bluuebunny/crossref_metadata_2025 huggingface dataset:
Total anomalous pulmonary venous connection in 80 patients: Primary sutureless repair and outcomes
Authors: Li Gefei , Meng Baoying , Zhang Cheng , Zhang Weimin , Zhou Xiaodong , Zhang Qing , Ding Yiqun
Published: January 2023

Introduction

Total anomalous pulmonary venous connection (TAPVC) is a rare but critical cardiac anomaly, in which pulmonary veins are connected to an abnormal location rather than the left atrium. The prognosis can be extremely poor without intervention, with a mortality of 80% during infancy. The purpose of this research is to summarize the outcomes and relevant risk factors of 80 total anomalous pulmonary venous connection (TAPVC) patients who underwent primary TAPVC sutureless repair and discuss the indications and benefits of primary sutureless repair.

Methods

This retrospective review included 80 patients with TAPVC who underwent primary sutureless repair at a single institution between January 2015 and December 2020. Patients were subdivided into 4 groups according to Darling's classification. Risk factors that increase the postoperative pulmonary vein flow velocity were explored by Multiple Linear regression.

Results

Anatomic TAPVC subtypes included supracardiac 35 (43.8%), cardiac 24 (30%), infracardiac 17 (21.2%), and mixed 4 (5%). Median age at repair was 16.5 days and median weight was 3.5 kg. Preoperative pulmonary venous obstruction (PVO)was presented in 20 (25%) patients. There were 2 early deaths and 1 late death. 2 patients developed postoperative PVO and none required reintervention. Prolonged cardiopulmonary bypass time (CPB) (p = 0.009), preoperative pneumonia (p = 0.022) and gender (p = 0.041) were found to be associated with the increase of postoperative pulmonary vein flow velocity.

Discussion

Under the primary sutureless technique, no statistical difference was observed among the 4 subgroups in terms of postoperative pulmonary vein flow velocity (p = 0.589). The primary sutureless technique may eliminate the differences between subtypes while decrease the postoperative PVO rate, which makes it applicable in any subtypes of TAPVC. Following the favorable outcomes in preventing postoperative PVO in all subtypes in this study, we advocate the indications for primary sutureless repair may expand further to all the TAPVC patients.
Automatic monitoring and detection of tail-biting behavior in groups of pigs using video-based deep learning methods
Authors: Hakansson Franziska , Jensen Dan Børge
Published: January 2023

Automated monitoring of pigs for timely detection of changes in behavior and the onset of tail biting might enable farmers to take immediate management actions, and thus decrease health and welfare issues on-farm. Our goal was to develop computer vision-based methods to detect tail biting in pigs using a convolutional neural network (CNN) to extract spatial information, combined with secondary networks accounting for temporal information. Two secondary frameworks were utilized, being a long short-term memory (LSTM) network applied to sequences of image features (CNN-LSTM), and a CNN applied to image representations of sequences (CNN-CNN). To achieve our goal, this study aimed to answer the following questions: (a) Can the methods detect tail biting from video recordings of entire pens? (b) Can we utilize principal component analyses (PCA) to reduce the dimensionality of the feature vector and only use relevant principal components (PC)? (c) Is there potential to increase performance in optimizing the threshold for class separation of the predicted probabilities of the outcome? (d) What is the performance of the methods with respect to each other? The study utilized one-hour video recordings of 10 pens with pigs prior to weaning, containing a total of 208 tail-biting events of varying lengths. The pre-trained VGG-16 was used to extract spatial features from the data, which were subsequently pre-processed and divided into train/test sets before input to the LSTM/CNN. The performance of the methods regarding data pre-processing and model building was systematically compared using cross-validation. Final models were run with optimal settings and evaluated on an independent test-set. The proposed methods detected tail biting with a major-mean accuracy (MMA) of 71.3 and 64.7% for the CNN-LSTM and the CNN-CNN network, respectively. Applying PCA and using a limited number of PCs significantly increased the performance of both methods, while optimizing the threshold for class separation did result in a consistent but not significant increase of the performance. Both methods can detect tail biting from video data, but the CNN-LSTM was superior in generalizing when evaluated on new data, i.e., data not used for training the models, compared to the CNN-CNN method.
An Algorithm for Solving Zero-Sum Differential Game Related to the Nonlinear H∞ Control Problem
Authors: Milić Vladimir , Kasać Josip , Lukas Marin
Published: January 2023

This paper presents an approach for the solution of a zero-sum differential game associated with a nonlinear state-feedback H∞ control problem. Instead of using the approximation methods for solving the corresponding Hamilton–Jacobi–Isaacs (HJI) partial differential equation, we propose an algorithm that calculates the explicit inputs to the dynamic system by directly performing minimization with simultaneous maximization of the same objective function. In order to achieve numerical robustness and stability, the proposed algorithm uses: quasi-Newton method, conjugate gradient method, line search method with Wolfe conditions, Adams approximation method for time discretization and complex-step calculation of derivatives. The algorithm is evaluated in computer simulations on examples of first- and second-order nonlinear systems with analytical solutions of H∞ control problem.
Variational Reduced-Order Modeling of Thermomechanical Shape Memory Alloy Based Cooperative Bistable Microactuators
Authors: Shamim Muhammad Babar , Hörsting Marian , Wulfinghoff Stephan
Published: January 2023

This article presents the formulation and application of a reduced-order thermomechanical finite strain shape memory alloy (SMA)-based microactuator model for switching devices under thermal loading by Joule heating. The formulation is cast in the generalized standard material framework with an extension for thermomechanics. The proper orthogonal decomposition (POD) is utilized for capturing a reduced basis from a precomputed finite element method (FEM) full-scale model. The modal coefficients are computed by optimization of the underlying incremental thermomechanical potential, and the weak form for the mechanical and thermal problem is formulated in reduced-order format. The reduced-order model (ROM) is compared with the FEM model, and the exemplary mean absolute percentage errors for the displacement and temperature are 0.973% and 0.089%, respectively, with a speedup factor of 9.56 for a single SMA-based actuator. The ROM presented is tested for single and cooperative beam-like actuators. Furthermore, cross-coupling effects and the bistability phenomenon of the microactuators are investigated.
Target Tracking of Snake Robot with Double-Sine Serpentine Gait Based on Adaptive Sliding Mode Control
Authors: Liu Zhifan , Wei Wu , Liu Xiongding , Han Siwei
Published: January 2023

This paper studies the target tracking control strategy of a snake robot and proposes an adaptive sliding mode control method. The strategy ensures the robot follows the target path by controlling the joint angle through feedback, pushing the robot to reach the target position through gait function. In order to achieve target tracking, a kinematic model of a snake robot was first established in this paper. Then, we used double-sine serpentine gait to solve the problem of low steering efficiency caused by regular serpentine gait, and we explored the relationship between control parameters and robot steering. On the basis of gait, in order to further improve the efficiency of target tracking for the snake robot, an adaptive sliding mode control method, based on a new sliding mode reaching law, was proposed. Finally, the effectiveness and practicability of the proposed strategy was demonstrated by comparative analysis and simulation experiments.
Entrepreneurship Education, a Challenging Learning Process towards Entrepreneurial Competence in Education
Authors: Miço Heliona , Cungu Jonida
Published: January 2023

Entrepreneurship education is a recent field in education. From a field mainly related to small business, it is extended towards enhancement of students’ entrepreneurial attitudes and skills. It can support students in developing an independent and versatile way by growing the spirit of entrepreneurship. Developing entrepreneurship competence among students requires the mastery of concepts by teachers. Training teachers in entrepreneurship education helps them apply specific competences, methods, and tools to encourage confidence in learners’ own capabilities and to stimulate flexibility, leadership, and initiative. To understand the teachers’ entrepreneurial competence, an online survey was developed to assess the level of mastery of such competence in Albanian teachers. The survey was designed to analyze the development of entrepreneurial competence of teachers, and their entrepreneurship education and training. The research goal of the survey is to evaluate the influence mechanisms of gaining entrepreneurship education competence and the way of implementing this competence in pre-university education schools. Results from the questionnaire highlighted the teachers’ need for the acquisition of entrepreneurial competence at every professional level, starting from initial teacher education. The findings from the survey are analyzed by taking into consideration the European policies regarding entrepreneurship education, such as the European Entrepreneurship Competence Framework (EntreComp), and their implementation in the Albanian educational sector.
Numerical Simulation of an Electrothermal Ice Protection System in Anti-Icing and Deicing Mode
Authors: Bennani Lokman , Trontin Pierre , Radenac Emmanuel
Published: January 2023

The design of efficient thermal ice protection systems is a challenging task as these systems operate in complex environments involving several coupled physical phenomena such as phase change, boundary-layer flow, and heat transfer. Moreover, certification rules are becoming more stringent, and there is a strong incentive for the reduction of fuel consumption. In this context, numerical tools provide a powerful asset during the design phase but also to gain insight into the physical mechanisms at play. This article presents modeling and simulation strategies for thermal ice protection systems. First, the model describing the behavior of the thermal protection system is presented. Second, a model and associated numerical method is presented for unsteady ice accretion. Third, the coupling methodology between the ice accretion solver and the heat conduction solver is described. In the fourth part, different methods to simulate the boundary-layer flow are described. Finally, some relevant examples are presented, both in steady and unsteady configurations.
Probabilistic Assessment of Cereal Rye Cover Crop Impacts on Regional Crop Yield and Soil Carbon
Authors: Rai Teerath , Lee Nicole , Williams Martin , Davis Adam , Villamil María , Dokoohaki Hamze
Published: January 2023

Field research for exploring the impact of winter cover crops (WCCs) integration into cropping systems is resource intensive, time-consuming and offers limited application beyond the study area. To bridge this gap, we used the APSIM model, to simulate corn (Zea mays L.)-rye (Secale cereale L.)-corn-rye and corn-rye-soybean (Glycine max L.)-rye rotations in comparison with corn-corn and corn-soybean rotations across the state of Illinois at a spatial resolution of 5 km × 5 km from 2000 to 2020 to study the impact of WCCs on soil organic carbon (SOC) dynamics and crop production. By propagating the uncertainty in model simulations associated with initial conditions, weather, soil, and management practices, we estimated the probability and the expected value of change in crop yield and SOC following WCC integration. Our results suggest that integrating cereal rye into the crop rotations imparted greater yield stability for corn across the state. It was found that the areas with low probability of increase in SOC (p < 0.75) responded equally well for soil carbon sequestration through long term adoption of WCCs. This study presents the most complete uncertainty accounting of WCC benefits across a broad region and provides greater insights into the spatiotemporal variability of WCCs benefits for increasing WCC adoption rate.
Development of a Knowledge-Based Expert System for Diagnosing Post-Harvest Diseases of Apple
Authors: Sottocornola Gabriele , Baric Sanja , Stella Fabio , Zanker Markus
Published: January 2023

Post-harvest diseases are one of the main causes of economical losses in the apple fruit production sector. Therefore, this paper presents an application of a knowledge-based expert system to diagnose post-harvest diseases of apple. Specifically, we detail the process of domain knowledge elicitation for constructing a Bayesian network reasoning system. We describe the developed expert system, dubbed BN-DSSApple, and the diagnostic mechanism given the evidence provided by the user, as well as a likelihood evidence method, learned from the estimated consensus of users’ and expert’s interactions, to effectively transfer the performance of the model to different cohorts of users. Finally, we detail a novel technique for explaining the provided diagnosis, thus increasing the trust in the system. We evaluate BN-DSSApple with three different types of user studies, involving real diseased apples, where the ground truth of the target instances was established by microbiological and DNA analysis. The experiments demonstrate the performance differences in the knowledge-based reasoning mechanism due to heterogeneous users interacting with the system under various conditions and the capability of the likelihood-based method to improve the diagnostic performance in different environments.
Design and Experiment of Side-Shift Stubble Avoidance System for No-Till Wheat Seeder Based on Deviation-Perception Fusion Technology
Authors: Zhang Zhenguo , Guo Quanfeng , He Jin , Zhao Minyi , Xing Zhenyu , Zeng Chao , Lin Han , Wang Quanyu
Published: January 2023

To improve the stubble avoidance rate of no-till wheat seeders under the environment of corn stubble, the side-shift stubble avoidance system was developed in the present study based on deviation-perception fusion technology. Firstly, the amount of implement deviation compensation was accurately obtained by the information sensing system. Then, a fuzzy PID algorithm was proposed to optimize the performance of the control system. Finally, the simulation model of the control system was developed by Matlab/Simulink. The simulation results showed that the regulation time required for the system response curve to reach the steady state was 1.0 s, and the maximum overshoot was 8.2%. To verify the performance of the side-shift stubble avoidance system, an orthogonal test was conducted. The optimal combination of parameters was obtained, including the operation speed of 1.3 m/s, the hydraulic cylinder speed of 25 mm/s, and the straw mulch amount of 1.2 kg/m2. The field verification test was performed under the optimal parameters, showing the stubble avoidance rate was 90.6%, and the mean value of the sowing variation coefficient was 27.12%, which fully satisfied the requirements of stubble avoidance and sowing operation.
Milk Fatty Acids: The Impact of Grazing Diverse Pasture and the Potential to Predict Rumen-Derived Methane
Authors: Loza Cecilia , Davis Hannah , Malisch Carsten , Taube Freidhelm , Loges Ralf , Magistrali Amelia , Butler Gillian
Published: January 2023

The sustainability of dairying has been questioned, yet cattle exploit non-food resources (especially forages) and provide key nutrients for consumers’ health. This study, using different forage types, considered milk’s nutritional quality, focusing on fatty acid profiles alongside methane emissions—investigating whether methane can be predicted from milk fatty acids (FAs). Compared with grass/clover/maize silage, cows grazing grass/clover pasture produced milk 70% higher in beneficial omega-3 FAs, which increased by an additional 15% when grazing more diverse pasture. Milk from grazing also had less omega-6 FAs (compared with silage diets), and their ratio with omega-3 FAs fell from 2.5:1 on silage to 1.2:1 when grazing grass/clover and 1.1:1 on diverse pasture. Measured methane emissions (at 8.7 g/kg energy-corrected milk) were lower than published values, and existing models for estimating methane from lactating cows were poor predictors for this dataset. The multiple regression of methane against milk FAs in this study provided predictions with an R2 of 0.56 for daily emissions and 0.65 relative to milk output. Grazing quality and a diverse pasture with productive cows were potentially beneficial to milk nutritional quality, and our results reinforce the theory that milk fat composition could be an accessible tool for methane prediction; however, they also suggest that more work is needed for alternative production systems.
Wheat Yield and Protein Estimation with Handheld and Unmanned Aerial Vehicle-Mounted Sensors
Authors: Walsh Olga S. , Marshall Juliet M. , Nambi Eva , Jackson Chad A. , Ansah Emmanuella Owusu , Lamichhane Ritika , McClintick-Chess Jordan , Bautista Francisco
Published: January 2023

Accurate sensor-based prediction of crop yield and grain quality in-season would enable growers to adjust nitrogen (N) fertilizer management for optimized production. This study assessed the feasibility (and compared the accuracy) of wheat (Triticum aestivum L.) yield, grain N uptake, and protein content prediction with in-season crop spectral reflectance measurements (Normalized Difference Vegetative Index, NDVI) obtained with a handheld GreenSeeker (GS) sensor and an Unmanned Aerial Vehicle (UAV)-mounted sensor. A strong positive correlation was observed between GS NDVI and UAV NDVI at Feekes 5 (R2 = 0.78) and Feekes 10 (R2 = 0.70). At Feekes 5, GS NDVI and UAV NDVI explained 42% and 43% of wheat yield, respectively. The correlation was weaker at Feekes 10 (R2 of 0.34 and 0.25 for GS NDVI and UAV NDVI, respectively). The accuracy of wheat grain N uptake prediction was comparable to that of yield: the R2 values for GS NDVI and UAV NDVI were 0.53 and 0.37 at Feekes 5 and 0.13 and 0.20 at Feekes 10. We found that neither GS NDVI nor UAV NDVI in-season data were useful in prediction of wheat grain protein content. In conclusion, wheat yield and grain N uptake can be estimated at Feekes 5 using either handheld or aerial based NDVI with comparable accuracy.
Genome-Wide Identification and Expression Analysis of GATA Gene Family under Different Nitrogen Levels in Arachis hypogaea L.
Authors: Li Xiujie , Deng Xiaoxu , Han Suoyi , Zhang Xinyou , Dai Tingbo
Published: January 2023

Nitrogen, one of the essential elements, is a key determinant for improving peanut growth and yield. GATA zinc finger transcription factors have been found to be involved in regulation of nitrogen metabolism. However, a systematic characterization of the GATA gene family and patterns of their expression under different nitrogen levels remains elusive. In this study, a total of 45 GATA genes distributed among 17 chromosomes were identified in the peanut genome and classified into three subfamilies I, II and III with 26, 13 and 6 members, respectively, whose physicochemical characteristics, gene structures and conserved motifs were also analyzed. Furthermore, the optimal level of nitrogen fertilizer on the growth of peanut cultivar Yuhua 23 was determined by pod yield and value cost ratio from 2020 to 2022, and the results revealed that 150 kg hm−2 nitrogen was the best for cultivation of peanut Yuhua 23 because of its highest pod yield and relatively higher VCR of more than four. In addition, expression patterns of peanut GATA genes under different nitrogen levels were detected by real-time quantitative PCR and several GATA genes were significantly changed under a nitrogen level of 150 kg hm−2. Overall, the above results would be helpful for further understanding biological functions of the GATA gene family in cultivated peanut.
Integration of a System Dynamics Model and 3D Tree Rendering—VISmaF Part II: Model Development, Results and Potential Agronomic Applications
Authors: Crimaldi Mariano , Cartenì Fabrizio , Bonanomi Giuliano , Giannino Francesco
Published: January 2023

Biological–mathematical models of trees can be exploited for a wide range of agronomic applications including crop management, visualization of ecosystem changes over time, in-field phenotyping, crop load effects, testing of plant functions, biomechanics, and many others. Some models propose a 3D output of tree that, in addition to having functionality to visualize the result, offers an additional tool for the evaluation of some parameters of the model itself (interception and amount of light, temperature, obstacles, physical competition between multiple trees). The present study introduces a biological–mathematical model of tree growth with a 3D output of its structure in a realtime 3D rendering environment (Unity©). Thanks to the virtual environment created in Unity©, it was possible to obtain variable environmental parameters (amount of light, temperature) used as inputs to the mathematical simulation of growth. The model is based on ordinary differential equations (ODEs) that compute the growth of each single internode in length (primary growth) and width (secondary growth) and the accumulation of growth inhibitors regulating the seasonal cyclicity of the tree. Virtual experiments were conducted varying environmental conditions (amount of light and temperature), and the species-specific characteristics of the simulated tree (number of buds, branching angle). The results have been analyzed showing also how the model can be adapted for the creation of different tree species and discussing the potential agronomic applications of model.
Soil Constraints in an Arid Environment—Challenges, Prospects, and Implications
Authors: Naorem Anandkumar , Jayaraman Somasundaram , Dang Yash P. , Dalal Ram C. , Sinha Nishant K. , Rao Ch. Srinivasa , Patra Ashok K.
Published: January 2023

Climate models project that many terrestrial ecosystems will become drier over the course of this century, leading to a drastic increase in the global extent of arid soils. In order to decrease the effects of climate change on global food security, it is crucial to understand the arid environment and the constraints associated with arid soils. Although the effects of aridity on aboveground organisms have been studied extensively, our understanding of how it affects soil processes and nutrient cycling is lacking. One of the primary agricultural constraints, particularly in arid locations, is water scarcity, due to which arid soils are characterized by sparse vegetation cover, low soil organic carbon, poor soil structure, reduced soil biodiversity, and a high rate of soil erosion via wind. Increased aridity will limit the availability of essential plant nutrients and crop growth, and subsequently pose serious threats to key ecological processes and services. The increasing rate of soil salinization is another major environmental hazard that further limits the agricultural potential of arid soils. These soil constraints can be ameliorated and the crop yields increased through case-specific optimization of irrigation and drainage management, enhancing the native beneficial soil microbes, and combinations of soil amendments, conditioners, and residue management. This review explores technologies to ameliorate soil constraints and increase yields to maintain crop output in arid soils.
Effects of Five Consecutive Years of Fallow Tillage on Soil Microbial Community Structure and Winter Wheat Yield
Authors: Zhong Rong , Zi Zhaolan , Wang Peiru , Noor Hafeez , Ren Aixia , Ren Yongkang , Sun Min , Gao Zhiqiang
Published: January 2023

To evaluate the effects of long-term fallow tillage on soil microbial community structure in different soil layers and winter wheat yield, we conducted a 5-year long-term field experiment in the Loess Plateau, China, using three fallow tillage methods: no-tillage (NT), subsoiling tillage (ST), and deep plowing (DP). The soil physical and chemical properties, community structure, and composition of soil bacteria and fungi in the 0–20 cm and 20–40 cm soil layers, and winter wheat yield were analyzed. The results showed that, compared with DP, NT and ST significantly increased soil moisture content (SWC), soil organic carbon (SOC) content, and dissolved organic carbon (DOC) contents in 0–20 cm soil layer (p < 0.05), and significantly increased soil microbial community Shannon and Simpson index in 0–40 cm soil layer (p < 0.05). Compared with NT, ST and DP significantly increased SWC and SOC contents in 20–40 cm soil layer (p < 0.05). Actinobacteria and Ascomycota were the most abundant bacteria and fungi in the soil of the experimental site. Redundancy analysis further showed that soil physicochemical properties (SWC, SOC, DOC, and DON) were closely related to the microbial community. PICRUSt2 prediction results showed that DP increased the metabolic functional diversity of bacteria and fungi. ST and DP significantly increased the yield of winter wheat, and DP had the best effect. In conclusion, subsoiling tillage and deep plowing were beneficial to the accumulation and utilization of natural precipitation and the improvement of soil microbial community structure. Deep plowing was beneficial to the decomposition and metabolism of straw and organic fertilizer, and improved the catabolic ability of microbial community, thus increasing the yield of winter wheat.
Candidate Genes Involved in Tolerance to Fenoxaprop-P-Ethyl in Rice Induced by Isoxadifen-Ethyl Hydrolysate
Authors: Zhao Yaning , Li Wenqing , Sun Lanlan , Wu Renhai , Xu Hongle , Su Wangcang , Lu Chuantao
Published: January 2023

The metabolic resistance of plants to herbicides is similar to the herbicide metabolism process accelerated by safeners. The tolerance to fenoxaprop-P-ethyl (FE) is distinct among different varieties of rice in which phytotoxicity forms easily, resulting in the restricted use of FE in paddy. Safener effectively resolves this issue. This study showed that rice 9311 and Meixiangzhan No. 2 (MXZ) had different tolerance mechanisms to FE. Isoxadifen-ethyl hydrolysate (IH) alleviated FE the inhibition of rice growth. Transcriptome sequencing revealed numerous differentially expressed genes (DEGs) between the two varieties. A total of 31 metabolic enzyme genes related to herbicide detoxification were screened by analyzing the DEGs in different rice varieties or treatments. The results of the quantitative reverse transcription polymerase chain reaction indicated that 12 genes were potential metabolic genes resistant to FE in rice. Additionally, the enhanced expression of GSTU6, DIMBOA UGT BX8, and ABCG39 was confirmed to be induced by safener. Taken together, our results demonstrated that the induced expression of these three genes might be crucial for resistance to herbicide phytotoxicity in crops. These results may help us to understand herbicide metabolism in crops and to develop novel strategies for the safe use of herbicides.
Evaluation of Precision Livestock Technology and Human Scoring of Nursery Pigs in a Controlled Immune Challenge Experiment
Authors: Bortoluzzi Eduarda M. , Goering Mikayla J. , Ochoa Sara J. , Holliday Aaron J. , Mumm Jared M. , Nelson Catherine E. , Wu Hui , Mote Benny E. , Psota Eric T. , Schmidt Ty B. , Jaberi-Douraki Majid , Hulbert Lindsey E.
Published: January 2023

The objectives were to determine the sensitivity, specificity, and cutoff values of a visual-based precision livestock technology (NUtrack), and determine the sensitivity and specificity of sickness score data collected with the live observation by trained human observers. At weaning, pigs (n = 192; gilts and barrows) were randomly assigned to one of twelve pens (16/pen) and treatments were randomly assigned to pens. Sham-pen pigs all received subcutaneous saline (3 mL). For LPS-pen pigs, all pigs received subcutaneous lipopolysaccharide (LPS; 300 μg/kg BW; E. coli O111:B4; in 3 mL of saline). For the last treatment, eight pigs were randomly assigned to receive LPS, and the other eight were sham (same methods as above; half-and-half pens). Human data from the day of the challenge presented high true positive and low false positive rates (88.5% sensitivity; 85.4% specificity; 0.871 Area Under Curve, AUC), however, these values declined when half-and-half pigs were scored (75% sensitivity; 65.5% specificity; 0.703 AUC). Precision technology measures had excellent AUC, sensitivity, and specificity for the first 72 h after treatment and AUC values were >0.970, regardless of pen treatment. These results indicate that precision technology has a greater potential for identifying pigs during a natural infectious disease event than trained professionals using timepoint sampling.
Stress Evaluation of Mouse Husbandry Environments for Improving Laboratory Animal Welfare
Authors: Lee Gwang-Hoon , Kim KilSoo , Jo Woori
Published: January 2023

Animal welfare is recognized as essential for the coexistence of humans and animals. Considering the increased demand and interest in animal welfare, many methods for improving animal welfare are being devised, but which method reduces animal stress has not been scientifically verified. Therefore, reducing animal stress by providing a proper breeding environment and environmental enrichment can be the basis for animal study. In this study, stress levels were assessed based on the mouse-breeding environment. We considered that the higher the body weight and the lower the corticosterone concentration, the lower the stress. According to the results, animals in the individual ventilation cages were determined to have lower serum cortisol concentrations, while the body weight of the animals was increased when in individual ventilation cages compared with individual isolated cages and when providing environmental enrichment compared with group breeding or not providing environmental enrichment. The results provide appropriate guidelines for improving laboratory animal welfare.
Repurposing Antidepressants and Phenothiazine Antipsychotics as Efflux Pump Inhibitors in Cancer and Infectious Diseases
Authors: Rácz Bálint , Spengler Gabriella
Published: January 2023

Multidrug resistance (MDR) is a major obstacle in the therapy of infectious diseases and cancer. One of the major mechanisms of MDR is the overexpression of efflux pumps (EPs) that are responsible for extruding antimicrobial and anticancer agents. EPs have additional roles of detoxification that may aid the development of bacterial infection and the progression of cancer. Therefore, targeting EPs may be an attractive strategy to treat bacterial infections and cancer. The development and discovery of a new drug require a long timeline and may come with high development costs. A potential alternative to reduce the time and costs of drug development is to repurpose already existing drugs. Antidepressants and antipsychotic agents are widely used in clinical practice in the treatment of psychiatric disorders and some somatic diseases. Antidepressants and antipsychotics have demonstrated various beneficial activities that may be utilized in the treatment of infections and cancer. This review aims to provide a brief overview of antibacterial and anticancer effects of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and phenothiazine antipsychotics, while focusing on EPs. However, it should be noted that the antimicrobial activity of a traditionally non-antibiotic drug may have clinical implications regarding dysbiosis and bacterial MDR.
The Role of the Respiratory Microbiome in the Pathogenesis of Aspiration Pneumonia: Implications for Diagnosis and Potential Therapeutic Choices
Authors: Vallianou Natalia G. , Skourtis Alexandros , Kounatidis Dimitris , Margellou Evangelia , Panagopoulos Fotis , Geladari Eleni , Evangelopoulos Angelos , Jahaj Edison
Published: January 2023

Although the lungs were considered to be sterile until recently, the advent of molecular biology techniques, such as polymerase chain reaction, 16 S rRNA sequencing and metagenomics has led to our expanding knowledge of the lung microbiome. These methods may be particularly useful for the identification of the causative agent(s) in cases of aspiration pneumonia, in which there is usually prior administration of antibiotics. The most common empirical treatment of aspiration pneumonia is the administration of broad-spectrum antibiotics; however, this may result in negative cultures from specimens taken from the respiratory tract. Therefore, in such cases, polymerase chain reaction or metagenomic next-generation sequencing may be life-saving. Moreover, these modern molecular methods may assist with antimicrobial stewardship. Based upon factors such as age, altered mental consciousness and recent hospitalization, there is a shift towards the predominance of aerobes, especially Gram-negative bacteria, over anaerobes in aspiration pneumonia. Thus, the therapeutic choices should be expanded to cover multi-drug resistant Gram-negative bacteria in selected cases of aspiration pneumonia.
Carbonic Anhydrase Inhibitors as Novel Antibacterials in the Era of Antibiotic Resistance: Where Are We Now?
Authors: Nocentini Alessio , Capasso Clemente , Supuran Claudiu T.
Published: January 2023

Resistance to antibiotic treatment developed by bacteria in humans and animals occurs when the microorganisms resist treatment with clinically approved antibiotics. Actions must be implemented to stop the further development of antibiotic resistance and the subsequent emergence of superbugs. Medication repurposing/repositioning is one strategy that can help find new antibiotics, as it speeds up drug development phases. Among them, the Zn2+ ion binders, such as sulfonamides and their bioisosteres, are considered the most promising compounds to obtain novel antibacterials, thus avoiding antibiotic resistance. Sulfonamides and their bioisosteres have drug-like properties well-known for decades and are suitable lead compounds for developing new pharmacological agent families for inhibiting carbonic anhydrases (CAs). CAs are a superfamily of metalloenzymes catalyzing the reversible reaction of CO2 hydration to HCO3− and H+, being present in most bacteria in multiple genetic families (α-, β-, γ- and ι-classes). These enzymes, acting as CO2 transducers, are promising drug targets because their activity influences microbe proliferation, biosynthetic pathways, and pathogen persistence in the host. In their natural or slightly modified scaffolds, sulfonamides/sulfamates/sulamides inhibit CAs in vitro and in vivo, in mouse models infected with antibiotic-resistant strains, confirming thus their role in contrasting bacterial antibiotic resistance.
Microbial Resistance to Antibiotics and Biofilm Formation of Bacterial Isolates from Different Carp Species and Risk Assessment for Public Health
Authors: Puvača Nikola , Ljubojević Pelić Dragana , Pelić Miloš , Bursić Vojislava , Tufarelli Vincenzo , Piemontese Luca , Vuković Gorica
Published: January 2023

The aim of this research was to investigate the effects of biofilm on antibiotic resistance of the bacterial isolates present in fish meat and to assess the risk of antibiotic residues for public health. Common carp, silver carp and grass carp fishes were purchased from retail stores for an in vitro biofilm investigation and a drug-resistant pattern determination. In all samples, up to 104 CFU/g of bacteria, such as Escherichia coli, Aeromonas hydrophila, Shewanella putrefaciens, Vibrio spp. and Staphylococcus spp., were observed. Isolates from the samples and their biofilms were subjected to an antibiogram assay using antibiotics such as amoxicillin, ampicillin, cefotaxime, ciprofloxacin, chloramphenicol, gentamicin, streptomycin, tetracycline and trimethoprim. Obtained results showed that some of the isolates were sensitive to antibiotics and some were resistant. Results of LC-MS/MS analysis showed that antibiotics residues were present in fish samples in the range between 4.9 and 199.4 µg/kg, with a total sum of 417.1 µg/kg. Estimated daily intake (EDI) was established to be 0.274 μg/kg of body weight/day for men and 0.332 μg/kg of body weight/day for women, with an acceptable daily intake (ADI) of 8.5 and 7.0 µg/kg of body weight/day for men and women, respectively. The results of the present study, therefore, highlight the safe consumption of fresh fish.
An Overview of the Impact of Bacterial Infections and the Associated Mortality Predictors in Patients with COVID-19 Admitted to a Tertiary Center from Eastern Europe
Authors: Timpau Amalia-Stefana , Miftode Radu-Stefan , Costache Irina-Iuliana , Petris Antoniu Octavian , Miftode Ionela-Larisa , Gheorghe Liliana , Timpau Razvan , Miftode Ioana Diandra , Prepeliuc Cristian Sorin , Coman Ioana , Anton-Paduraru Dana-Teodora , Tuchilus Cristina , Miftode Egidia Gabriela
Published: January 2023

1. Background: Literature data on bacterial infections and their impact on the mortality rates of COVID-19 patients from Romania are scarce, while worldwide reports are contrasting. 2. Materials and Methods: We conducted a unicentric retrospective observational study that included 280 patients with SARS-CoV-2 infection, on whom we performed various microbiological determinations. Based on the administration or not of the antibiotic treatment, we divided the patients into two groups. First, we sought to investigate the rates and predictors of bacterial infections, the causative microbial strains, and the prescribed antibiotic treatment. Secondly, the study aimed to identify the risk factors associated with in-hospital death and evaluate the biomarkers’ performance for predicting short-term mortality. 3. Results: Bacterial co-infections or secondary infections were confirmed in 23 (8.2%) patients. Acinetobacter baumannii was the pathogen responsible for most of the confirmed bacterial infections. Almost three quarters of the patients (72.8%) received empiric antibiotic therapy. Multivariate logistic regression has shown leukocytosis and intensive care unit admission as risk factors for bacterial infections and C-reactive protein, together with the length of hospital stay, as mortality predictors. The ROC curves revealed an acceptable performance for the erythrocyte sedimentation rate (AUC: 0.781), and C-reactive protein (AUC: 0.797), but a poor performance for fibrinogen (AUC: 0.664) in predicting fatal events. 4. Conclusions: This study highlighted the somewhat paradoxical association of a low rate of confirmed infections with a high rate of empiric antibiotic therapy. A thorough assessment of the risk factors for bacterial infections, in addition to the acknowledgment of various mortality predictors, is crucial for identifying high-risk patients, thus allowing a timely therapeutic intervention, with a direct impact on improving patients’ prognosis.
Microbiomes in Acne Vulgaris and Their Susceptibility to Antibiotics in Indonesia: A Systematic Review and Meta-Analysis
Authors: Legiawati Lili , Halim Paulus Anthony , Fitriani Magna , Hikmahrachim Hardya Gustada , Lim Henry W.
Published: January 2023

Hot and humid countries such as Indonesia have a higher prevalence of acne vulgaris (AV). The activity of skin microbes, not only Cutibacterium acnes, contribute to the formation of AV. Topical and oral antibiotics are routinely prescribed to treat AV. As antimicrobial resistance rates increase globally, there are concerns about decreased efficacy. This study intends to systematically evaluate the microbiomes isolated from AV lesions and their antibiotics susceptibility in Indonesia. The data were retrieved through PubMed, EMBASE, Google Scholar, and ScienceDirect searches for articles published until July 2022 using three multiword searches. Sixteen studies published between 2001 and 2022 were identified from which the data were pooled using a random effects model. The pooled prevalence estimates demonstrated that C. acnes, Staphylococcus epidermidis, and Staphylococcus aureus were the three common microbes associated with AV in Indonesia. Tetracyclines had lower resistance rates compared to those of macrolides and clindamycin, with C. acnes showing a resistance rate that is as high as 60.1% against macrolides. C. acnes resistance against minocycline showed an increasing trend, whereas the resistances to doxycycline, clindamycin, and macrolides stagnated. The high resistance prevalence and trends signify a public health concern. The results of this study call for the development of antibiotic stewardship programs in Indonesia, which may lead to improved acne outcomes.
Determinants of Knowledge, Attitude, and Practices of Veterinary Drug Dispensers toward Antimicrobial Use and Resistance in Main Cities of Malawi: A Concern on Antibiotic Stewardship
Authors: Kainga Henson , Phonera Marvin Collen , Chikowe Ibrahim , Chatanga Elisha , Nyirongo Hlupikire , Luwe Mike , Mponela James , Kachisi Vincent , Kamanga Nathani , Chulu Julius , Njunga Gilson , Nabadda Daisy , Fonchin Alyce , Kallu Simegnew Adugna , Mudenda Steward , Tembo Rabecca , Zulu Mildred , Mwaba Florence , Mbewe Natalia , Mpundu Prudence , Samutela Mulemba Tillika , Munyeme Musso , Muma John Bwalya , Simulundu Edgar
Published: January 2023

Antimicrobial resistance (AMR) is an emerging challenge to global public health. The use of antibiotics in the veterinary field is one of the contributing factors to AMR mostly due to poor knowledge, attitudes, and practices (KAP) of dispensers. Veterinary drug dispensers are expected to guide clients on indications, contraindications, and withdrawal periods of veterinary drugs. This study assessed veterinary drug dispensers’ KAP toward AMR and associated potential contributing factors. A cross-sectional study, using a structured questionnaire, was conducted in three main cities of Malawi, namely Mzuzu, Lilongwe, and Blantyre. A total of 68 agrovet shops were selected using a simple random sampling technique. The KAP level was presented descriptively. Bivariate and multivariable analyses were run to investigate the relationships between the independent and outcome variable. Overall, the KAP score for knowledge, attitude, and practices was 46.7%, 49.2%, and 41.6%, respectively. The significant determinants of the knowledge were the practice of asking for a written prescription (OR: 16.291, 95% CI: 11.6–24.2) (p = 0.024), female (OR: 0.609, 95% CI: 0.3–0.9) (p = 0.001), and old age (≥35) (OR: 0.227, 95% CI: 0.1–0.5) (p = 0.04). Poor knowledge, negative attitude, and poor practices were observed among most of the participants. Sensitization and training on AMR and antimicrobial stewardship are recommended to address the KAP score gaps and the observed determinants among veterinary drug dispensers.
Lyophilized Progenitor Tenocyte Extracts: Sterilizable Cytotherapeutic Derivatives with Antioxidant Properties and Hyaluronan Hydrogel Functionalization Effects
Authors: Laurent Alexis , Porcello Alexandre , Jeannerat Annick , Peneveyre Cédric , Coeur Agathe , Abdel-Sayed Philippe , Scaletta Corinne , Michetti Murielle , de Buys Roessingh Anthony , Jordan Olivier , Allémann Eric , Raffoul Wassim , Hirt-Burri Nathalie , Applegate Lee Ann
Published: January 2023

Cultured primary progenitor tenocytes in lyophilized form were previously shown to possess intrinsic antioxidant properties and hyaluronan-based hydrogel viscosity-modulating effects in vitro. The aim of this study was to prepare and functionally characterize several stabilized (lyophilized) cell-free progenitor tenocyte extracts for inclusion in cytotherapy-inspired complex injectable preparations. Fractionation and sterilization methods were included in specific biotechnological manufacturing workflows of such extracts. Comparative and functional-oriented characterizations of the various extracts were performed using several orthogonal descriptive, colorimetric, rheological, mechanical, and proteomic readouts. Specifically, an optimal sugar-based (saccharose/dextran) excipient formula was retained to produce sterilizable cytotherapeutic derivatives with appropriate functions. It was shown that extracts containing soluble cell-derived fractions possessed conserved and significant antioxidant properties (TEAC) compared to the freshly harvested cellular starting materials. Progenitor tenocyte extracts submitted to sub-micron filtration (0.22 µm) and 60Co gamma irradiation terminal sterilization (5–50 kGy) were shown to retain significant antioxidant properties and hyaluronan-based hydrogel viscosity modulating effects. Hydrogel combination products displayed important efficacy-related characteristics (friction modulation, tendon bioadhesivity) with significant (p < 0.05) protective effects of the cellular extracts in oxidative environments. Overall, the present study sets forth robust control methodologies (antioxidant assays, H2O2-challenged rheological setups) for stabilized cell-free progenitor tenocyte extracts. Importantly, it was shown that highly sensitive phases of cytotherapeutic derivative manufacturing process development (purification, terminal sterilization) allowed for the conservation of critical biological extract attributes.
Dynamic Metabolic and Transcriptional Responses of Proteasome-Inhibited Neurons
Authors: Suciu Ilinca , Delp Johannes , Gutbier Simon , Ückert Anna-Katharina , Spreng Anna-Sophie , Eberhard Philipp , Karreman Christiaan , Schreiber Falk , Madjar Katrin , Rahnenführer Jörg , Celardo Ivana , Amelio Ivano , Leist Marcel
Published: January 2023

Proteasome inhibition is associated with parkinsonian pathology in vivo and degeneration of dopaminergic neurons in vitro. We explored here the metabolome (386 metabolites) and transcriptome (3257 transcripts) regulations of human LUHMES neurons, following exposure to MG-132 [100 nM]. This proteasome inhibitor killed cells within 24 h but did not reduce viability for 12 h. Overall, 206 metabolites were changed in live neurons. The early (3 h) metabolome changes suggested a compromised energy metabolism. For instance, AMP, NADH and lactate were up-regulated, while glycolytic and citric acid cycle intermediates were down-regulated. At later time points, glutathione-related metabolites were up-regulated, most likely by an early oxidative stress response and activation of NRF2/ATF4 target genes. The transcriptome pattern confirmed proteostatic stress (fast up-regulation of proteasome subunits) and also suggested the progressive activation of additional stress response pathways. The early ones (e.g., HIF-1, NF-kB, HSF-1) can be considered a cytoprotective cellular counter-regulation, which maintained cell viability. For instance, a very strong up-regulation of AIFM2 (=FSP1) may have prevented fast ferroptotic death. For most of the initial period, a definite life–death decision was not taken, as neurons could be rescued for at least 10 h after the start of proteasome inhibition. Late responses involved p53 activation and catabolic processes such as a loss of pyrimidine synthesis intermediates. We interpret this as a phase of co-occurrence of protective and maladaptive cellular changes. Altogether, this combined metabolomics–transcriptomics analysis informs on responses triggered in neurons by proteasome dysfunction that may be targeted by novel therapeutic intervention in Parkinson’s disease.