bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning Analytics for Diagnosing Cognitive Load in E-Learning Using Bayesian Network Analysis
Authors: Choi Younyoung , Kim Jigeun
Published: September 2021

A learner’s cognitive load is highly associated with their academic achievement within learning systems. Diagnostic information about a learner’s cognitive load is useful for achieving optimal learning, by enabling the learner to manage and control their cognitive load in the e-learning environment. However, little empirical research has been conducted to obtain diagnostic information about the cognitive load in e-learning systems. The purpose of this study was to analyze a personalized diagnostic evaluation for a learner’s cognitive load in an e-learning system, using the Bayesian Network (BN) as a learning analytic method. Data from 700 learners were collected from Cyber University. A learner’s cognitive load level was measured in terms of three components: extraneous cognitive load, intrinsic cognitive load, and germane cognitive load. The BN was built by representing the relationship among the extraneous cognitive load, intrinsic cognitive load, germane cognitive load, and academic achievement. The conditional and marginal probabilities in the BN were estimated. This study found that the BN provided diagnostic information about a learner’s level of cognitive load in the e-learning system. In addition, the BN predicted the learner’s academic achievement in terms of their different cognitive load patterns. This study’s results imply that diagnostic information related to cognitive load helps learners to improve academic achievement by managing and controlling their cognitive loads in the e-learning environment. In addition, instructional designers are able to offer more appropriately customized instructional methods by considering learners’ cognitive loads in online learning.
Sustainable Exterior Lighting for Cultural Heritage Buildings and Monuments
Authors: Kobav Matej Bernard , Eržen Matic , Bizjak Grega
Published: September 2021

The improper illumination of cultural heritage buildings and monuments can be a source of enormous light pollution, which can have a major impact on the overall environment of the illuminated area. Such lighting can be the result of carelessness or a poorly designed lighting system. This paper presents one of the methodologies that can significantly reduce light pollution, especially spilt light out of building façades. The methodology is based on using luminaires with specially made shutters and an appropriate silhouette of the object. The shutters are designed with the help of photos of the object and the location’s sizes measured. The methodology was tested during the renovation of the lighting systems of different churches in Slovenia and is described using the example of the Church of St. Thomas near Ptuj, Slovenia (N 46°28.9554′, E 16°0.7416′). The results show that the methodology is effective and can significantly reduce light pollution that occurs when such buildings are incorrectly lit.
Pulling on Heartstrings: Three Studies of the Effectiveness of Emotionally Framed Communication to Encourage Workplace Pro-Environmental Behavior
Authors: Russell Sally V. , Ashkanasy Neal M.
Published: September 2021

We investigated whether the emotional framing of climate change communication can influence workplace pro-environmental behavior. In three quasi-experimental studies, we examined whether emotional displays in climate change communication affected participants’ subsequent workplace pro-environmental behavior. In Studies 1 and 2, undergraduate and master’s students viewed a fictional news video about climate change, where the newsreader displayed one of five emotions: sadness, fear, anger, contentment, and hope. The dependent variable was recycling behavior following the viewing. In Study 3, office employees viewed the same news videos online; the dependent variable was requesting further information to increase pro-environmental behavior in the workplace. The results from all three studies show that displayed emotion significantly affected pro-environmental behavior and that sadness, in particular, resulted in significantly less workplace pro-environmental behavior. These results indicate the need to study the effect of discrete emotions, rather than assuming that emotions of the same valence have similar effects. The results also underscore the importance of using experimental designs in advancing the field. We conclude with a discussion of the implications of our findings for research, theory, and practice of emotionally framed communication of sustainability messages.
Allantoin from Valuable Romanian Animal and Plant Sources with Promising Anti-Inflammatory Activity as a Nutricosmetic Ingredient
Authors: Dinica Rodica Mihaela , Sandu Cristina , Dediu Botezatu Andreea Veronica , Cazanevscaia Busuioc Anna , Balanescu Fanica , Ionica Mihaila Maria Daniela , Dumitru Caterina Nela , Furdui Bianca , Iancu Alina Viorica
Published: September 2021

Helix aspersa (HA), Helix pomatia (HP) and Symphytum officinale are common organisms in Romania’s biosphere, widely known for their allantoin content and their therapeutic properties. Herein, the allantoin was separated and quantified from the aqueous extracts of Romanian comfrey root and the secretions of HA and HP snails. This study also focused on determining the antioxidant and anti-inflammatory activities of these Romanian allantoin-rich samples. The plant extracts were obtained through two methods: ultrasonic extraction and enzymatic ultrasonic extraction. A microplate method was used for the quantitative determination of allantoin content. The antioxidant activity was measured by using the DPPH radical scavenging method. The antioxidant capacity of the samples was studied in order to observe the type of interactions generated by the chemical complex present in their composition. High concentrations of allantoin were obtained by enzymatic ultrasonic extraction method (EUE—102 ± 0.74 μg/mL), and also in the water-soluble fraction of the snail secretion (FS1—22.051 μg/mL). The antioxidant screening suggests that Symphytum officinale and snail mucus extracts could be used as promising natural substitutes for synthetic antioxidants in products used for therapeutic purposes. The evaluation of anti-inflammatory activity was also investigated, allantoin-rich samples showing a promising action (FS1—81.87 ± 2.34%). In future, the inclusion of allantoin-rich extracts in various novel pharmaceutical forms for new therapeutic applications could be achieved. The study will continue with the formulation of a nutricosmetic product with snail mucus and Symphytum officinale extract as principal bioactive ingredients.
Antibiotic Resistance of Escherichia coli Isolated from Processing of Brewery Waste with the Addition of Bulking Agents
Authors: Wolny-Koładka Katarzyna , Zdaniewicz Marek
Published: September 2021

The aim of the study was to determine the drug resistance profile and to assess the presence of genes responsible for the production of extended-spectrum beta-lactamases in Escherichia coli isolated from energy-processed hop sediment with the addition of bulking agents. Antibiotic resistance was determined by the disk diffusion method and the PCR technique to detect genes determining the extended-spectrum beta-lactamases (ESBLs) mechanism. A total of 100 strains of E. coli were collected. The highest resistance was found to aztreonam, tetracycline, ampicillin, ticarcillin, and ceftazidime. The bacteria collected were most often resistant to even 10 antibiotics at the same time and 15 MDR strains were found. The ESBL mechanism was determined in 14 isolates. Among the studied genes responsible for beta-lactamase production, blaTEM was the most common (64%). The study revealed that the analysed material was colonised by multi-drug-resistant strains of E. coli, which pose a threat to public health. The obtained results encourage further studies to monitor the spread of drug resistance in E. coli.
A Prospective Social Life Cycle Assessment (sLCA) of Electricity Generation from Municipal Solid Waste in Nigeria
Authors: Nubi Oluwaseun , Morse Stephen , Murphy Richard J.
Published: September 2021

This research assesses the social impacts that could arise from the potential waste-to-energy (WtE) generation of electricity from municipal solid waste (MSW) in the cities of Lagos and Abuja in Nigeria. Social life cycle assessment (sLCA) was the main analytical approach used coupled with a participatory approach to identify relevant social issues to serve as the potential sLCA impact ‘subcategories’. Focus group research in both cities led to the identification of 11 social issues that were transformed into social impact subcategories with appropriate indicators for the sLCA. These were populated with data from a questionnaire-based survey with approximately 140 stakeholders. The results indicated that the impact subcategories “Improved Electricity Supply” and “Income” were ranked respectively as having the most and the least significant social impacts associated with the potential adoption of WtE in these two cities in Nigeria. Overall, the research showed that the expected social impact was higher for WtE electricity generation in Lagos than in Abuja. This difference may be related to the higher population and greater amounts of waste in Lagos and its position as a hub for many of the country’s commercial and industrial activities which have long been affected by inadequate electricity supply. This study also provides an example of the use of participatory processes as an important approach in sLCA for the elucidation of social issues that are directly pertinent to key local perspectives when considering such technology implementations.
Sustainable Education through E-Learning: The Case Study of iLearn2.0
Authors: Chen Fu-Hsuan
Published: September 2021

The present paper studies a blended learning approach provided by a university in central Taiwan from 2018 to 2020. In this approach, a Moodle E-learning platform called iLearn2.0 was used along with an onsite classroom. iLearn 2.0 has four major features, including cloud services, mobile learning, flipped classroom, and data analysis. The platform was used during 2018–2020 in the Citizen Participation course, helping the researcher/teacher to design an interactive course content and aiding students to complete classroom activities through their devices. In total, 127 students enrolled in citizen participation courses were taught during 2018–2020, using different teaching methods. In 2018, students studied in a physical classroom. iLearn2.0 was integrated with the physical classroom for the 2019 course; lastly, the iLearn2.0 platform was used alone in 2020. To evaluate the effect of virtual teaching on the students’ performance, the researcher used summative assessment as the dependent variable. The findings show that the class that received the iLearn2.0- assisted teaching had a significantly better learning performance than the other two classes. However, when researchers used iLearn2.0 alone, both the scores and the feedback from students were lower than those in blended and face-to-face teaching. The results suggest the effectiveness of iLearn2.0 assistance, while learners’ performance did not show any significant change in a totally online class. Results were assessed in the view of sustainability, and three sustainability dimensions were found to be improved in the hybrid classroom. The researcher suggests that iLearn2.0 be integrated with other learning tools for maximum results, as it allows students to have a more diverse learning experience, strengthen sustainable learning, and grasp the progress of their courses and learning activities in a timely manner.
Acquired Facial, Maxillofacial, and Oral Asymmetries—A Review Highlighting Diagnosis and Management
Authors: Iyer Janaki , Hariharan Arvind , Cao Uyen Minh Nha , Tran Simon D.
Published: September 2021

Facial asymmetry refers to the absence of, or the deviation from the regular mirror image of facial structures, relative to a referenced midline axis. It can be attributed to a wide spectrum of deformities, including congenital, developmental, or acquired conditions, which can originate either prenatally or postnatally. Though highly prevalent, asymmetry commonly goes undiagnosed due to its subtle or relative nature. Among the spectrum of conditions, acquired cases are triggered postnatally, in previously normal individuals, thus subjecting them to sudden, eventful psychological and psychosocial disharmony. When detected early, timely management may help intervene progressive growth of these conditions. This, therefore, emphasizes the need for a thorough diagnostic workup including medical/dental history, clinical examinations, study models, photographic and radiographic records for a case-by-case basis to prevent severe functional and aesthetic complications. Recently, advanced diagnostic procedures, such as stereophotogrammetry, 3D stereolithographic models, skeletal scintigraphy (radionucleotide scans), 3D computed tomographic scans, cone-beam computed tomography, and magnetic resonance imaging, have provided innovative diagnostic instruments for numerous craniofacial defects. This descriptive review aims at focusing on the factors leading to frequently encountered conditions of acquired facial asymmetry and highlights their clinical evaluation, conservative and surgical interventions by a multi-disciplinary team of clinicians.
Correction: Cabrera Martínez et al. On the Secure Total Domination Number of Graphs. Symmetry 2019, 11, 1165
Authors: Cabrera Martínez Abel , Montejano Luis P. , Rodríguez-Velázquez Juan A.
Published: September 2021

The authors wish to make the following corrections on paper [...]
A Topological Selection of Folding Pathways from Native States of Knotted Proteins
Authors: Barbensi Agnese , Yerolemou Naya , Vipond Oliver , Mahler Barbara I. , Dabrowski-Tumanski Pawel , Goundaroulis Dimos
Published: September 2021

Understanding how knotted proteins fold is a challenging problem in biology. Researchers have proposed several models for their folding pathways, based on theory, simulations and experiments. The geometry of proteins with the same knot type can vary substantially and recent simulations reveal different folding behaviour for deeply and shallow knotted proteins. We analyse proteins forming open-ended trefoil knots by introducing a topologically inspired statistical metric that measures their entanglement. By looking directly at the geometry and topology of their native states, we are able to probe different folding pathways for such proteins. In particular, the folding pathway of shallow knotted carbonic anhydrases involves the creation of a double-looped structure, contrary to what has been observed for other knotted trefoil proteins. We validate this with Molecular Dynamics simulations. By leveraging the geometry and local symmetries of knotted proteins’ native states, we provide the first numerical evidence of a double-loop folding mechanism in trefoil proteins.
Depthwise Separable Relation Network for Small Sample Hyperspectral Image Classification
Authors: Wang Aili , Liu Chengyang , Xue Dong , Wu Haibin , Zhang Yuxiao , Liu Meihong
Published: September 2021

Although hyperspectral data provide rich feature information and are widely used in other fields, the data are still scarce. Training small sample data classification is still a major challenge for HSI classification based on deep learning. Recently, the method of mining sample relationships has been proved to be an effective method for training small samples. However, this strategy requires high computational power, which will increase the difficulty of network model training. This paper proposes a modified depthwise separable relational network to deeply capture the similarity between samples. In addition, in order to effectively mine the similarity between samples, the feature vectors of support samples and query samples are symmetrically spliced. According to the metric distance between symmetrical structures, the dependence of the model on samples can be effectively reduced. Firstly, in order to improve the training efficiency of the model, depthwise separable convolution is introduced to reduce the computational cost of the model. Secondly, the Leaky-ReLU function effectively activates all neurons in each layer of neural network to improve the training efficiency of the model. Finally, the cosine annealing learning rate adjustment strategy is introduced to avoid the model falling into the local optimal solution and enhance the robustness of the model. The experimental results on two widely used hyperspectral remote sensing image data sets (Pavia University and Kennedy Space Center) show that compared with seven other advanced classification methods, the proposed method achieves better classification accuracy under the condition of limited training samples.
Coupling between Trigeminal-Induced Asymmetries in Locus Coeruleus Activity and Cognitive Performance
Authors: Tramonti Fantozzi Maria Paola , Marconi Ottavia , Simoni Federica , De Cicco Vincenzo , De Cicco Davide , Cataldo Enrico , Barresi Massimo , Bruschini Luca , d’Ascanio Paola , Faraguna Ugo , Manzoni Diego
Published: September 2021

In humans, the asymmetry in the masseter electromyographic (EMG) activity during clenching is positively correlated with the degree of pupil size asymmetry (anisocoria) at rest. Anisocoria reveals an asymmetry in LC activity, which may lead to an imbalance in cortical excitability, detrimental to performance. Hereby, we investigated, in individual subjects, the possibility that occlusal correction, which decreases EMG asymmetry, improves performance by balancing LC activity. Cognitive performance, task-related mydriasis, and pupil size at rest were modified by changing the occlusal condition. Occlusal-related changes in performance and mydriasis were negatively correlated with anisocoria changes in only 12/20 subjects. Within this population, spontaneous fluctuations in mydriasis and anisocoria also appeared negatively coupled. Occlusal-related changes in performance and mydriasis were negatively correlated with those in average pupil size (a proxy of average LC activity) in 19/20 subjects. The strongest association was observed for the pupil changes occurring on the side with higher EMG activity during clenching. These findings indicate that the effects of occlusal conditions on cognitive performance were coupled to changes in the asymmetry of LC activity in about half of the subjects, while they were related to changes in the average tonic LC activity in virtually all of them.
Model-Free Non-Cascade Integral Sliding Mode Control of Permanent Magnet Synchronous Motor Drive with a Fast Reaching Law
Authors: Li Tong , Liu Xudong
Published: September 2021

Electric vehicle has become the main trend of the development of automobile industry. As a highly symmetrical system, the characteristics of drive motor will have a great impact on the driving comfort. Aiming at the control regulation of permanent magnet synchronous motor (PMSM) drive, a model-free and non-cascade sliding mode control with a fast-reaching law is proposed in this paper. Firstly, the mathematical model of PMSM is constructed as an ultra-local model without considering any motor parameters. Then, to improve the response speed, an integral sliding mode method with a fast reaching law is proposed, and the fast convergence can be realized. The controller system adopts single loop non-cascade control, which greatly simplifies the system structure. In order to further improve the anti-disturbance performance of the system, the dual disturbance observers are used to compensate the disturbance through feed-forward control. The stability of the system is proved by Lyapunov. Finally, the experimental results show that the proposed method has faster convergence speed and stronger anti-disturbance ability.
Calculations of the Thermodynamic Characteristics and Physicochemical Properties of Symmetric and Asymmetric Isomeric Compounds for Identification in Chromatography-Mass Spectrometry
Authors: Fedorova Elizaveta , Stavrianidi Andrey , Minenkova Irina , Buryak Aleksey
Published: September 2021

A combination of theoretical and experimental approaches was applied to determine the chromatographic rules of isomeric compounds’ behavior for preliminary identification. In gas chromatography-mass spectrometry (GC-MS), identification is performed by spectra matching, however, difficulties arise with isomeric compounds, which cannot be distinguished from each other without additional information. The thermodynamic characteristics of the adsorption of symmetric and asymmetric isomers of chlorophenylphenols, dimethoxybiphenyls, tri- and tetrachlorobiphenyls were determined using molecular statistical calculations. By-products in the chlorination of 4-hydroxybiphenyl were identified: 4-hydroxy-2,3′- and 3,2′-dichlorobiphenyls, 4-hydroxy-3,5,2′- and 2,3,6-trichlorobiphenyls. A developed theoretical approach was applied to predict the retention order of tri- and tetra-chlorobiphenyls. The GC-MS data and molecular statistical calculations made it possible to determine the main products of methoxybenzene dimerization as well as identify impurities. Thermodynamic parameters were received to describe the unusual retention behavior of epimers in reversed-phase high-performance liquid chromatography. Molecular descriptors were calculated to determine correlation with retention of both structural isomers and epimers. Descriptor combining surface area and partial charge information turned out to be useful in evaluating retention order for isomers.
Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure
Authors: Hsu Chung-Yao , Chuang Yao-Chung , Chang Fang-Chia , Chuang Hung-Yi , Chiou Terry Ting-Yu , Lee Chien-Te
Published: September 2021

Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep–wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague–Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep–wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including rPer1, rPer2, and rBmal1b, were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep–wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of rPer1 and rPer2 and the feedback repression of rBmal1b. We concluded that chronic lead exposure has a negative impact on the sleep–wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus.
Toxicity in Peripheral Nerves: An Overview
Authors: Grisold Wolfgang , Carozzi Valentina
Published: September 2021

Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of substances and by different mechanisms. Toxic agents are numerous and can be distinguished between drugs, recreational agents, heavy metals, industrial agents, pesticides, warfare agents, biologic substances and venoms. Toxic agents reach the nervous system by ingestion, transcutaneously, via the mucous membranes, parenterally and by aerosols. The most frequent types are cumulative toxicities. Other types are acute or delayed toxicities. Pathogenetic mechanisms range from a specific toxic substance profile causing axonal or demyelinating lesions, towards ion channel interferences, immune-mediated mechanisms and a number of different molecular pathways. In addition, demyelination, focal lesions and small fiber damage may occur. Clinically, neurotoxicity presents most frequently as axonal symmetric neuropathies. In this work, we present a panoramic view of toxic neuropathy, in terms of symptoms, causes, mechanisms and classification.
Removal of Cyanobacteria and Cyanotoxins in Waters
Authors: Serrà Albert , Philippe Laetitia , Gómez Elvira
Published: September 2021

Harmful cyanobacterial algal blooms and cyanotoxins currently pose a major threat to global society, one that exceeds local and national interests due to their extremely destructive effects on the environment and human health [...]
Biomarkers of Uremic Cardiotoxicity
Authors: Stopic Bojan , Dragicevic Sandra , Medic-Brkic Branislava , Nikolic Aleksandra , Stojanovic Marko , Budisavljevic Sreten , Dimkovic Nada
Published: September 2021

Cardiovascular (CV) morbidity and mortality increase along with the progression of chronic kidney disease (CKD). The potential novel biomarkers of cardiotoxicity have been tested with the aim of the early detection of patients at high CV risk, and among them are markers of inflammation, oxidative stress, acute renal injury, and microRNAs. The study analyzed biomarkers in non-dialysis-dependent (NDD; stage 3a–4 CKD) and dialysis-dependent (DD) CKD patients. The prospective cohort study included 87 patients who were followed for 18 months, during which period newly occurred CV events were recorded. Cox regression analysis confirmed serum albumin, urea, interventricular septum thickness diameter (IVST), the use of calcium antagonist, and erythropoiesis-stimulating agent to be significant predictors of CV outcome. No significant difference was observed in biomarkers of inflammation, oxidative stress, acute kidney injury (IL-18, CRP, ferritin, IMA, SOD, NGAL, and KIM-1), and miR-133a, in regards to the presence/absence of CV event, CV death, and left ventricular hypertrophy. Serum albumin, urea, IVST, and the use of calcium antagonist and erythropoiesis-stimulating agents were confirmed to be factors associated with CV events in CKD patients. Apart from traditional risk factors, new research is needed to define novel and reliable biomarkers of cardiotoxicity in CKD patients.
A Four-Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotypes C and D
Authors: Garcia-Rodriguez Consuelo , Yan Shude , Geren Isin N. , Knopp Kristeene A. , Dong Jianbo , Sun Zhengda , Lou Jianlong , Conrad Fraser , Wen Wei-Hua , Farr-Jones Shauna , Smith Theresa J. , Brown Jennifer L. , Skerry Janet C. , Smith Leonard A. , Marks James D.
Published: September 2021

Human botulism can be caused by botulinum neurotoxin (BoNT) serotypes A to G. Here, we present an antibody-based antitoxin composed of four human monoclonal antibodies (mAbs) against BoNT/C, BoNT/D, and their mosaic toxins. This work built on our success in generating protective mAbs to BoNT /A, B and E serotypes. We generated mAbs from human immune single-chain Fv (scFv) yeast-display libraries and isolated scFvs with high affinity for BoNT/C, BoNT/CD, BoNT/DC and BoNT/D serotypes. We identified four mAbs that bound non-overlapping epitopes on multiple serotypes and mosaic BoNTs. Three of the mAbs underwent molecular evolution to increase affinity. A four-mAb combination provided high-affinity binding and BoNT neutralization of both serotypes and their mosaic toxins. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing and neutralizing BoNT/C and BoNT/D serotypes and their mosaic toxins. A derivative of the four-antibody combination (NTM-1634) completed a Phase 1 clinical trial (Snow et al., Antimicrobial Agents and Chemotherapy, 2019) with no drug-related serious adverse events.
Effect of Botulinum Toxin on Non-Motor Symptoms in Cervical Dystonia
Authors: Costanzo Matteo , Belvisi Daniele , Berardelli Isabella , Maraone Annalisa , Baione Viola , Ferrazzano Gina , Cutrona Carolina , Leodori Giorgio , Pasquini Massimo , Conte Antonella , Fabbrini Giovanni , Defazio Giovanni , Berardelli Alfredo
Published: September 2021

Patients with cervical dystonia (CD) may display non-motor symptoms, including psychiatric disturbances, pain, and sleep disorders. Intramuscular injection of botulinum toxin type A (BoNT-A) is the most efficacious treatment for motor symptoms in CD, but little is known about its effects on non-motor manifestations. The aim of the present study was to longitudinally assess BoNT-A’s effects on CD non-motor symptoms and to investigate the relationship between BoNT-A-induced motor and non-motor changes. Forty-five patients with CD participated in the study. Patients underwent a clinical assessment that included the administration of standardized clinical scales assessing dystonic symptoms, psychiatric disturbances, pain, sleep disturbances, and disability. Clinical assessment was performed before and one and three months after BoNT-A injection. BoNT-A induced a significant improvement in dystonic symptoms, as well as in psychiatric disturbances, pain, and disability. Conversely, sleep disorders were unaffected by BoNT-A treatment. Motor and non-motor BoNT-A-induced changes showed a similar time course, but motor improvement did not correlate with non-motor changes after BoNT-A. Non-motor symptom changes after BoNT-A treatment are a complex phenomenon and are at least partially independent from motor symptom improvement.
Neutrinoless Double Beta Decay with Germanium Detectors: 1026 yr and Beyond
Authors: D’Andrea Valerio , Di Marco Natalia , Junker Matthias Bernhard , Laubenstein Matthias , Macolino Carla , Morella Michele , Salamida Francesco , Vignoli Chiara
Published: September 2021

In the global landscape of neutrinoless double beta (0νββ) decay search, the use of semiconductor germanium detectors provides many advantages. The excellent energy resolution, the negligible intrinsic radioactive contamination, the possibility of enriching the crystals up to 88% in the 76Ge isotope as well as the high detection efficiency, are all key ingredients for highly sensitive 0νββ decay search. The Majorana and Gerda experiments successfully implemented the use of germanium (Ge) semiconductor detectors, reaching an energy resolution of 2.53 ± 0.08 keV at the Qββ and an unprecedented low background level of 5.2×10−4 cts/(keV·kg·yr), respectively. In this paper, we will review the path of 0νββ decay search with Ge detectors from the original idea of E. Fiorini et al. in 1967, to the final recent results of the Gerda experiment setting a limit on the half-life of 76Ge 0νββ decay at T1/2>1.8×1026 yr (90% C.L.). We will then present the LEGEND project designed to reach a sensitivity to the half-life up to 1028 yr and beyond, opening the way to the exploration of the normal ordering region.
Data-Driven Management—A Dynamic Occupancy Approach to Enhanced Rabies Surveillance Prioritization
Authors: Davis Amy J. , Kirby Jordona D. , Chipman Richard B. , Nelson Kathleen M. , Gilbert Amy T.
Published: September 2021

Rabies lyssavirus (RABV) is enzootic in raccoons across the eastern United States. Intensive management of RABV by oral rabies vaccination (ORV) has prevented its spread westward and shown evidence of local elimination in raccoon populations of the northeastern US. The USDA, Wildlife Services, National Rabies Management Program (NRMP) collaborates with other agencies to implement broad-scale ORV and conducts extensive monitoring to measure the effectiveness of the management. Enhanced Rabies Surveillance (ERS) was initiated during 2005 and updated in 2016 to direct surveillance efforts toward higher-value specimens by assigning points to different methods of encountering specimens for collection (strange-acting, roadkill, surveillance-trapped, etc.; specimen point values ranged from 1 to 15). We used the 2016–2019 data to re-evaluate the point values using a dynamic occupancy model. Additionally, we used ERS data from 2012–2015 and 2016–2019 to examine the impact that the point system had on surveillance data. Implementation of a point system increased positivity rates among specimens by 64%, indicating a substantial increase in the efficiency of the ERS to detect wildlife rabies. Our re-evaluation found that most points accurately reflect the value of the surveillance specimens. The notable exception was that samples from animals found dead were considerably more valuable for rabies detection than originally considered (original points = 5, new points = 20). This work demonstrates how specimen prioritization strategies can be used to refine and improve ERS in support of wildlife rabies management.
Variability in Codon Usage in Coronaviruses Is Mainly Driven by Mutational Bias and Selective Constraints on CpG Dinucleotide
Authors: Daron Josquin , Bravo Ignacio
Published: September 2021

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human-emerged virus of the 21st century from the Coronaviridae family, causing the ongoing coronavirus disease 2019 (COVID-19) pandemic. Due to the high zoonotic potential of coronaviruses, it is critical to unravel their evolutionary history of host species breadth, host-switch potential, adaptation and emergence, to identify viruses posing a pandemic risk in humans. We present here a comprehensive analysis of the composition and codon usage bias of the 82 Orthocoronavirinae members, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses, is only weakly dependent on their primary host, and is dominated by mutational bias towards AU-enrichment and by CpG avoidance. Indeed, variation in GC3 explains around 34%, while variation in CpG frequency explains around 14% of total variation in codon usage bias. Further insight on the mutational equilibrium within Orthocoronavirinae revealed that most coronavirus genomes are close to their neutral equilibrium, the exception being the three recently infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that, while replicating in humans, SARS-CoV-2 is slowly becoming AU-richer, likely until attaining a new mutational equilibrium.
Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay
Authors: Rego Natalia , Salazar Cecilia , Paz Mercedes , Costábile Alicia , Fajardo Alvaro , Ferrés Ignacio , Perbolianachis Paula , Fernández-Calero Tamara , Noya Veronica , Machado Matias R. , Brandes Mariana , Arce Rodrigo , Arleo Mailen , Possi Tania , Reyes Natalia , Bentancor María Noel , Lizasoain Andrés , Bortagaray Viviana , Moller Ana , Chappos Odhille , Nin Nicolas , Hurtado Javier , Duquía Melissa , González Maria Belén , Griffero Luciana , Méndez Mauricio , Techera Maria Pía , Zanetti Juan , Pereira Emiliano , Rivera Bernardina , Maidana Matías , Alonso Martina , Smircich Pablo , Arantes Ighor , Mir Daiana , Alonso Cecilia , Medina Julio , Albornoz Henry , Colina Rodney , Bello Gonzalo , Moreno Pilar , Moratorio Gonzalo , Iraola Gregorio , Spangenberg Lucía
Published: September 2021

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020–February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay’s capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest.
Development of an mRNA-LNP Vaccine against SARS-CoV-2: Evaluation of Immune Response in Mouse and Rhesus Macaque
Authors: Naderi Sohi Alireza , Kiani Jafar , Arefian Ehsan , Khosrojerdi Arezou , Fekrirad Zahra , Ghaemi Shokoofeh , Zim Mohammad Kazem , Jalili Arsalan , Bostanshirin Nazila , Soleimani Masoud
Published: September 2021

Among the vaccines have been developed thus far against SARS-CoV-2, the mRNA-based ones have demonstrated more promising results regarding both safety and efficacy. Two remarkable features of the mRNA vaccines introduced by the Pfizer/BioNTech and Moderna companies are the use of (N1-methyl-pseudouridine-) modified mRNA and the microfluidics-based production of lipid nanoparticles (LNPs) as the carrier. In the present study, except Anti-Reverse Cap Analog (ARCA), no other nucleoside analogs were employed to synthesize Spike-encoding mRNA using the in vitro transcription (IVT) method. Furthermore, LNPs were prepared via the ethanol injection method commonly used for liposome formation as an alternative for microfluidics-based approaches. The produced mRNA-LNP vaccine was evaluated for nanoparticles characteristics, encapsulation and transfection efficiencies, in vitro cytotoxicity as well as stability and storability. The safety of vaccine was assessed in Balb/c mice injected with mRNA-LNPs containing 10 µg of spike-encoding mRNA. Eventually, the vaccine efficacy in inducing an immune response against SARS-CoV-2 was studied in Balb/c and C57BL/6 mice (received either 1 or 10 µg of mRNA) as well as in rhesus macaque monkeys (infused with mRNA-LNPs containing 100 µg of mRNA). The ELISA and virus neutralizing test (VNT) results showed a significant augmentation in the level of neutralizing antibodies against SARS-CoV-2. Moreover, the ELISA assay showed virus-specific IFN-γ secretion in immunized mice as a marker of TH1 cell-based immune response, whereas favorably no change in the production of IL-4 was detected.
Varicella Zoster Virus Reactivation Following COVID-19 Vaccination: A Systematic Review of Case Reports
Authors: Katsikas Triantafyllidis Konstantinos , Giannos Panagiotis , Mian Imran Tariq , Kyrtsonis George , Kechagias Konstantinos S.
Published: September 2021

The newly developed COVID-19 vaccines have established a safe profile, yet some individuals experience a wide range of adverse events. Recently, reactivation of varicella zoster virus (VZV) has been observed after administration of different COVID-19 vaccines, although causality remains a matter of debate. The aim of this systematic review was to examine the available literature and provide an overview of reported cases of VZV reactivation following COVID-19 vaccination. We identified 12 eligible articles which included 91 patients with herpes zoster (HZ) following COVID-19 vaccination. Hypertension was the main comorbidity present in 18% of patients (16/91). Additionally, 13% of patients (12/91) had an autoimmune condition with rheumatoid arthritis being the most common (4/12). Moreover, 10% of patients (9/91) were receiving immunosuppressants. The dermatomal distribution of skin lesions varied among patients, with the mammary region being most affected. On average, symptoms developed 5.8 days post-vaccination irrespective of dose and treatment with oral valacyclovir as a monotherapy was employed in most patients (23/91). HZ is possibly a condition clinicians may expect to encounter in patients receiving COVID-19 vaccines. While causality has not yet been established increased awareness and early recognition of the disorder would be crucial for the optimal management of these patients.
Molecular Detection and Characterization of Blastocystis sp. and Enterocytozoon bieneusi in Cattle in Northern Spain
Authors: Abarca Nadia , Santín Mónica , Ortega Sheila , Maloney Jenny G. , George Nadja S. , Molokin Aleksey , Cardona Guillermo A. , Dashti Alejandro , Köster Pamela C. , Bailo Begoña , Hernández-de-Mingo Marta , Muadica Aly S. , Calero-Bernal Rafael , Carmena David , González-Barrio David
Published: September 2021

Some enteric parasites causing zoonotic diseases in livestock have been poorly studied or even neglected. This is the case in stramenopile Blastocystis sp. and the microsporidia Enterocytozoon bieneusi in Spain. This transversal molecular epidemiological survey aims to estimate the prevalence and molecular diversity of Blastocystis sp. and E. bieneusi in cattle faecal samples (n = 336) in the province of Álava, Northern Spain. Initial detection of Blastocystis and E. bieneusi was carried out by polymerase chain reaction (PCR) and Sanger sequencing of the small subunit (ssu) rRNA gene and internal transcribed spacer (ITS) region, respectively. Intra-host Blastocystis subtype diversity was further investigated by next generation amplicon sequencing (NGS) of the ssu rRNA gene in those samples that tested positive by conventional PCR. Amplicons compatible with Blastocystis sp. and E. bieneusi were observed in 32.1% (108/336, 95% CI: 27.2–37.4%) and 0.6% (2/336, 95% CI: 0.0–1.4%) of the cattle faecal samples examined, respectively. Sanger sequencing produced ambiguous/unreadable sequence data for most of the Blastocystis isolates sequenced. NGS allowed the identification of 10 Blastocystis subtypes including ST1, ST3, ST5, ST10, ST14, ST21, ST23, ST24, ST25, and ST26. All Blastocystis-positive isolates involved mixed infections of 2–8 STs in a total of 31 different combinations. The two E. bieneusi sequences were confirmed as potentially zoonotic genotype BEB4. Our data demonstrate that Blastocystis mixed subtype infections are extremely frequent in cattle in the study area. NGS was particularly suited to discern underrepresented subtypes or mixed subtype infections that were undetectable or unreadable by Sanger sequencing. The presence of zoonotic Blastocystis ST1, ST3, and ST5, and E. bieneusi BEB4 suggest cross-species transmission and a potential risk of human infection/colonization.
The Long-Term Clinical Course of Canine Degenerative Myelopathy and Therapeutic Potential of Curcumin
Authors: Kobatake Yui , Nakata Kohei , Sakai Hiroki , Sasaki Jun , Yamato Osamu , Takashima Satoshi , Nishii Naohito , Maeda Sadatoshi , Islam Md , Kamishina Hiroaki
Published: September 2021

Canine degenerative myelopathy (DM), recognized as a spontaneous model of amyotrophic lateral sclerosis, is known as a late-onset progressive degenerative disease of the spinal cord. Because of the progressive nature of DM, many dogs are elected to be euthanized, resulting in limited information on the end-stage clinical presentation. We investigated the long-term clinical course from diagnosis to natural death to further deepen our understanding of the entire clinical picture of this disease. Because curcumin was administered in some cases, the therapeutic effect of curcumin on DM was also examined. Forty dogs included in this study were client-owned Pembroke Welsh Corgis with a definitive diagnosis of DM by necropsy and histopathology. Dogs were excluded from this study if they died from another disease or were elected to be euthanized. Information on the long-term clinical symptoms of DM was investigated based on a questionnaire, which was collected from the dog owners. Urinary incontinence and respiratory disorder were observed in most dogs, as was respiratory impairment-correlated death. In contrast, signs consistent with brainstem dysfunction were noticed at the terminal stage in a small portion of dogs. Although further studies with more cases are needed, the results of this study suggest that administration of curcumin is effective in slowing the progression of DM.
Evaluation of the First Negative Ion-Based Cloud Seeding and Rain Enhancement Trial in China
Authors: Zheng Wei , Ma Hengben , Zhang Ming , Xue Fengming , Yu Kexun , Yang Yong , Ma Shaoxiang , Wang Chuliang , Pan Yuan , Shu Zhiliang , Mu Jianhua , Yang Wenqing , Yin Xianzhi
Published: September 2021

Negative ion-based cloud seeding has been shown to be an effective means in the laboratory. China’s first negative ion-based cloud seeding outfield trial was conducted in the northwestern interior. This paper briefly introduces the principle of the ion-based precipitation enhancement, and the trial location is described. The design of the ionization system and meteorological monitoring network are presented. The implementation plan of the outfield trial is explained. In addition, the evaluation of experimental effects is detailed in this paper. We designed various analytical methods to investigate both the overall precipitation variation of the experimental area and the precipitation variation within the experimental area. The overall precipitation of the experimental area was predicted using a neural network, and then the actual precipitation was compared with the predicted precipitation to evaluate the effectiveness of the experiment. The effectiveness of the experiment was also evaluated using historical precipitation data and the result of the randomized comparative trial. This paper also explores the effects of geographic location differences and wind direction differences on the precipitation differences within the trial area. The changes in the number of negative ions and clouds in the sky were also analyzed. From these analyses, we obtained quantitative assessment results. These results could indicate that the outfield trial basically met the expected requirements, which is to increase the rainfall of the trial area by 20%.
Using Statistical Control Charts to Monitor Building Water Consumption: A Case Study on the Replacement of Toilets
Authors: Freitas Lucas Lepinski Golin , Kalbusch Andreza , Henning Elisa , Walter Olga Maria Formigoni Carvalho
Published: September 2021

This manuscript proposes the usage of Statistical Control Charts (SCC) to monitor water consumption in buildings. The charts were employed to study the impact of replacing toilets, providing visual and statistical feedback to measure the efficiency gain resulting from the replacement of outdated flushing equipment with newer devices. The case study was conducted in a building from a university in the South of Brazil. The building has four restrooms, from which a total of 41,554 readings were collected during a 15-month period using digital water meters. After the toilets were replaced, a reduction averaging 30.22% in water consumption was observed (from 7.51 L/flush/day to 5.24 L/flush/day). Additionally, the control charts were able to pinpoint dates when unique events happened during the water-consumption monitoring process.