bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Severe Hypertriglyceridemia in Pregnancy With Niacin: Reevaluating Safety and Therapeutic Benefits
Authors: Suda Nisha , Leon-Martinez Daisy , Peter Patricia R. , Flannery Clare A. , Irani Roxanna A.
Published: January 2025

Background: Severe hypertriglyceridemia (triglycerides (TGs) >1000 mg/dL, >11.3 mmol/L) is a rare but potentially morbid condition in pregnancy. Physiological changes in pregnancy may unmask or exacerbate an underlying defect in TG metabolism. When conventional therapies are ineffective in controlling TG levels, a personalized management approach is needed. We present a case of severe hypertriglyceridemic pancreatitis successfully managed with niacin, a treatment that has seen limited use in pregnancy due to the paucity of available data.

Case Presentation: A 29‐year‐old pregnant woman with a history of cholecystectomy and a prepregnancy BMI of 30.6 kg/m2 presented at 12 weeks’ gestation with acute pancreatitis and severe hypertriglyceridemia (6900 mg/dL, 77.9 mmol/L). After initial management with intravenous (IV) fluids, insulin infusion, and a low‐fat diet, her TG levels improved. However, she was readmitted at 23 weeks’ gestation with recurrent hypertriglyceridemia (2872 mg/dL, 32.4 mmol/L), requiring a more aggressive insulin regimen. Despite various interventions, including omega‐3 fatty acids (O3FAs), fenofibrate, and central venous catheter insulin infusion, her TG levels remained elevated, necessitating early delivery at 34 weeks’ gestation. Her postpartum recovery included continued TG management with fenofibrate and O3FAs. Four years later, during a second pregnancy, she presented with similar hypertriglyceridemia, managed with diet, metformin, fenofibrate, and insulin. Due to persistent hypertriglyceridemia (>3000 mg/dL, 33.9 mmol/L), niacin was added as an additional therapy and titrated to 2000 mg/day, which successfully sustained TG levels below 1000 mg/dL (11.3 mmol/L) through the remainder of her pregnancy. She delivered her second child via cesarean section at 35 weeks’ gestation due to preeclampsia. Both children had developmental issues, with her first child diagnosed with attention‐deficient hyperactivity disorder (ADHD) and her second child with autism spectrum disorder and motor delays. The patient was encouraged to remain on long‐term management for her metabolic condition.

Conclusions: Managing severe hypertriglyceridemia during pregnancy is challenging due to uncertainties about treatment efficacy and safety. Timely reduction of maternal TGs is essential to prevent complications and requires adjustments throughout pregnancy. This case demonstrates the effectiveness and safety of niacin, often underutilized due to perceived side effects, in managing severe hypertriglyceridemia in pregnancy when other treatments were inadequate.
Multiphysics Analysis of Natural Circulation‐Driven Operation of Passive Molten Salt Fast Reactor and Effect of Guide Structure
Authors: Lee Juhyeong , Song Min Seop , Jae Seungug , Yang Won Sik , Kim Sung Joong
Published: January 2025

A new molten salt reactor (MSR) design has been developed aiming for long‐term operation and high safety. In order to enhance the integrity and economy of the system during the long‐term operation, pumps were removed from the primary system, and the fuel salt flow was developed by natural circulation. In terms of thermal–fluidic, the natural circulation operation without a pump increases the reactor safety and resistance to accidents. The normal operation feasibility of the reactor was evaluated with the multiphysics analysis conducted with the Generalized Nuclear Foam (GeN‐Foam) code. It was shown that the reactor can maintain stable power under a fixed heat exchanger outlet temperature condition. To increase the natural circulation, the active core region was designed to have a simple cylindrical shape, which induced a stagnation zone with slow velocity near the side wall. Due to the slow velocity, the stagnation zone has a substantially high temperature, and a flow guide was introduced to mitigate the stagnation effect. The impact of the flow guide was evaluated, including the reactivity feedback and delayed neutron precursor drift effect. The results highlight the importance of analyzing the flow distribution within the core in an MSR and demonstrate the effectiveness of the guide structure in ensuring stable core flow.
Incorporating Nanopore Sequencing Into a Diverse Diagnostic Toolkit for Incontinentia Pigmenti
Authors: Ahting Simone , Popp Denny , Oppermann Henry , Strehlow Vincent , Fasshauer Maria , Popp Bernt , Karnstedt Maike , Schumann Isabell
Published: January 2025

Incontinentia pigmenti (IP) is a rare hereditary disorder affecting 1.2 in 100,000 live births, predominantly females. Genetic analysis of IP is complicated by a homologous pseudogene, making conventional short‐read sequencing challenging. While long‐range PCR is typically used to overcome this, skewed X‐inactivation detection can also aid in assigning variants to IKBKG. We employed a comprehensive approach, incorporating whole‐exome sequencing (WES), long‐range PCR, RT‐PCR, X‐inactivation analysis, and nanopore sequencing, to identify and accurately phase a small heterozygous deletion, NM_001099857.5: c.363_367del, p.(Leu122Glyfs ∗14), in the IKBKG gene in an IP‐affected family. The deletion was initially detected via WES, with skewed X‐inactivation observed in both the proband and her mother. Long‐range PCR specific to IKBKG confirmed the variant’s location in the IKBKG gene, not in the pseudogene. On the RNA level, the variant was undetectable, suggesting nonsense‐mediated decay of the transcript. Nanopore sequencing precisely mapped the variant to IKBKG and analyzed the methylation status of both alleles, confirming the skewed X‐inactivation, with the variant‐carrying allele predominantly inactivated. This demonstrates the nanopore sequencing’s value in genetic diagnosis, enabling precise variant localization and analysis of X chromosome activation status in females with skewed X‐inactivation, aiding in accurate diagnosis and understanding of IP.
Exploring Ultrasound‐Induced Changes on Bioactive Content and Color Properties of Sour Cherry Juice Involving Insights From Image Processing Analysis
Authors: Aktı Nursena , Yildiz Semanur
Published: January 2025

Thermal processing can intensify the degradation of beneficial compounds in fruit juices produced from concentrate, which underwent prior evaporation, leading to duplicated processing and likely increased quality deterioration. This study aims to (i) investigate the potential of ultrasound (US) to retain bioactive compounds and quality of sour cherry juice (SCJ) produced from concentrate and (ii) involve insights from digital image processing (IP) to evaluate color attributes of processed SCJs. US was optimized considering amplitude (60%–100%) and time (2–15 min) as independent variables, maximizing total anthocyanin content (TAC) and total phenolic content (TPC) at 67% amplitude for 7 min. Process‐dependent changes in TAC, TPC, antioxidant activity, and color were compared for optimal US and conventional thermal (90°C for 1 min) treatments. US maintained similar TAC to untreated SCJ (160.4 mg/L); however, thermal processing reduced TAC to 154.4 mg/L (p < 0.05). TPC (417.89 mg/100 mL) significantly decreased by both treatments, while antioxidant activity remained stable. IP technology and conventional colorimetric methods were used to evaluate color properties. The two methods showed differing results on color properties, with IP suggesting an increase in redness and yellowness while colorimetric analysis suggests a reduction after processing. This study highlights the evaluation of the process‐induced changes for better preservation of bioactive content and quality of fruit juices as well as establishes a baseline for evaluating the quality of nonthermally processed fruit juices through computer vision‐based techniques.
Inhibition of the Transforming Growth Factor‐β Signaling Pathway Confers Neuroprotective Effects on Beta‐Amyloid‐Induced Direct Neurotoxicity and Microglia‐Mediated Neuroinflammation
Authors: Tiong Shao Qin , Mohgan Raxshanaa N. , Quek Jia Yee , Liew Jennifer Yue Suan , Wong Grace Yee Seen , Thang Zi Qing , Chan Zhi Ling , Gan Sook Yee , Chan Elaine Wan Ling
Published: January 2025

Background: Abnormal elevation of transforming growth factor‐beta (TGF‐β) has been observed among Alzheimer’s disease (AD) patients. This may be due to microglia‐mediated release of proinflammatory cytokines, which promote neuroinflammation and neuronal apoptosis. Silencing of TGFBR1, a gene encoding TGF‐β receptor type I (TGF‐βR1), has resulted in neuronal survival from amyloid‐beta (Aβ)‐induced neurotoxicity. Therefore, the present study investigated the neuroprotective effect of TGF‐βR1 inhibitors (RepSox, Galunisertib, and Vactosertib) against Aβ‐induced direct neurotoxicity and microglia‐mediated neuroinflammation.

Methods: The neuroprotective effect of TGF‐βR1 inhibitors against Aβ‐induced direct neurotoxicity and microglia‐mediated neuroinflammation were investigated using the RealTime‐Glo™ MT Cell Viability Assay. The inhibitory effect of TGF‐βR1 inhibitors on Aβ‐induced microglia‐mediated production of proinflammatory cytokines (TNF‐α and IL‐1β) was determined using enzyme‐linked immunosorbent assay (ELISA).

Results: TGF‐βR1 inhibitors (RepSox, Galunisertib, and Vactosertib) at the tested concentrations (6.25–150 nM) showed no significant cytotoxicity effects on SH‐SY5Y and BV‐2 cells. Moreover, treatments with these inhibitors exhibited neuroprotection on SH‐SY5Y cells against Aβ‐induced direct neurotoxicity. The trend of cell viability after 24 h treatment also supports the microscopic images of the cells’ morphology. Furthermore, pretreatment with these inhibitors conferred indirect neuroprotective effect against Aβ‐induced microglia‐mediated neuroinflammation by attenuating the production of proinflammatory cytokines (TNF‐α and IL‐1β).

Conclusion: The inhibition of the TGF‐β signaling pathway in neuronal and microglia cells by TGF‐βR1 inhibitors resulted in neuroprotection against Aβ‐induced direct neurotoxicity and microglia‐mediated neuroinflammation. Hence, targeting the TGF‐β signaling pathway in both neuronal and microglia cells could provide a promising therapeutic strategy in AD.
Amebicidal and Antiadhesion Activities of Knema retusa Extract Against Acanthamoeba triangularis T4 Genotype on Contact Lenses and Modeling Simulation of Its Main Compound, E2N, Against Acanthamoeba Beta‐Tubulin
Authors: Mitsuwan Watcharapong , Sama-ae Imran , Sangkanu Suthinee , Khan Dhrubo Ahmed , Biswas Partha , Hasan Md. Nazmul , Chuprom Julalak , Jimoh Tajudeen O. , Wiart Christophe , Zulkipli Masyitah Binti , Abdullah Nor Hayati , Pereira Maria de Lourdes , Oliveira Sonia M. Rodrigues , Saravanabhavan Shanmuga Sundar , Wilairatana Polrat , Mahboob Tooba , Nissapatorn Veeranoot
Published: January 2025

Medicinal plants have been used as alternative agents for the treatment of infections. This study aimed to investigate bioactivities of medicinal plant extracts including Knema retusa extract (Kre) against Acanthamoeba triangularis T4 in vitro and in silico. Anti‐Acanthamoeba activities of 44 extracts from 5 plant species were determined. From 44 tested extracts, a chloroform extract of Kre bark showed the strongest anti‐Acanthamoeba activities against both trophozoites and cysts, with MIC values of 32.25 and 62.50 μg/mL, respectively. Then, amebicidal and antiadhesion activities of Kre against A. triangularis were investigated. Kre reduced the growth by 3 logs within 8 h at 4 × MIC. Disruption of the cells with abnormal shapes was observed when trophozoites were treated with Kre. Trophozoites had lost their robust acanthopodia and began to shrink after treatment with Kre. Treated cysts exhibited wall disruption and dramatically showed forms of marked retraction. Treatment of Kre at 1/2 × MIC showed about 87% reduction in the trophozoite adhesion, while treatment at 2 × MIC exhibited a 59% reduction in the trophozoite adhesion to the plastic surface, compared with the control. Furthermore, 1 log cells/mL (90%) of the contact lens adhesive trophozoites were reduced and removed after treatment with Kre. Molecular docking indicated that E2N, the main compound in Kre, exhibited strong binding to the ligand binding sites at β‐tubulin, with a binding energy of −7.01 kcal/mol and an inhibitory constant of 2.43–7.32 μM. E2N generated multiple connections via hydrogen, hydrophobic, ionic, and water bridge bonding and maintained these connections until the simulation finished, facilitating the creation of stable bindings with the β‐tubulin protein as measured by molecular dynamics simulation. These findings suggest that Kre exhibits amebicidal and antiadhesion activities which could be used for the prevention of A. triangularis adhesion to contact lenses.
Comparative Analysis of Healthy Lifestyles in Peruvian University Students During and After the COVID‐19 Pandemic
Authors: Baltazar-Meza Carme Y. , Custodio María
Published: January 2025

The COVID‐19 pandemic has provoked a worldwide mental health crisis, affecting university students in an exacerbated way, exposing them to the risk of emotional isolation and development of eating disorders. The present study aimed to examine the quality of healthy lifestyle practices in university students from the Faculty of Human Medicine and the Faculty of Education of a Peruvian university during and after the COVID‐19 pandemic. This study was conducted during the academic period 2020 and 2023. Data collection was performed between July and August 2020, during the first wave of the COVID‐19 pandemic (M1) and between November and December 2023, post‐pandemic (M2). In M1 and M2, 370 and 82 students participated, respectively. The results of the Mann–Whitney test revealed significant differences between the total healthy lifestyle score of students in M1 and M2. In the nutrition domain, there are significant differences between the scores obtained in M1 and M2, revealing a decrease in nutritional care. Significant differences were also found between both faculties in substance use in M1 and physical activity practice in M2. Although a trend toward the adoption of healthy habits was observed in the initial stages, the longitudinal analysis reveals a generalized decrease in concern for health and well‐being. Medical students, on the other hand, showed greater resilience and more successful adaptation to new circumstances, evidencing the importance of academic training in the promotion of healthy lifestyles. These results underscore the need to implement intervention strategies aimed at promoting healthy habits in the student population, especially in contexts of health crisis.
Replication-Poison Treatment in BRCA1-Deficient Breast Cancer Causes MRE11 Over-Resection that Induces Single-Stranded DNA Accumulation and Mitotic Catastrophe
Authors: Tabet Imene , Orhan Esin , Candiello Ermes , Fenou Lise , Velázquez Carolina , Orsetti Beatrice , Rodier Geneviéve , Jacot William , Ribeyre Cyril , Sardet Claude , Theillet Charles
Published: January 2025

BRCA1 deficiency is observed in approximately 25% of triple-negative breast cancer (TNBC). BRCA1, a key player of homologous recombination (HR) repair, is also involved in stalled DNA replication fork protection and repair. Here, we investigated the sensitivity of BRCA1-deficient TNBC models to the frequently used replication chain terminator gemcitabine, which does not directly induce DNA breaks. A large fraction of BRCA1-deficient cells was sensitive to gemcitabine, in contrast to their isogenic BRCA1-proficient counterparts. Gemcitabine treated BRCA1-deficient cells accumulated massive levels of single strand DNA (ssDNA) and presented no RPA or RAD51 nuclear foci. The gemcitabine-induced accumulation of ssDNA in BRCA1-deficient cells was strongly diminished by targeting MRE11 with inhibitors and by siRNA attenuation. In contrast, treatment with the PARP1/2 inhibitor olaparib did not result in MRE11 dependent over-resection. Furthermore, a fraction of gemcitabine treated BRCA1-deficient cells that showed massive ssDNA accumulation slipped into mitosis, producing mitotic bridges and strongly stained BrdU and γH2AX micronuclei (MN). The BrdU-positive MN and DNA bridges also stained positively for cGAS. In conclusion, these data suggest that gemcitabine treatment in BRCA1-deficient TNBC exposes unprotected nascent DNA linked to replication fork reversal, which leads to MRE11 over-resection and ssDNA accumulation. Therefore, the observed hypersensitivity to gemcitabine indicates that it could be a beneficial addition to BRCA1-deficient TNBC treatment.
Significance of TYMS Polymorphism rs3819102 as a Prognostic Marker for Nonsmoking Lung Cancer Patients of the Han Ethnicity in China
Authors: Du Wei , Xu Chang , Cheng Zhiyuan , Sun Zhenyu , Guo Shicheng , Li Qiang , Song Yuanlin , Shen Bo , Bao Yang , Wu Junjie
Published: January 2025

Introduction: With high incidence and mortality rates, lung cancer is now one of the most common cancers in the world. The 5-year survival rate of lung cancer patients is very low, and predicting the prognosis of lung cancer patients and using it to develop treatment strategies and interventions is important for prolonging the survival time of patients. Folate metabolism involves various aspects such as methylation of DNA, RNA, proteins, lipids, etc. Disorders of folate metabolism are closely related to cardiovascular diseases, immunodeficiencies, tumors, etc., and TYMS is a key enzyme in the folate metabolic pathway. We investigated and analyzed the relationship between single nucleotide polymorphism rs3819102 synergistic clinical features in the TYMS and prognosis in lung cancer. Methods: A total of 888 Han Chinese patients with primary lung cancer were recruited between January and November 2009 (10 months), including Changhai Hospital Affiliated to the Naval Military Medical university (Second Military Medical University) and Taizhou Institute of Health Sciences of Fudan University. Of these, 49 were excluded due to incomplete data collected for various reasons. The study was approved by the Ethics Committee of the School of Life Sciences, Fudan University, and written informed consent was obtained from all participating subjects. This study does not include minors. Genomic DNA was extracted from patient blood samples using the Qiagen Blood Kit (Qiagen, Chatsworth, California) and genotyped using SNPscan technology. The association between TYMS polymorphism rs3819102 and prognostic was analyzed by the Kaplan-Meier (KM) analysis, log-rank test, and Cox proportional-hazards model. Results: In the Han nationality nonsmoking patients in China, compared with AA + AG genotype, the GG genotype (GG vs. AA + AG: adjusted hazard ratio = 1.69, 95% confidence interval: 1.00–2.83, p = 0.048401) of rs3819102 conferred a worse prognosis. TYMS rs3819102 A > G mutation shortened lung cancer patients’ survival and worse prognosis. Conclusion: TYMS rs3819102 may be a prognostic factor for deterioration in lung cancer patients.
Description and performance of two diet quality scores based on the Nova classification
Authors: Costa Caroline dos Santos , Santos Francine Silva dos , Gabe Kamila Tiemann , Steele Eurídice Martinez , Marrocos-Leite Fernanda Helena , Khandpur Neha , Rauber Fernanda , Louzada Maria Laura da Costa , Levy Renata Bertazzi
Published: January 2025

OBJECTIVE: To describe two low-burden diet quality scores and evaluate their performance in reflecting the dietary share of the least and most processed foods defined within the Nova food system classification.METHODS: This cross-sectional study included data from the NutriNet-Brasil cohort. Participants answered the Nova24hScreener, a 3-minute self-administered questionnaire measuring the consumption of a set of foods on the day before. Food items included in this tool belong to two main groups of the Nova classification: unprocessed or minimally processed whole plant foods (WPF, 33 items) and ultra-processed foods (UPF, 23 items). Two scores were obtained by summing the number of items checked: the Nova-WPF and the Nova-UPF. We compared the scores, respectively, with the dietary intake (% of total energy) of all unprocessed or minimally processed whole plant foods and all ultra-processed foods obtained from a full self-administered web-based 24-hour recall performed on the same day.RESULTS: The approximate quintiles of each score had a direct and linear relationship with the corresponding % of energy intake (p-value for linear trend < 0.001). We found a substantial agreement between the intervals of each score and the corresponding % of energy intake (Nova-WPF score: Prevalence-Adjusted and Bias-Adjusted Kappa (PABAK) 0.72, 95%CI 0.64–0.81; Nova-UPF score: PABAK 0.79, 95%CI 0.69–0.88).CONCLUSIONS: These two scores performed well against the dietary share of unprocessed or minimally processed whole plant foods and ultra-processed foods in Brazil and can be used to evaluate and monitor diet quality.
Abstract 108:
APOE
Epsilon 4 Carriers Derive Greater Benefit from Genetically Reduced Factor XI Levels
Authors: Clocchiatti-Tuozzo Santiago , Rivier Cyprien , Huo Shufan , Hawkes Maximiliano , Schwamm Lee , Ohno-Machado Lucila , Sheth Kevin , Gill Thomas , Falcone Guido
Published: January 2025

Introduction:
Coagulation factor XI (FXI) inhibitors have shown a better safety profile than other anticoagulants, offering similar reductions in ischemic stroke (IS) risk with a lower risk of intracerebral hemorrhage (ICH). The
APOE
ε4 genotype is associated with increased risks of both IS and ICH, likely due to its effects on lipid levels, intracranial atherosclerosis, and cerebral amyloid angiopathy. We hypothesized that
APOE
ε4 carriers would gain greater therapeutic benefit from genetically reduced FXI levels compared to non-carriers.

Methods:
We conducted a two-stage Mendelian randomization (MR) analysis using the random-effects, inverse-variance weighted method. First, we estimated the effect of genetically proxied FXI inhibition on IS and ICH risk in the general population using summary data from genome-wide association studies of FXI levels (16,169 participants), IS (1,503,898 controls and 110,182 cases), and ICH (3,745 controls and 3,226 cases). Second, we performed stratified analyses to estimate the effect of genetically determined FXI levels on IS (10,343 cases and 476,838 controls) and ICH (2,236 cases and 484,945 controls) risk across
APOE
ε4 carriership strata (0, 1, or 2 alleles) using UK Biobank data.

Results:
In the general population, random-effects, inverse-variance weighted MR analyses showed that every 1 unit decrease in natural log-transformed FXI levels was associated with a 37% reduction in IS risk (OR:0.63; 95%CI:0.52–0.77;
p
<0.001) without a significant increase in ICH risk (OR:0.86; 95%CI:0.37–2.00;
p
=0.73). Stratified MR analyses indicated that genetically determined reductions in FXI levels had varying protective effects on IS risk based on
APOE
ε4 status: 31% in non-carriers (OR:0.69, 95%CI:0.53–0.91;
p
=0.008), 43% in carriers of 1 allele (OR:0.57, 95%CI:0.36–0.91;
p
=0.02), and 75% in carriers of 2 alleles (OR:0.25, 95%CI:0.06–1.06;
p
=0.06). Similar MR analyses showed no significant increase in ICH risk with genetically determined reductions in FXI levels in any
APOE
ε4 strata (all
p
>0.38, Figure 1).

Conclusion:
This two-stage genetic study provides causal evidence that lower FXI levels reduce IS risk in the general population, with an even stronger effect among
APOE
ε4 carriers, while not increasing ICH risk. These results indicate that FXI inhibitors might be a safer and more effective alternative to other anticoagulants among
APOE
ε4 carriers, who are known to be at higher risk for both ischemic and hemorrhagic events.
Abstract 113: Real-Time Detection of Cerebral Ischemia Using Optical Brain Pulse Monitoring in a Sheep Model of Stroke
Authors: Teo Elliot , Sharkey Jessica , Chung Sung Wook , Grace Sally , Hellerstedt Jack , Petautschnig Sigrid , Turner Renee , Krieg Thomas , Murphy Mike , Sorby-Adams Annabel , Dixon Barry
Published: January 2025

Background:
Early detection and intervention of cerebral ischemia is critical to improving patient outcomes. Optical brain pulse monitoring (OBPM) is a unique technique that offers non-invasive, continuous monitoring of brain hemodynamics via brain pulse waveform visualization. This method has the potential to identify ischemic changes and facilitate expeditious intervention. Here, we assessed OBPM signal changes during middle cerebral artery occlusion (MCAo) and following reperfusion in a clinically relevant sheep model to enable pre-clinical waveform characterization.

Methods:
Eleven Merino wethers underwent MCAo for 4 hours followed by reperfusion for 6 hours. Brain tissue oxygen monitoring (PbtO
2
; n=11) and OBPM (n=11) were performed in the MCAo hemisphere overlying the MCA territory, while intracranial pressure (ICP; n=11) and OBPM (n=6) were performed in the contralateral MCA territory. OBPM measurements were taken at baseline, MCAo, and following reperfusion. Magnetic resonance imaging (MRI) was used to measure infarct volume at 1 hour post reperfusion. Brain pulse waveforms were grouped into 5 classes by 3 blinded observers. Interrater agreement and frequency distributions were analyzed using Fleiss k and Fischer’s exact test, respectively. Generalized estimating equations (GEE) identified neuromonitoring changes (OBPM, StO
2
%, PbtO
2
, ICP) at each time point, adjusted with the Benjamini-Hochberg method.

Results:
Observers were in moderate agreement (k=0.433;
p<
0.0001). Consensus classification of the OBP waveforms showed significant differences in the distribution of classes in the ipsilesional hemisphere over time (
p
=0.02), but not the contralesional hemisphere (
p
>0.99). One waveform class was observed only during MCAo. Reductions in brain pulse amplitude were found during MCAo when infarct volume was controlled for (
p
<0.05 for all time points). Slow wave activity was observed in the OBPM optical signal and was associated with changes in ICP and PbtO
2
. OBPM StO
2
% showed significant decreases in both ipsi- and contra-lesional hemispheres (
p
<0.001). A significant reduction in PbtO
2
(
p
< 0.001) was observed during MCAo.

Conclusion:
MCAo was associated with distinct changes in the OBPM brain pulse waveform class and reductions in StO
2
% in a sheep model. These findings demonstrate that the OBPM captures cerebrovascular signatures of MCAo identifiable by human observers or by a drop in StO
2
%, providing an initial preclinical characterization of waveforms.
Abstract 115: Microglial AXL Promotes Ischemic White Matter Recovery by Clearing Myelin Debris after Stroke
Authors: Jia Junqiu , Gan Yonghui , Zhang Meijuan , Xu Yun
Published: January 2025

Background:
Ischemic white matter injury leads to long-term neurological deficits and lacks effective medication. Accumulating evidence suggests that microglia contribute to pro-remyelinating after brain injury. We previously obtained a picture of microglial dynamic changes after the transient middle cerebral artery occlusion (tMCAO) through RNA-seq and found that AXL, a member of the TAM family of receptor tyrosine kinases with phagocytosis and remyelinating functions, continued to increase until one-month post-tMCAO. This study examines the role of microglial Axl in mediating white matter damage after ischemic stroke.

Methods:
Immunofluorescence staining and flow cytometry were used to verify the spatial and temporal characteristics of AXL expression. Inducible microglial-specific AXL knockout (Axl
flox/flox
Cx3cr1
CreERT2+/−
, cKO) and littermate control WT (CreERT2-/-) mice were administrated tamoxifen two weeks before tMCAO surgery. Neurobehavioral functions were evaluated by rotarod, adhesive removal, and Morris water maze tests. White matter injury and demyelination axons were examined by MRI, electron microscopy, and SMI32/MBP staining. Myelin debris accumulation and lipid droplet deposition were assessed by dMBP (degraded myelin basic protein), Oil Red O, FluoroMyelin, and BODIPY staining. Transcriptome analysis was conducted to explore mechanisms.

Results:
AXL was mainly expressed in microglia in the peri-infarct area and was significantly up-regulated on the 7
th
and 14
th
day post-tMCAO. AXL
+
microglia possessed stronger phagocytosis capacity and wrapped myelin debris most obviously in striatum after stroke. Compared to WT controls, AXL cKO mice exhibited worse sensorimotor and cognitive deficits in the chronic phase of stroke and more severe white matter injury four weeks after tMCAO. More myelin debris was accumulated in the peri-infarcted area and more lipid droplets were deposited in the microglia of AXL cKO mice. KEGG analysis showed “immune system” and “lipid metabolism” processes were changed significantly in AXL cKO mice.
In vitro
, the expression of cholesterol esterification and hydroxylase genes (
Acat1
,
Ch25h
,
Dhcr24
) were decreased, while the inflammation-related genes (
Il6
,
Il1b
,
Tgfb
,
Tnf
) were increased in AXL cKO microglia after the stimulation of myelin debris.

Conclusions:
AXL improved white matter injury after ischemic stroke by promoting microglial phagocytosis of myelin debris and mediating intracellular cholesterol metabolism.
Abstract 120: Comparative trends in decompressive hemicraniectomy in the era of mechanical thrombectomy among stroke patients (2016-2021) in the US National inpatient Sample.
Authors: Sohaib Muhammad , Maaz Hafiz , Chaychi Muhammad Tayyab Muzaffar , Rahman Haseeb , Saeed Daniaal , Kamal Haris , Ahmed Muhammad
Published: January 2025

Background:
Decompressive hemicraniectomy (DHC) and mechanical thrombectomy (MT) are critical interventions for acute ischemic stroke. This study examined trends in their use from 2016 to 2021, the relationship between them, and associated patient demographics and outcomes.

Methods:
National inpatient Sample (NIS) (n=798,712) was analyzed. Trends in DHC and MT per year were analyzed using the Cochran-Armitage test for trend to assess changes in DHC use over time and assessed overall and stratified by MT status. Logistic regression evaluated the association between year, MT, and their interaction with DHC odds. Patient demographics and outcomes were also examined.

Results:
Overall, DHC use increased significantly from 2016 to 2021 with a non-linear trend (chi2(4)=86.69, p<0.0001), indicating a notable increase in DHC utilization between 2016 and 2021. The test for departure from trend was also significant (chi2(4)=86.69, p<0.0001), MT was associated with higher DHC likelihood (OR 4.43, p<0.001). The interaction between MT and year was insignificant, indicating a consistent effect of MT on DHC over time. MT use also increased significantly (ORs 1.27-2.43, all p<0.0001). In MT patients, DHC odds increased (ORs 1.69-2.24, p<0.013). In non-MT patients, DHC odds also increased (ORs 1.82-2.04, all p<0.0001). The MT with DC group had a higher proportion of females (43.61% vs 42.59%) and African Americans (25.04% vs 19.75%). %). The overall in-hospital mortality rate was 6.96%.

Conclusions:
Both DHC and MT use are increasing in stroke patients. These findings underscore the evolving landscape of acute stroke care, with an increasing emphasis on aggressive and comprehensive management.
Abstract 123: Factors Associated with Post-stroke Neurology Appointment Attendance and the Impact on Functional Outcomes and Readmissions
Authors: Pope Leslie , Hackett Chris , Heintz Rebekah , Dellostretto Nicole , Noah Patty , Cerejo Russell
Published: January 2025

Introduction:
Neurology follow-up appointments are an essential part of post-stroke care, treatment and secondary stroke prevention. We aimed to determine factors contributing to patient attendance at neurology appointments and its impact on 90-day outcomes and readmissions.

Methods:
Retrospective analysis on acute ischemic stroke (AIS) patients with care coordinated by a nurse navigator from 7 hospitals (January 2021-March 2024). Patients excluded if: died during index hospitalization, discharged to hospice or long term acute care hospitals, or had incomplete data. Primary outcome: factors contributing to patients attending post-discharge neurology appointments and secondary outcome: 90 day all cause readmission rates utilizing binomial stepwise logistic regression models. Ninety-day utility weighted modified rankin scale (UWmRS) evaluated using hierarchical linear regression. Sensitivity analyses examined secondary outcomes in patients discharged home. Subgroup analysis compared latency of patient follow up and association of 90 day all cause readmission rates using a binomial stepwise logistic regression. All outcome analyses were adjusted for potential confounding variables as identified in the univariate analyses.

Results:
A total of 6121 AIS patients were evaluated, after exclusions 3450 were included in this study. Patients were more likely to attend a neurology appointment if discharged home,OR=1.47 [95%CI,1.23, 1.74],p<0.001, had private insurance,OR=1.53 [95%CI,1.27,1.84],p<0.001, had an active patient portal account,OR=1.65 [95%CI,1.41,1.94],p<0.001, or had a better baseline UWmRS,OR=4.18 [95%CI,2.58,6.76],p<0.001. Patients who attended appointments were less likely to be readmitted within 90 days,OR=0.42 [95%CI,0.36,0.50],p<0.001. After adjusting for baseline UWmRS and other confounding variables, patients who attended neurology appointments had better UWmRS at 90 days,B=0.17 [95%CI,0.15,0.19], SE=0.01,p<0.001. Similar results were seen in sensitivity analysis, all p<0.001. Subgroup analysis showed that longer delays to outpatient neurology follow-up led to increased likelihood of readmission,OR=1.005, [95%CI,1.001,1.009],p=0.01.

Conclusion:
Discharge home, private insurance, better baseline UWmRS and active patient portal accounts were key contributors to patient attendance at neurology follow up appointments which may have contributed to better UWmRS at 90-days. Avoiding delays to follow-up appointments may result in a decrease in readmissions.
Abstract 131: Intracranial and Femoral Whole Blood Display Distinct Transcriptomic Signatures
Authors: Devarajan Alex , Seah Carina , Philbrick Brandon , Bazil Maximilian , Bonet Jessica , Sorscher Michelle , Richter Felix , Kellner Christopher , Berenstein Alejandro , Shigematsu Tomoyoshi , Fifi Johanna
Published: January 2025

Introduction:
Vein of Galen malformations (VOGM) are embryonic choroid plexus-derived arteriovenous malformations which may develop secondary to mosaicism. Sequencing of peripheral whole blood is often ineffective in identifying novel mutations responsible for VOGM development. Whole blood is typically considered to be a transcriptionally homogenous tissue, although vascular microenvironments may impart site-specific transcriptional changes. Here, we investigated whether peripherally collected whole blood samples would yield a different transcriptomic signature compared to targeted blood collection near a biologically active lesion.

Methods:
Whole blood was prospectively collected from femoral access (peripheral) and catheterized intracranial feeding vessels (intralesional) during endovascular embolization of 8 patients for management of VOGM. All blood samples were matched and collected within the same endovascular procedure. RNA sequencing of 15,730 genes from 23 samples after quality-control was aligned, normalized, and residualized using Rsubread, sva, and limma/voom. Differentially expressed genes (DEGs) were identified between peripheral and intralesional blood draws. Gene set enrichment analysis (GSEA) was conducted using Gene Ontology biological processes and cellular components.

Results:
430 genes (196 upregulated, 234 downregulated) were differentially expressed in whole blood collected from intracranial feeders to the VOGM versus the femoral artery. When comparing matched samples, tissue-specific choroid plexus and VOGM-associated genes were significantly upregulated in intralesional whole blood. This included IQUB, a gene involved in ciliary formation and function, expressed at high degrees in the brain in the ventricular ependyma and choroid plexus; UBXN10, a cilium assembly gene which demonstrates body-wide tissue specificity for the choroid plexus; and PTGIS, a nonspecific prostacyclin synthase secreted by neovessels developing in the context of CNS inflammation.

Conclusion:
We demonstrate the first evidence of differential whole blood transcriptomic signatures by anatomical location. Intracranially collected whole blood of VOGM patients demonstrated upregulation of choroid plexus-specific genes compared to femoral arterial blood collected during the same procedure. Future studies assessing peripheral whole blood transcriptomes should consider the added prognostic value of targeted endovascular blood draws for cell-free molecular profiling.
Abstract 134: Use of Large Language Model to Allow Reliable Data Acquisition for International Pediatric Stroke Study
Authors: Bhayana Kriti , Wang Dulin , Jiang Xiaoqian , Fraser Stuart
Published: January 2025

Introduction:
Pediatric stroke research is hindered by lack of funding and relative disease rarity. Shared data in pediatric stroke is done via non-reimbursed data input by clinical investigators at participating children’s hospitals with the International Pediatric Stroke Study (IPSS). Large Language Models (LLM) can potentially reduce investigator workload through automated data entry. In prior research, investigators were able to achieve 94% accuracy while using a prompt engineering approach with Generative Pretrained Transformer 4 (GPT4) to enter subject outcome forms of the IPSS using clinical notes. However, GPT4 performed only moderately (~50% correct) while attempting to answer some of the data questions. In this study we aim to utilize another toolkit called the “Instructor” to improve the performance of the LLM in areas where the prior method achieved less than 90% accuracy.

Methods:
This retrospective study used de-identified clinical notes of 50 patients who presented to UTHealth Pediatric Stroke Clinic between January 2020 and July 2023 with ischemic stroke. Each note was run through the offline HIPAA compliant LLM “GPT4o” to answer questions in the outcome form of IPSS. We focused on areas of the IPSS outcome form where prior approach yielded less than 90% accuracy. We implemented the "Instructor", a Python library built on Pydantic, to enhance prompt engineering and ensure structured outputs. Accuracy was measured as percent agreement between the LLM generated and investigator-entered data. We used simple descriptive statistics to compare the accuracy (% correct) of Instructor method with clinical investigator-entered data and previously reported results from traditional prompt engineering method.

Results:
We analyzed neurological deficit severity and post discharge rehabilitation questions. This algorithm reported 100% accuracy for both neurological deficit severity and post discharge rehabilitation as compared to accuracy with the previous method (46-54% and 26-62% respectively).

Conclusion:
In this study, utilization of the “Instructor” shows promising results for reliable data retrieval. Moving forward, we will use Instructor to analyze the neurological deficit type, follow-up imaging type and findings based on imaging, and expand this approach to other sections of the IPSS forms. LLMs may reduce investigator workload and increase the efficiency of observational research for rare, underserved diseases like pediatric stroke in the future.
Abstract 143: Remote Telemedicine Based Enrollment in Acute Stroke Studies at Non-Academic Acute Stroke Ready and Primary Stroke Centers: A Multi-Center Experience of the TIMELESS and FASTEST Trials.
Authors: Sangha Navi , Staugaitis Abbey , Audea Vanessa , Chakravarthula Nitin Ramanujam , Tessmer Megan , Gaffney Denise , Zhang Jing , Albers Greg , Broderick Joe , Streib Christopher
Published: January 2025

Introduction:
Clinical trials of acute stroke are often conducted at Comprehensive Stroke Centers (CSC). Limiting enrollment to CSCs can result in slower recruitment, diminished enrollment diversity, and decreased dwell time for recanalization medications. We report the impact of remote telemedicine (TM)-based enrollment at Acute Stroke Ready and Primary Stroke Centers (Non-CSC) in the TIMELESS and FASTEST trials.

Methods:
Both trials were conducted in 2 large health systems with CSC and spoke Non-CSC. Non-CSCs were enabled via video-based TM to remotely screen, consent, randomize and administer study drug locally with a possible transfer to CSC. Follow ups were conducted in person, over the phone or via video TM. Data were retrospectively gathered from the TIMELESS (entire study period) and FASTEST (August 1, 2023-March 31, 2024) studies. Baseline demographics, clinical trial enrollment time metrics, adverse events, missed follow ups and protocol deviations and violations were collected. Data were analyzed with Chi-Square and Kruskall-Wallis.

Results:
96 patients were enrolled: 75 in TIMELESS and 21 in FASTEST. Twenty-three (24%) were enrolled at Non-CSC:19 (82.6%) in TIMELESS and 4 (17.4%) in FASTEST. There were no differences between CSC vs. Non-CSC enrollments in age, gender, door to consent, door to randomization, door to study drug order placement, door to study drug administration, major adverse events, death at 90 days, protocol violations and missed follow up visits. There was higher racial diversity at Non-CSC enrollments: 30.4% Asian and 17.4% Black vs. CSC: 5.5% Asian and 11.0% Black (p=0.022). There were more protocol deviations identified at the CSC (45.2%) vs. Non-CSC (17.4%) p=0.02. Patients enrolled in TIMELESS at a Non-CSC had a longer median drug dwell time before thrombectomy: 52.0 mins (IQR 35.0-69.0) vs CSC: 9.5 mins (IQR 1.5-26.0) p<.0001. TIMELESS Monthly enrollment increased from 1.24 (CSC) to 1.67 with the addition of Non-CSCs. Similarly, FASTEST monthly enrollment increased from 0.65 to 0.81.

Conclusion:
This is the first study to demonstrate that remote enrollment and study drug administration in acute stroke trials at Non-CSCs are feasible without differences in clinical trial enrollment parameters. It can increase total enrollments, enrich the study populations racial diversity, and increase study drug dwell time which may be important in future studies of extended window thrombolysis and adjunctive recanalization medications.
Abstract 148: "Is Air Transport Truly Faster? A Comparative Study of Stroke Transfer Times"
Authors: Maali Laith , Langston Sarah , Choudhry Mughees , Houghton Margaret , Sowers Sabriya
Published: January 2025

Introduction:
Efficient transfer of acute ischemic stroke (AIS) patients is critical for optimizing clinical outcomes, as time-sensitive interventions can significantly reduce morbidity and mortality. Stroke transfers are commonly conducted using either ground ambulances or air ambulances (helicopters). While air transport is often perceived as faster, there are concerns that many patients arrive later than expected, impacting treatment outcomes. This study aims to evaluate and compare the performance of ground versus air transfers in terms of actual transfer times and the discrepancies between projected and actual arrival times.

Methods:
This retrospective analysis was conducted at our comprehensive stroke center at the University of Kansas Health System (TUKHS) over a five-year period (2019-2023). Data were sourced from our transfer center registry and the Get With The Guidelines® (GWTG) Stroke registry, focusing on AIS patient transfers from referring hospitals within a 2.5-hour driving radius that had utilized both ground and air methods at least three times over the last 5 years. Data acquisition was approved by the local Institutional Review Board (IRB). Actual transfer times and the discrepancies between projected and actual times were calculated and analyzed.

Results:
456 transfer entries were analyzed, comprising 252 air transfers and 204 ground transfers from 16 hospitals. Ground transfers were found to be faster overall and had a significantly shorter discrepancy between projected and actual arrival times. Specifically, the average actual transfer time for air was 131 ± 59 minutes, compared to 125 ± 67 minutes for ground (p = 0.039). The discrepancy in transfer times was notably higher for air at 62 ± 58 minutes versus 24 ± 59 minutes for ground (p < 0.0001), with a scaled transfer discrepancy of 87% ± 80% for air compared to 26% ± 56% for ground (p < 0.0001).

Conclusion:
While air transport is generally expected to expedite stroke transfers, this retrospective analysis demonstrates that ground transfers are not only faster in actual time but also exhibit a lower discrepancy between projected and actual transfer times. These findings suggest that air transport may not always provide the anticipated time advantage and that ground transfers could be a more reliable option within certain parameters. Further studies are warranted to analyze potential confounding factors for delays, optimize transfer protocols, and improve patient outcomes.
Abstract 162: Imbalanced VWF–ADAMTS13 axis mediates the detrimental impact of preceding bacterial or COVID-19 respiratory tract infections on stroke
Authors: Patel Rakeshkumar , Jha Abhishek , Verma Abhishek , Jain Aditi , Muia Joshua , Gurung Prajwal , Perlman Stanley , Budnik Ivan , Chauhan Anil
Published: January 2025

Background:
Preceding respiratory tract infections (RTIs) caused by bacteria or viruses are associated with worse stroke outcomes, likely due to an exaggerated inflammatory immune response, endothelial dysfunction, platelet activation, and coagulopathy. Recent studies have revealed increased plasma von Willebrand factor (VWF) levels and reduced ADAMTS13 activity (the risk factors for stroke) in patients with RTIs, including COVID-19. However, it remains unclear whether an imbalance in the VWF–ADAMTS13 axis plays a causative role in the pathophysiology of
S. aureus
- or COVID-19-associated stroke severity or is merely an associative marker of disease status.

Objective:
To examine whether an imbalance in the VWF–ADAMTS13 axis is a causal link between RTIs and stroke severity.

Methods:
Wild-type (WT) mice (3–4 months old) were infected intranasally with sublethal doses of
S. aureus
(on days 0, 2, and 5) or mouse-adapted SARS-CoV-2 (on day 0). On day 6 (
S. aureus
) or day 3 (SARS-CoV-2), the infection was confirmed to be localized in the lungs (but not in the brain) and the plasma VWF levels and ADTMTS13 activity were quantified. In another set of experiments, WT,
Vwf
−/−
, and
Adamts13
−/−
mice (3–4 months old) with respective littermate controls were subjected to transient (30 or 45 min) cerebral ischemia (filament stroke model) followed by reperfusion. For the
S. aureus
experiments, brain infarcts were assessed on day 2 post-reperfusion and functional outcomes (corner test, wire hanging test, modified neurological severity score, and rotarod test) on week 1 and 4 post-reperfusion. For the SARS-CoV-2 experiments, brain infarcts and functional outcomes (the Bederson score) were assessed on day 1 post-reperfusion.

Result:
We demonstrated that
S. aureus
or SARS-CoV-2 infection localized to the lungs in the WT mice resulted in increased (2–3 fold) plasma VWF levels and reduced ADAMTS13 activity, concomitant with larger infarcts and worse functional outcomes (P<0.05 vs. mock-infected mice) up to day 28 post-reperfusion.
S. aureus
- or SARS-CoV-2-infected VWF-deficient mice exhibited reduced infarcts and improved functional outcomes (P<0.05 vs. infected

Vwf
+/+

). In contrast,
S. aureus
or SARS-CoV-2-infected ADAMTS13-deficient mice displayed greater stroke severity (P<0.05 vs. infected

Adamts13
+/+

).

Conclusion:
In the experimental models of RTI preceding stroke, VWF plays a causal role in worsening stroke outcomes, while ADAMTS13 is protective.