bluuebunny/crossref_metadata_2025 huggingface dataset:
Tregitopes Improve Asthma by Promoting Highly Suppressive and Antigen-Specific Tregs
Authors: Dembele Marieme , Tao Shao , Massoud Amir H. , Miah S. M. Shahjahan , Lelias Sandra , De Groot Anne S. , Mazer Bruce D.
Published: April 2021

Tregitopes (T regulatory epitopes) are IgG-derived peptides with high affinity to major histocompatibility complex class II (MHCII), that are known to promote tolerance by activating T regulatory cell (Treg) activity. Here we characterized the effect of IgG Tregitopes in a well-established murine model of allergic asthma, demonstrating in vivo antigen-specific tolerance via adoptive transfer of Tregitope-and-allergen-activated Tregs. Asthma is a heterogeneous chronic inflammatory condition affecting the airways and impacting over 300 million individuals worldwide. Treatment is suppressive, and no current therapy addresses immune regulation in severely affected asthmatics. Although high dose intra-venous immunoglobulin (IVIg) is not commonly used in the asthma clinic setting, it has been shown to improve severe asthma in children and in adults. In our laboratory, we previously demonstrated that IVIg abrogates airway hyperresponsiveness (AHR) in a murine model of asthma and induces suppressive antigen-specific T-regulatory cells. We hypothesized that IgG-derived Tregitopes would modulate allergic airway disease by inducing highly suppressive antigen-specific Tregs capable of diminishing T effector cell responses and establishing antigen-specific tolerance. Using ovalbumin (OVA-) and ragweed-driven murine models of allergic airway disease, we characterized the immunoregulatory properties of Tregitopes and performed Treg adoptive transfer to OVA- and ragweed-allergic mice to test for allergen specificity. Treatment with Tregitopes attenuated allergen-induced airway hyperresponsiveness and lung inflammation. We demonstrated that Tregitopes induce highly suppressive allergen-specific Tregs. The tolerogenic action of IgG Tregitopes in our model is very similar to that of IVIg, so we foresee that IgG Tregitopes could potentially replace steroid-based treatment and can offer a synthetic alternative to IVIg in a range of inflammatory and allergic conditions.
Decoding Neuromuscular Disorders Using Phenotypic Clusters Obtained From Co-Occurrence Networks
Authors: Díaz-Santiago Elena , Claros M. Gonzalo , Yahyaoui Raquel , de Diego-Otero Yolanda , Calvo Rocío , Hoenicka Janet , Palau Francesc , Ranea Juan A. G. , Perkins James R.
Published: April 2021

Neuromuscular disorders (NMDs) represent an important subset of rare diseases associated with elevated morbidity and mortality whose diagnosis can take years. Here we present a novel approach using systems biology to produce functionally-coherent phenotype clusters that provide insight into the cellular functions and phenotypic patterns underlying NMDs, using the Human Phenotype Ontology as a common framework. Gene and phenotype information was obtained for 424 NMDs in OMIM and 126 NMDs in Orphanet, and 335 and 216 phenotypes were identified as typical for NMDs, respectively. ‘Elevated serum creatine kinase’ was the most specific to NMDs, in agreement with the clinical test of elevated serum creatinine kinase that is conducted on NMD patients. The approach to obtain co-occurring NMD phenotypes was validated based on co-mention in PubMed abstracts. A total of 231 (OMIM) and 150 (Orphanet) clusters of highly connected co-occurrent NMD phenotypes were obtained. In parallel, a tripartite network based on phenotypes, diseases and genes was used to associate NMD phenotypes with functions, an approach also validated by literature co-mention, with KEGG pathways showing proportionally higher overlap than Gene Ontology and Reactome. Phenotype-function pairs were crossed with the co-occurrent NMD phenotype clusters to obtain 40 (OMIM) and 72 (Orphanet) functionally coherent phenotype clusters. As expected, many of these overlapped with known diseases and confirmed existing knowledge. Other clusters revealed interesting new findings, indicating informative phenotypes for differential diagnosis, providing deeper knowledge of NMDs, and pointing towards specific cell dysfunction caused by pleiotropic genes. This work is an example of reproducible research that i) can help better understand NMDs and support their diagnosis by providing a new tool that exploits existing information to obtain novel clusters of functionally-related phenotypes, and ii) takes us another step towards personalised medicine for NMDs.
Primary Tumor Resection Improves Survival for EGFR-TKI-Treated Patients With Occult M1a Lung Adenocarcinoma
Authors: Fu Fangqiu , Wen Zhexu , Gao Zhendong , Zhao Yue , Li Yuan , Zhang Yang , Chen Haiquan
Published: April 2021

Background

The role of primary tumor resection in occult M1a lung adenocarcinoma remains unclear, especially for patients receiving targeted therapy. The purpose of this study is to assess the effect of primary tumor resection on overall survival (OS) in lung adenocarcinoma patients with occult pleural disseminations receiving targeted therapy.

Methods

Lung adenocarcinoma patients with intraoperatively-confirmed occult pleural dissemination (M1a), who hospitalized in the Department of Thoracic Surgery in Fudan Shanghai Cancer Center from May 2008 to December 2017 and received EGFR-TKIs therapy, were enrolled. Log-rank tests were used to compare the survival differences between groups.

Results

34 patients receiving EGFR-TKIs were enrolled. The majority of them were never smokers (29/34, 85.3%). Among the enrolled patients, 20 (58.8%) patients underwent primary tumor resection, while 14 (41.2%) patients not. There was no distributional difference of baselines between patients undergoing and not undergoing primary tumor resection. Further analyses demonstrated that the patients undergoing primary tumor resection had a prolonged OS compared with those not (log-rank P= 0.042). The 2-year and 5-year OS for patients receiving primary tumor resection and EGFR-TKIs was 90.0% and 60.1%.

Conclusions

Primary tumor resection was associated with improved survival in patients with occult intraoperatively-confirmed M1a adenocarcinoma receiving EGFR-TKIs.
Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain
Authors: Xu Hang , Zhang Xiang Yang , Wang Wei Wen , Wang Jiesi
Published: April 2021

Hydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for COVID-19, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta, corticotropin-releasing hormone (Crh), a serotonin transporter (Slc6a4), and a microglia maker (Aif1) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Lots of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders.
Exposure-Response Modeling to Support Dosing Selection for Phase IIb Development of Kukoamine B in Sepsis Patients
Authors: Wang Huanhuan , Hu Xiaoyun , Wang Teng , Cui Cheng , Jiang Ji , Dong Kai , Chen Shuai , Jin Chunyan , Zhao Qian , Du Bin , Hu Pei
Published: April 2021

Aim: Kukoamine B, a small molecule compound, is being developed for the treatment of sepsis in a Phase II clinical trial. The objective of this study was to optimize dosing selection for a Phase IIb clinical trial using an exposure-response model.

Methods: Data of 34 sepsis patients from a Phase IIa clinical trial were used in the model: 10 sepsis patients from the placebo group and a total of 24 sepsis patients from the 0.06 mg/kg, 0.12 mg/kg, and 0.24 mg/kg drug groups. Exposure-response relationship was constructed to model the impact of the standard care therapy and area under curve (AUC) of kukoamine B to the disease biomarker (SOFA score). The model was evaluated by goodness of fit and visual predictive check. The simulation was performed 1,000 times based on the built model.

Results: The data of the placebo and the drug groups were pooled and modeled by a nonlinear mixed-effect modeling approach in sepsis. A latent-variable approach in conjunction with an inhibitory indirect response model was used to link the standard care therapy effect and drug exposure to SOFA score. The maximum fraction of the standard care therapy was estimated to 0.792. The eliminate rate constant of the SOFA score was 0.263/day for the standard care therapy. The production rate of SOFA score (Kin) was estimated at 0.0569/day and the AUC at half the maximal drug effect (EAUC50) was estimated at 1,320 h*ng/mL. Model evaluation showed that the built model could well describe the observed SOFA score. Model-based simulations showed that the SOFA score on day 7 decreased to a plateau when AUC increased to 1,500 h*ng/mL.

Conclusion: We built an exposure-response model characterizing the pharmacological effect of kukoamine B from the standard care therapy in sepsis patients. A dose regimen of 0.24 mg/kg was finally recommended for the Phase IIb clinical trial of kukoamine B based on modeling and simulation results.
Insight into the Role of the STriatal-Enriched Protein Tyrosine Phosphatase (STEP) in A2A Receptor-Mediated Effects in the Central Nervous System
Authors: Domenici Maria Rosaria , Mallozzi Cinzia , Pepponi Rita , Casella Ida , Chiodi Valentina , Ferrante Antonella , Popoli Patrizia
Published: April 2021

The STriatal-Enriched protein tyrosine phosphatase STEP is a brain-specific tyrosine phosphatase that plays a pivotal role in the mechanisms of learning and memory, and it has been demonstrated to be involved in several neuropsychiatric diseases. Recently, we found a functional interaction between STEP and adenosine A2A receptor (A2AR), a subtype of the adenosine receptor family widely expressed in the central nervous system, where it regulates motor behavior and cognition, and plays a role in cell survival and neurodegeneration. Specifically, we demonstrated the involvement of STEP in A2AR-mediated cocaine effects in the striatum and, more recently, we found that in the rat striatum and hippocampus, as well as in a neuroblastoma cell line, the overexpression of the A2AR, or its stimulation, results in an increase in STEP activity. In the present article we will discuss the functional implication of this interaction, trying to examine the possible mechanisms involved in this relation between STEP and A2ARs.
Integrating Ethnobotany, Phytochemistry, and Pharmacology of Cotinus coggygria and Toxicodendron vernicifluum: What Predictions can be Made for the European Smoketree?
Authors: Antal Diana Simona , Ardelean Florina , Jijie Robert , Pinzaru Iulia , Soica Codruta , Dehelean Cristina
Published: April 2021

The smoketree (Cotinus coggygria) is a historically known medicinal plant from Southeast Europe. Its ethnomedicinal use in skin and mucosal lesions is commonly accepted across countries. Other utilizations reported locally include fever reduction, cardiac diseases, hypertension, urinary diseases, cough, asthma, hemorrhoids, diabetes, numbness of arm, liver disease, and cancer. Departing from the smoketree’s traditional uses, this review summarizes investigations on the phytochemistry and bioactivity of the plant.In vitroandin vivoexperiments supporting wound-healing, anti-inflammatory, antibacterial, cytotoxic, antioxidative, hepatoprotective, and antidiabetic effects are presented. Metabolites from smoketree that are responsible for the main pharmacological effects of smoketree are pointed out. Furthermore, the review performs a comparison betweenC. coggygriaand the lacquer tree (Toxicodendron vernicifluum). The latter is a comprehensively studied species used in Asian phytotherapy, with whom the European smoketree shares a consistent pool of secondary metabolites. The comparative approach aims to open new perspectives in the research of smoketree and anticipates an optimized use of C. coggygria in therapy. It also points out the relevance of a chemosystematic approach in the field of medicinal plants research.
Comparative Proteomic Analysis of Sweet Orange Petiole Provides Insights Into the Development of Huanglongbing Symptoms
Authors: Li Bo , Zhang Yi , Qiu Dewen , Francis Frédéric , Wang Shuangchao
Published: April 2021

Huanglongbing (HLB) is the most destructive citrus disease worldwide. This is associated with the phloem-limited bacterium Candidatus Liberibacter, and the typical symptom is leaf blotchy mottle. To better understand the biological processes involved in the establishment of HLB disease symptoms, the comparative proteomic analysis was performed to reveal the global protein accumulation profiles in leaf petiole, where there are massive HLB pathogens of Ca. L. asiaticus-infected Newhall sweet orange (Citrus sinensis) plants at the asymptomatic and symptomatic stages compared to their healthy counterpart. Photosynthesis, especially the pathway involved in the photosystem I and II light reactions, was shown to be suppressed throughout the whole Ca. L. asiaticus infection cycle. Also, starch biosynthesis was induced after the symptom-free prodromal period. Many defense-associated proteins were more extensively regulated in the petiole with the symptoms than the ones from healthy plants. The change of salicylic and jasmonic acid levels in different disease stages had a positive correlation with the abundance of phytohormone biosynthesis-related proteins. Moreover, the protein–protein interaction network analysis indicated that an F-type ATPase and an alpha-1,4 glucan phosphorylase were the core nodes in the interactions of differentially accumulated proteins. Our study indicated that the infected citrus plants probably activated the non-unified and lagging enhancement of defense responses against Ca. L. asiaticus at the expense of photosynthesis and contribute to find out the key Ca. L. asiaticus-responsive genes for tolerance and resistance breeding.
Adaptive Damping Variable Sliding Mode Control for an Electrohydrostatic Actuator
Authors: Li Linjie , Wang Mingkang , Yang Rongrong , Fu Yongling , Zhu Deming
Published: April 2021

An electrohydrostatic actuator (EHA) is a basic mechanical/hydraulic system with deficiencies including significant nonlinearity and parametric uncertainties. In line with the challenges of designing a high-precision control strategy, an adaptive damping variable sliding mode controller is established, which extends our previous work on EHA control. The proposed controller integrates variable-damping sliding mode control, parametric adaptation, and an extended state observer. The parametric uncertainties are effectively captured and compensated by employing an adaptive control law, while system uncertainties are reduced, and disturbances are estimated and compensated with a fast and stable response. We evaluated the proposed control strategy on a variety of position tracking tasks. The experimental results demonstrate that our controller significantly outperforms the widely used methods in overshoot suppression, settling time, and tracking accuracy.
Self-Oscillations of The Free Turbine Speed in Testing Turboshaft Engine with Hydraulic Dynamometer
Authors: Lytviak Oleksandr , Loginov Vasyl , Komar Sergii , Martseniuk Yevhen
Published: April 2021

Self-oscillations are one of the common problems in the complex automatic system, that can occur due to the features of the workflow and the design of the governor. The development of digital control systems has made it possible to damp self-oscillations by applying complex control laws. However, for hydromechanical systems, such way is unacceptable due to the design complexity and the governor cost. The objective of this work is to determine the parameters of the hydromechanical free turbine speed controller, ensuring the absence of self-oscillations during ground tests of the turboshaft engine with a hydraulic dynamometer. The TV3-117VM engine (Ukraine) with the NR-3VM regulator pump (Ukraine) was selected as the object of the study. However, self-oscillations can also occur in any modifications of the TV3-117 engine with any NR-3 regulator pump. The results of the research may be of interest to engineers and scientists who investigate the dynamics of automatic control systems for similar engines. The paper analyses the nonlinear features of the empirical characteristics of the FTSC leading to self-oscillations of the engine speed. The authors propose the mathematical model of the automatic control system dynamics, which takes into account all the features of the engine and regulator pump. It is shown that the load characteristics of the water brake and the helicopter main rotor can differ significantly. Research of the dynamic characteristics of the TV3-117VM engine was carried out. The analysis showed a good agreement between the calculation results and the field test results, and made it possible to determine the parameters of the controller, which lead to self-oscillations during test. Two cases are considered. The first case includes ground tests of the engine with a water brake; the second case—flight tests of the engine as part of the helicopter’s power plant. The data obtained make it possible to develop recommendations for adjusting the hydromechanical governor without testing it on the engine.
Multi-Aircraft Trajectory Collaborative Prediction Based on Social Long Short-Term Memory Network
Authors: Xu Zhengfeng , Zeng Weili , Chu Xiao , Cao Puwen
Published: April 2021

Aircraft trajectory prediction is the basis of approach and departure sequencing, conflict detection and resolution and other air traffic management technologies. Accurate trajectory prediction can help increase the airspace capacity and ensure the safe and orderly operation of aircraft. Current research focuses on single aircraft trajectory prediction without considering the interaction between aircraft. Therefore, this paper proposes a model based on the Social Long Short-Term Memory (S-LSTM) network to realize the multi-aircraft trajectory collaborative prediction. This model establishes an LSTM network for each aircraft and a pooling layer to integrate the hidden states of the associated aircraft, which can effectively capture the interaction between them. This paper takes the aircraft trajectories in the Northern California terminal area as the experimental data. The results show that, compared with the mainstream trajectory prediction models, the S-LSTM model in this paper has smaller prediction errors, which proves the superiority of the model’s performance. Additionally, another comparative experiment is conducted on airspace scenes with aircraft interactions, and it is found that S-LSTM has a better prediction effect than LSTM, which proves the effectiveness of the former considering aircraft interaction.
A New Identification Method Reveals the Resistance of an Extensive-Source Radish Collection to Plasmodiophora brassicae Race 4
Authors: Yang Haohui , Yuan Yuxiang , Wei Xiaochun , Zhang Xiaohui , Wang Haiping , Song Jiangping , Li Xixiang
Published: April 2021

Raphanus sativus, an important cruciferous vegetable, has been increasingly affected by clubroot disease. Establishing a stable and accurate resistance identification method for screening resistant germplasms is urgently needed in radish. In this study, the influence of inoculum concentration, inoculation methods, and pH of the substrate on disease occurrence was studied. The result showed that the disease index (DI) was highest at 2 × 108 spores/mL, the efficiency of two-stage combined inoculation methods was higher than others, and pH 6.5 was favorable for the infection of P. brassicae. By using this new method, DIs of 349 radish germplasms varying from 0.00 to 97.04, presented significantly different levels of resistance. Analysis showed that 85.06% germplasms from China were susceptible to P. brassicae, whilst 28 accessions were resistant and mainly distributed in east, southwest, northwest, and south-central China. Most of the exotic germplasms were resistant. Repeated experiments verified the stability and reliability of the method and the identity of germplasm resistance. In total, 13 immune, 5 highly resistant and 21 resistant radish accessions were identified. This study provides an original clubroot-tolerance evaluation technology and valuable materials for the development of broad-spectrum resistant varieties for sustainable clubroot management in radish and other cruciferous crops.
Organic Fertilization in Maize Cropping Systems: Measures to Reduce N Losses
Authors: Olfs Hans-Werner
Published: April 2021

Maize is one of the most important crops around the world [...]
Dynamic of Morphological and Physiological Parameters and Variation of Soil Characteristics during Miscanthus × giganteus Cultivation in the Diesel-Contaminated Land
Authors: Pidlisnyuk Valentina , Herts Andriy , Khomenchuk Volodymyr , Mamirova Aigerim , Kononchuk Oleksandr , Ust’ak Sergey
Published: April 2021

Miscanthus × giganteus (M. × giganteus) is a perspective plant produced on marginal and contaminated lands with biomass used for energy or bioproducts. In the current study, M. × giganteus development was tested in the diesel-contaminated soils (ranged from 250 mg kg−1 to 5000 mg kg−1) and the growth dynamic, leaves quantity, plants total area, number of harvested stems and leaves, SPAD and NPQt parameters were evaluated. Results showed a remarkable M. × giganteus growth in a selected interval of diesel-contaminated soil with sufficient harvested biomass. The amendment of soil by biochar 1 (produced from wastewater sludge) and biochar 2 (produced from a mixture of wood waste and biohumus) improved the crop’s morphological and physiological parameters. Biochar 1 stimulated the increase of the stems’ biomass, while biochar 2 increased the leaves biomass. The plants growing in the uncontaminated soil decreased the content of NO3, pH (KCl), P2O5 and increased the content of NH4. Photosynthesis parameters showed that incorporating biochar 1 and biochar 2 to the diesel-contaminated soil prolonged the plants’ vegetation, which was more potent for biochar 1. M. × giganteus utilization united with biochar amendment can be recommended to remediate diesel-contaminated land in concentration range 250–5000 mg kg−1.
Effect of Low Temperature on Germination, Growth, and Seed Yield of Four Soybean (Glycine max L.) Cultivars
Authors: Szczerba Anna , Płażek Agnieszka , Pastuszak Jakub , Kopeć Przemysław , Hornyák Marta , Dubert Franciszek
Published: April 2021

During germination at low temperatures, seeds rich in proteins may experience damage to their cytoplasmic membranes. The study aimed to investigate the influence of the germination temperature on growth, development, and yield of four cultivars of soybean, a typical thermophilic species. The seeds were germinated at 10, 15, and 25 °C in the dark. After 48 h, one part of the seeds was analyzed for their amylase and dehydrogenase activity, cell membrane permeability, and germination vigor. The other part was transferred into soil and cultivated up to yielding. Chlorophyll fluorescence, fresh (FW) and dry weight (DW) of shoots, pod and seed number, and seed DW were analyzed. The plants of cvs. ‘Abelina’, ‘Malaga’, and ‘Merlin’, germinating at low temperature, produced the highest number of seeds. Seed number negatively correlated with their DW and positively with the number of active reaction centers (RC/CSm) in all cultivars. In cvs. ‘Abelina’ and ‘Malaga’, the number of seeds also positively correlated with the index performance of photosystem II (PSII), which was the highest in all plants germinating at low temperature. We suggest cultivating cv. ‘Abelina’ in cooler regions, while cvs. ‘Petrina’ and ‘Malaga’ in warmer areas.
High Soil Phosphorus Application Significantly Increased Grain Yield, Phosphorus Content but Not Zinc Content of Cowpea Grains
Authors: Mohammed Saba B. , Dzidzienyo Daniel K. , Yahaya Adama , L. Umar Muhammad , Ishiyaku Mohammad F. , Tongoona Pangirayi B. , Gracen Vernon
Published: April 2021

To ameliorate the impact of soil phosphorus (P) deficiency on cowpea, the use of P-based fertilizers is recommended. Plant zinc (Zn) is an essential nutrient required by plants in a wide range of processes, such as growth hormone production and metabolism. However, a negative association between plant Zn content and high P application has been reported in some crops. There are few reports about soil P application and plant Zn content relationship on cowpea. Thus, this study investigated the response of cowpeas to three P rates in the screenhouse (0, 1.5, and 30 mg P/kg) and field (0, 10, and 60 kg P2O5/ha) and their effects on plant P and Zn content, biomass, and grain yield. In the screenhouse, shoot and root dry weights, and shoot P and Zn content were measured. Shoot dry weight, grain yield, grain P, and Zn contents were determined from field plants. Higher rates of P led to increased shoot biomass and grain yield of the field experiment but were not associated with a significant change in shoot or grain Zn content. There was not a significant correlation between grain yield and Zn content in high soil P (p < 0.05). The effect of higher P application on reduced plant Zn contents may be genotype-dependent and could be circumvented if genotypes with high Zn content under high soil P are identified.
An Optimized Extraction Procedure for Determining Acaricide Residues in Foundation Sheets of Beeswax by Using Gas Chromatography-Mass Spectrometry
Authors: Nozal María Jesús , Imaz Edgar , Bernal José Luis , Nieto José Luis , Higes Mariano , Bernal José
Published: April 2021

Pesticides can be found in beehives for several reasons, including contamination from surrounding cultivars; yet one of the most pertinent is related to the fact that beekeepers employ acaricides to control various types of mites, which may accumulate in beeswax due to their lipophilic nature. In the present study, foundation sheets of different origins, collected over a period of three years, were analyzed to detect the residues of seven acaricides (atrazine, chlorpyrifos, chlorfenvinphos, alpha-endosulfan, bromopropylate, coumaphos, tau-fluvalinate) by gas chromatography with mass spectrometric detection. An efficient sample treatment (recoveries between 90% and 108%) is proposed, involving solvent extraction with 1% acetic acid in acetonitrile mixture followed by dispersive solid-phase extraction (enhanced matrix removal lipid) and a polishing step. An evaluation was made of the analytical performance of the proposed method. It was shown to be selective, linear from a limit of quantification to 5000 µg/kg, precise (relative standard deviation values were below 6%), and with a goo sensitivity (limit of quantification ranging from 5 to 10 µg/kg). Finally, results showed that a large majority of the sheets analyzed (>90%) contained residues of at least one of these compounds. Coumaphos and tau-fluvalinate residues were the most common, with chlorpyrifos and chlorfenvinphos detected to a lesser extent.
Segmental Posthetomy in a Four Stallions Case Series
Authors: Palozzo Adriana , Celani Gianluca , Guerri Giulia , Straticò Paola , Varasano Vincenzo , Petrizzi Lucio
Published: April 2021

Segmental posthetomy, also referred to as circumcision, reefing or posthioplasty, consists of removing a circumferential segment of the internal preputial lamina (internal preputial fold) followed by end-to-end anastomosis of skin edges. The purpose of this case series is to describe the successful outcome of segmental posthetomy for treating different diseases involving the internal or/and external preputial fold, while restoring the normal telescopic function. In this paper, we report the first case of complete degloving injury of the equine penis in the literature (case 1) and describe three different common lesions of the equine prepuce/penis (preputial scar tissue in case 2, preputial sarcoid in case 3 and penile/preputial wound in case 4). The amount of prepuce (safe minimums) that can be removed from a stallion without disrupting the proper telescopic function of the internal/external preputial fold and normal copulatory ability, has not been established. In this case series, all Equidae stallions maintained the telescopic function after preputial surgical resection. However, the surgeon must carefully evaluate every single case, especially when performing the Adam’s procedure.
Thermal Tolerance and Physiological Changes in Mud Crab, Scylla paramamosain Crablet at Different Water Temperatures
Authors: Syafaat Muhammad Nur , Azra Mohamad Nor , Mohamad Faridah , Che-Ismail Che Zulkifli , Amin-Safwan Adnan , Asmat-Ullah Mohammad , Syahnon Mohammad , Ghazali Azmie , Abol-Munafi Ambok Bolong , Ma Hongyu , Ikhwanuddin Mhd
Published: April 2021

This study was carried out to determine the physiological changes (survival, growth, molting cycle, sex differentiation, and gill condition) of mud crab, Scylla paramamosain crablet at different water temperatures of 24, 28 and 32 °C, and ambient temperature of 27 to 30 °C. Thermoregulatory behavior, represented by preferred temperature (29.83 ± SD 2.47 °C), critical thermal minimum (17.33 ± SD 0.58 °C), critical thermal maximum (40 ± SD 0.00 °C), and thermal tolerance interval (22.67 ± SD 0.58 °C), were checked for Crablet 1 stage only (with ambient temperature as acclimation temperature).Both low (24 °C) and high (32 °C) temperatures were associated with lower growth performance, and survival rate (p < 0.05), in comparison with both 28 °C and ambient temperature treatments.Male ratio at low temperaturetreatment (24 °C) was higher (80.09 ± SD 18.86%) than for other treatments (p < 0.05), observed as 44.81 ± D 10.50%, 41.94 ± SD 19.44%, and 76.30 ± SD 5.13% for 28 °C, 32 °C and ambient temperature treatments, respectively. However, there was no significant difference observed between 24 °C, 28 °C, and ambient temperature treatments. Anatomical alterations of gill lamellae of S. paramamosain crablet for both 32 °C, and 24 °C treatments, appeared thinner and paler than at both 28 °C, and ambient temperature treatments. Based on this study, temperature of 28 to 30 °C was recommended as the optimal temperature for the long-term nursery phase of S. paramamosain.
Improving the Quality and Safety of Fresh Camel Meat Contaminated with Campylobacter jejuni Using Citrox, Chitosan, and Vacuum Packaging to Extend Shelf Life
Authors: Yehia Hany M. , Al-Masoud Abdulrahman H. , Elkhadragy Manal F. , Korany Shereen M. , Nada Hend M. S. , Albaridi Najla A. , Alzahrani Abdulhakeem A. , AL-Dagal Mosffer M.
Published: April 2021

Camel meat is one of the most consumed meats in Arab countries. The use of natural antimicrobial agents to extend the shelf life of fresh camel meat, control Campylobacter jejuni contamination, and preserve meat quality is preferred. In this study, we determined the antimicrobial effects of using 1% or 2% Citrox alone or in combination with 1% chitosan on the survival of C. jejuni in vitro and on camel meat samples during storage at 4 or 10 °C for 30 days in vacuum packaging. We determined the total viable count (TVC (cfu/g)), total volatile base nitrogen (TVB-N) content, and pH of the treated camel meat samples every three days during storage. The shelf lives of camel meat samples treated with 2% Citrox alone or in combination with 1% chitosan were longer than those of camel meat samples treated with 1% Citrox alone or in combination with 1% chitosan at both the 4 and 10 °C storage temperatures, with TVCs of <100 cfu/g after the first ten days and six days of storage at 4 and 10 °C, respectively. The addition of Citrox (1% and 2%) and 1% chitosan to camel meat samples and the application of vacuum storage were more effective than using Citrox (1% and 2%) alone and led to a reduction in C. jejuni in approximately 4.0 and 3.5 log cycles at 4 and 10 °C, respectively. The experimental results demonstrated that using a Citrox-chitosan combination improved the quality of camel meat and enhanced the long-term preservation of fresh meat for up to or more than 30 days at 4 °C.
The Effect of Rosemary (Rosmarinus officinalis) and Blackcurrant Extracts (Ribes nigrum) Supplementation on Performance Indices and Oxidative Stability of Chicken Broiler Meat
Authors: Sierżant Kamil , Korzeniowska Małgorzata , Orda Janusz , Wojdyło Aneta , Gondret Florence , Półbrat Tomasz
Published: April 2021

The effects of dietary supplementation with extracts of rosemary (RO) and blackcurrant (BC) on the performance indices and the oxidative stability of broiler meat were investigated during a 35-d experiment. For the experiment, 120 one-day-old male Hubbard Flex broiler chicks were randomly allocated to 5 experimental groups (control group and 4 treatments, each in 6 replications, 24 birds per group, 4 birds per replicate) and fed control starter and grower diets or basal diets containing two concentrations (2.5 and 5 g/kg) of the RO and BC extracts. Basic performance traits (body weight gain, feed intake, feed conversion) were recorded during the trial. At the end of the experiment, pectoral and thigh muscles were collected. Thiobarbituric acid (TBA) assays using the muscles samples were performed after 1 and 5 d of chilling (4 °C) and after 90 d of frozen storage (−18 °C). The inclusion of RO and BC in the birds’ diet had no significant effects on weight gain and feed conversion ratio of chickens, or on carcass characteristics, compared with control group. Enrichment of chicken diet with RO and BC did not affect the oxidative stability of chicken breast muscles, but the tested extracts significantly reduced the malondialdehyde (MDA) formation in frozen thigh muscles.
Effects of Different Patterns and Sources of Trace Elements on Laying Performance, Tissue Mineral Deposition, and Fecal Excretion in Laying Hens
Authors: Yang Kaili , Hu Shengjun , Mu Rui , Qing Yiqing , Xie Liang , Zhou Liyuan , Ajuwon Kolapo M. , Fang Rejun
Published: April 2021

This study was conducted to investigate the effects of different patterns and sources of Zn, Fe, Cu, Mn, and Se on performance, mineral deposition (liver, kidney, pancreas, spleen, pectorals muscle, and tibia), and excretion of laying hens, then to find an optimal dietary supplemental pattern of trace elements in laying hens. A total of 864 healthy laying hens with similar laying rate (Roman, 26-week-old) were randomly divided into nine treatments, with six replications of 16 birds per replication, including a control treatment and four patterns with different element sources (inorganic or organic): (1) Control treatment (basic diet without added extra trace minerals, CT); pattern 1, NRC (1994) recommended level (NRC-L): (2) inorganic minerals of NRC-L pattern (IN), (3) organic minerals of NRC-L pattern (ON); pattern 2, NY/T 33-2004 recommended level (NY/T-L): (4) inorganic minerals of NY/T-L pattern (IY), (5) organic minerals of NY/T-L pattern (OY); pattern 3, 50% NRC (1994) recommended level (50% NRC-L): (6) inorganic minerals of 50% NRC-L pattern (IHN), (7) organic minerals of 50% NRC-L pattern (OHN); pattern 4, the ratio of minerals in blood of laying hens was taken as the supplement proportion of trace elements, and Zn was supplemented depended on NRC recommended level (TLB): (8) inorganic minerals of TLB pattern (IB), (9) organic minerals of TLB pattern (OB). Two weeks were allowed for adjustment to the conditions and then measurements were made over eight weeks. Supplementation of trace elements led to increased daily egg weight (p < 0.05). Patterns of minerals in diets affected the content of liver Mn, pancreas Mn, tibia Mn, and the tissues Se (p < 0.05). Sources of minerals had positive effects on daily egg weight (p < 0.05), the concentrations of liver Fe, kidney Cu, tissues Se (except spleen), and fecal Se (p < 0.05). In conclusion, diet supplemented with the organic trace minerals of 50% NRC-L pattern (OHN) in laying hens promoted optimum laying performance, mineral deposition, and reduced mineral excretion.
A Moderate Reduction of Dietary Crude Protein Provide Comparable Growth Performance and Improve Metabolism via Changing Intestinal Microbiota in Sushan Nursery Pigs
Authors: Liu Riliang , He Jianwen , Ji Xu , Zheng Weijiang , Yao Wen
Published: April 2021

In this paper, we investigated the effects of a diet with a moderate reduction of dietary crude protein (CP) level, supplemented with five crystalline amino acids (Lys, Met, Thr, Try, and Val), on the growth, metabolism, and fecal microbiota of Sushan nursery pigs. Seventy Sushan nursery pigs with an average body weight of 19.56 ± 0.24 kg were randomly allocated to two experimental dietary treatments: 18% CP (high protein; group HP), and 15% CP (low protein; group LP). We found that the differences in the two diets had no significant effect on the growth performance of Sushan nursery pigs. Nursery pigs on the 15% CP diet showed significantly improved protein, amino acid, and energy utilization. Furthermore, the LP diet cloud optimized the gut microflora composition to some extent. The functional structure of bacterial communities implied improved metabolic capabilities in group LP. Additionally, correlation analysis between fecal microbiota and metabolic profiles confirmed that the increase of beneficial bacterial in the feces was beneficial to the health and metabolism of the nursery pigs. In conclusion, a moderate reduction in the dietary protein level can improve growth and metabolism due to the improvement of intestinal microbiota in Sushan nursery pigs. This finding could provide useful reference data for the application of a different nutrition strategy in indigenous pig production.
Therapeutic Efficacy of Anti-Bestrophin Antibodies against Experimental Filariasis: Immunological, Immune-Informatics and Immune Simulation Investigations
Authors: Das Nabarun Chandra , Ray Anindya Sundar , Bayry Jagadeesh , Mukherjeee Suprabhat
Published: April 2021

Lymphatic filariasis (LF) is a debilitating parasitic disease caused by filarial parasites and it is prevalent across the underprivileged population throughout the globe. The inadequate efficacy of the existing treatment options has provoked the conception of alternative strategies, among which immunotherapy is steadily emerging as a promising option. Herein, we demonstrate the efficacy of an antibody-based immunotherapeutic approach in an experimental model of filariasis, i.e., Wistar rat infected with Setaria cervi (a model filarial parasite). The polyclonal antibodies were raised against filarial surface antigen bestrophin protein (FSAg) in mice using the purified Wuchereria bancrofti FSAg. The adoptive transfer of anti-FSAg antibody-containing serum resulted in the significant reduction of parasite burden in filaria-infected rats. Intriguingly, anti-FSAg sera-treated animals also displayed a reduction in the level of proinflammatory cytokines as compared to the infected but untreated group. Furthermore, our in silico immunoinformatics data revealed eight B-cell epitopes and several T-cell epitopes in FSAg and these epitopes were linked to form a refined antigen in silico. The immune simulation suggested IgM and IgG1 as the predominant immunoglobulins induced in response to FSAg. Taken together, our experimental and simulation data collectively indicated a therapeutic potential of anti-FSAg sera against LF.
Candida Periprosthetic Joint Infection: Is It Curable?
Authors: Escolà-Vergé Laura , Rodríguez-Pardo Dolors , Corona Pablo S. , Pigrau Carles
Published: April 2021

Candida periprosthetic joint infection (CPJI) is a rare and very difficult to treat infection, and high-quality evidence regarding the best management is scarce. Candida spp. adhere to medical devices and grow forming biofilms, which contribute to the persistence and relapse of this infection. Typically, CPJI presents as a chronic infection in a patient with multiple previous surgeries and long courses of antibiotic therapy. In a retrospective series of cases, the surgical approach with higher rates of success consists of a two-stage exchange surgery, but the best antifungal treatment and duration of antifungal treatment are still unclear, and the efficacy of using an antifungal agent-loaded cement spacer is still controversial. Until more evidence is available, focusing on prevention and identifying patients at risk of CPJI seems more than reasonable.
Multidrug-Resistant Healthcare-Associated Infections in Neonates with Severe Respiratory Failure and the Impacts of Inappropriate Initial Antibiotic Therap
Authors: Hsu Jen-Fu , Chu Shih-Ming , Wang Hsiao-Chin , Liao Chen-Chu , Lai Mei-Yin , Huang Hsuan-Rong , Chiang Ming-Chou , Fu Ren-Huei , Tsai Ming-Horng
Published: April 2021

Background: Multidrug-resistant (MDR) pathogens have emerged as an important issue in neonatal intensive care units (NICUs), especially in critically ill neonates with severe respiratory failure. We aimed to investigate neonatal healthcare-associated infections (HAIs) caused by MDR pathogens and the impacts of inappropriate initial antibiotic therapy on the outcomes. Methods: We retrospectively analyzed all cases of HAIs in neonates with severe respiratory failure in a tertiary-level NICU in Taiwan between January 2014 and May 2020. All clinical features, microbiology, therapeutic interventions, and outcomes were compared between the MDR-HAI and non-MDR HAI groups. Multivariate regression analyses were used to investigate independent risk factors for sepsis-attributable mortality. Results: A total of 275 critically ill neonates with severe respiratory failure who had HAIs were enrolled. Ninety-five cases (34.5%) were caused by MDR pathogens, and 141 (51.3%) cases had positive bacterial cultures from multiple sterile sites. In this cohort, the MDR-HAI group was more likely to receive inappropriate initial antibiotic therapy (51.0% versus 4.7%, respectively; p < 0.001) and exhibit delayed control of the infectious focus (52.6% versus 37.8%, respectively; p = 0.021) compared with the non-MDR HAI group. The sepsis-attributable and final in-hospital rates were 21.8% and 37.1%, respectively, and they were comparable between the MDR-HAI and non-MDR HAI groups. Empirically broad-spectrum antibiotics were prescribed in 76.7% of cases, and inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. Independent risk factors for sepsis-attributable mortality in neonates with severe respiratory failure included the presence of septic shock (OR: 3.61; 95% CI: 1.54–8.46; p = 0.003), higher illness severity (OR: 1.33; 95% CI: 1.04–1.72; p = 0.026), and neonates with bronchopulmonary dysplasia (OR: 2.99; 95% CI: 1.47–6.09; p = 0.003). Conclusions: MDR pathogens accounted for 34.5% of all neonatal HAIs in the NICU, but neither MDR pathogens nor inappropriate initial antibiotics were associated with final adverse outcomes. Because the overuse of broad-spectrum antibiotics has emerged as an important issue in critically ill neonates, the implementation of antimicrobial stewardship to promote the appropriate use of antimicrobials is urgently needed.
Barriers and Facilitators in Perioperative Antibiotic Prophylaxis: A Mixed-Methods Study in a Small Island Setting
Authors: Mun Liza A. M. van , Bosman Sabien J. E. , Vocht Jessica de , Kort Jaclyn de , Schouten Jeroen
Published: April 2021

Few studies have addressed antibiotic guideline adherence in small island settings, such as Aruba. This study aimed to evaluate the appropriateness of perioperative antibiotic prophylaxis (PAP) and identify barriers for PAP guideline adherence. A mixed-methods study was carried out at the operating theatre (OT) in the Dr. Horacio E. Oduber Hospital (HOH) in Aruba. First, a prospective audit was performed on the appropriateness of guideline-derived quality indicators (QIs). Then, interviews based on the Flottorp framework were conducted to identify barriers for guideline adherence. Finally, a survey was distributed to verify the outcomes of the interviews. The appropriateness of QIs was measured: correct indication (50.6%); antimicrobial agent (30.8%); dose (94.4%); timing (55.0%); route of administration (100%); duration (89.5%); and redosing (95.7%). The overall appropriateness was 34.9%. The main barriers discovered were poor knowledge about PAP and the guidelines and professional interactions regarding PAP, specifically poor communication and lack of clarity about responsibilities regarding PAP. This study was the first to evaluate the appropriateness and to identify barriers for PAP guideline adherence in a small island hospital. The overall appropriateness of PAP was poor with just 34.9%. Future interventions should be focused on communication, education and awareness of the possibility to consult an ID physician or microbiologist.
Estrogen Decreases Cytoskeletal Organization by Forming an ERα/SHP2/c-Src Complex in Osteoclasts to Protect against Ovariectomy-Induced Bone Loss in Mice
Authors: Park Hyun-Jung , Gholam-Zadeh Malihatosadat , Yoon Sun-Young , Suh Jae-Hee , Choi Hye-Seon
Published: April 2021

Loss of ovarian function is closely related to estrogen (E2) deficiency, which is responsible for increased osteoclast (OC) differentiation and activity. We aimed to investigate the action mechanism of E2 to decrease bone resorption in OCs to protect from ovariectomy (OVX)-induced bone loss in mice. In vivo, tartrate-resistant acid phosphatase (TRAP) staining in femur and serum carboxy-terminal collagen crosslinks-1 (CTX-1) were analyzed upon E2 injection after OVX in mice. In vitro, OCs were analyzed by TRAP staining, actin ring formation, carboxymethylation, determination of reactive oxygen species (ROS) level, and immunoprecipitation coupled with Western blot. In vivo and in vitro, E2 decreased OC size more dramatically than OC number and Methyl-piperidino-pyrazole hydrate dihydrochloride (MPPD), an estrogen receptor alpha (ERα) antagonist, augmented the OC size. ERα was found in plasma membranes and E2/ERα signaling affected receptor activator of nuclear factor κB ligand (RANKL)-induced actin ring formation by rapidly decreasing a proto-oncogene tyrosine-protein kinase, cellular sarcoma (c-Src) (Y416) phosphorylation in OCs. E2 exposure decreased physical interactions between NADPH oxidase 1 (NOX1) and the oxidized form of c-Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), leading to higher levels of reduced SHP2. ERα formed a complex with the reduced form of SHP2 and c-Src to decrease c-Src activation upon E2 exposure, which blocked a signal for actin ring formation by decreased Vav guanine nucleotide exchange factor 3 (Vav3) (p–Y) and Ras-related C3 botulinum toxin substrate 1 (Rac1) (GTP) activation in OCs. E2/ERα signals consistently inhibited bone resorption in vitro. In conclusion, our study suggests that E2-binding to ERα forms a complex with SHP2/c-Src to attenuate c-Src activation that was induced upon RANKL stimulation in a non-genomic manner, resulting in an impaired actin ring formation and reducing bone resorption.