bluuebunny/crossref_metadata_2025_split huggingface dataset:
On redshift evolution and negative dark energy density in Pantheon + Supernovae
Authors: Malekjani M. , Mc Conville R. , Ó Colgáin E. , Pourojaghi S. , Sheikh-Jabbari M. M. 
Published: March 2024

AbstractWithin the Friedmann–Lemaître–Robertson–Walker (FLRW) framework, the Hubble constant $$H_0$$

H
0

is an integration constant. Thus, consistency of the model demands observational constancy of $$H_0$$

H
0

. We demonstrate redshift evolution of best fit $$\Lambda $$
Λ
CDM parameters $$(H_0, \Omega _{m})$$

(

H
0

,

Ω
m

)

in Pantheon+ supernove (SNe). Redshift evolution of best fit cosmological parameters is a prerequisite to finding a statistically significant evolution as well as identifying alternative models that are competitive with $$\Lambda $$
Λ
CDM in a Bayesian model comparison. To assess statistical significance, we employ three different methods: (i) Bayesian model comparison, (ii) mock simulations and (iii) profile distributions. The first shows a marginal preference for the vanilla $$\Lambda $$
Λ
CDM model over an ad hoc model with 3 additional parameters and an unphysical jump in cosmological parameters at $$z=1$$

z
=
1

. From mock simulations, we estimate the statistical significance of redshift evolution of best fit parameters and negative dark energy density ($$\Omega _m > 1$$

Ω
m

>
1

) to be in the $$1-2 \sigma $$

1
-
2
σ

range, depending on the criteria employed. Importantly, in direct comparison to the same analysis with the earlier Pantheon sample we find that statistical significance of redshift evolution of best fit parameters has increased, as expected for a physical effect. Our profile distribution analysis demonstrates a shift in $$(H_0, \Omega _m)$$

(

H
0

,

Ω
m

)

in excess of $$95\%$$

95
%

confidence level for SNe with redshifts $$z > 1$$

z
>
1

and also shows that a degeneracy in MCMC posteriors is not equivalent to a curve of constant $$\chi ^2$$

χ
2

. Our findings can be interpreted as a statistical fluctuation or unexplored systematics in Pantheon+ or $$\Lambda $$
Λ
CDM model breakdown. The first two possibilities are disfavoured by similar trends in independent probes.
HEIGHT-TO-LENGTH RATIOS OBTAINED BY WRIST RADIOGRAPHY TO ASSESS SCAPHOID MALUNION: RADIOGRAPHIC AND CLINICAL OUTCOMES OF 32 CASES
Authors: Bezirgan Uğur , Özyıldıran Mustafa , Acar Erdinç , Yoğun Yener , Erdoğan Yasin , Armangil Mehmet 
Published: March 2024

Purpose: Scaphoid nonunion and malunion can be observed after scaphoid fracture. While the diagnosis of nonunion is well defined in the literature, there is no consensus on the diagnostic criteria and clinical outcomes of scaphoid malunion. The aim of the study is to define the direct radiography parameters of scaphoid malunion and determine the clinical outcomes. Methods: Patients applied to our clinic with the diagnosis of scaphoid fracture between January 2020 and June 2021, and were analyzed retrospectively. 32 patients treated with surgical or conservative methods were included in the study. Nonunions and cases with a follow-up period of less than 12 months were excluded. Scapholunate (SL) angles and height-to-length (H/L) ratios of scaphoid were measured on wrist radiography to assess scaphoid malunion. Malunion was defined as SL angle >60∘ and ROC analysis was applied to determine cutoff H/L ratio in wrist radiography. Wrist functionality and pain were evaluated with the Patient-Rated Wrist Evaluation (PRWE) and MAYO scores. The range of motion (ROM) and grip strength were also recorded. Results: Seventeen patients (53.1%) underwent surgery while conservative treatment was applied to the other 15 (46.9%). Of these, six patients (18.8%) met the definition of malunion. According to receiver operating curve (ROC) analysis, the cutoff H/L ratio in posteroanterior wrist radiographs was 0.602 ([Formula: see text] < 0.001) and the cutoff H/L ratio in lateral wrist radiographs was 0.692 ([Formula: see text] = 0.003). The ROM values for flexion/extension and radial/ulnar deviation was smaller in the malunion group ( [Formula: see text] = 0.023 and [Formula: see text] = 0.014, respectively). However, no significant difference was observed in pronation/supination values ([Formula: see text] > 0.05). Mean MAYO score was 75.0 in malunion group and 90.0 in nonmalunion group ([Formula: see text] = 0.003). While the mean PRWE value was 24.50 in malunion, it was 14.15 in nonmalunion ([Formula: see text] = 0.023). Conclusion: Evaluation of H/L ratio in wrist radiography provides valuable information in the diagnosis of scaphoid malunion. Scaphoid malunions have poorer functional outcomes.
Abstract 1028: Assessment of the diagnostic accuracy of Oncuria-Detect® for detection of upper tract urothelial carcinoma
Authors: Sakatani Toru , Tanaka Sunao , Fujita Kazutoshi , Linehan Jennifer , Murakami Kaoru , Lee Riko , Pagano Ian , Rosser Charles J. , Furuya Hideki 
Published: March 2024

Abstract
Introduction and Objective: Due to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with upper tract urothelial carcinoma (UTUC). The application of a robust urine-based multiplex assay, Oncuria-Detect®, to aid in the detection of UTUC has the potential to address this deficiency and to assist with accurate, non-invasive diagnosis.
Methods: To evaluate the performance of Oncuria-Detect®, a multiplex immunoassay capable of querying a voided urine sample for 10 protein biomarkers associated with urothelial carcinoma (A1AT, APOE, ANG, CA9, IL8, MMP9, MMP10, PAI1, SDC1 and VEGFA). Its application to UTUC was evaluated in a multi-institutional cohort of 35 prospectively collected subjects presenting for evaluation of upper tract mass along with 46 prospective collected matched controls (i.e., non-tumor bearing). The ability of the test to identify patients harboring UTUC was assessed. UTCU status was confirmed by endoscopy and tissue biopsy or definitive surgery. Diagnostic performance was assessed using ROC curves.
Results: Oncuria-Detect® provided an AUC of 0.886 (95% CI: 0.807-0.964) with an overall sensitivity of 91.4%, specificity of 73.9%, NPV 91.9% and PPV 72.7%. Sensitivity values of the diagnostic panel for low-grade UTUC, high-grade UTUC, non-invasive UTUC and invasive UTUC were 86.7%, 90.9%, 88.9% and 94.1%, respectively. Urinary cytology or selective ureteral washing/cytology was associated with an overall sensitivity of 54.2%, specificity of 100%, NPV 63.3% and PPV 100%. Sensitivity values of cytology for low-grade UTUC, high-grade UTUC, non-invasive UTUC and invasive UTUC were 100%, 100%, 100%, and 77.8%, respectively.
Conclusions: Urinary levels of a biomarker panel enabled the accurate discrimination of UTUC and controls non-tumor bearing individuals. The multiplex Oncuria-Detect® test can achieve the efficient and accurate detection of UTUC in a non-invasive patient setting.
Citation Format: Toru Sakatani, Sunao Tanaka, Kazutoshi Fujita, Jennifer Linehan, Kaoru Murakami, Riko Lee, Ian Pagano, Charles J. Rosser, Hideki Furuya. Assessment of the diagnostic accuracy of Oncuria-Detect® for detection of upper tract urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1028.
Abstract 1036: Development of a comprehensive RNA-based NGS panel for detecting tyrosine kinase fusion genes associated with primary hypereosinophilia
Authors: Lee Bongyong , Chern Andrew , Zhang Aiguo , Lu Chuanyi M. , Sha Michael Y. 
Published: March 2024

Abstract
Hypereosinophilia (HE) is a medical condition diagnosed when the count of eosinophils in the blood is greater than 1.5 × 109 per liter. Primary HE is a clonal stem cell disorder manifesting as myeloid and/or lymphoid malignancies and is typically driven by aberrant fusion genes involving a tyrosine kinase (TK) gene (e.g., PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, ABL1). The precise identification of the underlying molecular genetic abnormalities is crucial for timely diagnosing and managing primary HE. There has been no HE-specific assay that can concomitantly detect all known or novel TK fusion genes. We've developed an RNA-based panel for detecting TK fusion genes in HE. This panel, developed using 5' RACE technology, allows for the identification of fusion transcripts in total RNA extracted from whole blood sample. It covers 48 known TK fusion genes and also has the capability of detecting novel gene fusions. We balanced and optimized the panel using an in-house fusion RNA mix containing 11 fusion transcripts. We additionally validated the panel using samples from five patients with hematopoietic neoplasms and two fusion-positive cell lines to ensure its accuracy. The Limit of Detection (LoD) was established by analyzing the in-house RNA mix and normal whole blood RNA. It was found that the minimum RNA input required to detect all 11 fusion transcripts was 3540 copies in the presence of a background of 10 ng normal whole blood RNA. The panel successfully identified two fusion transcripts using 10 ng of total RNA obtained from cancer cell lines. The panel was then used to test five patient RNA samples extracted from whole blood. We successfully confirmed the presence of BCR-ABL1 fusion in 3 patient samples and ETV6-PDGFRB fusion in 1 patient sample, respectively. In summary, we developed HE-specific NGS panel for detecting all known and novel TK fusion genes and demonstrated its analytical accuracy and clinical effectiveness. The next phase of our study is to further validate the tests on a large patient cohort.
Citation Format: Bongyong Lee, Andrew Chern, Aiguo Zhang, Chuanyi M. Lu, Michael Y. Sha. Development of a comprehensive RNA-based NGS panel for detecting tyrosine kinase fusion genes associated with primary hypereosinophilia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1036.
Abstract 1114: Evaluating strategies to harness metabolic vulnerabilities in cervical
Authors: Schwarz Dr Julie K. , Gabriel Dr Nishanth , Banik Aunannya 
Published: March 2024

Abstract
Tumor cells frequently alter their metabolism to generate biomolecular intermediates for tumor maintenance and proliferation. Previous reports from Dr. Julie Schwarz’s laboratory have shown that cervical cancer cells with altered AKT/mTOR pathways show increased reliance on glucose and exogenous glutamine. The laboratory has introduced PIK3CA E545K mutation and PTEN null mutation in cervical cancer cell line SiHa. Further, to evaluate the role of glutamine metabolism in these genotypes, these cells were cultured in sequentially lower levels of glutamine until these cells were able to proliferate without exogenous glutamine supplementation. These isogenic long-term glutamine-deprived (QD) cells allow us to tease out the role of these specific mutations in cellular metabolism. In our study, long-term glutamine deprivation inhibits the proliferation of rapidly proliferating PI3K-AKT-altered cell lines. Even though glutamine is required for GSH synthesis, which quenches reactive oxygen species, QD cells were refractory to cisplatin and irradiation. Since PI3K-AKT altered were dependent on exogenous glutamine, it was expected that QD cells would have lower GLS levels to inhibit glutaminolysis. However, GLS levels in WT and QD were similar. Altogether, these data indicate that in PI3K-AKT altered cervical tumor glutamine antagonists can reduce tumor proliferation. Further glutamine reduction does not alter GLS levels and hence GLS can be targeted as well to further improve treatment outcomes. To evaluate the alternate metabolic dependencies in cervical cancer tumors, both cellular as well as secreted metabolites were evaluated. To identify alternative pathways that are activated in these glutamine-deprived cell lines, we cultured these cells in uniformly labeled 13C glucose. Mass spectrometric studies also evaluated the protein levels of various metabolic intermediates in glutamine-deprived cell lines compared to control cells. To confirm our observations, we used kit-based assays to evaluate metabolites in the cells. To further confirm the change in the metabolite pathway we evaluated changes in transcriptional changes of regulating proteins/enzymes. This pre-clinical study reinforced efforts that are anticipated to reveal new metabolic vulnerabilities of cancer cells that can be targeted by therapeutic interventions. This study also helped us evaluate druggable metabolic targets that can be targeted for effective tumor eradication along with conventional treatment. This understanding will help advance the pre-clinical trials persistent to the cure of cervical cancer.
Citation Format: Dr Julie K. Schwarz, Dr Nishanth Gabriel, Aunannya Banik. Evaluating strategies to harness metabolic vulnerabilities in cervical [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1114.
Abstract 1247: PPARsing epigenetic memory in intestinal stem cells: High-fat diet and oncogenic susceptibility
Authors: Saiz Dominic R. , Hartley-McDerrmott Thomas , Barrera-Millan Yesenia , Castro-Ochoa Karla Fabiola , Shukla Abhigyan , Torel Matthew , Mana Miyeko D. 
Published: March 2024

Abstract
Diet has a profound impact on health and susceptibility to cancer. Adaptation to a Western diet is strongly associated with increased colorectal cancer (CRC) and obesity prevalence. This study demonstrates the epigenetic changes in intestinal stem cells (ISCs) induced by a pro-obesity high-fat Western diet (HFD) and the heightened risk of oncogenic transformation. A HFD induces a phenotype characterized by increased ISC frequency, proliferation, regenerative capacity, and ability to initiate adenomas. We hypothesized that a HFD generates lasting epigenetic alterations in ISCs thereby enhancing oncogenic susceptibility. We evaluated the chromatin landscape of intestinal stem cells (ISCs) and the reversibility of the epigenetic changes. Mice carrying a fluorescent reporter of the ISC marker Lgr5, were subjected to a control diet, HFD, or HFD with a return to control. We isolated ISCs by flow cytometry and used an assay for transposase-accessible chromatin sequencing (ATAC-seq) to identify differentially accessible genomic regions correlated with the ISC phenotype. We found that a HFD induces distinct changes in the chromatin landscape that persist after removal from the HFD. These accessible regions are associated with genes involved in lipid metabolism and are enriched with PPAR (Peroxisome Proliferator-Activated Receptor) binding motifs. We demonstrate that these lipid metabolism regulators, PPAR-delta and PPAR-alpha, are necessary for the majority of significant accessible regions. We further show that HFD-induced accessibility significantly correlates with early chromatin alterations seen by loss of tumor suppressor APC. Our data supports a mechanistic pathway for diet-induced epigenetic reprogramming due to PPAR activity and suggests that the HFD imposes a preneoplastic stem cell chromatin state that stokes the risk of oncogenic change.
Citation Format: Dominic R. Saiz, Thomas Hartley-McDerrmott, Yesenia Barrera-Millan, Karla Fabiola Castro-Ochoa, Abhigyan Shukla, Matthew Torel, Miyeko D. Mana. PPARsing epigenetic memory in intestinal stem cells: High-fat diet and oncogenic susceptibility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1247.
Abstract 1267: Projected impact of liquid biopsy screening strategies with high sensitivity in focused populations and high specificity in broad populations
Authors: Bach Peter B. , Trivedi Niti U. , Cotton Lindsey 
Published: March 2024

Abstract
Purpose: Two 'liquid biopsy' cancer screening approaches exist: Focused and Broad. The Focused approach targets specific cancers and populations lacking adequate screening, emphasizing high sensitivity. The Broad approach aims to detect various cancers in the population, prioritizing high specificity to minimize false-positives but potentially compromising sensitivity. The public health impact and testing burden of these approaches remain unexplored.
Methods: Projected cancer mortality reduction and annual test volumes are based on published data for liquid biopsy tests. Focused screening is modeled for patients not undergoing guideline-recommended screening for lung, liver, and colorectal cancers. Broad screening is modeled for individuals aged 50-80, assuming the detection of all cancer types. Averted deaths are calculated by combining published mortality reduction estimates or assumed at 20% if not available. Reductions are adjusted for reported test sensitivities. Liquid biopsy cannot prevent deaths from cancers recommended for screening if the person has already undergone the recommended test.
Results: Focused and broad screening strategies annually prevented around 20,000 cancer deaths. Focused screening necessitated testing only one-fifth of the people compared to broad screening (30MM vs. 150MM). The projected reduction in mortality for focused testing relied entirely on randomized studies, while the equivalent statistic for the broad strategy was 53%.
Conclusions: Equivalent reductions in cancer deaths can be achieved with focused screening at high sensitivity and broad screening at high specificity, with only one-fifth of the testing burden. The influence of false positives in focused testing and false reassurance in broad testing may impact these findings, which could also be influenced by testing and follow-up costs.
Table 1 Annual cancer deaths averted (thousands) Focused cancer testing Broad cancer testing Lung 10-12 4-8 Liver 4-5 1 Colorectal 3-4 1 Other screened cancers* Not modeled 1-2 Unscreened cancers Not modeled 6-10 Total 17-20 14-22 Annual test volume (millions) 30 150 *Other screened cancers includes prostate, breast, cervical. Range reflects the application of reported Stage I or overall sensitivity, respectively.
Citation Format: Peter B. Bach, Niti U. Trivedi, Lindsey Cotton. Projected impact of liquid biopsy screening strategies with high sensitivity in focused populations and high specificity in broad populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1267.
Abstract 1318: Targeting multiple myeloma with BCMA-CAR NK cells expressing a GPRC5D-NKG2D bispecific antibody
Authors: Tian Lei , Chen Victoria , Barr Tasha , Li Zhiyao , Chen Yuqing , Zhang Jiaying , Caligiuri Michael A. , Yu Jianhua 
Published: March 2024

Abstract
Recently developed therapeutics for multiple myeloma (MM) include targeted therapy, immunomodulatory drugs, and immunotherapy, the latter of which consists of B-cell maturation antigen (BCMA)-CAR cells, bispecific antibodies (BsAbs) to engage T cells. However, challenges including relapse and toxicity still exist. The orphan G protein-coupled receptor, class C group 5 member D (GPRC5D), emerged as a novel target for MM therapy. Therefore, following our established system [Cancer Immunol Res PMID: 29769244; Leukemia, PMID:24067492], we generated a BsAb by fusing anti-GPCR5D single-chain variable fragment (scFv) and an anti-NKG2D scFv (GPRC5D-NKG2D BsAb) in a human IgG4 platform and expressed it from BCMA-CAR and soluble IL15 natural killer (NK) cells (s15.BsAb.BCMA-CAR NK) to address the current known limitations. Our data showed that s15.BsAb.BCMA-CAR NK cells secreted GPRC5D-NKG2D BsAb both in vitro and in vivo. To evaluate the function of GPRC5D- NKG2D BsAb expressed from NK cells in vivo, we treated MM tumor-bearing mice with the purified antibody. The data showed that GPRC5D-NKG2D BsAb demonstrated a significantly better survival effect than saline (P≤0.01). We tested s15.BsAb.BCMA-CAR NK cells for cytotoxicity against a homogenous tumor cell mode (BCMA + GPRC5D + ) and a heterogeneous MM tumor cell model, including 50% BCMA + GPRC5D + , 25% BCMA ─ GPRC5D + , and 25% BCMA + GPRC5D ─ cells. Real-time cell analysis (RTCA) data showed s15.BsAb.BCMA-CAR NK cells killed tumor cells in vitro better than both BCMA-CAR NK cells and empty vector-transduced NK cells in an antigen-dependent manner. To test the efficacy of s15.BsAb.BCMA-CAR NK cells in vivo, we established a heterogeneous MM tumor cell mouse model, by mixing BCMA + GPRC5D + OPM2 cells and BCMA + GPRC5D ─ OPM2 cells at the ratio of 2:1. MM mice were treated with “off-the-shelf” different construct NK cells. The results showed that s15.BsAb.BCMA-CAR NK cells significantly prolonged survival compared to other NK cells(s15.BsAb.BCMA-CAR vs. BCMA-CAR P = 0.0012). Our data demonstrated that this all-in-one, multifaceted modality provides 2 ready-to-use biologics simultaneously, CAR NK cells and BsAb, for MM treatment.
Citation Format: Lei Tian, Victoria Chen, Tasha Barr, Zhiyao Li, Yuqing Chen, Jiaying Zhang, Michael A. Caligiuri, Jianhua Yu. Targeting multiple myeloma with BCMA-CAR NK cells expressing a GPRC5D-NKG2D bispecific antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1318.
Abstract 1515: Tertiary lymphoid structures restrain cancer evolution by supporting stem-like CD8+ T cells for sustained anti-tumor immunity
Authors: Wang Pengxiang , Zhou Chi , Wei Zhiting , Wang Yue , Gao Yuli , Meng Fangliangzi , Zhou Jian , Fan Jia , Liu Qi , Sun Yunfan 
Published: March 2024

Abstract
Currently, our understanding of the mechanism underlying the immune response on extending the survival of patients with aggressive tumors remains limited. In this study, we generated multi-regional genomic and transcriptional data coupled with digital pathology from 28 long-term survivors (LTSs) and 34 stage-matched short-term survivors, with intrahepatic cholangiocarcinoma (iCCA). Our investigation unveiled that mature tertiary lymphoid structures (TLSs) within the tumors of LTSs exerted significant immune pressure on the tumor, leading to the restriction in generating clonal mutations and increased subclonal diversity. Employing single-cell profiling, we identified significant enrichment of IgM+ naïve B cells and TCF7+ stem-like CD8+ T cells in TLS-positive tumors. Spatial profiling further highlighted that TCF7+ stem-like CD8+ T cells preferentially localized in TLS, facilitating reduced vulnerability to unfavorable environmental factors. Functionally, TCF7+ stem-like CD8+ T cells displayed strong capacity to differentiate into effector subsets while maintaining a diverse T-cell receptor repertoire. Mechanistically, we identified that naïve B cells promote activation and differentiation of stem-like CD8+ T cells within the TLS niche through IgM-FcμR axis, which primed these T cells for enhanced anti-tumor immunity. In summary, our findings underscore that TLS plays a pivotal role in orchestrating enduring and effective anti-tumor immunity, which yield strong immune stress on cancer evolution and ultimately contributing to better prognosis of patients.
Citation Format: Pengxiang Wang, Chi Zhou, Zhiting Wei, Yue Wang, Yuli Gao, Fangliangzi Meng, Jian Zhou, Jia Fan, Qi Liu, Yunfan Sun. Tertiary lymphoid structures restrain cancer evolution by supporting stem-like CD8+ T cells for sustained anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1515.