bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Modeling to Support Post-Yield Acceptance Criteria for Spent Nuclear Fuel Cladding
Authors: Klymyshyn Nicholas , Sakalaukus Peter , Kadooka Kevin 
Published: November 2024

Abstract
Spent nuclear fuel (SNF) is evaluated for structural failure during storage and transportation scenarios. The U.S. Department of Energy’s Spent Fuel and Waste Science and Technology (SFWST) program has sponsored significant research in quantifying mechanical loads on SNF during storage and transportation scenarios using experimental and modeling methods. The SFWST program has also performed significant research on measuring the mechanical behavior of irradiated SNF as defueled cladding segments and cladding with fuel pellets to measure composite behavior. This paper considers some of the key material data from the Sibling Pin testing and uses structural modeling and analysis methods that have been informed by testing to consider post-yield acceptance criteria for SNF cladding structural analysis.
Test data published by Oak Ridge National Laboratory (ORNL) and Pacific Northwest National Laboratory (PNNL) are the foundation for informing the material behavior of the models developed in this study. In particular, four-point bend (4PB) tests of fueled cladding segments together with data from axial tube tensile testing of defueled cladding segments provide significant information about the bending failure mode of SNF. ORNL’s 4PB test data is on fueled cladding segments, so the composite behavior of SNF is demonstrated. This paper describes PNNL’s coincident beam model that was developed to approximate the composite behavior of SNF.
This paper also presents PNNL’s structural dynamic finite element models of a cask tip-over scenario, which is predicted to cause the strongest mechanical loads on SNF of all postulated storage and transportation scenarios. SNF bending loads predicted in the cask tip-over scenario and cladding acceptance criteria beyond yield are considered, with justification based on the Sibling Pin test data. ASME Boiler and Pressure Vessel code stress intensity limits are also considered. The ultimate goal of this work is to aid in the justification of structural acceptance criteria for SNF cladding beyond the cladding’s irradiated yield strength for use in structural analysis of all storage and transportation scenarios.
Stress Intensity Factor Solution Comparison for Very Long Circumferential Flaws in Cylinders Using Finite Element Analysis
Authors: Glunt Nathan , Xu Steven X. , Cipolla Russell C. 
Published: November 2024

Abstract
Section XI of the ASME Boiler and Pressure Vessel Code provides analytical evaluation procedures to determine the acceptability of flaws detected during in-service inspection of structural components and piping. Linear elastic fracture mechanics-based evaluation procedures require calculation of the stress intensity factor. Article A-3000 of Appendix A in Section XI provides closed-form relations for the stress intensity factor influence coefficients at both the deepest and surface points of the flaw, which were developed based on tabular data in API 579-1/ASME FFS-1 2007. The API 579-1/ASME FFS-1 2007 data do not cover very long flaws, e.g., flaws close to being fully circumferential flaws. Stress intensity factor solutions are provided by separate equations for fully circumferential flaws in Article A-3000, but there is no guidance on evaluating very long flaws that are beyond the current closed form solutions and still fall short of being fully circumferential. Finite element calculations have been performed to obtain stress intensity factors for very long circumferential flaws in cylinders. The finite element results are used to assess the applicability of the current closed-form relations in Section XI Appendix A to very long circumferential flaws on the inside and outside surfaces of cylinders. The paper presents the finite element results and assessment of the applicability of the current Section XI equations.
Utilizing Probabilistic Analyses to Explore Performance Margins of Natural Gas Infrastructure for the Transport and Delivery of Hydrogen and Hydrogen Blends
Authors: Schroeder Benjamin , San Marchi Chris , Ronevich Joseph , Devin Michael , Duell Joshua , Potts Steve 
Published: November 2024

Abstract
Gaseous hydrogen is known to embrittle most steels, including the steels used in natural gas pipelines. As injection of hydrogen into the existing natural gas infrastructure is considered globally by the pipeline industry, the structural integrity of pipelines transporting gaseous hydrogen must be investigated. Hydrogen Extremely Low Probability of Rupture (HELPR) is a publicly available and open-source probabilistic fatigue and fracture mechanics toolkit recently developed at Sandia National Laboratories. HELPR is intended to incorporate the influence of hydrogen into structural integrity assessments of natural gas transmission and distribution infrastructure. HELPR utilizes engineering models, such as those specified in ASME B31.12 and API 579, with relatively low computational costs to perform large sample ensembles, enabling estimation of performance distributions including low probability tail estimates. Leveraging the probabilistic capabilities built into HELPR, the sensitivity of fatigue and fracture calculations to specific modeling parameters on performance margins can be quantified. Through applying HELPR’s probabilistic capabilities to realistic scenarios, the impact of uncertainty in specific model parameter descriptions on performance margins, such as cycles to unstable crack growth or rupture in gaseous hydrogen, can be characterized; this same approach can then be used to assess the impact of reducing uncertainty sources on the resulting performance metrics, margins, and associated risks. A few industry-motivated scenarios are used to demonstrate this approach.
Application of Torsional Fatigue Testing of Helical Springs to Explore the Effect of Mean Stress on Inconel X-750 Fatigue Resistance
Authors: Metzger Donald , Gagnon Andre 
Published: November 2024

Abstract
In a particular nuclear application, separation between structural components is maintained by a helical spring such that the separating load bears across the diameter of the spring coils. Relative motion between the structural components due to changing load and temperature is accommodated by rolling of the spring. This rolling motion while under radial load results in cyclic loading of the spring material. Fatigue analysis of the cyclic loading must take into consideration the material degradation due to the unique operating environment, so testing of ex-service material is required. Standard fatigue test specimens are not possible due to the small dimensions and helical form of the spring component.
A fatigue test system has been developed in which cyclic stress is achieved by applying torsional load with respect to the axis of the helical spring. This load results in a pure bending state of stress in the cross-section of the coils. The relationship between applied load and stress is achieved analytically through curved beam analysis. The fatigue test has previously only been applied with fully reversed load cycles with zero mean stress. In this work, test with non-irradiated specimens are done with mean stress controlled to be nonzero such that the effect mean stress on the S-N curve can be quantified. The outcome of the tests demonstrates that the test method is effective in producing valid fatigue data over a range of mean stress and alternating stress. Also, the test results add to the fatigue data available for Inconel alloy X-750.
Pharmacist Perceptions and Future Scope of Telepharmacy in New Zealand: A Qualitative Exploration
Authors: Saeed Hina , Scahill Shane , Kim Julie , Moyaen Raevienne , Natarajan Dharini , Soga Ayaka , Wong Manvis , Martini Nataly 
Published: November 2024

Background: Telepharmacy is the delivery of pharmacy services through telecommunications technology when patients and pharmacists are separated by physical distance. Falling under the broader term of telehealth, telepharmacy has been adopted globally and proved invaluable during the COVID‐19 pandemic.Objective: The study is aimed at investigating New Zealand pharmacists’ perceptions of telepharmacy adoption and assessing its potential impact on their future scope of practice.Methods: New Zealand registered pharmacists were recruited through convenience sampling to participate in semistructured interviews conducted between July and August 2022. Interviews were transcribed and coded with NVivo and analyzed using inductive thematic analysis to develop themes. Themes and subthemes were mapped to the Clinical Adoption Framework (CAF) to interpret the findings.Results: From 23 participants, 70% were community pharmacists. The COVID‐19 pandemic accelerated telepharmacy adoption in New Zealand and most pharmacists perceived it as convenient and beneficial to increase access to pharmacy services. Barriers such as the lack of resources, technology issues, inadequate remuneration, and existing legislation were highlighted, as was the need for better staff training, patient education, better access to technology, regulatory reforms, and integration with existing services.Conclusion: There is a need for reforms and initiatives for sustainable and equitable telehealth use in New Zealand. While preparing for digital infrastructure and capabilities presents challenges, this investment can transform pharmacy practice in the long term, benefiting both patients and pharmacy professionals.
Unveiling the Link Between Breast Cancer Treatment and Osteoporosis: Implications for Anticancer Therapy and Bone Health
Authors: Goel Bhawna , Virmani Tarun , Jain Vikas , Kumar Girish , Sharma Ashwani , Al Noman Abdullah 
Published: November 2024

Background: The interplay between breast cancer treatment and osteoporosis has important consequences for anticancer therapy and patient bone health. Many breast cancer therapies involve hormonal treatments that lower estrogen levels, which can lead to an increased risk of osteoporosis due to reduced bone mineral density. Aromatase inhibitors, chemotherapy, and surgeries such as oophorectomy can further aggravate bone loss, highlighting the necessity of prioritizing bone health during cancer treatment.Objective: This review is aimed at investigating the complex relationship between breast cancer therapies and bone health by examining the molecular and cellular mechanisms through which anticancer treatments lead to bone loss. It also seeks to assess the effects of various treatment options, such as selective estrogen receptor modulators (SERMs) and bisphosphonates, on reducing bone loss and maintaining bone health during cancer therapy.Method: The review explores the mechanisms underlying bone loss in breast cancer patients undergoing treatment, focusing on factors such as estrogen depletion, inflammatory cytokines, and changes in bone remodelling processes. Additionally, it evaluates the efficacy of different therapeutic interventions, including pharmacological treatments like bisphosphonates and third‐generation SERMs, in mitigating bone‐related side effects.Results: The findings indicate a critical need to balance the effectiveness of breast cancer treatments with the preservation of bone health. Pharmacological treatments like bisphosphonates and denosumab have been identified as essential for managing bone health in breast cancer patients. Furthermore, third‐generation SERMs show potential in reducing bone loss associated with cancer therapy.
Abstract A005: APC mutations dysregulate alternative polyadenylation in cancer
Authors: Gabel Austin M , Belliville Andrea E , Thomas James D , Mario B Pineda Jose , Bradley Robert K 
Published: November 2024

Abstract
Alternative polyadenylation (APA) affects most human genes and is recurrently dysregulated in cancers. However, the mechanistic origins of this dysregulation are incompletely understood. We completed an unbiased computational analysis of molecular regulators of poly(A) site selection across The Cancer Genome Atlas and identified that colorectal adenocarcinoma is distinct from all other cancer subtypes. We linked this distinction to the frequent presence of loss-of-function APC mutations in colorectal adenocarcinoma, which were strongly associated with expression of long 3′ UTRs relative to tumors lacking APC mutations. APC knockout similarly dysregulated APA in human colon organoids, and reduced APC expression was associated with APA dysregulation in tumor types lacking APC mutations. Building on previous work that identified APC as an RNA-binding protein that preferentially binds 3′ UTRs during mouse neurogenesis, we found that APC binding is most significantly enriched just upstream of proximal poly(A) sites within 3′ UTRs. Our results suggest that APC promotes proximal poly(A) site use and that APC loss contributes to pervasive APA dysregulation in human cancers.
Citation Format: Austin M Gabel, Andrea E Belliville, James D Thomas, Jose Mario B Pineda, Robert K Bradley. APC mutations dysregulate alternative polyadenylation in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A005.
Abstract A007: Characterization of miR-141 and miR-145 expression in cancer stem cells of metastatic prostate cancer patients
Authors: Shukla Kamla Kant , Choudhary Gautam Ram 
Published: November 2024

Abstract
Background: Prostate cancer (PCA) is the second most prevalent cancer globally and the fifth leading cause of cancer-related mortality. However, effective prognostic biomarkers for metastatic PCA remain lacking. Recent research highlights the role of microRNAs (miRNAs) in regulating cancer stem cells (CSCs) and influencing tumour progression across various cancers. Therefore, in this we investigated the effects of miR-141 and miR-145 expression on the metastatic PCA of CSCs and assessed their potential role as biomarkers for metastatic PCA prognosis. Methods: The expression levels of miR-141 and miR-145 were quantified using real-time qPCR. Flow cytometry was employed to assess the levels of prostate cancer stem cells (PCSCs) in tissue samples from patients with localized (non-metastatic) and metastatic PCA. Results: Our findings revealed a significant increase in miR-141 expression, accompanied by elevated levels of CD44^high/CD24^low and CD133^high, in metastatic PCA compared to localized PCA. Conversely, reduced miR-145 expression was associated with enhanced stemness characteristics, as indicated by increased CD44^high/CD24^low and CD133^high levels, in metastatic PCA compared to localized PCA. Additionally, prostate-specific antigen (PSA) and testosterone levels exhibited a significant rise (p&lt;0.001), while apoptosis rates decreased in both localized and metastatic PCA compared to localized PCA. Conclusions: The collective findings of this study suggest that miR-141 and miR-145, in conjunction with CSC markers, hold promise as diagnostic and prognostic tools for PCA. They may also be valuable for detecting minimal residual disease and improving therapeutic strategies for managing metastatic PCA.
Citation Format: Kamla Kant Shukla, Gautam Ram Choudhary. Characterization of miR-141 and miR-145 expression in cancer stem cells of metastatic prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A007.
Abstract A008: Identification of EYA2 as a promising biomarker for DICER1-related tumor predisposition
Authors: Wu Mona , Zhou Shengmei , Kommoss Felix , Wang Yemin , Amatruda James F 
Published: November 2024

Abstract
Background: DICER1-related tumor predisposition (DRTP), also known as DICER1 syndrome, is a genetic condition associated with an increased risk of developing various tumors, including pleuropulmonary blastoma, thyroid gland neoplasia, ovarian tumors, and cystic nephroma. Currently, the diagnosis and surveillance of DRTP primarily relies on genetic testing for DICER1 mutations. There is a pressing need for surrogate diagnostic biomarkers to improve early detection and monitoring. Objective: To identify and validate EYA2 as a potential biomarker for DICER1-related tumor predisposition. Methods: Murine mesenchymal stromal cell lines were developed to model the consequences of DICER1 mutations, including the DICER1E1705K mutation found in DRTP. Both bulk RNA sequencing (RNAseq) and microRNA sequencing (miRNAseq) were employed to identify differentially expressed mRNAs in these cell lines. The RNA and protein levels of Eya2 were measured by qRT-PCR and Western blot, respectively. De-repression of Eya2 mRNA by miRNA was evaluated by dual luciferase assay to link overexpression with the DICER1 defect of DRTP. Then, immunohistochemistry staining of EYA2 was performed on a panel of DRTP tumors. Results: We found that more than 2000 mRNAs were derepressed in mesenchymal stromal cells expressing DICER1E1705K as compared to DICER1WT. Among these, Eya2 emerged as a top candidate. We observed elevated Eya2 mRNA and protein levels in DICER1E1705K -expressing mesenchymal stromal cells. Utilizing a reporter assay, we also observed de-repression of the 3’ UTR of Eya2 upon expression of DICER1E1705K as compared to DICER1WT. Strong nuclear EYA2 staining was observed in a subset of DRTP tumor samples. Conclusion: Elevated EYA2 expression in tumor tissues from DRTP patients supports its potential use in both diagnostic and surveillance contexts. Further studies are warranted to validate EYA2 as a clinical biomarker and explore its utility in improving early detection and monitoring strategies for individuals at risk of DRTP.
Citation Format: Mona Wu, Shengmei Zhou, Felix Kommoss, Yemin Wang, James F Amatruda. Identification of EYA2 as a promising biomarker for DICER1-related tumor predisposition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A008.
Abstract A020: LncTransformer: Identifying novel prognostic long-noncoding RNA biomarkers for pancreatic cancer using deep learning
Authors: Singh Shivali 
Published: November 2024

Abstract
Pancreatic cancer remains a formidable challenge due to high mortality rates and limited therapeutic options due to late detection of the cancer. Recent literature has focused on investigating the potential of long noncoding RNAs (lncRNAs) as biomarkers in several cancers. To identify significantly altered expression of lncRNA in pancreatic cancer, I collected information from the Cancer Genome Atlas (TCGA) and extracted RNA- sequencing (RNA-seq) transcriptomic profiles of pancreatic carcinomas. Out of 60,660 gene transcripts shared between 151 pancreatic cancer patients, 38 lncRNAs were identified to be significantly differentially expressed. To find the lncRNAs related to metastatic progression of pancreatic cancer, different machine learning algorithms, including logistic regression (LR), support vector machine (SVM), random forest classifier (RFC), and a custom autoencoder model were trained to identify potential prognostic biomarkers. The custom deep learning model predicted metastatic prognostic biomarkers with a 92% accuracy, with the second-best accuracies coming from the SVM and RFC models, having an accuracy of 76%. Using the deep learning model, the following novel lncRNA and gene biomarkers were identified: LINC01300, SERPINB13, AC010789.1, TMPRSS15, DUSP5- DT, AL513128.3, MIR205HG, LINC00486, RF00019, LINC01115, and AC133530.1. Further investigating these results, specifically the identified lncRNA, the LINC01300 was identified to be potentially circulating in the blood. If further analysis proves this hypothesis correct then LINC01300 along with other identified genes could serve as biomarkers in a liquid biopsy. The identified biomarkers would be especially helpful in rural areas with lower accessibility to healthcare as it would allow for an easier, more efficient, and cost-effective method of pancreatic cancer detection. Based on these findings, further investigations of this gene panel in vitro and in vivo will be conducted, as they could be targeted for improved outcomes in pancreatic cancer patients and assist in the diagnosis of metastatic progression based on RNA-seq data of primary pancreatic tumors or the development of a liquid biopsy.
Citation Format: Shivali Singh. LncTransformer: Identifying novel prognostic long-noncoding RNA biomarkers for pancreatic cancer using deep learning [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A020.
Abstract B002: A therapeutically targetable positive feedback loop between long noncoding RNA-HLX-2-7, HLX, and MYC that promotes childhood cancer group 3 medulloblastoma
Authors: Perera Ranjan R 
Published: November 2024

Abstract
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MB is categorized into four main molecular subgroups: wingless pathway (WNT)-activated, sonic hedgehog pathway (SHH)-activated, group 3 (G3), and group 4 (G4). Although the driver pathways for G3 and G4 MB are unclear, most of these tumors are characterized by c-Myc and MYCN signatures, respectively. Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma formation and progression. We have identified lncRNA, lnc-HLX-2-7, as an oncogene and a potential therapeutic target in group 3 (G3) medulloblastomas. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of its host coding gene HLX, a sense overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC. Intravenous treatment with cerium oxide nanoparticle–coated antisense oligonucleotides targeting lnc-HLX-2-7 (CNP-ASO-lnc-HLX-2-7) and lipid nanoparticle-coated HLX (LNP-si-HLX) inhibits tumor growth by 40-50% in an intracranial medulloblastoma xenograft mouse model (p&lt;0.01). Combining nanoparticle-coated lnc-HLX-2-7 and HLX with standard-of-care cisplatin further inhibits tumor growth and significantly prolongs mouse survival compared with monotherapy (p&lt;0.01). Thus, the lnc-HLX-2-7–HLX–MYC axis is important for regulating G3 medulloblastoma progression, providing a strong rationale for using lnc-HLX-2-7 and HLX as therapeutic targets for G3 MBs.
Citation Format: Ranjan R Perera. A therapeutically targetable positive feedback loop between long noncoding RNA-HLX-2-7, HLX, and MYC that promotes childhood cancer group 3 medulloblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B002.