bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the Microenvironment to Overcome Gemcitabine Resistance in Pancreatic Cancer
Authors: Carpenter Eileen S. , Steele Nina G. , Pasca di Magliano Marina 
Published: August 2020

Abstract
Pancreatic cancer is characterized by an extensive and complex microenvironment, and is resistant to both chemotherapy and immune checkpoint blockade. The study by Principe and colleagues in this issue of Cancer Research proposes a combinatorial approach based on targeting the very mechanisms of resistance to gemcitabine, a commonly used chemotherapeutic agent. The authors show that gemcitabine treatment causes profound changes in the pancreatic cancer microenvironment, including elevated TGFβ signaling and immune checkpoint expression, as well as increased antigen presentation in tumor cells. Accordingly, they show that the combination of chemotherapy, TGFβ signaling inhibition, and immune checkpoint blockade effectively restores antitumor immunity and results in a significant survival benefit.
See related article by Principe et al., p. 3101
PIM Kinase Inhibitors Block the Growth of Primary T-cell Acute Lymphoblastic Leukemia: Resistance Pathways Identified by Network Modeling Analysis
Authors: Lim James T. , Singh Neha , Leuvano Libia A. , Calvert Valerie S. , Petricoin Emanuel F. , Teachey David T. , Lock Richard B. , Padi Megha , Kraft Andrew S. , Padi Sathish K.R. 
Published: August 2020

Abstract
Despite significant progress in understanding the genetic landscape of T-cell acute lymphoblastic leukemia (T-ALL), the discovery of novel therapeutic targets has been difficult. Our results demonstrate that the levels of PIM1 protein kinase is elevated in early T-cell precursor ALL (ETP-ALL) but not in mature T-ALL primary samples. Small-molecule PIM inhibitor (PIMi) treatment decreases leukemia burden in ETP-ALL. However, treatment of animals carrying ETP-ALL with PIMi was not curative. To model other pathways that could be targeted to complement PIMi activity, HSB-2 cells, previously characterized as a PIMi-sensitive T-ALL cell line, were grown in increasing doses of PIMi. Gene set enrichment analysis of RNA sequencing data and functional enrichment of network modules demonstrated that the HOXA9, mTOR, MYC, NFκB, and PI3K-AKT pathways were activated in HSB-2 cells after long-term PIM inhibition. Reverse phase protein array–based pathway activation mapping demonstrated alterations in the mTOR, PI3K-AKT, and NFκB pathways, as well. PIMi-tolerant HSB-2 cells contained phosphorylated RelA-S536 consistent with activation of the NFκB pathway. The combination of NFκB and PIMis markedly reduced the proliferation in PIMi-resistant leukemic cells showing that this pathway plays an important role in driving the growth of T-ALL. Together these results demonstrate key pathways that are activated when HSB-2 cell line develop resistance to PIMi and suggest pathways that can be rationally targeted in combination with PIM kinases to inhibit T-ALL growth.
A LHFPL3-AS1/miR-580-3p/STAT3 Feedback Loop Promotes the Malignancy in Melanoma via Activation of JAK2/STAT3 Signaling
Authors: Peng Qian , Liu Linbo , Pei Hui , Zhang Jianwen , Chen Minjing , Zhai Xiaomei 
Published: August 2020

Abstract

Melanoma is one of the severe skin cancers, accounting for three fourths of all deaths caused by skin cancers and gathering attention from researchers. Previous studies have elucidated that long noncoding RNAs (lncRNA) engage actively in tissue physiology and disease development, especially in tumorigenesis. LncRNA LHFPL3 antisense RNA 1 (LHFPL3-AS1) has rarely been mentioned in researches regarding cancers; therefore, the underlying role and function of LHFPL3-AS1 in melanoma arouse our interest. Data from our work suggested that LHFPL3-AS1 expression was markedly elevated in melanoma tissues and cells. Of note, patients with melanoma with high level of LHFPL3-AS1 were burdened with unfavorable prognosis. Functionally, it has been revealed that LHFPL3-AS1 exerted pro-growth, pro-invasion, and pro-EMT functions in melanoma. Mechanistically, it was figured out that LHFPL3-AS1 could be transcriptionally activated by STAT3. In turn, LHFPL3-AS1 served as a sponge of miR-580-3p to augment STAT3 expression, resulting in activated JAK2/STAT3 signaling pathway in melanoma.

Implications:
Our study revealed a novel positive feedback loop LHFPL3-AS1/miR-580-3p/STAT3 in melanoma, which might contribute to finding potential therapeutic targets for melanoma.
Phosphorylation of PLCγ1 by EphA2 Receptor Tyrosine Kinase Promotes Tumor Growth in Lung Cancer
Authors: Song Wenqiang , Kim Laura C. , Han Wei , Hou Yuan , Edwards Deanna N. , Wang Shan , Blackwell Timothy S. , Cheng Feixiong , Brantley-Sieders Dana M. , Chen Jin 
Published: August 2020

Abstract

EphA2 receptor tyrosine kinase (RTK) is often expressed at high levels in cancer and has been shown to regulate tumor growth and metastasis across multiple tumor types, including non–small cell lung cancer. A number of signaling pathways downstream of EphA2 RTK have been identified; however, mechanisms of EphA2 proximal downstream signals are less well characterized. In this study, we used a yeast-two-hybrid screen to identify phospholipase C gamma 1 (PLCγ1) as a novel EphA2 interactor. EphA2 interacts with PLCγ1 and the kinase activity of EphA2 was required for phosphorylation of PLCγ1. In human lung cancer cells, genetic or pharmacologic inhibition of EphA2 decreased phosphorylation of PLCγ1 and loss of PLCγ1 inhibited tumor cell growth in vitro. Knockout of PLCγ1 by CRISPR-mediated genome editing also impaired tumor growth in a KrasG12D-p53-Lkb1 murine lung tumor model. Collectively, these data show that the EphA2-PLCγ1 signaling axis promotes tumor growth of lung cancer and provides rationale for disruption of this signaling axis as a potential therapeutic option.

Implications:
The EphA2-PLCG1 signaling axis promotes tumor growth of non–small cell lung cancer and can potentially be targeted as a therapeutic option.
A novel comprehensive database for arabic and english off-line handwritten digits recognition
Authors: Subhi Abdalkafor Ahmed , Kareem Awad Waleed , Ali Alheeti Khattab M. 
Published: August 2020

<span>The recognition of Arabic handwritten is received at the same interest as other Latin languages. In Optical Character Recognition (OCR), handwriting Arabic recognition is considered as one of the critical and difficult tasks in the various scientific area. The main issues of this matter were due to the lack of public Arabic handwriting databases and the cursive nature of Arabic writing. In this paper, a new benchmark database is built for the Arabic and English off-line handwritten digits Recognition. The original form is divided into three groups: Arabic digits, English digits, and word Arabic digits which written five times by 100 different academic staff and students of university writers. Our database contains 14500 images; divided into two subsets of training and testing to help researchers through evaluating and comparing results obtained from their systems. </span>
Sensitivity analysis based artificial neural network approach for global solar radiation prediction in India
Authors: Meenal Rajasekaran , Selvakumar A. Immanuel , Michael Prawin Angel , Rajasekaran Ekambaram 
Published: August 2020

<p>The objective of this paper is to build an artificial neural network model to predict Global Solar Radiation (GSR) with improved accuracy using less number of best input parameters selected using sensitivity analysis. In this work, the input parameters used for training the artificial neural network (ANN) models are bright sunshine duration, maximum and minimum temperature, day length, months, extra terrestrial radiation (<em>H<sub>0</sub></em>), relative humidity and geographical parameters of the locations namely the latitude and longitude. Sensitivity analysis is used to discover how the output data are influenced by the changeability of the input data.Three ANN models namely T-ANN, S-ANN and TS-ANN are proposed with most suitable input parameters selected using sensitivity analysis. The principle of this feature selection using sensitivity analysis is to improve the prediction accuracy of solar radiation models with less number of inputs. The proposed ANN model is also tested under noisy data and proved that ANN is able to perform reasonably good in GSR prediction on practical applications where the data is affected by noise caused by errors on measuring, fault of data acquisition system, recording problems, and so on.</p>
ICT-supported for participatory engagement within E-learning community
Authors: Natrah Aziz Noor Hida , Haron Haryani , Fathiyah Harun Afdallyna 
Published: August 2020

This paper presents ICT-supported for participatory engagement learning within the e-learning community. Effectively tools in e-Learning facilitate interactive learning and the achievement of desired learning outcomes for learners. However, the intensity of its usage is not very remarkable; there is a need to understand ICT- supported for learners from the perspectives of participatory engagement. Therefore, integrating suitable technology into e-learning is expected to strengthen learner's engagement within the e-learning community. The objective of the study is to identify technology that could effectively support learners' engagement. This study analyzes the available technology in the market to integrate into e-learning using the technology evaluation process. Interview sessions with experts were held to validated and suggested other technology uses in e-learning. This research is carrying out with three experts (academic staff) of the e-technologies within the University. This study uses semi-structured interviews to captured expert suggestions, knowledge, and expertise about technologies. Understanding learner's requirements toward technology are essential to ensure learners can reap the benefits of technology usage. This study uses a thematical analysis to identify and organize key themes from qualitative data. The result reveals mobile technology, wireless technology, live streaming technology, authoring tool, summative assessment, cloud computing, gamification and Instagram is suitable technologies that support participatory engagement activities.
IMU sensor-based data glove for finger joint measurement
Authors: Wa’ie Hazman Muhammad Ajwad , Aimi Mohd Nordin Ili Najaa , Mohd Noh Faridah Hanim , Khamis Nurulaqilla , M. Razif M. R. , Athif Faudzi Ahmad , Mohd Hanif Asyikin Sasha 
Published: August 2020

<p>The methods used to quantify finger range of motion significantly influence how hand disability is reported. To date, the accuracy of sensors being utilized in data gloves from the literature has been ascertained yet need further analysis. This paper presents an inertial measurement unit sensor-based data glove for finger joint measurement developed for collecting a range of motion data of distal interphalangeal, proximal interphalangeal and metacarpophalangeal finger joints of an index finger. In this study, three inertial measurement sensors, MPU-6050 and two flexible bend sensors which are capable to detect angle displacement were attached to the distal interphalangeal, proximal interphalangeal and metacarpophalangeal finger joint points on the glove. The data taken from inertial measurement unit sensors and flexible bend sensors were acquired using Arduino and MATLAB software interface. The data obtained were compared with the reference data measured from goniometer to allow for accurate comparative measurement. The percentage of error resulted from MPU-6050 sensor unit were ranged from 0.81 % to 5.41 % were very low which indicates high accuracy when compared with the measurements obtained using goniometer. On the other hand, flexible bend sensor shows low accuracy (11.11 % to 19.35 % error). In conclusion, the inertial measurement unit sensor-based data glove using MPU-6050 sensors can be a reliable solution for tracking the progress of finger rehabilitation exercises. In order to motivate patients to adhere to the therapy exercises, interactive rehabilitation game will be developed in the future incorporating MPU-6050 sensors on all five fingers.</p>
A variant of hybrid conjugate gradient methods based on the convex combination for optimization
Authors: Hassan Basim Abbas , Owaid Ahmed Obeid , Yasen Zena T. 
Published: August 2020

<p><span>On some studies a conjugate parameter plays an important role for the conjugate gradient methods. In this paper, a variant of hybrid is provided in the search direction based on the convex combination. This search direction ensures that the descent condition holds. The global convergence of the variant of hybrid is also obtained. Our strong evidence is a numerical analysis showing that the proposed variant of hybrid method is efficient than the Hestenes and Stiefel method. </span></p>
Review of space charge measurement by pulsed electro-acoustic technique
Authors: Asyraf Shee Kandar Mohd Haris , Mohd Jamail Nor Akmal , Azlin Othman Nordiana , Ezani Kamarudin Qamarul , Mohd Jamail Nor Shahida , Bagchi Susama 
Published: August 2020

<p>Pulsed electro-acoustic (PEA) is well known as a non-destructive technique for testing and describing space charge profiles in the insulation. Degradation due to moisture, ageing, external flashover, partial discharge and space charge are considered as insulation defects that is an issue in high voltage insulator. Space charge may distort the internal electric field that may lead to an electrical breakdown. For instance, a method based on an acoustic phenomenon can be used to describe the space charge profiles. This paper compares several earlier researches on different specimen of PEA method and reviews their results to find the space charge distribution profiles. The scope of the review includes types of methods used. The acoustic technique is considered for this study. It has been observed that the PEA technique successfully gives the same result as theoretical that is based on the obtained profile. Linear low-density polyethylene (LLDPE) composite demonstrates about 89 % lower charge density value compared to cross-linked polyethylene (XLPE) and polypropylene (PP) composite. While the electric field value of ethylene-vinyl acetate (EVA) sample is 75 % lower than low-density polyethylene (LDPE) sample. This study found that the time interval, specimen thickness and the electric field sway the space charge profiles. </p>
Economic power dispatch for an interconnected power system based on reliability indices
Authors: Athab Falah Abodahir , Majeed Wafaa Saeed 
Published: August 2020

Reliability indices are always one of the most important factors in the power systems. In this paper, the problem of the economic load dispatch (ELD) and the problem of economic emission load dispatch (CEELD) have been improved taking into account reliability indices. That is, the problem and reliability of ELD are proposed as combined economic load dispatch reliability (CELDR) and the problem CEELD is suggested as (CEELDR). In solving CELDR and CEELDR problems, tried to use power generators in a very reliable way to save system load, as well as minimum fuel and emission costs. In this effort, the ELD of power plants is successfully implemented in a single system containing 6 generating units, taking into account the reliability and emissions of the system with and without system power loss, inequality and inequality constraints, and valve point effects using the exchange market algorithm(EMA). The results suggest that reliability indicators in ELD can be used to create greater reliability in providing consumers with uninterrupted power.
Modelling foreign exchange rates: a comparison between markov-switching and markov-switching GARCH
Authors: Nunian Mohd Azizi Amin , Zahari Siti Meriam , Shariff S.Sarifah Radiah 
Published: August 2020

Foreign exchange rate is important as it determines a country's economic condition. It is used to carry out transfers of purchasing power between two or more countries. Volatility in exchange rates may result in difficulty in decision making especially, in financial sectors as high volatility could increase the risk in exchange rates. Thus, Markov switching model is employed in this study as it is believed to be efficient in handling not only volatilility but also nonlinearity characteristics in exchange rates. The aims of this study are to model the foreign exchange rates using two models; Markov Switching (M-S) models and Markov Switching Generalized Autoregressive Conditional Heteroscedasticity (M-S GARCH) and to compare these two models based on log-likelihood, AIC and BIC criteria. This study used the quarterly data of foreign exchange rates for Singapore Dollar (SGD), Korean Won (KRW), China Yuan Renminbi (CNY), Japanese Yen (JPY) and the US Dollar (USD) against Malaysia Ringgit (MYR) which were collected from Quarter 4, 2006 to Quarter 1, 2018. The findings indicate that Markov Switching is the best model since it has the highest log-likelihood value, and the lowest AIC and BIC values. The results show that JPY and SGD have highly persistent trends on regime 1 with probability values 0.96 and 0.84, respectively as compared to CNY, KRW and USD, while the latter have high persistent trends on regime 2 with probability values, 0.99, 0.95, 0.82, respectively.
Real‐World Analysis of Guideline‐Based Therapy After Hospitalization for Heart Failure
Authors: Wirtz Heidi S. , Sheer Richard , Honarpour Narimon , Casebeer Adrianne W. , Simmons Jeff D. , Kurtz Christopher E. , Pasquale Margaret K. , Globe Gary 
Published: August 2020

Background
Patients hospitalized with heart failure (HF) with reduced ejection fraction have high risk of rehospitalization or death. Despite guideline recommendations based on high‐quality evidence, a substantial proportion of patients with HF with reduced ejection fraction receive suboptimal care and/or do not comply with optimal care following hospitalization.

Methods and Results
This retrospective observational study identified 17 106 patients with HF with reduced ejection fraction with an incident HF‐related hospitalization using the Humana Medicare Advantage database (2008–2016). HF medication classes (beta‐blockers, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, or mineralocorticoid receptor antagonists) received in the year after hospitalization were recorded, and categorized by treatment intensity (ie, number of concomitant medication classes received: none [23% of patients; n=3987], monotherapy [22%; n=3777], dual therapy [41%; n=7056], or triple therapy [13%; n=2286]). Compared with no medication, risk of primary outcome (composite of death or rehospitalization) was significantly reduced (hazard ratio [95% CI]) with monotherapy (0.68 [0.64–0.71]), dual therapy (0.56 [0.53–0.59]), and triple therapy (0.45 [0.41–0.50]). Nearly half (46%) of patients who received post‐discharge medication had no dose escalation. Overall, 59% of patients had follow‐up with a primary care physician within 14 days of discharge, and 23% had follow‐up with a cardiologist.

Conclusions
In real‐world clinical practice, increasing treatment intensity reduced risk of death and rehospitalization among patients hospitalized for HF, though the use of guideline‐recommended dual and triple HF therapy remained low. There are opportunities to improve post‐discharge medical management for patients with HF with reduced ejection fraction such as optimizing dose titration and improving post‐discharge follow‐up with providers.
<p><strong>The taxonomy and nomenclature of <em>Kalanchoe humilis</em>, <em>K. prasina</em>, and <em>K. figueiredoi</em> (Crassulaceae subfam. Kalanchooideae)</strong></p>
Authors: SMITH GIDEON F. 
Published: August 2020

The taxonomy and nomenclature of Kalanchoe humilis, K. prasina, and K. figueiredoi (Crassulaceae subfam. Kalanchooideae) are discussed. Based on available evidence K. humilis and K. prasina are accepted as two species from eastern and south-tropical Africa, and K. figueiredoi is included in the synonymy of K. prasina.
Assessment of HF Radar in Mapping Surface Currents under Different Sea States
Authors: Wei Guomei , He Zhigang , Xie Yanshuang , Shang Shaoping , Dai Hao , Wu Jingyu , Liu Ke , Lin Rui , Wan Yan , Lin Hang , Chen Jinrui , Li Yan 
Published: August 2020

AbstractTwo Ocean State Monitoring and Analyzing Radar (OSMAR071) (7.8 MHz) high-frequency (HF) radars and four moored ADCPs were operated concurrently in the southwestern Taiwan Strait during January–March 2013. Qualitative and quantitative comparisons of surface currents were conducted between the HF radars and the ADCPs. Except for a location probably affected by shallow water and sand waves on the Taiwan Banks, the HF-radar-derived radial currents (radials) showed good agreement with the ADCP measured results (correlation coefficient: 0.89–0.98; rms difference: 0.07–0.13 m s−1). To provide further insight into the geophysical processes involved, the performance of the HF-radar-derived radials was further evaluated under different sea states (sea states: 2–6). It was found that both the data returns of the radar-derived radials and the differences between the radar-derived radials and the ADCP-derived radials varied with sea state. The HF radar performed best at sea state 4 in terms of data returns. The spatial coverage increased rapidly as the waves increased from sea state 2 to 4. However, it decreased slowly from sea state 4 to 6. Second, the radial differences were relatively high under lower sea states (2 and 3) at the location where the best agreement was obtained between the radar and ADCP radials, whereas the differences increased as the sea states increased at the other three locations. The differences between the radials measured by the HF radars and the ADCPs could be attributed to wave-induced Stokes drift and spatial sampling differences.
Virtual Reality as Distraction Analgesia for Office‐Based Procedures: A Randomized Crossover‐Controlled Trial
Authors: Gray Mingyang L. , Goldrich David Y. , McKee Sean , Schaberg Madeleine , Del Signore Anthony , Govindaraj Satish , Iloreta Alfred Marc 
Published: August 2020

ObjectiveThe purpose of this study was to explore the use of immersive and interactive virtual reality (VR) for analgesia, anxiety reduction, and overall satisfaction in patients undergoing outpatient postoperative debridements.Study DesignRandomized crossover‐controlled trial.SettingAcademic outpatient clinic.Subjects and MethodsAdult patients who had functional endoscopic sinus surgery and skull base surgery and were undergoing office‐based postoperative nasal endoscopy and debridement were recruited and followed for 2 consecutive office visits. Participants were randomized to receive either the control or experimental analgesia for the first postoperative visit (PO1) and crossed over into the opposite treatment arm during the second postoperative visit (PO2). Outcomes included procedural pain, anxiety and satisfaction scores, procedural time, and reflexive head movements per minute (RHM).ResultsEighty‐two participants were recruited. At PO1, 39 received standard analgesia, and 43 received an immersive VR experience. At PO1, the VR group experienced significantly less anxiety (P =. 043) and fewer RHM (P =. 00016) than the control group. At PO2, the VR group experienced significantly fewer RHM (P =. 0002). At PO2, patients who received the experimental treatment after initially receiving the control treatment had significantly decreased pain, anxiety, and RHM. This effect was not seen in the second group. Overall, 69.51% of patients felt that the VR treatment was better; 19.51% thought that it was the same; and 9.76% found it to be worse.ConclusionVR technology holds promise as a nonpharmacologic analgesic and anxiolytic intervention for otolaryngology office‐based procedures. Further study of VR use in other procedures is warranted.Level of Evidence:1, randomized controlled trial.