bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A027: Exploring autoantibody response to proteins encoded by prostate cancer driver genes
Authors: Zhang Jian-Ying , Qiu Cuipeng , Wang Xiao , Wang Bofei 
Published: December 2023

Abstract
Prostate cancer (PCa) is a complex disease driven by genomic alterations, and understanding the immune response to these alterations can provide valuable insights into the pathogenesis. This study aimed to explore the immunogenicity of proteins encoded by PCa driver genes and to further identify corresponding autoantibodies as potential biomarkers. Through a comprehensive screening process involving bioinformatics analysis based on published studies, a set of PCa driver genes was identified for further investigation. Three strategies were employed to identify candidate driver genes: (1) utilizing the IntOGen database (Martínez-Jiménez et.al, Nature Reviews Cancer 2020), nine cohorts comprising 1503 primary PCa patient samples were analyzed, resulting in the identification of 63 PCa driver genes, with the top 20 genes exhibiting high mutation rates and frequencies in these cohorts; (2) employing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, 16 driver genes that were enriched in prostate cancer pathways were identified from the initial 63 genes; (3) referring to a published article (Dietlein et.al, Nature Genetics 2020), the top 17 driver genes specific to prostate cancer across 28 tumor types were selected. A final set of 15 PCa driver genes, which appeared in at least two of the screening strategies, were included in subsequent analyses. To assess the presence of autoantibodies targeting proteins encoded by these 15 PCa driver genes, an enzyme-linked immunosorbent assay (ELISA) was performed. Autoantibodies to proteins encoded by the selected PCa driver genes were evaluated using serum samples from PCa patients and normal controls. The results revealed that seven out of the 15 autoantibodies showed significantly elevated levels in the sera of PCa patients compared to normal controls. Notably, the autoantibody targeting SPOP (speckle-type POZ protein) exhibited the highest frequency of 42.4%, followed by the autoantibody to PTEN (phosphatase and tensin homolog) at 37.4% in the PCa group. These findings suggest that proteins encoded by PCa driver genes may possess immunogenic properties, leading to the production of corresponding autoantibodies. The identification of specific autoantibodies associated with PCa driver genes could offer novel opportunities for the discovery of autoantibody-based biomarkers in prostate cancer. Further validation and characterization of these autoantibodies are warranted to evaluate their diagnostic or prognostic potential and elucidate their functional roles in PCa pathogenesis.
Citation Format: Jian-Ying Zhang, Cuipeng Qiu, Xiao Wang, Bofei Wang. Exploring autoantibody response to proteins encoded by prostate cancer driver genes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A027.
Abstract PR02: Lyn kinase regulates myeloid-cell responses to mammary tumors
Authors: Greene Joseph T , Brian Ben F , Bapat Aditi , Freedman Tanya S 
Published: December 2023

Abstract
Myeloid-cell enrichment in tumors is correlated with increased metastasis, reduced survival times, and poor treatment outcomes in multiple cancers, including breast cancer. Many signals (CSF, Il-6, chemokine) to myeloid cells in the tumor microenvironment are transduced through the Src-family kinase Lyn. Expression of both isoforms of Lyn (LynA and LynB) is regulated by cytokine signaling and cell type, and total Lyn expression is negatively correlated with breast cancer patient survival. Lyn expression in macrophages contributes to leukemogenesis, but the functional contributions of LynA and LynB in solid tumors have not been studied. We are examining the contributions of Lyn in trafficking of myeloid cells to mammary tumors, pro-tumor polarization of tumor-associated macrophages, and growth and metastasis of mammary tumors. In an E0771 orthotopic transplant model in hosts expressing or lacking LynA or LynB expression, we have discovered that Lyn expression in the mammary tumor microenvironment promotes the early recruitment of monocytes, macrophages, neutrophils, and dendritic cells, as determined by flow cytometry analysis of tumors early in development. Furthermore, Lyn promotes pro-tumor polarization of tumor-associated macrophages. Tumors from Lyn knockout animals contained populations of inflammatory, anti-tumor macrophages that were not significantly different in size from WT, but the CD206+, anti-inflammatory population was reduced. Finally, we have observed that expression of either Lyn isoform in the tumor microenvironment can promote tumor growth and decrease survival in orthotopically transplanted mice. In contrast, our studies suggest that only LynB promotes metastasis to the lungs of transplanted mice, as determined by in vivo imaging of a hyper-metastatic, luciferase-expressing variant of E0771. Together, our findings suggest that Lyn kinase plays a role in the signaling response of myeloid cells, which are major factors in disease course and treatment response, to tumor-associated stimuli. Modulation of Lyn activity, specifically the LynB isoform, or the activity of its downstream signaling partners, is thus a potential strategy for influencing the trafficking and polarization of myeloid cells within breast tumors to benefit patients.
Citation Format: Joseph T Greene, Ben F Brian, Aditi Bapat, Tanya S Freedman. Lyn kinase regulates myeloid-cell responses to mammary tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr PR02.
Abstract PR04: Temporal single cell profiling identifies B-cell specific checkpoint molecules that regulate anti-tumor immunity
Authors: Bod Lloyd 
Published: December 2023

Abstract
B cells play key roles in both innate and adaptive immunity. Distinct specialized B cell subsets engage a range of responses from antigen presentation to antibody production and B cells are one of the most abundant cell types of tumor infiltrating leukocytes (TILs), especially in melanoma. However, their role in anti-tumor immunity remains unclear. Here, we examined the B cell repertoire at single cell resolution from tumor-infiltrating B cells and tumor-draining lymph nodes (dLN) and identify and characterize a subset of B cells expressing the checkpoint molecule TIM-1 and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. While conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumor burden, selective deletion of Havcr1 (the gene encoding TIM-1) in B cells both dramatically inhibited tumor growth and enhanced effector T cell responses. Mechanistically, loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumor-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumor immunity and inhibit tumor growth.
Citation Format: Lloyd Bod. Temporal single cell profiling identifies B-cell specific checkpoint molecules that regulate anti-tumor immunity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr PR04.
Necessary Role of Ceramides in the Human Microvascular Endothelium During Health and Disease
Authors: SenthilKumar Gopika , Katunaric Boran , Zirgibel Zachary , Lindemer Brian , Jaramillo-Torres Maria J. , Bordas-Murphy Henry , Schulz Mary E. , Pearson Paul J. , Freed Julie K. 
Published: December 2023

Background:
Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitric oxide (NO). Here, we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium. We further define the mechanism through which ceramide exerts beneficial effects and discern key mechanistic differences between arterioles from otherwise healthy adults (non–coronary artery disease [CAD]) and patients diagnosed with CAD.

Methods:

Human arterioles were dissected from discarded surgical adipose tissue (n=166), and vascular reactivity to flow and C2-ceramide was assessed. Shear-induced NO and mitochondrial hydrogen peroxide (H
2
O
2
) production were measured in arterioles using fluorescence microscopy. H
2
O
2
fluorescence was assessed in isolated human umbilical vein endothelial cells.

Results:

Inhibition of NSmase in arterioles from otherwise healthy adults induced a switch from NO to NOX-2 (NADPH-oxidase 2)–dependent H
2
O
2
-mediated flow-induced dilation. Endothelial dysfunction was prevented by treatment with sphingosine-1-phosphate (S1P) and partially prevented by C2-ceramide and an agonist of S1P-receptor 1 (S1PR1); the inhibition of the S1P/S1PR1 signaling axis induced endothelial dysfunction via NOX-2. Ceramide increased NO production in arterioles from non-CAD adults, an effect that was diminished with inhibition of S1P/S1PR1/S1P-receptor 3 signaling. In arterioles from patients with CAD, inhibition of NSmase impaired the overall ability to induce mitochondrial H
2
O
2
production and subsequently dilate to flow, an effect not restored with exogenous S1P. Acute ceramide administration to arterioles from patients with CAD promoted H
2
O
2
as opposed to NO production, an effect dependent on S1P-receptor 3 signaling.

Conclusion:
These data suggest that despite differential downstream signaling between health and disease, NSmase-mediated ceramide formation is necessary for proper functioning of the human microvascular endothelium. Therapeutic strategies that aim to significantly lower ceramide formation may prove detrimental to the microvasculature.
Trends in Ductus Arteriosus Stent Versus Blalock‐Taussig‐Thomas Shunt Use and Comparison of Cost, Length of Stay, and Short‐Term Outcomes in Neonates With Ductal‐Dependent Pulmonary Blood Flow: An Observational Study Using the Pediatric Health Information Systems Database
Authors: Lemley Bethan A. , Wu Lezhou , Roberts Amy L. , Shinohara Russell T. , Quarshie William O. , Qureshi Athar M. , Smith Christopher L. , Dori Yoav , Gillespie Matthew J. , Rome Jonathan J. , Glatz Andrew C. , Amaral Sandra , O'Byrne Michael L. 
Published: December 2023

Background
The modified Blalock‐Taussig‐Thomas shunt is the gold standard palliation for securing pulmonary blood flow in infants with ductal‐dependent pulmonary blood flow. Recently, the ductus arteriosus stent (DAS) has become a viable alternative.

Methods and Results

This was a retrospective multicenter study of neonates ≤30 days undergoing DAS or Blalock‐Taussig‐Thomas shunt placement between January 1, 2017 and December 31, 2020 at hospitals reporting to the Pediatric Health Information Systems database. We performed generalized linear mixed‐effects modeling to evaluate trends in intervention and intercenter variation, propensity score adjustment and inverse probability weighting with linear mixed‐effects modeling to analyze length of stay and cost of hospitalization, and generalized linear mixed modeling to analyze differences in 30‐day outcomes. There were 1874 subjects (58% male, 61% White) from 45 centers (29% DAS). Odds of DAS increased with time (odds ratio [OR] 1.23, annually,
P
<0.01 [95% CI, 1.10–1.38]) with significant intercenter variation (median OR, 3.81 [95% CI, 2.74–5.91]). DAS was associated with shorter hospital length of stay (ratio of geometric means, 0.76 [95% CI, 0.63–0.91]), shorter intensive care unit length of stay (ratio of geometric means, 0.77 [95% CI, 0.61–0.97]), and less expensive hospitalization (ratio of geometric means, 0.70 [95% CI, 0.56–0.87]). Intervention was not significantly associated with odds of 30‐day transplant‐free survival (OR,1.18 [95% CI, 0.70–1.99]) or freedom from catheter reintervention (OR, 1.02 [95% CI, 0.65–1.58]), but DAS was associated with 30‐day freedom from composite adverse outcome (OR, 1.51 [95% CI, 1.11–2.05]).

Conclusions
Use of DAS is increasing, but there is variability across centers. Though odds of transplant‐free survival and reintervention were not significantly different after DAS, and DAS was associated with shorter length of stay and lower in‐hospital costs.
Changing Trends in Mechanical Circulatory Support Use and Outcomes in Patients Undergoing Percutaneous Coronary Interventions for Acute Coronary Syndrome Complicated With Cardiogenic Shock: Insights From a Nationwide Registry in Japan
Authors: Nishimoto Yuji , Inohara Taku , Kohsaka Shun , Sakakura Kenichi , Kawai Tsutomu , Kikuchi Atsushi , Watanabe Tetsuya , Yamada Takahisa , Fukunami Masatake , Yamaji Kyohei , Ishii Hideki , Amano Tetsuya , Kozuma Ken ,   J‐PCI Registry Investigators
Published: December 2023

Background
Temporal trends in the management of acute coronary syndrome complicated with cardiogenic shock after the revision of guideline recommendations for intra‐aortic balloon pump (IABP) use and the approval of the Impella require further investigation, because their impact remains uncertain.

Methods and Results

Using the Japanese Percutaneous Coronary Intervention (J‐PCI) registry database from 2019 to 2021, we identified 12 171 patients undergoing percutaneous coronary intervention for acute coronary syndrome complicated with cardiogenic shock under mechanical circulatory support. The patients were stratified into 3 groups: (1) IABP alone, (2) Impella, and (3) venoarterial extracorporeal membrane oxygenation (VA‐ECMO); the VA‐ECMO group was further stratified into (3a) VA‐ECMO alone, (3b) VA‐ECMO in combination with IABP, and (3c) VA‐ECMO in combination with Impella. The quarterly prevalence and outcomes were reported. The use of IABP alone decreased significantly from 63.5% in the first quarter of 2019 to 58.3% in the fourth quarter of 2021 (
P
for trend=0.01). Among 4245 patients requiring VA‐ECMO, the use of VA‐ECMO in combination with IABP decreased significantly from 78.7% to 67.3%, whereas the use of VA‐ECMO in combination with Impella increased significantly from 4.2% to 17.0% (
P
for trend <0.001 for both). After adjusting for the confounders, the risk difference in the fourth quarter of 2021 relative to the first quarter of 2019 for in‐hospital mortality was not significant (adjusted odds ratio, 0.84 [95% CI, 0.69–1.01]).

Conclusions
Our study revealed substantial changes in the use of different mechanical circulatory support modalities in acute coronary syndrome complicated with cardiogenic shock, but they did not significantly improve the outcomes.
Development as Structural Violence in Ethiopia
Authors: Getahun Binayew Tamrat 
Published: December 2023

Abstract
Development should not be done in a way that endangers the environment, human life, or non-human life that depends on it. However, in Ethiopia, economic development was carried out with little or no concern for the environment or indigenous and minority groups whose livelihoods directly depended on natural resources. Based on an examination of primary and secondary sources through the lens of structural violence theory, this article argues that Ethiopia’s economic growth was not equitable and happened at the expense of the country’s natural resources. Using the Negede Woyto of Lake Tana as a case study, this paper investigated how economic development projects in Ethiopia impacted minority communities. The conclusion reached was that the eprdf-led government actively worked to inflict structural violence on minority groups in the Lake Tana region, using sustainable economic development as a justification.
Scythians and ξεινικὰ νόμαια
Authors: Sinitsyn Alexander 
Published: December 2023

Abstract
Herodotus’ logos about Scythians and ξεινικὰ νόμαια—amusing and ominous, as is typical of him, yet insightful—consists of two stories about the sad lots of Anacharsis and Scyles; the story begins with a statement that Scythians shun practicing customs of other peoples, particularly those of Hellas; it ends as an adage asserting the initial statement: that is the way Scythians guard their customs (4.76–80). Herodotus describes the barbarian neighbors’ attitude towards foreign and alien customs. But these two examples are about their own, Scythian, heroes or rather antiheroes. Both the philhellenes forswear their native religion and customs and abandon themselves to Greek ritual practices; therefore, they suffer for their behavior. The author of the article holds that Herodotus was sympathetic to Scythians’ resentment against ξεινικὰ νόμαια. The Greek historian speaks about piety and patriotism of Scythians, who believe that the offence against νόμαια is a threat to the very foundation of their culture.
Sefer Yeṣirah’s Dating, Geographic Provenance and the Open Question of Its Composer’s Religious Affiliation and Identity
Authors: Zinner Samuel 
Published: December 2023

Abstract
In 2018, Weiss has ended centuries of speculation about the enigmatic Hebrew Sefer Yeṣirah’s dating and geographical provenance, demonstrating with a high level of confidence (specifically on the basis of Sefer Yeṣirah’s Syriac grammarian loanwords) a seventh-century C.E. Syrian origin. Weiss and others have also shown that Sefer Yeṣirah’s closest parallels are in Syriac Christian grammarian and theological sources. Given that abundant evidence points to a Rabbinic form of Judaism present in ancient Syria, the theory of a Jewish composer is odd because of the text’s non-Rabbinic character. Similarly, the theory of a Syriac Christian or “Jewish-Christian” author is odd in view of the text’s composition in Hebrew instead of Syriac. It remains for future research to solve this final enigma of the religious identity of Sefer Yeṣirah’s composer.
Seventy-Two and The One Nation
Authors: Nicolaus Peter , Rodziewicz Artur 
Published: December 2023

Abstract
The current article sheds light on the symbolism of the number 72 in Yezidism and briefly outlines its roots in ancient Mesopotamian religions, Judaism, Christianity, and Islam. Furthermore, it highlights the link between 72 nations and 72 genocides in Yezidi perception.
Tétouan et la littérature généalogique à l’époque de Mawlāy Ismāʿīl. Motivations et caractéristiques de deux enquêtes de vérification des généalogies
Authors: Dahia Bilal 
Published: December 2023

Abstract
This article looks at the phenomenon of the writing of Cherifian genealogies, which came to the fore in Morocco in general, and in northern Morocco in particular, with the emergence of the Alawite dynasty. The case of Tétouan, which was the center of the governors of northern Morocco at the time, will be studied, examining the city’s relationship to the phenomenon of Sherifism. The article examines the reason for the emergence of works specializing in chorfa genealogies at the time of Mawlāy Ismāʿīl in Tetouan. We’ll see how attempts were made to distinguish the chorfa as a noble class distinct from the masses in certain tribes, particularly among the Banī ʿArūs and the Banī Ḥassān, and their consequences, including the phenomenon of the “so-called chorfa” (al-mutašarrifah) since the 15th century. This phenomenon was at the origin of the genealogical registration movement in the Alawite period. In this study, we will examine two examples of the oldest treatises on the genealogy of the chorfa in Tétouan, these are Dawaʿī al-ṭarab fī -ẖtisāri ansāb al-ʿarab written by Ibn al-ʿĀfiyah al-Zaǧnī, and Šaḏar al-ḏahab fī ẖayr nasab written by Ibn Raḥmūn al-Ḥasanī. These two books share very similar characteristics in terms of the nature of the content, based on literal transmission and data collection in the first instance, with very limited scope for discussion and analysis. In conclusion, we will discuss the degree of success they achieved in combating the mutašarrifah phenomenon in northern Morocco.
Right-Moving Supercell Tornadogenesis during Interaction with a Left-Moving Supercell’s Rear-Flank Outflow
Authors: Edwards Roger , Thompson Richard L. 
Published: December 2023

Abstract
On the local afternoon of 29 May 2012, a long-lived, right-moving (RM) supercell formed over northwestern Oklahoma and turned roughly southeastward. For >3 h, as it moved toward the Oklahoma City, Oklahoma, metro area, this supercell remained nontornadic and visually high-based, producing a nearly tornadic gustnado and a swath of significantly severe, sometimes giant hail up to 5 in. (12.7 cm) in diameter. Meanwhile, a left-moving (LM) supercell formed over southwestern Oklahoma about 100 mi (161 km) south-southwest of the RM storm, and moved northeastward, with a rear-flank gust front that became well defined on radar imagery as the LM storm approached southern and central parts of the metro. The authors, who had been observing the RM supercell in the field since genesis, surmised its potential future interaction with the LM storm’s trailing gust front about 1 h beforehand. We repositioned to near the gust front’s extrapolated collision point with the RM mesocyclone, in anticipation of maximized tornado potential, then witnessed a small tornado from the RM mesocyclone immediately following its interception of the boundary. Synchronized radar and photographic images of this remarkable sequence are presented and discussed in context of more recent findings on tornadic supercell–boundary interactions, with implications for operational utility.

Significance Statement
Supercells—well-organized, rotating thunderstorms mainly found in midlatitudes—commonly produce the largest hail, along with damaging gusts and most tornadoes. In radar imagery and photographs, we show the characteristics and merger of two supercell types: left-moving and right-moving, with respect to winds aloft. As the left-moving storm’s trailing gust front interacted with the right-mover’s mesocyclone, the latter strengthened quickly, soon producing a tornado. Observed evolution of these storms supports idealized numerical and conceptual models for supercell behavior and interactions with storm-scale boundaries, and may be useful in short-fused tornado forecast and warning operations.