bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-034: Increased physical activity delays development of obesity-induced pancreatic ductal adenocarcinoma in mice and modulates inflammation
Authors: Pita-Grisanti Valentina , Dubay Kelly , Lahooti Ali , Badi Niharika , Ueltschi Olivia , Chavez-Tomar Myrriah , Terhorst Samantha , Knoblaugh Sue , Coss Christopher , Mace Thomas , Choueiry Fouad , Hinton Alice , Mitchell Jennifer M , Basen-Engquist Karen , Cruz-Monserrate Zobeida 
Published: November 2020

Abstract
Background: Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), a deadly disease with no preventive strategies. Lifestyle interventions to decrease obesity might serve to prevent obesity-induced PDAC. We examined whether decreasing obesity via increased physical activity (PA) and/or diet-induced weight loss could prevent PDAC in mice and compared the levels of systemic inflammatory-associated cytokines in human subjects undergoing a PA intervention. Methods: Obesity-induced PDAC mouse models were exposed to various interventions before and after cancer initiation, that included increased PA, diet-induced weight loss, and/or chemotherapy. We evaluated body composition, tumor progression, growth, fibrosis, and inflammation. Circulating inflammatory-associated cytokines of overweight/obese human subjects before and after a PA intervention were also compared. Results: Genetically engineered PDAC mice on a PA intervention while on a HFD, gained less weight, displayed lower grade pancreatic intraepithelial neoplasias lesions, and fewer mice developed PDAC compared to controls. Similar results were observed in PDAC mice given a HFD to induce obesity, prior to a control diet (CD) and PA intervention, compared to mice given a CD after the HFD. PA alone or with a CD intervention decreased body weight but did not prevent tumor growth in an orthotopic mouse model of PDAC. PA combined with chemotherapy increased the percentage of splenic cluster of differentiation 8+ (CD8+) T cells in PDAC mice. Finally, PA prevented the increase of systemic inflammatory-associated cytokines in PDAC mice and in overweight/obese control human subjects. Conclusions: PA alone or with diet-induced weight loss delayed the progression of PDAC in genetically engineered mice and reduced inflammation. While these interventions did not prevent tumor growth in the orthotopic mouse model, it did modulate immune responses. Reducing obesity by increasing PA and decreasing dietary fat intake could be a way of reducing the incidence of PDAC in high-risk obese individuals.
Citation Format: Valentina Pita-Grisanti, Kelly Dubay, Ali Lahooti, Niharika Badi, Olivia Ueltschi, Myrriah Chavez-Tomar, Samantha Terhorst, Sue Knoblaugh, Christopher Coss, Thomas Mace, Fouad Choueiry, Alice Hinton, Jennifer M Mitchell, Karen Basen-Engquist, Zobeida Cruz-Monserrate. Increased physical activity delays development of obesity-induced pancreatic ductal adenocarcinoma in mice and modulates inflammation [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-034.
Abstract PO-042: FGFR1 expression correlates inversely with the in vitro and in vivo efficacy of FGFR inhibitors in pancreatic cancer
Authors: Lin Qingxiang , Serratore Andrea , Kandel Eugene , Straubinger Robert M. 
Published: November 2020

Abstract
Aberrant functions of fibroblast growth factor receptors (FGFR) have been implicated in the tumor progression of pancreatic cancer (PaCA). However, the mechanisms of FGFR action and the therapeutic utilities of FGFR inhibitors (FGFRi) in PaCA remain largely under-investigated. Here the mechanisms of FGFR inhibition in PaCA were investigated using pan-FGFRi that are under clinical development and specific shRNA against individual FGFRs. FGFRi treatment, such as BGJ398 and AZD4547, significantly inhibited cell proliferation, migration, and invasion, and cell expression of key markers associated with cell survival and invasiveness was suppressed, in multiple PaCA cell lines. Gemcitabine (Gem) is the standard-of-care for PaCA, and the development of Gem resistance (GemR) compromises its efficacy, thereby Gem only provides modest survival benefits. We found that FGFRi was effective in inhibiting cell proliferation, migration of strongly GemR cells and tumors (named as MIA-GR8 cells and MIA-GR8 tumors) that were all derived by increasing Gem exposure from MIA PaCa-2 cells in vitro and selected by Gem in vivo. These results suggest its potential clinical utility as a class of alternative drug candidates in tumors that acquired GemR. Downregulation of GemR markers mediated by FGFRi treatment in GemR cells also suggested its therapeutic application of FGFRi in combination with Gem, in order to overcome GemR. Mechanistically, the molecular mechanisms of individual FGFR were investigated. shRNA-mediated inhibition of FGFR2 or FGFR3 did not decrease cell growth, and the overexpression of FGFR1 promoted cell migration rather than proliferation. Furthermore, the efficacy of FGFRi treatment was investigated in multiple cell lines and patient-derived xenograft. The inhibitory effects of BGJ398 in PANC-1 cell growth and migration were compromised by exogenic overexpression of FGFR1, and its efficacy on cell viability suppression was correlated with FGFR1 in multiple cell lines. In patient-derived xenografts, the efficacy of FGFRi on tumor growth inhibition was also correlated with FGFR1 expression. These data provide evidence that precision medicine which targets FGFR using FGFRi in PaCA tumors which express relatively modest or low amount of FGFR1 could be more effective than that with a high FGFR1 expression.
Citation Format: Qingxiang Lin, Andrea Serratore, Eugene Kandel, Robert M. Straubinger. FGFR1 expression correlates inversely with the in vitro and in vivo efficacy of FGFR inhibitors in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-042.
Abstract PO-043: Interception of pancreatic cancer progression
Authors: McDermott Matthew L. , Ferguson Lesley P. , Chambers Kendall , Rajbhandari Nirakar , Reya Tannishtha 
Published: November 2020

Abstract
Pancreatic Cancer (PC) is projected to be one of the leading causes of cancer related death by 2030. Although other cancers have made significant strides towards improved treatment, PC still remains at a 9% fiver year survival rate due to end-stage diagnosis, aggressive metastasis, and a protective stromal wall. Therefore, to identify novel therapeutic targets, our lab focuses on studying cancer stem cells, a highly chemo-resistant sub-population of pancreatic cancer cells. RNA-seq analysis of these cancer stem cells has revealed a number of genes that are enriched compared to non-therapy resistant cells and normal pancreas. We hypothesize that genes turned on through pancreatic cancer progression contribute to therapy resistance. If PC could be targeted at earlier stages, it would be possible for therapeutics to bypass the wealth of issues that occur as it advances. By cross referencing our RNA-seq analysis to sequencing performed at various stages of pancreatic cancer development in mice, a subset of genes is not only up-regulated in therapy resistant cells, but increases in expression as normal pancreas progresses to an end stage tumor. Preliminary studies have shown that inhibition of these select genes reduces growth of mouse pancreatic cancer in vitro and in vivo. Ongoing studies are to (1) test if inhibition of these genes reduces early stage PC growth in vitro and in vivo, and (2) test how gene knockdown affects human pancreatic cancer cell growth in vitro and in vivo.
Citation Format: Matthew L. McDermott, Lesley P. Ferguson, Kendall Chambers, Nirakar Rajbhandari, Tannishtha Reya. Interception of pancreatic cancer progression [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-043.
Abstract PR-003: Tumor-cell-intrinsic epigenetic factors underlie the heterogeneity of immune infiltration and response to immunotherapy in pancreatic cancer
Authors: Li Jinyang , Yuan Salina , Norgard Robert J. , Yan Fangxue , Vonderheide Robert H. , Blanco Andres , Stanger Ben Z. 
Published: November 2020

Abstract
Resistance to immunotherapy is a major problem of current clinical care for cancer patients. While T cell abundance is essential for tumor responsiveness to immunotherapy, factors that dictate T cell infiltration in tumor microenvironments are not fully understood. To understand the tumor-cell-intrinsic factors underlying the heterogeneity of tumor immunity and sensitivity to immunotherapy, we established a new experimental system by generating a library of congenic pancreatic tumor cell clones from a genetic mouse model driven by mutant Kras and p53. These tumor cell clones robustly formed implanted tumors that recapitulated T-cell-inflamed and non-T-cell-inflamed tumor microenvironments, associated with distinct patterns of infiltration by T cells and myeloid cells. We found that the non-T-cell-inflamed phenotype was dominant over the T-cell-inflamed phenotype in the local tumor microenvironment. An integrated transcriptomic and epigenetic analysis revealed that tumor-cell-intrinsic expression of CXCL1, EPHA2 and PTGS2 as determinants of the non-T-cell-inflamed microenvironment, and ablation of tumor-cell-intrinsic CXCL1, EPHA2 or PTGS2 promoted T cell infiltration and sensitivity to a combination of chemotherapies, CD40 agonist, and checkpoint blockades. Similarly, we identified tumor cell-intrinsic epigenetic factor, USP22, as a key regulator of immune infiltration and immunotherapy response in pancreatic cancer. Ablation of tumor-cell-intrinsic USP22 enhanced T cell infiltration and suppressed myeloid cell infiltration in implanted pancreatic tumors as well as increased sensitivities of tumors to the combined immunotherapy. These results demonstrated that heterogeneity of tumor immune phenotypes is driven by tumor-cell-intrinsic factors, including epigenetic factors, that can be manipulated to influence the outcome of immunotherapies.
Citation Format: Jinyang Li, Salina Yuan, Robert J. Norgard, Fangxue Yan, Robert H. Vonderheide, Andres Blanco, Ben Z. Stanger. Tumor-cell-intrinsic epigenetic factors underlie the heterogeneity of immune infiltration and response to immunotherapy in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PR-003.
The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis
Authors: Hong Xin , Roh Whijae , Sullivan Ryan J. , Wong Keith H.K. , Wittner Ben S. , Guo Hongshan , Dubash Taronish D. , Sade-Feldman Moshe , Wesley Benjamin , Horwitz Elad , Boland Genevieve M. , Marvin Dieuwke L. , Bonesteel Todd , Lu Chenyue , Aguet François , Burr Risa , Freeman Samuel S. , Parida Laxmi , Calhoun Katherine , Jewett Michelle K. , Nieman Linda T. , Hacohen Nir , Näär Anders M. , Ting David T. , Toner Mehmet , Stott Shannon L. , Getz Gad , Maheswaran Shyamala , Haber Daniel A. 
Published: November 2020

Abstract

Circulating tumor cells (CTC) are shed by cancer into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastasis. We show that single CTCs from patients with melanoma coordinately upregulate lipogenesis and iron homeostasis pathways. These are correlated with both intrinsic and acquired resistance to BRAF inhibitors across clonal cultures of BRAF-mutant CTCs. The lipogenesis regulator SREBP2 directly induces transcription of the iron carrier Transferrin (TF), reducing intracellular iron pools, reactive oxygen species, and lipid peroxidation, thereby conferring resistance to inducers of ferroptosis. Knockdown of endogenous TF impairs tumor formation by melanoma CTCs, and their tumorigenic defects are partially rescued by the lipophilic antioxidants ferrostatin-1 and vitamin E. In a prospective melanoma cohort, presence of CTCs with high lipogenic and iron metabolic RNA signatures is correlated with adverse clinical outcome, irrespective of treatment regimen. Thus, SREBP2-driven iron homeostatic pathways contribute to cancer progression, drug resistance, and metastasis.

Significance:
Through single-cell analysis of primary and cultured melanoma CTCs, we have uncovered intrinsic cancer cell heterogeneity within lipogenic and iron homeostatic pathways that modulates resistance to BRAF inhibitors and to ferroptosis inducers. Activation of these pathways within CTCs is correlated with adverse clinical outcome, pointing to therapeutic opportunities.
This article is highlighted in the In This Issue feature, p. 521
Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments
Authors: Jung Young Hee , Jang Hyemin , Park Seong Beom , Choe Yeong Sim , Park Yuhyun , Kang Sung Hoon , Lee Jong Min , Kim Ji Sun , Kim Jaeho , Kim Jun Pyo , Kim Hee Jin , Na Duk L. , Seo Sang Won 
Published: November 2020

Background and Purpose:
We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy.

Methods:
We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups.

Results:

The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%;
P
<0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7,
P
=0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8,
P
=0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%,
P
=0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2,
P
=0.041) than the dentate group.

Conclusions:
Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.
Higher-Order Approximation to the Guidewire Model Used in Simulators of Cardiac Catheterization and Multiple Segment Relaxations
Authors: Baier-Saip Jürgen A. , Baier Pablo A. , Oliveira Jauvane C. , Baier Herbert 
Published: November 2020

Abstract
Cardiac catheterism is important because it offers many advantages in comparison to open surgery, for example, fewer injuries, lower risk of infections, and shorter recovery times. Simulators play a fundamental role in training packages, and virtual learning environments are less stressful. Moreover, they can also be used in certification boards and in performance assessments. A realistic and interactive simulator must be fast. In this work, the physical model of the guidewire used in catheter simulations has been improved. In particular, we determined a simple analytic expression to calculate the direction of a guidewire segment, which minimizes the total energy. The surface energy resulting from the guidewire--artery interaction and the bending energy of the guidewire is approximated up to the second order, which gives rise to interactions between segments. Furthermore, the multiple segment relaxations are introduced, enhancing the convergence especially at the beginning of the relaxation cycle. The formulas are written in matrix form of dimension 4M×4M, where M represents the number of segments varied in the update step. The method results in a more stable static solution.
Joshua Marshman and the Study of Spoken Chinese
Authors: Söderblom Saarela Mårten 
Published: November 2020

Abstract
Joshua Marshman, English Baptist missionary in India, spent the decade between 1805 and 1814 studying the Chinese language. Marshman’s unique vantage point in India makes him stand out among European Sinologists of his time. Marshman’s familiarity with Indian languages and the local traditions of studying them informed his speculative publications on Chinese. Learning Chinese from a native informant was not enough for him. He thought that only through a mastery of both Sanskrit and Mandarin could the Chinese language be really comprehended and put to use by foreign missionaries and scholars alike. This article examines Marsh­man’s course of study and his publications on the Chinese language. It argues that although Marshman’s hope to forge a hybrid, Sanskrit-infused Sinology appeared as a dead end in his time, he was right to focus on the importance of foreign contacts in the formation of the modern Chinese language.
Affect, Ethics, and Cognition
Authors: Mather Hannah R. K. 
Published: November 2020

Abstract
This article considers the Spirit’s role in the interpretation of Scripture, otherwise known as pneumatic interpretation. It outlines that whilst we may approach scripture seeking to interpret its written truth, the Spirit’s concern is with so much more than just our minds. Thus, pneumatic interpretation is holistic and cannot be restricted to interpretation of the scriptural text. The Spirit always works through and beyond the written words, seeking to interpret and appropriate scriptural truth affectively, ethically, and cognitively in our lives in ways that align with Scripture and transform us holistically into knowledge of and relationship with God as Father, Son, and Spirit. However, within this lies a paradox that whilst the Holy Spirit of God is all-powerful, discernment and reception of truth brought by the Spirit through Scripture (or in ways leading towards Scripture) is either helped or hindered by ethical action and choice.
‘Worship in the Spirit’ in the Acts of the Apostles
Authors: Twelftree Graham H. 
Published: November 2020

Abstract
Pentecostals and charismatics claim that their expressive corporate worship is ‘in the Spirit’. This claim is tested by seeing how Luke in Acts, often taken by Pentecostals and charismatics as providing prescriptions for worship, might respond to the claim. From an examination of those places in Acts where believers’ worship and the Spirit motifs are found together it is concluded that Luke would assume that not some, but that all worship by the followers of Jesus – in the temple or synagogue or homes – was ‘in the Spirit’. For Luke it is not what believers do or experience in worship that would cause him to describe it as ‘in the Spirit’, but what had already been done to them in being filled with the Spirit so that there is nothing about Pentecostal or charismatic worship that would cause him to think it any more ‘in the Spirit’ than other styles of worship.
Elements of the Dynamical Response to Climate Change over the Mediterranean
Authors: Tuel Alexandre , O’Gorman Paul A. , Eltahir Elfatih A. B. 
Published: November 2020

AbstractFuture climate simulations indicate that the Mediterranean Basin will experience large low-level circulation changes during winter, characterized by a strong anomalous ridge that drives a regional precipitation decline. Previous research highlighted how shifts in stationary wave structure and the atmospheric response to reduced warming of the Mediterranean Sea relative to land could explain the development of this anomalous pressure high. Here, we expand on these results and provide new arguments for why and how the Mediterranean is projected to experience large circulation changes during winter. First, we find that zonal asymmetries in the vertical structure of stationary waves are important to explain the enhanced circulation response in the region and that these asymmetries are related through the external mode to the vertical structure of the mean zonal wind. Second, in winter, the Mediterranean is located just to the north of the Hadley cell edge and consequently is relatively free of large-scale descent; together with low near-surface static stability above the sea, this condition allows the weaker warming trend above the sea to propagate to the low troposphere and trigger a major circulation response. During summer, however, remotely forced descent and strong static stability prevent the cooling anomaly from expanding upward. Most of the intermodel scatter in the projected low-level circulation response in winter is related to the spread in upper-tropospheric dynamical trends. Importantly, because climate models exhibit too much vertical coherence over the Mediterranean, they likely overestimate the sensitivity of Mediterranean near-surface circulation to large-scale dynamical changes.
Effect of statin on perioperative myocardial injury in isolated valve surgery
Authors: Kaushik Atul , Kapoor Aditya , Agarwal Surendra Kumar , Pande Shantanu , Kashyap Shiridhar , Sinha Archana , Khanna Roopali , Kumar Sudeep , Garg Naveen , Tewari Satyendra , Goel Pravin K 
Published: November 2020

Background Statins have known pleiotropic effects that confer protection from ischemia-reperfusion injury. Because cardiopulmonary bypass is a potentially reversible ischemia-reperfusion sequence, we aimed to assess whether statin loading could help to limit myocardial injury in patients undergoing isolated heart valve replacement under cardiopulmonary bypass. Methods One hundred patients with rheumatic valvular heart disease undergoing valve replacement received either a loading dose of rosuvastatin (40 mg initiated 7 days before surgery; loaded group) or no statins (non-loaded group). Cardiac troponin I, creatine kinase MB, and brain natriuretic peptide were measured at 8, 24, and 48 hours postoperatively. The primary endpoint was the extent of perioperative myocardial injury measured by the area under the curve for each biomarker. Results Despite similar baseline levels, all biomarkers at 8, 24, and 48 h were significantly lower in the loaded group. The area under the curve of each biomarker was significantly lower in the loaded group than in the non-loaded group (troponin I: 31.43 vs. 77.21 ng·h·mL−1, creatine kinase MB 309.31 vs. 429.12 ng·h·mL−1, brain natriuretic peptide 5176.11 vs. 16119.31 pg·h·mL−1, all p < 0.001). The mean changes from baseline to peak levels were also significantly lower in the loaded group. The loaded group had a shorter hospital stay but no significant difference was seen in ventilator time, inotrope time, aortic crossclamp time, cardiopulmonary bypass time, or intensive care unit stay. Conclusion In patients undergoing valve replacement, high-dose statin loading before surgery had a favorable impact on the release kinetics of various cardiac biomarkers.