bluuebunny/crossref_metadata_2025 huggingface dataset:
Green Supplier Evaluation and Selections: A State-of-the-Art Literature Review of Models, Methods, and Applications
Authors: Zhang Li-Jun , Liu Ran , Liu Hu-Chen , Shi Hua
Published: July 2020

The role of green supplier evaluation and selection (GSES) in supply chain management is increasingly appreciated due to the intensification of competition, raising public consciousness, and environmental issues. To improve GSES, a large number of approaches have been proposed in the past decades. However, few attempts have been made to systematically review and classify the literature in this field. The objective of this study is to afford a comprehensive review of the studies which aim to develop models and methods in helping enterprises to assess and select the right green suppliers. To achieve this goal, a total of 193 journal articles extracted from the Scopus database over the period of 2009 to 2020 were chosen and reviewed. These publications were classified into ten categories based on their adopted GSES models and analyzed concerning the evaluation criteria, criteria weighting methods, and performance evaluation methods. Moreover, a bibliometric analysis was conducted according to the frequency of supplier selection methods, citation number, publication year, journal, country, and application area. This study supports practitioners, managers, and researchers in effectively recognizing and applying the GSES models to enhance organizational competitiveness and provides an insight into its state of the art.
Droplet Impact on a Moving Thin Film with Pseudopotential Lattice Boltzmann Method
Authors: He Jinchao , Yuan Hao , He Xiaolong , Xie Chunhang , Peng Haonan , Hu Ruichang
Published: July 2020

The pseudopotential lattice Boltzmann method (LBM) with a tunable surface tension term is applied to study a droplet impact on a moving thin film. The Re effects of dimensionless parameters on the upstream and downstream crown evolution are studied, including Reynolds number (Re), Weber number (We), liquid film thickness, and horizontal velocity of the liquid film. The movement of the liquid film causes the asymmetry development of the upstream and downstream crown. Both the instability of upstream and downstream crowns increases with the increase of Re and We, and the upstream crown becomes more prone to break up. And a critical value of film thickness exists with the height of the upstream and downstream liquid crowns reaches the maximum value. And the velocity of liquid film restrains the development of the height of the upstream and downstream crowns, but it promotes the growth of the crown radius.
Disorder-Induced Superconductor-Insulator Transition
Authors: Deressa Zeleke , Singh P.
Published: July 2020

In this paper, we report the results of our theoretical investigation on the interplay of superconductivity and disorder in two-dimensional (2D) systems. The effect of disorder on superconductivity of 2D systems was found analytically using Green’s function formalism. The results of our calculation revealed that disorder induced due to randomly distributed superconducting islands enhances decoherence of Cooper pairs and suppresses superconductivity. We have also determined the critical value of disorder at which the 2D system completely loses its superconducting properties. Below this critical value of disorder, the system acts as a superconductor, a system with zero electrical resistance. Above the critical value, it acts as an insulator, a system with infinite electric resistance. This is a fascinating result because a direct transition from the state of the infinite conductivity to the opposite extreme of infinite resistivity is unexpected in the theory of condensed matter physics.
Prognostic Value of an m6A RNA Methylation Regulator‐Based Signature in Patients with Hepatocellular Carcinoma
Authors: Wu Xiaomin , Zhang Xiaojing , Tao Leilei , Dai Xichao , Chen Ping
Published: July 2020

Purposes. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Recent researches have demonstrated that m6A methylation regulators play a key role in various cancers, such as gastric cancer and colon adenocarcinoma. Several m6A methylation regulators are reported to predict the prognosis of HCC. Therefore, there is a need to further identify the predictive value of m6A methylation regulators in HCC. Methods. We utilized The Cancer Genome Atlas (TCGA) database to obtain the gene expression profile of m6A RNA methylation regulators and clinical information for patients with HCC. Besides, we identified two clusters of HCC with various clinical factors by consensus clustering analysis. Then the least absolute shrinkage and selection operator (LASSO) and the Cox regression analysis were applied to construct a prognostic signature. Results. Except for ZC3H13 and METTL14, a majority of the thirteen m6A RNA methylation regulators were significantly overexpressed in HCC specimens. HCC patients were classified into two groups (cluster 1 and cluster 2). The cluster 1 was with a significantly worse prognosis than cluster 2, and most of the 13 known m6A RNA methylation regulators were upregulated in cluster 1. Besides, we developed a prognostic signature consisting of YTHDF2, YTHDF1, METTL3, KIAA1429, and ZC3H13, which could successfully differentiate high‐risk patients. More importantly, univariate and multivariate Cox regression analysis indicated that the signature‐based risk score was an independent prognostic factor for patients with HCC. Conclusions. Our study showed these five m6A RNA methylation regulators can be used as practical and reliable prognostic tools of HCC, which might have potential value for therapeutic strategies.
Utilization of a Continuous Pericapsular Nerve Group (PENG) Block with an Opioid-Sparing Repair of a Femoral Neck Fracture in a Pediatric Patient
Authors: Wyatt Karla , Zidane Moustafa , Liu Chyong-jy Joyce
Published: July 2020

In the pediatric population, femoral neck fractures are usually associated with high-impact trauma and often present with pain in the groin area. Regional anesthesia can offer adjunctive therapy for acute pain management. Various techniques have been employed to circumvent pain related to hip fractures and resultant hip surgery. Neuraxial, lumbar plexus, caudal, epidural, fascia iliaca, and femoral continuous nerve block techniques are advantageous in mitigating hip pain. However, these approaches require patient repositioning during placement and carry the potential for motor blockade with resultant weakness. A newly described method, the Pericapsular Nerve Group (PENG) block, allows for analgesia of the anterior hip capsule via the obturator, accessory obturator, and femoral nerves while sparing motor blockade. PENG blockade has demonstrated efficacy in both adult and pediatric patients. Herein, we describe the perioperative course of a 9-year-old girl with a transcervical femoral neck fracture who underwent an opioid-sparing open repair with the utilization of a continuous PENG block. PENG blockade via a continuous nerve block resulted in optimal analgesia and markedly reduced perioperative opioid consumption with preserved motor function. Our experience facilitated early discharge and rehabilitation mobility while reducing potential rebound hyperalgesia and enabling parental/patient satisfaction.
Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease
Authors: Huang Yajing , Chi Jingwei , Wei Fanxiang , Zhou Yue , Cao Yihai , Wang Yangang
Published: July 2020

Diabetic kidney disease (DKD) is a common cause of end-stage renal disease, and diagnosis and treatment in time can help delay its progress. At present, there are more and more studies on the pathogenesis of DKD; mitochondrial dysfunction plays an important role in DKD. The occurrence and development of DKD is closely related to epigenetic changes and the interaction between mtDNA, ROS, inflammatory factors, and endothelial damage, which continuously aggravates kidney. The change of mtDNA is both the cause of DKD and the result of DKD. It is of great significance to incorporate the change of mtDNA into the monitoring of patients with diabetes. Existing evidence indicates that changes in mtDNA copy number in blood and urine reflect mitochondrial dysfunction and the severity of DKD. However, large-scale, long-term follow-up clinical trials are still needed to determine the threshold range. By the time, mitochondrial-targeted antioxidants will become a new method for the treatment of DKD and other diabetic complications; mtDNA also can be a therapeutic target for them.
Deadbeat-Based Model Predictive Voltage Control for a Sensorless Five-Phase Induction Motor Drive
Authors: Mossa Mahmoud A. , Vu Quynh Nguyen , Echeikh Hamdi , Do Ton Duc
Published: July 2020

This paper introduces a direct model predictive voltage control (DMP VC) for a sensorless five-phase induction motor drive. The operation of the proposed sensorless DMP VC is based on the direct control of the applied stator voltages instead of controlling the torque and flux as in model predictive direct torque control (MP DTC). Thus, the simplicity of the control system is enhanced, which saves the computational time and reduces the commutation losses as well. The methodology based on which the proposed sensorless DMP VC performs its operation depends on minimizing a cost function that calculates the error between the reference and actual values of the direct and quadrature (d-q) axes components of stator voltages. The reference values of d-q components of stator voltages are obtained through incorporating the deadbeat control within the proposed model predictive system. A robust back-stepping observer is proposed for estimating the speed, stator currents, rotor flux, and rotor resistance. The validity of the proposed sensorless DMP VC is confirmed through performing detailed and extensive comparisons between the proposed DMP VC and MP DTC approach. The obtained results state that the drive is exhibiting better performance under the proposed DMP VC with less ripples content and reduced computational burden. Moreover, the proposed back-stepping observer has confirmed its effectiveness in estimating the speed and other variables for a wide range of speed operation.
Existence of Solution for Double-Phase Problem with Singular Weights
Authors: Chen Zhi-Yuan , Ge Bin , Yuan Wen-Shuo , Cao Xiao-Feng
Published: July 2020

The aim of this paper is to establish the existence of solutions for singular double-phase problems depending on one parameter. This work improves and complements the existing ones in the literature. There seems to be no results on the existence of solutions for singular double-phase problems.
Hepatitis B Birth Dose among Children in District 2 Hospital, Ho Chi Minh City, Vietnam: Prevalence and Associated Factors
Authors: Huynh Giao , Nguyen Thanh Binh , Cao Ngoc Nga , Phan Minh Hoang , Dang Thi Bich Hop , Nguyen Thi Ngoc Han
Published: July 2020

Background. A birth dose of the hepatitis B vaccine will prevent most perinatally acquired infections and offers early protection from horizontal transmission. This article assessed the prevalence of the hepatitis B birth dose and associated factors among children in the District 2 Hospital. Methods. A prospective cross-sectional study between June and December 2017 recruited parents/caregivers of children aged 12–59 months who were randomly selected at the vaccination department in the District 2 Hospital. The structured questionnaire applied was to collect the characteristics of participants and check the vaccination schedule. The birth dose was defined as the hepatitis B vaccine, which was given to children within 24 hours after birth. Additionally, a semistructured questionnaire was used for interviews and focus group discussions (FGDs) to assess the risk perceptions and barriers to vaccination. Results. A total of 292 parents/caregivers had a mean age of 32.7 ± 6.8 years; among them, 88.7% were females. Their children had a mean age of 30.3 ± 13.9 months and 71.6% of these children received the hepatitis B birth dose, which correlated with the age of gestation (P<0.05). In-depth interviews and FGDs found that most participants did not know that hepatitis B could be transmitted through childbirth, and barriers that affected the birth dose vaccine included children being sick, premature infants, or reason relating to physicians. Conclusions. The rate of hepatitis B birth dose was low, which resulted from associated factors such as premature birth, likely to be linked with false contraindications and beliefs that, potentially, the 2013 incident is still fresh in people’s minds. Therefore, strategies to implement policies around the hepatitis B birth dose should be in line with current World Health Organization recommendations and strategies to modify current beliefs about vaccination.
Physicochemical Properties and Total Carotenoid Content of High-Quality Unripe Plantain Flour from Varieties of Hybrid Plantain Cultivars
Authors: Anajekwu Ekpereka Oluchukwu , Maziya-Dixon Busie , Akinoso Rahman , Awoyale Wasiu , Alamu Emmanuel Oladeji
Published: July 2020

Unripe plantain has been considered as having commercial potential or used as an ingredient for other foods. Information on the physicochemical and carotenoid properties of flours from hybrid plantain cultivars in the literature is limited. This study was conducted to determine the physicochemical properties and carotenoid contents of unripe plantain flour from selected hybrid plantain cultivars using standard laboratory methods. The unripe plantain pulps of four varieties (PITA 26, PITA 27, Mbi Egome and Agbagba (control)) used in this study were cabinet dried at 65°C for 48 h and milled into flour. The result showed that moisture content ranged from 6.15 to 7.27%, Ash (2.01–3.69%), Fat (0.49–1.20%), Protein (2.47–2.99%), Fibre (0.73–0.97%), Sugar (6.29–9.33%), starch (84.34–104.96%), total carotenoid content (2.96–24.19 µg/g). Potassium ranged from 328.30–528.50 mg/kg, Calcium (9.46–11.98 mg/kg), Magnesium (24.73–29.11 mg/kg), Sodium (6.30–7.24 mg/kg), Zinc (0.12–0.29 mg/kg), and manganese (0.03–0.15 mg/kg). The L∗ (Lightness) ranged from 62.88 to 67.00. Bulk density ranged from 0.72 to 0.77 g/ml, WAC (143.59–174.08), OAC (98.07–100.66%), swelling power capacity (10.63 to 11.82%), solubility (5.58–6.71%), and dispersibility (86.50–88.00%). Peak viscosity ranged from 568.17 to 761.64 RVU, final viscosity (378.53–496.58 RVU), and peak temperature (81.62–83.23°C). The results suggest that the hybrid plantain cultivars could be used to produce good quality plantain flours with improved physicochemical and pasting properties.
Vibration Analysis of Piezoelectric Composite Plate Resting on Nonlinear Elastic Foundations Using Sinc and Discrete Singular Convolution Differential Quadrature Techniques
Authors: Ragb Ola , Salah Mohamed , Matbuly M. S. , Amer R. B. M.
Published: July 2020

In this work, free vibration of the piezoelectric composite plate resting on nonlinear elastic foundations is examined. The three-dimensionality of elasticity theory and piezoelectricity is used to derive the governing equation of motion. By implementing two differential quadrature schemes and applying different boundary conditions, the problem is converted to a nonlinear eigenvalue problem. The perturbation method and iterative quadrature formula are used to solve the obtained equation. Numerical analysis of the proposed schemes is introduced to demonstrate the accuracy and efficiency of the obtained results. The obtained results are compared with available results in the literature, showing excellent agreement. Additionally, the proposed schemes have higher efficiency than previous schemes. Furthermore, a parametric study is introduced to investigate the effect of elastic foundation parameters, different materials of sensors and actuators, and elastic and geometric characteristics of the composite plate on the natural frequencies and mode shapes.
Prediction Model of In-Band Blocking Interference under the Electromagnetic Radiation of Dual-Frequency Continuous Wave
Authors: Zhao Kai , Wei Guanghui , Wang Yaping , Pan Xiaodong
Published: July 2020

Two hypotheses for the blocking effect mechanisms under the electromagnetic radiation are presented, and the corresponding dual-frequency interference prediction models are proposed, which can be used to predict the working state of equipment under the condition that the single-frequency susceptibility is known. By taking a radar and a communication radio as the EUT, the experiments of dual-frequency continuous wave electromagnetic radiation are designed and carried out to verify the prediction models. The test results show that the sensitive bandwidth of blocking interference effect for the tested radar and the communication station is consistent with their working bandwidth, respectively. By substituting the test data into the proposed prediction models, the prediction errors of the models are less than 13%. Moreover, it can be found that the tested radar is more sensitive to the peak value of electric field, and the tested communication station is more sensitive to the effective value of electric field.
A Descriptive Study on Sepsis: Causes, Outcomes, and Adherence to Guidelines on Patients with Sepsis at a Tertiary Care Hospital in Sri Lanka
Authors: Matthias Anne Thushara , Indrakumar J. , Ranasinghe Tharushi , Wijekoon Shalini , Yashodara Charuni
Published: July 2020

The global incidence of sepsis is increasing, and mortality remains high. The mortality is even higher in resource‐poor countries where facilities and equipment are limited. The Surviving Sepsis Campaign (SSC) recommends an updated hour‐1 bundle based on the evidence from the International Guidelines for Management of Sepsis and Septic Shock 2018. To reduce mortality from sepsis, compliance with the “bundle” is essential. Data from developing countries like Sri Lanka on the management of sepsis according to the SSC guidelines are not available. Hence, this study looks at the patient characteristics and management of septic patients at a tertiary care hospital in Sri Lanka. Patients admitted to the University Medical Unit of Colombo South Teaching Hospital from January to August 2019 fulfilling the inclusion criteria were included. The hour‐1 sepsis bundle adherence, demographic data, and management were recorded. There were 387 patients: 163 males and 224 females. The age range was 15‐95 with a mean age of 63. 83.7% were direct admissions while 16.3% were transfers from a peripheral hospital. The most common source of infection was urine (82 (21.2%)) followed by blood stream (105 (27.1%)) and skin and soft tissue (114 (29.5%)). One‐hour SSC bundle compliance is as follows: administration of intravenous fluids: 42 (10.9%), blood cultures before antibiotics: 225 (58.1%), first dose antibiotic: 15 (3.9%), and arterial blood gas: 60 (15.5%). Staffing capacity did not make a difference to adherence to the bundle. The study mortality rate was 37 (9.6%). Binary logistic regression indicates that quick sequential organ failure assessment (qSOFA) score is a significant predictor of mortality (chi‐square = 35.08, df = 3, and p = 0.001 (<0.05)) with an odds ratio (OR) of 7.529 (95% CI 3.597‐14.323). The other predictors, age, sex, adherence to sepsis care bundle, and comorbidities, were not significant. In conclusion, mortality of sepsis is high and adherence to sepsis care bundle is poor in Sri Lanka even at a tertiary care hospital. Education and training of staff are needed to boost adherence. This will in turn improve quality of care and outcomes of septic patients in resource‐poor countries.
Toxicokinetics of 11 Gelsemium Alkaloids in Rats by UPLC‐MS/MS
Authors: Shen Xiuwei , Ma Jianshe , Wang Xianqin , Wen Congcong , Zhang Meiling
Published: July 2020

Gelsemium elegans (Gardn. & Champ.) Benth. is a plant belonging to the genus Gelsemium (family Gelsemiaceae), and its main components are alkaloids. It is a Chinese traditional medicinal plant and notoriously known as a highly toxic medicine. However, a method has not yet been found for the simultaneous detection of 11 Gelsemium alkaloids in rat plasma, and the toxicokinetics of 11 Gelsemium alkaloids after intravenous administration has not been reported. In this work, we have developed a sensitive and rapid method of ultraperformance liquid chromatography/tandem mass spectrometry (UPLC‐MS/MS) for the detection of 11 Gelsemium alkaloids in rat plasma. The toxicokinetic behavior was also investigated, so as to provide a reference of the scientific properties of Gelsemium elegans and improve the efficacy and safety of drugs. Sixty‐six Sprague‐Dawley rats were randomly divided into 11 groups, six rats in each group. Each group was intravenously given one alkaloid (0.1 mg/kg), respectively. A Waters UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm) was used for chromatographic separation. Methanol and water (containing 0.1% formic acid) were used for the mobile phase with gradient elution. Multiple reactions were monitored, and positive electrospray ionization was used for quantitative analysis. The precision was less than 16%, and the accuracy was between 86.9% and 113.2%. The extraction efficiency was better than 75.8%, and the matrix effects ranged from 88.5% to 107.8%. The calibration curves were in the range of 0.1–200 ng/mL, with a correlation coefficient (R2) greater than 0.995. The UPLC‐MS/MS method was successfully applied to the toxicokinetics of 11 Gelsemium alkaloids in rats after intravenous administration (0.1 mg/kg for each alkaloid). The results of the toxicokinetics provide a basis for the pharmacology and toxicology of Gelsemium alkaloids and scientific evidence for the clinical use of Gelsemium alkaloids.
Investigation of the Anisotropic Characteristics of Layered Rocks under Uniaxial Compression Based on the 3D Printing Technology and the Combined Finite‐Discrete Element Method
Authors: He Fan , Liu Quansheng , Deng Penghai
Published: July 2020

The excavation in layered rocks is an issue for a number of geoengineering applications; these kinds of rocks all exhibit transverse isotropic features due to the process of metamorphic differentiation. This paper focuses on providing two methods, i.e., the 3D printing technology and the combined finite‐discrete element method, to simulate the anisotropic characteristics of layered rocks. The results showed that both the 3D‐printed samples and the FDEM numerical models are considered as a good match, and both revealed that as the inclined angle increased, the UCS of the sample first decreased and then increased, showing a U‐shaped pattern. The results of this paper served as a reference to the promotion of the 3D printing technology and the combined finite‐discrete element method in the geotechnical engineering field and laboratory test research.
A DE-LS Metaheuristic Algorithm for Hybrid Flow-Shop Scheduling Problem considering Multiple Requirements of Customers
Authors: Sun Yingjia , Qi Xin
Published: July 2020

In this paper, we address a hybrid flow-shop scheduling problem with the objective of minimizing the makespan and the cost of delay. The concerned problem considers the diversity of the customers’ requirements, which influences the procedures of the productions and increases the complexity of the problem. The features of the problem are inspired by the real-world situations, and the problem is formulated as a mixed-integer programming model in the paper. In order to tackle the concerned problem, a hybrid metaheuristic algorithm with Differential Evolution (DE) and Local Search (LS) (denoted by DE-LS) has been proposed in the paper. The differential evolution is a state-of-the-art metaheuristic algorithm which can solve complex optimization problem in an efficient way and has been applied in many fields, especially in flow-shop scheduling problem. Moreover, the study not only combines the DE and LS, but also modifies the mutation process and provides the novel initialization process and correction strategy of the approach. The proposed DE-LS has been compared with four variants of algorithms in order to justify the improvements of the proposed algorithm. Experimental results show that the superiority and robustness of the proposed algorithm have been verified.
Keratoconus with Central Serous Chorioretinopathy: A Rare Combination
Authors: Tsiogka Anastasia , Gkartzonikas Apostolos , Markopoulos Konstantinos , Georgiou Iordanis , Spaeth George L.
Published: July 2020

Keratoconus and central serous chorioretinopathy are two rare diseases. They can occur together in some individuals. We report a case of a 48-year-old man, who presented to our clinic with decreased visual acuity on his left eye. Physical examination, biomicroscopy, corneal topography, and optical coherence tomography revealed keratoconus and central serous chorioretinopathy. We discuss the possible connection between these two conditions.
3D Point Cloud Simplification Based on k-Nearest Neighbor and Clustering
Authors: Mahdaoui Abdelaaziz , Sbai El Hassan
Published: July 2020

While the reconstruction of 3D objects is increasingly used today, the simplification of 3D point cloud, however, becomes a substantial phase in this process of reconstruction. This is due to the huge amounts of dense 3D point cloud produced by 3D scanning devices. In this paper, a new approach is proposed to simplify 3D point cloud based on k-nearest neighbor (k-NN) and clustering algorithm. Initially, 3D point cloud is divided into clusters using k-means algorithm. Then, an entropy estimation is performed for each cluster to remove the ones that have minimal entropy. In this paper, MATLAB is used to carry out the simulation, and the performance of our method is testified by test dataset. Numerous experiments demonstrate the effectiveness of the proposed simplification method of 3D point cloud.
A Systematic Literature Review on Using Machine Learning Algorithms for Software Requirements Identification on Stack Overflow
Authors: Ahmad Arshad , Feng Chong , Khan Muzammil , Khan Asif , Ullah Ayaz , Nazir Shah , Tahir Adnan
Published: July 2020

Context. The improvements made in the last couple of decades in the requirements engineering (RE) processes and methods have witnessed a rapid rise in effectively using diverse machine learning (ML) techniques to resolve several multifaceted RE issues. One such challenging issue is the effective identification and classification of the software requirements on Stack Overflow (SO) for building quality systems. The appropriateness of ML-based techniques to tackle this issue has revealed quite substantial results, much effective than those produced by the usual available natural language processing (NLP) techniques. Nonetheless, a complete, systematic, and detailed comprehension of these ML based techniques is considerably scarce. Objective. To identify or recognize and classify the kinds of ML algorithms used for software requirements identification primarily on SO. Method. This paper reports a systematic literature review (SLR) collecting empirical evidence published up to May 2020. Results. This SLR study found 2,484 published papers related to RE and SO. The data extraction process of the SLR showed that (1) Latent Dirichlet Allocation (LDA) topic modeling is among the widely used ML algorithm in the selected studies and (2) precision and recall are amongst the most commonly utilized evaluation methods for measuring the performance of these ML algorithms. Conclusion. Our SLR study revealed that while ML algorithms have phenomenal capabilities of identifying the software requirements on SO, they still are confronted with various open problems/issues that will eventually limit their practical applications and performances. Our SLR study calls for the need of close collaboration venture between the RE and ML communities/researchers to handle the open issues confronted in the development of some real world machine learning-based quality systems.
Colchicine Alleviates Cholesterol Crystal-Induced Endothelial Cell Pyroptosis through Activating AMPK/SIRT1 Pathway
Authors: Yang Mengyue , Lv Hang , Liu Qi , Zhang Lu , Zhang Ruoxi , Huang Xingtao , Wang Xuedong , Han Baihe , Hou Shenglong , Liu Dandan , Wang Gang , Hou Jingbo , Yu Bo
Published: July 2020

Cholesterol crystal- (CC-) induced endothelial cell inflammation and pyroptosis play an important role in the development of cardiovascular diseases, especially in atherosclerosis (AS). Increasing evidence suggests that cholesterol crystals are known to be a pivotal pathological marker of atherosclerotic plaque vulnerability. As a classical nonspecific anti-inflammatory drug, colchicine has been widely used in the treatment of acute gout. However, whether colchicine could alleviate CC-induced endothelial cell injury and the related mechanisms remains to be addressed. In this study, the protective effect of colchicine on human umbilical vein endothelial cells (HUVECs) was confirmed. Our results revealed that after cotreatment with colchicine and cholesterol crystals in endothelial cells, the uptake of cholesterol crystals was significantly decreased, the cell viability was obviously increased, and the release of lactate dehydrogenase (LDH) and the number of pyroptotic cells decreased significantly; then, the expression of NLRP3 inflammasome-related proteins and various inflammatory factors was also visibly suppressed; moreover, as a potent activator of NLRP3 inflammasome, the intracellular ROS level was clearly reduced, while mitochondrial membrane potential improved significantly. In addition, the expression levels of AMP-dependent kinase (AMPK) pathway-related proteins as well as various antioxidant enzymes were elevated notably in varying degrees. However, the above effects of colchicine were completely offset by the treatment of siRNA targeting AMPKα and Sirtuin1 (SIRT1). Therefore, we conclude that colchicine plays a crucial role in alleviating the intracellular inflammatory response and NLRP3 inflammation activation, attenuating the levels of cellular oxidative stress and pyroptosis in endothelial cells via regulating AMPK/SIRT1 signaling, which may be a concrete mechanism for the secondary prevention of cardiovascular diseases.
Ganetespib in Combination with Pemetrexed–Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial
Authors: Fennell Dean A. , Danson Sarah , Woll Penella J. , Forster Martin , Talbot Denis , Child Jennifer , Farrelly Laura , Sharkey Annabel , Busacca Sara , Ngai Yenting , Hackshaw Allan , Wheeler Graham M.
Published: July 2020

Purpose:

Ganetespib, a highly potent, small-molecule Heatshock protein 90 inhibitor, has potential efficacy in malignant pleural mesothelioma (MPM) via activity on critical survival pathways and known synergies with antifolates and platinum chemotherapy. We conducted a dose-escalation study to identify the maximum tolerated dose (MTD) of ganetespib in patients with chemotherapy-naïve MPM.

Patients and Methods:

MESO-02 (ClinicalTrials.gov: NCT01590160) was a nonrandomized, multicenter, phase Ib trial of 3-weekly ganetespib (100 mg/m2, 150 mg/m2, 200 mg/m2; days 1 and 15) with pemetrexed (500 mg/m2; day 1) and cisplatin (75 mg/m2; day 1) or carboplatin (area under concentration–time curve 5; day 1) in patients with MPM. Dose escalation was performed using the 3 + 3 design (cisplatin) and accelerated titration design (carboplatin). Secondary endpoints included best response, progression-free survival (PFS), and pharmacogenomic analyses.

Results:

Of 27 patients enrolled (cisplatin, n = 16; carboplatin, n = 11), 3 experienced dose-limiting toxicities: grade 3 nausea (cisplatin, n = 1; carboplatin, n = 1) and grade 2 infusion-related reaction (carboplatin, n = 1). Ganetespib's MTD was 200 mg/m2. Partial response was observed in 14 of 27 patients (52%; 61% in 23 response-evaluable patients) and 13 of 21 (62%) with epithelioid histology. At the MTD, 10 of 18 patients (56%) had partial response, 15 of 18 (83%) had disease control, and median PFS was 6.3 months (95% CI, 5.0–10.0). One responder exhibited disease control beyond 50 months. Global loss of heterozygosity was associated with shorter time to progression (HR 1.12; 95% CI, 1.02–1.24; P = 0.018).

Conclusions:

Ganetespib can be combined safely with pemetrexed and platinum chemotherapy to treat patients with MPM. This class of agent should be investigated in larger randomized studies.
Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel
Authors: Faramand Rawan , Jain Michael , Staedtke Verena , Kotani Hiroshi , Bai Renyuan , Reid Kayla , Lee Sae Bom , Spitler Kristen , Wang Xuefeng , Cao Biwei , Pinilla Javier , Lazaryan Aleksander , Khimani Farhad , Shah Bijal , Chavez Julio C. , Nishihori Taiga , Mishra Asmita , Mullinax John , Gonzalez Ricardo , Hussaini Mohammad , Dam Marian , Brandjes Brigett D. , Bachmeier Christina A. , Anasetti Claudio , Locke Frederick L. , Davila Marco L.
Published: July 2020

Purpose:

One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel).

Experimental Design:

Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression.

Results:

We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity.

Conclusions:

These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.
Antiproliferative Effects of Monoclonal Antibodies against (Pro)Renin Receptor in Pancreatic Ductal Adenocarcinoma
Authors: Rahman Asadur , Matsuyama Makoto , Ebihara Akio , Shibayama Yuki , Hasan Arif Ul , Nakagami Hironori , Suzuki Fumiaki , Sun Jiao , Kobayashi Tomoe , Hayashi Hiroki , Nakano Daisuke , Kobara Hideki , Masaki Tsutomu , Nishiyama Akira
Published: July 2020

We previously reported that silencing of the PRR gene, which encodes the (pro)renin receptor [(P)RR], significantly reduced Wnt/β-catenin–dependent development of pancreatic ductal adenocarcinoma (PDAC). Here, we examined the effects of a panel of blocking mAbs directed against the (P)RR extracellular domain on proliferation of the human PDAC cell lines PK-1 and PANC-1 in vitro and in vivo. We observed that four rat anti-(P)RR mAbs induced accumulation of cells in the G0–G1-phase of the cell cycle and significantly reduced proliferation in vitro concomitant with an attenuation of Wnt/β-catenin signaling. Systemic administration of the anti-(P)RR mAbs to nude mice bearing subcutaneous PK-1 xenografts significantly decreased tumor expression of active β-catenin and the proliferation marker Ki-67, and reduced tumor growth. In contrast, treatment with the handle region peptide of (pro)renin did not inhibit tumor growth in vitro or in vivo, indicating that the effects of the anti-(P)RR mAbs were independent of the renin–angiotensin system. These data indicate that mAbs against human (P)RR can suppress PDAC cell proliferation by hindering activation of the Wnt/β-catenin signaling pathway. Thus, mAb-mediated (P)RR blockade could be an attractive therapeutic strategy for PDAC.
ARX788, a Site-specific Anti-HER2 Antibody–Drug Conjugate, Demonstrates Potent and Selective Activity in HER2-low and T-DM1–resistant Breast and Gastric Cancers
Authors: Skidmore Lillian , Sakamuri Sukumar , Knudsen Nick A. , Hewet Amha Gebre , Milutinovic Snezana , Barkho Wisam , Biroc Sandra Lyn , Kirtley Jessica , Marsden Robin , Storey Kristine , Lopez Ianina , Yu Wayne , Fang Shiao-Yan , Yao Sulan , Gu Yi , Tian Feng
Published: July 2020

First-generation antibody–drug conjugates (ADC) are heterogeneous mixtures that have shown clinical benefit, but generally exhibited safety issues and a narrow therapeutic window due, in part, to off-target toxicity caused by ADC instability. ARX788 is a next-generation, site-specific anti-HER2 ADC that utilizes a unique nonnatural amino acid–enabled conjugation technology and a noncleavable Amberstatin (AS269) drug-linker to generate a homogeneous ADC with a drug-to-antibody ratio of 1.9. ARX788 exhibits high serum stability in mice and a relatively long ADC half-life of 12.5 days. When compared in vitro against T-DM1 across a panel of cancer cell lines, ARX788 showed superior activity in the lower HER2-expressing cell lines and no activity in normal cardiomyocyte cells. Similarly, ARX788 significantly inhibited tumor growth, and generally outperformed T-DM1 in HER2-high and HER2-low expression xenograft models. Breast and gastric cancer patient-derived xenograft studies confirmed strong antitumor activity of ARX788 in HER2-positive and HER2-low expression tumors, as well as in a T-DM1-resistant model. The encouraging preclinical data support the further development of ARX788 for treatment of patients with HER2-positive breast and gastric cancer, including those who have developed T-DM1 resistance, and patients with HER2-low expression tumors who are currently ineligible to receive HER2-targeted therapy.
Primary Care Provider Beliefs and Recommendations About Colorectal Cancer Screening in Four Healthcare Systems
Authors: Ghai Nirupa R. , Jensen Christopher D. , Merchant Sophie A. , Schottinger Joanne E. , Lee Jeffrey K. , Chubak Jessica , Kamineni Aruna , Halm Ethan A. , Skinner Celette Sugg , Haas Jennifer S. , Green Beverly B. , Cannizzaro Nancy T. , Schneider Jennifer L. , Corley Douglas A.
Published: July 2020

Primary care provider's (PCP) perceptions of colorectal cancer screening test effectiveness and their recommendations for testing intervals influence patient screening uptake. Few large studies have examined providers’ perceptions and recommendations, including their alignment with evidence suggesting comparable test effectiveness and guideline recommendations for screening frequency. Providers (n = 1,281) within four healthcare systems completed a survey in 2017–2018 regarding their perceptions of test effectiveness and recommended intervals for colonoscopy and fecal immunochemical testing (FIT) for patients ages 40–49, 50–74, and ≥75 years. For patients 50–74 (screening eligible), 82.9% of providers rated colonoscopy as very effective versus 59.6% for FIT, and 26.3% rated colonoscopy as more effective than FIT. Also, for this age group, 77.9% recommended colonoscopy every 10 years and 92.4% recommended FIT annually. For patients ages 40–49 and ≥75, more than one-third of providers believed the tests were somewhat or very effective, although >80% did not routinely recommend screening by either test for these age groups. Provider screening test interval recommendations generally aligned with colorectal cancer guidelines; however, 25% of providers believed colonoscopy was more effective than FIT for mortality reduction, which differs from some modeling studies that suggest comparable effectiveness. The latter finding may have implications for health systems where FIT is the dominant screening strategy. Only one-third of providers reported believing these screening tests were effective in younger and older patients (i.e., <50 and ≥75 years). Evidence addressing these beliefs may be relevant if cancer screening recommendations are modified to include older and/or younger patients.
Cancer Research: The Lessons to Learn from COVID-19
Authors: Bailey Chris , Black James R.M. , Swanton Charles
Published: July 2020

The COVID-19 pandemic has caused widespread disruption of cancer clinical trials due to the restrictions on nonessential services and the reallocation of resources, and at the same time the urgent global effort toward discovering therapies that treat or prevent COVID-19 infection has led to shortening of traditional regulatory timelines. This experience should stimulate similar urgency in the way future cancer research is conducted.
Cognitive, Emotional, and Social Influences on Voice Production Elicited by Three Different Stroop Tasks
Authors: van Mersbergen Miriam , Payne Alexis E.
Published: July 2020

Introduction: The effects of emotion and cognition have been of interest to voice clinicians and research given the known correlations between psychological states and voice disorders. However, most voice research techniques investigate one psychological state at a time and do not necessarily consider other psychological states or the combination of two or more states occurring simultaneously. The purpose of this study is to employ three Stroop tasks, all known to elicit different psychological states, during a voice study to determine whether separate psychological states have a variable effect on vocalizations. Methods: Fifteen female participants were instructed to view a word on a computer screen and say the name of the color of the font of that word. Words were part of a Color Stroop, Emotional Stroop, or Taboo Stroop paradigm and designed to elicit cognitive, emotional, or the combination of cognitive/emotional interference. Behavioral measures of response time and acoustic measures of frequency, intensity, and noise ratio were extracted from each stimulus. Results: Participants had significantly greater response times for all experimental conditions compared to baseline. Additionally, intensity range was significantly less, and average fundamental frequency and cepstral peak prominence were significantly greater than baseline. However, there was no distinct pattern of response for any condition. Discussion/Conclusion: Although there are definite changes in vocalizations when participants were engaged in higher cognitive or emotional processing, no acoustic signatures for these separate conditions exist. These findings suggest that more specific acoustic measures or additional measures such as physiological or self-report may be necessary to parse out the differential effect on the voice in these three conditions.
Paraneoplastic Thromboembolism and Thrombophilia: Significance in Visceral Medicine
Authors: Pfrepper Christian
Published: July 2020

Background: Venous (VTE) and arterial thromboembolism (ATE) are frequent complications of cancer. Risk assessment models (RAM) for stratification of the thrombotic risk in patients with gastrointestinal (GI) cancer have several limitations. Summary: While pancreatic and stomach cancer are considered very high risk in all RAM, the risk of colorectal cancer differs between RAM, and esophageal cancer and cholangiocarcinoma were underrepresented or not included in any RAM. In addition, up to 49% of patients with pancreatic cancer develop splanchnic vein thrombosis (SVT). Prophylaxis with low-molecular-weight heparins (LMWH) in ambulatory cancer patients is associated with a positive risk-benefit ratio only in high-risk patients and LMWH have been the standard of care for the treatment of cancer-associated VTE and SVT over the last years. Direct oral anticoagulants (DOAC) have been shown to be equally effective compared to LMWH, but bleedings from the GI tract are more frequent. Therefore, recent guidelines suggest the use of DOAC for VTE treatment and for prophylaxis in ambulatory patients at high risk for VTE, but patients at high risk for bleeding, especially with active luminal cancer, should receive LMWH. Key Messages: This review discusses RAM and the current options for prophylaxis and treatment of cancer-associated ATE, VTE, and SVT focusing on GI cancers.
An experimental study on performace of starch extracted from wheat flour as filtration control agent in drilling fluid
Authors: Iqbal Raheel , Pirzada Fawad , Zubair Muhammad , Mehmood Ameer
Published: July 2020

The phenomenon of lost of mud filtrate into a porous permeable formation due to high hydrostatic pressure compared to the formation pressure is known as fluid loss. This cause some major problems in well during drilling as poor cementing job, pipe stuck, and formation damage. Thus, to safe the well from such problems and in order to make safe and effective drilling an additive from wheat flour is extracted which is starch, and acting as a fluid loss control agent. The purpose of this research is to investigate the potential of utilizing this additive to form environmentally safe, non-toxic, high biodegradability and low-cost water-based drilling fluid samples with varying the amount of starch. Experimental results showed that Efficiency of starch obtained from wheat-flour is showing increment in rheological properties as compare to starch present in market by using same and varying quantity of both and observed that wheat-flour starch is more efficient as compare to starch in market. On the other hand, the efficiency of starch is good but it has been also improved by the extraction of starch from wheat-flour by the centrifugation process.
História e Historiografia das crises
Authors: Grespan Jorge Luís
Published: July 2020

Partindo da experiência contemporânea das crises econômicas e políticas determinadas por fatores percebidos como incontroláveis, este artigo retoma algumas das mais importantes perspectivas historiográficas do século XIX ao XXI sobre o fenômeno. São examinadas concepções de colapso e tempo cíclico, mas de um ponto de vista que, além do seu conteúdo específico, busca estabelecer como cada concepção apreende a modalidade de sua ocorrência, ou seja, se as fases de um ciclo ou a derrocada de um sistema social resultam de condições casuais ou necessárias.
Discriminação Racial e Cidadania no Brasil do século XIX (1829-1833)
Authors: Pandolfi Fernanda Cláudia
Published: July 2020

O artigo analisa a questão da discriminação racial, abordando o tema no contexto da divulgação e implementação dos direitos constitucionais, no período de 1829 a 1833. Investiga-se, em especial, de que forma o direito de cidadania contribuiu para o surgimento da discriminação racial como agenda pública e ensejou novas maneiras de fazer política. Usaram-se como fontes jornais que adotavam enfoques políticos e raciais, os quais foram tomados não somente como fornecedores de informações, mas também como agentes, por sua capacidade de influir nos acontecimentos. Concomitantemente, foram aplicados à análise insights provenientes de estudos da área de direito e história que enfatizam a importância de mudanças da ordem jurídica para a compreensão da história política. Concluiu-se, principalmente, que a extensão do direito de cidadania aos homens livres de cor contribuiu para ampliar a influência política desse grupo, em um contexto de crescente partidarização da política.