bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Molecular Characteristics of ER-Positive Breast Cancer Tumors Identified as Ultralow Risk by the 70-Gene Signature in a Randomized Clinical Trial
Authors: Johansson Annelie , Yu Nancy Yiu-Lin , Iftimi Adina , Tobin Nicholas P. , Veer Laura van't , Nordenskjöld Bo , Benz Christopher C. , Fornander Tommy , Perez-Tenorio Gizeh , Stål Olle , Esserman Laura , Yau Christina , Lindström Linda S. 
Published: December 2020

Abstract
BackgroundBreast cancer tumors are heterogenous, including their metastatic potential and time to distant metastasis. Patients with estrogen receptor (ER)-positive tumors have a continuous long-term risk of fatal disease decades after diagnosis. Recently, ER-positive breast cancer patients classified as having ultralow risk tumors by the 70-gene expression signature (MammaPrint) were associated with a minimal risk of fatal disease. However, the underlying tumor characteristics of ultralow risk tumors are unknown.MethodsSecondary analysis of the Stockholm tamoxifen randomized trial (STO-3, 1976-1990) enrolling postmenopausal lymph node-negative breast cancer patients. Immunohistochemistry of the clinically used breast cancer markers (n=727 patients) and gene expression profiling by Agilent microarrays (n=652 patients) were performed in 2014. Ultralow risk tumors, identified by the 70-gene signature, were compared to other ER-positive tumors (of low/high risk) and Luminal A and B PAM50 subtype tumors (ER-positive, low/high risk) by the clinical markers and multi-gene modules, representative of specific biological processes and pathways, using Fisher’s exact test. Furthermore, differential gene expression analysis was performed contrasting ultralow risk tumors to other ER-positive tumors (of low/high risk) using t-statistics and false discovery rate (FDR).ResultsUltralow risk tumors were significantly (P<0.05) more likely to be of smaller tumor size, lower tumor grade, progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and Ki-67-low. Moreover, several multi-gene modules were significantly differentially expressed in ultralow risk tumors, including AKT/mTOR, proliferation-marker AURKA, HER2/ERBB2, IGF1, PTEN-loss, PI3KCA-mutations, and immune response-modules IMMUNE1 and STAT1. Furthermore, ultralow risk tumors showed significantly (FDR<0.001) lower expression of genes involved in the immune response, histone modulation, PI3K/Akt/mTOR pathway, and higher expression of homeobox genes and genes involved in epithelial-to-mesenchymal transition, among others.ConclusionsUltralow risk tumors have significantly different tumor characteristics compared to other ER-positive tumors. Identifying clinical and biological characteristics of low-risk tumors is important to improve our understanding of non-fatal versus fatal breast cancer.Trial registrationThe trial center for the STO-3 trial was the Regional Cancer Center Stockholm-Gotland in Sweden. However, the start of the trial in 1976 was well before trial registration started in Sweden, therefore information on trial number is not available.
Single Cell RNA-seq Data and Bulk Gene Profiles Reveal a Novel Signature of Disease Progression in Multiple Myeloma
Authors: Zeng Zhiyong , Lin Junfang , Zhang Kejie , Guo Xizhe , Zheng Xiaoqiang , Yang Apeng , Chen Junmin 
Published: December 2020

Abstract
BackgroundThe development of multiple myeloma (MM) is considered to involve a multistep transformation process, but the role of cytogenetic abnormalities and molecular alterations in determining the cell fate of multiple myeloma (MM) remains unclear. Here, we have analyzed single cell RNA-seq data and bulk gene profiles to reveal a novel signature associated with MM development.MethodsThe scRNA-seq data from GSE118900 was used to profile the transcriptomes of cells from MM patients at different stages. Pseudotemporal ordering of the single cells was performed using Monocle package to feature distinct transcriptomic states of the developing MM cells. The bulk microarray profiles fromGSE24080 and GSE9782 were applied to identify a signature associated with MM development.ResultsThe 597 cells were divided into 7 clusters according to different risk levels. They were initiated mainly from monoclonal gammopathy of undetermined significance (MGUS), newly diagnosed MM (NDMM), or relapsed and/or refractory myeloma (RRMM) with cytogenetically favorable t(11;14), moved towards the cells from smoldering MM (SMM) or NDMM without t(11;14) or t(4;14), and then finally to cells from SMM or RRMM with t(4;14). Based on the markers identified in the late stage, the bulk data was used to develop a 20-gene signature stratifying patients into high and low-risk groups (GSE24080: HR = 3.759, 95% CI 2.746-5.145; GSE9782: HR = 2.612, 95% CI 1.894-3.603), which was better than the previously published gene signatures (EMC92, UAMS70, and UAMS17) and International Staging System. The 20 genes were further verified by quantitative real-time polymerase chain reaction using samples obtained from the patients with MM.ConclusionsOur comprehensive analyses offered new insights in MM development, and established a 20-gene signature as an independent biomarker for MM.
Research on Traffic Analysis System Based on Machine Learning
Authors: Xie Feng , Wei Dongxue , Wang Zhencheng 
Published: December 2020

Abstract
With the rapid development of computer and mobile networks, the high frequency of network usage has caused a burst growth in the traffic of routers. At the same time, due to the rise of smart home, the network traffic formed by the aggregation of sensor data is also increasing. Traffic outbreaks form mixed network types, and network viral, worms, network theft, and malicious attacks are also involved. How to distinguish traffic type, block malicious traffic and effectively use the sensor data of smart home attracts more and more attention.
A Blockchain-Assisted Framework for Secure and Reliable Data Sharing in Distributed Systems
Authors: Guo Yu , Wang Shenling , Huang Jianhui 
Published: December 2020

Abstract
The explosive growth of big data is pushing forward the paradigm of cloud-based data store today. Among other, distributed storage systems are widely adopted due to their superior performance and continuous availability. However, due to the potentially wide attacking surfaces of the public cloud, outsourcing data store inevitably raises new concerns on user privacy exposure and unauthorized data access. Besides, directly introducing a centralized third-party authority for query authorization management is not work because it still can be compromised.
In this paper, we propose a blockchain-assisted framework that can support trustworthy data sharing services. In particular, data owners allow to outsource their sensitive data to distributed systems in encrypted form. By leveraging smart contracts of blockchain, a data owner can distribute secret keys for authorized users without extra round interaction to generate the permitted search tokens. Meanwhile, such blockchain-assisted framework naturally solves the trust issues of query authorization. Besides, we devise a secure local index framework to support encrypted keyword search with forward-privacy and mitigate blockchain overhead. To validate our design, we implement the prototype and deploy it at Amazon Cloud. Extensive experiments demonstrate the security, efficiency, and effectiveness of the design.
Anticoagulation in Patients With a Femoral Neck Fracture: Evaluating Daily Practice.
Authors: Rijckevorsel Veronique A.J.I.M. van , Jong Louis de , Klem Taco M.A.L. , Kuijper Tjallingius M. , Roukema Gert R. 
Published: December 2020

Abstract
Background: Geriatric hip fracture patients are fragile and mostly suffering from multiple comorbidities, such as cognitive or cardiovascular disease, in which the use of antiplatelet therapy or vitamin K antagonists is common. The aim of this study is to assess the effect of antiplatelet therapy and vitamin K antagonists on perioperative care and patient outcome after hip hemiarthroplasty in daily practice.Methods: Patients with a femoral neck fracture requiring hip hemiarthroplasty were included in the study. Data were extracted from a prospective hip fracture database and completed by retrospective review of the hospital records at two level II trauma centers between January 1st 2010 and May 16th 2016. Results: 907 patients (68% female) were included, with a median age of 84 (IQR 78-88), of which 415 (46%) used any sort of anticoagulation. Anticoagulation medication was associated with more packed cell supplementation; 0.33 units (±0.88) vs. 0.15 units (±0.61) (P=<0.001). Also, more hematoma’s were found for patients with anticoagulation, 19.5% versus 11.4%, P= 0.001. Patients using vitamin K antagonists needed more days to be ready for discharge compared to patients without anticoagulation, 5.5 days (4-9) versus 4 days (3-7), P = < 0.001.There was no significant difference in 30-day or 1-year mortality after surgery, nor in time to surgery. Conclusion: Patients using any sort of anticoagulation are in need of more packed cell supplementation, develop more hematomas and need more days to be ready for discharge, compared to patients without anticoagulation use. Also prolonged time to surgery was found for patients using vitamin K antagonists.
The impact of introducing ambulance and delivery fees in a rural hospital in Tanzania.
Authors: Vossius Corinna , Md Estomih , Moshiro Robert , M Paschal , Kvaløy Jan Terje , Kidanto Hussein , Lyanga Sara , Ersdal Hege 
Published: December 2020

Abstract
Background: Access to health care facilities is a key requirement to enhance safety for mothers and newborns during labour and delivery. Haydom Lutheran Hospital (HLH) is a regional hospital in rural Tanzania with a catchment area of about two million inhabitants. Up to June 2013 ambulance transport and delivery at HLH were free of charge, while a user fee for both services was introduced from January 2014. We aimed to explore the impact of introducing user fees on the population of women giving birth at HLH in order to document potentially unwanted consequences in the period after introduction of fees . Methods: Retrospective analysis of data from a prospective observational study. Data was compared between the period before introduction of fees from February 2010 through June 2013 and the period after from January 2014 through January 2017. Logistic regression modelling was used to construct risk-adjusted variable-life adjusted display (VLAD) and cumulative sum (CUSUM) plots to monitor changes. Results: A total of 28,601 births were observed. The monthly number of births was reduced by 17.3% during the post-introduction period. Spontaneous vaginal deliveries were registered less frequently, while labour complication and caesarean sections were more frequent. There was a reduction of newborns with birth weight less than 2500 grams. The observed changes were stable over time. For most variables, a significant change could be detected after a few weeks. Conclusion: After the introduction of ambulance and delivery fees an increase in labour complications and caesarean sections of about 80 per 1000 births and a decrease in non-cephalic presentations and newborns with low birthweight of about 17 per 1000 births each was observed. This might indicate that women delay the decision to seek skilled birth attendance or do not seek help at all, possibly due to financial reasons. Lower rates of births in a safe health care facility like HLH is of great concern, as access to skilled birth attendance is a key requirement in order to further reduce perinatal mortality. Therefore, free delivery care should be a high priority.
Mental health planning at a very early stage of the COVID-19 crisis: A systematic review of online international strategies and recommendations
Authors: Almeda Nerea , Garcia-Alonso Carlos R. , Salvador-Carulla Luis 
Published: December 2020

Abstract
Background: Mental health care systems have been dramatically affected by COVID-19. Containment measures have been imposed, with negative consequences on population mental health. Therefore, an increase in both symptomatology and mental disorder incidence is expected. This research aims to identify, describe and assess the empirical background on online strategies and recommendations developed by international organizations and governments to cope with the psychological impact of COVID-19 at a very early stage of the pandemic. Methods: The PRISMA guidelines were adapted to review online documents. A new questionnaire was developed to identify the existence of common patterns in the selected documents. Questions were classified into three domains: COVID-19 information, mental health strategies and mental health recommendations. A two-step cluster analysis was carried out to highlight underlying behaviours in the data (patterns). The results are shown as spider graphs (pattern profiles) and conceptual maps (multidimensional links between questions). Results: Twenty-six documents were included in the review. The questionnaire analysed document complexity and identified their common key mental health characteristics (i.e., does the respondent have the tools for dealing with stress, depression and anxiety?). Cluster analysis highlighted patterns from the questionnaire domains. Strong relationships between questions were identified, such as psychological tips for maintaining good mental health and coping with COVID-19 (question nº 4), describing some psychological skills to help people cope with anxiety and worry about COVID-19 (question nº 6) and promoting social connection at home (question nº 8). Conclusions: When fast results are needed to develop health strategies and policies, rapid reviews associated with statistical and graphical methods are essential. The results obtained from the proposed analytical procedure can be relevant to a) classify documents according to their complexity in structuring the information provided on how to cope with the psychological impact of COVID-19, b) develop new documents according to specific objectives matching population needs, c) improve document design to face unforeseen events, and d) adapt new documents to local situations. In this framework, the relevance of adapting e-mental health procedures to community mental health care model principles was highlighted, although some problems related to the digital gap must be considered.
IL-19 Induced by IL-13/IL-17A in the Nasal Epithelium of Patients with Chronic Rhinosinusitis Upregulates MMP-9 Expression via ERK/NF-kB Signaling Pathway
Authors: Li Xia , Huang Jiancong , Chen Xiaohong , Lai Xiaoping , Huang Zizhen , Li Yue , Li Shuaixiang , Chang Lihong , Zhang Gehua 
Published: December 2020

Abstract
Background: Tissue remodeling is a crucial characteristic of chronic rhinosinusitis (CRS). Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is crucial for the pathologic tissue remodeling in CRS. Elevation of interleukin (IL)-19 or MMP-9 levels in patients with CRS had been proven in previous studies. Here, we aimed to investigate the role of IL-19 in mediating MMP-9 expression in CRS. Methods: Nasal tissue samples were collected from 45 individuals having chronic rhinosinusitis with nasal polyps (CRSwNP), 24 CRS without nasal polyps (CRSsNP), and 17 controls. Expression of IL-19, its receptors (IL-20R1/IL-20R2), and MMP-9 were investigated using RT-qPCR and Immunofluorescence. Human nasal epithelial cells (HNECs) were stimulated by IL-19; ERK phosphorylation, NF-kB pathway activation, and MMP-9 level were detected by RT-qPCR, ELISA, western blot and Immunofluorescence. We also explored the effect of type1/2/3 cytokines on IL-19 production by RT-qPCR, and western blot. Results: Expression levels of IL-19, its receptors (IL-20R1/IL-20R2), and MMP-9 were increased in nasal tissues from individuals with CRSwNP compared to those with CRSsNP as well as the controls. IL-19 significantly elevated the production of MMP-9 in HNECs. Furthermore, IL-19 could activate the ERK and NF-kB pathways, accompanied by increased MMP-9 production in HNECs. Conversely, both ERK and NF-kB inhibitors significantly attenuated the role of IL-19 in MMP-9 production. siRNA knockdown of IL-20R1 suppressed ERK and NF-kB pathway activation, thereby decreasing MMP-9 expression. IL-13 and IL-17A were found to stimulate IL-19 production in HNECs.Conclusion: IL-19, promoted by IL-13 and IL-17A, contributes to the upregulation of secretion of the tissue remodeling factor MMP-9 in patients with CRS.
Spatiotemporal beam self-cleaning for high-resolution nonlinear fluorescence imaging with multimode fibres
Authors: Ould-Moussa Nawell , Mansuryan Tigran , Hage Charles-Henri , Fabert Marc , Krupa Katarzyna , Tonello Alessandro , Ferraro Mario , Leggio Luca , Zitelli Mario , Mangini Fabio , Niang Alioune , Millot Guy , Papi Massimiliano , Wabnitz Stefan , Couderc Vincent 
Published: December 2020

Abstract
Beam self-cleaning (BSC) in graded-index (GRIN) multimode fibres (MMFs) has been recently reported by different research groups. Driven by the interplay between Kerr effect and beam self-imaging, BSC counteracts random mode coupling, and forces laser beams to recover a quasi-single mode profile at the output of GRIN fibres. Here we show that the associated self-induced spatiotemporal reshaping allows for improving the performances of nonlinear fluorescence microscopy and endoscopy using multimode optical fibres. We experimentally demonstrate that the beam brightness increase, induced by self-cleaning, enables two and three-photon imaging of biological samples with high spatial resolution. Temporal pulse shortening accompanying spatial beam clean-up enhances the output peak power, hence the efficiency of nonlinear imaging. We also show that spatiotemporal supercontinuum generation is well-suited for large-band nonlinear fluorescence imaging in visible and infrared domains. We substantiated our findings by multiphoton fluorescence imaging in both microscopy and endoscopy configurations.
Pasolini e o fim: o lugar da literatura em tempos de consumo
Authors: Pimentel Davi Andrade 
Published: December 2020

Com base na leitura de Escritos corsários e de A nebulosa, de Pier Paolo Pasolini, este artigo pretende desenvolver dois movimentos de reflexão sobre o lugar da literatura em nossa contemporaneidade: o primeiro, como a crítica jornalística de Pasolini à sociedade de consumo pode vir a nos auxiliar a pensar sobre o lugar atual da literatura em nossa sociedade; e, o segundo, como o trágico, enquanto elemento estético retomado pela ficção de Pasolini, se caracteriza como crítica à classe burguesa e como mecanismo de escrita para o estabelecimento de um lugar para a literatura em nosso presente.
Paulus Vladimiri and Stanislaus de Scarbimiria – medieval Krakow law school and the Polish contribution to the formation of the rights of nations
Authors: Grzybowski Jacek 
Published: December 2020

The formation of medieval national communities constitutes the basis of political and cultural European history. However, it is almost forgotten nowadays that a significant contribution to reflections on sovereignty was made by Polish scholars. Stanisław of Skarbimierz (Stanislaus de Scarbimiria – 1365-1431) and Paweł Włodkowic (Paulus Vladimiri – 1370-1435), medieval Cracovian jurists and philosophers, are rather unknown in the Western milieu. Both of them added their voices to one of the most important disputes for European political culture. The 15th-century debate between Jagiellonian Poland and the Teutonic Order that conquered the Prussian lands became the basis for Polish lawyers to develop an ingenuous theory concerning human rights and the rights of nations. Stanisław of Skarbimierz and Paweł Włodkowic, the founders of the Polish school of law at the Cracow Academy, in their writings and letters, firmly demonstrated injustice, the breaking of basic human rights, injuries, and other crimes perpetrated by the Teutonic knights against the Prussians, Lithuanians, Yotvingians and Poles. The scholars elaborated on the most important problems of law and international relationships, concerning the issues of human rights, the right to self-determination, just war, respect for personal property and human dignity. The doctrine of the Polish School of international law elaborated by Paul Wladimiri and Stanislaw of Skarbimierz have had and still make a considerable impact on the understanding of human rights and rights of nations. Their works and sermons espouse the craving for international justice, while securing national interests, and for a model of Europe as a “family of independent and sovereign nations” whose coexistence is founded on the Christian anthropology according to which a man as endowed by God with dignity and freedom. The works of the Cracovian masters should impress us and make proud of our legacy, while in Europe they should awaken interest and creative thought.
Awareness and Acceptance in Using Smart Meter by Energy Customers in Malaysia
Authors: Mohd Nasir Siti Rashidah , Ibrahim Azmi , Hassan Rohana , Haron Halilah , Hassan Siti Hafizan , S. Garieb Siti Laila , Busrah Asnawi 
Published: December 2020

The common issues of energy services related to customers’ complaints are delays in billing, inaccurate consumption measurement, lack of breakdown information, lack of real-time billing, and energy consumption. A questionnaire survey was conducted using face-to-face methods during the pre-installation phase to determine the customers’ awareness, acceptance, knowledge, and benefits in using smart meters. The findings show that 69.6% of the customers are aware that the use of energy-efficient appliances can save electricity. This study shows that the customers, regardless of demographic profiles and background, portrayed overall good awareness of the smart metering and smart living concept.
Keywords: Awareness, Acceptance, Benefit, Smart Meter
eISSN: 2398-4287 © 2020. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.
DOI: https://doi.org/10.21834/ebpj.v5iSI2.2519.
Expression and characterization of Trichoderma reesei endoglucanase II in Pichia pastoris under the regulation of the GAP promoter
Authors: Tjandra Kezia Abib Yerah , Dewi Kartika Sari , Fuad Asrul Muhamad , Anindyawati Trisanti 
Published: December 2020

Trichoderma reesei is known to be one of the organisms capable for producing various types of cellulase in high concentrations. Among these cellulases, the highest catalytic efficiency of endoglucanases II (EGII, EC 3.2.1.4) are considered important for industrial application. The characterization of the EGII is necessary since it is widely used in high-temperature reactions in the industries. In this study, the recombinant EGII protein was expressed in Pichia pastoris and it has a molecular mass of approximately 52 kDa. Recombinant EGII was purified using Ni-NTA affinity chromatography and characterized by SDS-PAGE and western blot analyses. The enzyme activity of recombinant EGII was measured using the Nelson Somogyi method to determine its optimum pH and temperature. The result showed that the maximum EGII expression was achieved after 72 h of culture incubation. The crude enzyme has optimum activity at pH 5.0, resulting in 16.3 U/mL and 14.6 U/mL activity at 40 °C and 50 °C, respectively. While the purified enzyme gave the specific activity of 115.7 U/mg under the optimum condition. Finally, our study demonstrated that recombinant EGII could retain the endoglucanase activity for 89% and 80% at 40 °C and 50 °C, respectively.