bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning Forecasting for Supporting Terminal Operators in Port Business Development
Authors: Ferretti Marco , Fiore Ugo , Perla Francesca , Risitano Marcello , Scognamiglio Salvatore
Published: July 2022

Accurate forecasts of containerised freight volumes are unquestionably important for port terminal operators to organise port operations and develop business plans. They are also relevant for port authorities, regulators, and governmental agencies dealing with transportation. In a time when deep learning is in the limelight, owing to a consistent strip of success stories, it is natural to apply it to the tasks of forecasting container throughput. Given the number of options, practitioners can benefit from the lessons learned in applying deep learning models to the problem. Coherently, in this work, we devise a number of multivariate predictive models based on deep learning, analysing and assessing their performance to identify the architecture and set of hyperparameters that prove to be better suited to the task, also comparing the quality of the forecasts with seasonal autoregressive integrated moving average models. Furthermore, an innovative representation of seasonality is given by means of an embedding layer that produces a mapping in a latent space, with the parameters of such mapping being tuned using the quality of the predictions. Finally, we present some managerial implications, also putting into evidence the research limitations and future opportunities.
Length-Based Assessment Methods for the Conservation of a Pelagic Shark, Carcharhinus falciformis from the Tropical Pacific Ocean
Authors: Kindong Richard , Sarr Ousmane , Wu Feng , Tian Siquan
Published: July 2022

The silky shark, Carcharhinus falciformis is one of the most heavily exploited sharks, being the main by-catch species in both tuna longline and purse-seine fisheries in tropical waters worldwide. Despite this severe exploitation, little is known about the species’ life history and population status. Silky sharks, like many other sharks, exhibit slow growth and low fecundity, indicating the urgency of developing assessment studies to aid in the implementation of conservation plans for their stocks. Because information on the catch and effort of this species is scarce, some length-based data-limited methods were applied in the present study to provide estimates of the status of the tropical Pacific silky shark population. As evident from the LBSPR analysis, the current spawning potential ratio (SPR) was found to be below the target reference point of SPR 40% and slightly above the limit reference point of SPR 20%. In addition, the LBB model also confirmed that this stock’s status is overfished with relatively low biomass levels. Furthermore, both models showed estimates of size selectivity at 50% and 95% that were lower than the estimated size at sexual maturity. In conclusion, the data-limited models developed in this study indicated that the silky shark stock in the tropical Pacific Ocean may be at risk of further decline. Additionally, the results show that growth and recruitment overfishing may be occurring in the silky shark’s population calling for immediate intensification of monitoring programs for these sharks as a pre-requisite to develop efficient management and conservation plans in the Pacific Ocean.
Ultra-High-Energy Particles at the Border of Kerr Black Holes Triggered by Magnetocentrifugal Winds
Authors: Coimbra-Araújo Carlos H. , dos Anjos Rita C.
Published: July 2022

The source, origin, and acceleration mechanisms of ultra-high-energy cosmic rays (UHECR) (E>1020 eV, beyond the GZK limit) remain uncertain and unclear. The main explanations are associated with particular mechanisms, such as the Fermi mechanism, in which charged particles could be accelerated by clouds of magnetized gas moving within our Galaxy, or by the magnetic reconnection of field lines at, e.g., the core of high-energy astrophysical sources, where the topology of the magnetic field is rearranged and magnetic energy is converted into kinetic energy. However, the recent observation of extragalactic neutrinos may suggest that the source of UHECRs is likely an extragalactic supermassive black hole. In the present work, we propose that charged particles can be accelerated to ultrahigh energies in marginally bound orbits near extreme rotating black holes and could be triggered by collisions of magnetocentrifugal winds; the accretion disk surrounding the black hole would provide such winds. The ultra-high-energy process is governed by the frame-dragging effects of the black hole spacetime.
Evaluating the Effectiveness of Nanotechnology in Environmental Remediation of a Highly Metal-Contaminated Area—Minas Gerais, Brazil
Authors: Fonseca Rita , Araújo Joana , Pinho Catarina , Albuquerque Teresa
Published: July 2022

A column experiment at a laboratory level was carried out to assess the effect of the application of nanotechnology in the decontamination of soils and alluvial deposits with high levels of potentially toxic elements (PTEs). A suspension of zero-valent iron nanoparticles (nZVI) was injected at three different concentrations in selected samples (two sediments, one soil). For most of the elements, the retention by nZVI was proportional to the concentration of the suspension and the trend was similar. Metals were immobilized by adsorption on the surface layer of the nanoparticles and/or by complexation, co-precipitation, and chemical reduction. By day 60 following injection, the nZVI lost reactivity and the retained species were desorbed and back into the soluble phase. The definition of spatial patterns for PTEs’ distribution allowed for the construction of contamination risk maps using a geostatistical simulation approach. The analysis obtained from the extractable contents of five target elements (Zn, Cu, Cd, Pb, As) was cross-checked with the estimated map network to assess their retention efficiency. Data from the analysis of these elements, in the extractable phase and in the porewater of the sediments/soils, indicate the nZVI injection as a suitable technique for reducing the risk level of PTEs in contaminated Fe-rich tropical environments.
A Decade of Cave Drip Hydrographs Shows Spatial and Temporal Variability in Epikarst Storage and Recharge to Appalachian Karst Systems
Authors: Groce-Wright Nigel C. , Benton Joshua R. , Hammond Nicholas W. , Schreiber Madeline E.
Published: July 2022

We conducted recession analyses on cave drip hydrographs from a 10-year record (2008–2018) of three drip monitoring stations within James Cave (Pulaski County, VA, USA) to examine differences in hydrologic characteristics of the epikarst and quantify the storage volume of the epikarst feeding the drips. We used two recession analysis methods (correlation and matching strip) to calculate recession coefficients for multiple hydrographs at each site. Results show subtle differences between the three drip sites, suggestive of spatial heterogeneity in permeability and storage in the overlying epikarst. Storage volume calculations show that during the recharge season, up to 95% of recharge through the epikarst to the cave occurs through rapid pathways (i.e., fractures), and 5% of recharge occurs through diffuse pathways (i.e., pores). However, during the recession period, recharge through rapid pathways in the epikarst decreases and occurs predominantly through diffuse flow. Combined, these results underscore the importance of documenting spatial and temporal characterization of drip rates and other recharge inputs into karst systems.
Impact of Climate Change on Water Resources and Crop Production in Western Nepal: Implications and Adaptation Strategies
Authors: Risal Avay , Urfels Anton , Srinivasan Raghavan , Bayissa Yared , Shrestha Nirman , Paudel Gokul P. , Krupnik Timothy J.
Published: July 2022

Irrigation-led farming system intensification and efficient use of ground and surface water resources are currently being championed as a crucial ingredient for achieving food security and reducing poverty in Nepal. The potential scope and sustainability of irrigation interventions under current and future climates however remains poorly understood. Potential adaptation options in Western Nepal were analyzed using bias-corrected Regional Climate Model (RCM) data and the Soil and Water Assessment Tool (SWAT) model. The RCM climate change scenario suggested that average annual rainfall will increase by about 4% with occurrence of increased number and intensity of rainfall events in the winter. RCM outputs also suggested that average annual maximum temperature could decrease by 1.4 °C, and average annual minimum temperature may increase by 0.3 °C from 2021 to 2050. Similarly, average monthly streamflow volume could increase by about 65% from March–April, although it could decrease by about 10% in June. Our results highlight the tight hydrological coupling of surface and groundwater. Farmers making use of surface water for irrigation in upstream subbasins may inadvertently cause a decrease in average water availability in downstream subbasins at approximately 14%, which may result in increased need to abstract groundwater to compensate for deficits. Well-designed irrigated crop rotations that fully utilize both surface and groundwater conversely may increase groundwater levels by an average of 45 mm from 2022 to 2050, suggesting that in particular subbasins the cultivation of two crops a year may not cause long-term groundwater depletion. Modeled crop yield for the winter and spring seasons were however lower under future climate change scenarios, even with sufficient irrigation application. Lower yields were associated with shortened growing periods and high temperature stress. Irrigation intensification appears to be feasible if both surface and groundwater resources are appropriately targeted and rationally used. Conjunctive irrigation planning is required for equitable and year-round irrigation supply as neither the streamflow nor groundwater can provide full and year-round irrigation for intensified cropping systems without causing the degradation of natural resources.
Effect of Phase Change Materials and Phase Change Temperature on Optimization of Design Parameters of Anaerobic Reactor Thermal Insulation Structure
Authors: Zhen Feng , Pang Yuwan , Xing Tao , Zhang Hongqiong , Xu Yonghua , Li Wenzhe , Sun Yong
Published: July 2022

Direct-absorption anaerobic reactors can maintain the fermentation process of microorganisms by utilizing solar absorption and scattering media in the biogas reactor to improve the slurry temperature. Direct-absorption heating alone can save the corresponding electric energy and ensure the normal fermentation process of the biogas slurry in the reactor, but there is still the problem of temperature fluctuation. In order to improve the stability of the fermentation process, it is proposed to optimize the design of this kind of reactor by adding paraffin phase change material. This article mainly studies the influence of paraffin phase change material added on the top and side of the reactor in the fermentation process and gives the corresponding design parameters for different climatic conditions, which lays a theoretical reference for the design process of this kind of reactor.
Systematic Review of COVID-19-Related Physical Activity-Based Rehabilitations: Benefits to Be Confirmed by More Robust Methodological Approaches
Authors: Bailly Mélina , Pélissier Léna , Coudeyre Emmanuel , Evrard Bertrand , Bingula Rea , Rochette Corinne , Mériade Laurent , Blavignac Christelle , Fournier Anne-Cécile , Bignon Yves-Jean , Rannou Fabrice , Dutheil Frédéric , Thivel David , Duclos Martine
Published: July 2022

The first emergency was to receive and treat COVID-19 patients in their acute phase; today, there is a clear need to propose appropriate post-acute rehabilitation programs. The aim of this research was to systematically review the effects of physical activity programs in the recovery of post-COVID-19 patients. The literature search followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, was registered in the PROSPERO database (CRD42022289219), and was conducted between August and December 2021. A total of 35 studies out of the 1528 initially identified were finally included in the analysis. The systematic review clearly showed the health benefits of rehabilitation including physical activity in post-COVID-19 recovery, regardless of exercise modalities. These positive results were even observed using minor muscle re-mobilization for severe cases (i.e., postural changes, few steps—2 times/day) or using low volumes of exercise for mild-to-moderate cases (i.e., 120 min/week). A total of 97% of the 29 studies that performed statistical analyses demonstrated a significant increase in at least one parameter of functional capacity, and 96% of the 26 studies that statistically investigated the effects on the quality of life, mental health, and general state reported improvements. Yet, most of the studies were retrospective, uncontrolled, and enrolled aged people with comorbidities presented in severe forms of COVID-19. Physical activity programs, in addition to their high heterogeneity, remained poorly described in 83% of the studies and were part of a multidisciplinary program for 89% of the studies. Despite promising results, there is today a real need for prospective well-designed studies specifically assessing the effects of physical activity. In addition, it might appear relevant to propose standardized programs further considering the main characteristics of patients such as age, comorbidities, or the severity of COVID-19.
European Epidemiological Patterns of Cannabis- and Substance-Related Body Wall Congenital Anomalies: Geospatiotemporal and Causal Inferential Study
Authors: Reece Albert Stuart , Hulse Gary Kenneth
Published: July 2022

As body wall congenital anomalies (BWCAs) have a long history of being associated with prenatal or community cannabis exposure (CCE), it was of interest to investigate these epidemiological relationships in Europe given the recent increases in cannabis use prevalence, daily intensity, and Δ9-tetrahydrocannabinol (THC) potency. Methods: This study makes use of BWCA data from Eurocat, drug exposure data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Results: The mapping analysis showed that BWCARs increased in France, Spain, and the Netherlands. The bivariate mapping analysis showed that the BWCA rates (BWCAR) and the cannabis resin THC concentration rose simultaneously in France, the Netherlands, Bulgaria, Sweden, and Norway. The bivariate ranking of the BWCARs by median minimum E-value (mEV) was omphalocele > diaphragmatic hernia > abdominal wall defects > gastroschisis. With inverse probability weighted multivariable panel regression, the series of BWCAs, including gastroschisis, omphalocele, and diaphragmatic hernia, was positively related to various metrics of cannabis use from p = 2.45 × 10−14, 4.77 × 10−7 and <2.2 × 10−16. With geospatial regression, the same series of BWCAs was related to cannabis metrics from p = 0.0016, 5.28 × 10−6 and 4.88 × 10−9. Seventeen out of twenty-eight (60.7%) of the E-value estimates were >9 (high range), as were 14/28 (50.0%) of the mEVs. Conclusion: The data confirm the close relationship of the BWCARs with the metrics of CCE, fulfill the quantitative criteria of causal inference, and underscore the salience of the public health impacts of cannabinoid teratogenicity. Of major concern is the rising CCE impacting exponential cannabinoid genotoxic dose-response relationships. CCE should be carefully restricted to protect the food chain, the genome, and the epigenome of coming generations.
The Effects of the COVID-19 Pandemic in Oncology Patient Management
Authors: Forrester Mario , Breitenfeld Luiza , Castelo-Branco Miguel , Aperta Jorge
Published: July 2022

The COVID-19 pandemic has changed the way cancer patients should be managed. Using published literature on best practices on oncology patient management, we developed checklists to establish which recommendations were followed and differences between healthcare staff and institutions in a local health unit (overseeing two regional hospitals and 14 primary Healthcare Centers) in an interior region in Portugal. Checklists were delivered and completed by 15 physicians, 18 nurses and 5 pharmacists working at the Hospitals, and 29 physicians and 46 nurses from primary healthcare centers. Hospital staff do not show statistically significant differences regarding most proposed recommendations for the oncology clinical pathway, human resources, treatments, patient management and service management. Primary healthcare centers seem to follow a similar trend. As a local health unit, general recommendations for Oncology Patient Management show statistically significantly different values on education of suspected cases, identification, isolation procedures and samples collection; extension of work schedules; and education on cancer patient and COVID-19 positive referral procedures. All the checklists indicated good-to-high internal consistency. Our analysis showed cohesive work between groups regarding control and prevention of sources of infection; therefore, it is considered the highest priority to ensure that all other services, including oncology, continue functioning. Patient management measures such as adjustments in treatments, analysis, patient care, referrals and emergencies were not ranked higher by responders.
Non-Carcinogenic Health Risk Evaluation of Elevated Fluoride in Groundwater and Its Suitability Assessment for Drinking Purposes Based on Water Quality Index
Authors: Ullah Zahid , Xu Yifan , Zeng Xian-Chun , Rashid Abdur , Ali Asmat , Iqbal Javed , Almutairi Mikhlid H. , Aleya Lotfi , Abdel-Daim Mohamed M. , Shah Muddaser
Published: July 2022

Fluoride (F−) contamination in drinking groundwater is a significant human health risk in Pakistan. Moreover, high fluoride pollution in drinking water causes a variety of disorders, including dental, neurological, and skeletal fluorosis. The aim of this research was to evaluate the health risk of elevated fluoride in groundwater and its suitability assessment for drinking purposes. The total of (n = 37) samples were collected from community tube wells of Quetta Valley, Balochistan, Pakistan. The results show a mean pH value of 7.7, TDS of 404.6 mg/L, EC of 500 µs/cm, depth of 96.8 feet, and turbidity of 1.7 nephelometric turbidity units. The mean values of HCO3−, Ca2+, Mg2+, and Na+, were 289.5, 47.5, 30.6, and 283.3 mg/L, respectively. The mean values of SO42−, NO3−, K+, Cl−, and Fe2+, were 34.9, 1.0, 1.6, 25.6, and 0.01 mg/L, respectively. The F− concentration in the groundwater varied between 0.19 and 6.21, with a mean value of 1.8 mg/L, and 18 samples out of 37 were beyond the WHO recommended limit of 1.5 mg/L. The hydrochemical analysis results indicated that among the groundwater samples of the study area, 54% samples were Na-HCO3 type and 46% were mixed CaNaHCO3 type. The saturation indices of the mineral phases reveal that the groundwater sources of the study area were saturated with CaCO3 and halide minerals due to their positive (SI) values. Such minerals include calcite, dolomite, gypsum, and fluorite. The principal component analysis results reveal that the groundwater sources of the study area are contaminated due to geological and anthropogenic actions. The health risk assessment results of the F− concentrations show the ranges of ADDingestion for children, females, and males in the Quetta Valley, and their mean values were observed to be 0.093052, 0.068825, and 0.065071, respectively. The HQingestion mean values were 1.55086, 1.147089, and 1.084521 for children, females, and males, respectively. It was noticed that children had the highest maximum and average values of ADDingestion and HQingestion in the research area, indicating that groundwater fluoride intake poses the greatest health risk to children. The water quality index (WQI) analyses show that 44% of the samples belong to the poor-quality category, 49% were of good quality, and 8% of the samples of the study area belong to the excellent category.
Hypoxia in Aging and Aging-Related Diseases: Mechanism and Therapeutic Strategies
Authors: Wei Yaqin , Giunta Sergio , Xia Shijin
Published: July 2022

As the global aging process continues to lengthen, aging-related diseases (e.g., chronic obstructive pulmonary disease (COPD), heart failure) continue to plague the elderly population. Aging is a complex biological process involving multiple tissues and organs and is involved in the development and progression of multiple aging-related diseases. At the same time, some of these aging-related diseases are often accompanied by hypoxia, chronic inflammation, oxidative stress, and the increased secretion of the senescence-associated secretory phenotype (SASP). Hypoxia seems to play an important role in the process of inflammation and aging, but is often neglected in advanced clinical research studies. Therefore, we have attempted to elucidate the role played by different degrees and types of hypoxia in aging and aging-related diseases and their possible pathways, and propose rational treatment options based on such mechanisms for reference.
STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins
Authors: Rethi-Nagy Zsuzsanna , Abraham Edit , Udvardy Katalin , Klement Eva , Darula Zsuzsanna , Pal Margit , Katona Robert L. , Tubak Vilmos , Pali Tibor , Kota Zoltan , Sinka Rita , Udvardy Andor , Lipinszki Zoltan
Published: July 2022

The dynamic balance of transcriptional and translational regulation together with degron-controlled proteolysis shapes the ever-changing cellular proteome. While a large variety of degradation signals has been characterized, our knowledge of cis-acting protein motifs that can in vivo stabilize otherwise short-lived proteins is very limited. We have identified and characterized a conserved 13-mer protein segment derived from the p54/Rpn10 ubiquitin receptor subunit of the Drosophila 26S proteasome, which fulfills all the characteristics of a protein stabilization motif (STABILON). Attachment of STABILON to various intracellular as well as medically relevant secreted model proteins resulted in a significant increase in their cellular or extracellular concentration in mammalian cells. We demonstrate that STABILON acts as a universal and dual function motif that, on the one hand, increases the concentration of the corresponding mRNAs and, on the other hand, prevents the degradation of short-lived fusion proteins. Therefore, STABILON may lead to a breakthrough in biomedical recombinant protein production.
Insights into Domain Organization and Regulatory Mechanism of Cystathionine Beta-Synthase from Toxoplasma gondii
Authors: Conter Carolina , Fruncillo Silvia , Favretto Filippo , Fernández-Rodríguez Carmen , Dominici Paola , Martínez-Cruz Luis Alfonso , Astegno Alessandra
Published: July 2022

Cystathionine beta-synthase (CBS) is a key regulator of homocysteine metabolism. Although eukaryotic CBS have a similar domain architecture with a catalytic core and a C-terminal Bateman module, their regulation varies widely across phyla. In human CBS (HsCBS), the C-terminus has an autoinhibitory effect by acting as a cap that avoids the entry of substrates into the catalytic site. The binding of the allosteric modulator AdoMet to this region alleviates this cap, allowing the protein to progress from a basal toward an activated state. The same activation is obtained by artificial removal or heat-denaturation of the Bateman module. Recently, we reported the crystal structure of CBS from Toxoplasma gondii (TgCBS) showing that the enzyme assembles into basket-like dimers similar to the basal conformers of HsCBS. These findings would suggest a similar lid function for the Bateman module which, as in HsCBS, should relax in the absence of the C-terminal module. However, herein we demonstrate that, in contrast with HsCBS, removal of the Bateman module in TgCBS through deletion mutagenesis, limited proteolysis, or thermal denaturation has no effects on its activity, oligomerization, and thermal stability. This opposite behavior we have now found in TgCBS provides evidence of a novel type of CBS regulation.
Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model
Authors: Lee Su-Yel , Lee Min-Hyeok , Jo Seong-Kyeong , Yoo In-Ha , Sarankhuu Boler-Erdene , Kim Hyun-Jin , Kang Yea-Eun , Lee Seong-Eun , Kim Tae-Yeon , Park Moon-Hyang , Lee Choong-Sik , Han Seung-Yun , Moon Ji-Hyun , Jung Ju-Young , Hong Geum-Lan , Yoo Nam-Jeong , Yoon Eun-Sang , Choi Jae-Kyu , Won Ho-Ryun , Son Ji-Woong , Song Jae-Hwang
Published: July 2022

Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.
Exploring the Mechanism of Adjuvant Treatment of Glioblastoma Using Temozolomide and Metformin
Authors: Feng Shao-Wei , Chang Pei-Chi , Chen Hsuan-Yu , Hueng Dueng-Yuan , Li Yao-Feng , Huang Shih-Ming
Published: July 2022

Glioblastoma is the most frequent and lethal primary central nervous system tumor in adults, accounting for around 15% of intracranial neoplasms and 40–50% of all primary malignant brain tumors, with an annual incidence of 3–6 cases per 100,000 population. Despite maximum treatment, patients only have a median survival time of 15 months. Metformin is a biguanide drug utilized as the first-line medication in treating type 2 diabetes. Recently, researchers have noticed that metformin can contribute to antineoplastic activity. The objective of this study is to investigate the mechanism of metformin as a potential adjuvant treatment drug in glioblastoma. Glioblastoma cell lines U87MG, LNZ308, and LN229 were treated with metformin, and several cellular functions and metabolic states were evaluated. First, the proliferation capability was investigated using the MTS assay and BrdU assay, while cell apoptosis was evaluated using the annexin V assay. Next, a wound-healing assay and mesenchymal biomarkers (N-cadherin, vimentin, and Twist) were used to detect the cell migration ability and epithelial–mesenchymal transition (EMT) status of tumor cells. Gene set enrichment analysis (GSEA) was applied to the transcriptome of the metformin-treated glioblastoma cell line. Then, DCFH-DA and MitoSOX Red dyes were used to quantify reactive oxygen species (ROS) in the cytosol and mitochondria. JC-1 dye and Western blotting analysis were used to evaluate mitochondrial membrane potential and biogenesis. In addition, the combinatory effect of temozolomide (TMZ) with metformin treatment was assessed by combination index analysis. Metformin could decrease cell viability, proliferation, and migration, increase cell apoptosis, and disrupt EMT in all three glioblastoma cell lines. The GSEA study highlighted increased ROS and hypoxia in the metformin-treated glioblastoma cells. Metformin increased ROS production, impaired mitochondrial membrane potential, and reduced mitochondrial biogenesis. The combined treatment of metformin and TMZ had U87 as synergistic, LNZ308 as antagonistic, and LN229 as additive. Metformin alone or combined with TMZ could suppress mitochondrial transcription factor A, Twist, and O6-methylguanine-DNA methyltransferase (MGMT) proteins in TMZ-resistant LN229 cells. In conclusion, our study showed that metformin decreased metabolic activity, proliferation, migration, mitochondrial biogenesis, and mitochondrial membrane potential and increased apoptosis and ROS in some glioblastoma cells. The sensitivity of the TMZ-resistant glioblastoma cell line to metformin might be mediated via the suppression of mitochondrial biogenesis, EMT, and MGMT expression. Our work provides new insights into the choice of adjuvant agents in TMZ-resistant GBM therapy.
Alternatively Spliced Isoforms of the P2X7 Receptor: Structure, Function and Disease Associations
Authors: De Salis Sophie K. F. , Li Lanxin , Chen Zheng , Lam Kam Wa , Skarratt Kristen K. , Balle Thomas , Fuller Stephen J.
Published: July 2022

The P2X7 receptor (P2X7R) is an ATP-gated membrane ion channel that is expressed by multiple cell types. Following activation by extracellular ATP, the P2X7R mediates a broad range of cellular responses including cytokine and chemokine release, cell survival and differentiation, the activation of transcription factors, and apoptosis. The P2X7R is made up of three P2X7 subunits that contain specific domains essential for the receptor’s varied functions. Alternative splicing produces P2X7 isoforms that exclude one or more of these domains and assemble in combinations that alter P2X7R function. The modification of the structure and function of the P2X7R may adversely affect cellular responses to carcinogens and pathogens, and alternatively spliced (AS) P2X7 isoforms have been associated with several cancers. This review summarizes recent advances in understanding the structure and function of AS P2X7 isoforms and their associations with cancer and potential role in modulating the inflammatory response.
Biomedical Polyurethanes for Anti-Cancer Drug Delivery Systems: A Brief, Comprehensive Review
Authors: Sobczak Marcin , Kędra Karolina
Published: July 2022

With the intensive development of polymeric biomaterials in recent years, research using drug delivery systems (DDSs) has become an essential strategy for cancer therapy. Various DDSs are expected to have more advantages in anti-neoplastic effects, including easy preparation, high pharmacology efficiency, low toxicity, tumor-targeting ability, and high drug-controlled release. Polyurethanes (PUs) are a very important kind of polymers widely used in medicine, pharmacy, and biomaterial engineering. Biodegradable and non-biodegradable PUs are a significant group of these biomaterials. PUs can be synthesized by adequately selecting building blocks (a polyol, a di- or multi-isocyanate, and a chain extender) with suitable physicochemical and biological properties for applications in anti-cancer DDSs technology. Currently, there are few comprehensive reports on a summary of polyurethane DDSs (PU-DDSs) applied for tumor therapy. This study reviewed state-of-the-art PUs designed for anti-cancer PU-DDSs. We studied successful applications and prospects for further development of effective methods for obtaining PUs as biomaterials for oncology.
Genome-Wide Identification, Characterization, and Expression Analysis Related to Low-Temperature Stress of the CmGLP Gene Family in Cucumis melo L.
Authors: Zhang Zhengda , Wen Yongshuai , Yuan Luqiao , Zhang Yuhui , Liu Jingyi , Zhou Fan , Wang Qunning , Hu Xiaohui
Published: July 2022

Germin-like protein (GLP) participates in plant growth and development and plays an important role in plant stress. In the present study, 22 CmGLPs belonging to five classes were identified in the melon genome. Each member of the CmGLPs family contains a typical Cupin_1 domain. We conducted a genome-wide analysis of the melon GLP gene family characterization. CmGLPs were randomly distributed in the melon chromosomes, with the largest number on chromosome 8, having eight family members. Gene duplication events drive the evolution and expansion of the melon GLP gene family. Based on the phylogenetic tree analysis of GLP proteins in melon, rice, Arabidopsis, and cucumber, it was found that the GLP gene families of different species have diverged in evolution. Based on qRT-PCR results, all members of the CmGLP gene family could be expressed in different tissues of melon. Most CmGLP genes were up-regulated after low-temperature stress. The relative expression of CmGLP2-5 increased by 157.13 times at 48 h after low-temperature treatment. This finding suggests that the CmGLP2-5 might play an important role in low-temperature stress in melon. Furthermore, quantitative dual LUC assays indicated that CmMYB23 and CmWRKY33 can bind the promoter fragment of the CmGLP2-5. These results were helpful in understanding the functional succession and evolution of the melon GLP gene family and further revealed the response of CmGLPs to low-temperature stress in melon.
Putrescine Intensifies Glu/GABA Exchange Mechanism and Promotes Early Termination of Seizures
Authors: Kovács Zsolt , Skatchkov Serguei N. , Szabó Zsolt , Qahtan Saif , Méndez-González Miguel P. , Malpica-Nieves Christian J. , Eaton Misty J. , Kardos Julianna , Héja László
Published: July 2022

Endogenous anticonvulsant mechanisms represent a reliable and currently underdeveloped strategy against recurrent seizures and may recall novel original therapeutics. Here, we investigated whether the intensification of the astroglial Glu-GABA exchange mechanism by application of the GABA precursor putrescine (PUT) may be effective against convulsive and non-convulsive seizures. We explored the potential of PUT to inhibit spontaneous spike-and-wave discharges (SWDs) in WAG/Rij rats, a genetic model of absence epilepsy. Significant shortening of SWDs in response to intraperitoneally applied PUT has been observed, which could be antagonized by blocking GAT-2/3-mediated astrocytic GABA release with the specific inhibitor SNAP-5114. Direct application of exogenous GABA also reduced SWD duration, suggesting that PUT-triggered astroglial GABA release through GAT-2/3 may be a critical step in limiting seizure duration. PUT application also dose-dependently shortened seizure-like events (SLEs) in the low-[Mg2+] in vitro model of temporal lobe epilepsy. SNAP-5114 reversed the antiepileptic effect of PUT in the in vitro model as well, further confirming that PUT reduces seizure duration by triggering glial GABA release. In accordance, we observed that PUT specifically reduces the frequency of excitatory synaptic potentials, suggesting that it specifically acts at excitatory synapses. We also identified that PUT specifically eliminated the tonic depolarization-induced desynchronization of SLEs. Since PUT is an important source of glial GABA and we previously showed significant GABA release, it is suggested that the astroglial Glu-GABA exchange mechanism plays a key role in limiting ictal discharges, potentially opening up novel pathways to control seizure propagation and generalization.
Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models
Authors: Rupp Tristan , Debasly Solène , Genest Laurie , Froget Guillaume , Castagné Vincent
Published: July 2022

New therapies are required for patients with non-small cell lung cancer (NSCLC) for which the current standards of care poorly affect the patient prognosis of this aggressive cancer subtype. In this preclinical study, we aim to investigate the efficacy of Fingolimod, a described inhibitor of sphingosine-1-phosphate (S1P)/S1P receptors axis, and Dimethyl Fumarate (DMF), a methyl ester of fumaric acid, both already approved as immunomodulators in auto-immune diseases with additional expected anti-cancer effects. The impact of both drugs was analyzed with in vitro cell survival analysis and in vivo graft models using mouse and human NSCLC cells implanted in immunocompetent or immunodeficient mice, respectively. We demonstrated that Fingolimod and DMF repressed tumor progression without apparent adverse effects in vivo in three preclinical mouse NSCLC models. In vitro, Fingolimod did not affect either the tumor proliferation or the cytotoxicity, although DMF reduced tumor cell proliferation. These results suggest that Fingolimod and DMF affected tumor progression through different cellular mechanisms within the tumor microenvironment. Fingolimod and DMF might uncover potential therapeutic opportunities in NSCLC.
A Proteomic Platform Unveils the Brain Glycogen Phosphorylase as a Potential Therapeutic Target for Glioblastoma Multiforme
Authors: Ferraro Giusy , Mozzicafreddo Matteo , Ettari Roberta , Corsi Lorenzo , Monti Maria Chiara
Published: July 2022

In the last few years, several efforts have been made to identify original strategies against glioblastoma multiforme (GBM): this requires a more detailed investigation of the molecular mechanism of GBM so that novel targets can be identified for new possible therapeutic agents. Here, using a combined biochemical and proteomic approach, we evaluated the ability of a blood–brain barrier-permeable 2,3-benzodiazepin-4-one, called 1g, to interfere with the activity and the expression of brain glycogen phosphorylase (PYGB) on U87MG cell line in parallel with the capability of this compound to inhibit the cell growth and cycle. Thus, our results highlighted PYGB as a potential therapeutic target in GBM prompting 1g as a capable anticancer drug thanks to its ability to negatively modulate the uptake and metabolism of glucose, the so-called “Warburg effect”, whose increase is considered a common feature of cancer cells in respect of their normal counterparts.
Field-Induced Single Molecule Magnetic Behavior of Mononuclear Cobalt(II) Schiff Base Complex Derived from 5-Bromo Vanillin
Authors: Elemo Fikre , Schlittenhardt Sören , Sani Taju , Rajnák Cyril , Linert Wolfgang , Boča Roman , Thomas Madhu , Ruben Mario
Published: July 2022

A mononuclear Co(II) complex of a Schiff base ligand derived from 5-Bromo-vanillin and 4-aminoantipyrine, that has a compressed tetragonal bipyramidal geometry and exhibiting field-induced slow magnetic relaxation, has been synthesized and characterized by single crystal X-ray diffraction, elemental analysis and molecular spectroscopy. In the crystal packing, a hydrogen-bonded dimer structural topology has been observed with two distinct metal centers having slightly different bond parameters. The complex has been further investigated for its magnetic nature on a SQUID magnetometer. The DC magnetic data confirm that the complex behaves as a typical S = 3/2 spin system with a sizable axial zero-field splitting parameter D/hc = 38 cm−1. The AC susceptibility data reveal that the relaxation time for the single-mode relaxation process is τ = 0.16(1) ms at T = 2.0 K and BDC = 0.12 T.
Analysing Complex Problem-Solving Strategies from a Cognitive Perspective: The Role of Thinking Skills
Authors: Wu Hao , Molnár Gyöngyvér
Published: July 2022

Complex problem solving (CPS) is considered to be one of the most important skills for successful learning. In an effort to explore the nature of CPS, this study aims to investigate the role of inductive reasoning (IR) and combinatorial reasoning (CR) in the problem-solving process of students using statistically distinguishable exploration strategies in the CPS environment. The sample was drawn from a group of university students (N = 1343). The tests were delivered via the eDia online assessment platform. Latent class analyses were employed to seek students whose problem-solving strategies showed similar patterns. Four qualitatively different class profiles were identified: (1) 84.3% of the students were proficient strategy users, (2) 6.2% were rapid learners, (3) 3.1% were non-persistent explorers, and (4) 6.5% were non-performing explorers. Better exploration strategy users showed greater development in thinking skills, and the roles of IR and CR in the CPS process were varied for each type of strategy user. To sum up, the analysis identified students’ problem-solving behaviours in respect of exploration strategy in the CPS environment and detected a number of remarkable differences in terms of the use of thinking skills between students with different exploration strategies.
Bowel Preparation and Subsequent Colonoscopy Is Associated with the Risk of Atrial Fibrillation: A Population-Based Case-Crossover Study
Authors: Jung Yoon Suk , Jee Yongho , Im Eui , Kim Min-ho , Moon Chang Mo
Published: July 2022

This study aimed to clarify the association of the risk of atrial fibrillation (AF) with bowel preparation and subsequent colonoscopy through population-based case-crossover analysis. Patients who developed new-onset AF after undergoing colonoscopy following bowel preparation were included. For each patient, one hazard period and four control periods were matched at specified time windows. Among 189,613 patients with AF, 84 patients (mean age: 72.4 years) finally met the inclusion criteria. Most patients used polyethylene glycol (PEG)-based solutions (2 L PEG + ascorbic acid (n = 56), 4 L PEG (n = 21)) as purgatives and had hypertension (n = 75). A significant association of bowel preparation and colonoscopy with AF occurrence was found in all time windows. The proportion of patients with bowel preparation and colonoscopy was higher during the hazard period than during the control periods. In the 1-, 2-, 4-, 8-, and 12-week time windows, the proportions were 11.9% vs. 4.2%, 13.1% vs. 4.8%, 16.7% vs. 6.3%, 28.6% vs. 11.9%, and 29.8% vs. 14.0%, and the odd ratios (ORs) were 3.11, 3.01, 3.00, 2.96, and 2.61, respectively. Bowel preparation and undergoing colonoscopy was associated with the risk of AF and this examination need to be performed with caution especially in elderly patients with hypertension.
Prospective Evaluation of Intraorbital Soft Tissue Atrophy after Posttraumatic Bone Reconstruction: A Risk Factor for Enophthalmos
Authors: Dinu Cristian , Tamas Tiberiu , Agrigoroaei Gabriela , Stoia Sebastian , Opris Horia , Bran Simion , Armencea Gabriel , Manea Avram
Published: July 2022

Orbital fractures are a common finding in facial trauma, and serious complications may arise when orbital reconstruction is not performed properly. The virtual planning can be used to print stereolithographic models or to manufacture patient-specific titanium orbital implants (PSIs) through the process of selective laser melting. This method is currently considered the most accurate technique for orbital reconstruction. Even with the most accurate techniques of bone reconstruction, there are still situations where enophthalmos is present postoperatively, and it may be produced by intraorbital soft tissue atrophy. The aim of this paper was to evaluate the orbital soft tissue after posttraumatic reconstruction of the orbital walls’ fractures. Ten patients diagnosed and treated for unilateral orbital fractures were included in this prospective study. A postoperative CT scan of the head region with thin slices (0.6 mm) and soft and bone tissue windows was performed after at least 6 months. After data processing, the STL files were exported, and the bony volume, intraorbital fat tissue volume, and the muscular tissue volume were measured. The volumes of the reconstructed orbit tissues were compared with the volumes of the healthy orbit tissues for each patient. Our findings conclude that a higher or a lower grade of fat and muscular tissue loss is present in all cases of reconstructed orbital fractures. This can stand as a guide for primary or secondary soft tissue augmentation in orbital reconstruction.
Why Advertise on Short Video Platforms? Optimizing Online Advertising Using Advertisement Quality
Authors: Li Weifeng , Jiang Minghui , Zhan Wentao
Published: July 2022

The emergence of short videos has provided a new way for advertisers to place online video advertisements. On short video platforms, the quality of advertisements is the main factor that attracts consumers. This study constructs a model based on advertisers’ advertising behavior and formulates their optimal advertising quality strategies. We then expand on the quality strategy by considering advertisers’ pricing factors. In addition, we compare advertisement placement on short video platforms and on general video platforms and analyze how advertisers should choose their advertisement placement strategies. Our research shows that advertisers should improve the quality of their advertisements to gain more profit when the platform is operating well, so that users become more willing to buy and products become more profitable. In addition, advertisers should present their advertisements in the shortest possible duration and show them after a longer program. Users’ price sensitivity negatively affects advertisers’ optimal advertising quality strategies and profits. Furthermore, advertisers’ choice of platform mainly depends on the advertising nuisance cost to users and the platform’s cost of entry. Finally, we find an optimal budget allocation scheme for small companies joining short video platforms to invest in bidding and designing advertisements.
High-Temperature Oxidation Behavior of Cr-Ni-Mo Hot-Work Die Steels
Authors: Zhang Yuqi , Zhang Cheng , Li Fei , Wang Zhou , Wang Xiaodong , Wang Changji , Zhang Cheng , Huang Jinfeng , Mao Feng , Chen Chong , Jiang Tao , Wei Shizhong , Xiong Mei , Hu Jinmeng
Published: July 2022

The oxidation of 3Cr3Mo2NiW and 3CrNi3Mo steels was studied at 600 °C in air, and the test results suggest that the parabolic rate law fitted the oxidation kinetics of both steels. The microstructure, morphology, structure, and phase composition of the oxide film cross-sectional layers of the two Cr-Ni-Mo hot-work die steels were analyzed using scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), and X-ray diffraction (XRD). The influences of Cr, Ni, and Mo on the high-temperature oxidation resistance of the two Cr-Ni-Mo hot-work die steels are discussed, and the oxidation mechanism is summarized. Heat-treated samples were analyzed using electron backscattered diffraction (EBSD) to obtain inverse pole figures (IPFs) and average sample grain sizes, and the percentages of twin grain boundaries (TGBs) (θ = 60°) were also measured. After heat treatment, recrystallization was observed in both steels with a large portion of twin grain boundaries. After 10 h of oxidation, the dense chromium-rich oxide layer that formed in the inner oxide layer of 3Cr3Mo2NiW steel effectively prevented the continuation of oxidation. The inner oxide layer in 3CrNi3Mo steel formed an adhesion layer with a network structure composed mainly of Ni- and Cr-rich spinel oxide, without forming a barrier to prevent oxidation.