bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectory Tracking Control of Intelligent Electric Vehicles Based on the Adaptive Spiral Sliding Mode
Authors: Nie Yanxin , Zhang Minglu , Zhang Xiaojun
Published: December 2021

Aiming at the multi-objective control problem of the tracking effect and vehicle stability in the process of intelligent vehicle trajectory tracking, a coordinated control strategy of the trajectory tracking and stability of intelligent electric vehicles is proposed based on the hierarchical control theory. The vehicle dynamics model and trajectory tracking model are established. In order to tackle the chattering problem in the traditional sliding mode controller, an Adaptive Spiral Sliding Mode controller is designed by taking the derivative of the controller as the upper controller, which is intended to reduce the heading deviation and lateral deviation in the trajectory tracking process whilst ensuring the stability of the vehicle itself. In the lower controller, a four-wheel tire force optimal distribution method is designed. According to the requirements of the upper controller, combined with the yaw stability of the vehicle, the directional control distribution of the four-wheel tire force is realized. A joint simulation model was built based on CarSim and Simulink, and simulation experiments were performed. The results show that the proposed control strategy can effectively control the heading deviation and lateral deviation in the vehicle trajectory tracking while ensuring the lateral stability of the vehicle.
Chemical Profile of Ruta graveolens, Evaluation of the Antioxidant and Antibacterial Potential of Its Essential Oil, and Molecular Docking Simulations
Authors: Jianu Călin , Goleț Ionuț , Stoin Daniela , Cocan Ileana , Bujancă Gabriel , Mișcă Corina , Mioc Marius , Mioc Alexandra , Șoica Codruța , Lukinich-Gruia Alexandra Teodora , Rusu Laura-Cristina , Muntean Delia , Horhat Delia Ioana
Published: December 2021

The research aimed to investigate the chemical composition and antioxidant and antibacterial potential of the essential oil (EO) isolated from the aerial parts (flowers, leaves, and stems) of Ruta graveolens L., growing in western Romania. Ruta graveolens L. essential oil (RGEO) was isolated by steam distillation (0.29% v/w), and the content was assessed by gas chromatography-mass spectrometry (GC-MS). Findings revealed that 2-Undecanone (76.19%) and 2-Nonanone (7.83%) followed by 2-Undecanol (1.85%) and 2-Tridecanone (1.42%) are the main detected compounds of the oil. The RGEO exerted broad-spectrum antibacterial and antifungal effects, S. pyogenes, S. aureus, and S. mutans being the most susceptible tested strains. The antioxidant activity of RGEO was assessed by peroxide and thiobarbituric acid value, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), and β-carotene/linoleic acid bleaching testing. The results indicated moderate radical scavenging and relative antioxidative activity in DPPH and β-carotene bleaching tests. However, between the 8th and 16th days of the incubation period, the inhibition of primary oxidation compounds induced by the RGEO was significantly stronger (p < 0.001) than butylated hydroxyanisole (BHA). Molecular docking analysis highlighted that a potential antimicrobial mechanism of the RGEO could be exerted through the inhibition of D-Alanine-d-alanine ligase (DDl) by several RGEO components. Docking analysis also revealed that a high number RGEO components could exert a potential in vitro protein-targeted antioxidant effect through xanthine oxidase and lipoxygenase inhibition. Consequently, RGEO could be a new natural source of antiseptics and antioxidants, representing an option for the use of synthetic additives in the food and pharmaceutical industry.
Formulation of Shell Elements Based on the Motion Formalism
Authors: Bauchau Olivier , Sonneville Valentin
Published: December 2021

This paper presents a finite element implementation of plates and shells for the analysis of flexible multibody systems. The developments are set within the framework of the motion formalism that (1) uses configuration and motion to describe the kinematics of flexible multibody systems, (2) couples their displacement and rotation components by recognizing that configuration and motion are members of the Special Euclidean group, and (3) resolves all tensors components in local frames. The formulation based on the motion formalism (1) provides a theoretical framework that streamlines the formulation of shell elements, (2) leads to governing equations of motion that are objective, intrinsic, and present a reduced order of nonlinearity, (3) improves the efficiency of the solution process, (4) circumvents the shear locking phenomenon that plagues shell formulations based on classical kinematic descriptions, and (5) prevents the occurrence of singularities in the treatment of finite rotation. Numerical examples are presented to illustrate the advantageous features of the proposed formulation.
Air Quality Estimation Using Dendritic Neural Regression with Scale-Free Network-Based Differential Evolution
Authors: Song Zhenyu , Tang Cheng , Qian Jin , Zhang Bin , Todo Yuki
Published: December 2021

With the rapid development of the global economy, air pollution, which restricts sustainable development and threatens human health, has become an important focus of environmental governance worldwide. The modeling and reliable prediction of air quality remain substantial challenges because uncertainties residing in emissions data are unknown and the dynamic processes are not well understood. A number of machine learning approaches have been used to predict air quality to help alleviate air pollution, since accurate air quality estimation may result in significant social-economic development. From this perspective, a novel air quality estimation approach is proposed, which consists of two components: newly-designed dendritic neural regression (DNR) and customized scale-free network-based differential evolution (SFDE). The DNR can adaptively utilize spatio-temporal information to capture the nonlinear correlation between observations and air pollutant concentrations. Since the landscape of the weight space in DNR is vast and multimodal, SFDE is used as the optimization algorithm due to its powerful search ability. Extensive experimental results demonstrate that the proposed approach can provide stable and reliable performances in the estimation of both PM2.5 and PM10 concentrations, being significantly better than several commonly-used machine learning algorithms, such as support vector regression and long short-term memory.
High-Resolution Modeling of Mesoscale Circulation in the Atmospheric Boundary Layer over a Complex Coastal Area
Authors: Lim Hee-Jeong , Lee Young-Hee
Published: December 2021

We evaluated the performance of the high-resolution (333 m) Weather Research and Forecasting (WRF) model in simulating the flow structure at a complex coastal site in Boseong, South Korea, on 15 July 2018, against observations obtained from a 300 m tower and radiosonde, and analyzed the model results to interpret the measurements. The study site is surrounded by mountains, valleys, and bays, and is adjacent to the South Sea; thus, it is influenced by terrain-forced flow and thermally driven circulation. The study day was characterized by the development of nighttime low-level wind maximum (LLWM) and daytime sea breeze under weak synoptic wind conditions. Although the WRF model simulated the onset and cessation of a sea breeze later than was observed, it showed good skill in reproducing the near-surface temperatures, wind vectors, and vertical profiles of potential temperatures and wind vectors in the atmospheric boundary layer at the study site. We analyzed the model results at 05:30 and 14:30 LST when the model’s performance was good for wind. At 05:30 LST, hydraulic jump produced weak wind conditions below 300 m above ground level (AGL), and westerly down-valley flow developed near the surface, leading to an LLWM. At 14:30 LST, heating over land produced a thermal high over land at 1800 m AGL, counteracting the synoptic pressure gradient, and leading to weak wind conditions at this level. We performed three sensitivity simulations to examine the dependence of flow structure on the horizontal and vertical resolution. The results show that an early-morning hydraulic jump can be simulated by applying a high-resolution model in both the horizontal and vertical grids, and the simulated onset and cessation times of the sea breeze depend on the model’s resolution. The dependence of flow structure on the model resolution has been discussed.
Grassland Phenology’s Sensitivity to Extreme Climate Indices in the Sichuan Province, Western China
Authors: Adu Benjamin , Qin Gexia , Li Chunbin , Wu Jing
Published: December 2021

Depending on the vegetation type, extreme climate and drought events have a greater impact on the end of the season (EOS) and start of the season (SOS). This study investigated the spatial and temporal distribution characteristics of grassland phenology and its responses to seasonal and extreme climate changes in Sichuan Province from 2001 to 2020. Based on the data from 38 meteorological stations in Sichuan Province, this study calculated the 15 extreme climate indices recommended by the Expert Team on Climate Change Detection and Indices (ETCCDI). The results showed that SOS was concentrated in mid-March to mid-May (80–140 d), and 61.83% of the area showed a significant advancing trend, with a rate of 0–1.5 d/a. The EOS was concentrated between 270–330 d, from late September to late November, and 71.32% showed a delayed trend. SOS was strongly influenced by the diurnal temperature range (DTR), yearly maximum consecutive five-day precipitation (RX5), and the temperature vegetation dryness index (TVDI), while EOS was most influenced by the yearly minimum daily temperature (TNN), yearly mean temperature (TEMP_MEAN), and TVDI. The RX5 day index showed an overall positive sensitivity coefficient for SOS. TNN index showed a positive sensitivity coefficient for EOS. TVDI showed positive and negative sensitivities for SOS and EOS, respectively. This suggests that extreme climate change, if it causes an increase in vegetation SOS, may also cause an increase in vegetation EOS. This research can provide a scientific basis for developing regional vegetation restoration and disaster prediction strategies in Sichuan Province.
Green Leaf Volatiles in the Atmosphere—Properties, Transformation, and Significance
Authors: Sarang Kumar , Rudziński Krzysztof J. , Szmigielski Rafał
Published: December 2021

This review thoroughly covers the research on green leaf volatiles (GLV) in the context of atmospheric chemistry. It briefly takes on the GLV sources, in-plant synthesis, and emission inventory data. The discussion of properties includes GLV solubility in aqueous systems, Henry’s constants, partition coefficients, and UV spectra. The mechanisms of gas-phase reactions of GLV with OH, NO3, and Cl radicals, and O3 are explained and accompanied by a catalog of products identified experimentally. The rate constants of gas-phase reactions are collected in tables with brief descriptions of corresponding experiments. A similar presentation covers the aqueous-phase reactions of GLV. The review of multiphase and heterogeneous transformations of GLV covers the smog-chamber experiments, products identified therein, along with their yields and the yields of secondary organic aerosols (SOA) formed, if any. The components of ambient SOA linked to GLV are briefly presented. This review recognized GLV as atmospheric trace compounds that reside primarily in the gas phase but did not exclude their transformation in atmospheric waters. GLV have a proven potential to be a source of SOA with a global burden of 0.6 to 1 Tg yr−1 (estimated jointly for (Z)-hexen-1-ol, (Z)-3-hexenal, and 2-methyl-3-buten-2-ol), 0.03 Tg yr−1 from switch grass cultivation for biofuels, and 0.05 Tg yr−1 from grass mowing.
Satellite Data Applications for Site-Specific Air Quality Regulation in the UK: Pilot Study and Prospects
Authors: Potts Daniel A. , Ferranti Emma J. S. , Timmis Roger , Brown Andrew S. , Vande Hey Joshua D.
Published: December 2021

Atmospheric composition data from satellite platforms offers great potential for improving current understanding of anthropogenic emissions. Whilst this data has been used extensively in research, its use by governments to regulate and assess site-specific legislation compliance is minimal. Here, we outline the regulatory context for air quality regulation in the UK, and present a pilot study highlighting the potential of current instruments. The pilot study demonstrates the capabilities and limitations of the TROPOspheric Monitoring Instrument (TROPOMI) for detecting and isolating emissions of NO2 from regulated UK point sources. This study successfully isolated NO2 emissions from a cluster of three closely situated regulated sites in the north east of England, despite their proximity to large urban sources. This is the first time these sites have been resolved from satellite-based observations, and serves as a clear demonstration of the potential of current and future Earth observation data products for site-specific monitoring and investigation within the UK.
Impacts of Meteorological Factors, VOCs Emissions and Inter-Regional Transport on Summer Ozone Pollution in Yuncheng
Authors: Zhang Chenyue , Luo Shuzhen , Zhao Wenting , Wang Yuntao , Zhang Qiang , Qu Chengkai , Liu Xingang , Wen Xiaoyu
Published: December 2021

Summer ozone (O3) pollution in China has become increasingly serious in recent years. This study is based on hourly data of near-surface ozone (O3) and nitrogen oxides (NOx) and volatile organic compounds (VOCs) from June to August 2020 in Yuncheng, combined with meteorological data to analyse the characteristics of O3 pollution in summer and the influence of meteorological factors, precursors, and long-range transport on O3 pollution. In this paper, the VOCs/NOx characteristic ratio method was used to explore the sensitivity of O3 generation. Backward trajectories, cluster analysis, potential source contribution factor (PSCF) analysis and concentration weight trajectory (CWT) analysis were also calculated using Trajstat software. In 2020, Yuncheng had persistent O3 pollution, with the highest concentrations in June, significantly higher than July and August. Conditions of high temperature, low relative humidity and low wind speed contribute to the O3 accumulation. VOCs are the main precursors to the local production of O3. Besides, the long-range transport analysis shows that southeast-oriented air masses are the main direction influencing summer O3 pollution. The primary potential source areas of O3 are in the central and southern part of Henan province, the north-western Anhui province, and the northern Shaanxi. In addition, northern Hubei and southwestern Shandong also influence O3 pollution in summer Yuncheng.
Overexpression of Cu/Zn Superoxide Dismutase (Cu/Zn SOD) in Synechococcus elongatus PCC 7942 for Enhanced Azo Dye Removal through Hydrogen Peroxide Accumulation
Authors: Mohandass ShylajaNaciyar , Ragavan Mangalalakshmi , Gnanasekaran Dineshbabu , Lakshmanan Uma , Dharmar Prabaharan , Saha Sushanta Kumar
Published: December 2021

Discharge of recalcitrant azo dyes to the environment poses a serious threat to environmental health. However certain microorganisms in nature have developed their survival strategies by degrading these toxic dyes. Cyanobacteria are one such prokaryotic, photosynthetic group of microorganisms that degrade various xenobiotic compounds, due to their capability to produce various reactive oxygen species (ROS), and particularly the hydrogen peroxide (H2O2) when released in their milieu. The accumulation of H2O2 is the result of the dismutation of superoxide radicals by the enzyme superoxide dismutase (SOD). In this study, we have genetically modified the cyanobacterium Synechococcus elongatus PCC 7942 by integrating Cu/Zn SOD gene (sodC) from Synechococcus sp. PCC 9311 to its neutral site through homologous recombination. The overexpression of sodC in the derivative strain was driven using a strong constitutive promoter of the psbA gene. The derivative strain resulted in constitutive production of sodC, which was induced further during dye-treated growth. The genetically engineered Synechococcus elongatus PCC 7942 (MS-sodC+) over-accumulated H2O2 during azo dye treatment with a higher dye removal rate than the wild-type strain (WS-sodC−). Therefore, enhanced H2O2 accumulation through SODs overexpression in cyanobacteria may serve as a valuable bioremediation tool.
A Dual Electrode Biosensor for Glucose and Lactate Measurement in Normal and Prolonged Obese Mice Using Single Drop of Whole Blood
Authors: Thapa Mukesh , Sung Ryong , Heo Yun Seok
Published: December 2021

Understanding the levels of glucose (G) and lactate (L) in blood can help us regulate various chronic health conditions such as obesity. In this paper, we introduced an enzyme-based electrochemical biosensor adopting glucose oxidase and lactate oxidase on two working screen-printed carbon electrodes (SPCEs) to sequentially determine glucose and lactate concentrations in a single drop (~30 µL) of whole blood. We developed a diet-induced obesity (DIO) mouse model for 28 weeks and monitored the changes in blood glucose and lactate levels. A linear calibration curve for glucose and lactate concentrations in ranges from 0.5 to 35 mM and 0.5 to 25 mM was obtained with R-values of 0.99 and 0.97, respectively. A drastic increase in blood glucose and a small but significant increase in blood lactate were seen only in prolonged obese cases. The ratio of lactate concentration to glucose concentration (L/G) was calculated as the mouse’s gained weight. The results demonstrated that an L/G value of 0.59 could be used as a criterion to differentiate between normal and obesity conditions. With L/G and weight gain, we constructed a diagnostic plot that could categorize normal and obese health conditions into four different zones. The proposed dual electrode biosensor for glucose and lactate in mouse whole blood showed good stability, selectivity, sensitivity, and efficiency. Thus, we believe that this dual electrode biosensor and the diagnostic plot could be used as a sensitive analytical tool for diagnosing glucose and lactate biomarkers in clinics and for monitoring obesity.
Ischemic Stroke in a Patient with Stable CADASIL during COVID-19: A Case Report
Authors: Cruciani Alessandro , Pilato Fabio , Rossi Mariagrazia , Motolese Francesco , Di Lazzaro Vincenzo , Capone Fioravante
Published: December 2021

Background: SARS-CoV-2 infection has been associated with different neurological conditions such as Guillain-Barré, encephalitis and stroke. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease characterized by recurrent ischemic stroke, cognitive decline, migraine and mood disturbances. One of the mechanisms involved in CADASIL pathogenesis is endothelial dysfunction, which causes an increased risk of recurrent strokes. Since COVID-19 infection is also associated with coagulopathy and endothelial dysfunction, the risk of ischemic stroke might be even higher in this population. We describe the case of a CADASIL patient who developed an acute ischemic stroke after SARS-CoV-2 infection. In patients with diseases causing endothelial dysregulation, such as CADASIL, the hypercoagulability related to COVID-19 may contribute to the risk of stroke recurrence.
Neuroprotective Effect of Clobenpropit against Lipopolysaccharide-Induced Cognitive Deficits via Attenuating Neuroinflammation and Enhancing Mitochondrial Functions in Mice
Authors: Mani Vasudevan , Arfeen Minhajul , Ali Hussein M. , Abdel-Moneim Abdel-Moneim Hafez , Aldubayan Maha , Alhowail Ahmad
Published: December 2021

Clobenpropit (CLO), an antagonist on histamine H3 receptors (HH3R), has been shown to protect NMDA-induced neuronal necrosis in cortical neuronal cell culture from rats. In this work, we explored its potential on lipopolysaccharide (LPS)-induced memory deficits, neuroinflammation, and mitochondrial dysfunction in mice. CLO (1 and 3 mg/kg, p.o.) was treated continually for 30 days, and neurotoxicity was induced by four doses of LPS (250 µg/kg, i.p.). The radial arm maze (RAM) was used to access memory behaviors. After the REM test, brain tissue was collected from each mouse to estimate pro-inflammatory cytokines (TNFα and IL6), anti-inflammatory cytokines (TGF-β1 and IL-10), cyclooxygenase-2 (COX 2), and mitochondrial respiratory chain complex (MRCC- I, II and IV) enzymes. CLO treatment reversed the LPS-induced behavioral deficits by a significant reduction in time taken to consume all five bites (TTB), working memory error (WME), and reference memory error (REM) in the REM test. Regarding neuroinflammation, it attenuated the release of COX, TNF-α, and IL-6, and augmented TGF-β1 and IL-10 levels in the brain. Reversal of LPS-induced brain MRCC (I, II, and IV) levels also resulted with CLO treatment. From these findings, CLO promises neuroprotection against LPS-induced cognitive deficits by ameliorating neuroinflammation and restoring the MRCC enzymes in mice.
Social Isolation, Loneliness and Generalized Anxiety: Implications and Associations during the COVID-19 Quarantine
Authors: Wilkialis Linas , Rodrigues Nelson B. , Cha Danielle S. , Siegel Ashley , Majeed Amna , Lui Leanna M. W. , Tamura Jocelyn K. , Gill Barjot , Teopiz Kayla , McIntyre Roger S.
Published: December 2021

The COVID-19 pandemic has resulted in a predominantly global quarantine response that has been associated with social isolation, loneliness, and anxiety. The foregoing experiences have been amply documented to have profound impacts on health, morbidity, and mortality. This narrative review uses the extant neurobiological and theoretical literature to explore the association between social isolation, loneliness, and anxiety in the context of quarantine during the COVID-19 pandemic. Emerging evidence suggests that distinct health issues (e.g., a sedentary lifestyle, a diminished overall sense of well-being) are associated with social isolation and loneliness. The health implications of social isolation and loneliness during quarantine have a heterogenous and comorbid nature and, as a result, form a link to anxiety. The limbic system plays a role in fear and anxiety response; the bed nucleus of the stria terminalis, amygdala, HPA axis, hippocampus, prefrontal cortex, insula, and locus coeruleus have an impact in a prolonged anxious state. In the conclusion, possible solutions are considered and remarks are made on future areas of exploration.
A Combined Administration of Testosterone and Arginine Vasopressin Affects Aggressive Behavior in Males
Authors: Akkoc Altinok Dilsa Cemre , Votinov Mikhail , Henzelmann Friederike , Jo HanGue , Eisert Albrecht , Habel Ute , Wagels Lisa
Published: December 2021

Aggressive behavior is modulated by many factors, including personality and cognition, as well as endocrine and neural changes. To study the potential effects on the reaction to provocation, which was realized by an ostensible opponent subtracting money from the participant, we administered testosterone (T) and arginine vasopressin (AVP) or a respective placebo (PL). Forty males underwent a functional magnetic resonance imaging session while performing a provocation paradigm. We investigated differential hormone effects and the potential influence of Machiavellian traits on punishment choices (monetary subtractions by the participant) in the paradigm. Participants in the T/AVP group subtracted more money when they were not provoked but showed increased activation in the inferior frontal gyrus and inferior parietal lobule during feedback compared to PL. Higher Machiavellian traits significantly increased punishing behavior independent of provocation only in this group. The pilot study shows that T/AVP affects neural and behavioral responses during a provocation paradigm while personality characteristics, such as Machiavellian trait patterns, specifically interact with hormonal influences (T/AVP) and their effects on behavior.
Locus Coeruleus Optogenetic Modulation: Lessons Learned from Temporal Patterns
Authors: Harley Carolyn W. , Yuan Qi
Published: December 2021

After reviewing seminal studies using optogenetics to interrogate the functional role of the locus coeruleus in behavior, we conclude that differences in firing rates and firing patterns of locus coeruleus neurons contribute to locus coeruleus nucleus heterogeneity by recruiting different output circuitry, and differentially modifying behavior. The outcomes initiated by different optogenetic input activation patterns and frequencies can have opposite consequences for behavior, activate different neurons in the same target structure, be supported by distinct adrenoceptors and vary with behavioral state.
Body Schema Self-Awareness and Related Dream Content Modifications in Amputees Due to Cancer
Authors: Giordano Alessandra , Boffano Michele , Piana Raimondo , Mutani Roberto , Cicolin Alessandro
Published: December 2021

Purpose: the evaluation of body image perception, pain coping strategies, and dream content, together with phantom limb and telescoping phenomena in patients with sarcoma who underwent surgery for limb amputation. Material and Methods: consecutive outpatients were evaluated at T0 (within 3 weeks after surgery) and T1 (4–6 months after surgery) as follows: demographic and clinical data collection; the Groningen Questionnaire Problems after Arm Amputation; the West Haven-Yale Multidimensional Pain Inventory; the Body Image Concern Inventory, a clinical trial to identify telescoping; and a weekly diary of dreams. Dream contents were coded according to the Hall and Van de Castle coding system. Results: Twenty patients completed the study (15 males and 5 females, mean age: 53.9 ± 24.6, education: 7.8 ± 3.4). All subjects experienced phantom limb and 35% of them experienced telescoping soon after surgery, and 25% still after 4–6 months. Both at T0 and T1, that half of the subjects reported dreams about still having their missing limbs. At T1 the patients’ perceptions of being able to deal with problems were lower, and pain and its interference in everyday life were higher yet associated with significant engagement in everyday activities and an overall good mood. The dream content analysis highlighted that males were less worried about health problems soon after amputation, and women showed more initial difficulties that seemed to be resolved after 4–6 months after surgery. Conclusions: The dream content analysis may improve clinicians’ ability to support their patients during their therapeutic course.
Changes in the Orexin System in Rats Exhibiting Learned Helplessness Behaviors
Authors: Hsu Chung-Wei , Wang Sabrina
Published: December 2021

Orexin-A (OX-A) and orexin-B (OX-B) are neuropeptides produced in the hypothalamus. Preclinical and clinical studies suggest that depression and anxiety are associated with the orexin system. In the current study, we used the learned helplessness (LH) animal model of depression to identify rats displaying LH behaviors (LH rats) and those that did not (No-LH rats). We compared the number of orexin-containing neurons in the hypothalamus of LH, No-LH, and control rats. Orexin peptides, orexin receptor 1 (OXR1) and 2 (OXR2) in brain areas involved in major depression and serum OX-A and corticosterone (CORT) concentrations were quantified and compared between rat groups. We found that LH and No-LH rats displayed higher serum OX-A concentrations compared with control rats. Comparison between LH and No-LH rats revealed that No-LH rats had significantly higher OX-A levels in the brain, more OX-A neurons, and more OX-A neuron activation. LH rats had more OX-B neurons and more OX-B neuron activation. Orexin peptides and receptors in the brain areas involved in major depression exhibited different patterns in LH and NoLH rats. Our findings revealed that activation of OX-A neurons could promote resilient behaviors under stressful situations and OX-A and OX-B neuropeptides exhibit dissimilar functions in LH behaviors.
Recent Advances in Consumer Behavior Theory: Shocks from the COVID-19 Pandemic
Authors: Yin Bibo , Yu Yajing , Xu Xiaocang
Published: December 2021

Background: The COVID-19 pneumonia epidemic has had an enormous impact on people’s lives, particularly aspects of life such as consumption, and has therefore brought new elements to the expansion of Consumer behavior theory. Methods: This paper searches the literature on consumption research conducted from 1981 to 2021, including sources such as CNKI, Wanfang, Google Scholar, and Web of Science. Through the exploration of the existing relevant literature, this article found that the COVID-19 pneumonia epidemic has had a profound impact on consumption willingness, consumption patterns, and consumption objects, and, as such, has newly expanded the theoretical model of consumer behavior. Results: Through reviewing the literature, this paper found some results. For example with regard to consumption patterns, early studies and the impact of COVID-19 was focused on online consumption, however in the context of COVID-19, scholars proposed paying attention to the combination of online and offline development. Conclusion: The COVID-19 pneumonia epidemic has had a profound effect on consumer behavior worldwide. Under the current economic depression, the government should take adequate measures in order to respond to the new changes in consumer behavior and therefore promote economic growth. For example, the government should encourage the combination of online and offline business operation modes to break the boundaries of customer groups and supply chains, so that consumers can buy anytime and anywhere.
Experimental Investigation and Numerical Simulation of C-Shape Thin-Walled Steel Profile Joints
Authors: Taranu George , Toma Ionut-Ovidiu
Published: December 2021

The versatility of steel, its high resistance in relation to its low mass, as well as the easily accessible technology in the context of using recyclable materials and the low negative impact on the environment represent important arguments in using thin-walled steel profiles to make structures for buildings with a low height regime. This paper presents the results of an experimental program that investigated the behavior of three types of joints in a T-shape form made of thin-walled steel profiles to make shear wall panels or truss beam floors. Due to the small dimensions of the C-profiles of 89 × 41 × 12 × 1 mm, and of the technology of their joining, manufacturers prefer the hinged connections of elements with self-drilling screws. The purpose of the research presented in this paper is to assess the maximum capacity of the joints, the elastic and post-elastic behavior until failure, and also the mechanisms failure. The types of joints analyzed are commonly used in the production of structural systems for houses. The experimental program, which consisted of testing 5 specimens for each type of joint in tension (shear on screws), showed different behavior in terms of load-displacement. The experimental, tested models were analyzed by finite element simulations in an ANSYS nonlinear static structure with 3D solid models. The materials were defined by a bilinear true stress–strain curve obtained after some experimental tensile tests of the steel. The results of the experimental tests showed that the main failure mechanism is a yielding of the holes where the screws were mounted and a shearing of the profile walls. Adding an additional screw on each side increases the capacity of the joints, but not until a yield loss is obtained. In conclusion, it is shown that the solution is suitable for a low level of loading in a static manner; however, additional studies are necessary in order to develop and verify other solutions, thus improving the strength of the connection.
HLA Class II Histocompatibility Antigen γ Chain (CD74) Expression Is Associated with Immune Cell Infiltration and Favorable Outcome in Breast Cancer
Authors: Noer Julie B. , Talman Maj-Lis M. , Moreira José M. A.
Published: December 2021

The triple-negative breast cancer (TNBC) subtype, defined as negative for ER, PgR, and HER2, is biologically more aggressive and with a poorer prognosis than the other subtypes, in part due to the lack of suitable targeted therapies. Consequently, identification of any potential novel therapeutic option, predictive and/or prognostic biomarker, or any other relevant information that may impact the clinical management of this group of patients is valuable. The HLA class II histocompatibility antigen γ chain, or cluster of differentiation 74 (CD74), has been associated with TNBCs, and poorer survival. However, discordant results have been reported for immunohistochemical studies of CD74 expression in breast cancer. Here we report validation studies for use of a novel CD74 antibody, UMAb231. We used this antibody to stain a TMA including 640 human breast cancer samples, and found no association with the TNBC subtype, but did find a positive correlation with outcome. We also found associations between CD74 expression and immune cell infiltration, and expression of programmed death ligand 1 (PD-L1). Given that CD74 may play a role in innate immune system responses and the potential of immunotherapy as a viable treatment strategy for TNBCs, CD74 expression may have predictive value for immune checkpoint therapies.
Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers
Authors: Gracia-Hernandez Maria , Munoz Zuleima , Villagra Alejandro
Published: December 2021

Melanoma is the least common but deadliest type of skin cancer. Melanomagenesis is driven by a series of mutations and epigenetic alterations in oncogenes and tumor suppressor genes that allow melanomas to grow, evolve, and metastasize. Epigenetic alterations can also lead to immune evasion and development of resistance to therapies. Although the standard of care for melanoma patients includes surgery, targeted therapies, and immune checkpoint blockade, other therapeutic approaches like radiation therapy, chemotherapy, and immune cell-based therapies are used for patients with advanced disease or unresponsive to the conventional first-line therapies. Targeted therapies such as the use of BRAF and MEK inhibitors and immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA4 only improve the survival of a small subset of patients. Thus, there is an urgent need to identify alternative standalone or combinatorial therapies. Epigenetic modifiers have gained attention as therapeutic targets as they modulate multiple cellular and immune-related processes. Due to melanoma’s susceptibility to extrinsic factors and reversible nature, epigenetic drugs are investigated as a therapeutic avenue and as adjuvants for targeted therapies and immune checkpoint inhibitors, as they can sensitize and/or reverse resistance to these therapies, thus enhancing their therapeutic efficacy. This review gives an overview of the role of epigenetic changes in melanoma progression and resistance. In addition, we evaluate the latest advances in preclinical and clinical research studying combinatorial therapies and discuss the use of epigenetic drugs such as HDAC and DNMT inhibitors as potential adjuvants for melanoma patients.
Cervical Cancer Development: Implications of HPV16 E6E7-NFX1-123 Regulated Genes
Authors: Quist Kevin M. , Solorzano Isaiah , Wendel Sebastian O. , Chintala Sreenivasulu , Wu Cen , Wallace Nicholas A. , Katzenellenbogen Rachel A.
Published: December 2021

High-risk human papillomavirus (HR HPV) causes nearly all cervical cancers, half of which are due to HPV type 16 (HPV16). HPV16 oncoprotein E6 (16E6) binds to NFX1-123, and dysregulates gene expression, but their clinical implications are unknown. Additionally, HPV16 E7’s role has not been studied in concert with NFX1-123 and 16E6. HR HPVs express both oncogenes, and transformation requires their expression, so we sought to investigate the effect of E7 on gene expression. This study’s goal was to define gene expression profiles across cervical precancer and cancer stages, identify genes correlating with disease progression, assess patient survival, and validate findings in cell models. We analyzed NCBI GEO datasets containing transcriptomic data linked with cervical cancer stage and utilized LASSO analysis to identify cancer-driving genes. Keratinocytes expressing 16E6 and 16E7 (16E6E7) and exogenous NFX1-123 were tested for LASSO-identified gene expression. Ten out of nineteen genes correlated with disease progression, including CEBPD, NOTCH1, and KRT16, and affected survival. 16E6E7 in keratinocytes increased CEBPD, KRT16, and SLPI, and decreased NOTCH1. Exogenous NFX1-123 in 16E6E7 keratinocytes resulted in significantly increased CEBPD and NOTCH1, and reduced SLPI. This work demonstrates the clinical relevance of CEBPD, NOTCH1, KRT16, and SLPI, and shows the regulatory effects of 16E6E7 and NFX1-123.
Fully Automated MR Based Virtual Biopsy of Cerebral Gliomas
Authors: Haubold Johannes , Hosch René , Parmar Vicky , Glas Martin , Guberina Nika , Catalano Onofrio Antonio , Pierscianek Daniela , Wrede Karsten , Deuschl Cornelius , Forsting Michael , Nensa Felix , Flaschel Nils , Umutlu Lale
Published: December 2021

Objective: The aim of this study was to investigate the diagnostic accuracy of a radiomics analysis based on a fully automated segmentation and a simplified and robust MR imaging protocol to provide a comprehensive analysis of the genetic profile and grading of cerebral gliomas for everyday clinical use. Methods: MRI examinations of 217 therapy-naïve patients with cerebral gliomas, each comprising a non-contrast T1-weighted, FLAIR and contrast-enhanced T1-weighted sequence, were included in the study. In addition, clinical and laboratory parameters were incorporated into the analysis. The BraTS 2019 pretrained DeepMedic network was used for automated segmentation. The segmentations generated by DeepMedic were evaluated with 200 manual segmentations with a DICE score of 0.8082 ± 0.1321. Subsequently, the radiomics signatures were utilized to predict the genetic profile of ATRX, IDH1/2, MGMT and 1p19q co-deletion, as well as differentiating low-grade glioma from high-grade glioma. Results: The network provided an AUC (validation/test) for the differentiation between low-grade gliomas vs. high-grade gliomas of 0.981 ± 0.015/0.885 ± 0.02. The best results were achieved for the prediction of the ATRX expression loss with AUCs of 0.979 ± 0.028/0.923 ± 0.045, followed by 0.929 ± 0.042/0.861 ± 0.023 for the prediction of IDH1/2. The prediction of 1p19q and MGMT achieved moderate results, with AUCs of 0.999 ± 0.005/0.711 ± 0.128 for 1p19q and 0.854 ± 0.046/0.742 ± 0.050 for MGMT. Conclusion: This fully automated approach utilizing simplified MR protocols to predict the genetic profile and grading of cerebral gliomas provides an easy and efficient method for non-invasive tumor decoding.
Tumor Microenvironment in Pancreatic Intraepithelial Neoplasia
Authors: Opitz Friederike V. , Haeberle Lena , Daum Alexandra , Esposito Irene
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with a poor prognosis. A characteristic of PDAC is the formation of an immunosuppressive tumor microenvironment (TME) that facilitates bypassing of the immune surveillance. The TME consists of a desmoplastic stroma, largely composed of cancer-associated fibroblasts (CAFs), immunosuppressive immune cells, immunoregulatory soluble factors, neural network cells, and endothelial cells with complex interactions. PDAC develops from various precursor lesions such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), and possibly, atypical flat lesions (AFL). In this review, we focus on the composition of the TME in PanINs to reveal detailed insights into the complex restructuring of the TME at early time points in PDAC progression and to explore ways of modifying the TME to slow or even halt tumor progression.
Antagonistic Roles of the Tumor Suppressor miR-210-3p and Oncomucin MUC4 Forming a Negative Feedback Loop in Pancreatic Adenocarcinoma
Authors: Boukrout Nihad , Souidi Mouloud , Lahdaoui Fatima , Duchêne Belinda , Neve Bernadette , Coppin Lucie , Leteurtre Emmanuelle , Torrisani Jérôme , Van Seuningen Isabelle , Jonckheere Nicolas
Published: December 2021

Background: Pancreatic adenocarcinoma (PDAC) is a deadly cancer with an extremely poor prognosis. MUC4 membrane-bound mucin is neoexpressed in early pancreatic neoplastic lesions and is associated with PDAC progression and chemoresistance. In cancers, microRNAs (miRNAs, small noncoding RNAs) are crucial regulators of carcinogenesis, chemotherapy response and even metastatic processes. In this study, we aimed at identifying and characterizing miRNAs activated downstream of MUC4-associated signaling in pancreatic adenocarcinoma. MiRnome analysis comparing MUC4-KD versus Mock cancer cells showed that MUC4 inhibition impaired miR-210-3p expression. Therefore, we aimed to better understand the miR-210-3p biological roles. Methods: miR-210-3p expression level was analyzed by RT-qPCR in PDAC-derived cell lines (PANC89 Mock and MUC4-KD, PANC-1 and MiaPACA-2), as well as in mice and patients tissues. The MUC4-miR-210-3p regulation was investigated using luciferase reporter construct and chromatin immunoprecipitation experiments. Stable cell lines expressing miR-210-3p or anti-miR-210-3p were established using CRISPR/Cas9 technology or lentiviral transduction. We evaluated the biological activity of miR-210-3p in vitro by measuring cell proliferation and migration and in vivo using a model of subcutaneous xenograft. Results: miR-210-3p expression is correlated with MUC4 expression in PDAC-derived cells and human samples, and in pancreatic PanIN lesions of Pdx1-Cre; LstopL-KrasG12D mice. MUC4 enhances miR-210-3p expression levels via alteration of the NF-κB signaling pathway. Chromatin immunoprecipitation experiments showed p50 NF-κB subunit binding on miR-210-3p promoter regions. We established a reciprocal regulation since miR-210-3p repressed MUC4 expression via its 3′-UTR. MiR-210-3p transient transfection of PANC89, PANC-1 and MiaPACA-2 cells led to a decrease in cell proliferation and migration. These biological effects were validated in cells overexpressing or knocked-down for miR-210-3p. Finally, we showed that miR-210-3p inhibits pancreatic tumor growth and proliferation in vivo. Conclusion: We identified a MUC4-miR-210-3p negative feedback loop in early-onset PDAC, but also revealed new functions of miR-210-3p in both in vitro and in vivo proliferation and migration of pancreatic cancer cells, suggesting a complex balance between MUC4 pro-oncogenic roles and miR-210-3p anti-tumoral effects.
Intestinal Microbiota in Postmenopausal Breast Cancer Patients and Controls
Authors: Aarnoutse Romy , Hillege Lars E. , Ziemons Janine , De Vos-Geelen Judith , de Boer Maaike , Aerts Elvira M. E. R. , Vriens Birgit E. P. J. , van Riet Yvonne , Vincent Jeroen , van de Wouw Agnes J. , Le Giang N. , Venema Koen , Rensen Sander S. , Penders John , Smidt Marjolein L.
Published: December 2021

Background: Previous preclinical and clinical research has investigated the role of intestinal microbiota in carcinogenesis. Growing evidence exists that intestinal microbiota can influence breast cancer carcinogenesis. However, the role of intestinal microbiota in breast cancer needs to be further investigated. This study aimed to identify the microbiota differences between postmenopausal breast cancer patients and controls. Patients and methods: This prospective cohort study compared the intestinal microbiota richness, diversity, and composition in postmenopausal histologically proven ER+/HER2- breast cancer patients and postmenopausal controls. Patients scheduled for (neo)adjuvant adriamycin, cyclophosphamide (AC), and docetaxel (D), or endocrine therapy (tamoxifen) were prospectively enrolled in a multicentre cohort study in the Netherlands. Patients collected a faecal sample and completed a questionnaire before starting systemic cancer treatment. Controls, enrolled from the National Dutch Breast Cancer Screening Programme, also collected a faecal sample and completed a questionnaire. Intestinal microbiota was analysed by amplicon sequencing of the 16S rRNA V4 gene region. Results: In total, 81 postmenopausal ER+/HER2- breast cancer patients and 67 postmenopausal controls were included, resulting in 148 faecal samples. Observed species richness, Shannon index, and overall microbial community structure were not significantly different between breast cancer patients and controls. There was a significant difference in overall microbial community structure between breast cancer patients scheduled for adjuvant treatment, neoadjuvant treatment, and controls at the phylum (p = 0.042) and genus levels (p = 0.015). Dialister (p = 0.001) and its corresponding family Veillonellaceae (p = 0.001) were higher in patients scheduled for adjuvant treatment, compared to patients scheduled for neoadjuvant treatment. Additional sensitivity analysis to correct for the potential confounding effect of prophylactic antibiotic use, indicated no differences in microbial community structure between patients scheduled for neoadjuvant systemic treatment, adjuvant systemic treatment, and controls at the phylum (p = 0.471) and genus levels (p = 0.124). Conclusions: Intestinal microbiota richness, diversity, and composition are not different between postmenopausal breast cancer patients and controls. The increased relative abundance of Dialister and Veillonellaceae was observed in breast cancer patients scheduled for adjuvant treatment, which might be caused by a relative decrease in other bacteria due to prophylactic antibiotic administration rather than an absolute increase.
TGFβ Drives Metabolic Perturbations during Epithelial Mesenchymal Transition in Pancreatic Cancer: TGFβ Induced EMT in PDAC
Authors: Rajagopal Meena U. , Bansal Shivani , Kaur Prabhjit , Jain Shreyans K. , Altadil Tatiana , Hinzman Charles P. , Li Yaoxiang , Moulton Joanna , Singh Baldev , Bansal Sunil , Chauthe Siddheshwar Kisan , Singh Rajbir , Banerjee Partha P. , Mapstone Mark , Fiandaca Massimo S. , Federoff Howard J. , Unger Keith , Smith Jill P. , Cheema Amrita K.
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy wherein a majority of patients present metastatic disease at diagnosis. Although the role of epithelial to mesenchymal transition (EMT), mediated by transforming growth factor beta (TGFβ), in imparting an aggressive phenotype to PDAC is well documented, the underlying biochemical pathway perturbations driving this behaviour have not been elucidated. We used high-resolution mass spectrometry (HRMS) based molecular phenotyping approach in order to delineate metabolic changes concomitant to TGFβ-induced EMT in pancreatic cancer cells. Strikingly, we observed robust changes in amino acid and energy metabolism that may contribute to tumor invasion and metastasis. Somewhat unexpectedly, TGFβ treatment resulted in an increase in intracellular levels of retinoic acid (RA) that in turn resulted in increased levels of extracellular matrix (ECM) proteins including fibronectin (FN) and collagen (COL1). These findings were further validated in plasma samples obtained from patients with resectable pancreatic cancer. Taken together, these observations provide novel insights into small molecule dysregulation that triggers a molecular cascade resulting in increased EMT-like changes in pancreatic cancer cells, a paradigm that can be potentially targeted for better clinical outcomes.