bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Proximal Spaces Using Relators
Authors: Pataki Gergely
Published: June 2021

In this paper, we define uniformities and proximities as relators and show the equivalences of these definitions with classical ones. For this, we summarize the essential properties of relators, using their theory from earlier works of Á. Száz. Moreover, we prove implications between important topological properties of relators and disprove others. Finally, we add an analogous definition for uniformly and proximally filtered properties.
Reengineering Tumor Microenvironment with Sequential Interleukin Delivery
Authors: Figueiredo Marxa L. , Letteri Rachel , Chan-Seng Delphine , Kumar Shreya , Rivera-Cruz Cosette M. , Emrick Todd S.
Published: June 2021

Some cytokines can reengineer anti-tumor immunity to modify the tumor micro-environment. Interleukin-27 (IL-27) can partially reduce tumor growth in several animal models, including prostate cancer. We hypothesized that addition of IL-18, which can induce the proliferation of several immune effector cells through inducing IFNγ could synergize with IL-27 to enhance tumor growth control. We describe our findings on the effects of IL-27 gene delivery on prostate cancer cells and how sequential therapy with IL-18 enhanced the efficacy of IL-27. The combination of IL-27 followed by IL-18 (27→18) successfully reduced cancer cell viability, with significant effects in cell culture and in an immunocompetent mouse model. We also examined a novel chimeric cytokine, comprising an IL-27 targeted at the C-terminus with a short peptide, LSLITRL (27pepL). This novel cytokine targets a receptor upregulated in tumor cells (IL-6Rα) via the pepL ligand. Interestingly, when we compared the 27→18 combination with the single 27pepL therapy, we observed a similar efficacy for both. This efficacy was further enhanced when 27pepL was sequenced with IL-18 (27pepL→18). The observed reduction in tumor growth and significantly enriched canonical pathways and upstream regulators, as well as specific immune effector signatures (as determined by bioinformatics analyses in the tumor microenvironment) supported the therapeutic design, whereby IL-27 or 27pepL can be more effective when delivered with IL-18. This cytokine sequencing approach allows flexible incorporation of both gene delivery and recombinant cytokines as tools to augment IL-27’s bioactivity and reengineer efficacy against prostate tumors and may prove applicable in other therapeutic settings.
Interplay between Hypoxia and Extracellular Vesicles in Cancer and Inflammation
Authors: Venturella Marta , Criscuoli Mattia , Carraro Fabio , Naldini Antonella , Zocco Davide
Published: June 2021

Hypoxia is a severe stress condition often observed in cancer and chronically inflamed cells and tissues. Extracellular vesicles play pivotal roles in these pathological processes and carry biomolecules that can be detected in many biofluids and may be exploited for diagnostic purposes. Several studies report the effects of hypoxia on extracellular vesicles’ release, molecular content, and biological functions in disease. This review summarizes the most recent findings in this field, highlighting the areas that warrant further investigation.
Transcriptomic and Epigenomic Landscape in Rett Syndrome
Authors: Marano Domenico , Fioriniello Salvatore , D’Esposito Maurizio , Della Ragione Floriana
Published: June 2021

Rett syndrome (RTT) is an extremely invalidating, cureless, developmental disorder, and it is considered one of the leading causes of intellectual disability in female individuals. The vast majority of RTT cases are caused by de novo mutations in the X-linked Methyl-CpG binding protein 2 (MECP2) gene, which encodes a multifunctional reader of methylated DNA. MeCP2 is a master epigenetic modulator of gene expression, with a role in the organization of global chromatin architecture. Based on its interaction with multiple molecular partners and the diverse epigenetic scenario, MeCP2 triggers several downstream mechanisms, also influencing the epigenetic context, and thus leading to transcriptional activation or repression. In this frame, it is conceivable that defects in such a multifaceted factor as MeCP2 lead to large-scale alterations of the epigenome, ranging from an unbalanced deposition of epigenetic modifications to a transcriptional alteration of both protein-coding and non-coding genes, with critical consequences on multiple downstream biological processes. In this review, we provide an overview of the current knowledge concerning the transcriptomic and epigenomic alterations found in RTT patients and animal models.
The Neuroinflammatory Role of Pericytes in Epilepsy
Authors: Yamanaka Gaku , Takata Fuyuko , Kataoka Yasufumi , Kanou Kanako , Morichi Shinichiro , Dohgu Shinya , Kawashima Hisashi
Published: June 2021

Pericytes are a component of the blood–brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links between epilepsy and pericytes have been identified. Here, we review current knowledge about the role of pericytes in epilepsy. Clinical evidence has shown an accumulation of pericytes with altered morphology in the cerebral vascular territories of patients with intractable epilepsy. In vitro, proinflammatory cytokines, including IL-1β, TNFα, and IL-6, cause morphological changes in human-derived pericytes, where IL-6 leads to cell damage. Experimental studies using epileptic animal models have shown that cerebrovascular pericytes undergo redistribution and remodeling, potentially contributing to BBB permeability. These series of pericyte-related modifications are promoted by proinflammatory cytokines, of which the most pronounced alterations are caused by IL-1β, a cytokine involved in the pathogenesis of epilepsy. Furthermore, the pericyte-glial scarring process in leaky capillaries was detected in the hippocampus during seizure progression. In addition, pericytes respond more sensitively to proinflammatory cytokines than microglia and can also activate microglia. Thus, pericytes may function as sensors of the inflammatory response. Finally, both in vitro and in vivo studies have highlighted the potential of pericytes as a therapeutic target for seizure disorders.
Biologic Therapy and Severe Asthma in Children
Authors: Russo Daniele , Di Filippo Paola , Attanasi Marina , Lizzi Mauro , Di Pillo Sabrina , Chiarelli Francesco
Published: June 2021

Severe asthma is a heterogeneous, complex and chronic disease widespread in the pediatric population. According to the recent findings about the different endotypes of asthma in children, each one characterized by specific intracellular molecular pathways, several innovative biologic therapies have been developed. Due to their precise ability to target specific inflammatory type 2 mediators, biologics have revolutionized the care of chronic allergic diseases in the pediatric and adult population. In this review, we aim to provide the latest evidence about the use, indications, efficacy and safety of biologic therapies to treat severe asthma in children and adolescents.
A Novel Lightweight Wearable Soft Exosuit for Reducing the Metabolic Rate and Muscle Fatigue
Authors: Chen Lingxing , Chen Chunjie , Wang Zhuo , Ye Xin , Liu Yida , Wu Xinyu
Published: June 2021

Wearable robotic devices have been proved to considerably reduce the energy expenditure of human walking. It is not only suitable for healthy people, but also for some patients who require rehabilitation exercises. However, in many cases, the weight of soft exosuits are relatively large, which makes it difficult for the assistant effect of the system to offset the metabolic consumption caused by the extra weight, and the heavy weight will make people uncomfortable. Therefore, reducing the weight of the whole system as much as possible and keeping the soft exosuit output power unchanged, may improve the comfort of users and further reduce the metabolic consumption. In this paper, we show that a novel lightweight soft exosuit which is currently the lightest among all known powered exoskeletons, which assists hip flexion. Indicated from the result of experiment, the novel lightweight soft exosuit reduces the metabolic consumption rate of wearers when walking on the treadmill at 5 km per hour by 11.52% compared with locomotion without the exosuit. Additionally, it can reduce more metabolic consumption than the hip extension assisted (HEA) and hip flexion assisted (HFA) soft exosuit which our team designed previously, which has a large weight. The muscle fatigue experiments show that using the lightweight soft exosuit can also reduce muscle fatigue by about 10.7%, 40.5% and 5.9% for rectus femoris, vastus lateralis and gastrocnemius respectively compared with locomotion without the exosuit. It is demonstrated that decreasing the weight of soft exosuit while maintaining the output almost unchanged can further reduce metabolic consumption and muscle fatigue, and appropriately improve the users’ comfort.
The Impact of Social Cognition on the Real-Life of People with Epilepsy
Authors: Jasionis Arminas , Puteikis Kristijonas , Mameniškienė Rūta
Published: June 2021

Background. Previous research has demonstrated the impairment of social cognition (SC) in people with epilepsy. It is associated with worse social functioning and quality of life; however, the influence on real-life outcomes is unknown. The purpose of this study was to investigate how SC is associated with epilepsy variables and real-life outcomes (education, employment and relationships) among patients with epilepsy (PWE). Methods. Eighty-one PWE completed tasks of theory of mind (ToM) (faux pas recognition (FPRT) and Happé Strange Stories test (HST)) and emotion recognition (ER) (Reading of the Mind in the Eyes (RMET)). Variables reflecting their education, employment and relationship status were treated as endpoints in search of association with SC. Data from a matched group (n = 30) of healthy controls (HCs) were used for comparison of ToM abilities. Results. ToM scores were lower among PWE as compared to HCs (U = 1816.0, p < 0.0001 (HST), U = 1564.5, p = 0.020 (FPRT)). All SC tests were associated with the level of education (OR = 1.22, 95% confidence interval (CI) = 1.09 to 1.36 (RMET), OR = 1.20, 95% CI = 1.02 to 1.40 (HST), OR = 0.93, 95% CI = 0.87 to 1.00 (FPRT)). The results of ToM and ER testing were not associated with employment (χ2 = 33.423, p < 0.0001) if adjusted for the level of education (B = 0.804, OR = 2.23 (95% CI = 1.33 to 3.76), p = 0.002). SC abilities did not differ between PWE who were single and those in a relationship (U = 858.5, p = 0.541 (HST)), t= −1.236, p = 0.220 (RMET), U = 909.5, p = 0.271 (FPRT)). Conclusion. Better social cognition skills are linked to a higher level of education among PWE. SC probably has less influence on professional achievements and interpersonal relationships.
Predictive Role of Leptin Receptor (Ob-R) Overexpression in Patients with Early Breast Cancer Receiving Neoadjuvant Systemic Treatment
Authors: García-Estévez Laura , Calvo Isabel , Pérez Silvia , Gallegos Isabel , Díaz Eva , Sampayo-Cordero Miguel , Oltra Sara S , Moreno-Bueno Gema
Published: June 2021

The primary aim of this retrospective study was to investigate the correlation between the immunohistochemical expression of Ob-R (leptin receptor) with pCR (pathological complete response) in early breast cancer patients receiving neoadjuvant systemic treatment (NST). A total of 100 women with breast cancer receiving NST (2017–2020) followed by surgical resection were retrospectively obtained. Demographic parameters and clinicopathological factors (e.g., treatment modalities, immunohistochemistry (IHC), and cancer subtype) were obtained from the patient’s clinical records. In the analyzed breast cancer cohort, high expression of Ob-R was found in 52% of tumors and there was a significantly higher incidence in the HER2+ and TNBC subgroups. Overall, a significantly greater percentage of patients with Ob-R positive tumors achieved pCR compared with Ob-R negative patients (57.7% vs. 27.1%; p = 0.002). This result was observed in most breast cancer subtypes. In patients with HER2+ breast cancer, there was no difference in Ob-R expression in relation to the HR status. Ob-R cell positivity was significantly higher in younger breast cancer patients (p = 0.008), those who were premenopausal (p = 0.011), and in those with a BMI > 25 kg/m2 (p = 0.019). A significantly greater percentage of early breast cancer patients with Ob-R positive tumors achieved pCR compared with Ob-R negative patients. Furthermore, breast cancer patients with positive Ob-R expression were significantly younger than those with negative Ob-R expression. This association was not explained by differences in BMI between young and old patients.
Control of Skeletal Muscle Atrophy Associated to Cancer or Corticosteroids by Ceramide Kinase
Authors: Pierucci Federica , Frati Alessia , Battistini Chiara , Penna Fabio , Costelli Paola , Meacci Elisabetta
Published: June 2021

Apart from cytokines and chemokines, sphingolipid mediators, particularly sphingosine-1-phosphate (S1P) and ceramide 1-phosphate (C1P), contribute to cancer and inflammation. Cancer, as well as other inflammatory conditions, are associated with skeletal muscle (SkM) atrophy, which is characterized by the unbalance between protein synthesis and degradation. Although the signaling pathways involved in SkM mass wasting are multiple, the regulatory role of simple sphingolipids is limited. Here, we report the impairment of ceramide kinase (CerK), the enzyme responsible for the phosphorylation of ceramide to C1P, associated with the accomplishment of atrophic phenotype in various experimental models of SkM atrophy: in vivo animal model bearing the C26 adenocarcinoma or Lewis lung carcinoma tumors, in human and murine SkM cells treated with the conditioned medium obtained from cancer cells or with the glucocorticoid dexamethasone. Notably, we demonstrate in all the three experimental approaches a drastic decrease of CerK expression. Gene silencing of CerK promotes the up-regulation of atrogin-1/MAFbx expression, which was also observed after cell treatment with C8-ceramide, a biologically active ceramide analogue. Conversely, C1P treatment significantly reduced the corticosteroid’s effects. Altogether, these findings provide evidence that CerK, acting as a molecular modulator, may be a new possible target for SkM mass regulation associated with cancer or corticosteroids.
Lattice or Oxygen-Guided Radiotherapy: What If They Converge? Possible Future Directions in the Era of Immunotherapy
Authors: Ferini Gianluca , Valenti Vito , Tripoli Antonella , Illari Salvatore Ivan , Molino Laura , Parisi Silvana , Cacciola Alberto , Lillo Sara , Giuffrida Dario , Pergolizzi Stefano
Published: June 2021

Palliative radiotherapy has a great role in the treatment of large tumor masses. However, treating a bulky disease could be difficult, especially in critical anatomical areas. In daily clinical practice, short course hypofractionated radiotherapy is delivered in order to control the symptomatic disease. Radiation fields generally encompass the entire tumor mass, which is homogeneously irradiated. Recent technological advances enable delivering a higher radiation dose in small areas within a large mass. This goal, previously achieved thanks to the GRID approach, is now achievable using the newest concept of LATTICE radiotherapy (LT-RT). This kind of treatment allows exploiting various radiation effects, such as bystander and abscopal effects. These events may be enhanced by the concomitant use of immunotherapy, with the latter being ever more successfully delivered in cancer patients. Moreover, a critical issue in the treatment of large masses is the inhomogeneous intratumoral distribution of well-oxygenated and hypo-oxygenated areas. It is well known that hypoxic areas are more resistant to the killing effect of radiation, hence the need to target them with higher aggressive doses. This concept introduces the “oxygen-guided radiation therapy” (OGRT), which means looking for suitable hypoxic markers to implement in PET/CT and Magnetic Resonance Imaging. Future treatment strategies are likely to involve combinations of LT-RT, OGRT, and immunotherapy. In this paper, we review the radiobiological rationale behind a potential benefit of LT-RT and OGRT, and we summarize the results reported in the few clinical trials published so far regarding these issues. Lastly, we suggest what future perspectives may emerge by combining immunotherapy with LT-RT/OGRT.
Comparison of Surgical Outcomes between Robotic Transaxillary and Conventional Open Thyroidectomy in Pediatric Thyroid Cancer
Authors: Lee In A , Kim Kwangsoon , Kim Jin Kyong , Kang Sang-Wook , Lee Jandee , Jeong Jong Ju , Nam Kee-Hyun , Chung Woong Youn
Published: June 2021

Thyroid cancer in children is very uncommon. For pediatric thyroid cancer, robotic surgery has served as a minimally invasive surgical alternative to conventional open surgery. Our study aimed to evaluate the results of robotic versus open surgical treatment for patients with thyroid cancer younger than 20 years of age at the time of diagnosis. This retrospective review included 161 pediatric patients who underwent robotic transaxillary or conventional open thyroidectomy at our institution from 2008 to 2019. Of these patients, 99 comprised the robotic group and 62 the open group. Patient demographics, surgical outcomes, and disease-free survival rates were compared between the two groups. Patients in the open group were more likely to have advanced stage diseases with a larger tumor size and higher tumor-node-metastasis stage than those in the robotic group. Operation time and follow-up period were similar in both groups. Patients in the robotic group had a lower rate of postoperative complications and a shorter length of hospital stay, but they also had a lower average number of retrieved central lymph nodes. However, there were no significant between group differences in recurrence rates and disease-free survival. In the hands of an experienced surgeon, robotic thyroidectomy is a feasible and safe option for pediatric patients.
Early Detection and Dynamic Changes of Circulating Tumor Cells in Transgenic NeuN Transgenic (NTTg) Mice with Spontaneous Breast Tumor Development
Authors: Tsai Wen-Sy , Hung Tsung-Fu , Chen Jia-Yang , Huang Shu-Huan , Chang Ying-Chih
Published: June 2021

Background: This study used NeuN transgenic (NTTg) mice with spontaneous breast tumor development to evaluate the dynamic changes of circulating tumor cells (CTCs) prior to and during tumor development. Methods: In this longitudinal, clinically uninterrupted study, we collected 75 μL of peripheral blood at the age of 8, 12, 16, and 20 weeks in the first group of five mice, and at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability in the second group of four mice. Diluted blood samples were run through a modified mouse-CMx chip to isolate the CTCs. Results: The CTC counts of the first group of mice were low (1 ± 1.6) initially. The average CTC counts were 16 ± 9.5, 29.0 ± 18.2, and 70.0 ± 30.3 cells per 75 μL blood at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability, respectively. There was a significant positive correlation between an increase in CTC levels and tumor vascular density (p-value < 0.01). This correlation was stronger than that between CTC levels and tumor size (p-value = 0.076). The captured CTCs were implanted into a non-tumor-bearing NTTg mouse for xenografting, confirming their viability and tumorigenesis. Conclusion: Serial CTCs during an early stage of tumor progression were quantified and found to be positively correlated with the later tumor vascular density and size. Furthermore, the successful generation of CTC-derived xenografts indicates the tumorigenicity of this early onset CTC population.
A Synergistic Combination of Niclosamide and Doxorubicin as an Efficacious Therapy for All Clinical Subtypes of Breast Cancer
Authors: Lohiya Garima , Katti Dhirendra S.
Published: June 2021

Drug resistance is one of the major hurdles in the success of cancer chemotherapy. Notably, aberrantly expressed Wnt/β-catenin signaling plays a major role in the initiation and maintenance of oncogenesis along with development of chemoresistance. Therefore, the combinatorial approach of targeting Wnt/β-catenin pathway along with using a chemotherapeutic agent seems to be a promising strategy to improve cancer therapy. In the present study, we evaluated the combination of niclosamide (Nic), an FDA-approved antihelminthic drug repurposed as a Wnt signaling inhibitor, and doxorubicin (Dox), a conventional anticancer agent, in all clinical subtypes of breast cancer viz. triple negative breast cancer, HER2 positive breast cancer, and hormone receptor positive breast cancer. The results demonstrated that the combination induced apoptosis and caused synergistically enhanced death of all breast cancer cell types at multiple combinatorial concentrations using both the sequential and concurrent treatment regimens. Mechanistically, downregulation of Wnt/β-catenin signaling and cell cycle arrest at G0/G1 phase by Nic and increase in reactive oxygen species by both Nic and Dox along with the inherent cytotoxicity of Dox mediated the synergism between the two drugs in both the treatment regimens. Overall, the combination of Nic and Dox holds promise to be developed as an efficient therapeutic option for breast cancer irrespective of its clinical subtype.
Special Issue on Catalyst Deactivation and Regeneration
Authors: Castaño Pedro
Published: June 2021

Catalyst deactivation causes major losses in the chemical industry worldwide every year [...]
A Review of the Desulfurization Processes Used for Waste Tire Pyrolysis Oil
Authors: Hossain Muhammad Nobi , Choi Myung Kyu , Choi Hang Seok
Published: June 2021

The increasing global population and the rapid industrial development associated therewith have increased the demand for fossil-derived fuel oils. The sources of fossil fuels are limited, and many studies have been being conducted to find alternative fuel sources. Waste tire pyrolysis oil (WTPO) attracts considerable attention as an alternative fuel because its properties are similar to those of diesel oil. However, WTPO has a high sulfur content of >1.0 wt%, which is above the environmental standard limit of 0.1 wt%; therefore, it cannot be used in engines directly. It is thus highly necessary to remove sulfur compounds from tire-derived oils. However, finding an appropriate and environmentally friendly process is proving difficult. This review article presents the various desulfurization methods used to removal sulfur from WTPO, such as hydrodesulfurization (HDS), oxidative desulfurization (ODS), ultrasound-assisted oxidative desulfurization (UAOD), and acid treatment. Of these, HDS is the most expensive as it involves high consumption of hydrogen, high temperature (~450 °C), and high pressure (~200 bar), whereas UAOD is an efficient and economic method of reducing the sulfur content of WTPO.
Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury
Authors: Hernández Ivó H. , Villa-González Mario , Martín Gerardo , Soto Manuel , Pérez-Álvarez María José
Published: June 2021

Ischemic stroke is the second cause of mortality and the first cause of long-term disability constituting a serious socioeconomic burden worldwide. Approved treatments include thrombectomy and rtPA intravenous administration, which, despite their efficacy in some cases, are not suitable for a great proportion of patients. Glial cell-related therapies are progressively overcoming inefficient neuron-centered approaches in the preclinical phase. Exploiting the ability of microglia to naturally switch between detrimental and protective phenotypes represents a promising therapeutic treatment, in a similar way to what happens with astrocytes. However, the duality present in many of the roles of these cells upon ischemia poses a notorious difficulty in disentangling the precise pathways to target. Still, promoting M2/A2 microglia/astrocyte protective phenotypes and inhibiting M1/A1 neurotoxic profiles is globally rendering promising results in different in vivo models of stroke. On the other hand, described oligodendrogenesis after brain ischemia seems to be strictly beneficial, although these cells are the less studied players in the stroke paradigm and negative effects could be described for oligodendrocytes in the next years. Here, we review recent advances in understanding the precise role of mentioned glial cell types in the main pathological events of ischemic stroke, including inflammation, blood brain barrier integrity, excitotoxicity, reactive oxygen species management, metabolic support, and neurogenesis, among others, with a special attention to tested therapeutic approaches.
A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium–Host Interaction
Authors: Bao Yanqing , Wang Lin , Sun Jianjun
Published: June 2021

As a major effector of the ESX-1 secretion system, EsxA is essential for the virulence of pathogenic mycobacteria, such as Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm). EsxA possesses an acidic pH-dependent membrane permeabilizing activity and plays an essential role by mediating mycobacterial escape from the phagosome and translocation to the cytosol for intracellular replication. Moreover, EsxA regulates host immune responses as a potent T-cell antigen and a strong immunoregulator. EsxA interacts with multiple cellular proteins and stimulates several signal pathways, such as necrosis, apoptosis, autophagy, and antigen presentation. Interestingly, there is a co-dependency in the expression and secretion of EsxA and other mycobacterial factors, which greatly increases the complexity of dissecting the precise roles of EsxA and other factors in mycobacterium–host interaction. In this review, we summarize the current understandings of the roles and functions of EsxA in mycobacterial infection and discuss the challenges and future directions.
Human Species D Adenoviruses Isolated from Diarrheal Feces Show Low Infection Rates in Primary Nasal Epithelial Cells
Authors: Aydin Malik , Schellhorn Sebastian , Wirth Stefan , Zhang Wenli , Ehrhardt Anja
Published: June 2021

The importance of adenovirus (Ad) research is significantly increasing with respect to virotherapy for vaccine development, tumor, and gene therapy. Due to the different species and subtypes of this virus, the characterization of the biological significance of especially rare Ad is necessary. Previously, rare Ad types 70, 73, and 74 were originally isolated from fecal samples of immunocompromised patients and they represent recombinants of other Ad types. Here we investigated transduction experiments of these reporter gene tagged Ad types in primary cells exemplified by subject-derived primary nasal epithelial cells (NAEPCs). To analyze the transduction rates, we performed flow cytometry, quantitative polymerase chain reaction (PCR), and cytokine analyses 25 h post-infection. We found that, in contrast to Ad type 5 (as a positive control), the transduction rates of NAEPCs with Ad types 70, 73, and 74 were interestingly low. The major Ad receptor (coxsackievirus-adenovirus receptor and CD46) expression levels showed no significant change after infection with Ad types 70, 73 and 74. Moreover, Interleukin 6 (IL-6) was not released after in vitro Ad transduction. Due to the high risk of developing life-threatening complications in immunocompromised patients by these human species D Ads, even more attention needs to be investigated into the development of diagnostic and therapeutic concepts to prevent and treat those opportunistic infections in susceptible patients.
Cope or Perish? Managing Tipping Points in Developing Coping Strategies for Emergency Response during the First Wave of the COVID-19 Outbreak in Europe
Authors: van der Voorn Tom , de Jong Martin
Published: June 2021

When the first wave of the COVID-19 pandemic started to manifest itself across the globe at an unprecedented pace and magnitude, the various emergency response strategies pursued by highly affected countries in Europe raised many questions about their supposed effectiveness. To contain the outbreak, a rapid and adequate emergency response was vital to control emergent public health risks, but emergency management was challenged by large uncertainty due to many unknowns about crucial determinants of the outbreak, determining the effectiveness of the response, which was often derived from uncertain information. This paper aims to draw lessons from the first wave of the COVID-19 pandemic and it presents a review of strategies for emergency response pursued in eight European countries, including tipping points that triggered strategy shifts in emergency response. The paper shows that: (i) these countries have a culturally determined preference for policy response style (Mediterranean, continental and liberal style) depending on their relative scores on power distance and uncertainty avoidance, which (ii) is reflected in the initially adopted control paradigm and the associated strategy; (iii) Mediterranean countries (Italy, France, Spain) with high levels of power distance and uncertainty avoidance have a tendency to respond to new unknown situations by deploying strong rule-based regulatory systems which offer mental security and social order, whereas continental (Germany and Austria) and liberal countries (the Netherlands, the UK and Sweden) do this to medium and much lower extents.
Regulation of Platelet-Derived ADAM17: A Biomarker Approach for Breast Cancer?
Authors: Zhou Yanjun , Heitmann Jonas S. , Kropp Korbinian N. , Hinterleitner Martina , Koch André , Hartkopf Andreas D. , Salih Helmut R. , Hinterleitner Clemens , Maurer Stefanie
Published: June 2021

Tumor progression and metastasis are critically dependent on the tumor microenvironment. A disintegrin and metalloproteinase 17 (ADAM17) is associated with shedding of several substrates involved in tumor progression and known to be expressed by platelets of healthy donors and patients with solid tumors. Here, we report that platelet-derived ADAM17 (pADAM17) is regulated upon platelet activation of breast cancer patients, but not of healthy individuals. The observed downregulation of pADAM17 on platelets of cancer patients correlated with clinical parameters related to tumor progression including tumor stage and the occurrence of metastasis. Our data identify an association between platelet activation, modulation of platelet-derived ADAM17, and metastasis. In conclusion, we demonstrate that further development of pADAM17 as a liquid biomarker is warranted for monitoring disease progression in breast cancer.
Use of Lateral Flow Immunoassay to Characterize SARS-CoV-2 RBD-Specific Antibodies and Their Ability to React with the UK, SA and BR P.1 Variant RBDs
Authors: Tan Enqing , Frew Erica , Cooper Jeff , Humphrey John , Holden Matthew , Mand Amanda Restell , Li Jun , Anderson Shaya , Bi Ming , Hatler Julia , Person Anthony , Mortari Frank , Gould Kevin , Barry Shelly
Published: June 2021

Identifying anti-spike antibodies that exhibit strong neutralizing activity against current dominant circulating variants, and antibodies that are escaped by these variants, has important implications in the development of therapeutic and diagnostic solutions and in improving understanding of the humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We characterized seven anti-SARS-CoV-2 receptor binding domain (RBD) antibodies for binding activity, pairing capability, and neutralization activity to SARS-CoV-2 and three variant RBDs via lateral flow immunoassays. The results allowed us to group these antibodies into three distinct epitope bins. Our studies showed that two antibodies had broadly potent neutralizing activity against SARS-CoV-2 and these variant RBDs and that one antibody did not neutralize the South African (SA) and Brazilian P.1 (BR P.1) RBDs. The antibody escaped by the SA and BR P.1 RBDs retained binding activity to SA and BR P.1 RBDs but was unable to induce neutralization. We demonstrated that lateral flow immunoassay could be a rapid and effective tool for antibody characterization, including epitope classification and antibody neutralization kinetics. The potential contributions of the mutations (N501Y, E484K, and K417N/T) contained in these variants’ RBDs to the antibody pairing capability, neutralization activity, and therapeutic antibody targeting strategy are discussed.
Aggregated Gaze Data Visualization Using Contiguous Irregular Cartograms
Authors: Krassanakis Vassilios
Published: June 2021

Gaze data visualization constitutes one of the most critical processes during eye-tracking analysis. Considering that modern devices are able to collect gaze data in extremely high frequencies, the visualization of the collected aggregated gaze data is quite challenging. In the present study, contiguous irregular cartograms are used as a method to visualize eye-tracking data captured by several observers during the observation of a visual stimulus. The followed approach utilizes a statistical grayscale heatmap as the main input and, hence, it is independent of the total number of the recorded raw gaze data. Indicative examples, based on different parameters/conditions and heatmap grid sizes, are provided in order to highlight their influence on the final image of the produced visualization. Moreover, two analysis metrics, referred to as center displacement (CD) and area change (AC), are proposed and implemented in order to quantify the geometric changes (in both position and area) that accompany the topological transformation of the initial heatmap grids, as well as to deliver specific guidelines for the execution of the used algorithm. The provided visualizations are generated using open-source software in a geographic information system.
Emerging Role of Epigenetics in Explaining Relationship of Periodontitis and Cardiovascular Diseases
Authors: Hamza Syed Ameer , Asif Saba , Khurshid Zohaib , Zafar Muhammad Sohail , Bokhari Syed Akhtar Hussain
Published: June 2021

Cardiovascular diseases such as ischemic heart diseases or stroke are among the leading cause of deaths globally, and evidence suggests that these diseases are modulated by a multifactorial and complex interplay of genetic, environmental, and lifestyle factors. Genetic predisposition and chronic exposure to modifiable risk factors have been explored to be involved in the pathophysiology of CVD. Environmental factors contribute to an individual’s propensity to develop major cardiovascular risk factors through epigenetic modifications of DNA and histones via miRNA regulation of protein translation that are types of epigenetic mechanisms and participate in disease development. Periodontal disease (PD) is one of the most common oral diseases in humans that is characterized by low-grade inflammation and has been shown to increase the risk of CVDs. Risk factors involved in PD and CVD are determined both genetically and behaviorally. Periodontal diseases such as chronic inflammation promote DNA methylation. Epigenetic modifications involved in the initiation and progression of atherosclerosis play an essential role in plaque development and vulnerability. Epigenetics has opened a new world to understand and manage human diseases, including CVDs and periodontal diseases. Genetic medicine has started a new era of epigenetics to overcome human diseases with various new methodology. Epigenetic profiling may aid in better diagnosis and stratification of patients showing potential predisposed states for disease. A better understanding of the exact regulatory mechanisms of epigenetic pathways driving inflammation is slowly emerging and will aid in developing novel tools for the treatment of disease.
Comparison of the Performance of the Memristor Models in 2D Cellular Nonlinear Network
Authors: Isah Aliyu , Nguetcho Aurélien Serge Tchakoutio , Binczak Stéphane , Bilbault Jean-Marie
Published: June 2021

Many charge controlled models of memristor have been proposed for various applications. First, the original linear dopant drift model suffers discontinuities close to the memristor layer boundaries. Then, the nonlinear dopant drift model improves the memristor behavior near these boundaries but lacks physical meaning and fails for some initial conditions. Finally, we present a new model to correct these defects. We compare these three models in specific situations: (1) when a sine input voltage is applied to the memristor, (2) when a constant voltage is applied to it, and (3) how a memristor transfers charges in a circuit point of view involving resistance-capacitance network. In the later case, we show that our model allows for study of the memristor behavior with phase portraits for any initial conditions and without boundary limitations.
Analysis of Wood Chip Characteristics for Energy Production in Lithuania
Authors: Pedišius Nerijus , Praspaliauskas Marius , Pedišius Justinas , Dzenajavičienė Eugenija Farida
Published: June 2021

Wood chips and logging residues currently comprise the largest share of biomass fuels used for heat generation in district heating plants and are provided by a variety of suppliers. Ash and moisture contents, as well as the calorific value, may vary considerably depending on the composition of the fuel, seasonality, location, and other factors. This paper provides the summarized results of the main characteristics of wood chip moisture and ash content and calorific value, experimentally tested for a significant range of samples. Chip samples were collected from two district heating companies and tested for a significant range of samples. Chip samples were collected from two district heating companies and tested for a 3-year period. The data on fuel chip prices were taken from the electronic wood chip trading platform. The tests were performed using standard express methods, where two sub-samples were taken and analyzed from every chip sample. It was determined that the moisture content of the wood chips varied from 35% to 45%, the calorific value from 18.4 to 19.6 MJ/kg, and the ash content from 0.5% to 4.5%. The calculated relative expanded uncertainty of the moisture content measurement was ±2.1%, of calorific value—±1.5%, and of ash—±1.0%. The repeatability of the results was estimated as the pooled standard deviation.
Quantifying the Representation of Plant Communities in the Protected Areas of the U.S.: An Analysis Based on the U.S. National Vegetation Classification Groups
Authors: McKerrow Alexa , Davidson Anne , Rubino Matthew , Faber-Langendoen Don , Dockter Daryn
Published: June 2021

Plant communities represent the integration of ecological and biological processes and they serve as an important component for the protection of biological diversity. To measure progress towards protection of ecosystems in the United States for various stated conservation targets we need datasets at the appropriate thematic, spatial, and temporal resolution. The recent release of the LANDFIRE Existing Vegetation Data Products (2016 Remap) with a legend based on U.S. National Vegetation Classification allowed us to assess the conservation status of plant communities of the U.S. The map legend is based on the Group level of the USNVC, which characterizes the regional differences in plant communities based on dominant and diagnostic plant species. By combining the Group level map with the Protected Areas Database of the United States (PAD-US Ver 2.1), we quantified the representation of each Group. If the mapped vegetation is assumed to be 100% accurate, using the Aichi Biodiversity target (17% land in protection by 2020) we found that 159 of the 265 natural Groups have less than 17% in GAP Status 1 & 2 lands and 216 of the 265 Groups fail to meet a 30% representation target. Only four of the twenty ecoregions have >17% of their extent in Status 1 & 2 lands. Sixteen ecoregions are dominated by Groups that are under-represented. Most ecoregions have many hectares of natural or ruderal vegetation that could contribute to future conservation efforts and this analysis helps identify specific targets and opportunities for conservation across the U.S.
Estimating Rainfall Interception of Pinus hartwegii and Abies religiosa Using Analytical Models and Point Cloud
Authors: Bolaños-Sánchez Claudia , Prado-Hernández Jorge Víctor , Silván-Cárdenas José Luis , Vázquez-Peña Mario Alberto , Madrigal-Gómez José Manuel , Martínez-Ruíz Antonio
Published: June 2021

Rainfall interception plays a role in the hydrological cycle and is a critical component of water balances at the basin level, which is why understanding it is very important; as a result, in recent years, various authors have proposed different models to explain this process and identify which of them adapts better to each forest species. In this context, the aim of this research was to evaluate the Gash model and the sparse Gash analytical model in Pinus hartwegii Lindl. and Abies religiosa (Kunth) Schltdl. et. Cham., using measurements from 20 precipitation events recorded in May and June 2018 at the Zoquiapan Experimental Forest Station, Mexico. The evaporation rate was calculated using the Penman–Monteith method (PM) and Gash’s calculation procedure. The canopy parameters were also calculated with two methods, a graphical one (A) and a method proposed in this research (B), which is based on point cloud generated with drone photogrammetry. For P. hartwegii, the most accurate model to estimate interception per rainfall event was the Gash model with the A and Gash methods, which were used to calculate the canopy parameters and evaporation rates, respectively; for accumulated interception, the sparse Gash analytical model with the B and PM methods was used. For A. religiosa, the best fit for individual events was presented by the sparse Gash analytical model with the B and PM methods, and for accumulated interception, it was the Gash model with the B and Gash methods. The results allow concluding that the B method proposed in this research is a good alternative for the calculation of rainfall interception, since it tends to improve its estimation, shortening the time for acquiring information about the parameters of the canopy structure and thus minimizing the costs involved.
DNA Analysis Detects Different Mislabeling Trend by Country in European Cod Fillets
Authors: Feldmann Frederik , Ardura Alba , Blanco-Fernandez Carmen , Garcia-Vazquez Eva
Published: June 2021

Atlantic cod, Gadus morhua, is a highly appreciated fish in European seafood markets and is one of the most substituted fish species in the world. Fraud have been detected in European markets in the last decade, finding different substitute species sold as G. morhua or Atlantic cod on the label. In this study, we analyzed 252 samples of fresh and frozen cod fillets sold in Germany, the Netherlands, and France using DNA barcoding. Different trends were found in different countries: while the level of mislabeling found in Germany and the Netherlands remained at zero in the last years, a significant increase was found in the French markets comparing the current results with previous studies on fillets in France. On the one hand, this mislabeling proves the need to encourage European efforts to control seafood authenticity; on the other, zero mislabeling in two countries shows the success of current European regulations.
Transcriptomic Analysis of Drug-Resistance Acinetobacter baumannii under the Stress Condition Caused by Litsea cubeba L. Essential Oil via RNA Sequencing
Authors: Yang Yunqiao , Hao Kaiyuan , Jiang Mingsheng , Memon Fareed Uddin , Guo Lei , Zhang Geyin , Liu Tian , Wu Xianshi , Si Hongbin
Published: June 2021

Litsea cubeba L. essential oil (LCEO) can affect the growth of drug-resistance bacteria. However, research on stress response of drug-resistant A. baumannii under sub-lethal LCEO concentrations had been limited so far. Therefore, transcriptomic analysis of A. baumannii under 1/2 minimum inhibitory concentration (MIC, 0.54 mg/mL) of LCEO was performed. Results of transcriptomic analysis showed that 320/352 genes were significantly up/down-regulated, respectively, in LCEO-treated A. baumannii. Both up and down-regulated genes were significantly enriched in three GO terms (oxidation-reduction process; oxidoreductase activity; oxidoreductase activity, acting on the CH-CH group of donors), which indicated that the redox state of A. baumannii was significantly affected by LCEO. LCEO may also inhibit aerobic respiration, synthesis of ketone bodies and the metabolism of some amino acids while, meanwhile, promoting fatty acid degradation of A. baumannii according to Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The permeability and the stress of cell membrane of A. baumannii were significantly affected by LCEO. After crystal violet dyeing, the biofilm formation of A. baumannii was promoted/inhibited by extremely low/relatively high concentration of LCEO, respectively. LCEO and chloramphenicol have synergistic growth inhibitory effect against A. baumannii according to the Fractional Inhibitory Concentration Index (FICI) value = 0.375. Our results indicate that the growth of A. baumannii was inhibited by LCEO, and give insights into the stress response of A. baumannii under sub-lethal concentrations of LCEO. These results provided evidence that A. baumannii was inhibited by LCEO, and expanded knowledges of stress response of A. baumannii under sub-lethal concentration of LCEO.
De Novo Sporophyte Transcriptome Assembly and Functional Annotation in the Endangered Fern Species Vandenboschia speciosa (Willd.) G. Kunkel
Authors: Bakkali Mohammed , Martín-Blázquez Rubén , Ruiz-Estévez Mercedes , Garrido-Ramos Manuel A.
Published: June 2021

We sequenced the sporophyte transcriptome of Killarney fern (Vandenboschia speciosa (Willd.) G. Kunkel). In addition to being a rare endangered Macaronesian-European endemism, this species has a huge genome (10.52 Gb) as well as particular biological features and extreme ecological requirements. These characteristics, together with the systematic position of ferns among vascular plants, make it of high interest for evolutionary, conservation and functional genomics studies. The transcriptome was constructed de novo and contained 36,430 transcripts, of which 17,706 had valid BLAST hits. A total of 19,539 transcripts showed at least one of the 7362 GO terms assigned to the transcriptome, whereas 6547 transcripts showed at least one of the 1359 KEGG assigned terms. A prospective analysis of functional annotation results provided relevant insights on genes involved in important functions such as growth and development as well as physiological adaptations. In this context, a catalogue of genes involved in the genetic control of plant development, during the vegetative to reproductive transition, in stress response as well as genes coding for transcription factors is given. Altogether, this study provides a first step towards understanding the gene expression of a significant fern species and the in silico functional and comparative analyses reported here provide important data and insights for further comparative evolutionary studies in ferns and land plants in general.