bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Analysis Identifies Strategies Targeting Immune Response-Related Pathways to Control Enterotoxigenic Escherichia coli Infection in Porcine Intestinal Epithelial Cells
Authors: Wu Qiong , Cui Defeng , Chao Xinyu , Chen Peng , Liu Jiaxuan , Wang Yiding , Su Tongjian , Li Meng , Xu Ruyu , Zhu Yaohong , Zhang Yonghong
Published: August 2021

Enterotoxigenic Escherichia coli (ETEC) is an important cause of post-weaning diarrhea (PWD) worldwide, resulting in huge economic losses to the swine industry worldwide. In this study, to understand the pathogenesis, the transcriptomic analysis was performed to explore the biological processes (BP) in porcine intestinal epithelial J2 cells infected with an emerging ETEC strain isolated from weaned pigs with diarrhea. Under the criteria of |fold change| (FC) ≥ 2 and P < 0.05 with false discovery rate < 0.05, a total of 131 referenced and 19 novel differentially expressed genes (DEGs) were identified after ETEC infection, including 96 upregulated DEGs and 54 downregulated DEGs. The Gene Ontology (GO) analysis of DEGs showed that ETEC evoked BP specifically involved in response to lipopolysaccharide (LPS) and negative regulation of intracellular signal transduction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response-related pathways were mainly enriched in J2 cells after ETEC infection, in which tumor necrosis factor (TNF), interleukin 17, and mitogen-activated protein kinase (MAPK) signaling pathways possessed the highest rich factor, followed by nucleotide-binding and oligomerization domain-like receptor (NLRs), C-type lectin receptor (CLR), cytokine–cytokine receptor interaction, and Toll-like receptor (TLR), and nuclear factor kappa-B (NF-κB) signaling pathways. Furthermore, 30 of 131 referenced DEGs, especially the nuclear transcription factor AP-1 and NF-κB, participate in the immune response to infection through an integral signal cascade and can be target molecules for prevention and control of enteric ETEC infection by probiotic Lactobacillus reuteri. Our data provide a comprehensive insight into the immune response of porcine intestinal epithelial cells (IECs) to ETEC infection and advance the identification of targets for prevention and control of ETEC-related PWD.
V-Gel® Guided Endotracheal Intubation in Rabbits
Authors: Fusco Alessandra , Douglas Hope , Barba Adriana , Hopster Klaus , Stefanovski Darko , Sinder Benjamin , Cahill Patrick J. , Snyder Brian , Schaer Thomas P.
Published: August 2021

Background:General anesthesia in rabbits is associated with higher morbidity and mortality relative to other mammalian species commonly anesthetized. Unique challenges related to endotracheal intubation (ETI) in rabbits contribute to this risk.

Objective:To improve the safety of ETI in rabbits, we developed two new ETI methods using a supraglottic airway device (v-gel®) to facilitate ETI and compared them to traditional “blind” technique. We hypothesized that relative to blind ETI, v-gel®guided ETI provides more successful placement of the endotracheal tube (ETT) in a shorter time. Outcomes included number of intubation attempts, time for achievement of ETI, endoscopic findings, and serial arterial blood gas (ABG) analysis.

Study Design:Prospective, randomized, and crossover study.

Methods:Ten female, New Zealand White rabbits aged 1–2 years old, weighing 4.3 ± 0.4 kg, were anesthetized four times. Each time, ETI was performed with one of the following techniques: Method 1: v-gel®guided, polypropylene catheter facilitated, intubation using a cuffed ETT; Method 2: v-gel®guided intubation using an uncuffed ETT directly inserted through the device airway channel; Method 3 and 4: Blind intubation with uncuffed or cuffed ETT. Upper airway endoscopy was performed before intubation attempts and after extubation. Serial ABG analysis was performed during the peri-intubation process.

Results:V-gel®guided techniques allowed successful ETI on the initial attempt for 9/10 subjects using Method 1 and 10/10 using Method 2. Relative to the v-gel®guided techniques, the blind techniques required more intubation attempts. A median of 2 attempts (range 1–4,p< 0.007) were required for the uncuffed ETT, and a median of 4 (range 1–4,p< 0.001) attempts were performed for the cuffed ETT. The time to perform successful ETI was positively correlated with the number of attempts (ρ = 0.82), while successful ETI was negatively correlated with number of attempts (ρ = −0.82). Endoscopic findings showed mild to moderate laryngeal trauma. In the absence of oxygen supplementation, ABG analysis demonstrated low PaO2, while PaCO2remained consistent.

Conclusions:Facilitated ETI using the v-gel®guided techniques allows for the rapid establishment of a secure airway to provide ventilatory support for rabbits undergoing general anesthesia.
Computational Complexity and ILP Models for Pattern Problems in the Logical Analysis of Data
Authors: Lancia Giuseppe , Serafini Paolo
Published: August 2021

Logical Analysis of Data is a procedure aimed at identifying relevant features in data sets with both positive and negative samples. The goal is to build Boolean formulas, represented by strings over {0,1,-} called patterns, which can be used to classify new samples as positive or negative. Since a data set can be explained in alternative ways, many computational problems arise related to the choice of a particular set of patterns. In this paper we study the computational complexity of several of these pattern problems (showing that they are, in general, computationally hard) and we propose some integer programming models that appear to be effective. We describe an ILP model for finding the minimum-size set of patterns explaining a given set of samples and another one for the problem of determining whether two sets of patterns are equivalent, i.e., they explain exactly the same samples. We base our first model on a polynomial procedure that computes all patterns compatible with a given set of samples. Computational experiments substantiate the effectiveness of our models on fairly large instances. Finally, we conjecture that the existence of an effective ILP model for finding a minimum-size set of patterns equivalent to a given set of patterns is unlikely, due to the problem being NP-hard and co-NP-hard at the same time.
An Efficient Structure of an Agrophotovoltaic System in a Temperate Climate Region
Authors: Kim Sojung , Kim Sumin , Yoon Chang-Yong
Published: August 2021

The aim of this study was to identify an efficient agrophotovoltaic (APV) system structure for generating electricity from solar radiation without causing an adverse impact on crop growth. In a temperate climate region, it is critical to design an APV system with appropriate structure with the maximum amount of electricity generation because, unlike in desert areas, strong solar radiation is only available for a few hours a day. In this study, APV systems with three different shading ratios (i.e., 32%, 25.6%, and 21.3%) were considered, and the optimum structure in terms of electricity efficiency and profitability was investigated via nonlinear programming. Moreover, an estimation model of electricity generation was developed via a polynomial regression model based on remote sensing data given by the APV system located at Jeollanamdo Agricultural Research and Extension Services in South Korea. To evaluate the impact of the APV on crop production, five different grain crops—sesame (Sesamum indicum), mung bean (Vigna radiata), red bean (Vigna angularis), corn (Zea mays), and soybean (Glycine max)—were cultivated in the system. As a result, the proposed optimization model successfully identified the best APV system structure without reducing existing crop production.
A Parametric Model for Local Air Exchange Rate of Naturally Ventilated Barns
Authors: Doumbia E. Moustapha , Janke David , Yi Qianying , Prinz Alexander , Amon Thomas , Kriegel Martin , Hempel Sabrina
Published: August 2021

With an increasing number of naturally ventilated dairy barns (NVDBs), the emission of ammonia and greenhouse gases into the surrounding environment is expected to increase as well. It is very challenging to accurately determine the amount of gases released from a NVDB on-farm. Moreover, control options for the micro-climate to increase animal welfare are limited in an NVDB at present. Both issues are due to the complexity of the NVDB micro-environment, which is subject to temporal (such as wind direction and temperature) and spatial (such as openings and animals acting as airflow obstacles) fluctuations. The air exchange rate (AER) is one of the most valuable evaluation entities, since it is directly related to the gas emission rate and animal welfare. In this context, our study determined the general and local AERs of NVDBs of different shapes under diverse airflow conditions. Previous works identified main influencing parameters for the general AER and mathematically linked them together to predict the AER of the barn as a whole. The present research study is a continuation and extension of previous studies about the determination of AER. It provides new insights into the influence of convection flow regimes. In addition, it goes further in precision by determining the local AERs, depending on the position of the considered volume inside the barn. After running several computational fluid dynamics (CFD) simulations, we used the statistical tool of general linear modeling in order to identify quantitative relationships between the AER and the following five influencing parameters, the length/width ratio of the barn, the side opening configuration, the airflow temperature, magnitude and incoming direction. The work succeeded in taking the temperature into account as a further influencing parameter in the model and, thus, for the first time, in analysing the effect of the different types of flow convection in this context. The resulting equations predict the barn AER with an R2 equals 0.98 and the local AER with a mean R2 equals around 0.87. The results go a step further in the precise determination of the AER of NVDB and, therefore, are of fundamental importance for a better and deeper understanding of the interaction between the driving forces of AER in NVDB.
The Effect of Trichoderma citrinoviride Treatment under Salinity Combined to Rhizoctonia solani Infection in Strawberry (Fragaria x ananassa Duch.)
Authors: Sekmen Cetinel Askim Hediye , Gokce Azime , Erdik Erhan , Cetinel Barbaros , Cetinkaya Nedim
Published: August 2021

Trihoderma citrinoviride protects plants from diseases by functioning as antagonists of many pathogenic fungi or by triggering the antioxidant defense system in plants. In the present study, to uncover the possible alleviative role of Trichoderma against salinity and Rhizoctonia solani infection, strawberry plants were pretreated Trichoderma citrinoviride and then subjected to salinity, R. solani and combined salinity and R. solani. The effect of T. citrinoviride on the alleviation of the effects of salt stress and Rhizoctonia solani infection was investigated by analysing leaf dry weight, PSII efficiency, and the activity of some antioxidant enzymes in the leaves of strawberry plants. T. citrinoviride improved competitive capability against salinity and R. solani infection. It showed 79% inhibition of the growth of pathogen R. solani. T. citrinoviride reduced 63% of the severity of disease in the leaves. Trichoderma pretreatment maximized plant dry weight. The T. citrinoviride-pretreated plants showed higher levels of PSII efficiency (Fv/Fm). Decreased lipid peroxidation and H2O2 accumulation compared to untreated seedlings under salt stress and R. solani infection was observed. Trichoderma-pretreated and –untreated plants respond differently to salt stress and R. solani infection by means of antioxidant defense. As compared to untreated seedlings, treated seedlings showed significantly lower activities of antioxidant enzymes, superoxide dismutase (SOD), peroxidase (POX), cell wall peroxidase (CWPOX) under salt stress and R. solani infection, indicating that treated seedlings might sense lower stress as compared to untreated seedlings. The study reports the effective adaptive strategy and potential of T. citrinoviride in alleviating the negative impact of salt stress and R. solani infection in strawberry.
Chickpea Can Be a Valuable Local Produced Protein Feed for Organically Reared, Native Bulls
Authors: Serrapica Francesco , Masucci Felicia , De Rosa Giuseppe , Calabrò Serena , Lambiase Claudia , Di Francia Antonio
Published: August 2021

We assessed the effects of inclusion of chickpea from 24 to 21%, as feed basis, in diets for organically reared bulls. Sixteen young bulls (270 ± 6.4 days of age; 246 ± 0.13 kg in weight) belonging to a native Italian breed (Maremmana) were randomly assigned to two dietary treatments. The control diets were based on mixed grass hay, maize meal, and barley meal. In the experimental diets, barley was equally substituted by locally produced chickpea. Animals were weighed every 2 weeks until the prefixed slaughtering weight (630 kg). Plasma metabolites were measured at the 1st, 7th, and 14th month of the experiment. Chemical composition, colour, shear force, and water holding capacity of meat were assessed on Longissimus thoracis et lumborum 7 days after slaughter. The chickpea-fed animals showed a significantly greater average daily gain (1064 vs. 1168 kg/day), a shorter growing phase (364 vs. 335 days), and a better carcass conformation. Plasma metabolites and meat quality were not influenced by the treatments. The better growth performance and carcass quality of the chickpea fed bulls resulted in a higher economic profit for the chickpea-based diets. Results suggest that chickpea may allow sustainable performance improvement of native breeds within their traditional farming systems.
Comparison of Bovine Mammary Involution and Intramammary Infections Following Intramammary Treatment with Casein Hydrolysate and Other Conventional Treatments at Dry-Off
Authors: Britten Justine E. , Rood Kerry A. , Wilson David J.
Published: August 2021

Alternatives to routine antibiotic treatment of dairy cattle during the dry period before their next calving are of interest. This was a preliminary study of whether intramammary infusion of casein hydrolysate, administered alone or combined with standard dry treatment, accelerated the rate of mammary involution early in the dry period. Four treatments were studied in a split udder design. One udder half was assigned a treatment, and the contralateral half was administered dry cow treatment + internal teat sealant as a control. Treatments were casein hydrolysate, casein hydrolysate + dry cow treatment, casein hydrolysate + teat sealant and casein hydrolysate + dry cow treatment + teat sealant. Cows (n = 16) were blocked by a number of intramammary infections per udder half (0 or 1+) and randomized to treatments. Milk production was not different between control or treated udder halves post-calving. A generalized linear mixed model tested for differences between the treatment groups in the concentration of mammary involution indicators in milk: somatic cell count, bovine lactoferrin and bovine serum albumin. At 7 days, dry udder halves treated with casein hydrolysate had higher milk concentrations of lactoferrin than those treated with casein hydrolysate + dry cow treatment, casein hydrolysate + teat sealant and control. At 10 days dry, bovine serum albumin was higher in udder halves treated with casein hydrolysate than in those treated with casein hydrolysate + dry cow treatment, casein hydrolysate + dry cow treatment + teat sealant and control. Post-calving, casein hydrolysate-treated udder halves produced 51% of total milk, unchanged from before dry-off. There were seven total intramammary infections entering the dry period, all caused by coagulase-negative staphylococci. Cure rates (3/7, 43%) were not different among all treatments and control, partly because of the small sample size. Intramammary infusion of casein hydrolysate at the end of lactation may be an alternative or possible adjunct to antibiotic dry cow therapy.
Antibiotic Resistance and Genotypes of Mycoplasma genitalium during a Resistance-Guided Treatment Regime in a German University Hospital
Authors: Dumke Roger , Spornraft-Ragaller Petra
Published: August 2021

The treatment of infections from the sexually transmitted pathogen Mycoplasma genitalium is hampered by the rapidly increasing resistance to the recommended first- (macrolides) and second-line antibiotics (quinolones). Thus, resistance-guided therapy (RGT) is key for its successful eradication but the efficiency of this approach can be influenced by re-infections and treatment failures. The typing of strains is helpful to distinguish between ongoing colonization, re-infection or the development of resistance. In the present study, mgpB and MG_309 types as well as mutations associated with macrolide, quinolone and tetracycline resistance of strains in M. genitalium-positive samples accumulated in the years 2019 and 2020 at a university hospital were analyzed. Fifty-eight positive first and sixteen positive follow-up samples from patients (96.6% male, 84.5% men who have sex with men, 74.1% HIV-positive) were included. Twenty-three mgpB types (seven new types), nine MG_309 types and thirty-four mgpB/MG_309 types were identified. The prevalence of mutations associated with macrolide, quinolone and tetracycline resistance was 56.9%, 10.3% and 6.8%, respectively. Despite the fact that many asymptomatic patients were not treated and tests of cure were impossible in different cases, the preliminary rate of successful eradication (93.3%) in this study is promising for the continuation of the RGT strategy.
Imbalance of Systemic Redox Biomarkers in Children with Epilepsy: Role of Ferroptosis
Authors: Petrillo Sara , Pietrafusa Nicola , Trivisano Marina , Calabrese Costanza , Saura Francesca , Gallo Maria Giovanna , Bertini Enrico Silvio , Vigevano Federico , Specchio Nicola , Piemonte Fiorella
Published: August 2021

To assess if ferroptosis, a new type of programmed cell death accompanied by iron accumulation, lipid peroxidation, and glutathione depletion, occurs in children with epilepsy, and in order to identify a panel of biomarkers useful for patient stratification and innovative-targeted therapies, we measured ferroptosis biomarkers in blood from 83 unrelated children with a clinical diagnosis of epilepsy and 44 age-matched controls. We found a marked dysregulation of three ferroptosis key markers: a consistent increase of 4-hydroxy-2-nonenal (4-HNE), the main by-product of lipid peroxidation, a significant decrease of glutathione (GSH) levels, and a partial inactivation of the enzyme glutathione peroxidase 4 (GPX4), the mediator of lipid peroxides detoxification. Furthermore, we found a significant increase of NAPDH oxidase 2 (NOX2) in the blood of children, supporting this enzyme as a primary source of reactive oxygen species (ROS) in epilepsy. Additionally, since the nuclear factor erythroid 2-related factor 2 (NRF2) induction protects the brain from epileptic seizure damage, we also evaluated the NRF2 expression in the blood of children. The antioxidant and anti-inflammatory transcription factor was activated in patients, although not enough to re-establish a correct redox homeostasis for counteracting ferroptosis. Ferroptosis-mediated oxidative damage has been proposed as an emergent mechanism underlying the pathogenesis of epilepsy. Overall, our study confirms a crucial role for ferroptosis in epilepsy, leading to the identification of a panel of biomarkers useful to find new therapeutic targets. Developing innovative drugs, which act by inhibiting the ferroptosis signaling axis, may represent a promising strategy for new anti-seizure medications.
Luteolin Alleviates AflatoxinB1-Induced Apoptosis and Oxidative Stress in the Liver of Mice through Activation of Nrf2 Signaling Pathway
Authors: Rajput Shahid Ali , Shaukat Aftab , Wu Kuntan , Rajput Imran Rashid , Baloch Dost Muhammad , Akhtar Rana Waseem , Raza Muhammad Asif , Najda Agnieszka , Rafał Papliński , Albrakati Ashraf , El-Kott Attalla F. , Abdel-Daim Mohamed M.
Published: August 2021

Aflatoxin B1 (AFB1), a threatening mycotoxin, usually provokes oxidative stress and causes hepatotoxicity in animals and humans. Luteolin (LUTN), well-known as an active phytochemical agent, acts as a strong antioxidant. This research was designed to investigate whether LUTN exerts protective effects against AFB1-induced hepatotoxicity and explore the possible molecular mechanism in mice. A total of forty-eight mice were randomly allocated following four treatment groups (n = 12): Group 1, physiological saline (CON). Group 2, treated with 0.75 mg/kg BW aflatoxin B1 (AFB1). Group 3, treated with 50 mg/kg BW luteolin (LUTN), and Group 4, treated with 0.75 mg/kg BW aflatoxin B1 + 50 mg/kg BW luteolin (AFB1 + LUTN). Our findings revealed that LUTN treatment significantly alleviated growth retardation and rescued liver injury by relieving the pathological and serum biochemical alterations (ALT, AST, ALP, and GGT) under AFB1 exposure. LUTN ameliorated AFB1-induced oxidative stress by scavenging ROS and MDA accumulation and boosting the capacity of the antioxidant enzyme (CAT, T-SOD, GSH-Px and T-AOC). Moreover, LUTN treatment considerably attenuates the AFB1-induced apoptosis in mouse liver, as demonstrated by declined apoptotic cells percentage, decreased Bax, Cyt-c, caspase-3 and caspase-9 transcription and protein with increased Bcl-2 expression. Notably, administration of LUTN up-regulated the Nrf2 and its associated downstream molecules (HO-1, NQO1, GCLC, SOD1) at mRNA and protein levels under AFB1 exposure. Our results indicated that LUTN effectively alleviated AFB1-induced liver injury, and the underlying mechanisms were associated with the activation of the Nrf2 signaling pathway. Taken together, LUTN may serve as a potential mitigator against AFB1-induced liver injury and could be helpful for the development of novel treatment to combat liver diseases in humans and/or animals.
The Impact of Melatonin Supplementation and NLRP3 Inflammasome Deletion on Age-Accompanied Cardiac Damage
Authors: Sayed Ramy K. A. , Fernández-Ortiz Marisol , Rahim Ibtissem , Fernández-Martínez José , Aranda-Martínez Paula , Rusanova Iryna , Martínez-Ruiz Laura , Alsaadawy Reem M. , Escames Germaine , Acuña-Castroviejo Darío
Published: August 2021

To investigate the role of NLRP3 inflammasome in cardiac aging, we evaluate here morphological and ultrastructural age-related changes of cardiac muscles fibers in wild-type and NLRP3-knockout mice, as well as studying the beneficial effect of melatonin therapy. The results clarified the beginning of the cardiac sarcopenia at the age of 12 months, with hypertrophy of cardiac myocytes, increased expression of β-MHC, appearance of small necrotic fibers, decline of cadiomyocyte number, destruction of mitochondrial cristae, appearance of small-sized residual bodies, and increased apoptotic nuclei ratio. These changes were progressed in the cardiac myocytes of 24 old mice, accompanied by excessive collagen deposition, higher expressions of IL-1α, IL-6, and TNFα, complete mitochondrial vacuolation and damage, myofibrils disorganization, multivesicular bodies formation, and nuclear fragmentation. Interestingly, cardiac myocytes of NLRP3−/− mice showed less detectable age-related changes compared with WT mice. Oral melatonin therapy preserved the normal cardiomyocytes structure, restored cardiomyocytes number, and reduced β-MHC expression of cardiac hypertrophy. In addition, melatonin recovered mitochondrial architecture, reduced apoptosis and multivesicular bodies’ formation, and decreased expressions of β-MHC, IL-1α, and IL-6. Fewer cardiac sarcopenic changes and highly remarkable protective effects of melatonin treatment detected in aged cardiomyocytes of NLRP3−/− mice compared with aged WT animals, confirming implication of the NLRP3 inflammasome in cardiac aging. Thus, NLRP3 suppression and melatonin therapy may be therapeutic approaches for age-related cardiac sarcopenia.
Efficient Hair Damage Detection Using SEM Images Based on Convolutional Neural Network
Authors: Man Qiaoyue , Zhang Lintong , Cho Youngim
Published: August 2021

With increasing interest in hairstyles and hair color, bleaching, dyeing, straightening, and curling hair is being widely used worldwide, and the chemical and physical treatment of hair is also increasing. As a result, hair has suffered a lot of damage, and the degree of damage to hair has been measured only by the naked eye or touch. This has led to serious consequences, such as hair damage and scalp diseases. However, although these problems are serious, there is little research on hair damage. With the advancement of technology, people began to be interested in preventing and reversing hair damage. Manual observation methods cannot accurately and quickly identify hair damage areas. In recent years, with the rise of artificial intelligence technology, a large number of applications in various scenarios have given researchers new methods. In the project, we created a new hair damage data set based on SEM (scanning electron microscope) images. Through various physical and chemical analyses, we observe the changes in the hair surface according to the degree of hair damage, found the relationship between them, used a convolutional neural network to recognize and confirm the degree of hair damage, and categorized the degree of damage into weak damage, moderate damage and high damage.
Additive Manufacturing of Bone Scaffolds Using PolyJet and Stereolithography Techniques
Authors: Rasheed Shummaila , Lughmani Waqas , Obeidi Muhannad , Brabazon Dermot , Ahad Inam
Published: August 2021

In this study, the printing capability of two different additive manufacturing (3D printing) techniques, namely PolyJet and micro-stereolithography (µSLA), are investigated regarding the fabrication of bone scaffolds. The 3D-printed scaffold structures are used as supports in replacing and repairing fractured bone tissue. Printed bone scaffolds with complex structures produced using additive manufacturing technology can mimic the mechanical properties of natural human bone, providing lightweight structures with modifiable porosity levels. In this study, 3D scaffold structures are designed with different combinations of architectural parameters. The dimensional accuracy, permeability, and mechanical properties of complex 3D-printed scaffold structures are analyzed to compare the advantages and drawbacks associated with the two techniques. The fluid flow rates through the 3D-printed scaffold structures are measured and Darcy’s law is applied to calculate the experimentally measured permeability. The Kozeny–Carman equation is applied for theoretical calculation of permeability. Compression tests were performed on the printed samples to observe the effects of the printing techniques on the mechanical properties of the 3D-printed scaffold structures. The effect of the printing direction on the mechanical properties of the 3D-printed scaffold structures is also analyzed. The scaffold structures printed with the µSLA printer demonstrate higher permeability and mechanical properties as compared to those printed using the PolyJet technique. It is demonstrated that both the µSLA and PolyJet printing techniques can be used to print 3D scaffold structures with controlled porosity levels, providing permeability in a similar range to human bone.
On the Reversible Jump Markov Chain Monte Carlo (RJMCMC) Algorithm for Extreme Value Mixture Distribution as a Location-Scale Transformation of the Weibull Distribution
Authors: Rantini Dwi , Iriawan Nur , Irhamah
Published: August 2021

Data with a multimodal pattern can be analyzed using a mixture model. In a mixture model, the most important step is the determination of the number of mixture components, because finding the correct number of mixture components will reduce the error of the resulting model. In a Bayesian analysis, one method that can be used to determine the number of mixture components is the reversible jump Markov chain Monte Carlo (RJMCMC). The RJMCMC is used for distributions that have location and scale parameters or location-scale distribution, such as the Gaussian distribution family. In this research, we added an important step before beginning to use the RJMCMC method, namely the modification of the analyzed distribution into location-scale distribution. We called this the non-Gaussian RJMCMC (NG-RJMCMC) algorithm. The following steps are the same as for the RJMCMC. In this study, we applied it to the Weibull distribution. This will help many researchers in the field of survival analysis since most of the survival time distribution is Weibull. We transformed the Weibull distribution into a location-scale distribution, which is the extreme value (EV) type 1 (Gumbel-type for minima) distribution. Thus, for the mixture analysis, we call this EV-I mixture distribution. Based on the simulation results, we can conclude that the accuracy level is at minimum 95%. We also applied the EV-I mixture distribution and compared it with the Gaussian mixture distribution for enzyme, acidity, and galaxy datasets. Based on the Kullback–Leibler divergence (KLD) and visual observation, the EV-I mixture distribution has higher coverage than the Gaussian mixture distribution. We also applied it to our dengue hemorrhagic fever (DHF) data from eastern Surabaya, East Java, Indonesia. The estimation results show that the number of mixture components in the data is four; we also obtained the estimation results of the other parameters and labels for each observation. Based on the Kullback–Leibler divergence (KLD) and visual observation, for our data, the EV-I mixture distribution offers better coverage than the Gaussian mixture distribution.
Evaluating Prediction Models of Creep and Drying Shrinkage of Self-Consolidating Concrete Containing Supplementary Cementitious Materials/Fillers
Authors: Asaad Micheal , Morcous George
Published: August 2021

Supplementary cementitious materials (SCMs) and fillers play an important role in enhancing the mechanical properties and durability of concrete. SCMs and fillers are commonly used in self-consolidating concrete (SCC) mixtures to also enhance their rheological properties. However, these additives could have significant effects on the viscoelastic properties of concrete. Existing models for predicting creep and drying shrinkage of concrete do not consider the effect of SCM/filler on the predicted values. This study evaluates existing creep and drying shrinkage models, including AASHTO LRFD, ACI209, CEB-FIP MC90-99, B3, and GL2000, for SCC mixtures with different SCMs/fillers. Forty SCC mixtures were proportioned for different cast-in-place bridge components and tested for drying shrinkage. A set of eight SCC mixtures with the highest paste content was tested for creep. Shrinkage and creep test results indicated that AASHTO LRFD provides better creep prediction than the other models for SCC with different SCMs/fillers. Although all models underestimate drying shrinkage of SCC with different SCMs/fillers, the GL2000, CEB-FIP MC90-99, and ACI 209 models provide better prediction than AASHTO LRFD and B3 models. Additionally, SCC mixtures with limestone powder filler exhibited the highest creep, while those with class C fly ash exhibited the highest drying shrinkage.
Intelligent Stretch Optimization in Information Centric Networking-Based Tactile Internet Applications
Authors: Ahmad Hussain , Zubair Islam Muhammad , Ali Rashid , Haider Amir , Kim Hyungseok
Published: August 2021

The fifth-generation (5G) mobile network services are currently being made available for different use case scenarios like enhanced mobile broadband, ultra-reliable and low latency communication, and massive machine-type communication. The ever-increasing data requests from the users have shifted the communication paradigm to be based on the type of the requested data content or the so-called information-centric networking (ICN). The ICN primarily aims to enhance the performance of the network infrastructure in terms of the stretch to opt for the best routing path. Reduction in stretch merely reduces the end-to-end (E2E) latency to ensure the requirements of the 5G-enabled tactile internet (TI) services. The foremost challenge tackled by the ICN-based system is to minimize the stretch while selecting an optimal routing path. Therefore, in this work, a reinforcement learning-based intelligent stretch optimization (ISO) strategy has been proposed to reduce stretch and obtain an optimal routing path in ICN-based systems for the realization of 5G-enabled TI services. A Q-learning algorithm is utilized to explore and exploit the different routing paths within the ICN infrastructure. The problem is designed as a Markov decision process and solved with the help of the Q-learning algorithm. The simulation results indicate that the proposed strategy finds the optimal routing path for the delay-sensitive haptic-driven services of 5G-enabled TI based upon their stretch profile over ICN, such as the augmented reality /virtual reality applications. Moreover, we compare and evaluate the simulation results of propsoed ISO strategy with random routing strategy and history aware routing protocol (HARP). The proposed ISO strategy reduces 33.33% and 33.69% delay as compared to random routing and HARP, respectively. Thus, the proposed strategy suggests an optimal routing path with lesser stretch to minimize the E2E latency.
Predicting Wearing-Off of Parkinson’s Disease Patients Using a Wrist-Worn Fitness Tracker and a Smartphone: A Case Study
Authors: Victorino John Noel , Shibata Yuko , Inoue Sozo , Shibata Tomohiro
Published: August 2021

Parkinson’s disease (PD) patients experience varying symptoms related to their illness. Therefore, each patient needs a tailored treatment program from their doctors. One approach is the use of anti-PD medicines. However, a “wearing-off” phenomenon occurs when these medicines lose their effect. As a result, patients start to experience the symptoms again until their next medicine intake. In the long term, the duration of “wearing-off” begins to shorten. Thus, patients and doctors have to work together to manage PD symptoms effectively. This study aims to develop a prediction model that can determine the “wearing-off” of anti-PD medicine. We used fitness tracker data and self-reported symptoms from a smartphone application in a real-world environment. Two participants wore the fitness tracker for a month while reporting any symptoms using the Wearing-Off Questionnaire (WoQ-9) on a smartphone application. Then, we processed and combined the datasets for each participant’s models. Our analysis produced prediction models for each participant. The average balanced accuracy with the best hyperparameters was at 70.0–71.7% for participant 1 and 76.1–76.9% for participant 2, suggesting that our approach would be helpful to manage the “wearing-off” of anti-PD medicine, motor fluctuations of PD patients, and customized treatment for PD patients.
Design and Experiment of Electronically Tunable Voltage-Mode Biquad and Output Current Amplitude Oscillator
Authors: Wang San-Fu , Chen Hua-Pin , Ku Yitsen , Liu Fang-Yu
Published: August 2021

This study presents an electronically tunable configuration for the design of a voltage-mode (VM) biquad with four input terminals and three output terminals. The proposed circuit employs four operational transconductance amplifiers (OTAs) and two grounded capacitors. Depending on the selections of the four input voltage signals, all the standard filtering functions can be realized. The proposed configuration simultaneously provides VM inverting band-pass, non-inverting low-pass, and non-inverting band-reject filtering functions without any component-matching choices. It offers the features of a resistorless structure, high-input impedance, electronic control of the pole frequency and quality factor, and low active and passive sensitivities. The measured power dissipation of the biquad is 0.96 W under 32 mA constant output current. The measured 1 dB power gain compression point of the output inverting band-pass filter is −7 dBm. The measured value of the third-order intercept point is 5.136 dBm, and the measured value of the third-order intermodulation distortion is −50.83 dBc. Moreover, the measured value of the spurious-free dynamic range is 53.49 dB, and the figure-of-merit of the biquad is 268.75 × 103. In addition, an electronically controllable quadrature oscillator (QO) with amplitude of output current can be realized using the proposed biquad. The proposed electronically controllable QO can provide an amplitude modulation signal or an amplitude shift keying signal, and is widely applied in signal processing systems and electronic communication systems. PSpice simulations and experimental results are accomplished.
Identification of Potentially Related Genes and Mechanisms Involved in Skeletal Muscle Atrophy Induced by Excessive Exercise in Zebrafish
Authors: Sun Chen-Chen , Zhou Zuo-Qiong , Chen Zhang-Lin , Zhu Run-Kang , Yang Dong , Peng Xi-Yang , Zheng Lan , Tang Chang-Fa
Published: August 2021

Long-term imbalance between fatigue and recovery may eventually lead to muscle weakness or even atrophy. We previously reported that excessive exercise induces pathological cardiac hypertrophy. However, the effect of excessive exercise on the skeletal muscles remains unclear. In the present study, we successfully established an excessive-exercise-induced skeletal muscle atrophy zebrafish model, with decreased muscle fiber size, critical swimming speed, and maximal oxygen consumption. High-throughput RNA-seq analysis identified differentially expressed genes in the model system compared with control zebrafish. Gene ontology and KEGG enrichment analysis revealed that the upregulated genes were enriched in autophagy, homeostasis, circadian rhythm, response to oxidative stress, apoptosis, the p53 signaling pathway, and the FoxO signaling pathway. Protein–protein interaction network analysis identified several hub genes, including keap1b, per3, ulk1b, socs2, esrp1, bcl2l1, hsp70, igf2r, mdm2, rab18a, col1a1a, fn1a, ppih, tpx2, uba5, nhlrc2, mcm4, tac1, b3gat3, and ddost, that correlate with the pathogenesis of skeletal muscle atrophy induced by excessive exercise. The underlying regulatory pathways and muscle-pressure-response-related genes identified in the present study will provide valuable insights for prescribing safe and accurate exercise programs for athletes and the supervision and clinical treatment of muscle atrophy induced by excessive exercise.
Therapy Approaches for Stargardt Disease
Authors: Piotter Elena , McClements Michelle E , MacLaren Robert E
Published: August 2021

Despite being the most prevalent cause of inherited blindness in children, Stargardt disease is yet to achieve the same clinical trial success as has been achieved for other inherited retinal diseases. With an early age of onset and continual progression of disease over the life course of an individual, Stargardt disease appears to lend itself to therapeutic intervention. However, the aetiology provides issues not encountered with the likes of choroideremia and X-linked retinitis pigmentosa and this has led to a spectrum of treatment strategies that approach the problem from different aspects. These include therapeutics ranging from small molecules and anti-sense oligonucleotides to viral gene supplementation and cell replacement. The advancing development of CRISPR-based molecular tools is also likely to contribute to future therapies by way of genome editing. In this we review, we consider the most recent pre-clinical and clinical trial data relating to the different strategies being applied to the problem of generating a treatment for the large cohort of Stargardt disease patients worldwide.
Grape Pomace for Topical Application: Green NaDES Sustainable Extraction, Skin Permeation Studies, Antioxidant and Anti-Inflammatory Activities Characterization in 3D Human Keratinocytes
Authors: Punzo Angela , Porru Emanuele , Silla Alessia , Simoni Patrizia , Galletti Paola , Roda Aldo , Tagliavini Emilio , Samorì Chiara , Caliceti Cristiana
Published: August 2021

Food waste is a global problem due to its environmental and economic impact, so there is great demand for the exploitation of new functional applications. The winemaking process leads to an incomplete extraction of high-value compounds, leaving the pomace still rich in polyphenols. This study was aimed at optimising and validating sustainable routes toward the extraction and further valorisation of these polyphenols, particularly for cosmeceutical applications. New formulations based on red grape pomace polyphenols and natural deep eutectic solvents (NaDESs) were here investigated, namely betaine combined with citric acid (BET-CA), urea (BET-U) and ethylene glycol (BET-EG), in which DESs were used both as extracting and carrying agents for polyphenols. The flavonoid profile determined by HPLC-MS/MS analysis showed similar malvidin content (51–56 μg mL−1) in the DES combinations, while BET-CA gave the best permeation performance in Franz cells, so it was further investigated in 3D human keratinocytes (HaCat spheroids) injured with the pro-oxidant agent menadione. BET-CA treatment showed good intracellular antioxidant activity (IC50 0.15 ± 0.02 μg mL−1 in malvidin content) and significantly decreased (p < 0.001) the release of the pro-inflammatory cytokine IL-8, improving cell viability. Thus, BET-CA formulation is worthy of investigation for potential use as a cosmetic ingredient to reduce oxidative stress and inflammation, which are causes of skin aging.
Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant ALDH2*2 Gene Allele
Authors: Chen Yi-Chyan , Yang Li-Fang , Lai Ching-Long , Yin Shih-Jiun
Published: August 2021

Alcoholism is a complex behavior trait influenced by multiple genes as well as by sociocultural factors. Alcohol metabolism is one of the biological determinants that can significantly influence drinking behaviors. Alcohol sensitivity is thought to be a behavioral trait marker for susceptibility to develop alcoholism. The subjective perceptions would be an indicator for the alcohol preference. To investigate alcohol sensitivity for the variants ADH1B*2 and ALDH2*2, sixty healthy young males with different combinatory ADH1B and ALDH2 genotypes, ADH1B*2/*2–ALDH2*1/*1 (n = 23), ADH1B*2/*2–ALDH2*1/*2 (n = 27), and ADH1B*1/*1–ALDH2*1/*1 (n = 10), participated in the study. The subjective perceptions were assessed by a structured scale, and blood ethanol and acetaldehyde were determined by GC and HPLC after an alcohol challenge in two dose sessions (0.3 g/kg or 0.5 g/kg ethanol). The principal findings are (1) dose-dependent increase of blood ethanol concentration, unaffected by ADH1B or ALDH2; (2) significant build-up of blood acetaldehyde, strikingly influenced by the ALDH2*2 gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the ALDH2*2 heterozygotes; (4) no significant effect of ADH1B polymorphism in alcohol metabolism or producing the psychological responses. The study findings provide the evidence of acetaldehyde potentiating the alcohol sensitivity and feedback to self-control the drinking amount. The results indicate that ALDH2*2 plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.
RETRACTED: Nanonutraceuticals: Anti-Cancer Activity and Improved Safety of Chemotherapy by Costunolide and Its Nanoformulation against Colon and Breast Cancer
Authors: El-Far Ali , Godugu Kavitha , Salaheldin Taher , Darwish Noureldien , Saddiq Amna , Mousa Shaker
Published: August 2021

Costunolide (COS) is a sesquiterpene lactone with anticancer properties. The present study investigated the anticancer effects of COS against the human colon (HCT116) and breast (MDA-MB-231-Luc) cancer cell lines. Inhibition of cell lines viability and IC50 of COS were assessed via an MTT assay. Furthermore, the apoptotic rate was detected by assessment of Bcl2-associated X (Bax) and B-cell lymphoma 2 (Bcl2) protein levels by flow cytometry. Xenograft mice model of HCT116 and MDA-MB-231-Luc were carried out to determine the effect of COS and its nanoparticles (COS-NPs). The results demonstrated that COS inhibited the viability of HCT116 and MDA-MB-231-Luc cells, with a half maximal inhibitory concentration value (IC50) of 39.92 µM and 100.57 µM, respectively. COS significantly increased Bax and decreased Bcl2 levels in treated cells. COS and COS-NPs, in combination with doxorubicin (DOX), significantly decreased the tumor growth of HCT116 and MDA-MB-231-Luc implants in mice. Furthermore, oral administration of COS and COS-NPs significantly decreased the viable cells and increased necrotic/apoptotic cells of HCT116 and MDA-MB-231-Luc implants. Interestingly, both COS and COS-NPs protected the cardiac muscles against DOX’s cardiotoxicity. The current results indicated the promising anticancer and cardiac muscles protection of COS and COS-NPs when administered with chemotherapy.
The Bacterial Enzyme RfxCas13d Is Less Neurotoxic Than PspCas13b and Could Be a Promising RNA Editing and Interference Tool in the Nervous System
Authors: Wu Qin-Wei , Kapfhammer Josef P.
Published: August 2021

RNA therapies using RNA editing and interference are currently being developed for neurological diseases. The CRISPR-Cas13 system, based on bacterial enzymes, holds great promise for developing efficient tools for RNA therapies. However, neurotoxic activity has been reported for Cas13a, and recent studies have reported toxic effects of PspCas13b and RfxCas13d during zebrafish and Drosophila embryonic development. It is important to investigate the safety of these bacterial enzymes in the context of the nervous system and neuronal development. In this study, we used mouse cerebellar Purkinje cells as a complex neuron type to test for the potential neurotoxic actions of RfxCas13d and PspCas13b. We found that PspCas13b significantly impeded the dendritic development of cultured Purkinje cells, similar to the neurotoxic action of Cas13a. In contrast, RfxCas13d did not exhibit a significant inhibition of dendritic development. A similar trend was found for axonal outgrowth. These results suggest varying neurotoxic properties for different Cas13 ortholog enzymes. We call for more studies to investigate, and possibly mitigate, the neurotoxicity of Cas13 proteins in order to improve the safety of the CRISPR-Cas13 system for RNA therapies.