bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends of prescribing adherence of antiplatelet agents in Hong Kong patients with acute coronary syndrome: a 10-year retrospective observational cohort study
Authors: Lam Amy SM , Yan Bryan PY , Lee Vivian WY 
Published: December 2020

ObjectivesThe objective of this study is to examine the temporal trend of antiplatelet prescribing pattern during index hospitalisation discharge in Hong Kong (HK) acute coronary syndrome (ACS) population.DesignThe study is a retrospective observational cohort study.SettingThe study retrieved data from electronic health record from Hospital Authority (HA), HK.ParticipantsThe study included patients aged 18 years old or above, who were admitted to seven institutions under HA with diagnosis of ACS during 2008–2017.Primary and secondary outcome measuresThe primary outcome was the frequency of antiplatelet therapy prescription at the point of index hospitalisation discharge each year during 2008–2017. Association between demographics, baseline comorbidities, procedures and antiplatelet prescription were examined as secondary outcome using multivariate logistic regression model, with commonly used antiplatelet groups selected for comparison.ResultsAmong the included 14 716 patients, 5888 (40.0%) discharged with aspirin alone, 6888 (46.8%) discharged with dual antiplatelet therapy (DAPT) with clopidogrel, and 973 (6.6%) discharged with DAPT with prasugrel/ticagrelor. Prescribing rate of aspirin alone decreased substantially from 56.8% in 2008 to 27.5% in 2017. Utilisation of DAPT with clopidogrel increased from 33.7% in 2008 to 52.7% in 2017. Use of DAPT with prasugrel/ticagrelor increased from 0.3% in 2010 to 15.3% in 2017. Compared with those prescribed with DAPT with clopidogrel, male patients (adjusted OR (aOR) 1.34, 95% CI 1.09 to 1.65), patients with non-ST-elevation myocardial infarction (aOR 2.50, 1.98 to 3.16) or ST-elevation myocardial infarction (aOR 3.26, 2.59 to 4.09), use of glycoprotein IIb/IIIa (aOR 3.03, 2.48 to 3.68) or undergoing percutaneous coronary intervention (aOR 3.85, 3.24 to 4.58) or coronary artery bypass graft (aOR 6.52, 4.63 to 9.18) during index hospitalisation, concurrent use of histamine-2 receptor antagonists (aOR 1.35, 1.10 to 1.65) or proton pump inhibitors (aOR 3.57, 2.93 to 4.36) during index hospitalisation discharge were more likely to be prescribed with DAPT with prasugrel/ticagrelor. Patients with older age (aOR 0.97, 0.96 to 0.97), diabetes (aOR 0.68, 0.52 to 0.88), chronic kidney disease (aOR 0.43, 0.22 to 0.85) or concurrent use of oral anticoagulant (aOR 0.16, 0.07 to 0.42) were more likely to received DAPT with clopidogrel.ConclusionsUse of DAPT with prasugrel/ticagrelor was suboptimal yet improving during 2008–2017 in HK patients with ACS. Considering DAPT, predictors for clopidogrel prescription, compared with prasugrel/ticagrelor, were consistent with identified risk factors of bleeding.
Hospital managers’ perspectives with implementing quality improvement measures and a new regulatory framework: a qualitative case study
Authors: Øyri Sina Furnes , Braut Geir Sverre , Macrae Carl , Wiig Siri 
Published: December 2020

A new regulatory framework to support local quality and safety efforts in hospitals was introduced to the Norwegian healthcare system in 2017. This studyaimedto investigate hospital managers’ perspectives on implementation efforts and the resulting work practices, to understand if, and how, the new Quality Improvement Regulation influenced quality and safety improvement activities.DesignThis article reports one study level (the perspectives of hospital managers), as part of a multilevel case study. Data were collected by interviews and analysed according to qualitative content analysis.SettingThree hospitals retrieved from two regional health trusts in Norway.Participants20 hospital managers or quality advisers selected from different levels of hospital organisations.ResultsFour themes were identified in response to the study aim: (1) adaptive capacity in hospital management and practice, (2) implementation efforts and challenges with quality improvement, (3) systemic changes and (4) the potential to learn. Recent structural and cultural changes to, and development of, quality improvement systems in hospitals were discovered (3). Participants however, revealed no change in their practice solely due to the new Quality Improvement Regulation (2). Findings indicated that hospital managers are legally responsible for quality improvement implementation and participants described several benefits with the new Quality Improvement Regulation (2). This related to adaptation and flexibility to local context, and clinical autonomy as an inevitable element in hospital practice (1). Trust and a safe work environment were described as key factors to achieve adverse event reporting and support learning processes (4).ConclusionsThis study suggests that a lack of time, competence and/or motivation, impacted hospitals’ implementation of quality improvement efforts. Hospital managers’ autonomy and adaptive capacity to tailor quality improvement efforts were key for the new Quality Improvement Regulation to have any relevant impact on hospital practice and for it to influence quality and safety improvement activities.
Scattering of charged fermion to two-dimensional wormhole with constant axial magnetic flux
Authors: Pimsamarn Kulapant , Burikham Piyabut , Rojjanason Trithos 
Published: December 2020

AbstractScattering of charged fermion with $$(1+2)$$

(
1
+
2
)

-dimensional wormhole in the presence of constant axial magnetic flux is explored. By extending the class of fermionic solutions of the Dirac equation in the curved space of wormhole surface to include normal modes with real energy and momentum, we found a quantum selection rule for the scattering of fermion waves to the wormhole. The newly found momentum–angular momentum relation implies that only fermion with the quantized momentum $$k=m'/a\sqrt{q}$$

k
=

m
′

/
a

q

can be transmitted through the hole. The allowed momentum is proportional to an effective angular momentum quantum number $$m'$$

m
′

and inversely proportional to the radius of the throat of the wormhole a. Flux dependence of the effective angular momentum quantum number permits us to select fermions that can pass through according to their momenta. A conservation law is also naturally enforced in terms of the unitarity condition among the incident, reflected, and transmitted waves. The scattering involving quasinormal modes (QNMs) of fermionic states in the wormhole is subsequently explored. It is found that the transmitted waves through the wormhole for all scenarios involving QNMs are mostly suppressed and decaying in time. In the case of QNMs scattering, the unitarity condition is violated but a more generic relation of the scattering coefficients is established. When the magnetic flux $$\phi =mhc/e$$

ϕ
=
m
h
c
/
e

, i.e., quantized in units of the magnetic flux quantum hc/e, the fermion will tunnel through the wormhole with zero reflection.
Abstract IA02: Regulating amino acid metabolism can improve response to immunotherapy
Authors: Erez Ayelet , Ruppin Eytan 
Published: December 2020

Abstract
Aberrant expression of urea cycle enzymes occurs in multiple types of cancer. We have previously demonstrated that the urea cycle enzyme ASS1 is downregulated in different tumor types to increase the availability of its substrate aspartate for pyrimidine synthesis, supporting cell proliferation. Therapeutically, we demonstrated that high pyrimidine to purine ratio improves response to immunotherapy. Interestingly, in several prevalent types of cancer ASS1 expression is upregulated for a yet unknown metabolic benefit that associates with poor patients’ prognosis. We now find that ASS1 expression in cancer provides a survival advantage in nutrient deficiency states by generating NO that activates gluconeogenesis. The increase in gluconeogenic flux increases serine levels and leads to a nucleotide imbalance promoting pyrimidine to purine transversion mutations. Consequently, cancers with high ASS1 expression are less immunogenic. Reversing the nucleotide imbalance to favor pyrimidines leads to better response to immunotherapy. Our data establish ASS1 expression as a metabolic survival mechanism under nutrient deprivation that may also serve as a strong determinant of the immune response. Importantly, our findings suggest that we can metabolically regulate tumor mutations to improve patients’ responsiveness to immunotherapy.
Citation Format: Ayelet Erez, Eytan Ruppin. Regulating amino acid metabolism can improve response to immunotherapy [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA02.
Abstract IA05: Viral Mimicry in Pancreatic Cancer
Authors: Espinet Elisa , Trumpp Andreas 
Published: December 2020

Abstract
With an overall survival rate of about 8% after five years, ductal adenocarcinoma of the pancreas (PDAC) is one of the cancers with the worst prognosis (Cancer Research UK and American Cancer Society). A hallmark of PDAC is the immense contribution of desmoplastic stroma to the total tumour mass. Typically, epithelial PDAC cells represent only a minority of cells within the tumour (as low as 10%). The excessive stromal presence represents a major technical challenge when aiming to interrogate the specific molecular signals contributed by the neoplastic epithelial cell compartment from data generated using bulk tumour samples. To address this, we FACS-purified epithelial cells from PDAC and, as controls, healthy human pancreas and performed genome-wide transcriptome and DNA methylome analyses. Clustering based on DNA methylation revealed two distinct groups of PDAC with different methylation levels at genomic regions encoding repeat elements. Methylationlow tumours showed higher expression of endogenous retroviral (ERV) transcripts and a strong engagement of the dsRNA sensing machinery. This results in the cell intrinsic activation of an interferon response signature (IFNsign), leading to the reprogramming of stromal cells towards a pro-tumourigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells harboured distinct lineage traits specific for normal ductal or acinar pancreatic epithelial cells at the methylation and transcriptional level. Moreover, ductal-cell-derived KrasG12D/Trp53-/- mutant mouse PDACs showed higher expression of IFNsign compared to tumors initiated by the same genetic drivers in acinar cells. Collectively, our data point to two distinct origins and etiology of human PDACs, with the aggressive Methylationhigh/IFNsignlow tumour subtype potentially targetable by agents blocking cell intrinsic IFN-signaling.
Citation Format: Elisa Espinet, Andreas Trumpp. Viral Mimicry in Pancreatic Cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA05.
Abstract IA08: Metabolic compartmentalization in the regulation of chromatin modification
Authors: Wellen Kathryn 
Published: December 2020

Abstract
Metabolic processes are compartmentalized within cells. Many chromatin modifying enzymes utilize metabolites as substrates, and localized metabolite production may play important roles in the regulation of the epigenome. A number of metabolic enzymes have been detected and shown to be dynamically regulated within the nucleus. For example, nuclear localization and phosphorylation of the enzyme ATP-citrate lyase (ACLY) plays a key role in supplying acetyl-CoA for histone acetylation during DNA double strand break repair. A major barrier to understanding metabolic regulation of chromatin modification is the lack of methodology to reliably measure nuclear metabolite levels. In this talk, I will discuss efforts to quantify subcellular acyl-CoA levels, as well as insights into the regulation of nuclear metabolite pools emerging from this work.
Citation Format: Kathryn Wellen. Metabolic compartmentalization in the regulation of chromatin modification [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA08.
Abstract IA15: Metabolic coordination of cancer cell fate
Authors: Finley Lydia 
Published: December 2020

Abstract
Increasing evidence demonstrates that intracellular metabolic pathways can be critical drivers of tumor progression. Metabolites provide the biomass required for cancer cell proliferation and contribute to antioxidant defenses that promote survival and metastatic dissemination. Moreover, oncogenic mutations in several metabolic enzymes lead to accumulation of pathological levels of metabolites that interfere with histone and DNA demethylation and impose a block to differentiation. However, absent these mutations, whether the metabolic profile of cancer cells contributes to the establishment or maintenance of malignant cell identity remains poorly understood. Combining in vitro culture of cancer cells with mouse models of tumor progression, we aim to define the metabolic changes driven by common oncogenes and tumor suppressors and elucidate how these metabolic alterations affect cancer-associated phenotypes. In particular, we focus on how metabolic alterations influence regulation of the chromatin landscape and differentiation programs that antagonize tumor progression. These studies will provide insight into the mechanisms through which tumor cells evade differentiation and sustain malignancy.
Citation Format: Lydia Finley. Metabolic coordination of cancer cell fate [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA15.
Abstract IA19: Dietary Control of Stem Cells in Physiology and Disease
Authors: Yilmaz Omer H. 
Published: December 2020

Abstract
Organismal diet has a profound impact on tissue homeostasis and health in mammals. Adult stem cells mediate many aspects of tissue adaptation by balancing self-renewal and differentiation divisions to alter tissue composition in response to the environment. Because somatic stem cells may respond to organismal physiology to orchestrate tissue remodeling and some cancers are understood to arise from transformed stem cells, these findings raise the possibility that organismal diet, stem cell function, and cancer initiation are interconnected. Here I will present work from my group that describes our emerging view of how diet, metabolites and nutrient-sensing pathways instruct mammalian intestinal stem cell fate in homeostasis, adaptation to diet and diseases such as cancer.
Citation Format: Omer H. Yilmaz. Dietary Control of Stem Cells in Physiology and Disease [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA19.
Abstract IA21: Metabolic phenotypes and liabilities in human cancer
Authors: DeBerardinis Ralph J. 
Published: December 2020

Abstract
Metabolic reprogramming in cancer arises from a complex, incompletely-defined combination of factors intrinsic and extrinsic to malignant cells. In some cases, reprogrammed pathways contribute to the process of transformation, and in many others they enable cancer progression by supporting cell survival and excessive growth. The clinical relevance of cancer metabolism is emphasized by the fact that numerous imaging modalities and therapeutic strategies in cancer capitalize on the altered metabolic states present in tumors. Recent work has emphasized that metabolic phenotypes and liabilities evolve as cancer progresses, such that pathways required for cancer initiation may be dispensable in more advanced stages, and vice versa. A key challenge is to define metabolic properties that support key aspects of cancer progression, particularly metastasis and acquired therapy resistance, which account for the majority of cancer-related deaths. Because these processes are difficult to model in culture, we have developed clinical approaches to study cancer metabolism in vivo, in patients, and to uses these approaches to identify features that drive cancer progression. I will discuss approaches using metabolomics and intra-operative infusions with 13C-labeled nutrients to assess metabolic pathway utilization in human tumors. We use this approach to characterize metabolic heterogeneity among tumors arising in different organs, to identify areas of regional metabolic heterogeneity within solid tumors and to predict which activities support cancer progression. Our work to this point demonstrates marked diversity of fuel preferences in primary tumors and unexpected roles of particular pathways in cancer cell biology.
Citation Format: Ralph J. DeBerardinis. Metabolic phenotypes and liabilities in human cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA21.
Abstract PO-015: Hypermethylated genes in leiomyosarcoma can be targeted through guadecitabine treatment
Authors: Hasan Nesrin , De Carvalho Fischer Cynthia , Sharma Anup , Ahuja Nita 
Published: December 2020

Abstract
Leiomyosarcomas (LMS) are aggressive mesenchymal tumors of smooth muscle origin. Understanding the molecular alterations associated with LMS is needed to identify potential therapeutic targets. Epigenetic alterations such as hypermethylation of gene promoter regions with associated transcriptional silencing is a hallmark of most cancers. Epigenetic reprograming is fundamentally linked to tumor initiation, progression and metastasis. Frequent epigenetic alterations have been observed in LMS. Epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) have been used to reverse aberrant DNA methylation and restore expression of silenced genes. Our previous studies using DNMTi, including guadecitabine, have shown that DNMTi treatment has anti-proliferative and pro-apoptotic effects in in vitro and in vivo models of LMS. Our goal was to characterize the methylation changes following guadecitabine treatment of the leiomyosarcoma cell line SK-UT1. SK-UT1 cells were treated with guadecitabine (0.05 µM-0.1 µM) and methylation was determined using Illumina 450K platform. We filtered the promoter CpG island regions that respond to guadecitabine treatment and were associated with decreased methylation compared to untreated SK-UT1 control (p≤0.05, Δβ≥0.15). In order to assess the relevance of these differentially methylated regions, we compared them to the methylation and expression profiles of LMS patient samples (GSE68312). We focused on the genes that have decreased expression and are associated with increased methylation of the promoter CpG island regions in the patient LMS samples. In conclusion, treatment of SK-UT1 cell line with guadecitabine resulted in decrease of methylation of a subset of promoter CpG island regions that were differentially hypermethylated in LMS patient samples. Further studies are needed to explore the effect of differential methylation on gene expression in guadecitabine treated SK-UT1 cell line. Understanding the effect of DNMTi on LMS is needed to identify potential therapeutic applications targeting the epigenetic pathways. Funding supported by Astex Pharmaceuticals.
Citation Format: Nesrin Hasan, Cynthia De Carvalho Fischer, Anup Sharma, Nita Ahuja. Hypermethylated genes in leiomyosarcoma can be targeted through guadecitabine treatment [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-015.
Abstract PO-016: Modulating cancer stem cell pathways to enhance systemic therapeutic efficacy
Authors: Sadhukhan Pritam , Shibata Masahiro , Ugurlu M. Talha , Goldberg Rachel , Hoque Mohammad O. 
Published: December 2020

Abstract
Chemoresistance and poor immune sensitivity are one of the major challenges to treat different cancer types including lung, bladder and head & neck. Different epigenetic regulators and cancer stem cells (CSCs) regulatory pathways play a critical role in the development of therapeutic resistance. Prolonged chemotherapy treatment enriches CSCs in the tumor microenvironment and in a previous study we have shown that inhibition of the CSCs regulatory pathway/s combined with chemotherapy decreased CSC properties and efficiently inhibit tumor growth in patient-derived xenografts (PDXs) models. The purpose of this study is to determine the chemo and immunotherapeutic efficacy in combination with several CSC pathway/s modulatory agent/agents to treat different solid tumors. To identify relevant CSC regulating pathways, we tested the therapeutic efficacy of different agents such as 5-Azacytidine (DNA methyltransferase 1 inhibitor), Vismodegib (SMO inhibitor), Romidepsin (HDAC1 inhibitor), Olaparib (PARP1 inhibitor), and GSK343 (EZH2 inhibitor) using different bladder and head & neck cancer cell lines and also determined the numerous CSCs properties. Our data indicate that in vitro treatment with these potential therapeutic agents decreases cell viability, sphere formation and wound healing that suggest that, these drugs may be effective in reducing CSCs population when combined with chemo and/or immunotherapy. Our immunoblotting experiments indicate reduced expression of some CSCs markers and factors such as such as NANOG, OCT4, CD133 and CD24. Interestingly, after treating the cells with some of these agents and array analysis, we have found differential expression of some of the key genes regulating the immunogenic response. Further, to confirm the array-based data, selected candidate immune-associated genes were analyzed by qRT-PCR. Moreover, our preliminary data suggest that combination treatment with epigenetic drugs and an immune agent may effectively reduce tumor growth in vivo compared to either of these drugs. In conclusion, although comprehensive mechanistic studies are ongoing, our initial results highlight the importance of considering combination of epigenetic and immune therapy for patients with diverse cancer types that respond poorly to immune and chemotherapy.
Citation Format: Pritam Sadhukhan, Masahiro Shibata, M. Talha Ugurlu, Rachel Goldberg, Mohammad O. Hoque. Modulating cancer stem cell pathways to enhance systemic therapeutic efficacy [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-016.