bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking Behavior, Co-infection Patterns, and Viral Infection Risk With the Whole Gastrointestinal Helminth Community Structure in Mastomys natalensis
Authors: Vanden Broecke Bram , Bernaerts Lisse , Ribas Alexis , Sluydts Vincent , Mnyone Ladslaus , Matthysen Erik , Leirs Herwig
Published: August 2021

Infection probability, load, and community structure of helminths varies strongly between and within animal populations. This can be ascribed to environmental stochasticity or due to individual characteristics of the host such as their age or sex. Other, but understudied, factors are the hosts' behavior and co-infection patterns. In this study, we used the multimammate mouse (Mastomys natalensis) as a model system to investigate how the hosts' sex, age, exploration behavior, and viral infection history affects their infection risk, parasitic load, and community structure of gastrointestinal helminths. We hypothesized that the hosts' exploration behavior would play a key role in the risk for infection by different gastrointestinal helminths, whereby highly explorative individuals would have a higher infection risk leading to a wider diversity of helminths and a larger load compared to less explorative individuals. Fieldwork was performed in Morogoro, Tanzania, where we trapped a total of 214 individual mice. Their exploratory behavior was characterized using a hole-board test after which we collected the helminths inside their gastrointestinal tract. During our study, we found helminths belonging to eight different genera: Hymenolepis sp., Protospirura muricola, Syphacia sp., Trichuris mastomysi, Gongylonema sp., Pterygodermatites sp., Raillietina sp., and Inermicapsifer sp. and one family: Trichostrongylidae. Hierarchical modeling of species communities (HMSC) was used to investigate the effect of the different host-related factors on the infection probability, parasite load, and community structure of these helminths. Our results show that species richness was higher in adults and in females compared to juveniles and males, respectively. Contrary to our expectations, we found that less explorative individuals had higher infection probability with different helminths resulting in a higher diversity, which could be due to a higher exposure rate to these helminths and/or behavioral modification due to the infection.
Effect of Feeding Low Protein Diets on the Production Traits and the Nitrogen Composition of Excreta of Broiler Chickens
Authors: Such Nikoletta , Pál László , Strifler Patrik , Horváth Boglárka , Koltay Ilona Anna , Rawash Mohamed Ali , Farkas Valéria , Mezőlaki Ákos , Wágner László , Dublecz Károly
Published: August 2021

The main goal of the current study was to investigate the effects of feeding low protein (LP) diets on the performance parameters and excreta composition of broiler chickens. In total, 288 male Ross 308 day-old chickens were divided into two dietary treatment groups using six replicate pens with 24 chickens each. No LP diet was fed in the starter phase. The protein reduction in the grower and finisher phases were 1.8% and 2% respectively. Beside the measurements of production traits, on day 24 and 40 representative fresh excreta samples were collected, their dry matter, total N, NH4+-N and uric acid-N contents determined, and the ratio of urinary and fecal N calculated. Dietary treatments failed to cause significant differences in the feed intake, growth rate, and feed conversion ratio of animals. LP diets decreased the total nitrogen and uric acid contents of excreta significantly. The age of birds had also significant effect, resulting more reduction in the grower phase compared with the finisher. The ratio of urinary N was higher at day 40 compared with the age of day 24. The urinary N content of broiler chicken’s excreta is lower than can be found in the literature, which should be considered in the ammonia inventory calculations.
Brief Review of Minimum or No-Till Seeders in China
Authors: Jiang Shan , Wang Qingjie , Zhong Guangyuan , Tong Zhenwei , Wang Xiuhong , Xu Jing
Published: August 2021

Minimum or no-till seeding technology is the core of conservation tillage, which can effectively reduce soil degradation by water and wind erosion. It is an essential part of agricultural modernization. The anti-blocking technology is the key to realize minimum or no-till seeding technology. According to the principle, it can be divided into three types: straw-flowing type, gravity-cutting stubble type, and power-driven type. Emphasis is placed on the anti-blocking principle, technical characteristics, and development trends of minimum or no till seeders based on three different anti-blocking principles. In view of analyzing and summarizing the advantages and disadvantages of three technologies and typical machines, the future development trends of minimum or no-till seeders were prospected as follows: (1) strengthening research on basic theories and integration mechanisms; (2) building a big data-sharing platform for seeding operations; (3) establishing and improving specific systems of minimum and no-till seeders with China character.
Defense Response to Hemileia vastatrix in Susceptible Grafts onto Resistant Rootstock of Coffea arabica L.
Authors: Couttolenc-Brenis Edgar , Carrión Gloria , Villain Luc , Ortega-Escalona Fernando , Mata-Rosas Martín , Méndez-Bravo Alfonso
Published: August 2021

The use of resistant cultivars and fungicides are common methods to control coffee leaf rust (CLR), the main disease that affects the Arabica coffee crop. In this study, we evaluated the response of grafted and ungrafted plants during the early stage of Hemileia vastatrix infection. We used ungrafted plants of Oro Azteca (resistant cultivar) and Garnica (susceptible cultivar), and grafted plants, combining both as rootstock and graft (Garnica/Oro Azteca and Oro Azteca/Garnica). All plants were inoculated with H. vastatrix uredospores, and we quantified the development of fungal structures in the leaf tissue of inoculated plants using qRT-PCR to measure relative expression of two pathogenesis recognition genes (CaNDR1 and CaNBS-LRR) and three genes associated with the salicylic acid (SA) pathway (CaNPR1, CaPR1 and CaPR5). In Garnica grafted on Oro Azteca, the fungal structures recorded were significantly less than in Garnica ungrafted plants. In addition, the expression of defense-related genes in grafted plants was higher than in ungrafted plants. Our results indicate that the defense response to CLR is strongly influenced by the rootstock employed.
Effects of Natural Rehabilitation of Degraded Land by Exclosure on Selected Soil Physicochemical Properties in Eastern Ethiopia
Authors: Misebo Amisalu Milkias , Ayano Samuel Feyissa , Pietrzykowski Marcin
Published: August 2021

The use of exclosure for ecological restoration has become an increasingly vital approach to reversing degraded lands. Its effectiveness in restoring degraded lands could be varied with differences in climate, vegetation type and soil properties. Thus, the objective of this study was to determine the effect of exclosure on the selected physical and chemical properties of the soil. A six-year-old exclosure and adjacent open land with the same history of land-use types were selected. Soil samples were randomly collected from 0–20 and 20–40 cm depths of each land-use type and measured for texture, soil moisture content (SMC), bulk density (BD), soil organic carbon (SOC), available phosphorus (Av.P), cation exchange capacity (CEC), electrical conductivity (EC) and pH contents. The highest SMC, SOC and Av.P and the lowest BD values were measured from the exclosure. SMC, SOC and Av.P increased by 73, 51 and 55%, respectively, while BD decreased by 31% as compared to the open land. CEC, EC and pH were also influenced positively compared with the adjacent open land. The funding indicates exclosure had a positive effect on the restoration of soil nutrients, which are essential to promote vegetation growth and thereby minimize soil erosion.
Evaluation of Cardiac Arrhythmias before, during, and after Treadmill Exercise Testing in Poorly Performing Standardbred Racehorses
Authors: Alberti Elena , Stucchi Luca , Lo Feudo Chiara Maria , Stancari Giovanni , Conturba Bianca , Ferrucci Francesco , Zucca Enrica
Published: August 2021

The incidence of significant arrhythmias in sport horses and knowledge about their exact influence on athletic performance need to be clarified. The aims of the present study are to report the prevalence of cardiac arrhythmias during maximal treadmill exercise in poorly performing Standardbreds, and to investigate the possible relationship of demographic, cardiac and performance indices on premature complexes (PCs). Electrocardiographic Holter recordings before, during and after treadmill exercise testing of 158 poorly performing Standardbreds were analyzed retrospectively. Fifty horses did not have any type of arrhythmia. One hundred and eight horses had at least one type of arrhythmia, such as sinus arrhythmia (8.2%), sinoatrial block (3.2%), second-degree atrioventricular block (33.5%), supraventricular PCs (7.6%), and ventricular PCs (48.1%). A multiple regression analysis showed weak evidence that the occurrence of premature complexes decreases as the minimum heart rate increases, and a tendency for these arrhythmias to increase with increasing age and maximum lactate concentration. Our results suggest that PCs are frequent in poorly performing Standardbred racehorses, but further studies are necessary to clarify their role and clinical significance.
Factors, Perceptions and Beliefs Associated with Inappropriate Antibiotic Prescribing in German Primary Dental Care: A Qualitative Study
Authors: Böhmer Femke , Hornung Anne , Burmeister Ulrike , Köchling Anna , Altiner Attila , Lang Hermann , Löffler Christin
Published: August 2021

Dentists account for up to 10% of all prescribed antibiotics in primary care, with up to 80% being inappropriate. Targeted approaches to change prescription behavior are scarce. This study aimed at identifying specific barriers and facilitators for prudent antibiotic use in German dentistry by using qualitative methods. Nine in-depth interviews and two focus group discussions with another nine dentists were conducted and analyzed thematically. Dentists described being conflicted by the discordance of available treatment time and the necessity of thorough therapy. Lacking the opportunity of follow-up led to uncertainty. Dentists felt a lack of medical competency concerning prophylaxis for infectious endocarditis. A lack of empowerment to make therapeutic decisions interfered with guideline-conformity. The communication with fellow physicians is conflictual and improvement was wished for. In consequence, dentists felt pressure by potential medico-legal liability. Patients demanding quick and easy pain relief put extra strain on the interviewed dentists. Our hypotheses concord with preliminary data, mainly from the UK, but highlighted specifically medico-legal concerns and interprofessional communication as even greater barriers as described before. Tailored interventional concepts based on our findings may have the potential to lower antibiotic prescriptions in German primary dental care.
Ventilator-Associated Pneumonia in COVID-19 Patients: A Retrospective Cohort Study
Authors: Rouyer Maxence , Strazzulla Alessio , Youbong Tracie , Tarteret Paul , Pitsch Aurélia , de Pontfarcy Astrid , Cassard Bruno , Vignier Nicolas , Pourcine Franck , Jochmans Sébastien , Monchi Mehran , Diamantis Sylvain
Published: August 2021

Introduction: Aim of this study is to analyse the characteristics of ventilator-associated pneumonia (VAP) inpatients infected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Materials and Methods: A retrospective study was conducted, including coronavirus infectious disease 2019 (COVID-19) patients who developed VAP from March to May 2020 (VAP COVID-19). They were compared to non-COVID-19 patients who developed VAP from January 2011 to December 2019 (VAP NO COVID-19) and COVID-19 patients who did not develop VAP (NO VAP COVID-19). Results: Overall, 42 patients were included in the VAP COVID-19group, 37 in the NO VAP COVID-19 group, and 188 in the VAP NO COVID-19 group. VAP COVID-19 had significantly higher rates of shock (71% vs. 48%, p = 0.009), death in ICU (52% vs. 30%, p = 0.011), VAP recurrence (28% vs. 4%, p < 0.0001), positive blood culture (26% vs. 13%, p = 0.038), and polymicrobial culture (28% vs. 13%, p = 0.011) than VAP NO COVID-19. At the multivariate analysis, death in patients with VAP was associated with shock (p = 0.032) and SARS-CoV-2 (p = 0.008) infection. Conclusions: VAP in COVID-19 patients is associated with shock, bloodstream, and polymicrobial infections.
The Efficacy of Moina micrura Enriched with Probiotic Bacillus pocheonensis in Enhancing Survival and Disease Resistance of Red Hybrid Tilapia (Oreochromis spp.) Larvae
Authors: Samat Nur Amalina , Yusoff Fatimah Md , Rasdi Nadiah Wan , Karim Murni
Published: August 2021

The administration of probiotics via live feeds, such as Artemia and rotifers, has gained significant attention. Moreover, indiscriminate use of antibiotics in conventional aquaculture practices in order to prevent or control disease outbreaks has resulted in the occurrence of residues and antimicrobial resistance. Thus, the application of eco-friendly feed additives, such as probiotics, as a safer alternative has received increasing attention in recent years. However, only minimal information on the administration of probiotics via freshwater cladoceran Moina micrura is available despite being commonly used for larval and post-larval feeding of freshwater crustaceans and fish. Thus, this study aimed to evaluate the application of Bacillus pocheonensis strain S2 administered via M. micrura to red hybrid tilapia (Oreochromis spp.) larvae. Bacillus pocheonensis that has been previously isolated from Spirulina sp. was subjected to preliminary in vitro evaluation of antagonistic properties. The agar well-diffusion assay revealed that this probiont could inhibit the growth of Streptococcus agalactiae and Aeromonas hydrophila. The size of inhibition zones ranged from 8.8 ± 0.2 to 18.2 ± 0.4 mm. Moina micrura was later used as a biological model in preliminary in vivo bacterial challenge assays to evaluate the efficacy of B. pocheonensis in protecting the host from diseases. Moina micrura was pre-enriched with B. pocheonensis at 104 and 106 CFU mL−1 before S. agalactiae and A. hydrophila were introduced into the culture. The study revealed that B. pocheonensis at 104 CFU mL−1 was able to significantly enhance the survival of M. micrura after being challenged with both pathogens (63 ± 3%) in comparison to the control group. The relative percentage survival (RPS) of M. micrura was highest (p < 0.05) when treated with B. pocheonensis at both concentrations 104 and 106 CFU mL−1 (38.33) after being challenged against S. agalactiae. To assess the efficacy of B. pocheonensis in protecting red hybrid tilapia against streptococcosis, the larvae were fed with either unenriched (control) Moina or probiont-enriched Moina daily for 10 days. A significantly (p < 0.05) higher survival rate (77 ± 3%) was observed in larvae fed with probiont-enriched M. micrura compared to other treatments, and the RPS was recorded at 62.90. In addition, the S. agalactiae load was suppressed in larvae fed probiont-enriched M. micrura (6.84±0.39 CFU mL−1) in comparison to the control group (7.78±0.09 CFU mL−1), indicating that the probiont might have contributed to the improvement of tilapia health and survival. This study illustrated that M. micrura was suitable to be used as a vector for probiotics in freshwater fish larvae as an alternative to hazardous antibiotics for disease control.
Role of dipA and pilD in Francisella tularensis Susceptibility to Resazurin
Authors: Souder Kendall , Beatty Emma J. , McGovern Siena C. , Whaby Michael , Young Emily , Pancake Jacob , Weekley Daron , Rice Justin , Primerano Donald A. , Denvir James , Horzempa Joseph , Schmitt Deanna M.
Published: August 2021

The phenoxazine dye resazurin exhibits bactericidal activity against the Gram-negative pathogens Francisella tularensis and Neisseria gonorrhoeae. One resazurin derivative, resorufin pentyl ether, significantly reduces vaginal colonization by Neisseria gonorrhoeae in a mouse model of infection. The narrow spectrum of bacteria susceptible to resazurin and its derivatives suggests these compounds have a novel mode of action. To identify potential targets of resazurin and mechanisms of resistance, we isolated mutants of F. tularensis subsp. holarctica live vaccine strain (LVS) exhibiting reduced susceptibility to resazurin and performed whole genome sequencing. The genes pilD (FTL_0959) and dipA (FTL_1306) were mutated in half of the 46 resazurin-resistant (RZR) strains sequenced. Complementation of select RZR LVS isolates with wild-type dipA or pilD partially restored sensitivity to resazurin. To further characterize the role of dipA and pilD in resazurin susceptibility, a dipA deletion mutant, ΔdipA, and pilD disruption mutant, FTL_0959d, were generated. Both mutants were less sensitive to killing by resazurin compared to wild-type LVS with phenotypes similar to the spontaneous resazurin-resistant mutants. This study identified a novel role for two genes dipA and pilD in F. tularensis susceptibility to resazurin.
A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration
Authors: Rossino Maria Grazia , Amato Rosario , Amadio Marialaura , Rosini Michela , Basagni Filippo , Cammalleri Maurizio , Dal Monte Massimo , Casini Giovanni
Published: August 2021

Oxidative stress (OS) plays a key role in retinal dysfunctions and acts as a major trigger of inflammatory and neurodegenerative processes in several retinal diseases. To prevent OS-induced retinal damage, approaches based on the use of natural compounds are actively investigated. Recently, structural features from curcumin and diallyl sulfide have been combined in a nature-inspired hybrid (NIH1), which has been described to activate transcription nuclear factor erythroid-2-related factor-2 (Nrf2), the master regulator of the antioxidant response, in different cell lines. We tested the antioxidant properties of NIH1 in mouse retinal explants. NIH1 increased Nrf2 nuclear translocation, Nrf2 expression, and both antioxidant enzyme expression and protein levels after 24 h or six days of incubation. Possible toxic effects of NIH1 were excluded since it did not alter the expression of apoptotic or gliotic markers. In OS-treated retinal explants, NIH1 strengthened the antioxidant response inducing a massive and persistent expression of antioxidant enzymes up to six days of incubation. These effects resulted in prevention of the accumulation of reactive oxygen species, of apoptotic cell death, and of gliotic reactivity. Together, these data indicate that a strategy based on NIH1 to counteract OS could be effective for the treatment of retinal diseases.
Antiviral Filtering Capacity of GO-Coated Textiles
Authors: Valentini Federica , Cirone Mara , Relucenti Michela , Santarelli Roberta , Gaeta Aurelia , Mussi Valentina , De Simone Sara , Zicari Alessandra , Mardente Stefania
Published: August 2021

Background. New antiviral textiles for the protection and prevention of life-threatening viral diseases are needed. Graphene oxide derivatives are versatile substances that can be combined with fabrics by different green electrochemistry methods. Methods In this study, graphene oxide (GO) nanosheets were combined with textile samples to study GO antiviral potential. GO synthesized in the Chemistry laboratories at the University of Rome Tor Vergata (Italy) and characterized with TEM/EDX, XRD, TGA, Raman spectroscopy, and FTIR, was applied at three different concentrations to linen textiles with the hot-dip and dry method to obtain filters. The GO-treated textiles were tested to prevent infection of a human glioblastoma cell line (U373) with human herpesvirus 6A (HHV-6A). Green electrochemical exfoliation of graphite into the oxidized graphene nanosheets provides a final GO-based product suitable for a virus interaction, mainly depending on the double layer of nanosheets, their corresponding nanometric sizes, and Z-potential value. Results Since GO-treated filters were able to prevent infection of cells in a dose-dependent fashion, our results suggest that GO may exert antiviral properties that can be exploited for medical devices and general use fabrics.
Recommender Systems in the Real Estate Market—A Survey
Authors: Gharahighehi Alireza , Pliakos Konstantinos , Vens Celine
Published: August 2021

The shift to e-commerce has changed many business areas. Real estate is one of the applications that has been affected by this modern technological wave. Recommender systems are intelligent models that assist users of real estate platforms in finding the best possible properties that fulfill their needs. However, the recommendation task is substantially more challenging in the real estate domain due to the many domain-specific limitations that impair typical recommender systems. For instance, real estate recommender systems usually face the clod-start problem where there are no historical logs for new users or new items, and the recommender system should provide recommendations for these new entities. Therefore, the recommender systems in the real estate market are different and substantially less studied than in other domains. In this article, we aim at providing a comprehensive and systematic literature review on applications of recommender systems in the real estate market. We evaluate a set of research articles (13 journal and 13 conference papers) which represent the majority of research and commercial solutions proposed in the field of real estate recommender systems. These papers have been reviewed and categorized based on their methodological approaches, the main challenges that they addressed, and their evaluation procedures. Based on these categorizations, we outlined some possible directions for future research.
A Numerical Study of a Compressed Air Engine with Rotating Cylinders
Authors: Dižo Ján , Blatnický Miroslav , Sága Milan , Šťastniak Pavol
Published: August 2021

This article explores the possibility that, during the elimination of conventional combustion engines, the connecting rod becomes deflected. A larger connecting rod angle creates higher lateral pressure on the piston, also leading to greater loads on other engine components. This fact inspired us to develop an applied mechanism design that reduces the disadvantages of conventional combustion engines. The presented mathematical model that describes the designed engine working principle was created utilizing Lagrange’s equations of motion of the second kind and solved in MATLAB. This paper also includes a multibody simulation model of the engine mechanism created using the Simpack software. Based on a comparison of the two methods, the obtained waveforms of the selected kinematic quantities were found to yield minimal deviations. A real prototype was subsequently developed based on the mathematical model outputs. In this manner, we practically verified that the proposed theoretical solution for a non-conventional engine is fully functional.
New Materials and Effects in Molecular Nanomagnets
Authors: Blachowicz Tomasz , Ehrmann Andrea
Published: August 2021

Molecular magnets are a relatively new class of purely organic or metallo-organic materials, showing magnetism even without an external magnetic field. This interdisciplinary field between chemistry and physics has been gaining increased interest since the 1990s. While bulk molecular magnets are usually hard to build because of their molecular structures, low-dimensional molecular magnets are often easier to construct, down to dot-like (zero-dimensional) structures, which are investigated by different scanning probe technologies. On these scales, new effects such as superparamagnetic behavior or coherent switching during magnetization reversal can be recognized. Here, we give an overview of the recent advances in molecular nanomagnets, starting with single-molecule magnets (0D), typically based on Mn12, Fe8, or Mn4, going further to single-chain magnets (1D) and finally higher-dimensional molecular nanomagnets. This review does not aim to give a comprehensive overview of all research fields dealing with molecular nanomagnets, but instead aims at pointing out diverse possible materials and effects in order to stimulate new research in this broad field of nanomagnetism.
Development of a Mobile Robot That Plays Tag with Touch-and-Away Behavior Using a Laser Range Finder
Authors: Kasai Yoshitaka , Hiroi Yutaka , Miyawaki Kenzaburo , Ito Akinori
Published: August 2021

The development of robots that play with humans is a challenging topic for robotics. We are developing a robot that plays tag with human players. To realize such a robot, it needs to observe the players and obstacles around it, chase a target player, and touch the player without collision. To achieve this task, we propose two methods. The first one is the player tracking method, by which the robot moves towards a virtual circle surrounding the target player. We used a laser range finder (LRF) as a sensor for player tracking. The second one is a motion control method after approaching the player. Here, the robot moves away from the player by moving towards the opposite side to the player. We conducted a simulation experiment and an experiment using a real robot. Both experiments proved that with the proposed tracking method, the robot properly chased the player and moved away from the player without collision. The contribution of this paper is the development of a robot control method to approach a human and then move away safely.
Future Projections and Uncertainty Assessment of Precipitation Extremes in Iran from the CMIP6 Ensemble
Authors: Hong Juyoung , Javan Khadijeh , Shin Yonggwan , Park Jeong-Soo
Published: August 2021

Scientists who want to know future climate can use multimodel ensemble (MME) methods that combine projections from individual simulation models. To predict the future changes of extreme rainfall in Iran, we examined the observations and 24 models of the Coupled Model Inter-Comparison Project Phase 6 (CMIP6) over the Middle East. We applied generalized extreme value (GEV) distribution to series of annual maximum daily precipitation (AMP1) data obtained from both of models and the observations. We also employed multivariate bias-correction under three shared socioeconomic pathway (SSP) scenarios (namely, SSP2-4.5, SSP3-7.0, and SSP5-8.5). We used a model averaging method that takes both performance and independence of model into account, which is called PI-weighting. Return levels for 20 and 50 years, as well as the return periods of the AMP1 relative to the reference years (1971–2014), were estimated for three future periods. These are period 1 (2021–2050), period 2 (2046–2075), and period 3 (2071–2100). From this study, we predict that over Iran the relative increases of 20-year return level of the AMP1 in the spatial median from the past observations to the year 2100 will be approximately 15.6% in the SSP2-4.5, 23.2% in the SSP3-7.0, and 28.7% in the SSP5-8.5 scenarios, respectively. We also realized that a 1-in-20 year (or 1-in-50 year) AMP1 observed in the reference years in Iran will likely become a 1-in-12 (1-in-26) year, a 1-in-10 (1-in-22) year, and a 1-in-9 (1-in-20) year event by 2100 under the SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. We project that heavy rainfall will be more prominent in the western and southwestern parts of Iran.
Personalized Data Analysis Approach for Assessing Necessary Hospital Bed-Days Built on Condition Space and Hierarchical Predictor
Authors: Melnykova Nataliia , Shakhovska Nataliya , Melnykov Volodymyr , Melnykova Kateryna , Lishchuk-Yakymovych Khrystyna
Published: August 2021

The paper describes the medical data personalization problem by determining the individual characteristics needed to predict the number of days a patient spends in a hospital. The mathematical problem of patient information analysis is formalized, which will help identify critical personal characteristics based on conditioned space analysis. The condition space is given in cube form as a reflection of the functional relationship of the general parameters to the studied object. The dataset consists of 51 instances, and ten parameters are processed using different clustering and regression models. Days in hospital is the target variable. A condition space cube is formed based on clustering analysis and features selection. In this manner, a hierarchical predictor based on clustering and an ensemble of weak regressors is built. The quality of the developed hierarchical predictor for Root Mean Squared Error metric is 1.47 times better than the best weak predictor (perceptron with 12 units in a single hidden layer).
HMGB1-TIM3-HO1: A New Pathway of Inflammation in Skin of SARS-CoV-2 Patients? A Retrospective Pilot Study
Authors: Cazzato Gerardo , Colagrande Anna , Cimmino Antonietta , Cicco Gerolamo , Scarcella Vincenza Sara , Tarantino Paola , Lospalluti Lucia , Romita Paolo , Foti Caterina , Demarco Aurora , Sablone Sara , Candance Pragnell Maria Victoria , Cicco Sebastiano , Lettini Teresa , Ingravallo Giuseppe , Resta Leonardo
Published: August 2021

The SARS-CoV-2 pandemic has completely disrupted the health systems of the entire planet. From the earliest months, it became increasingly clear that in addition to affecting the upper airways and lungs, there were other organs that could be affected. Among these, the skin became a real “sentinel signal” to be able to even suspect COVID-19. Background: this study deals with a little-explored issue for now: the study of skin immunopathology in SARS-CoV-2 positive subjects ascertained using the most reliable methods available. Methods: we used skin biopsy samples from SARS-CoV-2 positive and negative patients, studying morphology (Hematoxylin-Eosin), T lymphocyte population (CD4 and CD8), three markers such as HMGB-1, TIM-3 and HO-1 by immunohistochemistry. Results: although the presence of the CD4 and CD8 T population did not differ statistically significantly, we found greater activation and release of HMGB-1 in skin samples from SARS-CoV-2 positive patients, greater immunolabeling for TIM-3 at the level of CD4 and CD8 and a reduced expression of Heme oxygenase 1. Conclusions: these results support the possibility that there is immune deregulation in SARS-CoV-2 positive patients who develop skin manifestations of various kinds.
Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance
Authors: Gorski Justin W. , Zhang Zhuwei , McCorkle J. Robert , DeJohn Jodi M. , Wang Chi , Miller Rachel W. , Gallion Holly H. , Dietrich Charles S. , Ueland Frederick R. , Kolesar Jill M.
Published: August 2021

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC50 values were determined. One organoid line, UK1254, was predicted to be resistant to carboplatin based on its EC50 value (50.2 µM) being above clinically achievable Cmax. UK1254 had a significantly shorter PFS than the rest of the subjects (p = 0.0253) and was treated as a platinum-resistant recurrence. Subsequent gene expression analysis revealed extensively interconnected, differentially expressed pathways related to NF-kB, cellular differentiation (PRDM6 activation), and the linkage of B-cell receptor signaling to the PI3K–Akt signaling pathway (PI3KAP1 activation). This study demonstrates that patient-derived tumor organoids can be developed from patients at the time of primary or interval debulking surgery and may be used to predict clinical platinum sensitivity status or to investigate drivers of carboplatin resistance.
Plasma-Based Bioinks for Extrusion Bioprinting of Advanced Dressings
Authors: Del Amo Cristina , Perez-Valle Arantza , Perez-Garrastachu Miguel , Jauregui Ines , Andollo Noelia , Arluzea Jon , Guerrero Pedro , de la Caba Koro , Andia Isabel
Published: August 2021

Extrusion bioprinting based on the development of novel bioinks offers the possibility of manufacturing clinically useful tools for wound management. In this study, we show the rheological properties and printability outcomes of two advanced dressings based on platelet-rich plasma (PRP) and platelet-poor plasma (PPP) blended with alginate and loaded with dermal fibroblasts. Measurements taken at 1 h, 4 days, and 18 days showed that both the PRP- and PPP-based dressings retain plasma and platelet proteins, which led to the upregulation of angiogenic and immunomodulatory proteins by embedded fibroblasts (e.g., an up to 69-fold increase in vascular endothelial growth factor (VEGF), an up to 188-fold increase in monocyte chemotactic protein 1 (MCP-1), and an up to 456-fold increase in hepatocyte growth factor (HGF) 18 days after printing). Conditioned media harvested from both PRP and PPP constructs stimulated the proliferation of human umbilical vein endothelial cells (HUVECs), whereas only those from PRP dressings stimulated HUVEC migration, which correlated with the VEGF/MCP-1 and VEGF/HGF ratios. Similarly, the advanced dressings increased the level of interleukin-8 and led to a four-fold change in the level of extracellular matrix protein 1. These findings suggest that careful selection of plasma formulations to fabricate wound dressings can enable regulation of the molecular composition of the microenvironment, as well as paracrine interactions, thereby improving the clinical potential of dressings and providing the possibility to tailor each composition to specific wound types and healing stages.
Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers
Authors: Alhusaini Abdullah , Cannon Aoife , Maher Stephen G. , Reynolds John V. , Lynam-Lennon Niamh
Published: August 2021

Gastrointestinal (GI) malignancies are a major global health burden, with high mortality rates. The identification of novel therapeutic strategies is crucial to improve treatment and survival of patients. The poly (ADP-ribose) polymerase (PARP) enzymes involved in the DNA damage response (DDR) play major roles in the development, progression and treatment response of cancer, with PARP inhibitors (PARPi) currently used in the clinic for breast, ovarian, fallopian, primary peritoneal, pancreatic and prostate cancers with deficiencies in homologous recombination (HR) DNA repair. This article examines the current evidence for the role of the DDR PARP enzymes (PARP1, 2, 3 and 4) in the development, progression and treatment response of GI cancers. Furthermore, we discuss the role of HR status as a predictive biomarker of PARPi efficacy in GI cancer patients and examine the pre-clinical and clinical evidence for PARPi and cytotoxic therapy combination strategies in GI cancer. We also include an analysis of the genomic and transcriptomic landscape of the DDR PARP genes and key HR genes (BRCA1, BRCA2, ATM, RAD51, MRE11, PALB2) in GI patient tumours (n = 1744) using publicly available datasets to identify patients that may benefit from PARPi therapeutic approaches.
Pathophysiological and Pharmacological Characteristics of KCNJ5 157-159delITE Somatic Mutation in Aldosterone-Producing Adenomas
Authors: Peng Kang-Yung , Liao Hung-Wei , Chueh Jeff S. , Pan Chien-Yuan , Lin Yen-Hung , Chen Yung-Ming , Chen Peng-Ying , Huang Chun-Lin , Wu Vin-Cent
Published: August 2021

Mutated channelopathy could play important roles in the pathogenesis of aldosterone-producing adenoma (APA). In this study, we identified a somatic mutation, KCNJ5 157-159delITE, and reported its immunohistological, pathophysiological and pharmacological characteristics. We conducted patch-clamp experiments on HEK293T cells and experiments on expression of aldosterone synthase (CYP11B2) and aldosterone secretion in HAC15 cells to evaluate electrophysiological and functional properties of this mutated KCNJ5. Immunohistochemistry was conducted to identify expressions of several steroidogenic enzymes. Macrolide antibiotics and a calcium channel blocker were administrated to evaluate the functional attenuation of mutated KCNJ5 channel in transfected HAC15 cells. The interaction between macrolides and KCNJ5 protein was evaluated via molecular docking and molecular dynamics simulation analysis. The immunohistochemistry analysis showed strong CYP11B2 immunoreactivity in the APA harboring KCNJ5 157-159delITE mutation. Whole-cell patch-clamp data revealed that mutated KCNJ5 157-159delITE channel exhibited loss of potassium ion selectivity. The mutant-transfected HAC15 cells increased the expression of CYP11B2 and aldosterone secretion, which was partially suppressed by clarithromycin and nifedipine but not roxithromycin treatment. The docking analysis and molecular dynamics simulation disclosed that roxithromycin had strong interaction with KCNJ5 L168R mutant channel but not with this KCNJ5 157-159delITE mutant channel. We showed comprehensive evaluations of the KCNJ5 157-159delITE mutation which revealed that it disrupted potassium channel selectivity and aggravated autonomous aldosterone production. We further demonstrated that macrolide antibiotics, roxithromycin, could not interfere the aberrant electrophysiological properties and gain-of-function aldosterone secretion induced by KCNJ5 157-159delITE mutation.
From Research to Practice: Toward the Examination of Combined Interventions for Autism Spectrum Disorders
Authors: London Eric Bart , Yoo Jiyeon Helen
Published: August 2021

The use of biological (i.e., medications) in conjunction with applied behavior analysis is relatively common among people with ASD, yet research examining its benefit is scarce. This paper provides a brief overview of the existing literature on the combined interventions, including promising developments, and examines the existing barriers that hinder research in this area, including the heavy reliance on RCTs. Recommendations for possible solutions, including the creation of health homes, are provided in order to move toward a more integrated approach.
Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization
Authors: Song Jing , Yang Peiyan , Li Xiuwen , Zhu Xinyi , Liu Mengxin , Duan Xuexin , Liu Ran
Published: August 2021

The disorganized polarization of tumor-associated macrophages (TAMs) exerts a critical effect on tumor progression. MicroRNAs (miRNAs) in extracellular vesicles (EVs) secreted from cancer cells may contribute to this process. However, the relationship between TAMs and EVs-miRNAs-mediated regulation in esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, immunoaffinity magnetic beads combined with antiepithelial cell adhesion molecules (EpCAM) were used to isolate and identify EVs-miR-21-5p from the plasma of ESCC patients. An in vitro coculture system was designed to evaluate the effect of esophageal cancer cells with miR-21-5p overexpression on macrophage polarization. We found that phorbol myristate acetate-induced THP-1 macrophages took up EVs-miR-21-5p from EC109 or EC9706 cells and were transformed into M2 macrophages. This, in turn, contributed to the excessive migration and invasion of esophageal cancer cells. The mechanism underlying these changes may involve activation of M2 macrophages by upregulated ESCC-derived EVs-miR-21-5p through the PTEN/AKT/STAT6 pathway. This may result in esophageal cancer cell epithelial-mesenchymal transition (EMT) via TGF-β/Smad2 signaling. Our results indicate positive feedback between M2 macrophage polarization and EMT of esophageal cancer cells in the tumor microenvironment via shuttling of miR-21-5p in tumor-derived EVs.
Pan-Cancer Analysis of Immune Complement Signature C3/C5/C3AR1/C5AR1 in Association with Tumor Immune Evasion and Therapy Resistance
Authors: Lawal Bashir , Tseng Sung-Hui , Olugbodi Janet , Iamsaard Sitthichai , Ilesanmi Omotayo , Mahmoud Mohamed , Ahmed Sahar , Batiha Gaber , Wu Alexander
Published: August 2021

Despite the advances in our understanding of the genetic and immunological basis of cancer, cancer remains a major public health burden with an ever-increasing incidence rate globally. Nevertheless, increasing evidence suggests that the components of the complement system could regulate the tumor microenvironment (TME) to promote cancer progression, recurrence, and metastasis. In the present study, we used an integrative multi-omics analysis of clinical data to explore the relationships between the expression levels of and genetic and epigenetic alterations in C3, C5, C3AR1, and C5AR1 and tumor immune evasion, therapy response, and patient prognosis in various cancer types. We found that the complements C3, C5, C3AR1, and C5AR1 have deregulated expression in human malignancies and are associated with activation of immune-related oncogenic processes and poor prognosis of cancer patients. Furthermore, we found that the increased expression levels of C3, C5, C3AR1, and C5AR1 were primarily predicted by copy number variation and gene methylation and were associated with dysfunctional T-cell phenotypes. Single nucleotide variation in the gene signature co-occurred with multiple oncogenic mutations and is associated with the progression of onco-immune-related diseases. Further correlation analysis revealed that C3, C5, C3AR1, and C5AR1 were associated with tumor immune evasion via dysfunctional T-cell phenotypes with a lesser contribution of T-cell exclusion. Lastly, we also demonstrated that the expression levels of C3, C5, C3AR1, and C5AR1 were associated with context-dependent chemotherapy, lymphocyte-mediated tumor killing, and immunotherapy outcomes in different cancer types. In conclusion, the complement components C3, C5, C3AR1, and C5AR1 serve as attractive targets for strategizing cancer immunotherapy and response follow-up.
Neutrophil Interactions with the Lymphatic System
Authors: Jakovija Arnolda , Chtanova Tatyana
Published: August 2021

The lymphatic system is a complex network of lymphatic vessels and lymph nodes designed to balance fluid homeostasis and facilitate host immune defence. Neutrophils are rapidly recruited to sites of inflammation to provide the first line of protection against microbial infections. The traditional view of neutrophils as short-lived cells, whose role is restricted to providing sterilizing immunity at sites of infection, is rapidly evolving to include additional functions at the interface between the innate and adaptive immune systems. Neutrophils travel via the lymphatics from the site of inflammation to transport antigens to lymph nodes. They can also enter lymph nodes from the blood by crossing high endothelial venules. Neutrophil functions in draining lymph nodes include pathogen control and modulation of adaptive immunity. Another facet of neutrophil interactions with the lymphatic system is their ability to promote lymphangiogenesis in draining lymph nodes and inflamed tissues. In this review, we discuss the significance of neutrophil migration to secondary lymphoid organs and within the lymphatic vasculature and highlight emerging evidence of the neutrophils’ role in lymphangiogenesis.
Gold Nanoparticles/Carbon Nanotubes and Gold Nanoporous as Novel Electrochemical Platforms for L-Ascorbic Acid Detection: Comparative Performance and Application
Authors: Tortolini Cristina , Tasca Federico , Venneri Mary Anna , Marchese Cinzia , Antiochia Riccarda
Published: August 2021

Herein, the effects of nanostructured modifications of a gold electrode surface in the development of electrochemical sensors for L-ascorbic acid detection have been investigated. In particular, a bare gold electrode has been modified by electrodeposition of gold single-walled carbon nanotubes (Au/SWCNTs) and by the formation of a highly nanoporous gold (h-nPG) film. The procedure has been realized by sweeping the potential between +0.8 V and 0 V vs. Ag/AgCl for 25 scans in a suspension containing 5 mg/mL of SWCNTs in 10 mM HAuCl4 and 2.5 M NH4Cl solution for Au/SWCNTs modified gold electrode. A similar procedure was applied for a h-nPG electrode in a 10 mM HAuCl4 solution containing 2.5 M NH4Cl, followed by applying a fixed potential of −4 V vs. Ag/AgCl for 60 s. Cyclic voltammetry and electrochemical impedance spectroscopy were used to characterize the properties of the modified electrodes. The developed sensors showed strong electrocatalytic activity towards ascorbic acid oxidation with enhanced sensitivities of 1.7 × 10−2 μA μM−1cm−2 and 2.5 × 10−2 μA μM−1cm−2 for Au/SWCNTs and h-nPG modified electrode, respectively, compared to bare gold electrode (1.0 × 10−2 μA μM−1cm−2). The detection limits were estimated to be 3.1 and 1.8 μM, respectively. The h-nPG electrode was successfully used to determine ascorbic acid in human urine with no significant interference and with satisfactory recovery levels.
Newborn Incubators Do Not Protect from High Noise Levels in the Neonatal Intensive Care Unit and Are Relevant Noise Sources by Themselves
Authors: Restin Tanja , Gaspar Mikael , Bassler Dirk , Kurtcuoglu Vartan , Scholkmann Felix , Haslbeck Friederike Barbara
Published: August 2021

Background: While meaningful sound exposure has been shown to be important for newborn development, an excess of noise can delay the proper development of the auditory cortex. Aim: The aim of this study was to assess the acoustic environment of a preterm baby in an incubator on a newborn intensive care unit (NICU). Methods: An empty but running incubator (Giraffe Omnibed, GE Healthcare) was used to evaluate the incubator frequency response with 60 measurements. In addition, a full day and night period outside and inside the incubator at the NICU of the University Hospital Zurich was acoustically analyzed. Results: The fan construction inside the incubator generates noise in the frequency range of 1.3–1.5 kHz with a weighted sound pressure level (SPL) of 40.5 dB(A). The construction of the incubator narrows the transmitted frequency spectrum of sound entering the incubator to lower frequencies, but it does not attenuate transient noises such as alarms or opening and closing of cabinet doors substantially. Alarms, as generated by the monitors, the incubator, and additional devices, still pass to the newborn. Conclusions: The incubator does protect only insufficiently from noise coming from the NICUThe transmitted frequency spectrum is changed, limiting the impact of NICU noise on the neonate, but also limiting the neonate’s perception of voices. The incubator, in particular its fan, as well as alarms from patient monitors are major sources of noise. Further optimizations with regard to the sound exposure in the NICU, as well as studies on the role of the incubator as a source and modulator, are needed to meet the preterm infants’ multi-sensory needs.