bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplemental Figure S13 from The EP3–ZNF488 Axis Promotes Self-Renewal of Glioma Stem-Like Cells to Induce Resistance to Tumor Treating Fields
Authors: Chen Dongjiang , Le Son B. , Manektalia Harshit , Liu Tianyi , Hutchinson Tarun E. , O’Dell Adam , Salhia Bodour , Tran David D.
Published: January 2025

Epistatic interaction between EP3 and ZNF488 in TTFields resistance in GBM cells. (Supporting Main Figure 8A)
Supplemental Figure S12 from The EP3–ZNF488 Axis Promotes Self-Renewal of Glioma Stem-Like Cells to Induce Resistance to Tumor Treating Fields
Authors: Chen Dongjiang , Le Son B. , Manektalia Harshit , Liu Tianyi , Hutchinson Tarun E. , O’Dell Adam , Salhia Bodour , Tran David D.
Published: January 2025

EP3 is co-localized with ZNF488 in the nucleus of TTFields-resistant GBM cells. (Supporting Main Figure 7)
Supplementary Table 10 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

ssGSEA enrichment of cell type specific gene signatures in bulk RNAseq tumors. For each sample, the highest scoring signature is shown.
Supplementary Figure 7 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

Orthotopic engraftment of cell lines derived from Foxr2 p53LOF murine model.
Figure 7 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

Foxr2 chromatin binding sites in Foxr2 p53LOF neurosphere show enrichment in ETS and glial pathways. A, Validation of FOXR2 overexpression and p53 downregulation in ex vivoFoxr2 p53LOF neurospheres by qRT-PCR. B, Validation of Nkx2-1, Lhx6, Dlx5, Dlx6, Emx2, Sox10, Olig1, Olig2, and Pdgfra expression in Foxr2 p53LOF neurospheres by qRT-PCR. Foxr2 p53LOF cell lines are positive for MGE markers and mirror the transcriptomic profile observed in patients. C, Kaplan–Meier curves depicting survival following orthotopic (striatal) injection of 150,000 Foxr2 p53LOF cells (n = 5). D, Intersection of Foxr2 CUT&RUN peaks (n = 2 replicates) with ATAC peaks from single-cell multiome profiling of the murine Foxr2 p53LOF model, used for filtering peaks. E, Top enriched TF motifs in filtered Foxr2 CUT&RUN peaks by adjusted P value. For visualization, the figure includes the top 13 motifs, colored and grouped by TF types. F, Tracks at Gad1 and Dlx5 genomic regions showing Foxr2 CUT&RUN and bulk RNA-seq in Foxr2 p53LOF murine cell lines and pseudobulk ATAC tracks of malignant cells by cell type from single-cell multiome profiling of Foxr2 p53LOF mouse model tissue. G, Tracks as in F at genomic regions for Hand2 and Ets1. H, Tracks as in F at genomic regions for Sox family glial TFs. I, Tracks as in F at genomic regions for key oligodendrocyte lineage genes. Adj, adjusted; Astro, astrocytes; INH, inhibitory neurons; LRL, lower rhombic lip; OL, oligodendrocytes.
Figure 3 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

FOXR2 does not induce expression of MGE or EC-NB TFs. A, Bulk RNA-seq expression of telencephalon patterning TFs. Top and third rows, tumor samples from this study cohort. Second row, EC-NB samples (Gartlgruber and colleagues, ref. 21) subset to high risk, stage 4 samples with FOXR2 expression (normalized expression >2). Bottom row, H9 human NSCs transduced with HA-FOXR2 or controls transduced with HcRed (Tsai and colleagues, ref. 7). All expression box plots except FOXR2 have a y-axis maximum value of 7,000. B, Comparison of TF expression with FOXR2 status in EC-NB (Gartlgruber and colleagues, ref. 21) subset to high risk, stage 4 samples (n = 229). Left, correspondence between FOXR2 expression and TF expression, annotated with Pearson correlation. Right, TF expression in samples split by FOXR2 positivity, annotated with P value (Wilcoxon test). FOXR2+ tumors, normalized expression >2. Y-axis for DLX5 and DLX6 violin plots are log10-scaled. C, Bulk RNA-seq expression in NB-FOXR2 of MGE and EC-NB TFs and markers. D, Bulk RNA-seq expression of ASCL1 across pediatric brain tumor types. DIPG-H3K27M-FOXR2, DIPG, H3K27M altered, and FOXR2 activated; DIPG-H3K27M, DIPG, H3K27M altered; EP-PFA, posterior fossa group A ependymoma; ETMR, embryonal tumors with multilayered rosettes; HGG-IDH, HGG, IDH-mutant; HGG-H3.3G34R/V, HGG, H3.3G34R/V-altered; MB-SHH, SHH medulloblastoma; MB-WNT, WNT medulloblastoma.
Supplementary Data from Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C–MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies
Authors: Pandey Apurva , Rohweder Peter J. , Chan Lieza M. , Ongpipattanakul Chayanid , Chung Dong hee , Paolella Bryce , Quimby Fiona M. , Nguyen Ngoc , Verba Kliment A. , Evans Michael J. , Craik Charles S.
Published: January 2025

Supplemental Data and Figures
Supplementary Figure 2 from KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition
Authors: Fey Sigrid K. , Najumudeen Arafath K. , Watt Dale M. , Millett Laura M. , Ford Catriona A. , Gilroy Kathryn , Simpson Rosalin J. , McLay Kathy , Upstill-Goddard Rosanna , Chang David , Clark William , Nixon Colin , Birch Joanna L. , Barry Simon T. , Morton Jennifer P. , Campbell Andrew D. , Sansom Owen J.
Published: January 2025

Release from AZD6244 treatment results in rapid acinar to ductal metaplasia in KC KrasG12D/fl.
Supplementary Data from The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma
Authors: Sudalagunta Praneeth Reddy , Canevarolo Rafael R. , Meads Mark B. , Silva Maria , Zhao Xiaohong , Cubitt Christopher L. , Sansil Samer S. , DeAvila Gabriel , Alugubelli Raghunandan Reddy , Bishop Ryan T. , Tungesvik Alexandre , Zhang Qi , Hampton Oliver , Teer Jamie K. , Welsh Eric A. , Yoder Sean J. , Shah Bijal D. , Hazlehurst Lori , Gatenby Robert A. , Van Domelen Dane R. , Chai Yi , Wang Feng , DeCastro Andrew , Bloomer Amanda M. , Siegel Erin M. , Lynch Conor C. , Sullivan Daniel M. , Alsina Melissa , Nishihori Taiga , Brayer Jason , Cleveland John L. , Dalton William , Walker Christopher J. , Landesman Yosef , Baz Rachid , Silva Ariosto S. , Shain Kenneth H.
Published: January 2025

This file contains four supplementary tables S1 - S4 and eight supplementary figures S1 - S8.
Data from The EP3–ZNF488 Axis Promotes Self-Renewal of Glioma Stem-Like Cells to Induce Resistance to Tumor Treating Fields
Authors: Chen Dongjiang , Le Son B. , Manektalia Harshit , Liu Tianyi , Hutchinson Tarun E. , O’Dell Adam , Salhia Bodour , Tran David D.
Published: January 2025

Abstract
Tumor treating fields (TTFields) use low-intensity, alternating electric fields to exert antitumor activity and have demonstrated efficacy against multiple cancers, including glioblastoma (GBM). Unfortunately, cancer cells inevitably develop resistance to TTFields, highlighting the need to elucidate the underlying mechanisms to develop approaches to induce durable responses. Using a gene network–based machine learning algorithm, we interrogated TTFields-resistant GBM cells and uncovered a regulatory axis anchored by the prostaglandin E2 receptor 3 (EP3) and the transcription factor zinc finger 488 (ZNF488). Mechanistically, TTFields induced EP3 upregulation and nuclear envelope localization, where it formed a complex with ZNF488 to induce resistance to TTFields by promoting self-renewal of glioma stem-like cells (GSC). Overexpression of EP3 and/or ZNF488 in TTFields-sensitive GSC conferred resistance and enhanced self-renewal, whereas expression of noninteracting mutants of these proteins abrogated the formation of the nuclear complex and prevented resistance. Inhibition of either partner in this protein complex in resistant GSC, including those freshly isolated from TTFields-resistant GBM tumors, resensitized cells to the cytotoxic effects of TTFields, concomitant with reduced self-renewal and in vivo tumorigenicity. Importantly, inhibition of EP3 in TTFields-sensitive GSC preemptively halted the development of resistance. The EP3–ZNF488 axis was significantly upregulated in TTFields-resistant GBM tumors, and coexpression of EP3 and ZNF488 in other cancers correlated with lower survival rates. Collectively, these results indicate that the nuclear EP3–ZNF488 axis is necessary and sufficient to establish TTFields resistance, underscoring the potential to target this axis to prevent or reverse resistance in GBM and possibly other cancers.

Significance: The EP3–ZNF488 master regulatory axis in cancer stem-like cells drives resistance to treatments like tumor treating fields, opening avenues for developing strategies to enhance therapeutic efficacy.
Data from ACE2 Enhances Sensitivity to PD-L1 Blockade by Inhibiting Macrophage-Induced Immunosuppression and Angiogenesis
Authors: Xie Peiyi , Guo Lei , Yu Qiang , Zhao Yufei , Yu Mincheng , Wang Hui , Wu Mengyuan , Xu Wenxin , Xu Min , Zhu Xiao-Dong , Xu Yongfeng , Xiao Yong-Sheng , Huang Cheng , Zhou Jian , Fan Jia , Hung Mien-Chie , Sun Huichuan , Ye Qing-Hai , Zhang Bo , Li Hui
Published: January 2025

Abstract
Anti–PD-L1–based combination immunotherapy has become the first-line treatment for unresectable hepatocellular carcinoma (HCC). However, the objective response rate is lower than 40%, highlighting the need to identify mechanisms of tolerance to immune checkpoint inhibitors and accurate biomarkers of response. In this study, we used next-generation sequencing to analyze HCC samples from 10 patients receiving anti–PD-L1 therapy. Activation of the renin–angiotensin system was elevated in nonresponders compared with responders, and angiotensin-converting enzyme 2 (ACE2) expression was significantly downregulated in nonresponders. ACE2 deficiency promoted HCC development and anti–PD-L1 resistance, whereas ACE2 overexpression inhibited HCC progression in immune-competent mice. Mass cytometry by time of flight revealed that ACE2-deficient murine orthotopic tumor tissues featured elevated M2-like tumor-associated macrophages, displayed a CCR5+PD-L1+ immunosuppressive phenotype, and exhibited high VEGFα expression. ACE2 downregulated tumor-intrinsic chemokine (C–C motif) ligand 5 expression by suppressing NF-κB signaling through the ACE2/angiotensin-(1–7)/Mas receptor axis. The lower chemokine (C–C motif) ligand 5 levels led to reduced activation of the JAK–STAT3 pathway and suppressed PD-L1 and VEGFα expression in macrophages, blocking macrophage infiltration and M2-like polarization. Pharmacologic targeting of CCR5 using maraviroc enhanced the tumor-suppressive effect of anti–PD-L1 therapy. Together, these findings suggest that activation of the ACE2 axis overcomes the immunosuppressive microenvironment of HCC and may serve as an immunotherapeutic target and predictive biomarker of response to PD-L1 blockade.

Significance: ACE2 regulates the immune landscape of hepatocellular carcinoma by abrogating M2-like macrophage polarization and sensitizes tumors to anti–PD-L1, suggesting that harnessing the ACE2 axis could be a promising strategy to improve immunotherapy efficacy.
Data from Spatial and Single-Cell Analyses Reveal Heterogeneity of DNAM-1 Receptor–Ligand Interactions That Instructs Intratumoral γδT-cell Activity
Authors: Wang Xiaolin , Wang Hui , Lu Zhengjing , Liu Xiangjun , Chai Wenjia , Wang Wei , Feng Jun , Yang Shen , Yang Wei , Cheng Haiyan , Chen Chenghao , Zhang Shihan , Sun Nian , Liu Qiaoyin , Li Qiliang , Song Wenqi , Jin Fang , Zeng Qi , Wang Shengcai , Su Yan , Wang Huanmin , Ni Xin , Gui Jingang
Published: January 2025

Abstract
The dynamic interplay between tumor cells and γδT cells within the tumor microenvironment significantly influences disease progression and immunotherapy outcome. In this study, we delved into the modulation of γδT-cell activation by tumor cell ligands CD112 and CD155, which interact with the activating receptor DNAM-1 on γδT cells. Spatial and single-cell RNA sequencing, as well as spatial metabolomic analysis, from neuroblastoma revealed that the expression levels and localization of CD112 and CD155 varied across and within tumors, correlating with differentiation status, metabolic pathways, and ultimately disease prognosis and patient survival. Both in vivo tumor xenograft experiments and in vitro coculture experiments demonstrated that a high CD112/CD155 expression ratio in tumors enhanced γδT cell–mediated cytotoxicity, whereas a low ratio fostered tumor resistance. Mechanistically, CD112 sustained DNAM-1–mediated γδT-cell activation, whereas CD155 downregulated DNAM-1 expression via E3 ubiquitin ligase tripartite motif–containing 21–mediated ubiquitin proteasomal degradation. By interacting with tumor cells differentially expressing CD112 and CD155, intratumoral γδT cells exhibited varying degrees of activation and DNAM-1 expression, representing three major functional subsets. This study underscores the complexity of tumor–immune cross-talk, offering insights into how tumor heterogeneity shapes the immune landscape.

Significance: Tumor cells in different intratumoral neighborhoods display divergent patterns of ligands that regulate γδT-cell activation, highlighting multilevel regulation of antitumor immunity resulting from the heterogeneity of intercellular interactions in the tumor microenvironment.
Data from An Autophagy-Targeting Chimera Induces Degradation of Androgen Receptor Mutants and AR-v7 in Castration-Resistant Prostate Cancer
Authors: Bae Tae Hyun , Sung Ki Woon , Pham Tri M. , Najy Abdo J. , Zamiri Alaleh , Jang Hyejeong , Mun Su Ran , Kim Seongho , Kwon Ha Kyoung , Son Yeon Sung , Shi Dongping , Kregel Steven , Heath Elisabeth I. , Cher Michael L. , Kwon Yong Tae , Kim Hyeong-Reh Choi
Published: January 2025

Abstract
Genetic alterations play a pivotal role in various human diseases, particularly cancer. The androgen receptor (AR) is a crucial transcription factor driving prostate cancer progression across all stages. Current AR-targeting therapies utilize competitive AR antagonists or pathway suppressors. However, therapy resistance often emerges due to AR mutations and AR splice variants, such as AR-v7. To overcome this, we developed ATC-324, an AR degrader using the innovative protein degradation technology platform AUTOphagy-TArgeting Chimera (AUTOTAC). ATC-324 was designed to comprise enzalutamide, an AR inhibitor, as a target-binding ligand and YT 6-2, a ligand of the autophagy receptor p62/SQSTM1, as an autophagy-targeting ligand. ATC-324 induces the formation of the AR/p62 complex, leading to autophagy–lysosomal degradation of AR. Importantly, ATC-324 effectively degrades AR mutants frequently detected in prostate cancer and codegrades AR-v7 as a heterodimer with full-length AR. ATC-324 reduces nuclear AR levels and downregulates the target gene expression of AR and AR-v7, leading to cytotoxicity in AR-positive prostate cancer cells. We also provide evidence of the therapeutic potential of ATC-324 in vivo as well as ex vivo bone organ culture. Moreover, ATC-324 remains potent in enzalutamide-resistant prostate cancer cells. These results demonstrate the potential of the AUTOTAC platform to target previously considered undruggable proteins and overcome certain drug resistance mechanisms.

Significance: The characterization of an AUTOTAC-based degrader capable of inducing autophagic degradation of wild-type and mutated androgen receptors demonstrates the potential of this approach for targeting castration-resistant prostate cancer and overcoming drug resistance.
Data from The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma
Authors: Sudalagunta Praneeth Reddy , Canevarolo Rafael R. , Meads Mark B. , Silva Maria , Zhao Xiaohong , Cubitt Christopher L. , Sansil Samer S. , DeAvila Gabriel , Alugubelli Raghunandan Reddy , Bishop Ryan T. , Tungesvik Alexandre , Zhang Qi , Hampton Oliver , Teer Jamie K. , Welsh Eric A. , Yoder Sean J. , Shah Bijal D. , Hazlehurst Lori , Gatenby Robert A. , Van Domelen Dane R. , Chai Yi , Wang Feng , DeCastro Andrew , Bloomer Amanda M. , Siegel Erin M. , Lynch Conor C. , Sullivan Daniel M. , Alsina Melissa , Nishihori Taiga , Brayer Jason , Cleveland John L. , Dalton William , Walker Christopher J. , Landesman Yosef , Baz Rachid , Silva Ariosto S. , Shain Kenneth H.
Published: January 2025

Abstract
Several therapeutic agents have been approved for treating multiple myeloma, a cancer of bone marrow–resident plasma cells. Predictive biomarkers for drug response could help guide clinical strategies to optimize outcomes. In this study, we present an integrated functional genomic analysis of tumor samples from patients multiple myeloma that were assessed for their ex vivo drug sensitivity to 37 drugs, clinical variables, cytogenetics, mutational profiles, and transcriptomes. This analysis revealed a multiple myeloma transcriptomic topology that generates “footprints” in association with ex vivo drug sensitivity that have both predictive and mechanistic applications. Validation of the transcriptomic footprints for the anti-CD38 mAb daratumumab (DARA) and the nuclear export inhibitor selinexor (SELI) demonstrated that these footprints can accurately classify clinical responses. The analysis further revealed that DARA and SELI have anticorrelated mechanisms of resistance, and treatment with a SELI-based regimen immediately after a DARA-containing regimen was associated with improved survival in three independent clinical trials, supporting an evolutionary-based strategy involving sequential therapy. These findings suggest that this unique repository and computational framework can be leveraged to inform underlying biology and to identify therapeutic strategies to improve treatment of multiple myeloma.

Significance: Functional genomic analysis of primary multiple myeloma samples elucidated predictive biomarkers for drugs and molecular pathways mediating therapeutic response, which revealed a rationale for sequential therapy to maximize patient outcomes.
Figure S4 from First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew
Published: January 2025

Supplemental Figure S4
Figure 2 from First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew
Published: January 2025

Patients were scanned and assessed by RECIST v1.1 approximately every 8 weeks. A, Swimmer plot showing the treatment duration and BOR for enrolled patients across all dose levels. BOR for PD (star), SD (circle), and PR (square) is shown. Additional annotations for first PD or death (upward gray triangle), the last non-PD assessment (X mark), and treatment ongoing (right-facing black triangle) are included. Each color represents the cohort/dose level. Eight patients that initially received doses ≤600 mg had their dose escalated during treatment. B, Waterfall plot showing the %change in baseline target lesion SoD and BOR for enrolled patients across all dose levels. Each color represents the cohort/dose level initially received. Best response is noted for PD (circle), SD (diamond), and PR (square). One patient remains on treatment as of the data cut date is noted with a black triangle. N = 2 patients were not evaluable due to missing postbaseline assessment; thus, only N = 26 patients with BOR data per RECIST v1.1. C, Baseline and week 64 scans and target lesion diameter summary for the patient with a well-differentiated pancreatic neuroendocrine tumor with confirmed PR. Data as of October 2, 2024. SoD, sum of diametres.
Instrumento musical como categoria de pensamento: reflexões sobre técnica e tecnologia desde uma Antropologia da Música
Authors: Gomes João Alexandre Straub , Noleto Rafael da Silva
Published: January 2025

Through ethnographic research developed with luthiers and other types of musical instrument builders in the state of Rio Grande do Sul, this article presents a reflection on the concepts of technique, technology, musical instrument and music. Starting from an epistemological approach of the Anthropology of Technique and Technology, we seek to reflect on how Musical Sciences, understood as an area of ​​knowledge production that concerns Music in its sound, epistemological and organological sense, can contribute in a peculiar way to the requalification of concepts used in other fields such as Philosophy and Anthropology itself. More than artifacts used to make music, we propose that musical instruments are categories of thought, which refer to a specific type of “technical object” or “thing” that is constituted in the flow of materials.
Assessing and Addressing Cardiovascular and Obstetric Risks in Patients Undergoing Assisted Reproductive Technology: A Scientific Statement From the American Heart Association
Authors: Mauricio Rina , Sharma Garima , Lewey Jennifer , Tompkins Rose , Plowden Torie , Rexrode Kathryn , Canobbio Mary , Skowronski Jenna , Hameed Afshan , Silversides Candice , Reynolds Harmony , Vaught Arthur ,   on behalf of the American Heart Association Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Lifelong Congenital Heart Disease and Heart Health in the Young
Published: January 2025

The use of assisted reproductive technology (ART) is growing, both to assist individuals with infertility and for fertility preservation. Individuals with cardiovascular disease (CVD), or risk factors for CVD, are increasingly using ART. Thus, knowing how to care for patients undergoing ART is important for the cardiovascular clinician. In this scientific statement, we review the ART process and known short-term and long-term risks associated with ART that can adversely affect patients with CVD. We review current knowledge on risks from ART for specific cardiac conditions and provide a suggested approach to evaluating and counseling patients with CVD contemplating ART as well as suggested management before and during the ART process. Individuals with CVD are at increased risk for pregnancy complications, and management of this unique population has been discussed previously. The focus of this scientific statement is on ART. Therefore, discussions on risk assessment, counseling, and management of individuals with CVD during pregnancy are limited, and established guidelines are referenced.
Abstract 045: First‐Line Mechanical Thrombectomy Device in Intracranial Atherosclerotic Large Vessel Occlusion
Authors: Mierzwa A. T. , Al Kasab S. , Almallouhi E. , Jumaa M. ,   RESCUE‐ICAS Registry
Published: January 2025

Introduction

First‐line mechanical thrombectomy devices are associated with heterogeneous functional and safety outcomes in large vessel ischemic stroke. Successful recanalization rates are influenced by associated technical difficulties of navigating torturous vessels and interactions with recalcitrant thrombi of atherosclerotic lesions. As such, studies are required to evaluate these devices to determine the optimal initial thrombectomy approach in patients with these lesions.

Method

This is an analysis of the RESCUE‐ICAS international prospective observational registry which included patients with residual stenosis (50‐99% reperfusion) following successful mechanical thrombectomy. Patients were dichotomized into those receiving first‐line aspiration catheter or stentriever devices. Primary and secondary efficacy outcomes were defined as excellent functional outcomes (modified Rankin Scale 0‐2) and procedure times, respectively. Primary safety outcomes were defined symptomatic intracranial hemorrhage (sICH) rates. Multivariate analysis was performed on the primary outcome.

Results

There were four‐hundred‐twenty‐six patients included in this analysis with 218 and 208 patients receiving first‐line aspiration catheter and stentriever devices, respectively. Patients were generally older (median 68 years old) Caucasian (59%) males (61%). Patients in the aspiration catheter cohort were more likely to have dyslipidemia (55% vs 45% p = 0.04) and prior stroke (28% vs 19% p = 0.03) compared to the stentriever cohort; no other significant differences were noted. At 90‐days, there were equivalent rates of excellent functional outcomes in the aspiration and stentriever cohorts (35.4% vs 31.4% p = 0.48) and redemonstrated following multivariate analysis (OR 0.90 95% CI 0.59 ‐ 1.37; p = 0.62). Yet, aspiration catheters were noted to have shorter procedure times (45 mins vs 62 mins p < 0.001). Additionally, there was a trend towards lower sICH rates in the aspiration cohort (5% vs 9.6% p =0.07) compared to the stentriever cohort.

Conclusion

There were equivalent primary functional outcomes in patients with atherosclerotic large vessel occlusions treated with either aspiration catheter or stentriever devices yet, procedure times favored aspiration catheters. There was a trend towards lower symptomatic ICH rates with first‐line aspiration catheters. Further randomized studies are required to further evaluate procedural benefits and risks.
Abstract 098: Endovascular Treatment of Symptomatic Bilateral Carotid Artery Occlusions
Authors: Fakih R. , Tolba H. , Detmer K. , Merriman W. , Elkolaly S. , Gillani S. , Qureshi A. I.
Published: January 2025

Introduction

The annual incidence of acute ischemic strokes or transient ischemic attacks due to chronic carotid occlusion (CCO) is estimated at 5‐10%. While initial trials did not show a clear benefit for surgical treatment of symptomatic CCO, emerging data suggests that endovascular treatment (EVT) may offer significant advantages over best medical management (BMM) in selected cases. However, the use of EVT for bilateral symptomatic CCO has not been previously investigated.

Method

We present the case of a 67‐year‐old male with a history of oropharyngeal carcinoma, treated with extensive neck radiation, leading to bilateral common carotid artery occlusions. The patient, initially presenting for elective gastric endoscopy, experienced hypotension during anesthesia induction and subsequently became comatose. Imaging revealed complete occlusion of the bilateral common carotid arteries and the right vertebral artery, with CT perfusion showing extensive global hypoperfusion correlating with severe EEG attenuation. Due to the failure of medical management, EVT was deemed necessary.

Results

A femoral approach was utilized for endovascular access to each common carotid artery. The procedure involved the use of a guide catheter, microwires for crossing occlusions, and multiple angioplasties with various balloon sizes to create a passage through the occlusions. An embolic protection device was employed to prevent iatrogenic distal embolization. Rheolytic thrombectomy aided in recanalization, followed by the placement of several stents in a telescopic fashion to achieve vessel patency. Intravascular ultrasound (IVUS) was performed pre‐ and post‐recanalization to evaluate vessel integrity. The procedure resulted in the complete recanalization of both carotid arteries, with subsequent resolution of perfusion abnormalities and normalization of electroencephalographic patterns. The patient returned to his neurological baseline within days post‐procedure.

Conclusion

This case demonstrates the safe and effective use of EVT for the treatment of bilateral chronic carotid artery occlusions. It highlights the potential of EVT as a promising therapeutic option in managing CCO, particularly in cases where medical management fails.
Abstract 105: Gaze, weakness, neglect and speech (GWNS), an LVO stroke sale is also predictive of distal medium vessel occlusion (DMVO) in the emergency department.
Authors: Lodi Y. M. , Khan I. , Saini H.
Published: January 2025

Background and objective

In acute ischemic stroke, DMVOs and LVOs are associated with disability and death. There are no stroke scales that predict DMVOs. The objective is to evaluate if the GWNS stroke scale predicts DMVO as it does for LVOs in hyper‐acute state.

Methods

Consecutive AIS with suspected PLVOs and DMVOs were prospectively enrolled from January 2020 to December 2022. NIHSS and GWNS scale were obtained prior to CTA and DSA. GWNS scale scores range from 0 to 4. We defined DMVO as distal terminal branches of middle cerebral artery (MCA); M2, M3, M4. Internal carotid artery (ICA), terminus and MCA, M1 were defines as PLVOs.

Results

We have enrolled 148 patients; mean age 68.74+/‐15.37, 52.70% female, GWNS 2 in 32 3 in 35 and 4 in 57. Time to obtain GWNS from arrival was 1.5 minutes (range 1 ‐3) and CTA was 30.3 plus‐minus 9 minutes. PLVOs were present in 61% and DMVOs in 39%. All GWNS scale 3 and 4 had vessel occlusion except in 2; one with seizure and other with formed stroke. None with GWNS scale 2 or less had occlusion. GWNS scale score 4 with gaze deviation were more frequent in PLVOs as opposed to GWNS 3 with gaze preferences, which were more frequent in DMVO. Patients with DVMOs demonstrated a lower NIHSS compared to PLVOs. GWNS 3 or 4 is associated with both PLVOs and DMVOs including M3 and M4. GWNS score predicts DMVO better (0.88) than NIHSS (0.66) irrespective of right or left hemispheric vessels. GWNS score 3/4 with Gage predicts the most for DMVOs (0.9).

Conclusions

GWNS stroke scale predicts DMVOs in our study. This is the only reported scale for DMVOs in our knowledge. The GWNS scale could be used for early detections of both DMVOs and PLVOs for faster perfusion therapy. Further studies are needed.
Abstract 122: Maternal Stroke and Malnutrition: a Cross‐Sectional Analysis of the National Inpatient Sample
Authors: Christopher K. M. , Lyons A. , Kaur G.
Published: January 2025

Introduction

Malnutrition is present on admission in approximately 20% of stroke patients, contributing to stroke morbidity and mortality. While stroke during the peripartum period is rare, it accounts for 18% of strokes in women aged 18‐35. Additionally, health inequities in stroke incidence persist, with previous studies reporting that Black mothers had 50% higher odds of having a stroke than white mothers. The objective of the current study was to (a) determine the prevalence of malnutrition in women during the peripartum hospital stay and (b) calculate the odds of ischemic and hemorrhagic stroke in women with malnutrition.

Methods

We utilized the National Inpatient Sample (NIS) years 2016‐2020, selecting women aged 18‐44 with a pregnancy related ICD‐10 code. The presence of ICD‐10 codes for malnutrition were used to determine malnutrition status. Weighted logistic regression models were fitted with ischemic stroke and hemorrhagic stroke as the outcomes; covariates included age, socioeconomic status, stroke history, hypertensive disorders of pregnancy, and having obesity. All analyses were completed in SAS v9.4.

Results

Malnutrition was associated with stroke occurrence, with 35 times increased odds of ischemic stroke in women with malnutrition as compared to women without malnutrition (aOR=35.10; 95% CI: 18.89, 65.22). History of stroke (aOR: 39.92; 95% CI: 23.83, 57.18), low and middle socioeconomic status (low SES aOR: 1.41; 95% CI: 1.10‐1.81; middle SES aOR: 1.34; 95% CI: 1.04‐1.72), hypertensive disorders of pregnancy (OR: 2.75; 95% CI: 2.20, 3.44), age (aOR: 1.05; 95% CI: 1.03, 1.07), and race (aOR: 1.33; 95% CI: 1.04, 1.70) were also significant covariates in this model. Obesity (aOR: 1.12; 95% CI: 0.85‐1.48) was not associated with ischemic stroke. Malnutrition was also two times more prevalent in black women as it was in white women in this sample (cOR=2.09, 95% CI: 1.88, 2.33).

Conclusions

Malnutrition has a significant impact on stroke occurrence during peripartum period, increasing the odds of stroke by 35 times. This relationship could contribute to the overall disparity in maternal morbidity and mortality between black and white mothers, since black women have 50 percent higher odds of stroke and two times higher odds of malnutrition. The overall higher prevalence of malnutrition among Black women could contribute to greater stroke risk in that population.
Abstract 147: System Improvements in Acute Stroke Management: Impact on Picture‐to‐Puncture Times
Authors: Elsayed M.
Published: January 2025

Introduction/Purpose

This study aims to investigate the impact of system improvements on picture‐to‐puncture (P2P) times in acute stroke management. Time efficiency is crucial in acute stroke care, andunderstanding how system enhancements affect P2P times can lead to improved patient outcomes.

Materials/Methods

A single‐center retrospective analysis was conducted using a prospective acutestroke database from October 2007 to October 2013. Patient demographics, stroke severity, andtreatment time points were collected to assess the annual trends in P2P times.

Results

The study identified a total of 189 patients, with 181 meeting the study criteria. Annual medianP2P times decreased over the 6‐year period, showing a significant trend towards improved efficiency. Factors such as stroke onset times and CT acquisition times were found to influence P2P times.

Conclusion

System improvements in acute stroke management have led to a significant reduction in P2Ptimes over the study period. Understanding the impact of these enhancements on time metrics isessential for optimizing acute stroke care and improving patient outcomes.
Abstract 168: A Case of Large Vessel Occlusion Presenting as a New‐Onset Focal Seizure
Authors: Furr T. , Blanden A. R. , Masoud H. E.
Published: January 2025

Introduction

Hemiparesis after a new onset seizure was originally considered a contraindication to lytic administration to avoid the hemorrhagic risk associated with thrombolysis in patients experiencing post‐ictal Todd's paralysis [1]. However, the observation window required to establish an improved diagnosis of a post‐ictal Todd's paralysis runs counter to the rapid treatment requirements for acute ischemic stroke. Seizure at stroke onset is a recognized but poorly studied phenomenon, and presents a critical diagnostic dilemma to patients in the hyper‐acute window, requiring rapid triage to a seizure vs a stroke treatment pathway.

Methods

Here we present a case of a 73‐year‐old woman with pancreatic cancer who developed focal status epilepticus due to an emergent large vessel occlusion (LVO).

Results

Patient is a 73‐year‐old woman with metastatic pancreatic cancer and a recent stroke taking aspirin and Plavix who initially presented to the emergency department with the concern for an NSTEMI. She was admitted to the medicine service and treated with a heparin drip. On day 7 a stroke code was called as the patient was unresponsive and had tonic activity on the right side of her body. Her NIHSS was 26 for decreased level of consciousness and intermittent right hemiparesis. She was given Ativan, Versed, loaded with Vimpat to control the seizures without success, and ultimately intubated and taken for a stat CT head and CT angiography. This showed a left distal ICA occlusion. She was taken for emergent thrombectomy with TICI IIb revascularization.

The patient was placed on video EEG showing severe slowing of background with no epileptiform abnormalities. Her transthoracic echocardiogram had moderate left atrium dilatation but was otherwise unremarkable. MRI brain without contrast presented a large left MCA acute ischemic stroke. The patient continued to have a poor hospital course and had persistent deficits from her left MCA territory stroke. Due to her poor prognosis from her pancreatic cancer and her deficits from her large left MCA stroke, comfort measures were pursued. The patient was pronounced deceased 11 days after being in the hospital. The reason for the stroke was determined to be a malignancy‐associated embolism.

Conclusions

Seizure stroke onset is a known presentation of a stroke but is poorly studied and under‐recognized [2]. The purpose of our report is to raise awareness of this presentation, particularly in patients with no history of epilepsy and with significant vascular risk factors presenting with new‐onset seizures with persistent localizable deficits. We would recommend CT angiography as the first imaging study in these patients rather than plain CT, with a low threshold to treat with thrombolytic if an alternative cause is not found and the patient is otherwise a candidate, or endovascular therapy in the instance of LVO, as in our case.
Abstract 205: Barriers in Acute Stroke Care for Patients with Limited English Proficiency
Authors: Trang I. , Ali A. , Ganne C. , Malagon C. Perez , Nguyen T. P. , Sharrief A. Z.
Published: January 2025

Introduction

Research shows that ischemic stroke patients with limited English proficiency (LEP) experience disparities in stroke care, including increased time to treatment with intravenous thrombolysis. During code strokes, translation devices are necessary to evaluate stroke patients with LEP, but the devices may not be readily available or may have poor reliability (e.g., poor connection, poor audio quality). This study aims to systematically evaluate the challenges that clinicians, nurses, and other healthcare professionals encounter when assessing stroke patients with LEP.

Methods

A survey was distributed to clinicians, nurses, and other healthcare personnel who provided care to stroke patients over a six‐month period. We collected information regarding role (e.g., physician, nurse), availability of translation devices, and reliability of translation devices in this survey. Descriptive statistics were used to analyze the data.

Results

Of the clinician respondents, 71% (12/17) reported inaccessibility to translation devices during code strokes. Additionally, 65% (11/17) experienced technical difficulties with translation devices during code strokes. Furthermore, 76% (13/17) of clinicians believed that inadequate or unreliable translation services have compromised their ability to manage code strokes for LEP patients. A significant majority of overall respondents, 88% (28/32) expressed interest in a mobile application to aid in evaluating stroke patients with LEP and 81% (26/32) showed interest in learning how to perform the NIH Stroke Scale in another language.

Conclusion

Despite the availability of translation services, issues with reliability and accessibility hinder the quality of care for stroke patients with LEP, highlighting the need for systemic improvements. Many clinicians call for improved services and technology, which our group will focus on developing.
Abstract 208: BIUXX
Authors: Betgeri S. Shankerappa
Published: January 2025

Introduction

Efficacy of transvenous endovascular complete embolisation of the superior ophthalmic vein (SOV) through external jugular venous approach in cranial and extra cranial arterio venous malformations.

Methods

Tranvenous endovascular embolisation of the superior ophthalmic vein was done in the following 3 patients. First patient, 40yr male had sudden onset right sided rapidly progressing proptosis and eye redness following a bout of cough during bronchoscopy for evaluation of a lung mass. Immediate CECT imaging brain and orbit showed phleboliths in a slow flow vascular malformation with rupture in the intra conal space with venous drainage into the SOV. No definite arterial feeders were identified. Second patient, 50 yr old lady, had gradually progressive right sided proptosis with peri orbital pain and eye redness over a period of 5 months. CECT brain and orbit showed indirect carotico cavernous fistula (CCF Barrow type B) with dilated right SOV. Third patient, 38yr old male, had a slowly progressive left sided peri orbital tortous swelling and mild proptosis over a period of 3 months following forehead trauma. CECT brain and face showed left frontal scalp and peri orbital arterio venous fistula with feeders from the superficial temporal artery and ophthalmic artery with venous drainage into the dilated SOV, facial vein and superficial temporal vein opening into the external jugular vein. Feeder from the superficial temporal artery was initially embolised from the arterial side in this patient followed by embolisation of the SOV through the trans venous approach. In all the 3 patients, SOV was the main or one of the major draining vein of the vascular malformations causing the orbital symptoms. In all the 3 patients, under general anaesthesia, USG guided access was taken from the ipsilateral external jugular vein with a 5F radial slender sheath. SOV was reached with a 2.4F microcatheter and 0.014 wire combinations manoeuvring the catheter via the facial vein and angular vein. Complete SOV embolisation was done using coils or glue mixed with lipiodol in1:1 ratio. Arterial access (Common femoral artery) was taken only in two patients. One with indirect CCF and another with left frontal arterio venous fistula to indentify the filling of the SOV in the former and to embolise the arterial feeders from the superficial temporal artery in the latter.

Results

Each of the 3 patients successfully underwent SOV embolisation via the trans venous approach. All the 3 patients had progressive decrease in proptosis and eye congestion in immediate post procedure period and follow up till now.

Conclusions

Endovascular trans venous SOV embolisation is simple and effective technique in treating indirect CCF, slow flow orbital venous malformations and extra cranial arterio venous fistula. This backdoor approach is also effective in cases where in there is no definite identifiable arterial feeder to the vascular malformation or when the feeder is a very tiny artery (ophthalmic artery) with difficult cannulation.
Abstract 212: Cardiac CT Imaging in Embolic Stroke of Undetermined Source (ESUS)
Authors: Seblani N. El , Madden S. , Srivastava R. , Lichtenberger J. , Gulati A.
Published: January 2025

Background

Up to 40% of ischemic strokes meet the definition of embolic stroke of undetermined source (ESUS). Although transthoracic echocardiography (TTE) is the conventional method for detecting cardiac structural abnormalities, Cardiac CT Angiography (CCTA) is emerging as a valuable non‐invasive alternative for evaluating intra‐cardiac thrombi, particularly in high‐risk patients.

Methods

A 42‐year‐old right‐handed male with a history of ischemic strokes, including a left ventricular (LV) thrombus previously managed with warfarin, coronary artery disease, and systolic congestive heart failure (EF 24‐30%), presented to the emergency department with acute aphasia, right facial paralysis, and right hemiparesis. His NIHSS score was 6, with a baseline mRS of 1. Non‐contrast CT of the head (NCCTH) showed multiple chronic strokes in the left frontal and parietal lobes, right frontal and parietal‐occipital regions, left pontine and midbrain areas, and bilateral thalami/internal capsules, as well as probable chronic lacunar infarcts. CTA revealed occlusion of the superior branch of the left M2 MCA and right V1‐V2 segments. CT perfusion (CTP) demonstrated a 39 cc penumbra and 5 cc core in the left MCA territory. Due to concerns about acute‐on‐chronic ischemic strokes with left M2 occlusion and a high risk of hemorrhagic transformation, thrombectomy was not performed. Brain MRI showed acute embolic strokes in the left frontal lobe, insular cortex, and right thalamus. TTE indicated severe left ventricular hypokinesia with an EF of 24% and a markedly dilated left atrium, but no shunt or intra‐cardiac thrombus was detected. Telemetry showed no arrhythmias. Given the suspicion of a cardioembolic source in this young patient with low ejection fraction heart failure, a CCTA was performed, revealing three LV thrombi (measuring 1.3 times 1.1 cm, 0.9 times 0.9 cm, and 0.7 times 0.7 cm) against the distal and apical lateral walls. The patient was subsequently started on Apixaban for LV thrombus treatment and secondary stroke prevention.

Conclusion

Although earlier retrospective studies have emphasized the value of CCTA in evaluating embolic strokes, the latest AHA guidelines still fall short in providing comprehensive diagnostic recommendations for ESUS. This case highlights the critical role of CCTA in identifying intra‐cardiac thrombi among high‐risk patients with cardioembolic strokes and concurrent heart failure.