bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Sealing of Laterally Localized Accessory Root Canal with Resin Containing S-PRG Filler in Combination with Non-Surgical Endodontic Treatment: A Case Report
Authors: Hirata-Tsuchiya Shizu , Suzuki Shigeki , Nakamoto Takashi , Kakimoto Naoya , Yamada Satoru , Shiba Hideki
Published: November 2020

The spread of root canal infection to surrounding periodontal tissue through accessory root canals reduces the success rate of endodontic treatment. In this case, cone-beam computed tomography revealed a lesion (4 mm from the apex) resulting from an accessory root canal of the maxillary left central incisor. First, non-surgical endodontic treatment was conducted but the sinus tract remained. Surgical preparation of the root cavity was then conducted to remove potentially infected dentin surrounding the accessory root canal. The cavity was filled and the foramen was sealed with resin containing bioactive surface pre-reacted glass (S-PRG) filler. The photopolymerized resin was then contoured and polished. In combination with subsequent supportive non-surgical endodontic treatment, a good clinical outcome with the disappearance of the sinus tract and clinical symptoms such as discomfort and pressure pain and the regeneration of the alveolar bone hanging over the cavity was obtained. In this case, the good clinical outcome may have been due to the dentin-adhesive property and durability of the pre-adhesive system and composite resin. The better biocompatibility of S-PRG fillers presumably facilitated periodontal tissue healing.
Spatial Patterns in Fiscal Impacts of Environmental Taxation in the EU
Authors: Pászto Vít , Zimmermannová Jarmila , Skaličková Jolana , Sági Judit
Published: November 2020

There are several reasons for environmental taxation implementation. Besides its environmental impact, the main reason for such taxation is its fiscal impact, particularly in generating revenues of public budgets. The main goal of this paper is to observe possible spatial patterns in fiscal impacts of environmental taxation in the EU countries, and to depict the groups of countries with the same (or similar) fiscal impact of these instruments on public budget revenues, including environmental and economic characteristics. Two methods of cluster analysis are used, Ward linkage and K-nearest neighbors (spatial) cluster analysis to observe potential geographical links or implication of fiscal impact. The study is performed for the years 2008 and 2017. Based on the results, we can say that in the year 2008, the EU countries were divided into “the west” and “the east”, with some exceptions. The western countries were characterized by high environmental tax revenues, the eastern countries by low environmental tax revenues. For 2017, the situation is different. The border between old and new EU member states is not so abrupt and clear. The results show higher diversification between EU countries concerning the fiscal impacts of environmental taxation.
Gateway to Outdoors: Partnership and Programming of Outdoor Education Centers in Urban Areas
Authors: O’Farrell Paige , Liu Hung-Ling (Stella)
Published: November 2020

The purpose of the study is to understand the challenges and opportunities of urban outdoor education centers in partnership and programming. The context for this study involves efforts by all-season outdoor education centers, Outdoor Campus (OC), in two urban areas in South Dakota (SD). Outdoor education scope and social-ecological framework were applied to guide this qualitative study. Semi-structured interview questions were used to interview eight outdoor educators in 2019, including four individuals from each service location composed of three males and five female educators. Qualitative content analysis was applied to identify common themes and essential quotations that emerged from the data analyzed through the interviews. Three main themes emerged: (1) gateway to our outdoor legacy (2) working together for outdoor education, including three sub-themes: formal partnership, programmatic partnership, and finding balance in partnership, (3) challenges as opportunities in outdoor education programs, including two sub-themes: common challenges and evolving process.
Holistic Learning Versus Instrumentalism in Teacher Education: Lessons from Values Pedagogy and Related Research
Authors: Lovat Terence
Published: November 2020

This article constitutes a literature review, focusing on the idea of holistic learning, as found in key sources, and its essential contrasting with instrumentalist approaches to learning. It will move to explore updated research on holistic learning factors, with special attention to insights gleaned from values pedagogy and the research that underpins it. The article will juxtapose those insights with the instrumentalism that, it will allege, too often dictates teacher education directions. The article will conclude with an argument that teacher education has become, in modern times, a service industry, too often serving the agendas of governments and teacher unions, rather than preparing teachers to follow the guidelines provided by the latest research into student wellbeing and societal betterment. The article will focus especially on a number of Australian examples to mount the argument that nonetheless applies more generally across Western domains.
Group Teaching Optimization Algorithm Based MPPT Control of PV Systems under Partial Shading and Complex Partial Shading
Authors: Zafar Muhammad Hamza , Al-shahrani Thamraa , Khan Noman Mujeeb , Feroz Mirza Adeel , Mansoor Majad , Qadir Muhammad Usman , Khan Muhammad Imran , Naqvi Rizwan Ali
Published: November 2020

The most cost-effective electrical energy is produced by photovoltaic (PV) systems, and with the smallest carbon footprint, making it a sustainable renewable energy. They provide an excellent alternative to the existing fossil fuel-based energy systems, while providing 4% of global electricity demand. PV system efficiency is significantly reduced by the intrinsic non-linear model, maximum power point (MPP), and partial shading (PS) effects. These two problems cause major power loss. To devise the maximum power point tracking (MPPT) control of the PV system, a novel group teaching optimization algorithm (GTOA) based controller is presented, which effectively deals with the PS and complex partial shading (CPS) conditions. Four case studies were employed that included fast-changing irradiance, PS, and CPS to test the robustness of the proposed MPPT technique. The performance of the GTOA was compared with the latest bio-inspired techniques, i.e., dragon fly optimization (DFO), cuckoo search (CS), particle swarm optimization (PSO), particle swarm optimization gravitational search (PSOGS), and conventional perturb and observe (P&O). The GTOA tracked global MPP with the highest 99.9% efficiency, while maintaining the magnitude of the oscillation <0.5 W at global maxima (GM). Moreover, 13–35% faster tracking times, and 54% settling times were achieved, compared to existing techniques. Statistical analysis was carried out to validate the robustness and effectiveness of the GTOA. Comprehensive analytical and statistical analysis solidified the superior performance of the proposed GTOA based MPPT technique.
Analysis of Polarization and Depolarization Currents of Samples of NOMEX®910 Cellulose–Aramid Insulation Impregnated with Mineral Oil
Authors: Wolny Stefan , Krotowski Adam
Published: November 2020

The article presents results of laboratory tests performed on samples of NOMEX®910 cellulose–aramid insulation impregnated with Nynas Nytro 10× inhibited insulating mineral oil using the polarization and depolarization current analysis method (PDC Method). In the course of the tests, the insulation samples were subjected to a process of accelerated thermal degradation of cellulose macromolecules, as well as weight-controlled dampening, thereby simulating the ageing processes occurring when using the insulation in power transformers. The effects of temperature in the ranges typical of normal transformer operation were also taken into account. On the basis of the obtained data, the activation energy was then fixed together with dominant time constants of cellulose–aramid insulation relaxation processes with respect to the temperature and degree of moisture, as well as thermal degradation of cellulose macromolecules. It was found that the greatest and predictable changes in the activation energy value were caused by the temperature and the degree of moisture in the samples. A similar conclusion applies to the dominant time constant of the relaxation process of cellulose fibers. Degree of thermal degradation samples was of marginal importance for the described parameters. The final outcome of the test results and analyses presented in the article are regression functions for the activation energy and the dominant time constants depending on the earlier listed parameters of the experiment, which may be used in the future diagnostics of the degree of technical wear of cellulose–aramid insulation performed using the PDC method.
Food Ingredients and Active Compounds against the Coronavirus Disease (COVID-19) Pandemic: A Comprehensive Review
Authors: Galanakis Charis M. , Aldawoud Turki M.S. , Rizou Myrto , Rowan Neil J. , Ibrahim Salam A.
Published: November 2020

As media reports have noted, the COVID-19 pandemic has accelerated market mainstreaming of immune-boosting food bioactives, supplements, and nutraceuticals. However, most studies reporting on the potential of bioactives against COVID-19 transmission have been uploaded as preprints with little opportunity to revise content for benefit and impact. The current review discusses current best evidence and information underpinning the role of food ingredients and bioactive compounds in supporting immune functions in humans and animals, specifically in the prevention and treatment of COVID-19 disease. Up to now, some evidence from randomized population and clinical trials has suggested that vitamin D levels may be linked to COVID-19 transmission and severity. Numerous theoretical studies have pointed to polyphenols and particularly flavonoids as potential inhibitors of SARS-CoV-2 infection. There is also inconclusive evidence to support the future use of β-glucan to address COVID-19 due in part to variability in immune response arising from heterogeneity in polysaccharide branch and chain length for different sources and the absence of a standardized extraction method. To confirm the promising outcomes and hypotheses for bioactive compounds, more randomized and controlled clinical studies are needed. The results of such studies would have a profound effect on the prospects of food supplements and nutraceuticals as potential prophylaxis against COVID-19 and serve to help consumers to protect themselves during the post-lockdown recovery era.
Modelling Coalitions: From Concept Formation to Tailoring Empirical Explanations
Authors: Lenine Enzo
Published: November 2020

The coalition literature has thrived during the 20th century, and now constitutes not only a consolidated field in political science, but also one of the most productive fields in terms of theoretical and methodological approaches. Throughout this history, coalition models have played a key role in tailoring explanations about various phenomena such as coalition formation, functioning, and breakdown. Nonetheless, a serious appreciation of their contribution to the development of the field is still lacking. In this context, this paper proposes a taxonomy of models that aims to assess the various functions that coalition models are designed for. I argue that models come in different flavours, namely: conceptual, whose goal consists in formalising abstract concepts via mathematical expressions; quasi-conceptual, which aim to explain empirical regularities; and extrapolative, which test hypotheses with empirical data. The paper surveys classical and more recent works, drawing attention to the different types of models, as well as their theoretical and empirical contributions to the coalition literature.
New Transcriptome-Based SNP Markers for Noug (Guizotia abyssinica) and Their Conversion to KASP Markers for Population Genetics Analyses
Authors: Tsehay Sewalem , Ortiz Rodomiro , Johansson Eva , Bekele Endashaw , Tesfaye Kassahun , Hammenhag Cecilia , Geleta Mulatu
Published: November 2020

The development and use of genomic resources are essential for understanding the population genetics of crops for their efficient conservation and enhancement. Noug (Guizotia abyssinica) is an economically important oilseed crop in Ethiopia and India. The present study sought to develop new DNA markers for this crop. Transcriptome sequencing was conducted on two genotypes and 628 transcript sequences containing 959 single nucleotide polymorphisms (SNPs) were developed. A competitive allele-specific PCR (KASP) assay was developed for the SNPs and used for genotyping of 24 accessions. A total of 554 loci were successfully genotyped across the accessions, and 202 polymorphic loci were used for population genetics analyses. Polymorphism information content (PIC) of the loci varied from 0.01 to 0.37 with a mean of 0.24, and about 49% of the loci showed significant deviation from the Hardy-Weinberg equilibrium. The mean expected heterozygosity was 0.27 suggesting moderately high genetic variation within accessions. Low but significant differentiation existed among accessions (FST = 0.045, p < 0.0001). Landrace populations from isolated areas may have useful mutations and should be conserved and used in breeding this crop. The genomic resources developed in this study were shown to be useful for population genetics research and can also be used in, e.g., association genetics.
Mutations in Collagen Genes in the Context of an Isolated Population
Authors: Zupan Andrej , Matjašič Alenka , Grubelnik Gašper , Tasić Velibor , Momirovska Ana
Published: November 2020

Genetic studies of population isolates have great potential to provide a unique insight into genetic differentiation and phenotypic expressions. Galičnik village is a population isolate located in the northwest region of the Republic of North Macedonia, established around the 10th century. Alport syndrome-linked nephropathy with a complex inheritance pattern has been described historically among individuals in the village. In order to determine the genetic basis of the nephropathies and to characterize the genetic structure of the population, 23 samples were genotyped using a custom-made next generation sequencing panel and 111 samples using population genetic markers. We compared the newly obtained population data with fifteen European population data sets. NGS analysis revealed four different mutations in three different collagen genes in twelve individuals within the Galičnik population. The genetic isolation and small effective population size of Galičnik village have resulted in a high level of genomic homogeneity, with domination of R1a-M458 and R1b-U106* haplogroups. The study explains complex autosomal in cis digenic and X-linked inheritance patterns of nephropathy in the isolated population of Galičnik and describes the first case of Alport syndrome family with three different collagen gene mutations.
Patient Awareness of Reported Adverse Effects Associated with Proton Pump Inhibitors in a Medically Underserved Community
Authors: White Brian , Drew Matthew , Gaughan John , Phadtare Sangita
Published: November 2020

Reports of adverse effects associated with proton pump inhibitors (PPIs) are concerning because of high usage and over-the-counter availability. We sought to determine the awareness of PPI adverse effects among our patient population, which is medically underserved, low-income, and racially diverse. A 21-item survey was administered to gastroenterology-clinic outpatients. It collected information about age, gender, education, race, specialty of the prescriber, specific PPI, indication, knowledge of dose, adherence, duration of use and awareness of any risks. Medical records were reviewed to verify survey responses pertaining to indication, dosing, and adherence. A vast majority (96%) of 101 participants were not aware of PPI adverse effects. In total, 63% of the patients completed a high school education or less, which was associated with a higher risk of long-term PPI use than completion of at least an undergraduate degree (p = 0.05). In contrast to other studies, the shockingly low patient awareness about PPI adverse effects in our patient population is particularly concerning, especially as it is tied to their demographic attributes. This may lead to long-term and high-dose PPI use. Our study highlights the need for effective provider-driven education regarding medication risks, especially in the communities with significant health disparities.
Breaking Bad News, a Pertinent Yet Still an Overlooked Skill: An International Survey Study
Authors: Alshami Abbas , Douedi Steven , Avila-Ariyoshi America , Alazzawi Mohammed , Patel Swapnil , Einav Sharon , Surani Salim , Varon Joseph
Published: November 2020

Delivering bad news to patients is a challenging yet impactful everyday task in clinical practice. Ideally, healthcare practitioners should receive formal training in implementing these protocols, practice in simulation environments, and real-time supervision with feedback. We aimed to investigate whether healthcare providers involved in delivering bad news have indeed received formal training to do so. We conducted a cross-sectional survey study that targeted all healthcare providers in the intensive care units of 174 institutions in 40 different countries. Participants included physicians, nurses, medical students, nursing students, pharmacists, respiratory technicians, and others. The survey tool was created, validated, and translated to the primary languages of these countries to overcome language barriers. A total of 10,106 surveys were collected. Only one third of participants indicated that they had received a formal training. Providers who had received formal training were more likely to deliver bad news than those who had not. Younger and less experienced providers tend to deliver bad news more than older, more experienced providers. The percentage of medical students who claimed they deliver bad news was comparable to that of physicians. Medical schools and post-graduate training programs are strongly encouraged to tackle this gap in medical education.
An Examination of Burnout Predictors: Understanding the Influence of Job Attitudes and Environment
Authors: Cavanaugh Katelyn J. , Lee Hwa Young , Daum Diane , Chang Shine , Izzo Julie G. , Kowalski Alicia , Holladay Courtney L.
Published: November 2020

Burnout amongst healthcare employees is considered an epidemic; prior research indicates a host of associated negative consequences, though more research is needed to understand the predictors of burnout across healthcare employees. All employees in a cancer-focused academic healthcare institution were invited to participate in a bi-annual online confidential employee survey. A 72% response rate yielded 9979 complete responses. Participants completed demographic items, a validated single-item measure of burnout, and items measuring eight employee job attitudes toward their jobs and organization (agility, development, alignment, leadership, trust, resources, safety, and teamwork). Department-level characteristics, turnover, and vacancy were calculated for group level analyses. A univariate F test revealed differences in burnout level by department type (F (3, 9827) = 54.35, p < 0.05) and post hoc Scheffe’s tests showed employees in clinical departments reported more burnout than other departments. Hierarchical multiple regression revealed that employee demographic and job-related variables (including department type) explained 8% of the variance of burnout (F (19, 7880) = 37.95, p < 0.001), and employee job attitudes explained an additional 27% of the variance of burnout (F (8, 7872) = 393.18, p < 0.001). Relative weights analysis at the group level showed that, of the constructs measured, alignment is the strongest predictor of burnout, followed by trust and leadership. The relationships are inverse in nature, such that more alignment is related to less burnout. Turnover and vacancy rates did not predict group level burnout. The results reported here provide evidence supporting a shift in the focus of research and practice from detection to prevention of employee burnout and from individual-focused interventions to organization-wide interventions to prevent burnout.
Functional Recovery after Surgery for Lumbar Spinal Stenosis in Patients with Hypertension
Authors: Roop Sanjesh C. , Battié Michele C. , Jhangri Gian S. , Hu Richard W. , Jones C. Allyson
Published: November 2020

Hypertension is a prevalent condition that is associated with lower health status in patients with lumbar spinal stenosis. The study determined whether hypertension is a prognostic factor associated with functional recovery after spine surgery for lumbar spinal stenosis. This was a secondary analysis of the Alberta Lumbar Spinal Stenosis Study in which patients were identified as participants at the time of lumbosacral magnetic resonance imaging or computed tomography in Calgary, Alberta, Canada. Multivariable linear regression analyses were performed to examine hypertension as a prognostic factor of functional recovery after surgery (Oswestry Disability Index, the Swiss Spinal Stenosis (SSS)-Symptom Severity and SSS-Physical Function scales). Of the 97 surgical participants, 49 who were hypertensive were older (76.8, SD 11.4 years) than the 48 non-hypertensive participants (66.7, SD 12.4 years) (p < 0.001). No significant associations between hypertension and post-operative function in any of the three multivariable models were seen. The Oswestry Disability Index mean score improved after surgery (effect size: 1.73; 95%CI: 1.39, 2.06), with no differences seen between those with and without hypertension (p = 0.699). Large changes were seen after surgery for the SSS-Symptom Severity (effect size: 1.0, 95%CI 0.7, 1.3) and SSS-Physical Function (effect size: 0.9, 95%CI 0.6, 1.2) scales. Hypertension alone does not negatively impact functional recovery following surgery.
Recommendations of the Polish Society of Diabetology and the Lifestyle of Patients with Type 2 Diabetes Mellitus: An Own Research
Authors: Gętek-Paszek Monika , Całyniuk Beata , Ganczarek-Gamrot Alicja , Janion Karolina , Muc-Wierzgoń Małgorzata , Nowakowska-Zajdel Ewa
Published: November 2020

Background and Objectives:Currently, diabetes is becoming a very serious challenge in medicine;type 2 diabetes mellitus (T2DM) is referred to as a noncontagious epidemic of the 21st century. The aim of the study is to assess the lifestyle of patients with type 2 diabetes, in particular eating habits, physical activity, and tobacco smoking, and to compare the obtained values with the latest recommendations of the Polish Society of Diabetology. Materials and Methods: The study group was comprised of 460 patients with type 2 diabetes, treated in the Diabetes Outpatient Clinic (n = 299) and the Clinical Department of Internal Medicine (n = 166). The study was conducted using a questionnaire, which included the Food Intake Frequency Questionnaire, 24 h dietary recall, and the International Physical Activity Questionnaire. Results: Abnormal excessive consumption of saturated fatty acids and salt and insufficient intake of dietary fiber was observed in the study group. Physical activity was insufficient in over 50% of the study group. In the study group, 17% of patients were smokers and the mean number of pack-years was 23. Conclusions:In the study group, excessive fat consumption (i.e.,saturated fatty acids) and dietary fiber deficiency were found in the daily diet.
Early Childhood Junk Food Consumption, Severe Dental Caries, and Undernutrition: A Mixed-Methods Study from Mumbai, India
Authors: Athavale Priyanka , Khadka Nehaa , Roy Shampa , Mukherjee Piyasree , Chandra Mohan Deepika , Turton Bathsheba (Bethy) , Sokal-Gutierrez Karen
Published: November 2020

In India, globalization has caused a nutrition transition from home-cooked foods to processed sugary snacks and drinks, contributing to increased early childhood caries (ECC). This mixed-methods study describes risk factors for ECC and associations with undernutrition in low-income communities in Mumbai. Interviews with mothers of 959 children, ages six-months through six-years, addressed maternal-child nutrition and oral health, and children received dental exams and anthropometric assessments. Focus groups with community health workers and mothers explored experiences and perceptions of oral health, nutrition, and ECC. Descriptive and logistic regression analyses of quantitative data, and content analysis of qualitative data were performed. Eighty percent of children lived 5 min from a junk-food store, over 50% consumed junk-food and sugary tea daily, 50% experienced ECC, 19% had severe deep tooth decay, 27% experienced mouth pain, and 56% experienced chronic and/or acute malnutrition. In children ages 3–6, each additional tooth with deep decay was associated with increased odds of undernutrition (Odds Ratio [OR] 1.10, Confidence Interval [CI] 1.02–1.21). Focus groups identified the junk-food environment, busy family life, and limited dental care as contributors to ECC. Policy interventions include limits on junk-food marketing and incorporating oral health services and counseling on junk-food/sugary drinks into maternal–child health programs.
Analyzing Land-Use Change Scenarios for Ecosystem Services and their Trade-Offs in the Ecological Conservation Area in Beijing, China
Authors: Li Zuzheng , Cheng Xiaoqin , Han Hairong
Published: November 2020

It is generally believed that land-use changes can affect a variety of ecosystem services (ES), but the relationships involved remain unclear due to a lack of systematic knowledge and gaps in data. In order to make rational decisions for land-use planning that is grounded in a systematic understanding of trade-offs between different land-use strategies, it is very important to understand the response mechanisms of various ecosystem services to changes in land-use. Therefore, the objective of our study is to assess the effects of land-use change on six ecosystem services and their trade-offs among the ecosystem services in the ecological conservation area (ECA) in Beijing, China. To do this, we projected future land-use in 2030 under three different scenarios: Business as Usual (BAU), Ecological Protection (ELP), and Rapid Urban Development (RUD), using GeoSOS-FLUS model. Then, we quantified six ecosystem services (carbon storage, soil conservation, water purification, habitat quality, flood regulation, and food production) in response to land-use changes from 2015 to 2030, using a spatially explicit InVEST model. Finally, we illustrated the trade-offs and/or synergistic relationships between each ecosystem service quantified under each of the different scenarios in 2030. Results showed that built-up land is projected to increase by 281.18 km2 at the cost of water bodies and cultivated land from 2015 to 2030 under the RUD scenario, while forest land is projected to increase by 152.38 km2 under the ELP scenario. The carbon storage, soil conservation, habitat quality, and the sum of ecosystem services (SES) would enrich the highest level under the ELP scenario. Land-use strategies that follow the ELP scenario can better maintain the ecosystem services and sustainable development of natural and social economic systems.
Generalization of Soundings across Scales: From DTM to Harbour and Approach Nautical Charts
Authors: Skopeliti Andriani , Stamou Leda , Tsoulos Lysandros , Pe’eri Shachak
Published: November 2020

This paper presents an integrated digital methodology for the generalization of soundings. The input for the sounding generalization procedure is a high resolution Digital Terrain Model (DTM) and the output is a sounding data set appropriate for portrayal on harbour and approach Electronic Navigational Charts (ENCs). The sounding generalization procedure follows the “ladder approach” that is a requisite for the portrayal of soundings on nautical charts, i.e., any sounding portrayed on a smaller scale chart should also be depicted on larger scale charts. A rhomboidal fishnet is used as a supportive reference structure based on the cartographic guidance for soundings to display a rhombus pattern on nautical charts. The rhomboidal fishnet cell size is defined by the depth range and the compilation scale of the charted area. Generalization is based on a number of rules and constraints extracted from International Hydrographic Organization (IHO) standards, hydrographic offices’ best practices and the cartographic literature. The sounding generalization procedure can be implemented using basic geoprocessing functions available in the most commonly used Geographic Information System (GIS) environments. A case study was performed in the New York Lower Bay area based on a high resolution National Oceanic and Atmospheric Administration (NOAA) DTM. The method successfully produced generalized soundings for a number of Harbour and Approach nautical charts at 10 K, 20 K, 40 K and 80 K scales.
Implementation of High-Throughput Sequencing (HTS) in Aptamer Selection Technology
Authors: Komarova Natalia , Barkova Daria , Kuznetsov Alexander
Published: November 2020

Aptamers are nucleic acid ligands that bind specifically to a target of interest. Aptamers have gained in popularity due to their high potential for different applications in analysis, diagnostics, and therapeutics. The procedure called systematic evolution of ligands by exponential enrichment (SELEX) is used for aptamer isolation from large nucleic acid combinatorial libraries. The huge number of unique sequences implemented in the in vitro evolution in the SELEX process imposes the necessity of performing extensive sequencing of the selected nucleic acid pools. High-throughput sequencing (HTS) meets this demand of SELEX. Analysis of the data obtained from sequencing of the libraries produced during and after aptamer isolation provides an informative basis for precise aptamer identification and for examining the structure and function of nucleic acid ligands. This review discusses the technical aspects and the potential of the integration of HTS with SELEX.
The Uniqueness of Tryptophan in Biology: Properties, Metabolism, Interactions and Localization in Proteins
Authors: Barik Sailen
Published: November 2020

Tryptophan (Trp) holds a unique place in biology for a multitude of reasons. It is the largest of all twenty amino acids in the translational toolbox. Its side chain is indole, which is aromatic with a binuclear ring structure, whereas those of Phe, Tyr, and His are single-ring aromatics. In part due to these elaborate structural features, the biosynthetic pathway of Trp is the most complex and the most energy-consuming among all amino acids. Essential in the animal diet, Trp is also the least abundant amino acid in the cell, and one of the rarest in the proteome. In most eukaryotes, Trp is the only amino acid besides Met, which is coded for by a single codon, namely UGG. Due to the large and hydrophobic π-electron surface area, its aromatic side chain interacts with multiple other side chains in the protein, befitting its strategic locations in the protein structure. Finally, several Trp derivatives, namely tryptophylquinone, oxitriptan, serotonin, melatonin, and tryptophol, have specialized functions. Overall, Trp is a scarce and precious amino acid in the cell, such that nature uses it parsimoniously, for multiple but selective functions. Here, the various aspects of the uniqueness of Trp are presented in molecular terms.
Interactions and Signal Transduction Pathways Involved during Central Nervous System Entry by Neisseria meningitidis across the Blood–Brain Barriers
Authors: Borkowski Julia , Schroten Horst , Schwerk Christian
Published: November 2020

The Gram-negative diplococcus Neisseria meningitidis, also called meningococcus, exclusively infects humans and can cause meningitis, a severe disease that can lead to the death of the afflicted individuals. To cause meningitis, the bacteria have to enter the central nervous system (CNS) by crossing one of the barriers protecting the CNS from entry by pathogens. These barriers are represented by the blood–brain barrier separating the blood from the brain parenchyma and the blood–cerebrospinal fluid (CSF) barriers at the choroid plexus and the meninges. During the course of meningococcal disease resulting in meningitis, the bacteria undergo several interactions with host cells, including the pharyngeal epithelium and the cells constituting the barriers between the blood and the CSF. These interactions are required to initiate signal transduction pathways that are involved during the crossing of the meningococci into the blood stream and CNS entry, as well as in the host cell response to infection. In this review we summarize the interactions and pathways involved in these processes, whose understanding could help to better understand the pathogenesis of meningococcal meningitis.
Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma
Authors: Larrea Erika , Fernandez-Mercado Marta , Guerra-Assunção José Afonso , Wang Jun , Goicoechea Ibai , Gaafar Ayman , Ceberio Izaskun , Lobo Carmen , Okosun Jessica , Enright Anton J. , Fitzgibbon Jude , Lawrie Charles H.
Published: November 2020

Follicular lymphoma (FL) is a common indolent B-cell lymphoma that can transform into the more aggressive transformed FL (tFL). However, the molecular process driving this transformation is uncertain. In this work, we aimed to identify microRNA (miRNA)-binding sites recurrently mutated in follicular lymphoma patients, as well as in transformed FL patients. Using whole-genome sequencing data from FL tumors, we discovered 544 mutations located in bioinformatically predicted microRNA-binding sites. We then studied these specific regions using targeted sequencing in a cohort of 55 FL patients, found 16 recurrent mutations, and identified a further 69 variants. After filtering for QC, we identified 21 genes with mutated miRNA-binding sites that were also enriched for B-cell-associated genes by Gene Ontology. Over 40% of mutations identified in these genes were present exclusively in tFL patients. We validated the predicted miRNA-binding sites of five of the genes by luciferase assay and demonstrated that the identified mutations in BCL2 and EZH2 genes impaired the binding efficiency of miR-5008 and miR-144 and regulated the endogenous levels of messenger RNA (mRNA).
Positive Correlation between Pesticide Consumption and Longevity in Solitary Bees: Are We Overlooking Fitness Trade-Offs?
Authors: Strobl Verena , Camenzind Domenic , Minnameyer Angela , Walker Stephanie , Eyer Michael , Neumann Peter , Straub Lars
Published: November 2020

The ubiquitous use of pesticides is one major driver for the current loss of biodiversity, and the common practice of simultaneously applying multiple agrochemicals may further contribute. Insect toxicology currently has a strong focus on survival to determine the potential hazards of a chemical routinely used in risk evaluations. However, studies revealing no effect on survival or even indicating enhanced survival are likely to be misleading, if potential trade-offs between survival and other physiological factors are overlooked. Here, we used standard laboratory experiments to investigate the sublethal (i.e., food consumption) and lethal (i.e., survival) effects of two common agricultural pesticides (Roundup® and clothianidin) on adult female solitary bees, Osmia bicornis. The data showed no significant effect of the treatment on cumulative survival; however, a significant positive correlation between herbicide and insecticide exposure and age was revealed, i.e., bees exposed to higher dosages lived longer. As no significant differences in daily food consumption were observed across treatment groups, increased food intake can be excluded as a factor leading to the prolonged survival. While this study does not provide data on fitness effects, two previous studies using solitary bees observed significant negative effects of neonicotinoid insecticides on fitness, yet not on survival. Thus, we conjecture that the observed non-significant effects on longevity may result from a trade-off between survival and reproduction. The data suggest that a focus on survival can lead to false-negative results and it appears inevitable to include fitness or at least tokens of fitness at the earliest stage in future risk assessments.
Hyponatremia in Patients with Hematologic Diseases
Authors: Koumpis Epameinondas , Florentin Matilda , Hatzimichael Eleftheria , Liamis George
Published: November 2020

Hyponatremia is the most common electrolyte disorder in clinical practice and is associated with increased morbidity and mortality. It is frequently encountered in hematologic patients with either benign or malignant diseases. Several underlying mechanisms, such as hypovolemia, infections, toxins, renal, endocrine, cardiac, and liver disorders, as well as the use of certain drugs appear to be involved in the development or the persistence of hyponatremia. This review describes the pathophysiology of hyponatremia and discusses thoroughly the contributing factors and mechanisms that may be encountered specifically in patients with hematologic disorders. The involvement of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion and renal salt wasting syndrome (RSWS) in the development of hyponatremia in such patients, as well as their differential diagnosis and management, are also presented. Furthermore, the distinction between true hyponatremia and pseudohyponatremia is explained. Finally, a practical algorithm for the evaluation of hyponatremia in hematologic patients, as well as the principles of hyponatremia management, are included in this review.
Effects on the Upper Airway Morphology with Intravenous Addition of Ketamine after Dexmedetomidine Administration in Normal Children
Authors: Mylavarapu Goutham , Fleck Robert J. , Ok Michale S. , Ding Lili , Kandil Ali , Amin Raouf S. , Das Bobby , Mahmoud Mohamed
Published: November 2020

General anesthesia decreases the tone of upper airway muscles in a dose-dependent fashion, potentially narrowing the pharyngeal airway. We examined the effects of adding ketamine on the airway configuration after dexmedetomidine administration in spontaneously breathing children with normal airways. 25 children presenting for Magnetic Resonance Imaging (MRI) of the brain/spine under general anesthesia were prospectively recruited in the study. Patients were anesthetized with dexmedetomidine bolus (2 mcg over 10 min) followed by dexmedetomidine infusion (2 mcg·kg−1·h) and ketamine and permitted to breathe spontaneously via the native airway. MR-CINE images of the upper airway were obtained with dexmedetomidine infusion alone (baseline) and 5, 10, and 15 min after administering ketamine bolus (2 mg·kg−1) in two anatomical axial planes at the nasopharynx and the retroglossal upper airway. Airway lumen is segmented with a semi-automatic image processing approach using a region-growing algorithm. Outcome measures of cross-sectional area, transverse and anterior-posterior diameters of the airway in axial planes at the level of the epiglottis in the retroglossal airway, and in the superior nasopharynx were evaluated for changes in airway size with sedation. Airway dimensions corresponding to the maximum, mean, and minimum sizes during a respiratory cycle were obtained to compare the temporal changes in the airway size. The dose-response of adding ketamine to dexmedetomidine alone condition on airway dimensions were examined using mixed-effects of covariance models. 22/25 patients based on inclusion/exclusion criteria were included in the final analysis. The changes in airway measures with the addition of ketamine, when compared to the baseline of dexmedetomidine alone, were statistically insignificant. The modest changes in airway dimensions are clinically less impactful and within the accuracy of the semi-automatic airway segmentation approach. The effect sizes were small for most airway measures. The duration of ketamine seems to not affect the airway size. In conclusion, adding ketamine to dexmedetomidine did not significantly reduce upper airway configuration when compared to dexmedetomidine alone.
Clinical Application of Whole Exome Sequencing to Identify Rare but Remediable Neurologic Disorders
Authors: Kim Min-Jee , Yum Mi-Sun , Seo Go Hun , Lee Yena , Jang Han Na , Ko Tae-Sung , Lee Beom Hee
Published: November 2020

Background: The aim of this study was to describe the application of whole exome sequencing (WES) in the accurate genetic diagnosis and personalized treatment of extremely rare neurogenetic disorders. Methods: From 2017 to 2019, children with neurodevelopmental symptoms were evaluated using WES in the pediatric neurology clinic and medical genetics center. The clinical presentation, laboratory findings including the genetic results from WES, and diagnosis-based treatment and outcomes of the four patients are discussed. Results: A total of 376 children with neurodevelopmental symptom were evaluated by WES, and four patients (1.1%) were diagnosed with treatable neurologic disorders. Patient 1 (Pt 1) showed global muscle hypotonia, dysmorphic facial features, and multiple anomalies beginning in the perinatal period. Pt 1 was diagnosed with congenital myasthenic syndrome 22 of PREPL deficiency. Pt 2 presented with hypotonia and developmental arrest and was diagnosed with autosomal recessive dopa-responsive dystonia due to TH deficiency. Pt 3, who suffered from intractable epilepsy and progressive cognitive decline, was diagnosed with epileptic encephalopathy 47 with a heterozygous FGF12 mutation. Pt 4 presented with motor delay and episodic ataxia and was diagnosed with episodic ataxia type II (heterozygous CACNA1A mutation). The patients’ major neurologic symptoms were remarkably relieved with pyridostigmine (Pt 1), levodopa (Pt 2), sodium channel blocker (Pt 3), and acetazolamide (Pt 4), and most patients regained developmental milestones in the follow-up period (0.4 to 3 years). Conclusions: The early application of WES helps in the identification of extremely rare genetic diseases, for which effective treatment modalities exist. Ultimately, WES resulted in optimal clinical outcomes of affected patients.
Is the Oxidative Stress in Obstructive Sleep Apnea Associated with Cardiovascular Complications?—Systematic Review
Authors: Fiedorczuk Piotr , Stróżyński Adam , Olszewska Ewa
Published: November 2020

Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease and is considered an independent risk factor for cardiovascular disease. The exact mechanism of cardiovascular complications (CVC) development as a complication of OSA is not entirely understood. Oxidative stress is suspected to be the essential factor in initiating various comorbidities in OSA. Biomarkers of nonenzymatic lipid and protein peroxidation, DNA repair and antioxidant capabilities measured in serum, plasma and urine are frequently used to assess the presence of oxidative stress. We conducted a systematic review and quality assessment of available observational analytic studies to determine whether there is an association between oxidative stress and OSA in patients with prevalent CV disease compared to (a) patients with prevalent CV disease but no OSA, (b) patients with prevalent CV disease and less severe OSA and (c) patients with OSA and no overt CV disease. This systematic review demonstrated that, while oxidative stress is associated with OSA, there was no clear difference in the severity of oxidative stress between OSA patients with or without cardiovascular complications.
Associations between Hypertension, Treatment, and Cognitive Function in the Irish Longitudinal Study on Ageing
Authors: Leong Sook Ling , Robertson Ian H. , Lawlor Brian , Vanneste Sven
Published: November 2020

Epidemiological studies have produced conflicting results regarding the associations between the use of different hypertensive drugs and cognition. Data from the Irish Longitudinal Study on Ageing (TILDA), a nationwide prospective longitudinal study of adults aged 50 or more years, was used to explore the associations between hypertensive status, categories of antihypertensive and cognitive function controlling for age, education, and other demographic and lifestyle factors. The study sample included 8173 participants. ANCOVAs and multivariate regressions were used to assess the cross-sectional and longitudinal associations between cognitive function and hypertension status and the different categories of hypertensive medication. Hypertension was not associated with decline in global cognitive and executive functions and were fully explained by age and education. Different hypertensive medications were not associated with cognitive function. Consistent with previous studies, changes in cognition can largely be explained by age and education. The use of antihypertensive medications is neither harmful nor protective for cognition.
Investigating Anti-Evasion Malware Triggers Using Automated Sandbox Reconfiguration Techniques
Authors: Mills Alan , Legg Phil
Published: November 2020

Malware analysis is fundamental for defending against prevalent cyber security threats and requires a means to deploy and study behavioural software traits as more sophisticated malware is developed. Traditionally, virtual machines are used to provide an environment that is isolated from production systems so as to not cause any adverse impact on existing infrastructure. Malware developers are fully aware of this and so will often develop evasion techniques to avoid detection within sandbox environments. In this paper, we conduct an investigation of anti-evasion malware triggers for uncovering malware that may attempt to conceal itself when deployed in a traditional sandbox environment. To facilitate our investigation, we developed a tool called MORRIGU that couples together both automated and human-driven analysis for systematic testing of anti-evasion methods using dynamic sandbox reconfiguration techniques. This is further supported by visualisation methods for performing comparative analysis of system activity when malware is deployed under different sandbox configurations. Our study reveals a variety of anti-evasion traits that are shared amongst different malware families, such as sandbox “wear-and-tear”, and Reverse Turing Tests (RTT), as well as more sophisticated malware samples that require multiple anti-evasion checks to be deployed. We also perform a comparative study using Cuckoo sandbox to demonstrate the limitations of adopting only automated analysis tools, to justify the exploratory analysis provided by MORRIGU. By adopting a clearer systematic process for uncovering anti-evasion malware triggers, as supported by tools like MORRIGU, this study helps to further the research of evasive malware analysis so that we can better defend against such future attacks.