bluuebunny/crossref_metadata_2025 huggingface dataset:
Moderating Effects of Age on the Longitudinal Associations Between IADL Disability, Self‐Rated Health, and Depression Among Middle‐Aged and Older Adults
Authors: Peng Man-Man , Wang Pengfei , Liang Zurong , Chen Ziyuan
Published: January 2025

Background: The potential association and underlying mechanisms between instrumental activities of daily living (IADL) and depressive symptoms in middle‐ and older‐aged adults remain unclear. This study explores the bidirectional relationship between IADL disability and depressive symptoms among Chinese middle‐aged and older adults and examines the mediating or moderating effects of self‐rated health (SRH) and age on this relationship.

Methods: We used data from five waves (2011, 2013, 2015, 2018, and 2020) of the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey. A total of 4830 participants aged 45 and older were included in the analysis. Longitudinal associations between IADL disability, SRH, and depressive symptoms were tested using cross‐lagged models to simultaneously evaluate the bidirectional association and the strength of the temporal association.

Results: Among middle‐aged and older adults, there was a significant bidirectional longitudinal relationship between IADL disabilities and depressive symptoms. Higher levels of IADL disability predicted an increased risk of depressive symptoms and vice versa. SRH mediated the bidirectional relationship between IADL disabilities and depressive symptoms. Higher levels of IADL disability led to lower SRH, which further increased the risk of depressive symptoms and vice versa. Age moderated the cross‐lagged models, indicating that the effect of SRH on the bidirectional relationship between IADL disability and depressive symptoms was stronger in the middle‐aged group than that in the older group.

Conclusion: The study results clarified the bidirectional relationship between IADL disability and depressive symptoms in middle‐aged and older adults. Healthcare providers can use the findings to design targeted interventions to address the decline in IADL function and potentially benefit mental health. Helping middle‐aged and older adults improve their SRH may interrupt the vicious cycle linking IADL disability and depressive symptoms, particularly in middle‐aged adults transitioning to old age.
Quality Assurance of Total Carotenoids and Quercetin in Marigold Flowers (Tagetes erecta L.) as Edible Flowers
Authors: Kusumiyati Kusumiyati , Putri Ine Elisa , Hadiwijaya Yuda , Kartika Agitha , Maulana Yusuf Eka , Sutari Wawan
Published: January 2025

Marigold flowers, which are also known as Tagetes erecta L., are widely recognized for their bright colors and health benefits. Therefore, the purpose of this research was to investigate the quality of total carotenoid content (TCC) and quercetin in marigold flowers, specifically the edible ones, using visible near‐infrared spectroscopy (Vis‐NIRS) technology. Both bioactive compounds in these flowers were assessed using Vis‐NIRS. The technology is considered to be a rapid and non‐destructive method for evaluating the quality of agricultural products. To ensure accuracy in the evaluation, Vis‐NIRS was validated against conventional methods such as spectrophotometry and chromatography. The results showed that the use of Vis‐NIRS helped to accurately determine the levels of TCC and quercetin in marigold flowers. Based on the analysis results, the best accuracy values for TCC were as follows: the correlation coefficient of the calibration set (Rcal) was 0.94, the root mean square error of the calibration set (RMSEC) was 125.57, the correlation coefficient of the prediction set (Rpred) was 0.87, the root mean square error of the prediction set (RMSEP) was 129.35, and the ratio of prediction to deviation (RPD) was 2.77. For quercetin, the best accuracy values were: Rcal was 0.96, RMSEC was 1.63, Rpred was 0.88, RMSEP was 2.37, and RPD was 2.09. These results demonstrate that the method provides a reliable alternative to destructive method. The research showed that Vis‐NIRS served as a reliable quality assurance tool for assessing bioactive compounds in marigold flowers.
Learning‐Based Progression Detection of Alzheimer’s Disease Using 3D MRI Images
Authors: Wu Jacky Chung-Hao , Chien Tzu-Chi , Chang Chiung-Chih , Chang Hsin-I , Tsai Hui-Ju , Lan Min-Yu , Wu Nien-Chen , Lu Henry Horng-Shing
Published: January 2025

Alzheimer’s disease (AD) is an irreversible brain disease. In addition to the functional deterioration of memory and cognition, patients with severe conditions lose their self‐care ability. Patients exhibiting symptoms are often attributed to aging and thus lack proper medical care. If it can be diagnosed early, the doctor can provide adequate treatments to mitigate the symptoms. Magnetic resonance imaging (MRI) can reflect the characteristics of different human tissues and organs, and is a common tool implemented in clinical examinations. In this study, we tested learning‐based approaches to detect disease progression in AD patients using MRI. Specifically, each patient is categorized as one of the following four classes: cognitive normal, early mild cognitive impairment, late mild cognitive impairment, and AD. To extract 3D information in MRI, we proposed a 3D convolutional neural network structure based on ResNet3D‐18. We designed various multiclass classification frameworks. Moreover, we implemented ensemble classification combining these frameworks. Experiments demonstrated great potential for learning‐based approaches on the Alzheimer’s Disease Neuroimaging Initiative dataset. The ensemble approach performed the best with an accuracy of 0.950, which is competitive with neurologists in diagnosing AD progression in clinical practice. With precise detection, patients can understand their conditions early and seek proper treatments.
Veracity‐Oriented Context‐Aware Large Language Models–Based Prompting Optimization for Fake News Detection
Authors: Jin Weiqiang , Gao Yang , Tao Tao , Wang Xiujun , Wang Ningwei , Wu Baohai , Zhao Biao
Published: January 2025

Fake news detection (FND) is a critical task in natural language processing (NLP) focused on identifying and mitigating the spread of misinformation. Large language models (LLMs) have recently shown remarkable abilities in understanding semantics and performing logical inference. However, their tendency to generate hallucinations poses significant challenges in accurately detecting deceptive content, leading to suboptimal performance. In addition, existing FND methods often underutilize the extensive prior knowledge embedded within LLMs, resulting in less effective classification outcomes. To address these issues, we propose the CAPE–FND framework, context‐aware prompt engineering, designed for enhancing FND tasks. This framework employs unique veracity‐oriented context‐aware constraints, background information, and analogical reasoning to mitigate LLM hallucinations and utilizes self‐adaptive bootstrap prompting optimization to improve LLM predictions. It further refines initial LLM prompts through adaptive iterative optimization using a random search bootstrap algorithm, maximizing the efficacy of LLM prompting. Extensive zero‐shot and few‐shot experiments using GPT‐3.5‐turbo across multiple public datasets demonstrate the effectiveness and robustness of our CAPE–FND framework, even surpassing advanced GPT‐4.0 and human performance in certain scenarios. To support further LLM–based FND, we have made our approach’s code publicly available on GitHub (our CAPE–FND code: https://github.com/albert-jin/CAPE-FND [Accessed on 2024.09]).
Study on Antibacterial Activities of Croton macrostachyus and Pycnostachys abyssinica Leaf Extracts Against Some Human Pathogens
Authors: Yemata Getahun , Yihune Endalamaw , Kebede Yewulsew
Published: January 2025

The present study was aimed to verify the medicinal value of Croton macrostachyus and Pycnostachys abyssinica traditionally used to treat human and animal ailments in Ethiopia. Fresh leaves of these species were collected, dried under shade, and ground into fine powder. The extraction was carried out by the maceration method using methanol as a solvent. The compounds in the crude extract were further profiled by thin layer chromatography (TLC). The antibacterial activity of the compounds was evaluated using the agar well diffusion method. C. macrostachyus had a higher percentage extract yield (22.5%) than P. abyssinica (13.7%). The phytochemical screening showed more abundant phenolic compounds and tannins in the extract of C. macrostachyus and alkaloid, flavonoid, phenolic compounds, and tannins in the extract of P. abyssinica. Overall, C. macrostachyus produced twofold higher growth inhibition zone (24.0 ± 0.5–43.0 ± 1.0 mm) against the tested pathogens than P. abyssinica (7.0 ± 0.5–24.0 ± 0.3 mm). Among the bacteria, Klebsiella pneumoniae was found to be the most sensitive to compounds of C. macrostachyus. The lowest minimum inhibitory concentration (MIC) values (25 mg/mL) were obtained from compounds 1 and 3 of C. macrostachyus leaf extract against Escherichia coli and K. pneumoniae and compounds 2 and 3 of the same against S. aureus. Similarly, compound 1 of P. abyssinica leaf extract produced the lowest MIC (25 mg/mL) against K. pneumoniae and Staphylococcus epidermidis and compound 3 of the same species against E. coli and K. pneumoniae. All the profiled compounds of the two species had both bactericidal and bacteriostatic properties against the tested pathogens. The results of the present study revealed that the compounds of C. macrostachyus had strong antibacterial activity against all the tested pathogens, indicating the high potential of the compounds. However, further characterization and identification of the specific compounds for the development of biocide formulations are suggested.
Progressive Collapse of Steel Structures Under Blast Loads Considering Soil‐Structure Interaction
Authors: Raminfar Emad , Zafarani Mohammad Mahdi , Birzhandi Mohammad Sadegh , Zareei Seyed Alireza
Published: January 2025

This study focuses on the effect of soil‐structure interaction on the occurrence of progressive collapse due to an external blast. Therefore, a 3‐story fixed base steel moment‐resisting frame structure was first modeled and subjected to an external blast load. Then, the same structure was modeled considering soil‐structure interaction. In another stage of this study, the effect of plan irregularity on progressive failure resulting from the explosion was investigated, assuming the presence or absence of soil‐structure interaction. The direct simulation method and alternative load path method are all employed to simulate the progressive collapse process of steel frames using the commercial finite element program LS‐DYNA. The results of the numerical simulations demonstrated that the presence of soil‐structure interaction, significantly influences the response of the structure to the blast and this interaction increases the likelihood of progressive failure occurring even at symmetric and asymmetric structures. It was also shown that silty sand soil yields more critical conditions than other types of soil in the event of failure after the occurrence of an explosion in the structure.
Supplemental Table S2 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

The top 10 nSCORE ranked master regulators in indicated temporal treatment periods, showing that EP3 is the most consistently top ranked MR in the 3 resistant GBM lines. (Supporting Main Figure 1)
Supplemental Figure S8 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 promotes self-renewal in TTFields-resistant GBM cells. (Supporting Main Figure 4)
Supplemental Figure S5 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 a Gai-coupled receptor of PGE2. (Supporting Main Figure 2)
Supplemental Figure S2 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

The adaptive immune hub 1.6 in TTFields-resistant cells. (Supporting Main Figure 1D-E)
Supplemental Figure S11 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 co-localizes with ZNF488 in the nucleus of TTFields-resistant GBM cells. (Supporting Main Figure 7)
Supplementary Table 1 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

Analyses and materials related to murine IUE and orthotopic models.
Supplemental Figure S1 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

Characterization of TTFields-resistant GBM cells, in which EP3 is the predicted master regulator. (Supporting Main Figure 1)
Supplementary Figure 6 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

Mouse models transcriptomically recapitulate human NB-FOXR2
Supplementary Figure 2 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

Transcription factor (TF) patterning in normal reference datasets.
Figure 4 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

NB-FOXR2 tumors transcriptionally resemble interneurons and OPC cells. A,t-Distributed stochastic neighbor embedding (t-SNE) of bulk RNA-seq profiles of pediatric brain tumors (left) and pediatric brain tumors with stage 4 high-risk EC-NBs from Gartlgruber and colleagues (ref. 21; right) using ssGSEA scores for N = 374 cell type–specific gene signatures from reference scRNA-seq datasets. t-Distributed stochastic neighbor embedding perplexity = 10 for left and perplexity = 30 for right. Color legend for pediatric brain tumors in the right panel matches labels in the left panel. FOXR2+ tumors, normalized expression >2. B, Tally of the top-scoring signatures across NB-FOXR2 bulk tumors (N = 25). The X-axis indicates the number of samples in which each signature is the top match by ssGSEA (Supplementary Table S10). HF nIN4/HF nIN5, human fetal interneuron 4 and 5; F-e12 CINHN, forebrain E12 cortical inhibitory neurons; F-e12 MGINH, forebrain E12 MGE inhibitory neurons; human fetal GE MGE/CGE, human fetal GE progenitors. C, Uniform Manifold Approximation and Projection joint representation of NB-FOXR2 tumors (N = 6) profiled by snRNA-seq. Top, points colored by consensus cell type annotation based on a reference dataset of the developing mouse brain. Gray, nonmalignant cells. Bottom, points colored by sample. Samples are joined without integration or batch correction. D, Number of malignant cells per consensus projected cell type across NB-FOXR2 tumors profiled by snRNA-seq (N = 6). Cell classes comprising >2% cells per sample are shown. E, Volcano plot for differential ssGSEA enrichment of cell type–specific signatures in bulk NB-FOXR2 compared with other tumor entities. Point size reflects −log10(adjusted P value). Differential testing was performed with t tests between NB-FOXR2 tumors and glial tumors (HGGs, DIPGs, posterior fossa group A ependymoma), followed by multiple testing correction using the Benjamini–Hochberg procedure. A positive FC represents enrichment in NB-FOXR2. Each point represents one signature, and signatures with positive log FCs and adjusted P value < 0.01 are colored. Color legend as in F. F, Differential ssGSEA enrichment as in E, comparing NB-FOXR2 tumors with neuronal tumors (ETMR, MB-SHH, and MB-WNT). Amp, amplified; EP-PFA, posterior fossa group A ependymoma; IPC, intermediate progenitor cell; NonAmp, nonamplified; RGC, radial glial cells.
Supplementary Information 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

Supplementary legends Supplementary Tables 1-3 Supplementary Figures 1-8
Supplementary Figure 6 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

MEK1/2 inhibition in KPC KrasG12D/fl mice with established tumours reverses enrichment of immune response related gene programmes.
Supplementary Figure 4 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

Loss of wild-type KRAS does not alter PI3K-AKT signalling.
Supplementary Figure 3 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

Acceleration of pancreatic tumour initiation after loss of wild-type Kras in KPC KrasG12D/fl mice.
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

Abstract
Antibody-based therapies have emerged as a powerful strategy for the management of diverse cancers. Unfortunately, tumor-specific antigens remain challenging to identify and target. Recent work established that inhibitor-modified peptide adducts derived from KRAS G12C are competent for antigen presentation via MHC I and can be targeted by antibody-based therapeutics, offering a means to directly target an intracellular oncoprotein at the cell surface with combination therapies. Here, we validated the antigen display of “haptenated” KRAS G12C peptide fragments on tumors in mouse models treated with the FDA-approved KRAS G12C covalent inhibitor sotorasib using PET/CT imaging of an 89Zr-labeled P1B7 IgG antibody, which selectively binds sotorasib-modified KRAS G12C–MHC I complexes. Targeting this peptide–MHC I complex with radioligand therapy using 225Ac- or 177Lu-P1B7 IgG effectively inhibited tumor growth in combination with sotorasib. Elucidation of the 3.1 Å cryo-EM structure of P1B7 bound to a haptenated KRAS G12C peptide–MHC I complex confirmed that the sotorasib-modified KRAS G12C peptide is presented via a canonical binding pose and showed that P1B7 binds the complex in a T-cell receptor–like manner. Together, these findings demonstrate the potential value of targeting unique oncoprotein-derived, haptenated MHC I complexes with radioligand therapeutics and provide a structural framework for developing next generation antibodies.

Significance: Radioligand therapy using an antibody targeting KRAS-derived, sotorasib-modified MHC I complexes elicits antitumor effects superior to those of sotorasib alone and provides a potential strategy to repurpose sotorasib as a hapten to overcome resistance.
Data 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

Abstract
Pancreatic cancer is characterized by the prevalence of oncogenic mutations in KRAS. Previous studies have reported that altered KRAS gene dosage drives progression and metastasis in pancreatic cancer. Whereas the role of oncogenic KRAS mutations is well characterized, the relevance of the partnering wild-type (WT) KRAS allele in pancreatic cancer is less well understood and controversial. Using in vivo mouse modeling of pancreatic cancer, we demonstrated that WT KRAS restrains the oncogenic impact of mutant KRAS and dramatically impacts both KRAS-mediated tumorigenesis and therapeutic response. Mechanistically, deletion of WT Kras increased oncogenic KRAS signaling through the downstream MAPK effector pathway, driving pancreatic intraepithelial neoplasia initiation. In addition, in the KPC mouse model, a more aggressive model of pancreatic cancer, lack of WT KRAS led to accelerated initiation but delayed tumor progression. These tumors had altered stroma and an enrichment of immunogenic gene signatures. Importantly, loss of WT Kras sensitized Kras mutant tumors to MEK1/2 inhibition though tumors eventually became resistant and then rapidly progressed. This study demonstrates the repressive role of WT KRAS during pancreatic tumorigenesis and highlights the critical impact of the presence of WT KRAS in both tumor progression and therapeutic response in pancreatic cancer.

Significance: KRAS allelic status impacts pancreatic cancer progression and has the potential to guide effective treatment in a substantial subset of patients.
Transcription Factor Fingerprint Provides Clues for Brain Tumor Cell of Origin
Authors: Orr Brent A.
Published: January 2025

Mouse models that faithfully represent the biology of human brain tumors are critical tools for unraveling the underlying tumor biology and screening for potential precision therapies. This is especially true of rare tumor types, many of which have correspondingly few xenograft or cell lines available. Although our understanding of the specific biological pathways driving cancer has improved significantly, identifying the appropriate progenitor populations to drive oncogenic processes represents a significant barrier to efficient mouse model production. In this issue of Cancer Research, Jessa and colleagues developed an innovative transcription factor fingerprinting method to map the cellular origin of central nervous system neuroblastoma, FOXR2-activated to medial ganglionic eminence–derived interneurons, which could then be efficiently targeted in the developing mouse brain using in utero electroporation. This approach serves as a blueprint for investigating other rare pediatric brain tumors, potentially accelerating progress toward the development of mouse models and identification of effective therapies.

See related article by Jessa et al., p. 231
Abstract 002: Efficacy and Safety of Acute Therapy in Cervical Artery Dissection‐Related Ischemic Stroke
Authors: Shu L. , Sousa J. André , Rodrigo-Gisbert M. , Akpokiere F. , Mandel D. , Sargento-Freitas J. , Furie K. , Requena M. , Yaghi S. ,   STOP‐CAD study group
Published: January 2025

Introduction

Cervical artery dissection (CeAD) is a significant cause of ischemic stroke in young adults, accounting for 25% of such cases. However, the optimal management strategies, including the use of intravenous thrombolysis (IVT) and endovascular treatment (EVT) with emergent carotid stenting, remain unclear. Current evidence does not adequately define the efficacy and safety of these interventions, particularly their impact on functional outcomes and the risk of symptomatic intracranial hemorrhage (ICH).

Method

We performed a secondary analysis using data from the retrospective STOP‐CAD study to assess the effectiveness and safety of IVT in patients with spontaneous CeAD presenting with acute ischemic stroke, as well as the outcomes of emergent carotid stenting during EVT in patients with tandem occlusion due to CeAD. Primary outcomes included 90‐day functional independence (modified Rankin Scale 0‐2) and the incidence of symptomatic ICH. Secondary outcomes for EVT included the rate of successful intracranial recanalization and stent‐related complications.

Result

Among 1,653 patients with spontaneous CeAD, 31.0% received IVT. IVT was associated with significantly higher odds of achieving 90‐day functional independence (adjusted odds ratio [aOR] = 1.67, 95% confidence interval [CI]: 1.23‐2.28, p = 0.001) without a corresponding increase in symptomatic ICH (aOR = 1.52, 95% CI: 0.79‐2.92, p = 0.215). In the EVT cohort of 328 patients with tandem occlusion, 45.7% underwent emergent carotid stenting. Stenting was linked to a higher rate of successful intracranial recanalization (aOR = 2.62, 95% CI: 1.52‐4.50, p < 0.001) but did not significantly affect 90‐day functional independence (aOR = 1.23, 95% CI: 0.82‐1.86, p = 0.32) or symptomatic ICH (aOR = 0.95, 95% CI: 0.41‐2.20, p = 0.91). Stent‐related complications included stent thrombosis in 14.0% of patients, symptomatic ICH in 6.7%, distal embolization in 5.3%, worsening dissection in 3.3%, access site complications in 2.7%, and stent migration in 0.7%.

Conclusion

Our findings indicate that IVT is beneficial in improving functional outcomes for patients with CeAD‐related ischemic stroke without increasing the risk of symptomatic ICH, supporting its recommended use in current clinical guidelines. Conversely, while emergent carotid stenting during EVT enhances recanalization success, it does not translate into improved functional outcomes or safety. These results underscore the necessity for randomized controlled trials to further investigate and refine the role of IVT and stenting in the management of CeAD‐related strokes, optimizing treatment strategies for this challenging condition.
Abstract 016: Natural evolution of incomplete reperfusion after endovascular therapy: systematic review and meta‐analysis
Authors: Mujanovic A. , Windecker D. , Cimflova P. , Meinel T. R. , Seiffge D. J. , Auer E. , Arnold M. , Serrallach B. L. , Rohner R. , Dobrocky T. , Hill M. D. , Goyal M. , Piechowiak E. I. , Gralla J. , Fischer U. , Kaesmacher J.
Published: January 2025

Introduction

Despite recent advances in endovascular therapy, up to half of acute ischemic stroke patients experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction, eTICI<3) after intervention. However, many of these patients will achieve complete delayed reperfusion at the 24h follow‐up, which is linked to good clinical outcome and minimal new infarct development. We aimed to systematically review literature and perform a meta‐analysis on the natural evolution of incomplete reperfusion after endovascular therapy.

Methods

We conducted a systematic review of MEDLINE, Embase and PubMed up until March 1, 2024 using a predefined search strategy. Only full‐text English written articles reporting rates of either favorable (i.e. delayed reperfusion) or unfavorable progression (i.e. persistent perfusion deficit) of incompletely reperfused tissue were included. Primary outcome was the rates of delayed reperfusion 24h post‐intervention and its association with functional independence (modified Rankin Scale, mRS 0‐2) at 90 days post‐intervention. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random‐effects model. Publication bias was assessed using funnel plots and the Luis Furuya‐Kanamori (LFK) index.

Results

Six studies involving 950 patients (50.7% female; median age 71, IQR 60 ‐ 79) were included. Four studies assessed the evolution of incomplete reperfusion on MRI perfusion imaging, while two studies used DWI and NCCT imaging, where new infarct was used to denote unfavorable progression. Complete delayed reperfusion, or absence of new infarct, occurred in 41% (inter‐quartile range, IQR 33% ‐ 51%) of cases 24h post‐intervention. Achieving delayed reperfusion was associated with higher likelihood of functional independence at 90 days (OR 2.53, 95%CI 1.88 ‐ 3.42). No evidence of publication bias was found (LFK=0.2).

Conclusion

Nearly half of patients with incomplete reperfusion achieve complete delayed reperfusion, leading to favorable clinical outcomes. This subgroup of eTICI<3 patients may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (e.g. intra‐arterial lytics or secondary distal thrombectomy). Accurately predicting the progression of incomplete reperfusion could optimize patient selection for adjunctive reperfusion attempts at the end of an intervention.
Abstract 049: Predictors of Hemorrhagic Transformation Following Mechanical Thrombectomy with Emergent Carotid Artery Angioplasty and Stenting for Tandem Occlusions of the Anterior Circulation
Authors: Jaikumar V. , Raygor K. P. , Shah S. , Stockman I. , Kruk M. , Scullen T. A. , Bouslama M. , Davies J. , Snyder K. V. , Levy E. I. , Siddiqui A. H.
Published: January 2025

Introduction

Hemorrhagic transformation of the ischemic core following mechanical thrombectomy (MT) for acute ischemic strokes can negate the benefits of the procedure. Previous regressions have identified variables suggesting larger strokes and longer procedural times as significant predictors of hemorrhagic transformation. Tandem occlusions add another layer of complexity, as the proximal carotid occlusion and the emergent carotid artery angioplasty and stenting (eCAS) introduces additional factors that can influence hemorrhagic transformation by altering the dynamics of reperfusion. We investigated predictors of hemorrhagic transformations following MT+eCAS performed for anterior circulation tandem occlusion in patients with baseline mRS 0‐2.;

Methods

Retrospective analysis of institutional thrombectomy database for patient characteristics, thrombectomy details, in‐hospital course, and follow‐up outcomes to shortlist significant univariate predictors to conduct multivariate binomial logistic regression and assess for significant predictors of hemorrhagic transformations following MT+eCAS during in‐hospital stay.;

Results

Multivariate binomial backwards logistic regression identified hypertension (p=0.042) and use of balloon guide catheters as opposed to conventional guide catheters (p=0.035) to significantly increase the risk of hemorrhagic transformation. Middle cerebral artery occlusions as opposed to internal carotid terminus occlusions (p=0.025), conscious sedation as opposed to general anesthesia (p=0.002), primary aspiration passes as opposed to primary stent retriever passes (p=0.007), retrograde as opposed to anterograde eCAS (p=0.004), intracranial slow flow following MT+eCAS (p=0.049) and oral aspirin/ticagrelor as opposed to intravenous eptifibatide load prior to eCAS (p=0.021) suggested reduced risk of hemorrhagic transformation, symptomatic or not.;

Conclusion

The study identified procedural predictors of hemorrhagic transformation specific to tandem occlusions. Patients undergoing mechanical thrombectomy with carotid artery stenting (MT+eCAS) under general anesthesia, using primary stent retriever passes, anterograde eCAS, and receiving an intravenous eptifibatide load before eCAS were particularly vulnerable to hemorrhagic transformation. Gradual reperfusion, shown to be protective against hemorrhagic transformation, was supported by the significance of intracranial slow flow.
Abstract 058: Outcomes in Patients with Spontaneous Intracranial Hemorrhage Who Underwent Thromboelastography Testing
Authors: Kaur G. , Rodriguez W. , Tseng S. , Wu N. , Guagliardo E. , Rheder J. , Christopher K. M. , Greene‐Chandos D. , Wang F.
Published: January 2025

Introduction

In the U.S., intracerebral hemorrhage (ICH) accounts for 10‐15% of all strokes, yet it carries a significantly higher risk of death or long‐term disability. While the Thromboelastography Platelet (TEG PM) mapping tool is well‐established for managing coagulopathy in trauma, organ transplantation, massive transfusions, and ECMO patients, its use in spontaneous ICH is not well understood. This study aims to evaluate patient outcomes in spontaneous ICH cases that received TEG testing compared to those that did not.

Method

Following IRB approval, we conducted a retrospective review of 215 patients with intracerebral hemorrhage (ICH) from June 2020 to June 2023. Out of these, 160 had spontaneous ICH, with 98 undergoing TEG‐PM testing and 62 not. The primary outcome was to evaluate the frequency of platelet transfusions and complications related to external ventricular drains (EVD). The secondary outcome was to compare discharge outcomes, using discharge status as a proxy for functional recovery, with discharge to home or acute rehab considered a good outcome. Chi‐square tests were performed to analyze differences between the TEG and non‐TEG groups, with all analyses conducted using IBM SPSS Statistics.

Results

We performed a Mann‐Whitney U test to compare ICH volume and initial National Institutes of Health Stroke Scale (NIHSS) scores between the two groups. The results showed that ICH volume was significantly lower in the non‐TEG‐PM group, with a p‐value of 0.002. The median ICH volume of TEG‐PM group was 13 (IQR 4.0‐36.0), while in non‐TEG‐PM group was 4.35 (IQR 1.0‐19.6). There was no significant difference in the initial NIHSS scores between the groups (p=0.063). In patients who underwent TEG‐PM, 10.2% received platelet transfusion as compared to non‐TEG‐PM group where 0% patients received platelet transfusion with p‐value of 0.009. In TEG‐PM group, 26.8 % patients had EVD placement vs 9.7 % in non‐TEG‐PM group with Odds Ratio 0.29 (0.11‐0.76). There was 1% EVD associated hemorrhage seen in patients of TEG‐PM group as compared to 0% in non‐TEG‐PM. 44.9% of the patients in the TEG‐PM had good discharge outcome as compared to 64.5% in non‐TEG‐PM group with p‐value of 0.1

Conclusion

The data indicates that TEG‐PM testing is not a reliable predictor of patient outcomes in spontaneous ICH. Interestingly, patients who underwent TEG‐PM testing received more platelet transfusions compared to those who did not, but this did not impact the discharge outcomes. The ICH volume in both groups were not clinically significant.
Abstract 061: A Multi Center Clinical Experience in Medellin, Colombia Using The Pipeline Vantage Device for the Treatment of Intracranial Aneurysms. Initial Results and One Year Follow‐Up
Authors: Mutis J. , Pabon B. , Torres V. , Brunet F. , Vergara J. , Pelaez F. , Patino M. , Arteaga J. , Cardozo M. , Vargas G.
Published: January 2025

Background and Purpose

Flow diverter technology has evolves trying to provide safe, stability and a good long‐term result. We report a local / regional experience with the fourth generation Pipeline Vantage Embolization Device in the treatment of intracranial aneurysms.

Methods

We present here a multi‐center, prospective, interventional, single‐arm trial of the Pipeline Vantage Embolization Device for the treatment of intracranial aneurysms. The primary end points were the effectiveness (the complete occlusion rate at 6‐ and 12‐month) and the safety (the presence or absence of serious adverse events during procedure and follow‐up) Univariable and multivariable logistic regression was performed to identify predictors of aneurysm persistence, periprocedural complications, and adverse events during follow‐up.

Results

Between October 2022 and January 2024, 73 patients harboring 91 intracranial aneurysms were treated in 76 interventions at 6 centers in Medellin, Colombia. Pipeline Vantage Embolization Device placement was technically successful in all patients. Most aneurysms (85.7%) were located at the anterior circulation, and the mean diameter was 6.7 mm. At 6 months, 56 of 70 (80%) aneurysms showed a complete occlusion and one year follow up revealed a complete occlusion in 56/63 (89.2%) Bifurcation aneurysms (odds ratio, 5.66; 95% CI, 1.01‐31.77) and the presence of a branch arising from the sac (odds ratio, 6.36; 95% CI, 2.11‐22.36) predicted persistence. A mild Neointimal hyperplasia (i.e < 25%) was evidenced in 10/63 (15.8%) and significant (i.e >50%)in 3/63. Of the 73 enrolled patients, 69 (94.5%) were treated without serious adverse events during the procedure or during the follow‐up. No mortality procedural related.

Conclusions

The treatment of intracranial aneurysms using the novel Pipeline Vantage Embolization Device was safe and effective. Our findings in terms of complete occlusion rates were similar to those seen in previously published studies with flow diverter devices and earlier generation Pipeline devices.
Abstract 077: Bilateral medial medullary infarction mimicking Guillain‐Barré Syndrome (GBS): Case report and qualitative systematic review
Authors: Chirinos J. M. Sequeiros , Alva-Diaz C. , Quispe-Vicuña C. , Salvador-Oscco E. , Capcha-Jimenez U. , Javier-Murillo N. , Guerrero-Yrene M. , Padilla-Santos M. , Saiki S. , Uribe-León A. , Terry F. , Geldres-Aranibar R. , Mori N.
Published: January 2025

Purpose

To summarize the medical literature related to the diagnosis of bilateral medial medullary infarction (MMI) mimicking GBS.

Methods

We identified all published case studies in five databases until February 2024. We performed a narrative synthesis to develop differential criteria on the included cases. A case report is also presented.

Results

We present the case of a patient with asymmetric and progressive motor weakness, bulbar dysfunction, albuminocytologic dissociation in cerebrospinal fluid (CSF), and negative brain CT scan in the acute stage. He was initially diagnosed with Guillain‐Barré Syndrome (GBS), treated with immunoglobulin without a favorable response, finally the diagnosis of MMI was made with re‐evaluation during the evolution and confirmed by brain magnetic resonance imaging. A systematic review of the literature of MMI case reports was carried out, focusing on an initial diagnosis of Guillain‐Barré Syndrome. We selected 8 studies (9 patients) of bilateral MMI with problems in the timely diagnosis and initial diagnosis of GBS. The most frequent clinical onset was respiratory problems (44.4%). The finding in CSF and nerve conduction studies were normal or negative in 60% of the cases. The delay occurred in the early stages of diagnosis in all cases. The use of immunosuppressive therapy was given in only one case. A discussion of the case report and the diagnostic challenges reported in the literature was made.

Conclusion

It is recommended to consider MMI for differential diagnosis in patients with symptoms of acute progressive quadriparesis and bulbar dysfunction, therefore a thorough assessment of the clinical presentation is necessary.
Abstract 078: Caresto heal: First multicenter experiences with a new 3rdgeneration carotid stent
Authors: Jansen O. , Nordmeyer H. , Schild D. , Wodarg F.
Published: January 2025

Introduction

The CARESTO heal is a coated carotid stent aiming to support atherosclerotic plaques by using a dense single‐layer mesh. Due to its great flexibility, it easily navigates through tortuous anatomies. Additionally, the CARESTO features the anti‐thrombogenic HEAL coating.

Aim of Study

The objective of this study is to examine the technical specifics, advantages, and possible obstacles associated with the innovative stent design of the CARESTO heal.

Method

The first CARESTO implantations including data on procedural safety and efficacy have been retrospectively analyzed. Pre‐treatment carotid plaque characterization was performed. For elective cases double antiplatelet medication was administered while acute cases were treated under Aspirin only.

Results

66 patients from ten European neurovascular centers have been treated, including Carotid Webs and ICA dissections. The mean age was 68 years with a median degree of pre‐treatment stenosis of 63%. Mean post‐treatment stenosis was 10% with a technical success rate of 100%. One peri‐procedural retinal ischemia occurred, but no other severe complications have been observed. Already available six weeks and six months ultra sound follow up showing no recurrence of stenosis nor new neurological events.

Conclusion

This multicenter study shows that the CARESTO heal Stent is both safe and effective in treating carotid stenosis. Additional analysis with full follow‐up data will offer thorough insights into the stent's long‐term safety and efficacy. The carotid stenting technique using the CARESTO heal differs technically from other carotid stents but is particularly advantageous in challenging, tortuous vessel anatomies and in the treatment of highly vulnerable plaques.
Abstract 123: Microcatheter Guided Blood Patch for Treatment of Cervical Cerebrospinal Fluid Leak
Authors: Tolba H. , Fakih R. , Khan M. , Qureshi A. I.
Published: January 2025

Introduction

Epidural blood patch (EBP) remains the therapy of choice in treating refractory headaches due to low cerebrospinal fluid (CSF) pressure. If a CSF leakage source is detected, targeted fluoroscopy‐guided EBP should be considered over non‐targeted (blind) technique. Cervical CSF leakage can be challenging to treat with targeted EBP given the high‐risk site.

Methods

We present a case of microcatheter‐guided targeted cervical EBP. A 44‐year‐old male with no significant past medical history presented with 4 weeks history of refractory headaches upon sitting and standing up. MRI brain showed bilateral subdural hygromas alongside diffuse pachymeningeal enhancement. A spinal myelogram showed evidence of a CSF leak at C4‐C5 level.

Results

The patient was placed in prone position to access the space between the spinous processes of L2 and L3 vertebrae. A 14‐gauge 6‐inch needle was then inserted at the interlaminar space, and CSF was observed. The needle was then exchanged over a microwire with a 4F introducer sheath under fluoroscopic guidance. Once the sheath was confirmed to be in the epidural space, a 0.014‐inch microwire was introduced and advanced into the cervical region. A 0.021‐inch ID microcatheter was advanced over the wire and parked at the C5‐C6 level. Then, 10cc of autologous blood mixed with Omni opaque contrast was injected through the microcatheter into the epidural space at the C5‐C6 level. Dyna CT demonstrated blood layering in the epidural space both anteriorly and posteriorly to the Dural sac, covering the entirety of the cervical region. Patient reported an instant relief of headache during the EBP and continued to be headache‐free by the time he was discharged.

Conclusion

We illustrated fluoroscopy‐guided microcatheter‐assisted EBP as an effective treatment of intracranial hypotension due to cervical CSF leak.
Abstract 138: Robotics in Mechanical Thrombectomy. Colombian Feasibility Experience Using the New Adaptive Tiger Device. First in Human Study (FIM)
Authors: Pabon B. , Torres V. M. , Vergara J. , Mutis J. , Brunet F. , Cardozo M. , Arteaga J. , Vargas G. , Pelaez F. , Patino M.
Published: January 2025

Purpose

The Adaptive Tiger is a novel radially adjustable stent retriever technology for Large Vessel Occlusion (LVO), The unique controllability of adaptive Tiger allows for employing a robotic controller to expand and relax the mesh automatically, using real‐time force measures to react accordingly for maximal encapsulation of the clot, and optimal radial forces during retrieval.The objective of this Registry Study is to evaluate the performance of the new Adaptive Tiger in restoring blood flow in patients with LVO who are ineligible for intravenous tissue plasminogen activator (IV t‐PA) or who fail IV t‐PA therapy.

Materials and Methods

A novel programmable electro‐mechanical sensor/controller is coupled with a Tigertriever. The sensor/controller automatically executes the operational phases and the optimal opening and closing of mesh throughout each phase. Five patients with AIS and LVO were consented and treated with Robotic Tiger.

Results

A total of 5 Adaptive Tiger devices were used. All cases with LVO secondary to MCA occlusion. The Adaptive Tiger console operated as intended in all passes. Using force measurements in real‐time and advanced control algorithms, the console expanded the mesh automatically up to wall opposition, executed the active integration technique, and relaxed the mesh for optimal clot retrieval. A final revascularization TICI > 2b‐c, 3 was obtained in all the cases at the end of the procedure. Non‐Major adverse events procedural related were registered in this small series.

Conclusion

This First ever experience with Robotic Tigertriever demonstrates the feasibility of utilizing robotically‐controlled Tigertriever technology for automatic thrombectomy easily and safely.