bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B047: Monitoring treatment response and toxicity in BRAF V600-mutant metastatic melanoma with circulating cell-free DNA
Authors: Jain Sidharth S , Patrick IV McDeed A. , McNamara Megan E , Alley Amber R , Rosenstrauch Dori S , Sun Harry , Thompson Natalie , Kirkwood John M , Gibney Geoffrey T , Atkins Michael B , Wellstein Anton 
Published: November 2024

Abstract
Background: The DREAMseq trial (EA6134, NCT02224781) was a national multi-center randomized phase III trial coordinated by ECOG-ACRIN that found that immune checkpoint inhibitor (IO) treatment achieves improved survival outcomes compared to targeted therapy (TT) in patients with BRAF V600-mutant metastatic melanoma. Still, approximately 40% of patients do not respond to IO, and existing biomarkers fail to distinguish this subset of patients who do not benefit from IO therapy. Additionally, as many as 80% of patients may experience immune- related adverse events (irAEs), which range from mild dermatological symptoms to life- threatening myocarditis. Here, we explore the use of the methylation status of cell-free DNA (cfDNA) in serially collected blood samples to measure response and toxicity in the context of IO- and TT-treated metastatic melanoma. Methods: Serial serum samples were collected from patients with BRAF V600-mutant metastatic melanoma treated with ipilimumab/nivolumab (IO) or dabrafenib/trametinib (TT). Circulating cfDNA was isolated from serially collected serum samples, enriched for regions of interest by hybridization capture and sequenced using enzymatic methyl-seq. Cell-type deconvolution was performed to determine the abundance of cell type- specific methylation patterns of cfDNA molecules in patient serum at different time points of treatment. The BRAF V600 mutation abundance in total cfDNA was also assessed. Results: We identified melanocyte lineage-specific DNA methylation regions and demonstrate that the methylation status of these regions remains conserved in malignant melanoma. We characterized the changes in abundance of the melanocyte-lineage cfDNA over the course of treatment and show that these changes distinguish responders from non-responders to either IO or TT. Furthermore, we track the abundance of cell type-specific DNA from normal tissues to identify markers indicative of adverse effects or disease progression. Conclusions: We established melanocyte-lineage methylation markers and evaluated the use of cell-type specific DNA methylation to monitor treatment effects of immune checkpoint or BRAF/MEK inhibitors in metastatic melanoma using serially collected blood samples.
Citation Format: Sidharth S Jain, A. Patrick IV McDeed, Megan E McNamara, Amber R Alley, Dori S Rosenstrauch, Harry Sun, Natalie Thompson, John M Kirkwood, Geoffrey T Gibney, Michael B Atkins, Anton Wellstein. Monitoring treatment response and toxicity in BRAF V600-mutant metastatic melanoma with circulating cell-free DNA [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B047.
Abstract B067: Dynamic chromatin landscapes of colorectal cancer development and cell-free DNA fragmentation
Authors: Vulpescu Nicholas A. , Foda Zachariah H. , Wisse Pieter H.A. , Cherry Christopher , Medina Jaime E. , Adleff Vilmos , Fijneman Remond J.A. , Scharpf Robert B. , Meijer Gerrit A. , Carvalho Beatriz , Velculescu Victor E. 
Published: November 2024

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR016) of the Conference Program/Proceedings.
Citation Format: Nicholas A. Vulpescu, Zachariah H. Foda, Pieter H.A. Wisse, Christopher Cherry, Jaime E. Medina, Vilmos Adleff, Remond J.A. Fijneman, Robert B. Scharpf, Gerrit A. Meijer, Beatriz Carvalho, Victor E. Velculescu. Dynamic chromatin landscapes of colorectal cancer development and cell-free DNA fragmentation [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B067.
Abstract B068: Inferring enhancer activity from cell-free DNA fragmentation patterns
Authors: Yang Alexis 
Published: November 2024

Abstract
We present a framework for inferring enhancer activity from cell-free DNA (cfDNA) fragmentation patterns, offering a novel feature set for cfDNA analysis that reflects gene regulation. Enhancers are promoter-distal regulatory elements that regulate gene expression programs that define cell types and cellular states. Despite advances in inferring gene regulation in cancer using liquid biopsy, it remains challenging to identify signals of enhancer activity from cell-free DNA (cfDNA). Active enhancers are characterized by transcription of short enhancer RNAs (eRNAs). Recent studies demonstrated that cfDNA from promoters of transcribed genes demonstrates high variation in DNA fragment length, or “fragmentation entropy”. We tested whether eRNA transcription can be inferred based on cfDNA fragmentation entropy. We quantified “enhancer fragmentation entropy” (EFE) to profile enhancer activity in plasma by measuring Shannon entropy of cfDNA fragments around enhancer transcription start sites (TSS). Using PRO-cap data from lymphoblastoid cell lines, we analyzed EFE signals at 70,000 transcribed enhancers and observed distinct patterns between active (expressed) and inactive enhancers in cfDNA from healthy individuals. cfDNA from patients with prostate cancer showed elevated EFE at enhancers activated in prostate cancer. EFE at these sites correlated with circulating tumor DNA (ctDNA) levels in a published cfDNA dataset of 41 prostate cancer plasma samples. Lower-dimensional projections of the entropy signals across 300 “modules” of co-regulated enhancers revealed tighter clustering of samples within the same cancer type, suggesting that these entropy patterns capture cell-type specific enhancer activity. Our findings suggest that enhancer fragmentation entropy captures cell-type specific signals and, when measured at cancer-specific enhancers in cfDNA, could serve as a promising biomarker for cancer detection and monitoring. Ongoing work is focused on validating these findings in larger cohorts and applying EFE to cancer monitoring and clinical subtyping.
Citation Format: Alexis Yang. Inferring enhancer activity from cell-free DNA fragmentation patterns [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B068.
Abstract PR001: The CTC RPL/RPS gene signature: Targeting translation and the cell cycle inversely affects CTC metabolism but not metastasis
Authors: Marchetti Dario 
Published: November 2024

Abstract
Melanoma brain metastasis (MBM) is the most devastating consequence of melanoma, is increasing in frequency, and is linked to poor prognosis and dismal survival. By employing an unbiased, multipronged approach, we discovered a CTC gene signature for ribosomal protein large/small subunits (RPL/RPS) which associated with MBM onset and progression. Experimental strategies involved capturing, transcriptional profiling, and interrogating CTCs, either directly isolated from blood of melanoma patients at distinct stages of progression, from CTC-driven MBM in experimental animals, or by developing/applying the first MRI CTC- derived MBM xenograft model (MRI-MBM CDX) to discriminate MBM spatial and temporal growth, thus faithfully recreating its clinical presentation. Accordingly, we hypothesized that targeting CTC ribogenesis can prevent melanoma metastasis in general, MBM in particular. We treated CDX cohorts with FDA-approved protein translation inhibitor omacetaxine in the presence or absence of CDK4/CDK6 inhibitor palbociclib, and monitored metastatic development and cell proliferation. Necropsies and IVIS imaging showed decreased MBM/extracranial metastasis in drug-treated mice, and RNA-Seq on mouse-blood-derived CTCs revealed downregulation of four RPL/RPS genes of the CTC signature. Notably, by performing the first-ever functional metabolic characterization of circulating neoplastic cells/CTCs in real- time, coupled with confirmatory RT-qPCR, we found that omacetaxine and palbociclib inversely affected glycolytic metabolism, and demonstrated that dual targeting of cell translation and proliferation is critical to suppress plasticity in metastasis-competent CTCs. This study identifies the relevance of targeting the CTC RPL/RPS signature to suppress melanoma metastasis, and set forward notions for novel therapies to affect metastasis by the deregulation of translation controlling CTC states. Studies involving structural and mechanistic analyses of CTC dormant vs active ribosomes by cryogenic electron microscopy are in progress.
Citation Format: Dario Marchetti. The CTC RPL/RPS gene signature: Targeting translation and the cell cycle inversely affects CTC metabolism but not metastasis [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR001.
Abstract 4140084: A Case of Transient Cortical Blindness occurring during Percutaneous Transluminal Coronary Angiography for Acute Coronary Syndrome.
Authors: Adelakun Adeniyi , Farouji Iyad , haddad ahmad , Szwed Stanley 
Published: November 2024

Description of case:
A 55 yo man with no PMHx presented with a few hours of intermittent left-sided chest tightness.

Serial EKG revealed dynamic ST-T wave changes in lateral leads—Figure 1.
His lipid panel was abnormal, and the High-Sensitive Troponin T trended up—table 1.
Based on the hemoglobin A1C result of 10.6, he was newly diagnosed with DM.
Coronary angiography shows two vessel diseases. The left circumflex artery's first obtuse marginal artery branch (LCX-OM1) received a stent in the first instance.
During the planned PTCA for treatment of LAD 48 hours after, he developed sudden bilateral loss of vision while on the table just before stent deployment.
In this case, with the emergence of the symptom of vision loss, PTCA was halted to allow the operator to rule out an acute cerebrovascular accident (CVA) through urgent CT head and MRI brain scans.
He consented to complete the LAD PTCA the day after, which achieved the intended restenosis without complications.

Discussion:
Bilateral transient cortical blindness (TCB) is a reversible syndrome of vision loss affecting both eyes in the presence of normal visual pathways due to a brief disturbance in the occipital cortices. TCB is more commonly associated with cerebral angiography but has been rarely reported after coronary angiography.

Angiographic contrast toxicity is one of the proposed pathophysiologic mechanisms. During our case, approximately 30 mL of iohexol was used before TCB, while about 120 mL of iodixanol was used for the repeat and conclusive procedure.
We are not aware of a previous report in which PTCA was recommenced hours after being halted due to TCB in a patient suffering acute coronary syndrome.
The absence of symptom recurrence when the PTCA was recommenced, which underscored the benign nature of TCB, enabled the patient to receive conclusive, definitive treatment for his acute coronary condition.
Abstract 4140419: Targeting Cardiac Fibrosis with Chimeric Antigen Receptor Neutrophils from Human Pluripotent Stem Cells
Authors: Jin Gyuhyung , Bao Xiaoping 
Published: November 2024

Cardiac fibrosis is a pathological hallmark of almost all forms of heart disease, characterized by excessive deposition of extracellular matrix (ECM) proteins by activated fibroblasts, leading to cardiomyocyte hypertrophy, arrhythmias, and heart failure. Current treatments, predominantly pharmacological, target signaling pathways involved in fibroblast activation but often come with side effects such as cardiac toxicities. There is a critical need for therapies that specifically target activated cardiac fibroblasts to mitigate these adverse effects.
Recent advances have shown that chimeric antigen receptor (CAR)-T cells targeting fibroblast activation protein (FAP), expressed by activated fibroblasts, can significantly reduce fibrosis and improve cardiac function in mouse models. However, CAR-T cell therapies face challenges such as the requirement for large quantities of healthy primary immune cells, lengthy process, and the high cost of personalized treatments. To address these issues, we propose an innovative strategy using off-the-shelf CAR-neutrophils derived from human pluripotent stem cells (hPSCs).
We hypothesize that hPSC-derived CAR-neutrophils engineered to target FAP will effectively reduce cardiac fibrosis and improve cardiac function post-injury due to their potent cytotoxic effects and ability to infiltrate infarct regions. To test this hypothesis, anti-FAP CAR hPSCs were generated by CRISPR/Cas9 genome editing and differentiated into neutrophils. The differentiated anti-FAP CAR hPSC-neutrophils exhibited molecular characteristics comparable to unmodified hPSC-neutrophils. We also established an in vitro cardiac fibrosis model utilizing a previously reported protocol for the generation of hPSC-derived epicardial fibroblasts. Importantly, our anti-FAP hPSC-neutrophils exhibited significant cytotoxicity against activated epicardial fibroblasts, while unmodified hPSC-neutrophils showed no/minimal killing efficiency.
This study suggests a proof-of-concept therapeutic approach against cardiac fibrosis utilizing FAP-targeting CAR-neutrophils. This strategy can potentially be adapted to treat fibrosis in other organs, thereby having a broad and significant impact on the treatment of various fibrotic diseases, ultimately contributing to longer, healthier human lives.
Abstract 4140763: A Case of Clozapine-Induced Myocarditis: An Under-described Side Effect
Authors: Ibrahim Rand , Clearo Kellie 
Published: November 2024

Case Descripton:
A 34-year-old male with Schizophrenia was transferred from inpatient Psychiatry unit for chest tightness, fevers andtachycardia after testing positive for COVID-19. Further history revealed antipsychotics had been recently adjusted with the addition of Clozapine 1 month prior to presentation.

On presentation, he was febrile (39.1°C) and tachycardic to the 146 in sinus tachycardiac on EKG and Telemetry. He was euvolemic on exam with tachycardia but no murmurs or discernable friction rub.
Labs revealed no leukocytosis but an elevated C-reactive protein (CRP) 168mg/L, high-sensitivity troponin (474ng/L) and brain-natriuretic peptide (BNP, 176 pg/mL, no baseline value). Otherwise, TSH, ANA and RF were normal. Repeat Respiratory Viral Panel, respiratory biofire and blood cultures were unrevealing. Imaging (CXR and Chest CTA) were normal. TTE showed normal function and small pericardial effusion. Cardiac MRI was limited by inability to tolerate the scan but reported preserved biventricular function. The home facility was contacted and reported initial COVID testing was expired and invalid. Psychiatry was consulted for suspected clozapine-induced myocarditis and recommending holding Clozapine while resuming Risperdione.
The patient reported subjective improvement in symptoms and return to baseline. Feversdefervesced and tachycardiac resolved.

Discussion:
Rare (0.06%-3.88% reported incidence) and not well-described, Clozapine-induced myocarditis can be a challenging entity to identify. In the literature, it is defined as having elevated CRP or detectable troponin and at least 1 sign or symptom of myocarditis, in the absence of alternative plausible etiologies. Symtoms typically onset between 1-4 weeks of medication initiation. Mortality can range between 10-30%. The acute history of symptoms, elevation in CRP and troponin shortly after medication initiation suggested a diagnosis of clozapine-induced myocarditis. The absence of reduction in systolic function and indeterminant MRI are nocompelling against clozapine-induced myocarditis in lieu of other more plausible diagnoses. Early cessation and symtpomatic managemnt is standard therapy.

Conclusion:
Clozapine-induced Myocarditis is an entity not well-described but carries a significant mortality risk. Perhaps cardiac-monitoring guidelines must be implemented in addition to the currently adopted montiroing for agranylocytosis with clozapine.
The Myth of a Bipartisan Golden Age for U.S. Foreign Policy: The Truman-Eisenhower Consensus Remains
Authors: Friedman Jeffrey A. 
Published: November 2024

Abstract
Scholars and practitioners of U.S. foreign policy commonly describe the early Cold War as a lost golden age of bipartisan consensus. This article uses public opinion data, congressional voting patterns, and party platform statements to refute this conventional wisdom. In fact, the core internationalist principles that enjoyed bipartisan agreement during the Truman and Eisenhower administrations retain widespread approval from Democrats and Republicans today. Enduring support for this Truman-Eisenhower consensus is concealed by the way that recent presidents have enlarged the United States’ foreign policy agenda to pursue policies that historically did not generate bipartisanship, such as fighting climate change or conducting decades-long projects in armed nation-building. Rising political divisions in U.S. foreign policy are thus primarily a result of Democrats and Republicans deploying global influence in new ways rather than renouncing traditional international commitments. These findings refute widespread claims that political polarization has undermined traditional conceptions of U.S. global leadership or depleted Washington's usable power.
Competing Visions of Restraint
Authors: Priebe Miranda , Schuessler John , Rooney Bryan , Castillo Jasen 
Published: November 2024

Abstract
At least since the U.S. invasion of Iraq in 2003, a subset of realists, conservatives, and progressives have called for greater restraint in U.S. grand strategy. Given that restraint is a key position in the grand strategy debate, this article explores the variations within restraint's big tent in greater detail. Drawing on writings by and interviews with advocates of restraint, we identify the underlying beliefs that have led these disparate groups to converge on restraint. We find that there are competing visions of restraint. Realists want to prevent the emergence of regional hegemons without provoking great power war; conservatives seek to preserve what they identify as the American way of life; and progressives are motivated by the desire to combat inequality and injustice at home and abroad. Even within each group, there are a range of underlying beliefs and foreign policy preferences, and more divisions have emerged in response to the Russian invasion of Ukraine and China's rise. We explore how these groups’ positions may evolve in the future as the threat environment continues to change and new policy questions emerge.
Needs and Potentials of Professional Diaspora Engagement in Knowledge, Skills and Technology Transfer in Ethiopia
Authors: Yesigat Abate , Bogale Mekonnen , Jibat Nega , Hadis Sebsib , Tafese Tibebu 
Published: November 2024

Abstract
This study was conducted with the aim of assessing the needs for knowledge, skills and technology transfer in Ethiopia and the potential of the Ethiopian professional diaspora to engage with these needs. To this effect, primary data was collected through key informant and group interviews, focus group discussions with ministries, universities, referral/teaching hospitals and other sector officials, and experts, selected purposively. In addition, primary data was collected through an online survey from the professional diaspora, selected using purposive and availability sampling techniques. Secondary data was collected from previous reports, academic works and archival sources. The results of this study show that most of Ethiopia’s institutions have enormous knowledge, skills and technology needs. Correspondingly, the data indicates that there is a large professional diaspora that could address these needs and that most of the professionals have the experience, interest and intent to support their home country. Based on the findings, there should be strong institutional arrangements and collaborative actions to facilitate and enhance professional diaspora engagement.
Between Representing a Story of Migration and Re-Imagining a Tale of Exoticism in Abdelkader Benali’s De Langverwachte
Authors: Baba Nouzha 
Published: November 2024

Abstract
In this article, I analyse the Moroccan-Dutch author Abdelkader Benali’s novel De Langverwachte (The Long-awaited, 2002), which narrates a story of migration from Morocco to the metropolitan city of Rotterdam. Through a close reading, I delve into the way the author employs exoticism as a particular practice of “cultural translation;” of seeing, speaking, and thinking onto migrant people as exotic Others. The novel represents migrant characters through exoticist cultural codes, among which: mystery, extraordinariness, strangeness, romantic fantasy, and superstition. Its mode of narration testifies to both a fascination with and a fear from the culturally unfamiliar and different Other. The narrator’s speculative representation of migrants’ cultural and mental world, both in their homeland and in the host society, reinforces the Other’s absolute difference, his unfamiliarity and strangeness. I argue, then, that the text represents a touching story of migration as if re-imagining a tale of exoticism.
The Arbitration Agreement from the Perspective of Qatari Law
Authors: El Farag Mohamed Salem Abou , Elgarhe Khaled 
Published: November 2024

Abstract
The arbitration agreement is the first stage of arbitration and the basis of the commitment of the parties to an arbitration. Arbitration is consensual by nature and cannot proceed without such an agreement. If there is no agreement to arbitrate, the disputing parties have no choice but to resort to the state courts to resolve their dispute. In this regard, the importance of the arbitration agreement becomes evident, as it requires several formal and substantive conditions for it to be valid. The consequences of the validity or otherwise of the arbitration agreement may include lack of jurisdiction, the non-extension of the arbitration agreement to third parties, and the ultimate invalidity of the arbitral award. Accordingly, this research will be dedicated to studying the arbitration agreement and its implications as provided by Qatar’s Arbitration Law No. 2 of 2017. The study will also analyze court judgments related to this agreement and its implications, both within Qatar and in other Middle-Eastern states that have adopted the uncitral Model Law on International Commercial Arbitration.
Introduction: Japonisme and Fashion
Authors: Emery Elizabeth , Rado Mei Mei 
Published: November 2024

Abstract
This introduction to a special issue dedicated to ‘Japonisme and Fashion’ evokes the influence of fashion within the field of Japonisme, sketches the history of the field, summarizes its recent developments, and outlines the issue’s contents. The modern sartorial practices and global fashion industry inspired by the styles, motifs, and concepts of Japanese dress shed new light on the inherent multiculturalism of Japonisme itself.