bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Urban Population Density Distribution and Land Use in Guangzhou, China: A Spatial Spillover Perspective
Authors: Peng Yisheng , Liu Jiahui , Zhang Tianyao , Li Xiangyang
Published: November 2021

Urban population density distribution contributes towards a deeper understanding of peoples’ activities patterns and urban vibrancy. The associations between the distribution of urban population density and land use are crucial to improve urban spatial structure. Despite numerous studies on population density distribution and land use, the significance of spatial dependence has attained less attention. Based on the Baidu heat map data and points of interests data in the main urban zone of Guangzhou, China, the current paper first investigated the spatial evolution and temporal distribution characteristics of urban population density and examined the spatial spillover influence of land use on it through spatial correlation analysis methods and the spatial Durbin model. The results show that the urban population density distribution is characterized by aggregation in general and varies on weekends and weekdays. The changes in population density within a day present a trend of “rapid growth-gentle decline-rapid growth-rapid decline”. Furthermore, the spatial spillover effects of land use exist and play the same important roles in population density distribution as the direct effects. Additionally, different types of land use show diverse direct effects and spatial spillover effects at various times. These findings suggest that balancing the population density distribution should consider the indirect effect from neighboring areas, which hopefully provide implications for urban planners and policy makers in utilizing the rational allocation of public resources and regarding optimization of urban spatial structure.
Analysis of Relationship between Electroencephalograms and Subjective Measurements for In-Vehicle Information System: A Preliminary Study
Authors: Kim Nahyeong , Choe Mungyeong , Park Jaehyun , Park Jungchul , Kim Hyun K. , Kim Jungyoon , Hussain Muhammad , Jung Suhwan
Published: November 2021

In this study, we explored the relationship between objective and subjective measures for usability evaluation in in-vehicle infotainment systems (IVISs). As a case study, four displays were evaluated based on cluster location and display orientation (that is, front–horizontal, front–vertical, right–horizontal, and right–vertical). Thirty-six participants performed tasks to manipulate the functions of the IVISs and data were collected through an electroencephalogram (EEG) sensor and questionnaire items. We analysed a model that estimated EEG-based objective indicators from subjective indicators. As a result, the objective indicators reflected the subjective indicators and were considered to explain the driver’s cognitive state. Although EEG data were collected from only four participants, this study proposed an experimental design that could be applied to the analysis of the relationship between the subject’s evaluation and EEG signals, as a preliminary study. We expect the experimental design and results of this study to be useful in analysing objective and subjective measures of usability evaluation.
Spatial Modelling of Kaolin Deposit Demonstrated on the Jimlíkov-East Deposit, Karlovy Vary, Czech Republic
Authors: Jarošová Marcela , Staněk František
Published: November 2021

The present study is focused on spatial modelling of a kaolin deposit in Karlovy Vary, Czech Republic, and the methodical procedure of development, evaluation and visualization of a 3D model are described step by step. The implementation of this methodology is performed in Visual Studio 2019 with use of the Surfer and Voxler objects from Golden Software. This methodology combined with the newly developed software (Kaolin_A and Kaolin_Viz programs) allow a user to create a variant dynamic model for the same or similar types of deposits. It enables a quick update of the model when changing the input data, based on the new mining exploration or when changing the modelling parameters. The presented approach leads to a more advanced evaluation of deposits, including various estimates of reserves according to pre-specified usability conditions. The efficiency of the developed methodology and the software for the evaluation of the deposit are demonstrated on the kaolin deposit Jimlíkov-East, located near the village Jimlíkov about 5 km west of Karlovy Vary in the Czech Republic.
Targeting PI3K/Akt/mTOR Pathway by Different Flavonoids: A Cancer Chemopreventive Approach
Authors: Zughaibi Torki A. , Suhail Mohd , Tarique Mohammad , Tabrez Shams
Published: November 2021

Cancer is, globally, one of the main causes of death. Even though various therapies are available, they are still painful because of their adverse side effects. Available treatments frequently fail due to unpromising responses, resistance to classical anticancer drugs, radiation therapy, chemotherapy, and low accessibility to tumor tissues. Developing novel strategies to minimize adverse side effects, improve chemotherapy sensitivity, and control cancer progression is needed. Many studies have suggested small dietary molecules as complementary treatments for cancer patients. Different components of herbal/edible plants, known as flavonoids, have recently garnered attention due to their broad biological properties (e.g., antioxidant, antiviral, antimicrobial, anti-inflammatory, anti-mutagenic, anticancer, hepatoprotective, and cardioprotective). These flavonoids have shown anticancer activity by affecting different signaling cascades. This article summarizes the key progress made in this area and discusses the role of flavonoids by specifically inhibiting the PI3K/Akt/mTOR pathway in various cancers.
Significance of GABAA Receptor for Cognitive Function and Hippocampal Pathology
Authors: Sakimoto Yuya , Oo Paw Min-Thein , Goshima Makoto , Kanehisa Itsuki , Tsukada Yutaro , Mitsushima Dai
Published: November 2021

The hippocampus is a primary area for contextual memory, known to process spatiotemporal information within a specific episode. Long-term strengthening of glutamatergic transmission is a mechanism of contextual learning in the dorsal cornu ammonis 1 (CA1) area of the hippocampus. CA1-specific immobilization or blockade of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor delivery can impair learning performance, indicating a causal relationship between learning and receptor delivery into the synapse. Moreover, contextual learning also strengthens GABAA (gamma-aminobutyric acid) receptor-mediated inhibitory synapses onto CA1 neurons. Recently we revealed that strengthening of GABAA receptor-mediated inhibitory synapses preceded excitatory synaptic plasticity after contextual learning, resulting in a reduced synaptic excitatory/inhibitory (E/I) input balance that returned to pretraining levels within 10 min. The faster plasticity at inhibitory synapses may allow encoding a contextual memory and prevent cognitive dysfunction in various hippocampal pathologies. In this review, we focus on the dynamic changes of GABAA receptor mediated-synaptic currents after contextual learning and the intracellular mechanism underlying rapid inhibitory synaptic plasticity. In addition, we discuss that several pathologies, such as Alzheimer’s disease, autism spectrum disorders and epilepsy are characterized by alterations in GABAA receptor trafficking, synaptic E/I imbalance and neuronal excitability.
Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions
Authors: Hassan Faiz-ul , Nadeem Asif , Li Zhipeng , Javed Maryam , Liu Qingyou , Azhar Jahanzaib , Rehman Muhammad Saif-ur , Cui Kuiqing , Rehman Saif ur
Published: November 2021

Peroxisome proliferator-activated receptors (PPARs) are the nuclear receptors that could mediate the nutrient-dependent transcriptional activation and regulate metabolic networks through energy homeostasis. However, these receptors cannot work properly under metabolic stress. PPARs and their subtypes can be modulated by nutrigenomic interventions, particularly under stress conditions to restore cellular homeostasis. Many nutrients such as polyunsaturated fatty acids, vitamins, dietary amino acids and phytochemicals have shown their ability for potential activation or inhibition of PPARs. Thus, through different mechanisms, all these nutrients can modulate PPARs and are ultimately helpful to prevent various metabolic disorders, particularly in transition dairy cows. This review aims to provide insights into the crucial role of PPARs in energy metabolism and their potential modulation through nutrigenomic interventions to improve energy homeostasis in dairy animals.
Chemical Exposures Affect Innate Immune Response to SARS-CoV-2
Authors: Arowolo Olatunbosun , Pobezinsky Leonid , Suvorov Alexander
Published: November 2021

Severe outcomes of COVID-19 are associated with pathological response of the immune system to the SARS-CoV-2 infection. Emerging evidence suggests that an interaction may exist between COVID-19 pathogenesis and a broad range of xenobiotics, resulting in significant increases in death rates in highly exposed populations. Therefore, a better understanding of the molecular basis of the interaction between SARS-CoV-2 infection and chemical exposures may open opportunities for better preventive and therapeutic interventions. We attempted to gain mechanistic knowledge on the interaction between SARS-CoV-2 infection and chemical exposures using an in silico approach, where we identified genes and molecular pathways affected by both chemical exposures and SARS-CoV-2 in human immune cells (T-cells, B-cells, NK-cells, dendritic, and monocyte cells). Our findings demonstrate for the first time that overlapping molecular mechanisms affected by a broad range of chemical exposures and COVID-19 are linked to IFN type I/II signaling pathways and the process of antigen presentation. Based on our data, we also predict that exposures to various chemical compounds will predominantly impact the population of monocytes during the response against COVID-19.
Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway
Authors: Nallasamy Palanisamy , Kang Zi Yae , Sun Xiaolun , Anandh Babu Pon Velayutham , Liu Dongmin , Jia Zhenquan
Published: November 2021

Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1 μm suppressed TNF-α-induced monocyte adhesion to human EA.hy926 endothelial cells (ECs), a key event in the initiation and development of atherosclerosis. Low concentrations of resveratrol (0.25–2 μm) also significantly attenuated TNF-α-stimulated mRNA expressions of MCP-1/CCL2 and ICAM-1, which are vital mediators of EC-monocyte adhesion molecules and cytokines for cardiovascular plaque formation. Additionally, resveratrol diminished TNF-α-induced IκB-α degradation and subsequent nuclear translocation of NF-κB p65 in ECs. In the animal study, resveratrol supplementation in diet significantly diminished TNF-α-induced increases in circulating levels of adhesion molecules and cytokines, monocyte adhesion to mouse aortic ECs, F4/80-positive macrophages and VCAM-1 expression in mice aortas and restored the disruption in aortic elastin fiber caused by TNF-α treatment. The animal study also confirmed that resveratrol blocks the activation of NF-κB In Vivo. In conclusion, resveratrol at physiologically achievable concentrations displayed protective effects against TNF-α-induced vascular endothelial inflammation in vitro and In Vivo. The ability of resveratrol in reducing inflammation may be associated with its role as a down-regulator of the NF-κB pathway.
HLA-G Is Widely Expressed by Mast Cells in Regions of Organ Fibrosis in the Liver, Lung and Kidney
Authors: Mouchet Nicolas , Vu Nicolas , Turlin Bruno , Rioux-Leclercq Nathalie , Jouneau Stéphane , Samson Michel , Amiot Laurence
Published: November 2021

We previously demonstrated that mast cells expressing HLA-G are associated with regions of hepatitis C virus-induced liver fibrosis. Here, we aimed to determine whether HLA-G expression in mast cells is specific to viral etiology, the liver, or to the general process of fibrosis. We enumerated HLA-G+ cells and mast cells by the immunohistochemistry of (i) liver blocks from 41 cases of alcoholic cirrhosis, (ii) 10 of idiopathic pulmonary fibrosis (IPF), and (iii) 10 of renal fibrosis. The nature of the HLA-G+ cells was specified by multiplex immunofluorescence using software. More than half of all HLA-G+ cells were mast cells in fibrotic areas of alcoholic cirrhosis and IPF. In the kidneys, subjected to fibrosis, the HLA-G+ cells were indeed mast cells but could not be counted. Moreover, in certain cases of the liver and lung, we observed a number of cellular nodes, which were secondary or tertiary follicles, in which HLA-G was highly expressed by B lymphocytes. In conclusion, HLA-G+ mast cells could be observed in the fibrotic regions of all organs studied. Previous studies suggest a protective role for HLA-G+ mast cells against inflammation and fibrosis. The observed follicles with B lymphocytes that express HLA-G may also reinforce their antifibrotic role.
Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation
Authors: Southey Bruce R. , Keever-Keigher Marissa R. , Rymut Haley E. , Rund Laurie A. , Johnson Rodney W. , Rodriguez-Zas Sandra L.
Published: November 2021

The inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and exposure to additional stressors later in life. The objectives of this study were to investigate the disruption of alternative splicing patterns associated with MIA in the offspring’s amygdala and characterize this disruption in the context of the second stress of weaning and sex. Differential alternative splicing was tested on the RNA-seq profiles of a pig model of viral-induced MIA. Compared to controls, MIA was associated with the differential alternative splicing (FDR-adjusted p-value < 0.1) of 292 and 240 genes in weaned females and males, respectively, whereas 132 and 176 genes were differentially spliced in control nursed female and male, respectively. The majority of the differentially spliced (FDR-adjusted p-value < 0.001) genes (e.g., SHANK1, ZNF672, KCNA6) and many associated enriched pathways (e.g., Fc gamma R-mediated phagocytosis, non-alcoholic fatty liver disease, and cGMP-PKG signaling) have been reported in MIA-related disorders including autism and schizophrenia in humans. Differential alternative splicing associated with MIA was detected in the gene MAG across all sex-stress groups except for unstressed males and SLC2A11 across all groups except unstressed females. Precise understanding of the effect of MIA across second stressors and sexes necessitates the consideration of splicing isoform profiles.
Risk Factors When Implementing ERP Systems in Small Companies
Authors: Svensson Ann , Thoss Alexander
Published: November 2021

Implementation of enterprise resource planning (ERP) systems often aims to improve the companies’ processes in order to gain competitive advantage on the market. Especially, small companies need to integrate systems with suppliers and customers; hence, ERP systems often become a requirement. ERP system implementation processes in small enterprises contain several risk factors. Research has concluded that ERP implementation projects fail to a relatively high degree. Small companies are found to be constrained by limited resources, limited IS (information systems) knowledge and lack of IT expertise in ERP implementation. There are relatively few empirical research studies on implementing ERP systems in small enterprises and there is a large gap in research that could guide managers of small companies. This paper is based on a case study of three small enterprises that are planning to implement ERP systems that support their business processes. The aim of the paper is to identify the risk factors that can arise when implementing ERP systems in small enterprises. The analysis shows that an ERP system is a good solution to avoid using many different, separate systems in parallel. However, the study shows that it is challenging to integrate all systems used by suppliers and customers. An ERP system can include all information in one system and all information can also easily be accessed within that system. However, the implementation could be a demanding process as it requires engagement from all involved people, especially the managers of the companies.
The Use of ICT for Communication between Teachers and Students in the Context of Higher Education Institutions
Authors: Batista João , Santos Helena , Marques Rui Pedro
Published: November 2021

Recently, the communication paradigm has been changing in society in the higher education context because of the ease of access to the Internet and the high number of mobile devices. Thus, universities have increased their interest in accepting different and sophisticated communication technologies to improve student participation in the educational process. This study aimed to assess how students and teachers use communication technologies to communicate with each other and what their expectations, satisfaction, and attitudes regarding the results of this use are. An analysis model was used in a case study at the University of Aveiro to support the study. Data were obtained through an online questionnaire, which collected 570 responses from students and 172 responses from teachers. These data were processed through descriptive statistics techniques and inference tests (t-tests). The primary outcomes are that publishing and sharing technologies and electronic mail are the most commonly used communication technologies by students and teachers, suggesting that their use will not decline soon. However, other communication technologies were also revealed to be widely used and accepted, with excellent levels of confirmation of expectation.
Personalized Advertising Computational Techniques: A Systematic Literature Review, Findings, and a Design Framework
Authors: Viktoratos Iosif , Tsadiras Athanasios
Published: November 2021

This work conducts a systematic literature review about the domain of personalized advertisement, and more specifically, about the techniques that are used for this purpose. State-of-the-art publications and techniques are presented in detail, and the relationship of this domain with other related domains such as artificial intelligence (AI), semantic web, etc., is investigated. Important issues such as (a) business data utilization in personalized advertisement models, (b) the cold start problem in the domain, (c) advertisement visualization issues, (d) psychological factors in the personalization models, (e) the lack of rich datasets, and (f) user privacy are highlighted and are pinpointed to help and inspire researchers for future work. Finally, a design framework for personalized advertisement systems has been designed based on these findings.
Diagnostic Reliability in the Assessment of Degradation in Precast Concrete Elements
Authors: Bossio Antonio , Faella Giuseppe , Frunzio Giorgio , Guadagnuolo Mariateresa , Serpieri Roberto
Published: November 2021

In the past century, precast reinforced concrete has become the most widely used construction material in infrastructure engineering, especially for long-span structures. Nowadays, a growing research area concerns the assessment of concrete strength degradation due to environmental exposure and reinforcement corrosion. This paper reports an experimental campaign on some prefabricated concrete elements that were exposed to atmospheric agents for approximately 20 years. The campaign took the uncommon opportunity to access the full inspection and sampling of rebar. The included activities had different invasiveness and encompassed inspections, core sampling, corrosion potential mapping, compressive strength tests, as well as neutralization depth assays on cored surfaces, on chisel-split surfaces, and on drilling powders. The results bring together a global diagnostic picture of very limited degradation and of elements that are fully able to attend their design service life; the latter is estimated to be considerably higher than 20 years and to exceed 75 years if the concrete mix does not show quality issues. Results also permit drawing considerations on a hierarchy of diagnostic reliability in the evaluation of RC degradation, in which concrete core sampling plays the role of golden standard.
Nine Mitochondrial Genomes of the Pyraloidea and Their Phylogenetic Implications (Lepidoptera)
Authors: Liu Xiaomeng , Qi Mujie , Xu Haizhen , Wu Zhipeng , Hu Lizong , Yang Mingsheng , Li Houhun
Published: November 2021

The Pyraloidea is one of the species-rich superfamilies of Lepidoptera and contains numerous economically important pest species that cause great loss in crop production. Here, we sequenced and annotated nine complete mitogenomes for Pyraloidea, and further performed various phylogenetic analyses, to improve our understanding of mitogenomic evolution and phylogeny of this superfamily. The nine mitogenomes were circular, double-stranded molecules, with the lengths ranging from 15,214 bp to 15,422 bp, which are comparable to other reported pyraloid mitogenomes in size. Gene content and arrangement were highly conserved and are typical of Lepidoptera. Based on the hitherto most extensive mitogenomic sampling, our various resulting trees showed generally congruent topologies among pyraloid subfamilies, which are almost in accordance with previous multilocus studies, indicating the suitability of mitogenomes in inferring high-level relationships of Pyraloidea. However, nodes linking subfamilies in the “non-PS clade” were not completely resolved in terms of unstable topologies or low supports, and future investigations are needed with increased taxon sampling and molecular data. Unexpectedly, Orybina Snellen, represented in a molecular phylogenetic investigation for the first time, was robustly placed as basal to the remaining Pyralidae taxa across our analyses, rather than nested in Pyralinae of Pyralidae as morphologically defined. This novel finding highlights the need to reevaluate Orybina monophyly and its phylogenetic position by incorporating additional molecular and morphological evidence.
Clinical Significance and Prognostic Value of Hemostasis Parameters in 337 Patients with Acute Infective Endocarditis
Authors: Zampino Rosa , Iossa Domenico , Ursi Maria Paola , Bertolino Lorenzo , Karruli Arta , Molaro Rosa , Esposito Gennaro , Vitrone Martina , D’Amico Fabiana , Albisinni Rosina , Durante-Mangoni Emanuele ,   on behalf of the Monaldi Hospital CardiovascularInfection Group
Published: November 2021

(1) Background: The aim of this study was to assess the clinical significance and prognostic role of the main hemostasis parameters in infective endocarditis (IE): prothrombin time as international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, platelet count, homocysteine. (2) Methods: We studied 337 patients with IE. Clinical, hemato-chemical and echocardiography parameters were analyzed. Coagulation parameters were measured on admission. (3) Results: D-dimers levels (p = 0.012) and a prolonged PT-INR (p = 0.013) were associated with higher in-hospital mortality, while prolonged aPTT (p = 0.021) was associated with increased 1-year mortality. Staphylococcus aureus (S. aureus) infection (p = 0.003), prosthetic valve endocarditis (PVE) (p = 0.001), surgical indication (p = 0.002) and higher D-dimer levels (p = 0.005) were independent predictors of in-hospital mortality. PVE (p = 0.001), a higher Charlson Comorbidity Index (p = 0.049), surgical indication (p = 0.001) and prolonged aPTT (p = 0.012) were independent predictors of 1-year mortality. Higher levels of D-dimers (p < 0.001) and a shorter aPTT (p < 0.001) were associated with embolic complications of IE. S. aureus etiology was bound to higher D-dimers levels (p < 0.001) and a shorter aPTT (p = 0.006). (4) Conclusions: Elevated D-dimers are associated with a higher risk for in-hospital mortality in IE patients. High D-dimers and a short aPTT are associated with a higher risk for embolic events in IE. A longer aPTT is associated with 1-year mortality.
Prognostic Impact of Sleep Patterns and Related-Drugs in Patients with Heart Failure
Authors: Bughin François , Jaussent Isabelle , Ayoub Bronia , Aguilhon Sylvain , Chapet Nicolas , Soltani Sonia , Mercier Jacques , Dauvilliers Yves , Roubille François
Published: November 2021

Sleep disturbances are frequent among patients with heart failure (HF). We hypothesized that self-reported sleep disturbances are associated with a poor prognosis in patients with HF. A longitudinal study of 119 patients with HF was carried out to assess the association between sleep disturbances and the occurrence of major cardiovascular events (MACE). All patients with HF completed self-administered questionnaires on sleepiness, fatigue, insomnia, quality of sleep, sleep patterns, anxiety and depressive symptoms, and central nervous system (CNS) drugs intake. Patients were followed for a median of 888 days. Cox models were used to estimate the risk of MACE associated with baseline sleep characteristics. After adjustment for age, the risk of a future MACE increased with CNS drugs intake, sleep quality and insomnia scores as well with increased sleep latency, decreased sleep efficiency and total sleep time. However, after adjustment for left ventricular ejection fraction and hypercholesterolemia the HR failed to be significant except for CNS drugs and total sleep time. CNS drugs intake and decreased total sleep time were independently associated with an increased risk of MACE in patients with HF. Routine assessment of self-reported sleep disturbances should be considered to prevent the natural progression of HF.
Immunosuppression as a Risk Factor for De Novo Angiotensin II Type Receptor Antibodies Development after Kidney Transplantation
Authors: Sorohan Bogdan Marian , Sinescu Ioanel , Tacu Dorina , Bucșa Cristina , Țincu Corina , Obrișcă Bogdan , Berechet Andreea , Constantinescu Ileana , Mărunțelu Ion , Ismail Gener , Baston Cătălin
Published: November 2021

(1) Background: Angiotensin II type I receptor antibodies (AT1R-Ab) represent a topic of interest in kidney transplantation (KT). Data regarding the risk factors associated with de novo AT1R-Ab development are lacking. Our goal was to identify the incidence of de novo AT1R-Ab at 1 year after KT and to evaluate the risk factors associated with their formation. (2) Methods: We conducted a prospective cohort study on 56 adult patients, transplanted between 2018 and 2019. Recipient, donor, transplant, treatment, and complications data were assessed. A threshold of >10 U/mL was used for AT1R-Ab detection. (3) Results: De novo AT1R-Ab were observed in 12 out of 56 KT recipients (21.4%). The median value AT1R-Ab in the study cohort was 8.5 U/mL (inter quartile range: 6.8–10.4) and 15.6 U/mL (10.8–19.8) in the positive group. By multivariate logistic regression analysis, induction immunosuppression with anti-thymocyte globulin (OR = 7.20, 95% CI: 1.30–39.65, p = 0.02), maintenance immunosuppression with immediate-release tacrolimus (OR = 6.20, 95% CI: 1.16–41.51, p = 0.03), and mean tacrolimus trough level (OR = 2.36, 95% CI: 1.14–4.85, p = 0.01) were independent risk factors for de novo AT1R-Ab at 1 year after KT. (4) Conclusions: De novo AT1R-Ab development at 1 year after KT is significantly influenced by the type of induction and maintenance immunosuppression.
Therapeutic Drug Monitoring of Carbamazepine: A 20-Year Observational Study
Authors: Grześk Grzegorz , Stolarek Wioleta , Kasprzak Michał , Grześk Elżbieta , Rogowicz Daniel , Wiciński Michał , Krzyżanowski Marek
Published: November 2021

Background: Carbamazepine (CBZ) is a first-generation anticonvulsant drug. Hence, in certain cases, therapeutic drug monitoring (TDM) supports pharmacotherapy. Methods: The presented research was based on a retrospective analysis including 710 ambulatory and hospitalized patients treated with CBZ between the years 1991 and 2011. The method used for the determination of the CBZ concentration was fluorescence polarization immunoassay (FPIA) performed using an Abbott GmbH TDx automatic analyzer, with the therapeutic range for carbamazepine being 4–12 µg/mL. Results: The therapeutic range was observed more often in patients between 3 and 17 years of age compared with the population ≥18 years of age (73.5% vs. 68.8%). The therapeutic level was exceeded less frequently in the population between 3 and 17 years of age despite them being given a significantly higher dose per kilogram of body weight than in the population ≥18 years of age (13.64 mg/kg vs. 10.43 mg/kg, p < 0.0001). Patients ≥18 years of age were statistically significantly more likely to be in the group with a suspected drug overdose (73.9% vs. 26.1%), and suicide attempts only occurred in elderly patients (100.0% vs. 0.0%, p = 0.003). Conclusion: The results of the TDM of CBZ showed that only 71% of all samples were at the therapeutic level. To ensure the maximum efficacy and safety of the therapy, it is necessary to monitor the concentration of CBZ regardless of sex and age.
Lifestyle and Chronic Pain in the Pelvis: State of the Art and Future Directions
Authors: Gutke Annelie , Sundfeldt Karin , De Baets Liesbet
Published: November 2021

During their lifespan, many women are exposed to pain in the pelvis in relation to menstruation and pregnancy. Such pelvic pain is often considered normal and inherently linked to being a woman, which in turn leads to insufficiently offered treatment for treatable aspects related to their pain experience. Nonetheless, severe dysmenorrhea (pain during menstruation) as seen in endometriosis and pregnancy-related pelvic girdle pain, have a high impact on daily activities, school attendance and work ability. In the context of any type of chronic pain, accumulating evidence shows that an unhealthy lifestyle is associated with pain development and pain severity. Furthermore, unhealthy lifestyle habits are a suggested perpetuating factor of chronic pain. This is of specific relevance during lifespan, since a low physical activity level, poor sleep, or periods of (di)stress are all common in challenging periods of women’s lives (e.g., during menstruation, during pregnancy, in the postpartum period). This state-of-the-art paper aims to review the role of lifestyle factors on pain in the pelvis, and the added value of a lifestyle intervention on pain in women with pelvic pain. Based on the current evidence, the benefits of physical activity and exercise for women with pain in the pelvis are supported to some extent. The available evidence on lifestyle factors such as sleep, (di)stress, diet, and tobacco/alcohol use is, however, inconclusive. Very few studies are available, and the studies which are available are of general low quality. Since the role of lifestyle on the development and maintenance of pain in the pelvis, and the value of lifestyle interventions for women with pain in the pelvis are currently poorly studied, a research agenda is presented. There are a number of rationales to study the effect of promoting a healthy lifestyle (early) in a woman’s life with regard to the prevention and management of pain in the pelvis. Indeed, lifestyle interventions might have, amongst others, anti-inflammatory, stress-reducing and/or sleep-improving effects, which might positively affect the experience of pain. Research to disentangle the relationship between lifestyle factors, such as physical activity level, sleep, diet, smoking, and psychological distress, and the experience of pain in the pelvis is, therefore, needed. Studies which address the development of management strategies for adapting lifestyles that are specifically tailored to women with pain in the pelvis, and as such take hormonal status, life events and context, into account, are required. Towards clinicians, we suggest making use of the window of opportunity to prevent a potential transition from localized or periodic pain in the pelvis (e.g., dysmenorrhea or pain during pregnancy and after delivery) towards persistent chronic pain, by promoting a healthy lifestyle and applying appropriate pain management.
Classification Tree to Analyze Factors Connected with Post Operative Complications of Cataract Surgery in a Teaching Hospital
Authors: Lanza Michele , Koprowski Robert , Boccia Rosa , Ruggiero Adriano , De Rosa Luigi , Tortori Antonia , Wilczyński Sławomir , Melillo Paolo , Sbordone Sandro , Simonelli Francesca
Published: November 2021

Background: Artificial intelligence (AI) is becoming ever more frequently applied in medicine and, consequently, also in ophthalmology to improve both the quality of work for physicians and the quality of care for patients. The aim of this study is to use AI, in particular classification tree, for the evaluation of both ocular and systemic features involved in the onset of complications due to cataract surgery in a teaching hospital. Methods: The charts of 1392 eyes of 1392 patients, with a mean age of 71.3 ± 8.2 years old, were reviewed to collect the ocular and systemic data before, during and after cataract surgery, including post-operative complications. All these data were processed by a classification tree algorithm, producing more than 260 million simulations, aiming to develop a predictive model. Results: Postoperative complications were observed in 168 patients. According to the AI analysis, the pre-operative characteristics involved in the insurgence of complications were: ocular comorbidities, lower visual acuity, higher astigmatism and intra-operative complications. Conclusions: Artificial intelligence application may be an interesting tool in the physician’s hands to develop customized algorithms that can, in advance, define the post-operative complication risk. This may help in improving both the quality and the outcomes of the surgery as well as in preventing patient dissatisfaction.
Assessment of Seasonal and Spatial Variations of Coastal Water Quality Using Multivariate Statistical Techniques
Authors: Alkhalidi Mohamad , Alsulaili Abdalrahman , Almarshed Badreyah , Bouresly Majed , Alshawish Sarah
Published: November 2021

This study investigates the seasonal and spatial trends in Kuwait’s coastal water’s physical, chemical, and biological parameters by applying multivariate statistical techniques, including cluster analysis (CA), principal component/factor analysis (PCA/FA), and the Pearson correlation (PC) method to the average daily reading of water quality parameters from fifteen stations over one year. The investigated parameters are pH, turbidity, chlorophyll-a, conductivity, dissolved oxygen (DO), phycoerythrin, salinity, and temperature. The results show that the coastal water of Kuwait is subjected to high environmental pressure due to natural and human interferences. During 2017, the DO levels were below the threshold limit, and at the same time, the water temperature and salinity were very high, causing a series of fish death events. CA resulted in three different regions based on the turbidity, including high, moderate, and low regions, and three seasons (winter, summer, and autumn). Spring is very short and overlaps with winter and summer. PCA/FA applied on the datasets assisted in extracting and identifying parameters responsible for the variations in the seasons and regions obtained from CA. Additionally, Pearson’s correlation resulted in a strong positive relation between chlorophyll and phycoerythrin in 7 out of the 15 stations. However, at high turbidity regions (stations 1 and 2), chlorophyll concentration was low. Additionally, the negative correlation between DO and temperature was observed at stations with rare human activities.
The Coevolutionary Process of Maritime Management of Shipping Industry in the Context of the COVID-19 Pandemic
Authors: Zhang Yan , Sun Zhikuan
Published: November 2021

This study investigates how international organizations, International Maritime Organization (IMO) member states, and associate members have embarked on maritime management (MM) measures to address dire situations in the context of the COVID-19 pandemic. It explores the evolution of MM practices from international organizations, IMO member states, and associate members to ensure the resilience and sustainability of the shipping industry. Corpus linguistics was employed as a computer-assisted method to assess a large number of naturally occurring texts. Circular letters from international organizations and member states listed on the IMO website from January 2020 to July 2021 were curated and built into three corpora. Through corpus linguistic analysis of circulars from three different crisis phases (Pre-/early-crisis, Crisis in progress, Post-COVID-19 crisis phase), we discovered an MM progression mechanism developed between stakeholders in conjunction with the post-crisis period. The study presented the “MM-as-process” vision to emphasize the time-varying dynamic nature of MM development during the disruption.
Global Prevalence of COVID-19-Associated Mucormycosis (CAM): Living Systematic Review and Meta-Analysis
Authors: Hussain Salman , Riad Abanoub , Singh Ambrish , Klugarová Jitka , Antony Benny , Banna Hasanul , Klugar Miloslav
Published: November 2021

Mucormycosis, a secondary fungal infection, gained much attention in the ongoing COVID-19 pandemic. This deadly infection has a high all-cause mortality rate and imposes a significant economic, epidemiological, and humanistic burden on the patients and healthcare system. Evidence from the published epidemiological studies showed the varying prevalence of COVID-19-associated mucormycosis (CAM). This study aims to compute the pooled prevalence of CAM and other associated clinical outcomes. MEDLINE, Embase, Cochrane COVID-19 Study Register, and WHO COVID-19 databases were scanned to retrieve the relevant articles until August 2021. All studies reporting the prevalence of mucormycosis among COVID-19 patients were eligible for inclusion. Two investigators independently screened the articles against the selection criteria, extracted the data, and performed the quality assessment using the JBI tool. The pooled prevalence of CAM was the primary outcome, and the pooled prevalence of diabetes, steroid exposure, and the mortality rate were the secondary outcomes of interest. Comprehensive Meta-Analysis software version 2 was used for performing the meta-analysis. This meta-analysis comprised six studies with a pooled sample size of 52,916 COVID-19 patients with a mean age of 62.12 ± 9.69 years. The mean duration of mucormycosis onset was 14.59 ± 6.88 days after the COVID-19 diagnosis. The pooled prevalence of CAM (seven cases per 1000 patients) was 50 times higher than the highest recorded background of mucormycosis (0.14 cases per 1000 patients). A high mortality rate was found among CAM patients with a pooled prevalence rate of 29.6% (95% CI: 17.2–45.9%). Optimal glycemic control and the judicious use of steroids should be the approach for tackling rising CAM cases.
Biomass and Cordycepin Production by the Medicinal Mushroom Cordyceps militaris—A Review of Various Aspects and Recent Trends towards the Exploitation of a Valuable Fungus
Authors: Kontogiannatos Dimitrios , Koutrotsios Georgios , Xekalaki Savvina , Zervakis Georgios I.
Published: November 2021

Cordyceps militaris is an entomopathogenic ascomycete with similar pharmacological importance to that of the wild caterpillar fungus Ophiocordyceps sinensis. C. militaris has attracted significant research and commercial interest due to its content in bioactive compounds beneficial to human health and the relative ease of cultivation under laboratory conditions. However, room for improvement exists in the commercial-scale cultivation of C. militaris and concerns issues principally related to appropriate strain selection, genetic degeneration of cultures, and substrate optimization. In particular, culture degeneration—usually expressed by abnormal fruit body formation and reduced sporulation—results in important economic losses and is holding back investors and potential growers (mainly in Western countries) from further developing this highly promising sector. In the present review, the main factors that influence the generation of biomass and metabolites (with emphasis on cordycepin biosynthesis) by C. militaris are presented and evaluated in conjunction with the use of a wide range of supplements or additives towards the enhancement of fungal productivity in large-scale cultivation processes. Moreover, physiological and genetic factors that increase or reduce the manifestation of strain degeneration in C. militaris are outlined. Finally, methodologies for developing protocols to be used in C. militaris functional biology studies are discussed.
Application of Metabolomics in the Study of Starvation-Induced Autophagy in Saccharomyces cerevisiae: A Scoping Review
Authors: Nasaruddin Muhammad Luqman , Tajul Arifin Khaizurin
Published: November 2021

This scoping review is aimed at the application of the metabolomics platform to dissect key metabolites and their intermediates to observe the regulatory mechanisms of starvation-induced autophagy in Saccharomyces cerevisiae. Four research papers were shortlisted in this review following the inclusion and exclusion criteria. We observed a commonly shared pathway undertaken by S. cerevisiae under nutritional stress. Targeted and untargeted metabolomics was applied in either of these studies using varying platforms resulting in the annotation of several different observable metabolites. We saw a commonly shared pathway undertaken by S. cerevisiae under nutritional stress. Following nitrogen starvation, the concentration of cellular nucleosides was altered as a result of autophagic RNA degradation. Additionally, it is also found that autophagy replenishes amino acid pools to sustain macromolecule synthesis. Furthermore, in glucose starvation, nucleosides were broken down into carbonaceous metabolites that are being funneled into the non-oxidative pentose phosphate pathway. The ribose salvage allows for the survival of starved yeast. Moreover, acute glucose starvation showed autophagy to be involved in maintaining ATP/energy levels. We highlighted the practicality of metabolomics as a tool to better understand the underlying mechanisms involved to maintain homeostasis by recycling degradative products to ensure the survival of S. cerevisiae under starvation. The application of metabolomics has extended the scope of autophagy and provided newer intervention targets against cancer as well as neurodegenerative diseases in which autophagy is implicated.
Sensing and Responding to Hypersaline Conditions and the HOG Signal Transduction Pathway in Fungi Isolated from Hypersaline Environments: Hortaea werneckii and Wallemia ichthyophaga
Authors: Plemenitaš Ana
Published: November 2021

Sensing and responding to changes in NaCl concentration in hypersaline environments is vital for cell survival. In this paper, we identified and characterized key components of the high-osmolarity glycerol (HOG) signal transduction pathway, which is crucial in sensing hypersaline conditions in the extremely halotolerant black yeast Hortaea werneckii and in the obligate halophilic fungus Wallemia ichthyophaga. Both organisms were isolated from solar salterns, their predominating ecological niche. The identified components included homologous proteins of both branches involved in sensing high osmolarity (SHO1 and SLN1) and the homologues of mitogen-activated protein kinase module (MAPKKK Ste11, MAPKK Pbs2, and MAPK Hog1). Functional complementation of the identified gene products in S. cerevisiae mutant strains revealed some of their functions. Structural protein analysis demonstrated important structural differences in the HOG pathway components between halotolerant/halophilic fungi isolated from solar salterns, salt-sensitive S. cerevisiae, the extremely salt-tolerant H. werneckii, and halophilic W. ichthyophaga. Known and novel gene targets of MAP kinase Hog1 were uncovered particularly in halotolerant H. werneckii. Molecular studies of many salt-responsive proteins confirm unique and novel mechanisms of adaptation to changes in salt concentration.
Utilizing a Human–Computer Interaction Approach to Evaluate the Design of Current Pharmacogenomics Clinical Decision Support
Authors: Elchynski Amanda L. , Desai Nina , D’Silva Danielle , Hall Bradley , Marks Yael , Wiisanen Kristin , Cicali Emily J. , Cavallari Larisa H. , Nguyen Khoa A.
Published: November 2021

A formal assessment of pharmacogenomics clinical decision support (PGx-CDS) by providers is lacking in the literature. The objective of this study was to evaluate the usability of PGx-CDS tools that have been implemented in a healthcare setting. We enrolled ten prescribing healthcare providers and had them complete a 60-min usability session, which included interacting with two PGx-CDS scenarios using the “Think Aloud” technique, as well as completing the Computer System Usability Questionnaire (CSUQ). Providers reported positive comments, negative comments, and suggestions for the two PGx-CDS during the usability testing. Most provider comments were in favor of the current PGx-CDS design, with the exception of how the genotype and phenotype information is displayed. The mean CSUQ score for the PGx-CDS overall satisfaction was 6.3 ± 0.95, with seven strongly agreeing and one strongly disagreeing for overall satisfaction. The implemented PGx-CDS at our institution was well received by prescribing healthcare providers. The feedback collected from the session will guide future PGx-CDS designs for our healthcare system and provide a framework for other institutions implementing PGx-CDS.
Foreign Direct Investment and Trade—Between Complementarity and Substitution. Evidence from European Union Countries
Authors: Voica Marian Catalin , Panait Mirela , Hysa Eglantina , Cela Arjona , Manta Otilia
Published: November 2021

This aim of this work is to study the relationship between foreign direct investment (FDI) and trade. FDI is a driving force for economic growth for host countries. The positive effects of FDI are seen in many aspects of the economy. However, the implications of FDI on foreign trade are questionable. Therefore, this study uses a Granger causality technique to test whether the relationship between FDI and foreign trade is complementary or substitutive. The findings of this study indicate that this relationship appears to be complementary, and FDI investment does cause an increase in trade flow in the countries that are taken into consideration. This research aims to make a comparison between the relations of FDI flows of three groups of countries from the European Union (EU)—Romania and Bulgaria, the Visegrád Group and the Euro area—for the period of 2005 to 2019. However, the results indicate that this link between the variables is not yet found for the three group of countries, and further research is required in this aspect. This leads to the conclusion that the FDI impact on foreign trade of the host country depends on the type of investment and absorptive capacity of the receiver, the economic development of host and home countries, and not every type of FDI leads to more trade.