bluuebunny/crossref_metadata_2025 huggingface dataset:
Flow modelling to quantify structural control on CO
2
migration and containment, CCS South West Hub, Australia
Authors: Langhi Laurent , Strand Julian , Ricard Ludovic
Published: February 2021

In order to reduce uncertainties around CO
2
containment for the South West Hub CCS site (Western Australia), conceptual fault hydrodynamic models were defined and numerical simulations were carried out. These simulations model worst-case scenarios with a plume reaching a main compartment-bounding fault near the proposed injection depth and at the faulted interface between the primary and secondary containment interval.

The conceptual models incorporate host-rock and fault properties accounting for fault-zone lithology, cementation and cataclastic processes but with no account made for geomechanical processes as the risk of reactivation is perceived as low. Flow simulations were performed to assess cross-fault and upfault migration in the case of plume–faults interaction.

Results near the injection depth suggest that the main faults are likely to experience a significant reduction in transmissivity and impede CO
2
flow. This could promote the migration of CO
2
vertically or along the stratigraphic dip.

Results near the interface between the primary and secondary containment intervals show that none of the main faults would critically control CO
2
flow nor would they act as primary leakage pathways. CO
2
flow is predicted to be primarily controlled by the sedimentological morphology. The presence of baffles in the secondary containment interval is expected to be associated with local CO
2
accumulations; additional permeability impacts introduced by faults are minor.

Thematic collection:
This article is part of the Geoscience for CO
2
storage collection available at:
https://www.lyellcollection.org/cc/geoscience-for-co2-storage
Using Word Embeddings to Deter Intellectual Property Theft through Automated Generation of Fake Documents
Authors: Abdibayev Almas , Chen Dongkai , Chen Haipeng , Poluru Deepti , Subrahmanian V. S.
Published: February 2021

Theft of intellectual property is a growing problem—one that is exacerbated by the fact that a successful compromise of an enterprise might only become known months after the hack. A recent solution called FORGE addresses this problem by automatically generating
N
“fake” versions of any real document so that the attacker has to determine which of the
N
+ 1 documents that they have exfiltrated from a compromised network is real. In this article, we remove two major drawbacks in FORGE: (i) FORGE requires ontologies in order to generate fake documents—however, in the real world, ontologies, especially good ontologies, are infrequently available. The WE-FORGE system proposed in this article completely eliminates the need for ontologies by using distance metrics on word embeddings instead. (ii) FORGE generates fake documents by first identifying “target” concepts in the original document and then substituting “replacement” concepts for them. However, we will show that this can lead to sub-optimal results (e.g., as target concepts are selected
without
knowing the availability and/or quality of the replacement concepts, they can sometimes lead to poor results). Our WE-FORGE system addresses this problem in two possible ways by performing a joint optimization to select concepts and replacements simultaneously. We conduct a human study involving both computer science and chemistry documents and show that WE-FORGE successfully deceives adversaries.
Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma
Authors: Rodriguez-Rodriguez Noe , Gogoi Mayuri , McKenzie Andrew N.J.
Published: February 2021

Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then distributing cytokine cues to elicit type 2 immune effector functions and potentiate CD4+ T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery.
Electrochemical Sulfenylation of 4-Hydroxycoumarins with Aryl Thiols Catalyzed by Potassium Iodide
Authors: Jin Jiali , Zhao Lingmin , Zhang Chao , Liu Xin , Yin Wenxu , Shen Zhenlu , Li Meichao
Published: February 2021

A KI-catalyzed indirect electrochemical oxidative method for the synthesis of sulfenylated 4-hydroxycoumarins via cross-coupling of 4-hydroxycoumarins and aryl thiols at a low potential has been reported. The electrocatalytic activity of KI for sulfenylation of 4-hydroxycoumarin was investigated by cyclic voltammetry. In situ FTIR data reflected the structural change of functional groups during the reaction process. The mechanism of electrochemical sulfenylation involved the generation of intermediate 1,2-bis(4-chlorophenyl)disulfane has been revealed by control experiments. Various sulfenylated 4-hydroxycoumarins were obtained under the optimum reaction conditions in moderate to excellent yields with good functional group tolerance.
Enhancing Proton Conductivity and Durability of Crosslinked PBI-Based High-Temperature PEM: Effectively Doping a Novel Cerium Triphosphonic-isocyanurate
Authors: Guo Hui , Li Zhongfang , Sun Peng , Pei Hongchang , Zhang Lei , Cui Weihui , Yin Xiaoyan , Hui Hongsen
Published: February 2021

Acid doping is an effective way to enhance the proton conduction of high temperature polybenzimidazole (PBI) based proton exchange membranes (HTPEMs). To overcome the problem of acid leaching from the membranes, a cerium triphosphonic-isocyanurate (Ce-TOPT) proton conductor was synthesized and doped into a crosslinked PBI backbone (c-mPBI). The TOPT organic compound contains three –PO3H2 groups, which can be complexed with high valent metal ions (Ce4+/3+, Zr4+, Fe3+) to ensure its water-insolubility. Ce-TOPT(1:2) exhibited high ion exchange capacity (IEC, up to 2.2 meq. g−1) and good thermal stability. The organic-inorganic Ce-TOPT shown a high doping level in c-mPBI/CeTOPT membranes and consequently high proton conductivity of the membranes at high temperature and low relative humidity (RH). At 180 °C, the conductivity of c-mPBI/CeTOPT(50) could reach 0.125, 0.0885 and 0.0363 S cm−1 at 100% RH, 50% RH and anhydrous conditions, respectively. After water-washing for 48 h, the proton conductivity loss of c-mPBI/CeTOPT(50) was 4.6%. The good mechanical properties, proton conductivity, durability and membrane selectivity indicate that the crosslinked PBI-based membrane doped with Ce-TOPT is a potential candidate as HTPEMs.
Determinants of cerebral blood flow velocity change during squat-stand maneuvers
Authors: Panerai Ronney B. , Batterham Angus , Robinson Thompson G. , Haunton Victoria J.
Published: February 2021

The large changes in mean arterial blood pressure (MABP) and cerebral blood flow velocity (CBFV) induced by squat-stand maneuvers (SSM) make this approach particularly suited for studying dynamic cerebral autoregulation (CA). However, the role of other systemic determinants of CBFV has not been described and could provide alternative physiological interpretations of SSM results. In 32 healthy subjects (16 female), continuous recordings of MABP (Finometer), bilateral CBFV (transcranial Doppler, MCA), end-tidal CO2 (EtCO2; capnography), and heart rate (HR; electrocardiogram) were performed for 5 min standing at rest, and during 15 SSM at the frequency of 0.05 Hz. A time-domain, multivariate dynamic model estimated the CBFV variance explained by different inputs, corresponding to significant contributions from MABP ( P < 0.00001), EtCO2 ( P < 0.0001), and HR ( P = 0.041). The autoregulation index (ARI; range 0–9) was estimated from the CBFV response to a step change in MABP. At rest, ARI values (typically 5.7) were independent of the number of model inputs, but during SSM, ARI was reduced compared with baseline ( P < 0.0001), and the three input model yielded lower values for the right and left MCA (3.4 ± 1.2, 3.1 ± 1.3) when compared with the single-input MABP–CBFV model (4.1 ± 1.1, 3.9 ± 1.0; P < 0.0001). The high coherence of the MABP–CBFV transfer function at 0.05 Hz (typically 0.98) was considerably reduced (around 0.71–0.73; P < 0.0001) when the contribution of CBFV covariates was taken into account. Not taking into consideration other determinants of CBFV, in addition to MABP, could be misleading and introduce biases in physiological and clinical studies.
Optimal Reactive Power Generation for Radial Distribution Systems Using a Highly Effective Proposed Algorithm
Authors: Kien Le Chi , Nguyen Thuan Thanh , Dinh Bach Hoang , Nguyen Thang Trung
Published: February 2021

In this paper, a proposed modified stochastic fractal search algorithm (MSFS) is applied to find the most appropriate site and size of capacitor banks for distribution systems with 33, 69, and 85 buses. Two single‐objective functions are considered to be reduction of power loss and reduction of total cost of energy loss and capacitor investment while satisfying limit of capacitors, limit of conductor, and power balance of the systems. MSFS was developed by performing three new mechanisms including new diffusion mechanism and two new update mechanisms on the conventional stochastic fractal search algorithm (SFS). As a result, MSFS can reduce 0.002%, 0.003%, and 0.18% of the total power loss from SFS for the three study systems. As compared to other methods, MSFS can reduce power loss from 0.07% to 3.98% for the first system, from 3.7% to 7.3% for the second system, and from 0.92% to 6.98% for the third system. For the reduction of total cost, the improvement level of the proposed method over SFS and two other methods is more significant. It is 0.03%, 1.22%, and 5.76% for the second system and 2.31%, 0.87%, and 3.77% for the third system. It is emphasized that the proposed method can find the global optimal solutions for all study cases while SFS was still implementing search process nearby or far away from the solutions. Furthermore, MSFS can converge to the best solutions much faster than these compared methods. Consequently, it can be concluded that the proposed method is very effective for finding the best location and size of added capacitors in distribution power systems.
A Network Pharmacology Approach to Explore the Mechanisms of Artemisiae scopariae Herba for the Treatment of Chronic Hepatitis B
Authors: He Asi , Wang Wei , Xia Yang , Niu Xiaoping
Published: February 2021

Background. As a traditional Chinese medicine, Artemisiae scopariae Herba (ASH) is used to treat various liver diseases. The purpose of this study was to explore the mechanisms of ASH for treating chronic hepatitis B (CHB) using a network pharmacological method. Methods. Bioactive ingredients and related targets of ASH were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Gene names of targets were extracted from UniProt database. Differentially expressed genes (DEGs) of CHB were obtained from microarray dataset GSE83148. The intersect genes between DEGs and target genes were annotated using clusterProfiler package. The STRING database was used to obtain a network of protein-protein interactions. Cytoscape 3.7.2 was used to construct the “ingredient-gene-pathway” (IGP) network. Molecular docking studies were performed using Autodock vina. Results. A total of 13 active components were extracted from TCMSP database. Fifteen intersect genes were obtained between 183 target genes and 403 DEGs of GSE83148. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that ASH against CHB mainly involved in toll-like receptor signaling pathway, cellular senescence, hepatitis B, and chemokine signaling pathway. We screened one hub compound, five core targets, and four key pathways from constructed networks. The docking results indicated the strong binding activity between quercetin and AKT1. Conclusions. This study provides potential molecular mechanisms of ASH against CHB based on exploration of network pharmacology.
Asymptomatic Ileal Neuroendocrine “Carcinoid” Tumor Incidentally Diagnosed on Colorectal Cancer Screening Colonoscopy: Does Routine TI Intubation Matter?
Authors: Zakaria Ali , Alnimer Lynna , Byrd Gregory , Piper Marc , Raphael Michael , Warren Bradley , Piper Michael
Published: February 2021

Gastrointestinal neuroendocrine tumors (GINETs) (also known as “carcinoids”) are rare tumors with reported incidence of up to 6.98 per 100,000 which has increased significantly due to the increased detection on imaging and endoscopy. They are most commonly located in the small bowel, particularly the terminal ileum. Patients with small bowel NETs may present with abdominal pain, diarrhea, or carcinoid syndrome. However, the disease is mostly asymptomatic, and patients are usually diagnosed incidentally during routine colonoscopy. Although the ileum is the most common site for GINETs, terminal ileal (TI) intubation is not always completed during routine colonoscopy. With terminal ileum intubation being successful in at least 70% of colonoscopies and the rate of neuroendocrine tumor detection 0.1–1% of those intubations, one critical question remains unanswered: should terminal ileal intubation be considered a part of the definition of a complete colonoscopy? Herein, we present nine cases of NETs found incidentally on routine colon cancer screening colonoscopy in asymptomatic patients. This case series adds to the sparse literature and highlights the importance of TI intubation technique in early detection of small bowel NETs which could potentially affect the outcome.
An ECG Signal Classification Method Based on Dilated Causal Convolution
Authors: Ma Hao , Chen Chao , Zhu Qing , Yuan Haitao , Chen Liming , Shu Minglei
Published: February 2021

The incidence of cardiovascular disease is increasing year by year and is showing a younger trend. At the same time, existing medical resources are tight. The automatic detection of ECG signals becomes increasingly necessary. This paper proposes an automatic classification of ECG signals based on a dilated causal convolutional neural network. To solve the problem that the recurrent neural network framework network cannot be accelerated by hardware equipment, the dilated causal convolutional neural network is adopted. Given the features of the same input and output time steps of the recurrent neural network and the nondisclosure of future information, the network is constructed with fully convolutional networks and causal convolution. To reduce the network depth and prevent gradient explosion or gradient disappearance, the dilated factor is introduced into the model, and the residual blocks are introduced into the model according to the shortcut connection idea. The effectiveness of the algorithm is verified in the MIT-BIH Atrial Fibrillation Database (MIT-BIH AFDB). In the experiment of the MIT-BIH AFDB database, the classification accuracy rate is 98.65%.
Experimental Investigation on Frost Heaving Force (FHF) Evolution in Preflawed Rocks Exposed to Cyclic Freeze-Thaw Conditions
Authors: Wang Yu , Sun Tao , Yang Haonan , Lin Jinfeng , Liu Hao
Published: February 2021

This work is aimed at investigating the structural deterioration and the frost heaving force evolution characteristics of flawed rocks using a self-developed frost heaving force (FHF) measurement system. Three kinds of preflawed rocks with different flaw geometry parameters were used to conduct the FHF measurement tests. The testing results reveal five distinguished stages from the frost heaving force evolution curve; they are the inoculation stage, explosive stage, decline to steady stage, recovery stage, and sudden drop stage. In addition, a secondary frost heaving phenomenon is found, and the secondary peak value is lower than the initial peak value. Moreover, the FHF decreases with increasing the F-T cycle number, and its decreasing rate becomes faster at a high F-T cycle. The frost heaving force is affected not only by flaw geometry but also by the lithology. For low-pore hard rock, damage propagates quickly after the occurrence of freeze-thaw damage. It is suggested that the mesoscopic structure of rock affects the water migration and water-ice phase transformation, and rock can be fractured by FHF in the preexisting flaws.
The Prevalence of Clinical Features in Patients with Aarskog–Scott Syndrome and Assessment of Genotype-Phenotype Correlation: A Systematic Review
Authors: Zanetti Drumond Victor , Sousa Salgado Lucas , Sousa Salgado Camila , Oliveira Vitor Augusto de Lima , de Assis Eliene Magda , Campos Ribeiro Michel , Furtado Valadão Analina , Orrico Alfredo
Published: February 2021

Aarskog–Scott syndrome is a genetically and clinically heterogeneous rare condition caused by a pathogenic variant in the FGD1 gene. A systematic review was carried out to analyse the prevalence of clinical manifestations found in patients, as well as to evaluate the genotype-phenotype correlation. The results obtained show that clinical findings of the craniofacial, orthopaedic, and genitourinary tract correspond to the highest scores of prevalence. The authors reclassified the primary, secondary, and additional criteria based on their prevalence. Furthermore, it was possible to observe, in accordance with previous reports, that the reported phenotypes do not present a direct relation to the underlying genotypes.
Periodontal Treatment Improves Serum Levels of Leptin, Adiponectin, and C-Reactive Protein in Thai Patients with Overweight or Obesity
Authors: Wanichkittikul Notkamon , Laohapand Penpan , Mansa-nguan Chayasin , Thanakun Supanee
Published: February 2021

Periodontitis and overweight or obesity independently change serum levels of leptin, adiponectin, and C-reactive protein (CRP). The aim of this study is to investigate the alterations of serum levels of leptin, adiponectin, and CRP after nonsurgical periodontal treatment (NSPT) in Thai patients with overweight or obesity (Owt/Ob) who did or did not exhibit severe periodontitis (SP) and normal weight (Nwt) patients with or without SP. Two hundred sixty patients were screened; 29 patients were included in this study. The study participants comprised 6 patients with Owt/Ob who exhibited SP, 11 patients with Owt/Ob who did not exhibit SP, 5 Nwt patients with SP, and 7 Nwt patients without SP. Periodontal disease status was evaluated; serum levels of leptin, adiponectin, and CRP were determined by enzyme-linked immunosorbent assay at baseline, as well as at 3 and 6 months after NSPT. At 3 months after NSPT, periodontal status was improved in all groups (

p

 < 0.05), except Nwt patients without SP. Serum levels of leptin and CRP were significantly reduced, while serum levels of adiponectin were elevated after NSPT, regardless of bodyweight or waist circumference (

p

 < 0.05). Improvement in serum levels of leptin after NSPT was also observed in the Nwt with SP group (

p

 = 0.015); these levels did not significantly differ in Nwt patients without SP. NSPT reduces serum levels of leptin and CRP and enhances serum levels of adiponectin in Thai patients with Owt/Ob, irrespective of periodontitis severity. These results suggest a role for periodontal treatment in the systemic inflammatory response of Thai people with Owt/Ob.
Mathematical Modelling of Glucose-Insulin System and Test of Abnormalities of Type 2 Diabetic Patients
Authors: Banzi Wellars , Kambutse Immaculate , Dusabejambo Vincent , Rutaganda Eric , Minani Froduald , Niyobuhungiro Japhet , Mpinganzima Lydie , Ntaganda Jean Marie
Published: February 2021

This paper presents a mathematical model of glucose-insulin dynamics which is specific for type 2 diabetic patients. The general modelling is obtained by simplification of a global compartmental model by John Thomas Sorensen. The model parameters are estimated using nonlinear optimization and data collected in Rwanda for type 2 diabetic patients. In order to identify and evaluate possible abnormalities of type 2 diabetic patients, the Sampling Importance Resampling (SIR) particle filtering algorithm is used and implemented through discretization of the developed mathematical model. This process is done by clamping insulin and glucose concentrations at around clinical trial values as proposed by Defronzo. Furthermore, for detecting potential abnormalities in type 2 diabetic patients, we compare our results with results obtained from a simulation of the mathematical model for healthy subjects. The proposed mathematical model allows further investigation of the dynamic behavior of glucose, insulin, glucagon, stored insulin, and labile insulin in different organs for type 2 diabetic patients.
The Optimized Multivariate Grey Prediction Model Based on Dynamic Background Value and Its Application
Authors: Lao Tongfei , Chen Xiaoting , Zhu Jianian
Published: February 2021

As a tool for analyzing time series, grey prediction models have been widely used in various fields of society due to their higher prediction accuracy and the advantages of small sample modeling. The basic GM (1, N) model is the most popular and important grey model, in which the first “1” stands for the “first order” and the second “N” represents the “multivariate.” The construction of the background values is not only an important step in grey modeling but also the key factor that affects the prediction accuracy of the grey prediction models. In order to further improve the prediction accuracy of the multivariate grey prediction models, this paper establishes a novel multivariate grey prediction model based on dynamic background values (abbreviated as DBGM (1, N) model) and uses the whale optimization algorithm to solve the optimal parameters of the model. The DBGM (1, N) model can adapt to different time series by changing parameters to achieve the purpose of improving prediction accuracy. It is a grey prediction model with extremely strong adaptability. Finally, four cases are used to verify the feasibility and effectiveness of the model. The results show that the proposed model significantly outperforms the other 2 multivariate grey prediction models.
Design of Real-Time Control Based on DP and ECMS for PHEVs
Authors: Wang Wei , Cai Zhenjiang , Liu Shaofei
Published: February 2021

A real-time control is proposed for plug-in-hybrid electric vehicles (PHEVs) based on dynamic programming (DP) and equivalent fuel consumption minimization strategy (ECMS) in this study. Firstly, the resulting controls of mode selection and series mode are stored in tables through offline simulation of DP, and the parallel HEV mode uses ECMS-based real-time algorithm to reduce the application of maps and avoid manual adjustment of parameters. Secondly, the feedback energy management system (FMES) is built based on feedback from SoC, which takes into account the charge and discharge reaction (CDR) of the battery, and in order to make full use of the energy stored in the battery, the reference SoC is introduced. Finally, a comparative simulation on the proposed real-time controller is conducted against DP, the results show that the controller has a good performance, and the fuel consumption value of the real-time controller is close to the value using DP. The engine operating conditions are concentrated in the low fuel consumption area of the engine, and when the driving distance is known, the SoC can follow the reference SoC well to make full use of the energy stored in the battery.
Intertillage during Natural Farming Rice Paddy Production Negatively Impacted the Microbial Abundances in Soils but Not Diversities
Authors: Lin Jin-Feng , Minarsch Eva-Maria , Ishiguro Munehide , Uchida Yoshitaka
Published: February 2021

In natural farming rice paddies, intertillage (tillage between rows, during rice growth period) is often performed mainly to remove weeds without the use of chemicals. Also, the intertillage disturbs soil surfaces, potentially impacting the characteristics of soil microbial communities, such as their diversity and abundance. Natural farming systems aim to maintain biodiversity, but it remains unclear whether the intertillage impacts soil microbes in rice paddies. Thus, this study aimed to understand to what extent “five times intertillage” treatment (5T) influences soil bacterial abundance and community structures compared with no tillage (NT), under a natural farming rice paddy system. Soils were sampled at rice proximity, soil surface, and 10 cm depth in a natural farming rice paddy, during the early to late vegetative phase (June to July), in Hokkaido, Japan. The 16S rRNA community structures and abundance were analyzed by next generation sequencing (NGS) and quantitative PCR, respectively. We observed that NT had significantly higher bacterial abundances at the soil surface than 5T. However, there were no clear differences between 5T and NT, regarding the bacterial community structures, including their diversity indices. Instead, the sampling timings markedly impacted the bacterial community structures for the rice proximity and soil surface, showing increasing diversity indices at the late vegetative stage, compared to the early vegetative stage, suggesting the interaction between the crop growth and bacterial communities. In this study, we did not observe the significant difference between the rice yield from NT (2.3 ± 0.7 t·ha−1) and 5T plots (2.7 ± 0.9 t·ha−1); however, the 5T might have negatively impacted soil bacterial abundances but not the community structure of the bacteria.
Simultaneous Determination of Methamphetamine and Its Isomer N-Isopropylbenzylamine in Forensic Samples by Using a Modified LC-ESI-MS/MS Method
Authors: Luo Yangxu , Du Juan , Xiao Huadi , Zheng Ling , Chen Xuncai , Ma Ande , Luo Qizhi
Published: February 2021

Accurate identification and quantification of methamphetamine (MA) and its related substances are essential for the investigation and fair trial of drug offenses. In this study, a modified LC-ESI-MS/MS method for the simultaneous determination of MA and its isomer N-isopropylbenzylamine (N-IBA) in forensic samples was developed and validated. Optimum chromatographic separation of the target analytes was achieved on an Agilent Poroshell 120 SB-C18 column (

4.6
×
100

 mm, 2.7 μm) at 40°C with isocratic elution at the flow rate of 0.40 mL/min. The mobile phase was acetonitrile and 20 mM ammonium acetate solution containing 0.1% formic acid (80 : 20,

v
/
v

). Positive ESI-MS/MS detection was performed in multiple reaction monitoring (MRM) mode to identify and quantify the target analytes. Method validation showed excellent linearity in the range of 0.51 ng/mL~51 ng/mL for MA and N-IBA. The low limit of detection (LLOD) and low limit of quantification (LLOQ) reached 0.1 ng/mL and 0.3 ng/mL for both analytes. The method showed a satisfactory accuracy with an inter- and intraday-relative error (RE) <20%, and a precision of inter- and intraday relative standard deviation (RSD) less than 15%. The validated method was successfully applied in real forensic samples and resulted in the detection of MA and N-IBA in 8 suspected samples in drug cases that only deemed MA positive using our previous routine screening procedure, which avoided the misidentification of N-IBA as MA.
Pain Treatment Evaluation in COVID-19 Patients with Hesitant Fuzzy Linguistic Multicriteria Decision-Making
Authors: Batur Sir G. Didem , Sir Ender
Published: February 2021

The coronavirus disease 2019 (COVID-19) has emerged as a worldwide pandemic since March 2020. Although most patients complain of moderate or severe pain, these symptoms are generally underestimated and appropriate treatment is not applied. This study aims to guide physicians in selecting and ranking various alternatives for the treatment of pain in COVID-19 patients. However, the choice of treatment for pain requires the consideration of many different conflicting criteria. Therefore, we have studied this problem as a multicriteria decision-making problem. Throughout the solution procedure, first, the criteria and subcriteria affecting the preferences are defined. Then, weight values are determined with respect to these criteria, as they have different degrees of importance for the problem. At this stage, hesitant fuzzy linguistic term sets (HFLTSs) are used, and thus, experts can convey their ideas more accurately. In this first phase of the study, an HFLTS integrated Analytic Hierarchy Process (AHP) method is utilized. Subsequently, possible treatment alternatives are evaluated by using the Vise Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method. According to the results obtained by considering expert evaluations, the most preferred treatment is the administration of paracetamol, followed by interventional treatments, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs), respectively. With this study, it is ensured that a more accurate method is followed by eliminating possible mistakes due to the subjective evaluations of experts in the process of determining pain treatment. This method can also be used in different patient and disease groups.
Overexpression of GSE1 Related to Trastuzumab Resistance in Gastric Cancer Cells
Authors: Wang Wenbin , Wang Shuanhu , Xu A. man , Yuan Xiao , Huang Liguo , Li Jun
Published: February 2021

Gastric cancer is one of the most prevalent human cancers with poor prognosis. Trastuzumab is a well‐used targeted drug for gastric cancer with HER2 amplification. Trastuzumab resistance restrains the clinical use of trastuzumab. In this study, we reported human Gse1 coiled‐coil protein (GSE1) promoted trastuzumab resistance in HER2‐positive gastric cancer cells. Acquired trastuzumab‐resistant gastric cancer cells overexpressed GSE1, and depletion of GSE1 decreased the trastuzumab resistance of trastuzumab‐resistant gastric cancer cells. BCL‐2 was a downstream gene positively regulated by GSE1 and also performed promoting the role of trastuzumab resistance in HER2‐positive gastric cancer cells. A high level of GSE1 was associated with a high risk of tumor lymph node metastasis and higher clinical stage in HER2‐positive gastric cancer patients. GSE1 was a potential target that could be used for HER2‐positive gastric cancer therapy.
Trends towards Effective Analysis of Fluorinated Compounds Using Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
Authors: Moirana Ruth Lorivi , Kivevele Thomas , Mkunda Josephine , Mtei Kelvin , Machunda Revocatus
Published: February 2021

Increased demand for monitoring and identification of novel and unknown fluorinated compounds (FCs) has demonstrated the need of sensitive fluorine-specific detectors for unknown FCs in both biological and environmental matrices. Inductively coupled plasma mass spectrometry (ICP-MS) is a promising technique for analysis of FCs and has been rated as the most powerful tool in analytical chemistry. However, direct determination of fluorine using this technique is challenged by high ionization potential of fluorine together with spectral and nonspectral interferences which affect the quality of results. To enhance the quality of results, several studies have reported modifications of a conventional ICP-MS analysis procedure on sample preparation, introduction, analysis, and instrument optimization. Therefore, the focus of this study is to discuss different ICP-MS optimizations and future trends towards the effective analysis of FCs using ICP-MS.
Geniposide, a Principal Component of Gardeniae Fructus, Protects Skin from Diesel Exhaust Particulate Matter-Induced Oxidative Damage
Authors: Nguyen Ly Thi Huong , Ahn Sang Hyun , Nguyen Uy Thai , Yang In Jun , Shin Heung Mook
Published: February 2021

Gardeniae Fructus (GF) is the fruit of Gardenia jasminoides Ellis and is traditionally prescribed to treat pyogenic infections and skin ulcers. This study investigated the protective effects of GF and the underlying mechanism responsible for these effects on diesel exhaust particulate matter- (DEP-) induced skin damage. The protective effects of an ethanolic extract of GF (GFE) and its constituents (geniposidic acid, gardenoside, geniposide, chlorogenic acid, and genipin) were examined by analyzing reactive oxygen species (ROS) production, apoptosis, and tight junction (TJ) protein expression in HaCaT cells. Treatment with GFE dose-dependently inhibited intracellular ROS production and apoptosis by regulating the protein expressions of Bax, Bcl-2, and cytochrome C in DEP-stimulated (100 μg/ml) HaCaT cells. Mechanistic studies revealed that the protective effects of GFE were related to its activation of Nrf2 and HO-1 signaling in HaCaT cells. Geniposide, a main constituent of GFE, enhanced the expression of occludin in DEP-stimulated HaCaT cells. Furthermore, topical application of geniposide reduced the expressions of 8-OHdG and Bax and increased the expression of occludin in the dorsal skin lesions of DEP-stimulated mice. Gardeniae Fructus and its main component geniposide are potential candidates for the repair of DEP-induced skin damage due to their antioxidant and antiapoptotic activities.
Risk Factors for Stillbirth among Pregnant Women Infected with Syphilis in the Zhejiang Province of China, 2010–2016
Authors: Duan Cui-Cui , Zhang Xiao-Hui , Li Shan-Shan , Wu Wei , Qiu Li-Qian , Xu Jian
Published: February 2021

Background. The World Health Organization estimated that about 1.36 million pregnant women suffered from syphilis in 2008, and nearly 66% of adverse effects occurred in those who were not tested or treated. Syphilis infection is one of the most common maternal factors associated with stillbirth. Objective. This study aimed to determine the risk factors for stillbirth among pregnant women infected with syphilis. Methods. In this retrospective study, data on stillbirth and gestational syphilis from 2010 to 2016 were extracted from the prevention of mother-to-child transmission (PMTCT) program database in the Zhejiang province. A total of 8,724 pregnant women infected with syphilis were included. Multiple logistic regression analysis was performed to determine the degree of association between gestational syphilis and stillbirth. Results. We found that the stillbirth percentage among pregnant women infected with syphilis was 1.7% (152/8,724). Compared with live births, stillbirth was significantly associated with lower maternal age, not being married, lower gravidity, the history of syphilis, nonlatent syphilis stage, higher maternal serum titer for syphilis, inadequate treatment for syphilis, and later first antenatal care visit. In multiple logistic analysis, nonlatent syphilis (adjusted odds ratio (AOR) = 2.03; 95% CI = 1.17, 3.53) and maternal titers over 1 : 4 (AOR = 1.78; 95% CI = 1.25, 2.53) were risk factors for stillbirth, and adequate treatment was the only protective factor for stillbirth (AOR = 0.16; 95% CI = 0.10, 0.25). Conclusions. Nonlatent syphilis and maternal titers over 1 : 4 were risk factors for stillbirth, and adequate treatment was the only protective factor for stillbirth.
Misfire Fault Diagnosis Method for Diesel Engine Based on MEMD and Dispersion Entropy
Authors: Gu Cheng , Qiao Xin-Yong , Li Huaying , Jin Ying
Published: February 2021

As a main source of power, diesel engines are widely used in large mechanical systems. Fire failure is a kind of common fault condition, which seriously affects the power and economy of the diesel engine. Previously, scholars mostly used single‐channel signal to diagnose the misfire fault of the diesel engine. However, the single‐channel signal has limitations in reflecting the information of fault. A novel fault diagnosis method based on MEMD and dispersion entropy is proposed in this paper. Firstly, the multichannel vibration signal of the diesel engine cylinder head is decomposed by multivariate empirical mode decomposition (MEMD), which obtains the IMF component groups with the same frequency in the same order. Then, the IMF component with a large correlation coefficient with the original signal in each group is selected to reconstruct new signal, and dispersion entropy (DE) of the reconstructed signal is calculated as a fault feature vector. Finally, the fault feature vector is input into the support vector machine (SVM) for misfire fault classification. Compared with the other three methods, the results show that the diagnosis method proposed in this paper can effectively extract the fault features and accurately identify the fault type, which is superior to the comparison method.
Suppression of RAD21 gene expression decreases cell growth and enhances cytotoxicity of etoposide and bleomycin in human breast cancer cells
Authors: Atienza Josephine M. , Roth Richard B. , Rosette Caridad , Smylie Kevin J. , Kammerer Stefan , Rehbock Joachim , Ekblom Jonas , Denissenko Mikhail F.
Published: February 2021

A genome-wide case-control association study done in our laboratory has identified a single nucleotide polymorphism located in RAD21 as being significantly associated with breast cancer susceptibility. RAD21 is believed to function in sister chromatid alignment as part of the cohesin complex and also in double-strand break (DSB) repair. Following our initial finding, expression studies revealed a 1.25- to 2.5-fold increased expression of this gene in several human breast cancer cell lines as compared with normal breast tissue. To determine whether suppression of RAD21 expression influences cellular proliferation, RNA interference technology was used in breast cancer cell lines MCF-7 and T-47D. Proliferation of cells treated with RAD21-specific small inhibitory RNA (siRNA) was significantly reduced as compared with mock-transfected cells and cells transfected with a control siRNA (Lamin A/C). This inhibition of proliferation correlated with a significant reduction in the expression of RAD21 mRNA and with an increased level of apoptosis. Moreover, MCF-7 cell sensitivity to two DNA-damaging chemotherapeutic agents, etoposide and bleomycin, was increased after inhibition of RAD21 expression with a dose reduction factor 50 (DRF50) of 1.42 and 3.71, respectively. At the highest concentrations of etoposide and bleomycin administered, cells transfected with a single siRNA duplex targeted against RAD21 showed 57% and 60% survival as compared with control cells, respectively. Based on these findings, we conclude that RAD21 is a novel target for developing cancer therapeutics that can potentially enhance the antitumor activity of chemotherapeutic agents acting via induction of DNA damage.
The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim
Authors: Nikrad Malti , Johnson Thomas , Puthalalath Hamsa , Coultas Leigh , Adams Jerry , Kraft Andrew S.
Published: February 2021

Previously, we showed that the proteasome inhibitor bortezomib/Velcade (formerly PS-341) synergizes with the protein tumor necrosis factor α–related apoptosis-inducing ligand (TRAIL), a ligand for certain death receptors, to induce apoptosis in cell lines derived from prostate and colon cancers. Because apoptosis is often triggered by BH3-only proteins of the Bcl-2 family, we have explored the hypothesis that bortezomib contributes to the apoptosis by up-regulating their levels. Indeed, bortezomib induced increases of Bik and/or Bim in multiple cell lines but not notably of two other BH3-only proteins (Puma and Bid) nor other family members (Bax, Bak, Bcl-2, and Bcl-xL). The increase in Bik levels seems to reflect inhibition by bortezomib of its proteasome-mediated degradation. Importantly, both Bik and Bim seem central to the proapoptotic function of bortezomib, because mouse embryo fibroblasts in which the genes for both Bik and Bim had been disrupted were refractory to its cytotoxic action. Similarly, the synergy between bortezomib and TRAIL in killing human prostate cancer cells was impaired in cells in which both Bik and Bim were down-regulated by RNA interference. Further evidence that bortezomib acts through the mitochondrial pathway regulated by the Bcl-2 family is that deficiency for APAF-1, which acts downstream of Bcl-2, also blocked its apoptotic effect. These results implicate BH3-only proteins, in particular both Bik and Bim, as important mediators of the antitumor action of bortezomib and establish their role in its enhancement of TRAIL-induced apoptosis.
Abstract IA08: What are some different ways to evaluate immunotherapy combinations?
Authors: Postow Michael
Published: February 2021

This talk will focus on new ways to consider clinical trials testing combinations of immunotherapy agents. Lessons learned from explorations of the combination of PD-1 + CTLA-4 blockade will be shared. Specifically, we will review data related to the concept of treatment free survival as well as highlight recent data using an adaptive/individualized approach to de-escalate combination immunotherapy in patients with advanced melanoma.

Citation Format: Michael Postow. What are some different ways to evaluate immunotherapy combinations? [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA08.
Abstract PO022: Somatic mutations in tumor infiltrating lymphocytes can affect the expression of immune system genes in the tumor microenvironment
Authors: Anandakrishnan Ramu , Varghese Robin T. , Kinney Nicholas A. , Garner Harold R.
Published: February 2021

Avoiding immune destruction is an emerging hallmark of cancer. It includes tumor cell mutations and epigenetic modifications that allow tumor cells to either evade detection by the immune system, or render the immune response ineffective. However, mutations in tumor infiltrating lymphocytes that inhibit immune response to tumor growth, have not been specifically identified as a hallmark of cancer. We have identified four distinct somatic mutations in tumor infiltrating lymphocytes that affect the expression of immune system genes in tumor samples, suggesting that these lymphocytic mutation may cause a deficient immune response, contributing to cancer progression. These rare mutations occurred frequently in specific cancer types. The T292Nfs*18 mutation in the FETUB gene, R216Gfs*20 in CCDC43, N377D in CLEC4M and V78Gfs*46 in RAB11FIP4 occurred in 13% of breast invasive carcinoma, 41% of colon adenocarcinoma, 12% of ovarian cystadenocarcinoma (OV) and 16% of OV samples respectively, compared to 0.002%, 0.003%, 0.014% and 0.001% in aggregated variant databases. These variants were found in 7-20% of DNA sequences in both tumor and matched normal blood samples, indicating that they originated in tumor infiltrating lymphocytes, rather than in the tumor cells. We argue that these mutations are unlikely to be passenger mutations since each of them occur in only 0-2% of normal tissue samples and in less than 2% of tumor samples from 24-32 of 32 cancer types other than the one noted above for each of the four mutations. The set of differentially expressed genes (FDR<0.05) in samples with each of the four variants, compared to samples without the variant, included 22-445 genes associated with the immune system pathway, suggesting a possible mechanism by which these mutations may affect tumor growth. Given the myriad of diverse mechanisms and genes implicated in cancer, it is not unexpected that mutations in tumor infiltrating lymphocytes could contribute to cancer progression. With further validation, genetic lesions in tumor infiltrating lymphocytes may represent a previously unstudied mechanism affecting tumor growth, and a new class of therapeutic targets. These mutations may also represent potential “somatic” risk markers that may present with age, supplementing traditional germline risk markers.

Citation Format: Ramu Anandakrishnan, Robin T. Varghese, Nicholas A. Kinney, Harold R. Garner. Somatic mutations in tumor infiltrating lymphocytes can affect the expression of immune system genes in the tumor microenvironment [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO022.
Abstract PO042: Oncostatin M receptor as a therapeutic target of radioimmune therapy in metastatic synovial sarcoma
Authors: Luelling Sarah , Kirkham Matthew , Barrott Jared
Published: February 2021

Synovial sarcoma is a soft tissue malignancy of the muscle that primarily affects adolescents. Due to it low incidence, little advancement has been made in the treatment of this cancer. With an overall survival rate of roughly 40%, the need for new treatments for synovial sarcoma is evident. Oncostatin M Receptor (OSMR) is a type I cytokine receptor and is overexpressed in metastatic synovial sarcoma. OSMR does not have high expression in normal tissues, making it an ideal target for cancer therapy. We hypothesize that by using an anti-OSMR monoclonal antibody conjugated to a radioactive Cu67 isotope, synovial sarcoma can be targeted at both primary and metastatic locations through systemic therapy. Copper67 is a beta radiation emitting isotope that is tissue damaging and able to induce cell death in cancer cells. By conjugating the chelating molecule p-SCN-Bn-NOTA to an anti-OSMR antibody, Cu67 was able to be captured to the antibody. Capture efficiency of Cu67 was measured after TLC separation and found to be 80% efficient. This data suggests that targeting OSMR through radioimmunotherapy (RIT) is a viable treatment and indicates further testing in animal models.

Citation Format: Sarah Luelling, Matthew Kirkham, Jared Barrott. Oncostatin M receptor as a therapeutic target of radioimmune therapy in metastatic synovial sarcoma [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO042.