bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP379: Post-stroke whole body vibration therapy alters transcriptome and reduces ischemic brain damage in reproductively senescent female rats.
Authors: Patel Shahil , Bramlett Helen , Raval Ami
Published: January 2025

Introduction:
Rehabilitative physical therapy is essential for reducing stroke-related functional deficits; however, comorbidities may limit patient participation. Whole body vibration (WBV; 40 Hz) offers an exercise-like alternative. Our studies show that one month of post-stroke WBV reduces ischemic damage and improves motor and cognitive function in middle-aged rats. Notably, WBV significantly increased circulating irisin, a muscle-derived hormone. We hypothesize that post-stroke WBV modifies the cerebral transcriptome and irisin treatment improves stroke outcome in middle-aged female rats.

Methods:
Middle-aged Sprague-Dawley rats were randomized to sham or transient middle cerebral artery occlusion (tMCAO; 90 min) surgery and divided into two cohorts. A cohort received either no-WBV (steady platform) or WBV (platform vibrating at 40 Hz) for 15 minutes twice a day for a week. Cortical tissue was then collected for RNA sequencing (RNAseq) and gene enrichment analysis. The second cohort received either saline or irisin (PeproTech, 0.2 µg/g BW) treatment at 4.5 hours post-tMCAO and then once a week for a month. At 21 days post-tMCAO, rats were assessed for cognitive deficits via the Morris water maze. At 1-month post-tMCAO, brains were collected for histological analysis.

Results:
RNAseq revealed significant (p<0.05) differential expression of 581 genes in the cortex due to WBV. Specifically, there was downregulation (log
2
(fold change) = -2.9; p= 0.03943) of Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 7 (
Cacng7
) and calcium-release channel activity (GO:0015278), which are both implicated in excitotoxicity following stroke. The expression of Vacuolar Protein Sorting-Associated Protein 37C (
Vps37c
), a component of an endosomal sorting complex that mediates apoptosis, was also downregulated (log
2
(fold change) = -7.1; p= 0.01888). In our second cohort, rats treated with irisin for 1-month post-tMCAO, as compared to saline, demonstrated significantly (p<0.05) reduced cognitive deficits in spatial learning (hidden platform) and memory (probe trial). Additionally, irisin treatment significantly (p<0.05) reduced infarct damage at 1-month post-tMCAO.

Conclusion:
Post-stroke WBV increases the expression of genes responsible for ischemic tolerance and irisin treatment improves cognitive outcomes in middle-aged rats. Future studies are needed to understand the underlying mechanism(s) responsible for irisin-conferred ischemic protection.
Abstract TP386: Impaired Bioenergetics in the Aging Cerebral Microvasculature: Effect of Angiotensin-(1-7) or Alamandine
Authors: Jarajapu Yagna , Rozario Henryata , Chittimalli Kishore , Sakamuri Anil
Published: January 2025

Background:
Aging increases risk for the development of vascular cognitive impairment and dementia (VCID). Impaired bioenergetics, mitochondrial oxidative phosphorylation (OxPhos) and glycolysis, in the brain microvascular endothelium induce neurovascular uncoupling, which is one of the underlying mechanisms of VCID. Angiotensin (Ang)-(1-7) and Alamandine (Ala) are vascular protective peptides of renin angiotensin system. Ang-(1-7) is generated by angiotensin-converting enzyme-2 (ACE2) from Ang II, and produces vascular protective effects by acting on Mas receptor (MasR). Ala has been shown to be derived from Ang A by ACE2 or from Ang-(1-7) by an enzyme, which is yet to be characterized, with decarboxylase activity or Mas related G-protein-coupled receptor, member D (MrgD), respectively. This study evaluated the effect of aging on cellular bioenergetics in brain microvasculature (BMV) and tested the potential beneficial effects of Ang-(1-7) or Ala.

Methods:
BMVs were obtained from Young (Y) and Old (O) mice of age 3 - 4 and 22 – 24 months, respectively, by using ultracentrifugation method. Protein expression of receptors or mitochondrial complexes in BMVs were evaluated by western blotting. Seahorse bioanalyzer was used to determine OxPhos and glycolysis in BMVs.

Results:
Expression of MasR or MrgD was higher in the O-BMVs compared to the Young (
P
< 0.05, n = 4). Expression of mitochondrial respiratory complex proteins, II, IV and V, was lower in the O-BMVs (vs Y-BMVs,
P
< 0.05, n = 4). MitoStress test revealed that the basal and maximal respiration, and the spare capacity are lower in the O-BMVs compared to the Y-BMVs (
P
< 0.05). Ang-(1-7) or Ala (100 nM) increased the basal and maximal respiration, spare capacity and ATP production in the O-BMVs compared to the untreated (
P
< 0.05). Glycolysis rate assay (GRA) showed that basal glycolysis and basal proton efflux rate were lower in the O-BMVs (
P
< 0.01 vs Y-BMVs) that were increased by Ang-(1-7) or Ala.

Conclusion:
The study shows that aging is associated with impaired cellular bioenergetics in the brain microvasculature and that the angiotensin peptides, Ang-(1-7) or Ala, restore the bioenergetics therefore have the potential to reverse neurovascular uncoupling in aging.
Abstract TP390: Anaerobic glycolysis mediates hyperglycemia in cytoplasm during ischemia
Authors: Lee Seeun , Zhong Wenliang , Lee Eun-Hye , Jiao Qian , Jang Dongyeol , Cho Suin , Lim Chiyeon , Lim Sehyun , Elsayed Mahmoud , Kim Nain , You Zerong , Kim Hyung-Hwan
Published: January 2025

Background and rationale:
Glucose is the most important metabolic fuel for the brain. Acute hyperglycemia due to cerebral ischemia causes mitochondrial dysfunction and slows cell cycle progression, resulting in oxidative stress and cell proliferation inhibition. Glycolysis usually occurs in the cytoplasm during ischemia. The mechanism of cerebral ischemia-induced hyperglycemia was investigated.

Methods:
Both non-fasting young (2-month-old) and aged (18-month-old) mice were subjected to middle cerebral artery occlusion (MCAO) for 1, 2 or 3 hours without reperfusion. Relative cerebral blood flow was measured by Laser Doppler and peripheral blood glucose was measured by glucometer after induction of MCAO at various time points. The ipsilateral cerebral cortex tissue of the brain was harvested. Total cellular protein and protein in cytoplasmic fraction was prepared and analyzed by western blot.

Results:
In both young and aged mice, MCAO induced hyperglycemic condition as peripheral blood glucose levels were increased in MCAO mice compared to non-MCAO (sham) mice. Relative cerebral blood flow was decreased during the course of MCAO, indicating ischemia status. In ipsilateral cerebral cortex tissue, phosphorylated (Ser1177) endothelial nitric oxide synthase (eNOS) levels were decreased in total protein and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) levels were increased in cytoplasmic fraction in a MCAO-time dependent manner.

Conclusion:
Ischemia induced hyperglycemia condition in both young and aged mice. In the ischemia brain, levels of phosphorylated eNOS were decreased, whereas the levels of GAPDH were increased. Taken together, these data suggest that MCAO induces hyperglycemia via enhancing glycolysis in the brain.

Key words:
Stroke, Ischemia, middle cerebral artery occlusion, glycolysis, glycolytic enzyme, GAPDH, eNOS
Abstract TP391: CGRP Monoclonal Antibody Does Not Exacerbate Stroke Outcomes in Mice
Authors: JIN XUYAN , Sasaki Yuichi , Zhai Qingling , Ayata Cenk
Published: January 2025

Background:
Calcitonin gene-related peptide (CGRP) is a potent vasodilator that plays a role in migraine. Monoclonal antibodies targeting CGRP, such as fremanezumab, is now widely used for migraine prevention. However, inhibition of CGRP system may also lead to vasoconstriction, raising concerns about whether the long-term treatment with these antibodies in migraine patients might increase the risk of stroke or worsen outcomes if a stroke occurs while taking these medications. Here, we aimed to investigate whether fremanezumab exacerbates stroke outcomes in a mouse model of ischemic stroke.

Methods:
Two middle cerebral artery occlusion (MCAO) models were used: a 12-minute occlusion simulating a transient ischemic attack (TIA) and a 60-minute occlusion representing a conventional stroke model. Fremanezumab was administered intraperitoneally at either 2 days or 7 days before MCAO induction in both models; one cohort received treatment 28 and 7 days before MCAO. On day 2 after reperfusion, brain tissues were harvested for TTC staining to evaluate infarct volume. Neurological function was assessed using a neuro score and corner test. Additionally, an angiogram using black ink was performed to visualize cerebral vasculature, and vessel diameters were measured to determine the impact of fremanezumab on vascular dimensions.

Results:
Angiographic arterial diameters in the fremanezumab arm did not differ from the saline arm, suggesting that fremanezumab does not cause vasoconstriction. In the TIA model, the fremanezumab group exhibited a trend towards increased infarct incidence and volume and hemorrhagic transformation, although these did not reach statistical significance. Additionally, there were no substantial changes in neurological scores and the corner test. In the 60-minute MCAO model, no significant changes or trends were observed in infarct volume or other outcomes between the two treatment arms. Outcomes were similar when fremanezumab was administered 2 or 7 days before MCAO.

Conclusion:
Despite previous concerns that long-term use of fremanezumab might exacerbate stroke risk by promoting vasoconstriction, our findings do not support this hypothesis and suggest that fremanezumab does not worsen stroke outcomes in these models. These findings have important implications for the management of stroke risk in patients using fremanezumab for migraine prevention, suggesting that it may be used with confidence regarding its impact on stroke risk.
Abstract TP392: Prior recurrent hypoglycemia exposure potentiates post-ischemic hypoperfusion in male insulin-treated diabetic rats.
Authors: Rehni Ashish , MALLEPALLI SURESH KUMAR REDDY , Dave Kunjan
Published: January 2025

Diabetes is a widespread disease, and stroke is one of the serious complications of diabetes. Antidiabetic therapy increases the risk of recurrent hypoglycemia (RH). We have previously shown that RH exposure leads to severe post-ischemic hypoperfusion at least up to 80 minutes after ischemia and increases the extent of ischemic brain injury in insulin-treated diabetic (ITD) rats. However, the total duration for which these perfusion deficits last is unknown. Thus, we evaluated cerebral blood flow up to 7 days post-ischemia in RH-exposed ITD rats using laser speckle imaging. Diabetic male rats were treated for hyperglycemia using insulin pellets, were assigned randomly to either hyperinsulinemic euglycemia (ITD+RH+Glucose control; n=7) or hyperinsulinemic hypoglycemia (ITD+RH; n=7) groups (3 h duration) (Figure B-C) and were subjected to transient global cerebral ischemia overnight after the last episode of hyperinsulinemic euglycemia or hyperinsulinemic hypoglycemia. We evaluated cerebral perfusion at baseline (pre-ischemia), 1 h, 24 h, 3 d, 5 d, and 7 d post-ischemia. The cerebral ischemia in RH-exposed ITD rats resulted in a significant decrease in percentage change in cerebral blood flow as compared to the control rats when quantified 1 hour (23%, p<0.01) and 1 day (17%, p<0.05) after cerebral ischemia. However, the percentage changes in cerebral blood flow in ITD+RH group were not significantly different from that of the control group at 3, 5, and 7 days after ischemia (Figure A, D). The cerebral blood flow post-ischemia at 1-hour (24%) and 1-day (18%) was significantly lower (p<0.001 each) while at 3 (12%, p<0.05), 5 (25%, p<0.05), and 7 days (29%, p<0.01) was significantly higher than that of the baseline values in RH-exposed ITD rats. The cerebral blood flow at 1 hour, 1 day, and 3 days after ischemia in ITD + RH + glucose rats was not significantly different from the baseline values. The cerebral blood flow at 5 (19%, p<0.05) and 7 (42%, p<0.001) days after ischemia in ITD + RH + glucose rats was significantly higher than the baseline values. Our results show that RH exposure induces severe post-ischemic hypoperfusion for at least ≈24 hours after ischemia in young male ITD rats. Next, we aim to study the duration of the effect of RH on post-ischemic hypoperfusion in female ITD rats and to identify the underlying mechanism causing this effect in the animal model of diabetes.
Acknowledgment:
NIH (NS122808).
Abstract TP393: Reducing Neutrophil Sialic Acid Residues Alleviates Cerebral Hypoperfusion in Alzheimer’s Models
Authors: Bhatt Nairuti , Tabrizi Zeynab , Franciosa Sofia , CHAKRABORTY SUPRIYA , Agatemor Christian , Bracko Oliver
Published: January 2025

Dysregulation of the immune system is a contributing factor in the progression of Alzheimer’s Disease (AD), likely by increased vascular inflammation triggered by brain or peripheral inflammation. Our research has demonstrated that neutrophils play a role in causing hypoperfusion by adhering to and obstructing blood vessels, as seen in both mouse models for and patients with AD. Notably, protein glycosylation of membrane proteins is essential for regulating the adhesion properties of neutrophils to immune cells and the vasculature.

Here, we utilize lectin blots to show that sialic acid residues, which are the terminal caps of glycosylation chains, are increased on neutrophil membrane proteins from an amyloidosis Alzheimer’s mouse model. Furthermore, we evaluated the efficacy of the sialyltransferase inhibitor alpha 2,3 sialyltransferase-IN-1 by lectin blot analyses, identifying it to be an effective compound for removing sialic acid from neutrophil membrane proteins. Notably, we performed
in vivo
multiphoton imaging of cerebral blood flow and capillary stalling in AD mice injected with alpha 2,3 sialyltransferase-IN-1. Our findings demonstrated that reducing sialic acid residues on neutrophils improved cerebral blood flow and capillary stalling.

This work suggests that the altered glycosylation pattern, specifically aberrant sialylation residues of neutrophil glycoproteins, are a significant contributing factor to the hypoperfusion observed in AD mouse models and patients. Modulating the glycosylation profile may present a potential therapeutic approach for improving the vascular dysfunction associated with AD pathogenesis.
Abstract TP394: Electrical Stimulation Therapy Improves Mitochondrial Calcium Uptake in Induced Neurons under Hypoxic Conditions
Authors: Thompson Kamila , Liquidano Cortes Lizbeth , Chan Tamara , Wernig Marius , George Paul
Published: January 2025

Introduction:
Electrical stimulation has proven itself to be a powerful and novel tool in stroke recovery. However, it is unknown why this therapy significantly improves behavioral outcomes in rodent models of stroke. In a hypoxic environment, neural cells lack the proper glucose and oxygen to survive leading to many cell death pathways like Ca
2+
toxicity. Healthy neural cells can uptake excess intracellular Ca
2+
through the mitochondria as mitochondrial membrane potential increases. Neural cells under hypoxic conditions, however, are unable to uptake as much calcium due to mitochondrial dysfunction. We hypothesize that electrical stimulation therapy increases mitochondrial membrane potential in neural cells under hypoxia leading to increased Ca
2+
uptake and less Ca
2+
toxicity in the cell.

Methods:
To test our hypothesis, we used two innovative methodologies: (1) neuron conversion from induced pluripotent stem cells (iPSCs) with neurogenin-2 (Ngn2) overexpressed for a period of 28 days developed in the Wernig Lab, and (2) a custom
in vitro
stimulation setup consisted of a gold layer sputtered onto cell culture inserts and a copper sheet placed below the 24-well plate creating an electric field across the iN cells (Figure 1). Induced neurons (iN) underwent oxygen glucose deprivation (5% CO
2,
10% H
2
, and 85% N
2
) for a period of four hours in glucose deprived media. One hour after exposure, iN cells were electrically stimulated at 50mV, 100Hz, and a 20% duty cycle for 20 minutes at 37°C. One day after stimulation, iN cells were stained with Rhod-2, a labeled calcium indicator that increases in fluorescence as a function of mitochondrial Ca
2+
, and DAPI to confirm cell presence.

Results and Conclusions:
Stimulation significantly increased mitochondrial Ca
2+
concentration in healthy iN cells seen in Figure 2 (N = 5, p = 0.014). In Figure 3, stimulation also significantly increased mitochondrial Ca
2+
in hypoxic cells (N = 5, p = 0.0024). Increased mitochondrial Ca
2+
in both cases indicates that mitochondrial calcium uptake appears to be improving. Electrical stimulation increasing mitochondrial membrane potential and improving calcium uptake could be a mechanism by which electrical stimulation facilitates stroke recovery. Future work will include additional staining for cytosolic calcium concentration (Calcium Green) and mitochondrial membrane potential (TMRM) to better track the relationship between the two.
Abstract TP396: Effects of low-intensity pulsed focal ultrasound-mediated delivery of endothelial progenitor-derived exosomes in MCAo stroke
Authors: Alptekin Ahmet , Khan Mohammad B. , Parvin Mahrima , Chowdhury Hasanul , Kashif Sawaiz , Selina Fowzia , Williams Dylan , Blumling Emily , Frank Joseph A. , DHANDAPANI Krishnan , Arbab Ali
Published: January 2025

Exosomes have been used for therapeutic purposes to target stroke and other disorders. Repeated administration of mesenchymal stem cell (MSC)-derived exosomes in rats showed improved functionality and reduced stroke injury. However, exosomes from endothelial progenitor cells (EPCs) have not been tested in any stroke model, and in vivo bio-distribution study is lacking.

Targeted delivery of IV-administered exosomes has been a great challenge. Modifying the exosomal surface to carry different ligands or peptides has been tried to increase delivery to target tissues. However, the overall results are not encouraging. Delivery of exosomes to the brain is a daunting task, and a blood-brain barrier(BBB)-penetrable peptide is being considered. However, a method that can deliver naïve (unmodified) exosomes to the site of stroke without destroying host tissues, disrupting BBB, or the membranes of the delivery vehicles (such as exosomes) will be a breakthrough.

Low-intensity pulsed ultrasound (LIPUS) is approved for clinical use in musculoskeletal and physiotherapy clinics. The use of focused LIPUS to deliver exosomes has yet to be explored in stroke. The objectives of the proposed studies were to determine whether LIPUS-mediated increased delivery of EPC exosomes enhances stroke recovery and functional improvement in mice with tMCAo stroke. In this study, we used EPC-derived exosomes for stroke treatment. To enhance exosome delivery to the stroke area, we utilized focused LIPUS, which temporarily disrupts BBB. We evaluated stroke volume with MRI at different time points. We also conducted behavioral studies in parallel to MRI to determine the recovery. In the end, we studied the brain tissue with immunohistochemistry studies to evaluate the extent of stroke and tissue regeneration.

In vivo, imaging showed a higher accumulation of EPC exosomes following focused LIPUS without any damage to the underlying brain tissues. Four groups (Vehicle, LIPUS only, EPC-exosomes only, and LIPUS+EPC-exosomes) of aged animals were enrolled in the studies. The focused LIPUS + EPC exosomes group showed a decreased stroke volume (p=0.08) on day 7, decreased FluoroJade+ cells, and significantly higher numbers of neovascularization in and around the stroke areas although rCBF was not increased compared to that of other groups. There were no differences in the white matter tract volumes, ventricular volumes, astrogliosis, or neurobehavioral functions among the treated groups.
Abstract TP399: Modulation of cytotoxic T cells by Poly-Glu/Tyr attenuates neuroinflammation after ischemic stroke
Authors: Kim Jiwon , Kim Jong Youl , Lee Jong Eun
Published: January 2025

After ischemic stroke (IS), the cytotoxic T (Cyto T) cells infusing to the infarct site enhance the neuroinflammation. Previous studies have shown that increasing the proportion of regulatory T (Treg) cells relative to Cyto T cells can alleviate inflammatory conditions. Poly-Glu/Tyr polypeptide (Poly-YE; P-YE) was reported as a one of the key immune modulators to just modulate T cell balance. Therefore, we focused on screening target protein that affect T cell balance by P-YE. To screen target protein, we carried out protein microarray and showed that P-YE strongly bound to neutrophil cytosolic factor (NCF1) which is a one part of NOX complex. In the inflammatory response, activated NCF1 is known to bind to Moesin (MSN) to migrate forward to the membrane and assemble into the NOX complex. Also, recent study showed that unbound MSN to NCF1 induces FOXP3 expression in helper T cells. Based on this data, we hypothesized that 'NCF1+ P-YE' binding leads to the inhibition of NOX complex assembly and the conversion of Cyto T cells to Treg cells in neuroinflammation. P-YE loaded on Nanoparticles (Np P-YE; 3ug/mL) was treated to primary Cyto T (CD8+ T) cell isolated from the spleen of 8-week-old C57BL/6 male mouse. These cells were cultured in Oxygen-Glucose Deprivation-conditioned microglia medium (OGD-conditioned medium; CM) to mimic exposure to neuroinflammation. The results showed that Np P-YE fused to the cell membrane and entered to cytosol of CD8+ T cell. In the CM group treated with P-YE, superoxide was remarkably decreased and CD8+ T cells expressed FOXP3. In Co-IP, we confirmed that the binding of NCF1 and P-YE liberated MSN. Also, Proteome cytokine array showed that P-YE treatment group reduced cytokines compared with non-treatment group. In tMCAO modeling mice injected with P-YE (1mg/kg), the infarct area decreased and the pro-inflammatory phenotype of microglia was reduced. Finally, through behavior tests, the mice injected P-YE after tMCAO surgery showed improvement in stereotyped behavior and weakness due to ischemic damage. Taken together, NCF1 bound to P-YE can’t form NOX complex and MSN dissociated from NCF1 may lead to FOXP3 expression. Therefore, P-YE binds to NCF1 under neuroinflammatory conditions, converting some CD8+ T cells into CD8+FOXP3+ cells, thereby inhibiting ROS production and exerting anti-inflammatory effects.
Abstract WP90: Cost of Stroke Treatment: A Comparative Analysis of Mobile Stroke and Standard Treatment
Authors: Davis Nicolle , Lykens David , Khanna Anna , Jacobs Molly
Published: January 2025

Introduction:
Over the past decade, Mobile Stroke Treatment Units (MSTU) have enhanced the quality of stroke care in the United States by bringing the hospital to the patient. While MSTUs improve stroke patient outcomes compared to standard hospital care, there are still limited units operating. The implementation of a MSTU requires considerable initial and long-term investment limiting their widespread programmatic formation. We evaluated a MSTU program in Florida between August 2023 and April 2024 for comparative patient associated out of pocket costs with MSTU and standard stroke care.

Methods:
A discrete time Markov Chain Monte Carlo (MCMC) model was used to estimate incremental cost-savings associated with MSTU treatment compared to standard hospital care. The Markov model captured treatment costs for the care of patients at two functional levels as defined by the modified Rankin Scale (mRS). The potential cost-savings was determined by comparing the estimated costs incurred by the MSTU cohort to a counterfactual scenario of standard care of Emergency Medical Services (EMS) transport to the Emergency Department (ED). Since the model focused on the cost of patient care, costs included only billed ED, inpatient, and outpatient hospital care and services provided in the baseline year and then estimated cost of care over the next four years. All values represent 2024 dollars ($) and a 3% discount rate was applied to years two through four.

Results:
The MSTU treated 59 acute stroke patients with an average age of 71.86 (SD=13.78). Overall, 76% (N=45) were diagnosed with ischemic stroke, 9% with intracerebral hemorrhage (ICH), and 15% with transient ischemic attack (TIA). At discharge, 54% were independent and 46% dependent. In Year 1 (baseline), out of pocket cost differential between MSTU patients and the standard care was estimated to be $5,306 and $6,485 for the independent and dependent patients respectively. Projected future cost differentials in Years 2 to 4 were $4,571, $3,845, and $2,817 for the independent functioning cohort and $5,586, $4,700, and $4,188 for the dependent functioning cohort.

Conclusion:
These results suggest that the out of pocket cost for MSTU patients was significantly lower than standard care both at baseline and over the first four years post-stroke, making MSTU acute stroke management a better economic system of care for time metrics, long term patient outcomes, and cost effectiveness.
Abstract WP94: Early supported discharge program decreases length of hospital stay and demonstrates high clinic follow-up rates after stroke
Authors: Tenberg Amelia , Zink Elizabeth , Bahouth Mona
Published: January 2025

Background:
The transition period after hospitalization for stroke is a vulnerable time for patients as all adapt to new physical, cognitive, or emotional changes and destabilized comorbid conditions. Transitional care programs designed for post-stroke care carry the promise of improved outcomes and reduced hospital readmission rates, however attendance rates to these scheduled visits in other stroke early supported discharge programs are reported as low as 35%. In addition to patient specific consequences, missed stroke clinic visits impact system efficiency and workflow which carry broad regional consequences. We sought to understand the impact of our early supported discharge program on hospital length of stay and clinic attendance patterns to prepare for ongoing iteration of this program.

Methods:
All hospitalized stroke patients who are discharged to home are enrolled in the Joint Stroke Transitional Technology-Enhanced Program (JSTTEP) and seen by a stroke specialist using telemedicine platform within the first 2 weeks of hospital discharge. Following JSTTEP, patients receive usual care which includes a stroke clinic visit 2-3 months after discharge, either by telemedicine or in-person based on patient preference and clinical needs.

Results:
There has been no change in demographics since the inception of JSTTEP in 2020 with the average age of patients 61 years, 40% female, and nearly 50% black. In calendar year 2023, 309 patients were enrolled in the JSTTEP following hospitalization for acute stroke. Of those, 277 (90%) completed the first JSTTEP telemedicine visit. The mean time from hospital discharge to the first JSTTEP visit was 7.6 days. Hospital length of stay has decreased from 4.5 days prior to JSTTEP to 4.0 days in 2023. Modified Rankin Scale scores at 90 days decreased from 2.2 to 1.1 in a subset of patients with available scores.

Conclusion:
Since the implementation of JSTTEP, hospital length of stay has decreased for stroke patients who are discharged to home. We note a high show rate to this clinic and suspect that there are a variety of contributors to these successes including close proximity to hospitalization, rapid attention to evolving post-discharge needs, interaction with stroke specialists, and use of telemedicine to facilitate access during a time period where driving is prohibited. The intentional design of the JSTTEP resulting in high level of engagement is likely a strong factor in the early success of the JSTTEP program.
Abstract WP95: Impact of First Imaging Protocol Changes on Door-to-Puncture Time in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy
Authors: Kim Jun Yup , Kang Jihoon , Kim Beom Joon , Kim Do Yeon , Han Moon-Ku , BAE Hee-joon , Baik Sung Hyun , Jung Cheolkyu
Published: January 2025

Introduction:
The choice of initial imaging modality significantly impacts door-to-puncture time (DPT) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT). Studies have shown that using CT as the first imaging modality can reduce DPT compared to MRI. In July 2023, we revised critical pathway (CP) protocols including first image modalities from MRI to CT regardless of last known normal time (LNT). Therefore, we evaluated the impact of process modification including first image modalities could reduce the DPT for the EVT candidates.

Methods:
Prior to July 2023, EVT candidate AIS patients who visited Seoul National University Bundang Hospital, comprehensive stroke center, received CT as the first imaging modality if they arrived within 6 hours after onset, while others underwent MRI. From July 2023, all patients with disabling symptoms or an NIHSS score of 6 or higher received CT as the initial imaging, irrespective of LNT. We retrospectively analyzed the single center quality indicators, including DPT, door-to-image time, door-to-reperfusion time, and proportion of symptomatic intracerebral hemorrhage (sICH) comparing outcomes before and after the protocol change.

Results:
The total number of AIS patients undergoing EVT increased from 396 in the first half of 2022 to 442 in the second half of 2023. Median DPT decreased from 71 minutes in early 2022 to 60 minutes after the protocol change, with a corresponding increase in the proportion of patients achieving DPT within 60 minutes from 37.5% to 52.2%. The median door-to-image time for patients receiving CT decreased from 27 minutes to 22.5 minutes, with 94% achieving imaging within 30 minutes post-change compared to 70% pre-change. MRI, on the other hand, showed a median door-to-image time reduction from 30 minutes to 28.5 minutes, but only 50% achieved imaging within 30 minutes. Overall, the median door-to-reperfusion time decreased from 130 minutes to 105 minutes, with the proportion of patients achieving reperfusion within 120 minutes increasing from 37.9% to 62.5%. There was no significant change in proportion of sICH.

Conclusions:
The protocol change to a CT-first approach significantly improved key EVT quality indicators, particularly in reducing door-to-puncture time. These findings underscore the importance of optimizing imaging strategies to enhance outcomes in AIS patients undergoing EVT.
Transforming Early Stroke Care Through Mobile Stroke Treatment Unit Rendezvous With Rural Emergency Medical Services
Authors: Davis Nicolle W. , Fayed Mahmoud , Hardee Evan , Lykens David , Hester Jeannette M. , Magnuson Ashley E. , Singh Amita , Peng Teng J. , Khanna Anna
Published: January 2025

BACKGROUND:

Mobile stroke units, also sometimes called Mobile Stroke Treatment Units (MSTUs) are changing the paradigm of acute stroke care and are considered to be an extension of the time is brain concept. Of the <20 active Mobile Stroke Programs in the United States, most are rooted in urban settings. In July 2023, the first MSTU in Florida was launched in Alachua County, implementing a unique and innovative rendezvous process with rural emergency medical services (EMS). We compared stroke outcome metrics between the MSTU, including rendezvous patients, and the standard process of EMS to the emergency department (ED).

METHODS:

We performed a retrospective analysis of patients with acute stroke evaluated in the MSTU and those transported to the ED by the standard EMS stroke alert process at an academic Comprehensive Stroke Center between July 25, 2023 and May 31, 2024. Patient demographic and acute stroke metrics were extracted to complete univariate and multivariate logistic regression analysis.

RESULTS:

Across all 3 groups, both MSTU patients with (n=76) and without (n=291) rendezvous compared with EMS-to-ED patients (n=807), had significantly shorter mean dispatch-to-door times (29.4 versus 28.5 versus 73.2 minutes, respectively;
P
<0.01), dispatch-to-needle times (41.3 versus 44.6 versus 104.1 minutes, respectively;
P
<0.01), and dispatch-to-puncture (92.7 versus 81.9 versus 138.0 minutes, respectively;
P
<0.01). In rural counties, MSTU rendezvous patients (n=76) compared with EMS-to-ED patients (n=206), had shorter mean dispatch-to-door and dispatch-to-needle times (41.3 versus 97.8 minutes, respectively;
P
<0.001). After adjusting for age and sex, these differences remained significant (odds ratio, 1.21 [95% CI, 1.07–1.37];
P
<0.01 and odds ratio, 1.80 [95% CI, 1.07–3.04];
P
=0.03, respectively).

CONCLUSIONS:

Our study demonstrates the effectiveness of MSTUs in Florida and establishes that the MSTU rendezvous process significantly improves timely stroke care in underserved rural counties.
Effect of Remote Ischemic Conditioning on the Form and Function of Red Blood Cells in Patients With Acute Ischemic Stroke
Authors: Blauenfeldt Rolf Ankerlund , Waller Jennifer , Drasbek Kim Ryun , Bech Jesper Nørgaard , Hvas Anne-Mette , Larsen Julie Brogaard , Andersen Morten Nørgaard , Nielsen Marlene Christina , Kjølhede Maria , Kjeldsen Mathilde , Gude Martin Faurholdt , Khan Mohammad Badruzzaman , Baban Babak , Andersen Grethe , Hess David Charles
Published: January 2025

BACKGROUND:

Remote ischemic conditioning (RIC) is a simple and low-cost intervention that is thought to increase collateral blood flow through the vasodilatory effects of nitric oxide (NO) produced by the endothelium and red blood cells (RBCs). This study aims to investigate whether RIC affects RBC deformability and levels of NO and nitrite in patients with ischemic stroke.

METHODS:

This is a predefined substudy to the RESIST (Remote Ischemic Conditioning in Patients With Acute Stroke Trial) randomized clinical trial conducted in Denmark. RIC was started in the ambulance and continued at the hospital for seven days. Blood samples were collected at different time points: prehospital in the ambulance, in-hospital upon arrival, 2 hours postadmission, and 24 hours postadmission. RBC deformability and erythrocyte aggregation rate were assessed using ektacytometry, NO using flowcytometry, and nitrite content using ozone chemiluminescence.

RESULTS:

Of 1500 prehospital randomized patients, 486 patients were included in this study between July 28, 2020, and November 11, 2023, and had blood samples taken. Of these, 249 (51%) had AIS, and here RIC treatment was not associated with increased RBC maximal deformability (RIC, 0.549; sham, 0.548;
P
=0.31), RBC NO (RIC, 35 301 median fluorescence intensity; sham, 34979 median fluorescence intensity;
P
=0.89), or nitrite (RIC, 0.036 µmol/L; sham, 0.034 µmol/L;
P
=0.38), but RIC treatment was associated with a significantly reduced aggregation pressure and a slower erythrocyte aggregation rate (RIC, 323.76 millipascal; sham, 352.74 millipascal;
P
=0.0113).

CONCLUSIONS:

Prehospital and in-hospital RIC significantly reduced erythrocyte aggregation rate in patients with acute ischemic stroke, while there was no change in RBC deformability, NO content, or whole blood nitrite levels.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03481777.
Exploring neuroendocrine influences on the sensorimotor-association
axis in a female and a male individual
Authors: Serio Bianca , Yilmaz Deniz , Pritschet Laura , Grotzinger Hannah , Jacobs Emily G. , Eickhoff Simon B. , Valk Sofie L.
Published: January 2025

Human neuroimaging studies consistently show multimodal patterns of variability along a key principle of macroscale cortical organization—the sensorimotor-association (S-A) axis. However, little is known about day-to-day fluctuations in functional activity along this axis within an individual, including sex-specific neuroendocrine factors contributing to such transient changes. We leveraged data from two densely sampled healthy young adults, one female and one male, to investigate intra-individual daily variability along the S-A axis, which we computed as our measure of functional cortical organization by reducing the dimensionality of functional connectivity matrices. Daily variability was greatest in temporal limbic and ventral prefrontal regions in both participants, and was more strongly pronounced in the male subject. Next, we probed local- and system-level effects of steroid hormones and self-reported perceived stress on functional organization. Beyond shared patterns of effects, our findings revealed subtle and unique associations between neuroendocrine fluctuations and intra-individual variability along the S-A axis in the female and male participants. In sum, our study points to neuroendocrine factors as possible modulators of intra-individual variability in functional brain organization, highlighting the need for further research in larger samples to assess the sex specificity of these effects.
A compact time-domain diffuse optical tomography system for cortical neuroimaging
Authors: Chekin Yaroslav , Decker Dakota , Dehghani Hamid , Dubois Julien , Field Ryan M. , Gopalakrishnan Viswanath , Koch Erin M. , Lerner Gabriel , Aghajan Zahra M. , Miller Naomi , Olvera Isai , Patel Milin J. , Perdue Katherine L. , Schmidt Joshua , Szczepanski Victor
Published: January 2025

Recent years have witnessed a rise in research utilizing neuroimaging for precision neuromedicine, but clinical translation has been hindered by scalability and cost. Time-domain functional near infrared spectroscopy (TD-fNIRS), the gold standard of optical neuroimaging techniques, offers a unique opportunity in this domain since it provides superior depth sensitivity and enables resolution of absolute properties unlike its continuous wave counterparts. However, current TD systems have limited commercial availability, slow sampling rates, and sparse head coverage. Our team has overcome the technical challenges involved in developing a whole-head time-domain diffuse optical tomography (TD-DOT) system. Here, we present the system characterization results using standardized protocols and compare them with other state-of-the-art systems. Furthermore, we showcase the system performance in retrieving cortical activation maps during standard hemodynamic, sensory, and motor tasks. A combination of the system performance, signal quality, and ease of use can enable future studies aimed at investigating TD-DOT clinical applications.
Meta Unveiling: Exploring Aesthetic Canons and the Global Impact of Chinese Metaverse Style
Authors: De Masi Vincenzo , Di Qinke , Li Siyi , Song Yuhan
Published: January 2025

The metaverse represents the cutting edge of the creative industry, guiding in new horizons in content production, particularly within the realms of virtual reality (vr), argument reality (ar), and mixed reality (mr). Anticipating the significant future worth of the metaverse sector, certain countries have initiated the allocation of resources towards its advancement. China stands prominently as a key player in metaverse content development, with the Chinese government allocating substantial resources to this burgeoning sector. According to Statista, the projected value of the metaverse market is expected to reach US$12.6 billion in 2023. This market is poised to exhibit a remarkable compound annual growth rate (cagr 2023–2030) of 31.93%, resulting in a projected market volume of US$87.6 billion by 2030.

Due to substantial market expansion and increased investments, production studios and the creative sector are witnessing the emergence of novel content formats. These activities encompass the development of games and arcade experiences, as well as the creation of content for advertising and marketing. Currently, noticeable patterns are already apparent in several industries. Video games set in the metaverse in China generally adhere to traditional aesthetics, primarily influenced by Japanese designs and canons, with less input from American styles. This article embarks on an in-depth exploration of the intersection between traditional Chinese aesthetic principles and the burgeoning technological innovations within the metaverse, shedding light on China’s strategic positioning at the forefront of this digital evolution. Through a meticulous analysis of current platforms and ai-driven content creation, we unveil how China’s rich cultural heritage and contemporary digital strategies converge to craft a unique metaverse aesthetic. This fusion not only amplifies the global digital narrative but also catalyzes the cross-cultural exchange and adoption of Chinese digital paradigms, projecting significant implications for the global creative industries. By emphasizing the interaction of art and technology, this study forecasts a shift in the global digital landscape towards a more inclusive and diverse metaverse, underpinned by the internationalization of Chinese aesthetic canons. This analysis aims to contribute to the academic discourse on digital culture, offering insights into the potential trajectories of global digital aesthetics and the role of cultural heritage in shaping future digital realms.
10. A brief conservationist’s guide to self-governance with illustrations from small-scale fisheries
Authors: Basurto Xavier
Published: January 2025

Xavier Basurto outlines the current thinking and empirical data supporting this innovative field. He recently led Illuminating Hidden Harvests for the Food and Agriculture Organization of the United Nations (FAO). This approach fully integrates natural science, social science, and governance to map pathways to solutions in these complex social-ecological systems.
12. Modern marine conservation using environmental nucleic acids (eDNA and eRNA)
Authors: Closek Collin , Claassens Louw , Killeen Helen J.
Published: January 2025

Collin J. Closek, Louw Claassens, and Helen J. Killeen. Over the last 10+ years, rapid increases in technological approaches to the assessment of environmental DNA (eDNA), and even more rapid declines in costs for sampling and sequencing eDNA and eRNA, have opened a whole new door for employing this amazing molecular technology to assess biodiversity and dynamics. Closek et al. walk us through these developments and point to how these ever more available methods could accelerate key research and allow many scholars and practitioners to address questions that were previously inaccessible. Research into environmental DNA opens new fundamental science doors and allows us to probe key conservation issues with speed and accuracy. The authors detail the current methods and point to potential future applications.
13. Building the scientific and analytical framework for Dynamic Ocean Management
Authors: Hazen Elliott , Abrahms Briana , Blondin Hannah , Scales Kylie , Welch Heather
Published: January 2025

Elliott L. Hazen, Briana Abrahms, Hannah Blondin, Kylie Scales and Heather Welch also address managing marine ecosystems under climate variation from seasonal cycles, such as the El Nino-La Nina cycles and directional climate change. In pelagic systems, predators and prey move, but so also do people, including fishermen and shippers. Because all this movement overlays an “ocean in motion”, we must recognize these dynamics in order to reduce spatio-temporal conflicts. Bycatch of marine megafauna in fisheries, or ship strikes on whales, require a deep understanding of the relationship between environmental variation and animal movement. But we must also understand how environmental variation alters the behavior of people pursuing their living on the sea. The authors introduce exciting new scientific and analytical frameworks that set the stage for the emerging field of dynamic ocean management.
14. Power, politics, and culture: The human dimensions of marine conservation technology
Authors: Jenkins Lekelia “Kiki”
Published: January 2025

Lekelia D. Jenkins is a scholar who has focused on these human dimension issues, primarily in small-scale fisheries and coastal communities. A major focus of her work has been Marine Conservation Technology, which often involves inventing a device, or technological approach, that can contribute to resolving a conflict, such as bycatch in fisheries. She has probed the importance of power, politics, and culture in the invention/diffusion process. Who leads the invention and modification of these solutions has a big influence on how willing the community is to adopt the new technology. Thus, successful pathways to solutions require sensitive engagement of individuals and communities to foster the uptake of a workable solution.
18. Advancing youth-led movements for the ocean is essential
Authors: Fernandez Daniela
Published: January 2025

Daniela V. Fernandez founded Sustainable Ocean Alliance (SOA) when she was just 19 years old and here explains and promotes youth-led movements for the oceans.
23. Strengthening NGO networks and capacity building for ocean sustainability in China
Authors: Han Han
Published: January 2025

Han Han is the founder and CEO of China Blue, one of the first marine conservation NGOs in China. Here she shares her perspectives on building capacity among individuals and networks to promote ocean sustainability.
On the Predictability of Springtime Ozone Depletion Events using the ECCC Global Deterministic Prediction System
Authors: de Grandpré Jean , Ivanova Irena , Rochon Yves J. , Jouan Caroline , Vaillancourt Paul A.
Published: January 2025

Ozone depletion events are recurring phenomena in both polar regions, characterized by significant interannual variability. In this study, the Environment and Climate Change Canada (ECCC) Global Deterministic Prediction System is used to investigate the medium-range predictability of ozone and weather throughout the anomalous polar ozone depletion events of 2020. The system includes ozone assimilation and makes use of a prognostic ozone field for the computation of heating rates. The ozone scheme uses simplified photochemical modules to represent the impact of both gas-phase and heterogeneous reactions throughout polar ozone depletion events. The study shows that during the boreal and austral spring seasons, the predictability of the total ozone column exceeds 10 days and is comparable to the predictability of large-scale weather variables. It also demonstrates that over both polar regions, the inclusion of ozone radiative coupling has a significant impact on the temperature and wind distributions throughout the stratosphere. Over Antarctica, the ozone-coupled forecasts are systematically colder at all lead times, which helps eliminate a temperature bias present in the model using climatological ozone. The strength of the polar vortex also increases significantly throughout the lower stratosphere, in better agreement with zonal wind analyses. Over the Arctic, the use of an ozone-interactive model also produces significant changes in the temperature and wind forecasts, but the impact on the quality of the weather forecasts is generally neutral. The study shows the overall benefits of using ozone-coupled models in the highly perturbed springtime conditions of the polar regions.

Significance Statement

Ozone hole events which occur during springtime over polar regions can be predicted several days ahead using numerical weather prediction (NWP) systems. The ozone decrease associated with such events reduces the absorption of solar radiation, impacting the temperature and wind fields in the lower stratosphere at an altitude of about 15–20 km. This study shows that including this process within an NWP model can improve weather forecasts in the lower stratosphere. The impact of this process has been evaluated during the severe springtime ozone depletion events that took place in both polar regions in 2020. The study demonstrates that over Antarctica, using an ozone-coupled model produces a stronger and colder stratospheric polar vortex in better agreement with temperature and wind analyses. Overall, the study highlights the benefits of using ozone-coupled models in the highly perturbed springtime conditions of the polar regions.