 67.6y, 50.8% female). Stroke survivors were more often food insecure compared to the general NHANES population (17.6% [SE:1.3%] vs. 14.3% [SE:0.4%], p=0.0038). Among 1,754 (78.9%) stroke survivors with linked death records, 801 died during a median follow-up of 105 months (IQR 56-159). The 10-year all-cause mortality rate among stroke survivors was 36.2% (SE: 3.0%) for the food secure and 48.4% (SE: 1.8%) for the food insecure group. In the general NHANES population, the corresponding rates were 10.9% (SE: 0.2%) and 14.2% (SE: 0.4%), respectively (Fig 1). Regression analysis showed that food insecurity was associated with a 31% increased risk of mortality in stroke survivors (HR: 1.31, 95%CI:1.00-1.73, P=0.049) and a 40% increase in the general NHANES population (HR: 1.40, 95%CI:1.25-1.57, P<0.001) (Fig 2).

Conclusion:
Food insecurity is associated with increased mortality rates in both the NHANES general population and stroke survivors, with a more pronounced difference in mortality rates among stroke survivors based on their food security status. Future research should focus on characterizing the biological and social mechanisms underlying these associations.
Abstract TMP110: Impact of Microplastics and Nanoplastics on Ischemic Stroke in Mice
Authors: Maeda Takuma , Nisson Peyton , Cisneros Oscar , Lawton Michael , Hashimoto Tomoki
Published: January 2025

Introduction:
Over the past few decades, plastics have been widely used in many products. Recently, the potential ingestion of plastic debris called microplastics and nanoplastics (MNPs) and their toxicity to organs and tissues have been reported. They can enter the bloodstream not only by ingestion, but also by inhalation and dermal contact. MNPs are emerging as a potential risk factor for cerebrovascular events such as myocardial infarction and stroke in recent clinical study. However, the relationship between MNPs exposure and ischemic stroke is not well elucidated. In this study, we investigated the effect of MNPs on ischemic stroke using the transient middle cerebral artery occlusion (tMCAO) model in mice.

Methods:
We used 12-week-old male C57BL/6J mice. Mice (n = 48) were divided into four groups based on the materials administered. After daily pretreatment with either pure water as vehicle, polystyrene (PS, 150 mg/kg/day), polyethylene (PE, 150 mg/kg/day), and polyvinyl chloride (PVC, 150 mg/kg/day) for 35 days, mice were subjected to tMCAO for 60 minutes. Treatment with MNPs was continued until postoperative day 2. As a safety study, we measured the body weight and blood pressure during the pretreatment. We compared Garcia score, neurological deficit score (NDS), rotarod performance (% baseline), and infarction volume (% ipsilateral) between the groups 3 days after tMCAO.

Results:
No significant side effects such as weight loss or blood pressure changes were observed during pretreatment. Garcia scores were significantly lower in the PE (7.5 ± 4.0) and PVC (9.1 ± 2.1) groups compared to the vehicle group (11.9 ± 3.7) on day 3 (Fig. A,
P
<0.05, respectively). Similarly, NDS was significantly higher in the PE (2.5 ± 1.3) and PVC (2.3 ± 0.5) groups compared to the vehicle group (1.4 ± 1.0) on day 3 (Fig. B,
P
<0.05). There was a significant difference in rotarod performance between PE (55.6%) and vehicle (100.2%) groups on day 3 (Fig. C,
P
<0.05). Infarct volumes were significantly larger in the PE (30.2%) and PVC (27.3%) groups compared to the vehicle group (14.2%) on day 3 (Fig. D,
P
<0.05). These results were not confirmed in the PS group.

Conclusions:
This preliminary study revealed the potential negative effects of microplastics and nanoplastics on ischemic stroke in mice. Future research should evaluate the long-term outcomes and the mechanisms by which microplastics and nanoplastics exacerbate the ischemic stroke.
Abstract TMP112: Histological and Transcriptomic Analysis of Ischemic Stroke Thrombi Identifies Neutrophil Extracellular Trap Enrichment as an Indicator of First Pass Outcome
Authors: Santo Briana , Poppenberg Kerry , Patel Tatsat Rajendra , Baig Ammad , Levy Elad , Siddiqui Adnan , Tutino Vincent
Published: January 2025

Introduction:
Both histological and transcriptomic analyses of acute ischemic stroke (AIS) clots have identified features associated with mechanical thrombectomy (MT) outcome. However, few studies have explored how fluorescence histology and mRNA sequencing from the same clot can pinpoint specific biological phenomena associated with MT failure.

Hypothesis:
Joint analysis of paired clot immunofluorescence histology and mRNA sequencing will identify Neutrophil Extracellular Trap (NET) enrichment as a biomarker of MT first pass (FP) outcome.

Methods:
We performed paired histological and transcriptomic analysis of 32 stroke clots retrieved by MT (n=16 each of FP success and failure). Immunofluorescence histology was completed by co-staining 4µm clot tissue sections with antibodies against NET components (neutrophil elastase [ELANE], citrullinated histone [CitHis]) and super resolution imaging with instant structured illumination microscopy (ISIM) at 100X magnification. Differentially expressed genes (DEGs) were identified between transcriptomes of FP success and failure using the criteria of logFC≥1.5 and q<0.05. Principal component analysis (PCA) and Ingenuity Pathway Analysis (IPA) were completed to evaluate how well DEGs separated clots based on FP outcome and to identify enriched biological processes.

Results:
44 DEGs were identified, most of which were downregulated in clots with successful FP. Expression of DEGs was able to separate clots by FP outcome. The NET signaling pathway was identified as the most enriched biological process in the FP failure group, with related genes downregulated in the FP success group. NETs were detected in clots with FP failure.

Conclusion:
Our results suggest that future multi-omic models, upon integration with pre-MT CT radiomics, can be developed to inform thrombolytic therapy and device selection, as well as predict FP outcome.
Abstract TMP116: Gut-derived extracellular vesicles promote neurovascular damage and cognitive impairment in diabetic mice
Authors: Liu Xianshuang , Chopp Michael , Fan Baoyan , Wang Xinli , Cui Xu , Powell Brianna , Mccann Mikkala , Landschoot-Ward Julie , Zhang Zheng Gang
Published: January 2025

Background and Purpose:
Gut microbiota dysfunction is associated with diabetic cognitive impairment (DCI). However, the mechanisms underlying the interaction of gut microbiota dysbiosis and DCI remain poorly understood. We tested the hypothesis that extracellular vesicles generated by diabetic gut microbiota exacerbate DCI by promoting the impairment of cerebral vascular function.

Methods:
Gut-EVs from the stools of male non-diabetic dm (dm-gut-EVs) and diabetic (db/db mice) with DCI (db-gut-EVs) mice at 20 weeks of age (20W) were isolated and characterized by means of ultracentrifugation and 16S rRNA sequencing, respectively. Given that db/db mice develop cognitive deficits at 20W, prediabetic db/db mice at 8 weeks of age (8W) were treated with gut-EVs at a dose of 1x10
10
particles/injection intravenously twice a week for 12 weeks. Cognitive performance was assessed using a battery of behavioral tests.

Results:
16S rRNA analysis revealed significant alterations in the microbiota composition of db-gut-EVs derived from 20W db/db mice with DCI compared to dm-gut-EVs (n=5/group). Db/db mice treated with db-gut-EVs extracted at 20W, but not with dm-gut-EVs, exhibited a significant decline in learning and memory function, as assayed by the Novel object recognition, Social recognition memory, and Morris water maze assay, starting at 16W and worsening at 20W, compared to db/db mice treated with saline (n=10/group). Additionally, db/db mice treated with db-gut-EVs exhibited increased cerebral vascular thrombosis (18±2 vs 11±2 Fibrin+ vessels/mm
2
in saline, p<0.05, n=5/group), whereas db/db mice treated with dm-gut-EVs showed a reduction of thrombosis (5±0.5 Fibrin+ vessels/mm
2
, p<0.05). In vitro, treatment of human cerebral endothelial cells (hCECs) with db-gut-EVs significantly (p<0.05) upregulated pro-coagulation and inflammatory proteins, including plasminogen activator inhibitor-1 (PAI-1), tissue factor (TF), NF-κB, and intercellular adhesion molecule 1 (ICAM-1), while reducing tight junction protein ZO-1 expression.

Conclusions:
Our findings indicate that db-gut-EVs promote DCI by inducing cerebral vascular damage, and underscore a major role for gut microbiota-brain communication in the development of DCI.
Abstract TMP118: Validation and Reliability of the SPAN Score for Assessing Neurological Function in Mouse Stroke Models following MCAO
Authors: Aykan Sanem A , Imai Takahiko , JIN XUYAN , Morais Andreia , Wang Qian , zhang shasha , Wang Haichen , Yang Wei , Sheng Huaxin , Ayata Cenk
Published: January 2025

Introduction:
Neuroanatomy-based functional examinations are crucial for understanding the extent and effects of infarcts in stroke studies. Despite the importance of correlating neurological function with brain anatomy, a comprehensive neurological score that correlates with infarction volume and location following middle cerebral artery occlusion (MCAO) in mice is lacking. During the pilot phase of the Stroke Preclinical Assessment Network (SPAN), a new scoring system—SPAN score—was developed. This study aims to evaluate the reliability and validity of the SPAN score, a 9-item tool rated on a 0-3 Likert scale.

Methods:
The SPAN 2.0 pilot database was utilized for analysis. Reliability was assessed using Cronbach's alpha (α) and intraclass correlation coefficient (ICC) for individual items and the total score. Multivariate regression was performed for item selection and to determine the weight of each item. Concurrent validity was examined by correlating post-operative day 2 infarction volume, as measured by MRI, with the SPAN score.

Results:
The total SPAN score demonstrated acceptable reliability, with Cronbach's α and ICC both at 0.751. Item-total correlation coefficients of each item ranged from 0.092 to 0.638. The Pearson correlation coefficient between the total SPAN score and infarction volume was 0.539. Notably, spontaneous activity showed a reversed relationship with other items; excluding this item increased Cronbach's α to 0.766.

Conclusion:
The SPAN score proves to be a reliable and valid tool for neuroanatomy-based functional assessment in mouse stroke models following MCAO. Ongoing analysis will focus on refining the score by reducing the number of items, adjusting the Likert scale, incorporating lesion area, and further exploring item relationships.