bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6032: Exploiting metabolic vulnerabilities of ovarian cancer with upregulated succinate dehydrogenase
Authors: Wang Lin , Bulicz Magdalena , Mucha Patryk , Kinter Michael , Pranay Atul , Griffin Timothy M. , Miller Benjamin F. , Bieniasz Magdalena 
Published: June 2023

Abstract
Ovarian cancer remains the deadliest of all gynecologic malignancies nationwide due to limited therapeutic options and chemotherapy resistance. The response to chemotherapy is substantially influenced by the high metabolic flexibility of ovarian cancer cells, which allows the cells to reprogram their metabolism and survive the treatment. Better understanding mechanisms regulating ovarian tumor metabolism could be exploited to develop new improved therapies. Our work demonstrated that the upregulation of mitochondrial enzyme succinate dehydrogenase (SDHA) is particularly prevalent (~20% of patients) in ovarian carcinoma and contributes to high energy tumor metabolism and cell survival. We observed that SDHA overexpressing ovarian cancer cells showed improved ability to survive and generate colonies in anchorage-independent conditions, which is an important feature of ovarian tumor cells surviving and spreading in peritoneal fluid (ascites). Proteomics data revealed that the SDHA overexpressing tumor cells showed reduced levels of proteins promoting anaerobic glycolysis (LDHA and HIF1α), and increased levels of mitochondrial pyruvate carrier (MPC) proteins. In addition, our tracer-based metabolomics data revealed that the elevated SDHA stimulates glutaminolysis by increasing mitochondrial glutamine supply fueling the TCA cycle with essential metabolites. We also demonstrated that the overexpression of SDHA is associated with a significant increase of OXPHOS and ATP production rate. Further, we reasoned that the SDHA overexpressing tumor cells could be particularly vulnerable to drugs disrupting glucose and/or glutamine metabolism. We performed a drug screening and identified an anti-metabolic compound shikonin known to disrupt glucose and amino acid metabolism. In in vitro studies, shikonin exhibited a profound anti-tumor efficacy and selectivity towards SDHA overexpressing tumor cells superior to that observed with chemotherapy. Importantly, our in vivo study validated the in vitro observations, and showed that shikonin is highly effective in suppressing SDHA overexpressing patient-derived tumor growth. In summary, the unique metabolic state of ovarian cancer associated with SDHA amplification could be successfully targetable offering a potential new treatment strategy for ovarian cancer patients.
Citation Format: Lin Wang, Magdalena Bulicz, Patryk Mucha, Michael Kinter, Atul Pranay, Timothy M. Griffin, Benjamin F. Miller, Magdalena Bieniasz. Exploiting metabolic vulnerabilities of ovarian cancer with upregulated succinate dehydrogenase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6032.
Abstract 6284: SUV420H1 as a novel target in HPV-negative head and neck squamous cell carcinoma
Authors: Moshiri Arfa , Cheng Hui , Kim Sohyoung , Saloura Vassiliki 
Published: June 2023

Abstract
Human Papilloma Virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type in the world and its outcomes are mostly unchanged for the past few decades, especially for HPV-negative HNSCC. The TCGA recently revealed a plethora of genetic alterations in chromatin modifiers in HPV-negative HNSCC, including protein lysine methyltransferases which methylate lysine residues on histone tails and regulate gene expression. One of these enzymes, SUV420H1, is known to trimethylate H4K20 and is recurrently amplified in approximately 6% of HPV-negative HNSCC tumors (TCGA). It has also been found to be significantly overexpressed in multiple HNSCC cell lines compared with normal keratinocytes. This study aims to investigate whether SUV420H1 has oncogenic activity and could be a novel therapeutic target in HPV-negative HNSCC. To evaluate the effect of SUV420H1 depletion on HPV-negative HNSCC cell lines, siRNA-mediated knockdown was performed in four SUV420H1 overexpressing HPV-negative HNSCC cell lines, and MTT assays showed significantly reduced cell viability by approximately 80-90% after 12 days of siRNA treatment. Colony formation assays, cell cycle analysis and apoptosis assays are ongoing, and these assays are planned in SUV420H1 CRISPR KO cell lines. Gene Set Enrichment Analysis in 434 HPV-negative HNSCC tumors (TCGA) showed significant enrichment of immune signatures, EMT, cell cycle and apoptosis pathways. Ongoing experiments aim to investigate the effects of SUV420H1 knockdown on the global histone methylome, and to identify direct downstream targets of SUV420H1 through combined genome-wide mapping of SUV420H1 using CUT&RUN assays and RNA-seq in HPV-negative HNSCC cell lines. Syngeneic and xenograft mouse models are also planned to evaluate the effect of SUV420H1 depletion on flank tumor growth in vivo. These studies may elucidate the oncogenic effects and mechanisms of SUV420H1, and may provide evidence to support SUV420H1 as a potential novel target in the treatment of HPV-negative HNSCC tumors with SUV420H1 amplification or overexpression.
Citation Format: Arfa Moshiri, Hui Cheng, Sohyoung Kim, Vassiliki Saloura. SUV420H1 as a novel target in HPV-negative head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6284.
Abstract 6307: A novel pegylated bispecific antibody-drug conjugate (P-BsADCpb-adc) targeting cancers co-expressing PD-L1 and CD47
Authors: Liu Shumin , Lyu Weidong , Yin Shuqiang , Lei Yang , Zhuo Qiudong , Zheng Liling , Sun Bin , Tan Shuangyu , Jiang Lidong , Zhang Teng , Gao Bo , Xu Rui , Huang Dechang , Li Yong , Wu Zibin , Wu David , Wen Yvonne (Yu) 
Published: June 2023

Abstract
ADCs have demonstrated improved efficacy and target selectivity comparing to the non-specific small molecule cytotoxicity drugs in cancer treatment. Yet, in solid tumor therapies, effort for further improvement of efficacy and safety has been hindered by the poor tumor penetration of conventional IgG based ADC, low internalization efficiency, undesired efflux of ADC from tumor cells, narrow therapeutic window due to the on-target/off tumor and Fc induced toxicity, etc. To address those issues, we previously reported that the compound JY201, a Polyethylene Glycol (PEG)-based bispecific ADC (P-BsADC) targeting two epitopes of Her2, demonstrated advantages in tumor penetration, internalization efficiency, lysosome trafficking, no Fc related toxicity, and better efficacy in tumor inhibition than transtuzumab deruxtecan (Ds-8201). In this study, we reveal another novel pegylated P-BsADC (JY207) formed by site-specific conjugation of a bispecific single chain fusion protein targeting PD-L1 and CD47 with PEG-MMAE (a pegylated cytotoxic payload MMAE). As expected, the compound JY207 retains all the advantages that JY201 possesses. Furthermore, JY207 does not bind to human red blood cells, but preferentially binds to CD47/PD-L1 double positive tumor cells, thus reduces the possibility of on-target toxicities. In vitro cytotoxicity studies showed that JY207 has strong potencies in CD47/PD-L1 double positive tumor cells, while showing almost no killing effect to CD47 or PD-L1 single positive tumor cells. In CDX models and a PDX model of transplanted tumor tissues from lung cancer patients, the compound demonstrated excellent tumor inhibition at low doses. In an in vitro plasma stability test, JY207 displays high stability in cynomolgus monkey and human serums. Preliminary repeated-dosing toxicological study has found the maximum tolerated dose of JY207 in CD47/PD-L1 double transgenic mice is 50mg/kg. In vivo pharmacokinetics and toxicological studies of JY207 are being conducted in cynomolgus monkeys and are expected to show desirable results. All those findings in this study warrant JY207 as a promising candidate for the clinical development for patients with CD47/PD-L1 double positive cancers.
Citation Format: Shumin Liu, Weidong Lyu, Shuqiang Yin, Yang Lei, Qiudong Zhuo, Liling Zheng, Bin Sun, Shuangyu Tan, Lidong Jiang, Teng Zhang, Bo Gao, Rui Xu, Dechang Huang, Yong Li, Zibin Wu, David Wu, Yvonne (Yu) Wen. A novel pegylated bispecific antibody-drug conjugate (P-BsADCpb-adc) targeting cancers co-expressing PD-L1 and CD47. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6307.
Abstract 6334: VBI-002, a CD47xICAM-1 bispecific antibody for the treatment of hepatocellular carcinoma, melanoma and non-small cell lung cancers
Authors: Wong Oi Kwan , Wang Xinhua , Post Leonard , Chen Xiaocheng 
Published: June 2023

Abstract
Intercellular Cell Adhesion Molecule 1 (ICAM-1, CD54) is a type I transmembrane protein and a member of the immunoglobulin superfamily. ICAM-1 is involved in many key processes such as cell-cell interactions, signal transduction and leukocytes trans-endothelial migration. ICAM-1 is constitutively present at low levels on healthy tissues but highly expressed in some hematological cancers and solid tumors, making it an attractive tumor target.
VBI-002 is a novel human IgG1 based CD47xICAM-1 bispecific antibody with excellent safety profile and potent single agent activities in xenograft models of lymphoma, multiple myeloma and some solid tumors (Cancer Res 2022;82(12_Suppl):Abstract nr 3430). The bispecific design allows VBI-002 to selectively block CD47/SIRPα binding in tumor cells with high ICAM-1 expression. In contrast to the benchmark CD47 monoclonal antibody, VBI-002 exhibits minimal red blood cell binding and does not cause hemagglutination. In non-human primate (NHP) safety study, four weekly doses of 60 mg/kg VBI-002 were well-tolerated with only mild and reversible reduction in hemoglobin and platelets.
Here we further investigate the anti-tumor activities of VBI-002 in solid tumors. Gene expression analysis suggested that ICAM-1 is highly expressed in non-small cell lung cancers (NSCLC), melanoma and a subset of hepatocellular carcinoma. Flow cytometry studies confirmed the frequent co-expression of ICAM-1 and CD47 in these tumors. VBI-002 has potent ICAM-1 dependent SIRPα blocking, antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity activities against cell lines of NSCLC, hepatocellular carcinoma, and melanoma. Furthermore, in vivo efficacy studies demonstrated that VBI-002 has potent single agent activities in cell line derived xenograft (CDX) models of NSCLC, hepatocellular carcinoma, and melanoma. Weekly dose of 20 mg/kg VBI-002 is sufficient to stop tumor growth or drive tumor regression in most models. Notably, VBI-002 is highly effective against NSCLC CDX models carrying Kras mutation and it synergizes with paclitaxel to provide additional anti-tumor activity. In conclusion, VBI-002 is a versatile novel CD47xICAM-1 bispecific antibody with potent single agent activity in various solid tumors and combined well with standard of care chemotherapies for added activity. Thus, VBI-002 warrants clinical evaluations as a single agent and in combination with standard of care chemotherapies.
Citation Format: Oi Kwan Wong, Xinhua Wang, Leonard Post, Xiaocheng Chen. VBI-002, a CD47xICAM-1 bispecific antibody for the treatment of hepatocellular carcinoma, melanoma and non-small cell lung cancers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6334.
Validation of the National Institutes of Health Stroke Scale in Intracerebral Hemorrhage
Authors: Dusenbury Wendy , Tsivgoulis Georgios , Chang Jason , Goyal Nitin , Swatzell Victoria , Alexandrov Andrei V. , Lyden Patrick , Alexandrov Anne W. 
Published: June 2023

Background
We sought to determine if the National Institutes of Health Stroke Scale (NIHSS) has a greater discriminative power than Glasgow coma scale (GCS) to identify patients at risk of poor early functional outcomes and large hematoma volumes.

Methods

We prospectively collected clinical assessments, imaging, and outcome data in consecutive patients with intracerebral hemorrhage, and determined the ability of GCS and NIHSS to predict poor functional outcome (modified Rankin scale 3–6) and hematoma volume >30 cm
3
using receiver operating characteristics analysis, C‐statistics, and the DeLong test.

Results

We studied 672 patients with intracerebral hemorrhage (mean age 62±14 years; 56% men; median intracerebral hemorrhage score=1, interquartile range (IQR) 0–2; median intracerebral hemorrhage volume 7 cm
3
, IQR 2–19) with median NIHSS of 8 (IQR 3–18) and GCS 15 (IQR 7–15). NIHSS correlated strongly to GCS (r=−0.773;
P
<0.001). Admission NIHSS (C‐statistic: 0.91; 95% CI, 0.89–0.93) predicted better than GCS (0.78; 95% CI, 0.75–0.81) discharge poor functional outcome (DeLong test
P
<0.001). NIHSS (0.82; 95% CI, 0.78–0.86) also discriminated better than GCS (0.78; 95% CI, 0.73–0.83) patients with large hematoma volume (DeLong test
P
=0.029).

Conclusion
The NIHSS has a greater discriminative power than GCS to identify patients at risk of poor early functional outcomes and large hematoma volumes.
Who Were the Gods of Panamuwa I?
Authors: Dušek Jan 
Published: June 2023

Abstract
Panamuwa I, king of Samʾal/Yʾdy, commissioned a statue of Hadad in approximately the second quarter of the eighth century BCE. The inscription on the statue, written in the Samʾalian language, contains four lists of gods. In lines 2–3 and 18–19, these gods are Hadad, El, Rešef, Rākib-El, and Šamaš. The list in line 11, however, contains a theonym that is not attested in the other three lists; it is usually read Arqû-Rešef. A collation of the inscription yields a new reading and interpretation of the text in line 11 that sheds light not only on the identity of the enigmatic Arqû-Rešef, but also on the whole list of gods in line 11.
‘As Far as the East Is from the West, and the North Is from the South’
Authors: Cherkashina Anna 
Published: June 2023

Abstract
This article continues a series of studies dedicated to Syriac love magic as attested by texts found in Syriac magical codices dated to the 18th–20th century. Here I address five Syriac recipes that I consider to belong to the category of separation spells. Four of them are titled ‘For Hatred’ and are edited for the first time. Another one can be found in The Nestorians and Their Rituals and exists only in the English translation provided by G.P. Badger. Based on their supposed proto-text, the five texts can be divided into three spells. The separation spells are also compared with Syriac spells for attraction. The comparison involves the textual level as well as the magical practices for inducing hatred or love. In the third section of the article, I address the phenomenon of Syriac hate spells in a wider context by providing parallels from Jewish, Coptic, Mandaic, and Arabic magical traditions.
A Jewish Aramaic Circus Curse Tablet from Antioch
Authors: Folmer Margaretha , Elitzur-Leiman Rivka 
Published: June 2023

Abstract
In this contribution we publish a lead circus curse tablet written in Jewish Palestinian Aramaic (Princeton Art Museum excavation no. 3608-I57). The tablet was found in 1935 during excavations near the first turning-post at the hippodrome of Antioch on the Orontes (modern-day Antakya, Turkey). The use of Greek and Latin defixiones agonisticae (agonistic binding spells) in chariot races was a wide-spread phenomenon during the Roman Byzantine Period. Curse tablets were inscribed with aggressive incantations that aimed at the defeat of rivals in the chariot races. The tablet under discussion is a unique piece: It is the only known lead circus curse tablet that was written in a Jewish language and script. The tablet is datable to the fifth or sixth century CE.
Blue Berets, Burning Brushfires
Authors: Adebajo Adekeye 
Published: June 2023

Abstract
This article makes three important arguments. The first is that one of the most crucial factors in explaining the various outcomes of UN peacekeeping cases over the past seventy-five years can be found in the role of contingencies: the idiosyncratic circumstances that have combined to enable success or failure. The second is that these peacekeeping missions critically demonstrate the importance of focusing attention on the significant role of key domestic, regional, and external actors. The third is that contingencies at these three important levels, rather than any established security patterns or theories, are often the most critical factors in explaining the outcomes of UN peacekeeping missions over the past seven and a half decades. The choices of national and regional actors as well as external great powers often shape how these missions start, develop, and end. Examining interests and motivations in detail thus helps explain how and why UN peacekeeping missions have succeeded or failed.
Retaining Flexibility
Authors: Drohan Brian 
Published: June 2023

Abstract
Although UN peace operations began with unarmed observer missions in 1948–1949, the first armed force—the UN Emergency Force (UNEF)—was deployed in 1956 due to the Suez crisis. Scholars and practitioners have since interpreted the UN Secretariat’s 1958 study of that experience, called the Summary Study, as a foundational text in the history of UN peacekeeping because it supposedly codified the key principles of impartiality, nonuse of force, and consent. But much of the Summary Study’s origin story is inaccurate or unknown. By explaining Secretary-General Dag Hammarskjöld’s intentions for the study, as well as how those intentions changed, this article argues that far from “codifying” foundational principles, the Summary Study did the opposite: it ensured that future peacekeeping operations would continue on an ad hoc, flexible basis that permitted the Secretary-General and Member States to exercise a wide range of discretion in determining how to conduct future operations.
Challenges in and Opportunities for International Collaboration: Costing Flood Damages and Losses across Canada, Mexico, and the United States
Authors: Adeel Zafar , Bakkensen Laura , Cabrera-Rivera Orlando , Franco Ernesto , Garfin Gregg M. , McPherson Renee A. , Méndez Karla , Wen Xin 
Published: June 2023

Abstract
Flooding, including inland and coastal flooding, is one of the most devastating and costly natural hazards in Canada, Mexico, and the United States. Recent research conducted by an international team has focused on understanding the true and comprehensive economic costs of floods, with an eye toward addressing their impacts, allocating adequate resources for monitoring and preparedness, and building resilient communities. Flood-costing methods vary greatly among federal and subnational jurisdictions across the three North American countries. Because the rigor and consistency of existing datasets across the three countries vary significantly, it is also difficult to determine the economic impacts of cross-border events. This paper aims to critically analyze the research methods used to conduct this trinational project and develop recommendations for enhancing impacts of such work in the future. We discuss three major research barriers: gaps in knowledge and research capacity, differences in data collation and analysis methods across the three countries, and linguistic barriers in working across disciplines and economic sectors. We also explore how the COVID-19 pandemic significantly added to these three barriers. We propose creation of new institutional mechanisms that can play a major role in developing comprehensive, consistent, and cohesive data gathering approaches in Canada, Mexico, and the United States.
Did stopping ultrasound surveillance during COVID-19 result in an increase of the dialysis access thrombosis rate?
Authors: Allsopp Karen , Smith Lindsay 
Published: June 2023

Purpose: The COVID-19 pandemic resulted in cessation and subsequent reduction of routine care including the outpatient ultrasound surveillance of AVF. This un-planned service disruption allowed evaluation of effectiveness of US surveillance in reducing AVF/AVG thrombosis. Methods: This study was a secondary data analysis of monthly access patency for all in-centre patients receiving haemodialysis using an AVF or AVG over a 2-year period (April 2019-March 2021). The study included 298 patients with age, access type, patency and COVID status measured as variables. Thrombosis rates for the 12 months prior to COVID-19 and then during the first 12 months of the pandemic were also measured. Statistical analysis to assess mean and standard deviation for relevant variables was used. A p-value of <0.05 was deemed significant. Results: At the end of the study an increase in thrombosis rate (%) in the non-surveillance year was observed ((1.20) thrombosis/patient/year in the surveillance group vs (1.68) thrombosis/patient/year in the non-surveillance group). Monthly mean of thrombosed access during surveillance ( M = 3.58, 95% CI 2.19–4.98, SD = 2.193) and non-surveillance ( M = 4.92, 95% CI 3.52–6.31, SD = 2.19); t(7148) = 2.051, p = 0.038. Conclusion: Reduction in routine Ultrasound surveillance following the COVID-19 pandemic was associated with a significant increase in access thrombosis rate. Further research is needed to unpick whether the associations seen were directly due to service changes, associated with COVID-19 or other factors during the pandemic. This association was independent of SARS-CoV-2 infection status. Clinical teams should consider alternative service delivery options including out-reach, bedside surveillance to balance risks of access thrombosis versus reducing the risk of nosocomial infection with hospital visits.
Magnitude of Incapability and Pain Intensity are Associated More with Unhelpful Thoughts Than Stressful Life Events
Authors: Broekman Melle M , Brinkman Niels , Ramtin Sina , Ngoue Marielle , Ring David , Jayakumar Prakash 
Published: June 2023

Prior studies show that stressful life events are associated with greater magnitude of incapability and symptom intensity. We sought to understand the association of such events (i.e., both adverse childhood experiences and recent difficult life events [DLEs]) alongside feelings of worry or despair and unhelpful, on the magnitude of incapability and symptom intensity in musculoskeletal patients. One hundred and thirty-six patients presenting for musculoskeletal specialty care completed measures of incapability, pain intensity, adverse childhood experiences, DLEs in the last year, unhelpful thoughts, symptoms of anxiety and depression, and sociodemographic factors. Factors associated with the magnitude of incapability and pain intensity were sought in multivariable analysis. Accounting for potential confounders, greater incapability was associated with greater unhelpful thoughts (RC  =  −0.81; 95% CI  =  −1.2 to −0.42; P  ≤  .001), but not with stressful life events (either during childhood or more recently). Greater pain intensity was associated with greater unhelpful thoughts(RC  =  0.25; 95% CI  =  0.16 to 0.35; P  ≤  .001) and being divorced or widowed (RC  =  1.8; 96% CI  =  0.43 to 3.2; P  =  .011), but again, not with stressful life events. The strong association of unhelpful thoughts with magnitude of incapability and pain intensity can motivate musculoskeletal specialists to anticipate patients expressing negative pain thoughts and behaviors. Future studies might account for social and environmental context behind stressful life events and the influence of resiliency and pain-coping strategies on these interactions. Level of Evidence: Level III, prognostic study