bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous Drive Friction Welding of AISI 8630 Low-Alloy Steel: Experimental Investigations on Microstructure Evolution and Mechanical Properties
Authors: Banerjee Amborish , Ntovas Michail , Silva Laurie Da , O’ Neill Ryan , Rahimi Salaheddin 
Published: November 2021

Abstract
Continuous drive friction welding (CDW) is a state-of-the-art solid-state welding technology for joining metallic components used in aerospace, oil and gas, and power generation industries. This study summarizes the results of mechanical and microstructural investigations on a modified AISI-8630 steel subjected to CDW. The effects of welding process parameters, including rotational speed, friction, and forge forces, during CDW were explored to determine an optimum welding condition. The mechanical properties of the weld, and microstructural characteristics across different regions of the weld were measured and examined. The microstructure characterization results suggest that the weld zone (WZ) experiences temperatures above the Ac3 and the thermo-mechanically affected zone (TMAZ) experiences temperatures between Ac1 and Ac3 of the material. Investigations with electron backscatter diffraction (EBSD) demonstrated the occurrence of strain-induced dynamic recrystallization in the weld. The weld demonstrated higher yield and ultimate tensile strengths at the expense of ductility and hardening capacity compared to the base metal (BM). The strain-hardening profiles of the welds exhibited a dual-slope characteristic, an indication of different levels of plastic deformation experienced by the constituent phases (i.e., martensite, bainite and ferrite) present in the microstructure. The maximum strength-to-ductility combination and static toughness values were obtained for the weld produced under the highest rotational speed, maximum friction force and an intermediate forge force of 1200–1400 rpm, 375–425 kN, and 600–650 kN, respectively.
On the Divergence Mechanisms Analysis of a Vibrating Blade Subjected to Repetitive Rubs With an Abradable Coating
Authors: Goldspiegel F. , Portemont G. , Berthe J. 
Published: November 2021

Abstract
Aeronautical compressor fans, currently, operate with minimal blade–casing clearance. Therefore, this makes the occurrence of rub events very likely. Under specific circumstances, the blade undergoes excessive amplification of contact-induced oscillations, called hereafter divergence, which can be critical for the structural integrity of the engine. This article proposes an investigation of the mechanisms responsible for the blade divergence. Experiments are conducted on a fully instrumented laboratory setup, consisting of a single flat blade being moved toward a rotating cylinder to initiate interactions, while monitoring the vibrations and the evolution of wear on the abradable coating. Two synchronization mechanisms have been identified as facilitating the divergence: (i) the inherent setup synchronization between the vibration modes related to the horizontal and vertical motion of the blade; (ii) the preferential blade–coating interactions in the vicinity of periodically distributed irregularities of the abradable coating, which act as a source of excitation of the vibrations.
Prevalence of eating disorders on male team sports players
Authors: Baldó Vela Daniel , Villarino Marín Antonio Luis , Bonfanti Noelia , Lázaro Martínez José Luis 
Published: November 2021

ObjectiveTo determinate the prevalence of EDs in national adult male team sports players.MethodologyAn observational study was conducted with 124 football, rugby, volleyball, handball, water polo, baseball and hockey players ranging between 18 and 55 years old. All subjects signed the informed consent before participating in the study. Data were collected via an online form including four validated questionnaires: The Eating Habits Questionnaire for Athletes, the Eating Attitudes Test (EAT-40), the Eating Disorders Inventory-2 and the Body Shape Questionnaire. Data analysis was conducted with the software IBM SPSS V.23.0.0.Results18.5% of the population presented a clinical profile compatible with an ED diagnosis. We cannot confidently say that the prevalence of EDs within our sample is conditioned by the analysed variables.ConclusionMale team sports players may also be a high-risk group in the development of EDs. Risk factors such as young age, semiprofessional sporting status and body fat composition could influence its development.
Outcomes in patients with a first episode of chest pain undergoing early coronary CT imaging
Authors: Siegersma Klaske R , Onland-Moret N Charlotte , Appelman Yolande , van der Harst Pim , Tulevski Igor I , Somsen G Aernout , Narula Jagat , den Ruijter Hester M , Hofstra Leonard 
Published: November 2021

ObjectivesTo investigate the impact of a CT-first strategy on all-cause and cardiovascular mortality in patients presenting with chest pain in outpatient cardiology clinics.MethodsPatients with a first presentation of suspected angina pectoris were identified and their data linked to the registrations of Statistics Netherlands for information on mortality. The linked database consisted of 33 068 patients. CT-first patients were defined as patients with a CT calcium score and coronary CT angiography, within 6 weeks after their initial visit. Propensity score matching (1:5) was used to match patients with and without a CT-first strategy. After matching, 12 545 patients were included of which 2308 CT-first patients and 10 237 patients that underwent usual care.ResultsMean age was 57 years, 56.3% were women and median follow-up was 4.9 years. All-cause mortality was significantly lower in CT-first patients (n=43, 1.9%) compared with patients without CT (n=363, 3.5%) (HR: 0.51, 95% CI 0.37 to 0.70). Furthermore, CT-first patients were more likely to receive cardiovascular preventative and antianginal medication (aspirin: 44.9% vs 27.1%, statins: 48.7% vs 30.3%, beta-blockers: 37.8% vs 25.5%, in CT-first and without CT-first patients, respectively) and to undergo downstream diagnostics and interventions (coronary interventions: 8.5% vs 5.7%, coronary angiography: 16.2% vs 10.6% in CT-first and without CT-first patients, respectively).ConclusionsIn a real-world regular care database, a CT-first strategy in patients suspected of angina pectoris was associated with a lowering of all-cause mortality.
Combination immunotherapy with nivolumab and ipilimumab in patients with rare gynecological malignancies: results of the CA209-538 clinical trial
Authors: Klein Oliver , Kee Damien , Gao Bo , Markman Ben , da Gama Duarte Jessica , Quigley Luke , Jackett Louise , Linklater Richelle , Strickland Andrew , Scott Clare , Mileshkin Linda , Palmer Jodie , Carlino Matteo , Behren Andreas , Cebon Jonathan 
Published: November 2021

BackgroundPatients with rare cancers represent 55% of all gynecological malignancies and have poor survival outcomes due to limited treatment options. Combination immunotherapy with the anti-programmed cell death protein 1 (anti-PD-1) antibody nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab has demonstrated significant clinical efficacy across a range of common malignancies, justifying evaluation of this combination in rare gynecological cancers.MethodsThis multicenter phase II study enrolled 43 patients with advanced rare gynecological cancers. Patients received induction treatment with nivolumab and ipilimumab at a dose of 3 mg/kg and 1 mg/kg, respectively, every 3 weeks for four doses. Treatment was continued with nivolumab monotherapy at 3 mg/kg every 2 weeks until disease progression or a maximum of 2 years. The primary endpoint was the proportion of patients with disease control at week 12 (complete response, partial response or stable disease (SD) by Response Evaluation Criteria In Solid Tumor V.1.1). Exploratory evaluations correlated clinical outcomes with tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB).ResultsThe objective response rate in the radiologically evaluable population was 36% (12/33 patients) and in the intention-to-treat population was 28% (12/43 patients), with additional 7 patients obtaining SD leading to a disease control rate of 58% and 44%, respectively. Durable responses were seen across a range of tumor histologies. Thirty-one (72%) patients experienced an immune-related adverse event (irAE) with a grade 3/4 irAE observed in seven (16%) patients. Response rate was higher among those patients with baseline PD-L1 expression (≥1% on tumor cells) but was independent of TMB.ConclusionsIpilimumab and nivolumab combination treatment has significant clinical activity with a favorable safety profile across a range of advanced rare gynecological malignancies and warrants further investigation in these tumor types.
mTOR-Dependent ARID1A Degradation: A New Twist in the Genetic–Epigenetic Interplay Driving Hepatocellular Carcinoma
Authors: Pease David R. , Fernandez-Zapico Martin E. 
Published: November 2021

Abstract
The importance of the cross-talk between the genetic and epigenetic alterations promoting cancer development is well understood; however, the molecular details underlying the mechanism of how oncogenic signaling remodels the epigenome to generate a procancer transcriptome require further elucidation. The study by Zhang and colleagues in this issue of Cancer Research reveals a novel role for oncogenic mTOR signaling leading to the degradation of a prominent chromatin remodeler, ARID1a, establishing an altered, protumor chromatin landscape in hepatocellular carcinoma (HCC) controlling tumor deve-lopment and treatment resistance. These findings highlight oncogenic effects on chromatin remodelers as an important factor in both HCC pathobiology and therapeutic response. As strategies for cancer therapy begin to move in an increasingly individualized direction, increased knowledge into the impact of restoring the function of chromatin remodelers on response to therapy is warranted.
See related article by Zhang et al., p. 5652
Abstract IA-001: Molecular subtypes and vulnerabilities in pancreatic cancer
Authors: Aguirre Andrew 
Published: November 2021

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with few effective treatment options. Understanding the molecular underpinnings of PDAC is critical to developing new biomarker strategies and therapeutic approaches for patients. In this talk, I will review our understanding of the genetics and biology of PDAC, including the major genomic subtypes and transcriptional programs of the disease. I will discuss how single-cell RNA sequencing has refined our understanding of subtype heterogeneity and evolution in the context of therapy and PDAC model systems. Moreover, I will discuss new KRAS inhibitors, their mechanisms of resistance and their potential to impact the treatment landscape for pancreatic cancer patients. Lastly, I will discuss our recent efforts to use functional genetic screening approaches to define new therapeutic targets in pancreatic cancer, highlighting our work on the VPS4A ATPase as a potential new target in tumors with 18q/SMAD4 deletion.
Citation Format: Andrew Aguirre. Molecular subtypes and vulnerabilities in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr IA-001.
Abstract IA-003: Proteogenomic characterizations of pancreatic ductal adenocarcinoma
Authors: Cao Liwei , Huang Chen , Zhou Daniel Cui , Hu Yingwei , Lih Mamie , Savage Sara R. , Krug Karsten , Clark David J. , Schnaubelt Michael , Chen Lijun , Leprevost Felipe da Veiga , Eguez Rodrigo Vargas , Nesvizhskii Alexey I. , Mani D.R. , Omenn Gilbert S. , Boja Emily S. , Mesri Mehdi , Robles Ana I. , Rodriguez Henry , Bathe Oliver F. , Chan Daniel W. , Hruban Ralph H. , Ding Li , Zhang Bing , Zhang Hui ,   Clinical Proteomic Tumor Analysis Consortium
Published: November 2021

Abstract
Pancreatic cancer is one of the deadliest cancers and the five-year survival rate is less than 10%. Pancreatic ductal adenocarcinoma (PDAC) represents more than 90% of all pancreatic malignancies, and is responsible for the majority of pancreatic cancer-related deaths. Towards understanding the underlying molecular alterations that drive PDAC oncogenesis and identify therapeutic targets for personalized treatments, we comprehensively characterized 140 pancreatic cancers and 67 normal adjacent tissues. To ensure robust, downstream analyses, tumor neoplastic cellularity was assessed via multiple, orthogonal strategies using molecular features, and verified via pathological estimation of tumor cellularity based on histological review to select tumors with sufficient tumor cellularity. We also included the analysis of 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole genome sequencing, whole exome sequencing, methylation, RNA-seq, and miRNA-seq were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. These characterizations revealed functional impacts of genomic and epigenomic alterations on proteins and protein modifications, delineated PDAC cell microenvironment compositions and the immune signatures for immunotherapy, also uncovered putative kinase inhibitors that could be tested for therapy. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets.
Citation Format: Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Alexey I. Nesvizhskii, D.R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana I. Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang, Clinical Proteomic Tumor Analysis Consortium. Proteogenomic characterizations of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr IA-003.
Abstract PO-004: Basal-like, Classical A, and Classical B subtypes of pancreatic cancer show distinct immuno-suppressive molecular profiles
Authors: LaPlante Emily L. , Liu Dongliang , Milosavljevic Aleksandar , Yao Qizhi 
Published: November 2021

Abstract
With recent advances in distinguishing Pancreatic Ductal Adenocarcinoma (PDAC) subtypes based on transcriptional profiles, it is becoming clear that different subtypes have distinct therapeutic responses– e.g. Basal-like tumors tend to show less response to chemotherapy than Classical tumors. Here, we asked if the Basal-like, Classical A, and Classical B PDAC subtypes show distinct immuno-suppressive molecular profiles of relevance for targeted immunotherapy of PDAC. Toward this goal, we leveraged two large, public sequencing cohorts – TCGA and ICGC. To accommodate the large variation in cell type composition among the tumors across these cohorts, we applied the novel expression deconvolution (XDec) method to computationally deconvolute the bulk RNA-seq profiles. The method identified cell-type composition of each tumor and identified distinct Basal-like, Classical A, and Classical B subtypes, thus allowing classification of each tumor based on the state of its constituent cancer cell fraction. We further extended the method to also infer cell-type specific gene expression for each tumor sample and to identify correlation of cell-type specific gene expression levels across cohorts. Using the extended method, we determined that Basal-like cancer cells are CD274 high, Classical B cancer cell CD274 expression correlated strongly with MSLN and RELA (a recently proposed mechanism controlling PD-L1), and Classical A cancer cells had low CD274 expression. Because heterotypic interactions may also contribute toward an immuno-suppressive microenvironment, we next correlated expression levels between cancer and stromal cell types. Cancer cell MSLN expression correlated strongly with stromal CD274 expression which also correlated with stromal IFNGR1 and IFNγ. Using co-culture experiments we validated the causative relationship between cancer cell MSLN and stromal INFGR1 and CD274. Taken together, our results suggest that PDAC subtypes have distinct therapeutic vulnerabilities, with Basal-like and MSLN-high Classical B patients more likely to respond to PD-L1 targeting therapies. Moreover, we provided a methodological advance by extending the XDec method and by making it web-accessible, thus allowing the community to derive hypotheses testable in cell line models by performing correlations of cell-type specific gene expression levels deconvoluted from bulk RNA-seq profiles of PDAC patient tumors.
Citation Format: Emily L. LaPlante, Dongliang Liu, Aleksandar Milosavljevic, Qizhi Yao. Basal-like, Classical A, and Classical B subtypes of pancreatic cancer show distinct immuno-suppressive molecular profiles [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-004.
Abstract PO-006: CircRTN4 promotes pancreatic cancer progression through a novel circRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein
Authors: Wong Chi Hin , Lou Ut Kei , Fung Frederic Khe-Cheong , Tong Joanna H. M. , To Ka-Fai , Chan Stephen Lam , Chen Yangchao 
Published: November 2021

Abstract
Background & Aims: Circular RNAs (circRNAs) play important roles in many biological processes. However, the detailed mechanism underlying the critical roles of circRNAs in cancer remains largely unexplored. We aim to explore the molecular mechanisms of circRTN4 with critical roles in pancreatic ductal adenocarcinoma (PDAC). Methods: CircRTN4 expression level was examined in PDAC primary tumors. The oncogenic roles of circRTN4 in PDAC tumor growth and metastasis were studied in mouse tumor models. Bioinformatics analysis, luciferase assay and miRNA pulldown assay were performed to study the novel circRTN4-miRNA-lncRNA pathway. To identify circRTN4-interacting proteins, we performed circRNA-pulldown and mass spectrometry in PDAC cells. Protein stability assay and 3-Dimensional structure modeling were performed to reveal the role of circRTN4 in stabilizing RAB11FIP1. Results: circRTN4 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that circRTN4 promoted PDAC tumor growth and liver metastasis. Mechanistically, circRTN4 interacted with tumor suppressor miR-497-5p in PDAC cells. CircRTN4 knockdown upregulated miR-497-5p to inhibit the oncogenic lncRNA HOTTIP expression. Furthermore, we identified critical circRTN4-intercting proteins by circRNA-pulldown in PDAC cells. CircRTN4 interacted with important epithelial-mesenchymal transition (EMT)- driver RAB11FIP1 to block its ubiquitination site. We found that circRTN4 knockdown promoted the degradation of RAB11FIP1 by increasing its ubiquitination. Also, circRTN4 knockdown inhibited the expression of RAB11FIP1-regulating EMT-markers Slug, Snai1, Twist, Zeb1 and N-cadherin in PDAC. Conclusion: The upregulated circRTN4 promotes tumor growth and liver metastasis in PDAC through the novel circRTN4-miR-497-5p-HOTTIP pathway. Also, circRTN4 stabilizes RAB11FIP1 to contribute EMT.
Citation Format: Chi Hin Wong, Ut Kei Lou, Frederic Khe-Cheong Fung, Joanna H. M. Tong, Ka-Fai To, Stephen Lam Chan, Yangchao Chen. CircRTN4 promotes pancreatic cancer progression through a novel circRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-006.
Abstract PO-019: Reprogramming of naïve B cells in pancreatic cancer subverts humoral immunity
Authors: Mirlekar Bhalchandra , Pylayeva-Gupta Yuliya 
Published: November 2021

Abstract
B cells frequently infiltrate human tumors, and the intra-tumoral abundance of plasma cells can correlate with improved patient prognosis. However, many tumors are devoid of plasma B cells, and strategies to enhance anti-tumor B cell responses are needed. We report the existence of a negative regulatory signaling network that reprograms naïve B cells in pancreatic cancer to antagonize anti-tumor plasma B cells. This network is driven by IL-35-mediated STAT3 activation, which directly stimulates upregulation of the pioneer transcription factors Pax5 and Bcl6 in naïve B cells and impedes plasma cell differentiation while simultaneously activating regulatory B cell phenotypes. Significantly, inhibition of Bcl6 reversed this tumor-associated reprogramming of naïve B cells, enabling intra-tumoral accumulation of plasma cells, and reduced tumor growth. Our data provide evidence that B cell dysfunction in cancer involves a potentially targetable suppression program that alters the differentiation potential of naïve B cells.
Citation Format: Bhalchandra Mirlekar, Yuliya Pylayeva-Gupta. Reprogramming of naïve B cells in pancreatic cancer subverts humoral immunity [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-019.