bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Correlation between Continuity of Care and Quality of Life for Patients with Coronary Heart Disease
Authors: Pai Hsiang-Chu , Hu Yi-Fang , Chao Shu-Yuan , Chen Hsiao-Mei
Published: December 2020

Background: As coronary heart disease (CHD) is a highly complex disease, complex continuity of care (CoC) service should be provided for the patients, and the quality of life (QoL) needs to be regarded as an important measuring indicator for the health-care outcome. Purpose: To understand the general situation of CHD QoL and important predictors. Method: A cross-sectional study design was adopted from August 2019 to July 2020 by structured questionnaires. A total of 163 patients were enrolled, and data were statistically analyzed using SPSS 25.0. Result: The average score of the QoL questionnaire is 56.56/80, and the CoC is 4.32. The overall regression model can explain 58.7% of the variance regarding QoL. Patients’ instrumental activities of daily living (IADLs) (26.1%), age (18.1%), living situation (7%), information transfer (4.8%), main source of income (1.8%), and risk of disability are significantly different from their overall QoL in depression (0.9%). Conclusions: In order to improve the QoL of patients, it is suggested that medical teams should assess the needs of patients immediately upon hospitalization, provide patients with individual CoC, encourage them to participate in community health promotion activities, and strengthen the function of IADL to improve the QoL of patients.
Sociodemographic and Built Environment Associates of Travel to School by Car among New Zealand Adolescents: Meta-Analysis
Authors: Mandic Sandra , Ikeda Erika , Stewart Tom , Garrett Nicholas , Hopkins Debbie , Mindell Jennifer S. , Tautolo El Shadan , Smith Melody
Published: December 2020

Travelling to school by car diminishes opportunities for physical activity and contributes to traffic congestion and associated noise and air pollution. This meta-analysis examined sociodemographic characteristics and built environment associates of travelling to school by car compared to using active transport among New Zealand (NZ) adolescents. Four NZ studies (2163 adolescents) provided data on participants’ mode of travel to school, individual and school sociodemographic characteristics, distance to school and home-neighbourhood built-environment features. A one-step meta-analysis using individual participant data was performed in SAS. A final multivariable model was developed using stepwise logistic regression. Overall, 60.6% of participants travelled to school by car. When compared with active transport, travelling to school by car was positively associated with distance to school. Participants residing in neighbourhoods with high intersection density and attending medium deprivation schools were less likely to travel to school by car compared with their counterparts. Distance to school, school level deprivation and low home neighbourhood intersection density are associated with higher likelihood of car travel to school compared with active transport among NZ adolescents. Comprehensive interventions focusing on both social and built environment factors are needed to reduce car travel to school.
Cellular Consequences of Coenzyme Q10 Deficiency in Neurodegeneration of the Retina and Brain
Authors: Manzar Haider , Abdulhussein Dalia , Yap Timothy E. , Cordeiro M. Francesca
Published: December 2020

Coenzyme Q10 (CoQ10) is a ubiquitous cofactor in the body, operating in the inner mitochondrial membrane, where it plays a vital role in the generation of adenosine triphosphate (ATP) through the electron transport chain (ETC). In addition to this, CoQ10 serves as an antioxidant, protecting the cell from oxidative stress by reactive oxygen species (ROS) as well as maintaining a proton (H+) gradient across lysosome membranes to facilitate the breakdown of cellular waste products. Through the process of ageing, the body becomes deficient in CoQ10, resulting in several systemic manifestations. On a cellular level, one of the consequences of CoQ10 deficiency is apoptosis, which can be visualised in tissues of the central nervous system (CNS). Diseases affecting the retina and brain such as age-related macular degeneration (AMD), glaucoma, Alzheimer’s disease (AD) and Parkinson’s disease (PD) have shown defects in cellular biochemical reactions attributed to reduced levels of CoQ10. Through further research into the pathogenesis of such conditions, the effects of CoQ10 deficiency can be counteracted through supplementation, early detection and intervention.
Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer’s Disease
Authors: Toniolo Sofia , Sen Arjune , Husain Masud
Published: December 2020

People with Alzheimer’s disease (AD) have significantly higher rates of subclinical and overt epileptiform activity. In animal models, oligomeric Aβ amyloid is able to induce neuronal hyperexcitability even in the early phases of the disease. Such aberrant activity subsequently leads to downstream accumulation of toxic proteins, and ultimately to further neurodegeneration and neuronal silencing mediated by concomitant tau accumulation. Several neurotransmitters participate in the initial hyperexcitable state, with increased synaptic glutamatergic tone and decreased GABAergic inhibition. These changes appear to activate excitotoxic pathways and, ultimately, cause reduced long-term potentiation, increased long-term depression, and increased GABAergic inhibitory remodelling at the network level. Brain hyperexcitability has therefore been identified as a potential target for therapeutic interventions aimed at enhancing cognition, and, possibly, disease modification in the longer term. Clinical trials are ongoing to evaluate the potential efficacy in targeting hyperexcitability in AD, with levetiracetam showing some encouraging effects. Newer compounds and techniques, such as gene editing via viral vectors or brain stimulation, also show promise. Diagnostic challenges include identifying best biomarkers for measuring sub-clinical epileptiform discharges. Determining the timing of any intervention is critical and future trials will need to carefully stratify participants with respect to the phase of disease pathology.
Study of the FTM Detector Performance with Garfield++
Authors: Maghrbi Yasser , Yehia Ahmed , Maggi Marcello , Verwilligen Piet
Published: December 2020

The Fast Timing Micro-Pattern Gaseous Detector (FTM) has been recently introduced as a promising alternative for applications that require improved time resolution, such as high-luminosity accelerators and medical imaging. The FTM consists of a stack of several coupled gas layers alternating drift and multiplication stages. The time resolution is determined by the time of the fastest signal among all amplification stages, read out by external electrodes through capacitive couplings. In the present work, we use the Garfield++ simulation toolkit in order to investigate and optimize the FTM performances. Gain, timing, and efficiency of the FTM are studied as a function of different parameters, such as detector geometry, gas mixture, and applied electric fields. The simulations that are presented in this paper show that a time resolution as low as 160 ps can be reached with a 32-layers FTM.
The Impact of Participants’ Anthropometry on Muscle Activation Levels While Interacting with the Level of Expertise, Task Type, and Single Muscles
Authors: Nagahi Morteza , Ibne Hossain Niamat Ullah , Dayarathna Vidanelage L. , Karam Sofia , Babski-Reeves Kari , Jaradat Raed
Published: December 2020

In this research paper, we implemented a mixed factor design in order to investigate the effect of four anthropometries: height, weight, lower-arm dimensions, and upper-arm dimensions on the muscle activation level of participants when interacting with three types of moderators: experiment expertise, task type, and muscle type. The research paper focused on two levels of expertise (novice and expert), two tasks (deck-building and picket installation), and four arm muscles (Brachioradialis (BR), Extensor Carpi Ulnaris (ECU), Flexor Carpi Radialis (FCR), and Flexor Carpi Ulnaris (FCU)), which resulted in 16 (2 × 2 × 4) groups. For each of the 16 groups, the data were analyzed in order to investigate the relationship between the four anthropometries and the four muscle activation levels of the participants. Amos software (IBM, Armonk, NY, USA), along with multiple group structural equation modeling, was used to test a total of 16 direct relationships, as well as the moderation effects in the designed experiment. The results show that the participants’ expertise can moderate the relationship between their height and muscle activation levels, the relationship between their weight and muscle activation levels, and the relationship between their lower arm dimensions and muscle activation levels. Moreover, the findings of this research paper demonstrate that the relationship between the lower arm dimensions and muscle activation levels, and the relationship between weight and muscle activation levels are moderated by the type of muscle used by the participants (i.e., BR, ECU, FCR, and FCU).
Leaping into the Unknown World of Sporisorium scitamineum Candidate Effectors
Authors: Teixeira-Silva Natália Sousa , Schaker Patrícia Dayane Carvalho , Rody Hugo Vianna Silva , Maia Thiago , Garner Christopher M. , Gassmann Walter , Monteiro-Vitorello Claudia Barros
Published: December 2020

Sporisorium scitamineum is a biotrophic fungus causing sugarcane smut disease. In this study, we set up a pipeline and used genomic and dual transcriptomic data previously obtained by our group to identify candidate effectors of S. scitamineum and their expression profiles in infected smut-resistant and susceptible sugarcane plants. The expression profile of different genes after infection in contrasting sugarcane genotypes assessed by RT-qPCR depended on the plant genotypes and disease progression. Three candidate effector genes expressed earlier only in resistant plants, four expressed in both genotypes, and three later in susceptible plants. Ten genes were cloned and transiently expressed in N. benthamiana leaves to determine their subcellular location, while four localized in more than one compartment. Two candidates, g3890 having a nucleoplasmic and mitochondrial location and g5159 targeting the plant cell wall, were selected to obtain their possible corresponding host targets using co-immunoprecipitation (CoIP) experiments and mass spectrometry. Various potential interactors were identified, including subunits of the protein phosphatase 2A and an endochitinase. We investigated the presence of orthologs in sugarcane and using transcriptome data present their expression profiles. Orthologs of sugarcane shared around 70% similarity. Identifying a set of putative fungal effectors and their plant targets provides a valuable resource for functional characterization of the molecular events leading to smut resistance in sugarcane plants and uncovers further opportunities for investigation.
Hex1, the Major Component of Woronin Bodies, Is Required for Normal Development, Pathogenicity, and Stress Response in the Plant Pathogenic Fungus Verticillium dahliae
Authors: Vangalis Vasileios , Papaioannou Ioannis A. , Markakis Emmanouil A. , Knop Michael , Typas Milton A.
Published: December 2020

Woronin bodies are membrane-bound organelles of filamentous ascomycetes that mediate hyphal compartmentalization by plugging septal pores upon hyphal damage. Their major component is the peroxisomal protein Hex1, which has also been implicated in additional cellular processes in fungi. Here, we analyzed the Hex1 homolog of Verticillium dahliae, an important asexual plant pathogen, and we report its pleiotropic involvement in fungal growth, physiology, stress response, and pathogenicity. Alternative splicing of the Vdhex1 gene can lead to the production of two Hex1 isoforms, which are structurally similar to their Neurospora crassa homolog. We show that VdHex1 is targeted to the septum, consistently with its demonstrated function in sealing hyphal compartments to prevent excessive cytoplasmic bleeding upon injury. Furthermore, our investigation provides direct evidence for significant contributions of Hex1 in growth and morphogenesis, as well as in asexual reproduction capacity. We discovered that Hex1 is required both for normal responses to osmotic stress and factors that affect the cell wall and plasma-membrane integrity, and for normal resistance to oxidative stress and reactive oxygen species (ROS) homeostasis. The Vdhex1 mutant exhibited diminished ability to colonize and cause disease on eggplant. Overall, we show that Hex1 has fundamentally important multifaceted roles in the biology of V. dahliae.
Regime-Dependent Good and Bad Volatility of Bitcoin
Authors: Jha Kislay Kumar , Baur Dirk G.
Published: December 2020

This paper analyzes high-frequency estimates of good and bad realized volatility of Bitcoin. We show that volatility asymmetry depends on the volatility regime and the forecast horizon. For one-day ahead forecasts, good volatility commands a stronger impact on future volatility than bad volatility on average and in extreme volatility regimes but not across all quantiles and volatility regimes. For 7-day ahead forecasting horizons the asymmetry is similar to that observed in stock markets and becomes stronger with increasing volatility. Compared with stock markets, the persistence and predictability of volatility is low indicating high variations of volatility.
Scientific Trends in Clinical Research on Zirconia Dental Implants: A Bibliometric Review
Authors: Lorusso Felice , Noumbissi Sammy , Francesco Inchingolo , Rapone Biagio , Khater Ahmad G. A. , Scarano Antonio
Published: December 2020

Background: The clinical use of zirconia implants has been shown to increase steadily due to their biological, aesthetic, and physical properties; therefore, this bibliometric study aimed to review the clinical research and co-authors in the field of zirconia dental implant rehabilitation. Methods: We searched Scopus and Web of Science databases using a comprehensive search strategy to 5 October 2020, and independently paired reviewers who screened studies, and collected data with inclusion criteria restricted to clinical research only (either prospective or retrospective). Data on article title, co-authors, number of citations received, journal details, publication year, country and institution involved, funding, study design, marginal bone loss, survival rate, failure, follow-up, and the author’s bibliometric data were collected and evaluated. Results: A total of 29 clinical studies were published between 2008 and 2020 as 41.4% were prospective cohort studies and 48.3% originated from Germany. Most of the included studies had been published in Clinical Oral Implant Research (n = 12), and the most productive institution was the Medical Center of University of Freiburg. The author with the largest number of clinical studies on zirconia implants was Kohal R.J. (n = 10), followed by Spies B.C. (n = 8). Conclusions: This study revealed that zirconia implants have been more prominent in the last ten years, which is a valuable option for oral rehabilitation with marginal bone loss and survival rate comparable to titanium dental implants.
Cold Expansion Process with Multiple Balls—Numerical Simulation and Comparison with Single Ball and Tapered Mandrels
Authors: Curto-Cárdenas David , Calaf-Chica Jose , Bravo Díez Pedro Miguel , Preciado Calzada Mónica , Garcia-Tarrago Maria-Jose
Published: December 2020

Cold expansion technology is an extended method used in aeronautics to increase fatigue life of holes and hence extending inspection intervals. During the cold expansion process, a mechanical mandrel is forced to pass along the hole generating compressive residual hoop stresses. The most widely accepted geometry for this mandrel is the tapered one and simpler options like balls have generally been rejected based on the non-conforming residual hoop stresses derived from their use. In this investigation a novelty process using multiple balls with incremental interference, instead of a single one, was simulated. Experimental tests were performed to validate the finite element method (FEM) models and residual hoop stresses from multiple balls simulation were compared with one ball and tapered mandrel simulations. Results showed that the use of three incremental balls significantly reduced the magnitude of non-conforming residual hoop stresses and the extension of these detrimental zone.
Erratum: Ilie, N. Comparative Effect of Self- or Dual-Curing on Polymerization Kinetics and Mechanical Properties in a Novel, Dental-Resin-Based Composite with Alkaline Filler. Running Title: Resin-Composites with Alkaline Fillers. Materials 2018, 11, 108
Authors: Ilie Nicoleta
Published: December 2020

Incorrect Title [...]
Striped Non-Uniform Corrosion Behavior of Non-Equiatomic FeMnCoCr High-Entropy Alloy Prepared by Laser Melting Deposition in 0.1 M H2SO4 Solution
Authors: Zhang Zhijian , Yuan Tiechui , Li Ruidi
Published: December 2020

The corrosion behavior of the Fe50Mn30Co10Cr10 high-entropy alloy (HEA) manufactured via laser melting deposition (LMD) was investigated using open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy measurements. The microstructure and morphology of LMD samples before and after the electrochemical tests were compared using X-ray diffraction, optical microscopy, scanning electron microscopy, and electron backscatter diffraction techniques. After the corrosion tests, a striped morphology was observed on the surface of the LMD HEA, which is mainly caused by the interval distribution of high-density and low-density grain-boundary regions. The corrosion performances varied with different planes of the LMD HEA sample, which is mainly controlled by the grain size at each plane. Local corrosion in this HEA is concentrated at the melt pool boundary, which may be due to the abundant metallurgical defects and stress concentration at this location.
Improving Accuracy and Generalization Performance of Small-Size Recurrent Neural Networks Applied to Short-Term Load Forecasting
Authors: Matrenin Pavel V. , Manusov Vadim Z. , Khalyasmaa Alexandra I. , Antonenkov Dmitry V. , Eroshenko Stanislav A. , Butusov Denis N.
Published: December 2020

The load forecasting of a coal mining enterprise is a complicated problem due to the irregular technological process of mining. It is necessary to apply models that can distinguish both cyclic components and complex rules in the energy consumption data that reflect the highly volatile technological process. For such tasks, Artificial Neural Networks demonstrate advanced performance. In recent years, the effectiveness of Artificial Neural Networks has been significantly improved thanks to new state-of-the-art architectures, training methods and approaches to reduce overfitting. In this paper, the Recurrent Neural Network architecture with a small-size model was applied to the short-term load forecasting of a coal mining enterprise. A single recurrent model was developed and trained for the entire four-year operational period of the enterprise, with significant changes in the energy consumption pattern during the period. This task was challenging since it required high-level generalization performance from the model. It was shown that the accuracy and generalization properties of small-size recurrent models can be significantly improved by the proper selection of the hyper-parameters and training method. The effectiveness of the proposed approach was validated using a real-case dataset.
A Simple-FSDT-Based Isogeometric Method for Piezoelectric Functionally Graded Plates
Authors: Liu Tao , Li Chaodong , Wang Chao , Lai Joel Weijia , Cheong Kang Hao
Published: December 2020

An efficient isogeometric analysis method (IGA) based on a simple first-order shear deformation theory is presented to study free vibration, static bending response, dynamic response, and active control of functionally graded plates (FGPs) integrated with piezoelectric layers. Based on the neutral surface, isogeometric finite element motion equations of piezoelectric functionally graded plates (PFGPs) are derived using the linear piezoelectric constitutive equation and Hamilton’s principle. The convergence and accuracy of the method for PFGPs with various mechanical and electrical boundary conditions have been investigated via free vibration analysis. In the dynamic analysis, both time-varying mechanical and electrical loads are involved. A closed-loop control method, including displacement feedback control and velocity feedback control, is applied to the static bending control and the dynamic vibration control analysis. The numerical results obtained are accurate and reliable through comparisons with various numerical and analytical examples.
Radiographic Visibility Limit of Pores in Metal Powder for Additive Manufacturing
Authors: Jaenisch Gerd-Rüdiger , Ewert Uwe , Waske Anja , Funk Alexander
Published: December 2020

The quality of additively manufactured (AM) parts is determined by the applied process parameters used and the properties of the feedstock powder. The influence of inner gas pores in feedstock particles on the final AM product is a phenomenon which is difficult to investigate since very few non-destructive measurement techniques are accurate enough to resolve the micropores. 3D X-ray computed tomography (XCT) is increasingly applied during the process chain of AM parts as a non-destructive monitoring and quality control tool and it is able to detect most of the pores. However, XCT is time-consuming and limited to small amounts of feedstock powder, typically a few milligrams. The aim of the presented approach is to investigate digital radiography of AM feedstock particles as a simple and fast quality check with high throughput. 2D digital radiographs were simulated in order to predict the visibility of pores inside metallic particles for different pore and particle diameters. An experimental validation was performed. It was demonstrated numerically and experimentally that typical gas pores above a certain size (here: 3 to 4.4 µm for the selected X-ray setup), which could be found in metallic microparticles, were reliably detected by digital radiography.
Sulfates from the Pyrite Ore Deposits of the Apuan Alps (Tuscany, Italy): A Review
Authors: Biagioni Cristian , Mauro Daniela , Pasero Marco
Published: December 2020

The occurrence of sulfate minerals associated with the pyrite ores of the southern Apuan Alps has been known since the 19th century but modern mineralogical studies started only in the last decade. Sulfate assemblages were identified in all the pyrite ore deposits from the studied area but the more impressive associations were discovered in the Fornovolasco and Monte Arsiccio mines. Their study allowed to improve the knowledge of the sulfate crystal-chemistry and to achieve a better understanding of the acid mine drainage (AMD) systems associated with pyrite oxidation. More than 20 different mineral species were identified and, among them, four sulfates (volaschioite, giacovazzoite, magnanelliite, and scordariite) have their type localities in the pyrite ore deposits of the Apuan Alps. A review of the mineralogical results of a ten-year-long study is given here.
The Response to Impactful Interactivity on Spectators’ Engagement in a Digital Game
Authors: Brissette-Gendron Raphaëlle , Léger Pierre-Majorique , Courtemanche François , Chen Shang Lin , Ouhnana Marouane , Sénécal Sylvain
Published: December 2020

As gaming spectatorship has become a worldwide phenomenon, keeping the spectator in mind while designing games is becoming more important. Here, we explore the factors that influence spectators’ engagement. Through the use of GRiD Crowd, a game akin to life-size Pong, different levels of spectator influence on the game were tested and their impact on engagement via arousal measures were analyzed. Spectator influence on the game was accomplished via smartphone, where 78 participants put in different audience compositions (alongside friends or strangers) were tested. We found that when the spectators had an impact on the game, higher levels of emotional arousal were recorded, which generated an increase in engagement. These results provide a suggestion of design that could be used by game designers who wish to engage their spectatorship, a segment of their target market that is becoming impossible to ignore.
Oral Bovine Milk Lactoferrin Administration Suppressed Myopia Development through Matrix Metalloproteinase 2 in a Mouse Model
Authors: Ikeda Shin-Ichi , Kurihara Toshihide , Toda Masataro , Jiang Xiaoyan , Torii Hidemasa , Tsubota Kazuo
Published: December 2020

Recent studies have reported an association between myopia development and local ocular inflammation. Lactoferrin (LF) is an iron-binding protein present in saliva, tears, and mother’s milk. Furthermore, sequestering iron by LF can cause its antibacterial property. Moreover, LF has an anti-inflammatory effect. We aimed to determine the suppressive effect of LF against the development and progress of myopia using a murine lens-induced myopia (LIM) model. We divided male C57BL/6J mice (3 weeks old) into two groups. While the experimental group was orally administered LF (1600 mg/kg/day, from 3-weeks-old to 7-weeks-old), a similar volume of Ringer’s solution was administered to the control group. We subjected the 4-week-old mice to −30 diopter lenses and no lenses on the right and left eyes, respectively. We measured the refraction and the axial length at baseline and 3 weeks after using a refractometer and a spectral domain optical coherence tomography (SD-OCT) system in both eyes. Furthermore, we determined the matrix metalloproteinase-2 (MMP-2) activity, and the amount of interleukin-6 (IL-6), MMP-2, and collagen 1A1 in the choroid or sclera. The eyes with a minus lens showed a refractive error shift and an axial length elongation in the control group, thus indicating the successful induction of myopia. However, there were no significant differences in the aforementioned parameters in the LF group. While LIM increased IL-6 expression and MMP-2 activity, it decreased collagen 1A1 content. However, orally administered LF reversed these effects. Thus, oral administration of LF suppressed lens-induced myopia development by modifying the extracellular matrix remodeling through the IL-6–MMP-2 axis in mice.
Diet Advice for Crohn’s Disease: FODMAP and Beyond
Authors: Popa Stefan L. , Pop Cristina , Dumitrascu Dan L.
Published: December 2020

Crohn’s disease (CD) is a chronic, progressive, and destructive granulomatous inflammatory bowel disorder that can involve any part of the gastrointestinal tract. It has been presumed that different types of diet might improve gastrointestinal symptoms in CD patients. The aim of this review was to clarify the efficiency and indications of a low-“fermentable oligo-, di-, mono-saccharides and polyols” (FODMAP) diet (LFD) in CD and to further analyze the available data on other types of diets. PubMed, Cochrane Library, EMBASE and WILEY databases were screened for relevant publications regarding the effect of FODMAP diets on CD. Our search identified 12 articles analyzing the effect of an LFD in CD, 5 articles analyzing the effect of a Mediterranean diet (MD), 2 articles analyzing the effect of a vegetarian diet (VD), and 2 articles analyzing the effect of a low-lactose diet (LLD). The majority of the studies included in this review show the significant efficiency of the LFD in CD patients. We found significant evidence demonstrating that the LFD has a favorable impact on gastrointestinal symptoms in CD patients. Notwithstanding the evidence, it remains to be established if an LFD is more efficient than other types of diets in the short term and especially in the long term.
New Insights into the Binding Features of F508del CFTR Potentiators: A Molecular Docking, Pharmacophore Mapping and QSAR Analysis Approach
Authors: Righetti Giada , Casale Monica , Tonelli Michele , Liessi Nara , Fossa Paola , Pedemonte Nicoletta , Millo Enrico , Cichero Elena
Published: December 2020

Cystic fibrosis (CF) is the autosomal recessive disorder most recurrent in Caucasian populations. To combat this disease, many life-prolonging therapies are required and deeply investigated, including the development of the so-called cystic fibrosis transmembrane conductance regulator (CFTR) modulators, such as correctors and potentiators. Combination therapy with the two series of drugs led to the approval of several multi-drug effective treatments, such as Orkambi, and to the recent promising evaluation of the triple-combination Elexacaftor-Tezacaftor-Ivacaftor. This scenario enlightened the effectiveness of the multi-drug approach to pave the way for the discovery of novel therapeutic agents to contrast CF. The recent X-crystallographic data about the human CFTR in complex with the well-known potentiator Ivacaftor (VX-770) opened the possibility to apply a computational study aimed to explore the key features involved in the potentiator binding. Herein, we discussed molecular docking studies performed onto the chemotypes so far discussed in the literature as CFTR potentiator, reporting the most relevant interactions responsible for their mechanism of action, involving Van der Waals interactions and π–π stacking with F236, Y304, F305 and F312, as well as H-bonding F931, Y304, S308 and R933. This kind of positioning will stabilize the effective potentiator at the CFTR channel. These data have been accompanied by pharmacophore analyses, which promoted the design of novel derivatives endowed with a main (hetero)aromatic core connected to proper substituents, featuring H-bonding moieties. A highly predictive quantitative-structure activity relationship (QSAR) model has been developed, giving a cross-validated r2 (r2cv) = 0.74, a non-cross validated r2 (r2ncv) = 0.90, root mean square error (RMSE) = 0.347, and a test set r2 (r2pred) = 0.86. On the whole, the results are expected to gain useful information to guide the further development and optimization of new CFTR potentiators.
Renegotiating Disciplinary Fields in the Life Sciences
Authors: Minelli Alessandro
Published: December 2020

The general problem around which this Special Issue revolves is that the way in which science is organized into specialties can have negative consequences on the progress of knowledge [...]
Potentially Pathogenic Leptospira in the Environment of an Elephant Camp in Thailand
Authors: Chaiwattanarungruengpaisan Somjit , Thepapichaikul Wasinee , Paungpin Weena , Ketchim Kanokwan , Suwanpakdee Sarin , Thongdee Metawee
Published: December 2020

Leptospira is the causative agent of leptospirosis, a globally emerging zoonotic disease. The infection is commonly acquired through contact with the contaminated environment. To extend the knowledge on environmental source of leptospirosis, we investigated the presence of Leptospira in an elephant camp setting where the interaction between humans, animals, and the shared environment occur particularly when engaging in recreational activities. In this study, a total of 24 environmental samples were collected from an elephant camp area in western Thailand. All samples were processed for Leptospira isolation using the EMJH medium. The identification of Leptospira species was carried out by partial 16S rRNA and secY gene sequencing. Of those 24 samples, 18 samples (75%) were culture-positive for Leptospira. The recovered leptospires were mostly derived from water and soil sampled from a river and a mud pond, the main areas for recreational activities. The majority of the isolates were classified into “Pathogens” clade (89%, 16/18) and more than half of the isolates (61%, 11/18) contained species of the “Saprophytes” clade. Notably, two soil isolates from the river beach sampling area were found to contain leptospiral DNA with high similarity to the pathogenic L. interrogans and L. santarosai. The evidence of diverse Leptospira species, particularly those belonging to the “Pathogens” clade, suggest that the shared environments of an elephant camp can serve as potential infection source and may pose a risk to the elephant camp tourists and workers.
The State of the Art in Biodefense Related Bacterial Pathogen Detection Using Bacteriophages: How It Started and How It’s Going
Authors: Sozhamannan Shanmuga , Hofmann Edward R.
Published: December 2020

Accurate pathogen detection and diagnosis is paramount in clinical success of treating patients. There are two general paradigms in pathogen detection: molecular and immuno-based, and phage-based detection is a third emerging paradigm due to its sensitivity and selectivity. Molecular detection methods look for genetic material specific for a given pathogen in a sample usually by polymerase chain reaction (PCR). Immuno-methods look at the pathogen components (antigens) by antibodies raised against that pathogen specific antigens. There are different variations and products based on these two paradigms with advantages and disadvantages. The third paradigm at least for bacterial pathogen detection entails bacteriophages specific for a given bacterium. Sensitivity and specificity are the two key parameters in any pathogen detection system. By their very nature, bacteriophages afford the best sensitivity for bacterial detection. Bacteria and bacteriophages form the predator-prey pair in the evolutionary arms race and has coevolved over time to acquire the exquisite specificity of the pair, in some instances at the strain level. This specificity has been exploited for diagnostic purposes of various pathogens of concern in clinical and other settings. Many recent reviews focus on phage-based detection and sensor technologies. In this review, we focus on a very special group of pathogens that are of concern in biodefense because of their potential misuse in bioterrorism and their extremely virulent nature and as such fall under the Centers for Disease and Prevention (CDC) Category A pathogen list. We describe the currently available phage methods that are based on the usual modalities of detection from culture, to molecular and immuno- and fluorescent methods. We further highlight the gaps and the needs for more modern technologies and sensors drawing from technologies existing for detection and surveillance of other pathogens of clinical relevance.
Species D Adenoviruses as Oncolytic Viral Vectors
Authors: Bullard Brianna L. , Corder Brigette N. , Weaver Eric A.
Published: December 2020

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup and developed replication-competent species D Ads expressing the human sodium iodide symporter protein (hNIS) for combination radiovirotherapy. We evaluated the species D Ad vectors transduction, replication, cytotoxicity, and gene expression in six different cancer cell lines. Species D Ads showed the greatest transduction and cytotoxic killing in the SKBR3 breast cancer cells, followed by 293, A549, and HepG2 cells, however the cytotoxicity was less than the wild type Ad5 virus. In contrast, species D Ads showed limited transduction and cytotoxicity in the Hela and SKOV3 cancer cell lines. These species D Ad vectors also successfully expressed the hNIS gene during infection leading to increased iodide uptake in multiple cancer cell lines. These results, the low seroprevalence of anti-species D antibodies, and the lack of binding to blood coagulation FX, support further exploration of species D Ads as alternative oncolytic adenoviruses against multiple types of cancer.
Multiple SARS-CoV-2 Introductions Shaped the Early Outbreak in Central Eastern Europe: Comparing Hungarian Data to a Worldwide Sequence Data-Matrix
Authors: Kemenesi Gábor , Zeghbib Safia , Somogyi Balázs A , Tóth Gábor Endre , Bányai Krisztián , Solymosi Norbert , Szabo Peter M , Szabó István , Bálint Ádám , Urbán Péter , Herczeg Róbert , Gyenesei Attila , Nagy Ágnes , Pereszlényi Csaba István , Babinszky Gergely Csaba , Dudás Gábor , Terhes Gabriella , Zöldi Viktor , Lovas Róbert , Tenczer Szabolcs , Kornya László , Jakab Ferenc
Published: December 2020

Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019, the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of 21 April 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here, we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.
Increased HIV Subtype Diversity Reflecting Demographic Changes in the HIV Epidemic in New South Wales, Australia
Authors: Di Giallonardo Francesca , Pinto Angie , Keen Phillip , Shaik Ansari , Carrera Alex , Salem Hanan , Selvey Christine , Nigro Steven , Fraser Neil , Price Karen , Holden Joanne , Lee Frederick , Dwyer Dominic , Bavinton Benjamin , Grulich Andrew , Kelleher Anthony ,   on behalf of the NSW HIV Prevention Partnership Project
Published: December 2020

Changes over time in HIV-1 subtype diversity within a population reflect changes in factors influencing the development of local epidemics. Here we report on the genetic diversity of 2364 reverse transcriptase sequences from people living with HIV-1 in New South Wales (NSW) notified between 2004 and 2018. These data represent >70% of all new HIV-1 notifications in the state over this period. Phylogenetic analysis was performed to identify subtype-specific transmission clusters. Subtype B and non-B infections differed across all demographics analysed (p < 0.001). We found a strong positive association for infections among females, individuals not born in Australia or reporting heterosexual transmission being of non-B origin. Further, we found an overall increase in non-B infections among men who have sex with men from 50 to 79% in the last 10 years. However, we also found differences between non-B subtypes; heterosexual transmission was positively associated with subtype C only. In addition, the majority of subtype B infections were associated with clusters, while the majority of non-B infections were singletons. However, we found seven non-B clusters (≥5 sequences) indicative of local ongoing transmission. In conclusion, we present how the HIV-1 epidemic has changed over time in NSW, becoming more heterogeneous with distinct subtype-specific demographic associations.
HIV-1C env and gag Variation in the Cerebrospinal Fluid and Plasma of Patients with HIV-Associated Cryptococcal Meningitis in Botswana
Authors: Kelentse Nametso , Moyo Sikhulile , Mogwele Mompati L. , Ditshwanelo Doreen , Mokaleng Baitshepi , Moraka Natasha O. , Lechiile Kwana , Leeme Tshepo B. , Lawrence David S. , Musonda Rosemary , Kasvosve Ishmael , Harrison Thomas S. , Jarvis Joseph N. , Gaseitsiwe Simani
Published: December 2020

HIV-1 compartmentalization in reservoir sites remains a barrier to complete HIV eradication. It is unclear whether there is variation in HIV-1 env and gag between cerebrospinal fluid (CSF) and plasma of individuals with HIV-associated cryptococcal meningitis (CM). We compared HIV-1 env characteristics and the gag cytotoxic T-lymphocyte (CTL) escape mutations from CSF and plasma samples. Employing population-based Sanger sequencing, we sequenced HIV-1 env from CSF of 25 patients and plasma of 26 patients. For gag, 15 CSF and 21 plasma samples were successfully sequenced. Of these, 18 and 9 were paired env and gag CSF/plasma samples, respectively. There was no statistically significant difference in the proportion of CCR5-using strains in the CSF and plasma, (p = 0.50). Discordant CSF/plasma virus co-receptor use was found in 2/18 pairs (11.1%). The polymorphisms in the HIV-1 V3 loop were concordant between the two compartments. From the HIV-1 gag sequences, three pairs had discordant CTL escape mutations in three different epitopes of the nine analyzed. These findings suggest little variation in the HIV-1 env between plasma and CSF and that the CCR5-using strains predominate in both compartments. HIV-1 gag CTL escape mutations also displayed little variation in CSF and plasma suggesting similar CTL selective pressure.
Hybrids in Juncus section Juncotypus, with a description of J. x lancastriensis (Juncaceae)
Authors: Stace Clive A.
Published: December 2020

The differences between the five native species of Juncus section Juncotypus that occur in the British Isles are summarised, and the occurrence of five hybrids surveyed. The diagnostic morphological and anatomical details of the hybrids are presented, with emphasis on the endemic J. balticus x J. inflexus, which is described as J. x lancastriensis Stace and of which two nothovars are distinguished.
Galeopsis speciosa (Lamiaceae): an Open Vegetation seed bank community at Worsley in Salford (v.c.59), revealed during construction of the new Royal Horticultural Society Garden at Bridgewater
Authors: Crawley Michael J.
Published: December 2020

This paper provides a baseline flora for the site of the new garden of the Royal Horticultural Society at Worsley New Hall in Salford (v.c.59). During construction, 35,000 m3 of top-soil, sub-soil and spoil were stripped and stored onsite; species recruiting from these seed banks were monitored 2017-2020, leading to the description of a new Galeopsis speciosa Open Vegetation plant community. Four commercial wildflower mixes were used during post-construction landscaping in 2019, and their establishment was assessed in 2020. It will be interesting to follow the survival of these introduced species, many of which are not native to the site.
An Analysis of Patient Safety Events Submitted by Abortion Facilities in Pennsylvania 2017–2019
Authors: Kukielka Elizabeth
Published: December 2020

Induced abortion, also called elective abortion, therapeutic abortion, and termination of pregnancy, is widely considered a safe procedure, but complications are known to occur. In Pennsylvania, an induced abortion may be performed at an abortion facility as an outpatient procedure, and these facilities are required to report patient safety events to the Pennsylvania Patient Safety Reporting System (PA-PSRS). We extracted 736 events submitted to PAPSRS by abortion facilities from 2017 through 2019 and analyzed these events in order to better understand patient safety concerns at abortion facilities in particular. All patients were female, and they ranged in age from 14 to 47 years, with a median patient age of 27 years (interquartile range = 23 to 31 years). Complications related to an induced abortion comprised the majority of events (71.6%; n=527), followed by unplanned transfers to the emergency department or acute visits to a healthcare facility following an induced abortion (13.9%; n=102). The most common complication associated with induced abortion was an incomplete abortion (i.e., retained pregnancy tissue; n=343); other complications included failed abortions (i.e., a continuing intrauterine pregnancy following an abortion; n=101), infections (e.g., endometritis and pelvic inflammatory disease [PID]; n=45), and surgical complications (e.g., hematometra, uterine perforation, and cervical lacerations; n=66). The remainder of events (14.5%; n=107) described other patient safety events that occurred at abortion facilities, such as documentation failures and medication-related events.
ESTIMATION OF THERMAL INSULATION THICKNESS AND DEPTH OF UNDERGROUND POLYETHYLENE HEAT SUPPLY PIPELINES IN REGIONS WITH PERMAFROST
Authors: Akimov M. , Mordovskoy S. , Starostin N.
Published: December 2020

The process of thawing and freezing of the host soil of an underground polyethylene heat supply pipeline with thermal insulation, operated in areas of permafrost distribution, is considered. The task is to determine the thickness of the thermal insulation of the pipeline and the size of its depth based on the analysis of the temperature field in the ground during long-term cycle. The temperature field in the "insulated pipe-ground" system, which changes over time, is proposed to be determined by solving the heat conduction equations in polar coordinates. In this case, a bundle of pipes is considered as one pipe of equivalent radius. This approach allows to simplify the interface conditions of the pipe, thermal insulation, polyethylene shell and the host soil, as well as to use a simple numerical method for solving the equation – the finite difference method. The results of calculations of the maximum depth of soil thawing from the depth of the heat supply pipe at different thicknesses of thermal insulation are presented. It is proposed to determine the optimal depth of the underground heat supply pipeline from the condition of annual establishment of the zero isotherm of the host soil at the level of the boundary of the active soil layer by the beginning of the heating season. The possibility of finding a zero isotherm at this level is illustrated by calculations of isotherms by the beginning of the heating season (September) at various depths and thicknesses of thermal insulation. Based on the results of calculations the method of estimation the insulation thickness and depth of the pipeline from the condition of minimizing the functional that characterizes the measure of deviation of the ordinates of the zero isotherm on the left-hand boundary of the region from the depth of the active soil layer at the beginning of the heating season.
Franciscaanse Jeruzalems in Italië. Drie sacri monti nader bekeken (ca. 1480-1520)
Authors: Ritsema van Eck Marianne Petra
Published: December 2020

This short paper (in Dutch) investigates the earliest Italian sacri monti which are also Observant Franciscan new Jerusalems and explores what characterized these sanctuaries around 1500 CE. Most sacri monti are found in the Northern Italian Alps, date to the 16th and 17th centuries, and can be connected to the Counter Reformation. They are often dedicated to devotional themes such as the Virgin Mary and the Rosary. Of these Northern Italian examples I only pay attention to the sacro monte of Varallo, the oldest and most well-known example, which replicates Jerusalem and was founded by Observant Franciscans. My discussion raises the question: what was specifically Observant Franciscan about this sanctuary? To answer this question I consider the sacri monti of La Verna and San Vivaldo in Tuscany, which are also Observant Franciscan new Jerusalems.
USO DE OFICINAS COMO PRÁTICA PEDAGÓGICA PARA A ASSIMILAÇÃO E CONSTRUÇÃO DE CONCEITOS
Authors: Tamashiro Camila Baleiro Okado
Published: December 2020

USO DE OFICINAS COMO PRÁTICA PEDAGÓGICA PARA A ASSIMILAÇÃO E CONSTRUÇÃO DE CONCEITOS
UM DESCONHECIDO ENTRE NÓS: A HISTÓRIA E A CULTURA INDÍGENA NA SALA DE AULA
Authors: Melo Cristiane Dias de
Published: December 2020

UM DESCONHECIDO ENTRE NÓS: A HISTÓRIA E A CULTURA INDÍGENA NA SALA DE AULA
SENTIR O SER ALUNO...
Authors: Antonio Davi Gutierrez
Published: December 2020

SENTIR O SER ALUNO...