bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remote Monitoring of Cancer Patient Participation in a 12-Week Online Yoga Study: Challenges and Directions for Future Research
Authors: Eckert Ryan , Huberty Jennifer , Kosiorek Heidi , Clark-Sienkiewicz Shannon , Larkey Linda , Mesa Ruben 
Published: November 2020

Introduction: The delivery of online interventions in cancer patients/survivors has increased. The measurement of participation in online interventions is important to consider, namely, the challenges of the remote assessment of activity. The purpose of this study was to report the measures used to assess intervention compliance and other physical activity participation in two online yoga studies, the relationship between the multimethod measures used, and the ability of cancer patients to complete these measures. Methods: The methods described are of two online yoga studies (feasibility and pilot). Cancer patients were asked to participate in 60 min/week of online yoga for 12 weeks, complete a weekly yoga log, wear a Fitbit daily for 12 weeks, and complete a weekly physical activity log. Finally, Clicky®, a web analytics software, was used to track online yoga participation. Results: Eighty-four people participated across both studies, with 63/84 participating in online yoga, averaging 57.5 ± 33.2 min/week of self-reported yoga participation compared to 41.4 ± 26.1 min/week of Clicky® yoga participation (Lin concordance = 0.28). All 84 participants averaged 95.5 ± 111.8 min/week of self-reported moderate/vigorous physical activity compared with 98.1 ± 115.9 min/week of Fitbit-determined moderate/vigorous physical activity (Lin concordance = 0.33). Across both studies, 82.9% of the yoga logs were completed, the Fitbit was worn on 75.2% of the days, and 78.7% of the physical activity logs were completed. Conclusions: Weak relationships between self-report and objective measures were demonstrated, but the compliance rates were above 75% for the study measures. Future research is needed, investigating the intricacies of self-report physical activity participation in remote interventions and the validation of a gold standard measurement for online interventions.
Insulin sensitivity predicts cognitive decline in individuals with prediabetes
Authors: Willmann Caroline , Brockmann Kathrin , Wagner Robert , Kullmann Stephanie , Preissl Hubert , Schnauder Günter , Maetzler Walter , Gasser Thomas , Berg Daniela , Eschweiler Gerhard W , Metzger Florian , Fallgatter Andreas J , Häring Hans-Ulrich , Fritsche Andreas , Heni Martin 
Published: November 2020

IntroductionEpidemiological studies indicate an association between type 2 diabetes and cognitive dysfunction that appear to start already in the prediabetic state. Although cross-sectional studies have linked insulin resistance to impaired cognition, the potential predictive value of insulin resistance has not yet been sufficiently studied longitudinally without confounding by overt diabetes (and its pharmacological treatment).Research design and methodsWe investigated longitudinal data from participants of the ‘Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration’ Study. Subjects underwent a neurocognitive assessment battery (CERAD Plus battery; Consortium to Establish a Registry for Alzheimer’s Disease) at baseline and followed every 2 years (median follow-up 4.0 Q1–3: 2.2–4.3 years). Subjects within a pre-diabetic glycated hemoglobin range of 5.6%–6.5% underwent 5-point 75 g oral glucose tolerance tests (OGTTs) with assessment of insulin sensitivity and insulin secretion (n=175). Subjects with newly diagnosed diabetes mellitus or with major depressivity (Beck Depression Inventory >20) were excluded (n=15). Data were analyzed by mixed models using sex, age and glycemic trait as fixed effects. Subject and time since first measurement were used as random effects.ResultsInsulin sensitivity was positively associated with the CERAD sum score (higher is better) in a time-dependent manner (p=0.0057). This result is mainly driven by a steeper decrease in the memory domain associated with lower insulin sensitivity (p=0.029). The interaction between age and insulin sensitivity was independent of glycemia (p=0.02). There was also no association between insulin secretion and cognition.ConclusionsInsulin resistance rather than sole elevation of blood glucose predicts cognitive decline, specifically in the memory domain, in persons with prediabetes. Treatments of diabetes that improve insulin sensitivity might therefore have the potential to postpone or even prevent cognitive decline in patients with diabetes.
Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial
Authors: de Barros Barbara , Lambert Saba M , Shah Mahesh , Pai Vivek V , Darlong Joydeepa , Rozario Benjamin Jewel , Alinda Medhi Denisa , Sales Anna M , Doni Shimelis , Hagge Deanna A , Shrestha Dilip , Listiawan M. Yulianto , Yitaye Abeba M , Nery Jose A C , Neupane Kapil D , Dias Vivianne L A , Butlin C. Ruth , Nicholls Peter G , Lockwood Diana , Walker Stephen L 
Published: November 2020

IntroductionErythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the ‘MTX and prednisolone study in ENL’ (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL.Methods and analysisMaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients’ reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events.Ethics and disseminationResults will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.
SMART U(1)$$_X$$: standard model with axion, right handed neutrinos, two Higgs doublets and U(1)$$_X$$ gauge symmetry
Authors: Okada Nobuchika , Raut Digesh , Shafi Qaisar 
Published: November 2020

AbstractTo address five fundamental shortcomings of the Standard Model (SM) of particle physics and cosmology, we propose a phenomenologically viable framework based on a $$U(1)_X \times U(1)_{PQ}$$

U

(
1
)

X

×
U

(
1
)

PQ

extension of the SM, that we call “SMART U(1)$$_X$$

X

”. The $$U(1)_X$$

U

(
1
)

X

gauge symmetry is a well-known generalization of the $$U(1)_{B-L}$$

U

(
1
)

B
-
L

symmetry and $$U(1)_{PQ}$$

U

(
1
)

PQ

is the global Peccei–Quinn (PQ) symmetry. Three right handed neutrinos are added to cancel $$U(1)_X$$

U

(
1
)

X

related anomalies, and they play a crucial role in understanding the observed neutrino oscillations and explaining the observed baryon asymmetry in the universe via leptogenesis. Implementation of PQ symmetry helps resolve the strong CP problem and also provides axion as a compelling dark matter (DM) candidate. The $$U(1)_X$$

U

(
1
)

X

gauge symmetry enables us to implement the inflection-point inflation scenario with $$H_{inf} \lesssim 2 \times 10^{7}$$

H

inf

≲
2
×

10
7

GeV, where $$H_{inf}$$

H

inf

is the value of Hubble parameter during inflation. This is crucial to overcome a potential axion domain wall problem as well as the axion isocurvature problem. The SMART U(1)$$_X$$

X

framework can be successfully implemented in the presence of SU(5) grand unification, as we briefly show.
Abstract IA-07: Mechanisms of cellular heterogeneity in pancreatic cancer
Authors: Behrens Axel 
Published: November 2020

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic cancer and is predicted to be the second leading cause of cancer-related mortality in the next decade in Western countries. Treatment options are very limited, with even resectable tumours conferring a five-year survival rate of only 30%. Thus, there is an urgent need to better understand the biology of PDAC. Cancer cell heterogeneity is believed to be one of the main causes of tumour aggressiveness and resistance to therapy. I will describe our work to understand the sources of intratumoural PDAC diversity and the characterisation of a PDAC cancer stem cell population.
Citation Format: Axel Behrens. Mechanisms of cellular heterogeneity 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 IA-07.
Abstract IA-10: Overcoming the seven deadly hallmarks of pancreatic cancer
Authors: Tuveson David 
Published: November 2020

Abstract
Pancreatic cancer remains highly lethal, however recent insights regarding disease pathogenesis coupled with the emergence of new diagnostic methods and therapeutic agents engender a more hopeful outlook. We delineate 7 common characteristics of pancreatic cancer including desmoplastic stroma, dysregulated metabolism, chronic inflammation, undruggable KRAS, early metastasis, diagnostic deficiencies, and rapid deconditioning and posit that these hallmarks are collectively responsible for disease aggressiveness and clinical failure. Finally, we propose a strategic framework to address these challenges and thereby improve patient outcomes.
Citation Format: David Tuveson. Overcoming the seven deadly hallmarks of 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 IA-10.
Abstract IA-16: Metabolic adaptations in pancreatic cancer
Authors: Wellen Kathryn E. 
Published: November 2020

Abstract
Effective targeting of metabolism for cancer therapy is challenging in part because of extensive flexibility within metabolic pathways. For example, the enzyme ATP-citrate lyase (ACLY) has been of interest as a cancer therapeutic target because of its central role in generating nucleo-cytosolic acetyl-CoA for lipid synthesis and acetylation reactions. However, ACLY deficiency or inhibition triggers upregulation of the cytosolic acetyl-CoA synthetase ACSS2, enabling production of acetyl-CoA from acetate for the synthesis of fatty acids. In pancreatic cancer, tumor formation is suppressed in the absence of ACLY, but once tumors are established, ACSS2 is highly expressed and ACLY deficiency is tolerated. Despite this flexibility in acetyl-CoA generation, targeting of downstream processes that rely on acetyl-CoA, via combined BET inhibition and mevalonate pathway inhibition, suppresses tumor growth in mice. Analogously, it is possible that other metabolites whose abundance is tightly defended in cancer cells may point to targetable compensatory mechanisms or downstream processes on which tumor cells are reliant. Recent evidence suggests that the hexosamine biosynthesis pathway, which generates the glycosyl donor UDP-GlcNAc, holds promise for therapeutic targeting in pancreatic cancer, although its regulation in cancer cells remains poorly understood. In this presentation, I will discuss new data uncovering a key role for metabolic adaptation to nutrient deprivation in sustaining UDP-GlcNAc production and tumor growth.
Citation Format: Kathryn E. Wellen. Metabolic adaptations 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 IA-16.
Abstract IA-18: Epithelial cell plasticity in pancreatic cancer: The function and fate of metaplastic tuft cells
Authors: Crawford Howard C. 
Published: November 2020

Abstract
The pancreas is a notoriously plastic organ. In pancreatitis and early in the transformation process, pancreatic acinar cells give rise to a relatively homogeneous metaplastic duct phenotype. By modulating developmental transcription factor networks metaplastic duct cells then transdifferentiate to other epithelial derivatives including chemosensory tuft cells and neuroendocrine-like adenocarcinoma. To determine the function of metaplastic tuft cells (MTCs), we ablated the taste receptor associated G-protein GNAT3 in the context of pancreatic neoplasia. We found an accelerated progression of benign pancreatic neoplasia to pancreatic cancer, a phenotype attributable to a reactive upregulation of CXCL1 and CXCL2, and a resulting influx of immunosuppressive granulocytic MDSCs. To determine the fate of MTCs, we used a novel dual recombinase system to lineage trace their fate through pancreatic cancer progression, finding that they give rise to a unique subset of cells within invasive adenocarcinoma.
Citation Format: Howard C. Crawford. Epithelial cell plasticity in pancreatic cancer: The function and fate of metaplastic tuft cells [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 IA-18.
Abstract IA-19: Dissecting the immune complexity of pancreatic cancer survivors through team science
Authors: Balachandran Vinod P. 
Published: November 2020

Abstract
The advent of next-generation genomic sequencing has heralded unprecedented insight into the complexity of the interactions between the immune system and cancer. These tools to capture the genomes, exomes, and transcriptomes of cells in cancers has revealed the diversity of cancer antigens, the T cells and receptors that recognize them, and the supporting cells and states that regulate these associations. What is evident from these efforts is not only the high-dimensionality of the cancer space, but also the need for specialized analytical skills and cross-disciplinary expertise outside of the traditional biological sciences to integrate these vast data. Pancreatic cancer survivors represent a unique cohort of immunologic outliers to apply these tools to glean greater insight into rules governing immune recognition of cancer. In this talk, I will discuss our efforts to use a team of investigators spanning medical, computational, physical, and biological sciences to identify the immunogenicity, and evolution of cancer neoantigens in these unique patients, and how this antigen recognition is regulated by other novel cells in the environment.
Citation Format: Vinod P. Balachandran. Dissecting the immune complexity of pancreatic cancer survivors through team science [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 IA-19.
Abstract IA-20: Team science: Lessons from a few decades on the pancreatic cancer research team
Authors: Leach Steven D. 
Published: November 2020

Abstract
With the exception of a few examples of solitary genius embodied by Alfred Russell Wallace and Gregor Mendel, biomedical research has arguably always been a team sport. However, the genomic era has been associated with the increasing realization that large, multi-disciplinary scientific teams are required to push forward ambitious research programs combining computational and experimental work. At the same time, institutional promotions and tenure committees are increasingly recognizing participation and success in “team science” as worthy criteria for academic advancement. Opportunities for multi-institutional and multi-disciplinary collaboration are especially abundant in pancreatic cancer research, as our field is known for its particularly strong sense of community and for its collegial and collaborative spirit. Motivations for pursuing collaborative team science vary widely, and include the need to assemble the necessary workforce required to complete an ambitious body of work, transcend individual research disciplines, provide optimal educational opportunities for trainees, defuse unproductive competition, avoid being “scooped”, and simply to build fulfilling lifelong relationships with scientific colleagues. There are also many strategies by which investigators can effectively pursue team science, not all of which involve multiple authorship. In this short talk, I will review these motivations and strategies, drawing on lessons learned during several decades on the pancreatic cancer research team.
Citation Format: Steven D. Leach. Team science: Lessons from a few decades on the pancreatic cancer research team [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 IA-20.
Abstract PO-002: Detection of chemotherapy-resistant pancreatic cancer using a glycan Biomarker
Authors: Gao ChongFeng , Wisniewski Luke , Liu Ying , Staal Ben , Beddows Ian , Plenker Dennis , Aldakkak Mohammed , Hall Johnathan , Barnett Daniel , Gouda Mirna Kheir , Allen Peter , Drake Richard , Zureikat Amer , Huang Ying , Evans Douglas , Singhi Aatur , Brand Randall , Tuveson David , Tsai Susan , Haab Brian 
Published: November 2020

Abstract
A subset of pancreatic ductal adenocarcinomas (PDACs) is highly resistant to systemic chemotherapy, but no markers are available in clinical settings to identify this subset. In this study, we evaluate the role of sTRA, a glycan biomarker for PDAC, in predicting chemotherapeutic responses. We tested the correlation between chemosensitivity and glycan expression in PDACs in multiple systems including sets of cell lines, organoids, and isogenic cell lines; primary tumors; and blood plasma from human subjects. The sTRA-expressing models tended to have stem-like gene expression and the capacity for mesenchymal differentiation, in contrast to the non-expressing models. The sTRA cell lines also had significantly increased resistance to seven different chemotherapeutics commonly used against pancreatic cancer. Patients with primary tumors that were positive for a gene-expression classifier for sTRA received no statistically significant benefit from adjuvant chemotherapy, in contrast to those negative for the signature. In another cohort, based on direct measurements of sTRA in tissue microarrays, the patients who were high in sTRA again had no statistically significant benefit from adjuvant chemotherapy. Furthermore, a blood-plasma test for the sTRA glycan identified the PDACs that showed rapid relapse following neoadjuvant chemotherapy. This research demonstrates that a glycan biomarker could have value to detect chemotherapy resistant PDAC in clinical settings. This capability could aid in the development of stratified treatment plans and facilitate biomarker-guided trials targeting resistant PDAC.
Citation Format: ChongFeng Gao, Luke Wisniewski, Ying Liu, Ben Staal, Ian Beddows, Dennis Plenker, Mohammed Aldakkak, Johnathan Hall, Daniel Barnett, Mirna Kheir Gouda, Peter Allen, Richard Drake, Amer Zureikat, Ying Huang, Douglas Evans, Aatur Singhi, Randall Brand, David Tuveson, Susan Tsai, Brian Haab. Detection of chemotherapy-resistant pancreatic cancer using a glycan Biomarker [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-002.
Abstract PO-004: Identification of MLL4 as a novel therapeutic target of pancreatic ductal adenocarcinoma by in vivo genome-wide RNAi screening
Authors: Fung Frederic K. C. , Zhu Yinxin , Wong Chi Hin , Chen Yangchao 
Published: November 2020

Abstract
The prognosis of pancreatic ductal adenocarcinoma (PDAC) is extremely poor due to the lack of effective therapeutics. It is urgent to identify novel therapeutic target for PDAC. We performed in vivo genome-wide RNAi screening to identify cancer-associated candidate genes with critical roles in the tumorigenesis of PDAC. We identify mixed-lineage leukaemia 4 (MLL4 also known as KMT2B), which belongs to histone H3 lysine 4 (H3K4) methyltransferase of MLL family, as one of the cancer-associated gene to PDAC tumorigenesis. Here, we firstly report that MLL4 expression was frequently upregulated in PDAC cell lines as well as human PDAC tissue, depicting its potential role in PDAC tumorigenesis. Lysine methylation of different position of Histone is performed by SET (suppressor of variegation) domain of MLL family, aberrant expression of SET domain results in disruption of epigenetic gene regulation and leads to cancer. To characterize the in vitro tumorigenic role of SET domain of MLL4 in the development of PDAC, gain-of-function and loss-of-function approaches of SET domain of MLL4 and MLL4 were performed in PDAC cells, respectively. Ectopic SET expression promotes cell proliferation, colony formation, cell migration as well as invasion, demonstrating its oncogenic role in PDAC cells. Moreover, MLL4-depleted PDAC cells exhibited significantly reduction of tumor growth in nude mice xenograft model. Putative MLL4 activating and repressive targets were identified using gene expression microarray analysis in PDAC cell lines Capan2 and Panc-1. Expression alteration of these genes by regulated by MLL4 contribute to PDAC development and progression. To further delineate whether MLL4 regulates expression of the activating and repressing targets via H3K4 methylation, activity of H3K4 methylation was investigated in PDAC cells with MLL4 knockdown. Suppression of MLL4 reduced the H3K4Me2 and H3K4Me3 occupancies at promoter of MLL4 target genes, suggesting that MLL4 regulates downstream genes expression through H3K4 methylation. Taken together, our findings demonstrate that aberrant overexpression of MLL4 in PDAC cells alters its downstream oncogene and tumor suppressor genes, contributing to PDAC tumorigenesis. Thus, targeting MLL4 may serve as a potential therapeutic modality in the management of PDAC.
Citation Format: Frederic K. C. Fung, Yinxin Zhu, Chi Hin Wong, Yangchao Chen. Identification of MLL4 as a novel therapeutic target of pancreatic ductal adenocarcinoma by in vivo genome-wide RNAi screening [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-004.