bluuebunny/crossref_metadata_2025 huggingface dataset:
Student Volunteering as a Solution for Undergraduate Health Professions Education: Lessons From the COVID-19 Pandemic
Authors: Chawłowska Ewelina , Staszewski Rafał , Lipiak Agnieszka , Giernaś Bogusz , Karasiewicz Monika , Bazan Dominika , Nowosadko Maria , Cofta Mateusz , Wysocki Jacek
Published: January 2021

In response to the COVID-19 pandemic, many medical universities worldwide, including the Poznan University of Medical Sciences, launched student volunteering projects (SVPs). We examined our student volunteers' perceptions on the conditions, safety, costs and benefits of their participation in the SVP. Using this information, we attempted to assess the viability of SVPs as a solution for health professions education during and after the pandemic. The main research tool was a questionnaire on students' perceptions of their participation in the SVP. As a complementary qualitative method, we used semi-structured interviews with the volunteers. Our respondents (n = 158) perceived conditions and safety generally positively: most reported having personal protective equipment (89.24%), technical support (88.61%), and induction training (79.11%). Only 38.61% said they had access to psychological support. In our view, benefits (e.g., an opportunity to make new contacts or receiving positive reactions from patients and staff) seemed to outweigh costs. 65.82% of the respondents agreed that they learnt new interesting things. A majority noticed the development of their soft skills (social 86.08%; organisational 78.48%; stress management 68.99%), while 40.51% – the development of their medical skills. The interviews pointed to additional benefits for students such as gaining insight of the healthcare system, and costs such as distress caused by some patient interactions. We conclude that student volunteering could become a viable solution for health professions education. To maximise its educational potential, volunteers' needs must be explored, psychological support ensured, and opportunities for mentoring and reflection provided. The organisational framework of a SVP should be culturally sensitive.
Factors Associated With Self-Selected Step Rates Between Collegiate and High School Cross Country Runners
Authors: Luedke Lace E. , Rauh Mitchell J.
Published: January 2021

Introduction: Cross country is a popular high school and collegiate sport with a high rate of running-related injuries (RRI). Among high school runners, higher step rates have been associated with greater running experience and decreased body height, and lower step rates have been prospectively associated with increased risk of shin RRI. These associations have not been reported in collegiate cross country runners. The purpose of this study was to compare step rates between collegiate and high school cross country runners. Secondary objectives included determining if step rates in collegiate runners were related to experience and anthropometric variables, and whether their self-selected step rates were prospectively related to lower extremity RRI.

Materials and methods: Twenty-nine NCAA Division III collegiate cross country runners (13 females, mean ± SD age 19.7 ± 1.3 years) completed a survey and ran at their self-selected speed. Step rate was assessed with Polar RCX5 wristwatches and S3+ Stride Sensors™ on the first day of the season. Runners were followed during the season for occurrence of time-loss lower extremity RRI. A cohort of 68 high school runners was used for comparison of step rates at their self-selected speeds.

Results: Collegiate runners' self-selected step rates (177.1 ± 7.2 spm [steps per minute]) were higher than high school runners' (171.3 ± 8.3 spm) (p = 0.01). Collegiate runners ran at higher self-selected speeds (4.6 ± 0.5 m/s) than the high school runners (3.8 ± 0.5 m/s) (p < 0.001). A lower percentage of collegiate runners ran at ≤166 spm than high school runners. Body mass was negatively correlated with step rate in collegiate runners. During the season, 41.3% of collegiate runners experienced lower extremity RRI. Step rates for collegiate runners who did not experience RRI (178.9 ± 7.7 spm) were not significantly higher than runners who did experience RRI (174.5 ± 5.7 spm) (p = 0.10).

Discussion: Higher step rates were found in collegiate than high school runners, but the difference was partially explained by higher self-selected running speeds. Thus, variations in step rate between high school and collegiate runners may be expected based on experience, speed, and body mass.
A Practical Introduction to Mechanistic Modeling of Disease Transmission in Veterinary Science
Authors: Kirkeby Carsten , Brookes Victoria J. , Ward Michael P. , Dürr Salome , Halasa Tariq
Published: January 2021

Computer-based disease spread models are frequently used in veterinary science to simulate disease spread. They are used to predict the impacts of the disease, plan and assess surveillance, or control strategies, and provide insights about disease causation by comparing model outputs with real life data. There are many types of disease spread models, and here we present and describe the implementation of a particular type: individual-based models. Our aim is to provide a practical introduction to building individual-based disease spread models. We also introduce code examples with the goal to make these techniques more accessible to those who are new to the field. We describe the important steps in building such models before, during and after the programming stage, including model verification (to ensure that the model does what was intended), validation (to investigate whether the model results reflect the modeled system), and convergence analysis (to ensure models of endemic diseases are stable before outputs are collected). We also describe how sensitivity analysis can be used to assess the potential impact of uncertainty about model parameters. Finally, we provide an overview of some interesting recent developments in the field of disease spread models.
Altered Corneal Innervation and Ocular Surface Homeostasis in FHV-1-Exposed Cats: A Preliminary Study Suggesting Metaherpetic Disease
Authors: Sebbag Lionel , Thomasy Sara M. , Leland Adriana , Mukai Madison , Kim Soohyun , Maggs David J.
Published: January 2021

Metaherpetic disease is recognized in humans affected by herpes simplex virus-1 but is not reported in cats affected by feline herpesvirus-1 (FHV-1) despite the high prevalence of herpetic disease in this species and strong similarities in viral biology between alphaherpesviruses of humans and cats. This preliminary work evaluated cats naïve to FHV-1 (n = 9 cats, 18 eyes; control population) and cats naturally exposed to FHV-1 (n = 4 cats, 7 eyes), as confirmed by serologic testing and review of medical records. Antemortem assessment included clinical scoring, blink rate, corneal aesthesiometry, tear film breakup time (TFBUT), and Schirmer tear test-1 (STT-1) with or without the nasolacrimal reflex. Post-mortem assessment involved confocal microscopy of the corneas and evaluation of corneal nerves with ImageJ. Groups were compared with Student's t-tests and results are presented as mean ± standard deviation. Compared to control, herpetic cats had significantly higher (P ≤ 0.010) clinical scores (0.2 ± 0.4 vs. 4.6 ± 2.8) and response to nasolacrimal stimulation (7.8 ± 10.8% vs. 104.8 ± 151.1%), significantly lower (P < 0.001) corneal sensitivity (2.9 ± 0.6 cm vs. 1.4 ± 0.9 cm), STT-1 (20.8 ± 2.6 mm/min vs. 10.6 ± 6.0 mm/min), TFBUT (12.1 ± 2.0 s vs. 7.1 ± 2.9 s), and non-significantly lower blink rate (3.0 ± 1.5 blinks/min vs. 2.7 ± 0.5 blinks/min; P = 0.751). All parameters evaluated for corneal nerves (e.g., nerve fiber length, branching, occupancy) were notably but not significantly lower in herpetic vs. control cats (P ≥ 0.268). In sum, cats exposed to FHV-1 had signs suggestive of corneal hypoesthesia and quantitative/qualitative tear film deficiencies when compared to cats naïve to the virus. It is possible these are signs of metaherpetic disease as reported in other species.
Comparative Studies of Inhibitory and Antioxidant Activities, and Organic Acids Compositions of Postbiotics Produced by Probiotic Lactiplantibacillus plantarum Strains Isolated From Malaysian Foods
Authors: Chang Hui Mei , Foo Hooi Ling , Loh Teck Chwen , Lim Eric Teik Chung , Abdul Mutalib Nur Elina
Published: January 2021

Despite inflammation being a protective natural defense against imbalance stressors in the body, chronic inflammation could lead to the deterioration of immune response, low production, and poor performance in livestock as well as severe economic losses to the farmers. Postbiotics produced by Lactiplantibacillus plantarum has been reported recently to be a natural source of antioxidant, promoting growth performance, anti-inflammation, and immune responses. However, the effects of fermentation media on the compositions of L. plantarum postbiotic have not been reported elsewhere. Hence, a comparative study was conducted to compare the volatile compounds, organic acid composition, and antioxidant and antimicrobial activities of postbiotics produced by six strains of L. plantarum cultivated by using formulated media and the commercial de Man, Rogosa, and Sharpe (MRS) medium as a control. Postbiotics RG14, RI11, and UL4 produced by using formulated media exhibited higher inhibitory activity against Pediococcus acidilactici 446, Escherichia coli E-30, Salmonella enterica CS3, and vancomycin-resistant Enterococci except for Listeria monocytogenes LS55. As for the antioxidant activity, hydroxyl radical scavenging activity was enhanced in formulated media, whereas reducing power activity was the highest in postbiotic RI11. Three organic acids, namely, acetic acid, caproic acid, and lactic acid, were detected in the postbiotic produced by various L. plantarum strains. The concentration of acetic acid was influenced by the fermentation media, whereas caproic acid was detected as the highest in postbiotic RG11. Lactic acid was the predominant compound detected in all the postbiotics and had the significantly highest concentration in postbiotic RS5 when produced by using the MRS medium. Intermediary and pyrrole compounds were the other main compounds that were detected by using GC-MS. Positive correlations were found between organic acid production and inhibitory activity, as well as antioxidant activity exhibited by postbiotics. In conclusion, the compositions and functional characteristics of postbiotics produced by the six strains of L. plantarum were strain-dependent and affected greatly by the fermentation medium. The effects of postbiotic composition on the functional characteristics of postbiotics were elucidated in this study to warrant their applications as a promising beneficial natural growth promoter for the livestock industry.
A Multi-Platform Metabolomics Approach Identifies Urinary Metabolite Signatures That Differentiate Ketotic From Healthy Dairy Cows
Authors: Zhang Guanshi , Mandal Rupasri , Wishart David S. , Ametaj Burim N.
Published: January 2021

Ketosis and subclinical ketosis are widespread among dairy cows especially after calving. Etiopathology of ketosis has been related to negative energy balance. The objective of this study was to investigate metabolite fingerprints in the urine of pre-ketotic, ketotic, and post-ketotic cows to identify potential metabolite alterations that can be used in the future to identify susceptible cows for ketosis and metabolic pathways involved in the development of disease. In this study, NMR, DI/LC-MS/MS, and GC-MS-based metabolomics were used to analyze urine samples from 6 cows diagnosed with ketosis and 20 healthy control (CON) cows at −8 and −4 weeks prepartum, the week (+1 to +3) of ketosis diagnosis, and at +4 and +8 weeks after parturition. Univariate and multivariate analyses were used to screen metabolite panels that can identify cows at their pre-ketotic stage. A total of 54, 42, 48, 16, and 31 differential metabolites between the ketotic and CON cows were identified at −8 and −4 weeks prepartum, ketosis week, and at +4, and +8 weeks postpartum, respectively. Variable importance in projection (VIP) plots ranked the most significant differential metabolites, which differentiated ketotic cows from the CON ones. Additionally, several metabolic pathways that are related to ketosis were identified. Moreover, two promising metabolite panels were identified which clearly separated ketotic from CON cows with excellent level of sensitivity and specificity. Overall, multiple urinary metabolite alterations were identified in pre-ketotic, ketotic, and post-ketotic cows. The metabolite panels identified need to be validated in the future in a larger cohort of animals.
Probabilistic Prediction of Separation Buffer to Compensate for the Closing Effect on Final Approach
Authors: Förster Stanley , Schultz Michael , Fricke Hartmut
Published: January 2021

The air traffic is mainly divided into en-route flight segments, arrival and departure segments inside the terminal maneuvering area, and ground operations at the airport. To support utilizing available capacity more efficiently, in our contribution we focus on the prediction of arrival procedures, in particular, the time-to-fly from the turn onto the final approach course to the threshold. The predictions are then used to determine advice for the controller regarding time-to-lose or time-to-gain for optimizing the separation within a sequence of aircraft. Most prediction methods developed so far provide only a point estimate for the time-to-fly. Complementary, we see the need to further account for the uncertain nature of aircraft movement based on a probabilistic prediction approach. This becomes very important in cases where the air traffic system is operated at its limits to prevent safety-critical incidents, e.g., separation infringements due to very tight separation. Our approach is based on the Quantile Regression Forest technique that can provide a measure of uncertainty of the prediction not only in form of a prediction interval but also by generating a probability distribution over the dependent variable. While the data preparation, model training, and tuning steps are identical to classic Random Forest methods, in the prediction phase, Quantile Regression Forests provide a quantile function to express the uncertainty of the prediction. After developing the model, we further investigate the interpretation of the results and provide a way for deriving advice to the controller from it. With this contribution, there is now a tool available that allows a more sophisticated prediction of time-to-fly, depending on the specific needs of the use case and which helps to separate arriving aircraft more efficiently.
Staphylococcus aureus Interferes with Streptococci Spatial Distribution and with Protein Expression of Species within a Polymicrobial Oral Biofilm
Authors: Schnurr Etyene , Paqué Pune N. , Attin Thomas , Nanni Paolo , Grossmann Jonas , Holtfreter Silva , Bröker Barbara M. , Kohler Christian , Diep Binh An , Ribeiro Apoena de Aguiar , Thurnheer Thomas
Published: January 2021

We asked whether transient Staphylococcus aureus in the oral environment synergistically interacts with orally associated bacterial species such as Actinomyces oris, Candida albicans, Fusobacterium nucleatum, Streptococcus oralis, Streptococcus mutans, and Veillonella dispar (six-species control biofilm 6S). For this purpose, four modified biofilms with seven species that contain either the wild type strain of the S. aureus genotype (USA300-MRSA WT), its isogenic mutant with MSCRAMM deficiency (USA300-MRSA ΔMSCRAMM), a methicillin-sensitive S. aureus (ST72-MSSA-) or a methicillin-resistant S. aureus (USA800-MRSA) grown on hydroxyapatite disks were examined. Culture analyses, confocal-laser-scanning microscopy and proteome analyses were performed. S. aureus strains affected the amount of supragingival biofilm-associated species differently. The deletion of MSCRAMM genes disrupted the growth of S. aureus and the distribution of S. mutans and S. oralis within the biofilms. In addition, S. aureus caused shifts in the number of detectable proteins of other species in the 6S biofilm. S. aureus (USA300-MRSA WT), aggregated together with early colonizers such as Actinomyces and streptococci, influenced the number of secondary colonizers such as Fusobacterium nucleatum and was involved in structuring the biofilm architecture that triggered the change from a homeostatic biofilm to a dysbiotic biofilm to the development of oral diseases.
Relationship between General Jump Types and Spike Jump Performance in Elite Female and Male Volleyball Players
Authors: Fuchs Philip X. , Mitteregger Julia , Hoelbling Dominik , Menzel Hans-Joachim K. , Bell Jeffrey W. , von Duvillard Serge P. , Wagner Herbert
Published: January 2021

In performance testing, it is well-established that general jump types like squat and countermovement jumps have great reliability, but the relationship with volleyball spike jumps is unclear. The objectives of this study were to analyze the relationship between general and spike jumps and to provide improved models for predicting spike jump height by general jump performance. Thirty female and male elite volleyball players performed general and spike jumps in a randomized order. Two AMTI force plates (2000 Hz) and 13 Vicon MX cameras (250 Hz) captured kinematic and kinetic data. Correlation and stepwise-forward regression analyses were conducted at p < 0.05. Simple regression models with general jump height as the only predictor for spike jumps revealed 0.52 ≤ R2 ≤ 0.76 for all general jumps in both sexes (p < 0.05). Alternative models including rate of force development and impulse improved predictions during squat jumps from R2 = 0.76 to R2 = 0.92 (p < 0.05) in females and from R2 = 0.61 to R2 = 0.71 (p < 0.05) in males, and during countermovement jumps with arm swing from R2 = 0.52 to R2 = 0.78 (p < 0.01) in males. The findings include improved prediction models for spike jump height based on general jump performance. The derived formulas can be applied in general jump testing to improve the assessment of sport-specific spike jump performance.
Calculation and Verification of the Real-Time Working Characteristics of a Viscous Coupling
Authors: Jin Liqiang , Peng Xianglong , Wang Dehai , Guo Desheng , Chen Biao
Published: January 2021

During operation, the shear friction between the silicone oil and the plates of a viscous coupling (VC) will generate heat and increase the temperature of the silicone oil, inflate the volume, increase the internal pressure, and eventually deliver more torque, in what is called hump operation mode. Temperature is the root cause of the change of the operation characteristics in VCs. In this paper, the heat-transfer model for a VC is established based on the thermodynamical theory. The capacity of the heat transmission of each part of the VC are calculated to obtain the temperature of silicone oil. The real-time shear torque of the VC is finally obtained. Then, the theoretical analysis on hump phenomenon was done. The internal pressure was obtained by analyzing the characteristics of ideal gas, and the maximum torque during the hump phenomenon was calculated. The simulation of the key parameters and the entire working process for the VC were carried out based on the proposed calculation model. A prototype of a viscous limited-slip differential (VLSD) was developed to test the output torque characteristics. The test results were quite consistent with the simulation results, and the accuracy of the calculation model was verified.
Alternative Design of Binary Phase Diffractive Optical Element with Non-π Phase Difference
Authors: Xu Cheng , Pang Hui , Cao Axiu , Deng Qiling
Published: January 2021

It was found that binary phase diffractive optical element (DOE) with non-π phase difference had higher diffraction efficiency and adjustable zero-order intensity than a 0-π one. However, existing design methods are all based on the simulated annealing algorithm and thus computationally expensive. In this paper, a simple and efficient method using the iterative Fourier transform algorithm (IFTA) is proposed. In this method, the target pattern is first modified via reducing the zero-order intensity. Then, the IFTA is adopted to design the conventional 0-π DOE. Subsequently, the phase distribution remains unchanged and the phase difference is carefully adjusted to increase the zero-order intensity so that the reconstructed pattern is consistent with the target. To verify this method, several typical DOEs for beam splitting were designed and fabricated, and the result showed that the proposed method is effective.
Sources and Metal Pollution of Sediments from a Coastal Area of the Central Western Adriatic Sea (Southern Marche Region, Italy)
Authors: Spagnoli Federico , De Marco Rocco , Dinelli Enrico , Frapiccini Emanuela , Frontalini Fabrizio , Giordano Patrizia
Published: January 2021

Sediments represent a critical compartment of marine coastal ecosystems due to the toxic and long-lasting effects of the contaminants buried therein. Here, we investigated the properties of surficial sediments in front of the Southern Marche Region coast (Central Adriatic Sea, Italy). The grain size of the surficial sediments was determined by X-ray sedigraphy. TN and OC contents were determined by elemental analysis. The concentrations of Al, Fe, Mg, K, S, Ca, Ti, P, Na, Mn, Mg, Li, As, Ba, Ga, Pb, Sr, and Zn were determined by ICP-OES to evaluate their spatial patterns and temporal trends. A Q-mode Factor Analyses was applied and resulted in the identification of three compositional facies (Padanic, Coastal, and Residual) characterized by common biogeochemical, mineralogical, sedimentological properties, transport pathway, and source. Some pollution indicators, such as the enrichment factor, the geoaccumulation index, and the pollution load index were calculated to assess the deviation from the natural background levels. The results showed a pollution by As and Ba due to the human activities in the 20th century. Furthermore, a general decreasing of Al, Ti, P, Co, Cr, Cu, Ga, Ni, Pb, Sc, V, and Y concentrations from the background levels suggested a change in the sedimentation processes during the last decades.
Innovative Methods and Materials in Structural Health Monitoring of Civil Infrastructures
Authors: Zinno Raffaele , Artese Serena
Published: January 2021

Starting from the early years of the 21st century, the problem of monitoring the physical–chemical–mechanical conditions of structures and infrastructures for civil use began to be thought in a significantly different way than in the last century [...]
Multiaxial Fatigue Assessment for the Hanger Deck Connection of a High-Speed Steel-Truss-Arch Railway Bridge
Authors: Song Yongsheng , Ding Youliang , Jiang Fei , Wang Zhiwen , Lu Jun , Jia Huijuan
Published: January 2021

Steel-truss-arch bridges have been applied in high-speed railway bridges due to their excellent dynamic and static structural performance. Under the action of high-speed trains, the steel connections between hangers and decks suffer from repeated stresses, inducing potential fatigue problems or even fatigue failure. In this study, a multiaxial fatigue evaluation method was first created and established based on critical damage-plane methodology, following which the fatigue evaluation procedure was also created and recommended. The methodology was applied to real-life strain data from a high-speed railway bridge from which an assessment of fatigue damage and predicted fatigue life was estimated. The connection between the shortest hanger and deck on the downstream side was selected as the target due to its relatively high stress. A multiscale finite-element model of this bridge was created according to the design profile and monitoring results of traffic flow, where the finite-element model was calibrated and validated by comparing the calculation results with the monitoring data. Influence analysis was then carried out to investigate two factors—i.e., the total traffic flow and compositions of freight trains—having effects on the fatigue life of the steel connection. The results indicate that the applied multiaxial fatigue method is suitable for online fatigue evaluation of actual bridges. In addition, by using the multiaxial fatigue method, the fatigue-damage accumulation rate can be nearly 60 times that obtained by the uniaxial fatigue method. If freighting is taken into consideration, the fatigue damage will increase rapidly, and for the case 10% of proportion traffic as freighting, the actual fatigue life is estimated to be shorter than the design life.
Acknowledgment to Reviewers of Applied System Innovation in 2020
Authors:   Applied System Innovation Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Applied System Innovation maintains its standards for the high quality of its published papers [...]
Dry and Wet Climate Periods over Eastern South America: Identification and Characterization through the SPEI Index
Authors: Drumond Anita , Stojanovic Milica , Nieto Raquel , Gimeno Luis , Liberato Margarida L. R. , Pauliquevis Theotonio , Oliveira Marina , Ambrizzi Tercio
Published: January 2021

A large part of the population and the economic activities of South America are located in eastern regions of the continent, where extreme climate events are a recurrent phenomenon. This study identifies and characterizes the dry and wet climate periods at domain-scale occurring over the eastern South America (ESA) during 1980–2018 through the multi-scalar Standardized Precipitation–Evapotranspiration Index (SPEI). For this study, the spatial extent of ESA was defined according to a Lagrangian approach for moisture analysis. It consists of the major continental sink of the moisture transported from the South Atlantic Ocean throughout the year, comprising the Amazonia, central Brazil, and the southeastern continental areas. The SPEI for 1, 3, 6, and 12 months of accumulation was calculated using monthly precipitation and potential evapotranspiration time series averaged on ESA. The analysis of the climate periods followed two different approaches: classification of the monthly SPEI values as mild, moderate, severe, and extreme; the computation of the events and their respective parameters (duration, severity, intensity, and peak). The results indicate that wet periods prevailed in the 1990s and 2000s, while dry conditions predominated in the 2010s, when the longest and more severe dry events have been identified at the four scales.
Key Figure Based Incoming Inspection of Lithium-Ion Battery Cells
Authors: Ryll Kerstin , Hoffmann Louisa , Landrath Oliver , Lienesch Frank , Kurrat Michael
Published: January 2021

The cell characterization in the incoming inspection is an important but time and cost intensive process step. In order to obtain reliable parameters to evaluate and classify the cells, it is essential to design the test procedures in such a way that the parameters derived from the data allow the required statements about the cells. Before the focus is placed on the evaluation of cell properties, it is therefore necessary to design the test procedures appropriately. In the scope of the investigations two differently designed incoming inspection routines were carried out on 230 commercial lithium-ion battery cells (LIBs) with the aim of deriving recommendations for optimal test procedures. The derived parameters of the test strategies were compared and statistically evaluated. Subsequently, key figures for the classification were identified. As a conclusion, the capacity was confirmed as an already known important parameter and the average cell voltage was identified as a possibility to replace the usually used internal resistance. With regard to capacity, the integration of CV steps in the discharging processes enables the determination independently from the C-rate. For the average voltage cycles with high C-rates are particularly meaningful because of the significant higher scattering due to the overvoltage parts.
A Peptide-Nucleic Acid Targeting miR-335-5p Enhances Expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene with the Possible Involvement of the CFTR Scaffolding Protein NHERF1
Authors: Tamanini Anna , Fabbri Enrica , Jakova Tiziana , Gasparello Jessica , Manicardi Alex , Corradini Roberto , Finotti Alessia , Borgatti Monica , Lampronti Ilaria , Munari Silvia , Dechecchi Maria , Cabrini Giulio , Gambari Roberto
Published: January 2021

(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be up-regulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-335-5p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine.
Modifications in the Topological Structure of EEG Functional Connectivity Networks during Listening Tonal and Atonal Concert Music in Musicians and Non-Musicians
Authors: González Almudena , Santapau Manuel , Gamundí Antoni , Pereda Ernesto , González Julián J.
Published: January 2021

The present work aims to demonstrate the hypothesis that atonal music modifies the topological structure of electroencephalographic (EEG) connectivity networks in relation to tonal music. To this, EEG monopolar records were taken in musicians and non-musicians while listening to tonal, atonal, and pink noise sound excerpts. EEG functional connectivities (FC) among channels assessed by a phase synchronization index previously thresholded using surrogate data test were computed. Sound effects, on the topological structure of graph-based networks assembled with the EEG-FCs at different frequency-bands, were analyzed throughout graph metric and network-based statistic (NBS). Local and global efficiency normalized (vs. random-network) measurements (NLE|NGE) assessing network information exchanges were able to discriminate both music styles irrespective of groups and frequency-bands. During tonal audition, NLE and NGE values in the beta-band network get close to that of a small-world network, while during atonal and even more during noise its structure moved away from small-world. These effects were attributed to the different timbre characteristics (sounds spectral centroid and entropy) and different musical structure. Results from networks topographic maps for strength and NLE of the nodes, and for FC subnets obtained from the NBS, allowed discriminating the musical styles and verifying the different strength, NLE, and FC of musicians compared to non-musicians.
Poor Corticospinal Motor Neuron Health Is Associated with Increased Symptom Severity in the Acute Phase Following Repetitive Mild TBI and Predicts Early ALS Onset in Genetically Predisposed Rodents
Authors: Alkaslasi Mor R. , Cho Noell E. , Dhillon Navpreet K. , Shelest Oksana , Haro-Lopez Patricia S. , Linaval Nikhil T. , Ghoulian Josh , Yang Audrey R. , Vit Jean-Philippe , Avalos Pablo , Ley Eric J. , Thomsen Gretchen M.
Published: January 2021

Traumatic brain injury (TBI) is a well-established risk factor for several neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, however, a link between TBI and amyotrophic lateral sclerosis (ALS) has not been clearly elucidated. Using the SOD1G93A rat model known to recapitulate the human ALS condition, we found that exposure to mild, repetitive TBI lead ALS rats to experience earlier disease onset and shortened survival relative to their sham counterparts. Importantly, increased severity of early injury symptoms prior to the onset of ALS disease symptoms was linked to poor health of corticospinal motor neurons and predicted worsened outcome later in life. Whereas ALS rats with only mild behavioral injury deficits exhibited no observable changes in corticospinal motor neuron health and did not present with early onset or shortened survival, those with more severe injury-related deficits exhibited alterations in corticospinal motor neuron health and presented with significantly earlier onset and shortened lifespan. While these studies do not imply that TBI causes ALS, we provide experimental evidence that head injury is a risk factor for earlier disease onset in a genetically predisposed ALS population and is associated with poor health of corticospinal motor neurons.
Acknowledgment to Reviewers of Behavioral Sciences in 2020
Authors:   Behavioral Sciences Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Behavioral Sciences maintains its standards for the high quality of its published papers [...]
Raman Spectroscopy of Twisted Bilayer Graphene
Authors: Moutinho Marcus V. O. , Venezuela Pedro , Pimenta Marcos A.
Published: January 2021

When two periodic two-dimensional structures are superposed, any mismatch rotation angle between the layers generates a Moiré pattern superlattice, whose size depends on the twisting angle θ. If the layers are composed by different materials, this effect is also dependent on the lattice parameters of each layer. Moiré superlattices are commonly observed in bilayer graphene, where the mismatch angle between layers can be produced by growing twisted bilayer graphene (TBG) samples by CVD or folding the monolayer back upon itself. In TBG, it was shown that the coupling between the Dirac cones of the two layers gives rise to van Hove singularities (vHs) in the density of electronic states, whose energies vary with θ. The understanding of the behavior of electrons and their interactions with phonons in atomically thin heterostructures is crucial for the engineering of novel 2D devices. Raman spectroscopy has been often used to characterize twisted bilayer graphene and graphene heterostructures. Here, we review the main important effects in the Raman spectra of TBG discussing firstly the appearance of new peaks in the spectra associated with phonons with wavevectors within the interior of the Brillouin zone of graphene corresponding to the reciprocal unit vectors of the Moiré superlattice, and that are folded to the center of the reduced Brillouin Zone (BZ) becoming Raman active. Another important effect is the giant enhancement of G band intensity of TBG that occurs only in a narrow range of laser excitation energies and for a given twisting angle. Results show that the vHs in the density of states is not only related to the folding of the commensurate BZ, but mainly associated with the Moiré pattern that does not necessarily have a translational symmetry. Finally, we show that there are two different resonance mechanisms that activate the appearance of the extra peaks: the intralayer and interlayer electron–phonon processes, involving electrons of the same layer or from different layers, respectively. Both effects are observed for twisted bilayer graphene, but Raman spectroscopy can also be used to probe the intralayer process in any kind of graphene-based heterostructure, like in the graphene/h-BN junctions.
Single-Fraction Adjuvant Electronic Brachytherapy after Resection of Conjunctival Carcinoma
Authors: Sarria Gustavo R. , Serpa Solon , Buitrago Mario , Fuentes Rivera Paola , Ramirez Diego , Giordano Frank A. , Sarria Gustavo J.
Published: January 2021

A retrospective study was performed to assess the outcomes of a single-fraction adjuvant electronic brachytherapy (e-BT) approach for patients with squamous cell conjunctival carcinoma (SCCC). Forty-seven patients with T1–T3 SCCC were included. All patients underwent surgery followed by a single-fraction adjuvant e-BT with a porTable 50-kV device. Depending on margins, e-BT doses ranged between 18 to 22 Gy prescribed at 2 mm depth, resembling equivalent doses in 2 Gy (EQD2) per fraction of 46–66 Gy (α/β ratio of 8–10 Gy and a relative biological effect (RBE) of 1.3). The median age was 69 (29–87) years. Most tumors were T1 (40.4%) or T2 (57.5%) with a median size of 7 mm (1.5–20). Margins were positive in 40.4% of cases. The median time from surgery to e-BT was nine weeks (0–37). After a median follow-up of 24 (17–40) months, recurrence occurred in only two patients (6 and 7 months after e-BT), yielding a median disease-free survival (DFS) of 24 (6–40) months and DFS at two years of 95.7%. Acute grade 2 conjunctivitis occurred in 25.5%. E-BT is a safe and effective for SCCC treatment, with clinical and logistic advantages compared to classical methods. Longer follow-up and prospective assessment are warranted.
Radiotherapy–Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery?
Authors: Romano Erminia , Honeychurch Jamie , Illidge Timothy M.
Published: January 2021

Radiotherapy (RT) is highly effective at directly killing tumor cells and plays an important part in cancer treatments being delivered to around 50% of all cancer patients. The additional immunomodulatory properties of RT have been investigated, and if exploited effectively, have the potential to further improve the efficacy of RT and cancer outcomes. The initial results of combining RT with immunomodulatory agents have generated promising data in pre-clinical studies, which has in turn led to a large number of RT and immunotherapy clinical trials. The overarching aim of these combinations is to enhance anti-tumor immune responses and improve responses rates and patient outcomes. In order to maximize this undoubted opportunity, there remain a number of important questions that need to be addressed, including: (i) the optimal RT dose and fractionation schedule; (ii) the optimal RT target volume; (iii) the optimal immuno-oncology (IO) agent(s) to partner with RT; (iv) the optimal site(s)/route(s) of administration of IO agents; and finally, the optimal RT schedule. In this review, we will summarize progress to date and identify current gaps in knowledge that need to be addressed in order to facilitate effective clinical translation of RT and IO agent combinations.
Targeted Neoadjuvant Therapies in HR+/HER2−Breast Cancers: Challenges for Improving pCR
Authors: Dey Nandini , Aske Jennifer , De Pradip
Published: January 2021

A strong association of pCR (pathological complete response) with disease-free survival or overall survival is clinically desirable. The association of pCR with disease-free survival or overall survival in ER+/HER2−breast cancers following neoadjuvant systemic therapy (NAT) or neoadjuvant endocrine therapy (NET) is relatively low as compared to the other two subtypes of breast cancers, namely triple-negative and HER2+ amplified. On the bright side, a neoadjuvant model offers a potential opportunity to explore the efficacy of novel therapies and the associated genomic alterations, thus providing a rare personalized insight into the tumor’s biology and the tumor cells’ response to the drug. Several decades of research have taught us that the disease’s biology is a critical factor determining the tumor cells’ response to any therapy and hence the final outcome of the disease. Here we propose two scenarios wherein apoptosis can be induced in ER+/HER2− breast cancers expressing wild type TP53 and RB genes following combinations of BCL2 inhibitor, MDM2 inhibitor, and cell-cycle inhibitor. The suggested combinations are contextual and based on the current understanding of the cell signaling in the ER+/HER2− breast cancers. The two combinations of drugs are (1) BCL2 inhibitor plus a cell-cycle inhibitor, which can prime the tumor cells for apoptosis, and (2) BCL2 inhibitor plus an MDM2 inhibitor.
Hydrogen-Peroxide Synthesis and LDL-Uptake Controls Immunosuppressive Properties in Monocyte-Derived Dendritic Cells
Authors: Menzner Ann-Katrin , Rottmar Tanja , Voelkl Simon , Bosch Jacobus J. , Mougiakakos Dimitrios , Mackensen Andreas , Resheq Yazid J.
Published: January 2021

Background and Aims: Induction of myeloid-derived suppressor cells (MDSC) is a critical step in immune cell evasion by different cancer types, including liver cancer. In the liver, hepatic stromal cells orchestrate induction of MDSCs, employing a mechanism dependent on hydrogen peroxide (H2O2) depletion. However, the effects on monocyte-derived dendritic cells (moDCs) are unknown. Methods: Monocytes from healthy donors were differentiated to moDCs in the presence of extracellular enzymatic H2O2-depletion (hereinafter CAT-DCs), and studied phenotypically and functionally. To elucidate the underlying molecular mechanisms, we analyzed H2O2- and LDL-metabolism as they are interconnected in monocyte-driven phagocytosis. Results: CAT-DCs were of an immature DC phenotype, particularly characterized by impaired expression of the costimulatory molecules CD80/86. Moreover, CAT-DCs were able to suppress T-cells using indoleamine 2,3-dioxygenase (IDO), and induced IL10/IL17-secreting T-cells—a subtype reported to exert immunosuppression in acute myeloid leukemia. CAT-DCs also displayed significantly increased NADPH-oxidase-driven H2O2-production, enhancing low-density lipoprotein (LDL)-uptake. Blocking LDL-uptake restored maturation, and attenuated the immunosuppressive properties of CAT-DCs. Discussion: Here, we report a novel axis between H2O2- and LDL-metabolism controlling tolerogenic properties in moDCs. Given that moDCs are pivotal in tumor-rejection, and lipid-accumulation is associated with tumor-immune-escape, LDL-metabolism appears to play an important role in tumor-immunology.
Ovulatory Follicular Fluid Facilitates the Full Transformation Process for the Development of High-Grade Serous Carcinoma
Authors: Hsu Che-Fang , Chen Pao-Chu , Seenan Vaishnavi , Ding Dah-Ching , Chu Tang-Yuan
Published: January 2021

Background: High-grade serous carcinoma (HGSC) is mainly derived from the stepwise accumulation of driver mutations in the fallopian tube epithelium (FTE), and it subsequently metastasizes to the ovary and peritoneum that develops into a clinically evident ovarian carcinoma. The developmental process involves cell proliferation/clonal expansion, cell migration, anoikis resistance, anchorage-independent growth (AIG), peritoneum attachment, and cell invasion. Previously, we discovered FTE could be transformed by follicular fluid (FF) released from ovulation, the most crucial risk factor of ovarian cancer, and IGF axis proteins in FF confers stemness activation and clonal expansion via IGF-1R/AKT pathway. However, whether other phenotypes in advanced cancer development are involved is unknown. Methods: A panel of FTE and ovarian HGSC cell lines with different severity of transformation were treated with FF with or without IGF-1R and AKT inhibitors and analyzed for the transformation phenotypes in vitro, ex vivo, and in vivo. Results: FF largely promotes (by order of magnitude) cell migration, AIG, cell invasion, peritoneum attachment, anoikis resistance, and cell proliferation. Most of these activities worked in the full panel of cell lines. The AIG activity largely depends on IGF-1R/AKT phosphorylation, and the proliferation activity depends on an AKT phosphorylation not mediated by IGF-1R. In contrast, both AKT- and non-AKT-mediated signals are responsible for the other transformation activities. Conclusions: Our data demonstrate an extensive transformation activity of FF in the full journey of carcinogenesis, and endorsed ovulation-inhibition for the prevention and AKT-inhibition for the treatment of ovarian HGSC.
The CXCL12 Crossroads in Cancer Stem Cells and Their Niche
Authors: López-Gil Juan Carlos , Martin-Hijano Laura , Hermann Patrick C. , Sainz Bruno
Published: January 2021

Cancer stem cells (CSCs) are defined as a subpopulation of “stem”-like cells within the tumor with unique characteristics that allow them to maintain tumor growth, escape standard anti-tumor therapies and drive subsequent repopulation of the tumor. This is the result of their intrinsic “stem”-like features and the strong driving influence of the CSC niche, a subcompartment within the tumor microenvironment that includes a diverse group of cells focused on maintaining and supporting the CSC. CXCL12 is a chemokine that plays a crucial role in hematopoietic stem cell support and has been extensively reported to be involved in several cancer-related processes. In this review, we will provide the latest evidence about the interactions between CSC niche-derived CXCL12 and its receptors—CXCR4 and CXCR7—present on CSC populations across different tumor entities. The interactions facilitated by CXCL12/CXCR4/CXCR7 axes seem to be strongly linked to CSC “stem”-like features, tumor progression, and metastasis promotion. Altogether, this suggests a role for CXCL12 and its receptors in the maintenance of CSCs and the components of their niche. Moreover, we will also provide an update of the therapeutic options being currently tested to disrupt the CXCL12 axes in order to target, directly or indirectly, the CSC subpopulation.
Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma
Authors: Gąsior-Perczak Danuta , Kowalik Artur , Gruszczyński Krzysztof , Walczyk Agnieszka , Siołek Monika , Pałyga Iwona , Trepka Sławomir , Mikina Estera , Trybek Tomasz , Kopczyński Janusz , Suligowska Agnieszka , Ślusarczyk Rafał , Gonet Agnieszka , Jaskulski Jarosław , Orłowski Paweł , Chrapek Magdalena , Góźdź Stanisław , Kowalska Aldona
Published: January 2021

The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p < 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.