bluuebunny/crossref_metadata_2025 huggingface dataset:
Model-Informed Precision Dosing of Antibiotics in Pediatric Patients: A Narrative Review
Authors: Abdulla Alan , Edwina Elma , Flint Robert B. , Allegaert Karel , Wildschut Enno D. , Koch Birgit C. P. , de Hoog Matthijs
Published: February 2021

Optimal pharmacotherapy in pediatric patients with suspected infections requires understanding and integration of relevant data on the antibiotic, bacterial pathogen, and patient characteristics. Because of age-related physiological maturation and non-maturational covariates (e.g., disease state, inflammation, organ failure, co-morbidity, co-medication and extracorporeal systems), antibiotic pharmacokinetics is highly variable in pediatric patients and difficult to predict without using population pharmacokinetics models. The intra- and inter-individual variability can result in under- or overexposure in a significant proportion of patients. Therapeutic drug monitoring typically covers assessment of pharmacokinetics and pharmacodynamics, and concurrent dose adaptation after initial standard dosing and drug concentration analysis. Model-informed precision dosing (MIPD) captures drug, disease, and patient characteristics in modeling approaches and can be used to perform Bayesian forecasting and dose optimization. Incorporating MIPD in the electronic patient record system brings pharmacometrics to the bedside of the patient, with the aim of a consisted and optimal drug exposure. In this narrative review, we evaluated studies assessing optimization of antibiotic pharmacotherapy using MIPD in pediatric populations. Four eligible studies involving amikacin and vancomycin were identified from 418 records. Key articles, independent of year of publication, were also selected to highlight important attributes of MIPD. Although very little research has been conducted until this moment, the available data on vancomycin indicate that MIPD is superior compared to conventional dosing strategies with respect to target attainment. The utility of MIPD in pediatrics needs to be further confirmed in frequently used antibiotic classes, particularly aminoglycosides and beta-lactams.
Emerging Role of MiR-192-5p in Human Diseases
Authors: Ren Fu-jia , Yao Yao , Cai Xiao-yu , Fang Guo-ying
Published: February 2021

MicroRNAs (miRNAs) are a type of small non-coding RNAs that play an essential role in numerous biological processes by regulating the post-transcriptional expression of target genes. Recent studies have demonstrated that miR-192-5p, a member of the miR-192 family, partakes in several human diseases, especially various cancers, including cancers of the lung, liver, and breast. Importantly, the levels of miR-192-5p are abundant in biofluids, including the serum and urine, and the exosomal levels of miR-192-5p in circulation can aid in the diagnosis and prognosis of various diseases, such as chronic hepatitis B (CHB) infection disease. Notably, recent studies suggest that miR-192-5p is regulated by long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there are no comprehensive overviews on the role of miR-192-5p in human diseases. This review discusses the significant studies on the role of miR-192-5p in various human diseases, with special emphasis on the diseases of the respiratory and digestive systems.
The mTORC1/eIF4E/HIF-1α Pathway Mediates Glycolysis to Support Brain Hypoxia Resistance in the Gansu Zokor, Eospalax cansus
Authors: Lin Jinyan , Fan Lele , Han Yuming , Guo Juanjuan , Hao Zhiqiang , Cao Lingna , Kang Jiamin , Wang Xiaoqin , He Jianping , Li Jingang
Published: February 2021

The Gansu zokor (Eospalax cansus) is a subterranean rodent species that is unique to China. These creatures inhabit underground burrows with a hypoxia environment. Metabolic energy patterns in subterranean rodents have become a recent focus of research; however, little is known about brain energy metabolism under conditions of hypoxia in this species. The mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) coordinates eukaryotic cell growth and metabolism, and its downstream targets regulate hypoxia inducible factor-1α (HIF-1α) under conditions of hypoxia to induce glycolysis. In this study, we compared the metabolic characteristics of hypoxia-tolerant subterranean Gansu zokors under hypoxic conditions with those of hypoxia-intolerant Sprague-Dawley rats with a similar-sized surface area. We exposed Gansu zokors and rats to hypoxia I (44 h at 10.5% O2) or hypoxia II (6 h at 6.5% O2) and then measured the transcriptional levels of mTORC1 downstream targets, the transcriptional and translational levels of glycolysis-related genes, glucose and fructose levels in plasma and brain, and the activity of key glycolysis-associated enzymes. Under hypoxia, we found thathif-1α transcription was upregulatedviathe mTORC1/eIF4E pathway to drive glycolysis. Furthermore, Gansu zokor brain exhibited enhanced fructose-driven glycolysis under hypoxia through increased expression of the GLUT5 fructose transporter and ketohexokinase (KHK), in addition to increased KHK enzymatic activity, and utilization of fructose; these changes did not occur in rat. However, glucose-driven glycolysis was enhanced in both Gansu zokor and rat under hypoxia II of 6.5% O2for 6 h. Overall, our results indicate that on the basis of glucose as the main metabolic substrate, fructose is used to accelerate the supply of energy in Gansu zokor, which mirrors the metabolic responses to hypoxia in this species.
Does Exercise Influence the Susceptibility to Arterial Thrombosis? An Integrative Perspective
Authors: Olsen Line Nørregaard , Fischer Mads , Evans Phillip Adrian , Gliemann Lasse , Hellsten Ylva
Published: February 2021

Arterial thrombosis is the primary cause of death worldwide, with the most important risk factors being smoking, unhealthy diet, and physical inactivity. However, although there are clear indications in the literature of beneficial effects of physical activity in lowering the risk of cardiovascular events, exercise can be considered a double-edged sword in that physical exertion can induce an immediate pro-thrombotic environment. Epidemiological studies show an increased risk of cardiovascular events after acute exercise, a risk, which appear to be particularly apparent in individuals with lifestyle-related disease. Factors that cause the increased susceptibility to arterial thrombosis with exercise are both chemical and mechanical in nature and include circulating catecholamines and vascular shear stress. Exercise intensity plays a marked role on such parameters, and evidence in the literature accordingly points at a greater susceptibility to thrombus formation at high compared to light and moderate intensity exercise. Of importance is, however, that the susceptibility to arterial thrombosis appears to be lower in exercise-conditioned individuals compared to sedentary individuals. There is currently limited data on the role of acute and chronic exercise on the susceptibility to arterial thrombosis, and many studies include incomplete assessments of thrombogenic clotting profile. Thus, further studies on the role of exercise, involving valid biomarkers, are clearly warranted.
Sub 3-Hour Marathon Runners for Five Consecutive Decades Demonstrate a Reduced Age-Related Decline in Performance
Authors: Lepers Romuald , Burfoot Amby , Stapley Paul J.
Published: February 2021

Estimation of the age-related decline in athletic performance by analyzing age-group world record performances presents an inherent limitation because the records generally belong to different individuals. Longitudinal studies describing the changes in performance with advancing age for the same individuals with a consistent training regimen are more appropriate to determine age-related changes in performance. The aim of this longitudinal study was to examine the age-related decline in running performance of sub 3-h marathoners for five consecutive calendar decades. The best marathon performances for each decade from the 1970s to the 2010s were analyzed for 40 sub 3-h runners (39 males and 1 female). The cohort mean personal best performance was 2 h 23 min ± 9 min at an age of 28.6 ± 4.7 years. The mean difference in age between the first and the last sub 3-h marathon races was 32.9 ± 1.6 years. The time difference in marathon performance between the personal best and the worst performance during the 5th decade was 26 ± 9 min, corresponding to a mean increase of 1 min 4 s per year, i.e., a decrease in running speed of 0.67 ± 0.29% per year. These results suggest that with consistent training and racing regimens, it is possible to limit the age-related decline in marathon performance to less than 7% per decade at least until 60 years of age. Further studies are required to verify if such a low rate of age-related decline in endurance performance could be maintained after 60 years of age.
Novel and Transgressive Salinity Tolerance in Recombinant Inbred Lines of Rice Created by Physiological Coupling-Uncoupling and Network Rewiring Effects
Authors: Pabuayon Isaiah C. M. , Kitazumi Ai , Cushman Kevin R. , Singh Rakesh Kumar , Gregorio Glenn B. , Dhatt Balpreet , Zabet-Moghaddam Masoud , Walia Harkamal , de los Reyes Benildo G.
Published: February 2021

The phenomenon of transgressive segregation, where a small minority of recombinants are outliers relative to the range of parental phenotypes, is commonly observed in plant breeding populations. While this phenomenon has been attributed to complementation and epistatic effects, the physiological and developmental synergism involved have not been fully illuminated by the QTL mapping approach alone, especially for stress-adaptive traits involving highly complex interactions. By systems-level profiling of the IR29 × Pokkali recombinant inbred population of rice, we addressed the hypothesis that novel salinity tolerance phenotypes are created by reconfigured physiological networks due to positive or negative coupling-uncoupling of developmental and physiological attributes of each parent. Real-time growth and hyperspectral profiling distinguished the transgressive individuals in terms of stress penalty to growth. Non-parental network signatures that led to either optimal or non-optimal integration of developmental with stress-related mechanisms were evident at the macro-physiological, biochemical, metabolic, and transcriptomic levels. Large positive net gain in super-tolerant progeny was due to ideal complementation of beneficial traits while shedding antagonistic traits. Super-sensitivity was explained by the stacking of multiple antagonistic traits and loss of major beneficial traits. The synergism uncovered by the phenomics approach in this study supports the modern views of the Omnigenic Theory, emphasizing the synergy or lack thereof between core and peripheral components. This study also supports a breeding paradigm rooted on genomic modeling from multi-dimensional genetic, physiological, and phenotypic profiles to create novel adaptive traits for new crop varieties of the 21st century.
The Heat Shock Protein 40-Type Chaperone MASH Supports the Endoplasmic Reticulum-Associated Degradation E3 Ubiquitin Ligase MAKIBISHI1 in Medicago truncatula
Authors: Erffelinck Marie-Laure , Ribeiro Bianca , Gryffroy Lore , Rai Avanish , Pollier Jacob , Goossens Alain
Published: February 2021

Jasmonates (JA) are oxylipin-derived phytohormones that trigger the production of specialized metabolites that often serve in defense against biotic stresses. InMedicago truncatula, a JA-induced endoplasmic reticulum-associated degradation (ERAD)-type machinery manages the production of bioactive triterpenes and thereby secures correct plant metabolism, growth, and development. This machinery involves the conserved RING membrane-anchor (RMA)-type E3 ubiquitin ligase MAKIBISHI1 (MKB1). Here, we discovered two additional members of this protein control apparatus via a yeast-based protein–protein interaction screen and characterized their function. First, a cognate E2 ubiquitin-conjugating enzyme was identified that interacts with MKB1 to deliver activated ubiquitin and to mediate its ubiquitination activity. Second, we identified a heat shock protein 40 (HSP40) that interacts with MKB1 to support its activity and was therefore designated MKB1-supporting HSP40 (MASH).MASHexpression was found to be co-regulated with that ofMKB1. The presence of MASH is critical for MKB1 and ERAD functioning because the dramatic morphological, transcriptional, and metabolic phenotype ofMKB1knock-downM. truncatulahairy roots was phenocopied by silencing ofMASH. Interaction was also observed between theArabidopsis thaliana(Arabidopsis) homologs of MASH and MKB1, suggesting that MASH represents an essential and plant-specific component of this vital and conserved eukaryotic protein quality control machinery.
Parental Antecedents of Locus of Control of Reinforcement: A Qualitative Review
Authors: Carton John S. , Ries Mikayla , Nowicki Stephen
Published: February 2021

The construct of locus of control of reinforcement has generated thousands of studies since its introduction as a psychological concept by Julian Rotter (1966). Although evidence indicates its importance for a wide range of outcomes, comparatively little research has been directed toward identification of potential developmental antecedents of internal/external expectancies. A previous review of antecedent findings (Carton and Nowicki, 1994) called for more research to be completed, particularly using observational and/or longitudinal methodologies. The current paper summarizes and evaluates antecedent research published in the intervening years since Carton and Nowicki’s review. Results largely were consistent with expectations based on Rotter’s social learning theory, although there is still a need for researchers to use observational, rather than self-report methodologies, and to include data from non-western cultures.
Lexical Planning in People Who Stutter: A Defect in Lexical Encoding or the Planning Scope?
Authors: Zhao Liming , Lian Miaoqing
Published: February 2021

Developmental stuttering is a widely discussed speech fluency disorder. Research on its mechanism has focused on an atypical interface between the planning (PLAN) and execution (EX) processes, known collectively as the EXPLAN model. However, it remains unclear how this atypical interface influences people who stutter. A straightforward assumption is that stuttering speakers adopt a smaller scope of speech planning, whereas a defect in word retrieval can be confounding. To shed light on this issue, we took the semantic blocking effect as an index to examine lexical planning in word and phrase production. In Experiment 1, for word production, pictures from the same semantic category were combined to form homogeneous blocks, and pictures from different categories were combined to form heterogeneous blocks. A typical effect of semantic blocking showing longer naming latencies for homogeneous blocks than heterogeneous ones was observed for both stuttering and fluent speakers. However, this effect was smaller for stuttering speakers, when it was subject to lexical defects in stuttering. In Experiment 2, for a conjoined noun phrase production task, the pictures referring to the first noun were manipulated into homogeneous and heterogeneous conditions. The semantic blocking effect was also much smaller for stuttering speakers, indicating a smaller scope of lexical planning. Therefore, the results provided more evidence in support of the EXPLAN model and indicated that a smaller scope of lexical planning rather than lexical defects causes the atypical interface for stuttering. Moreover, a comparison between these two tasks showed that the study findings have implications for syntactic defects in stuttering.
Concretization as a Mechanism of Change in Psychodrama: Procedures and Benefits
Authors: Kushnir Aviv , Orkibi Hod
Published: February 2021

Concretization is a concept that has different meanings in different psychological theories and varying manifestations in different psychotherapies. In psychodrama, much of the available information on concretization draws on J. L. Moreno’s initial conceptualization, descriptive case studies, and interpretations in the various approaches. However, concretization has not been empirically studied as a concept or as a therapeutic mechanism of change. Therefore, the purpose of this qualitative study was to generate an empirically based conceptualization and operationalization of concretization as well as to identify its clinical benefits in psychodrama. To this end, semistructured in-depth interviews were conducted with seven experienced psychodrama therapists. Using a grounded theory approach for the data analysis, the model that emerged consists of three pathways toward concretization: realistic concretization, symbolic concretization, and integrated concretization. The findings suggest a sequential multistep operation that can be linear or nonlinear, depending on the protagonist’s need. The findings also underscore four benefits of concretization as a mechanism of change in psychodrama: reducing the ambiguity of the problem, externalizing the protagonist’s problem, enhancing the therapist-protagonist therapeutic bond, and bypassing the protagonist’s defense mechanisms. The model is discussed in light of the findings and the literature, and future directions are suggested.
“It Is Not the Robot Who Learns, It Is Me.” Treating Severe Dysgraphia Using Child–Robot Interaction
Authors: Gargot Thomas , Asselborn Thibault , Zammouri Ingrid , Brunelle Julie , Johal Wafa , Dillenbourg Pierre , Archambault Dominique , Chetouani Mohamed , Cohen David , Anzalone Salvatore M.
Published: February 2021

Writing disorders are frequent and impairing. However, social robots may help to improve children's motivation and to propose enjoyable and tailored activities. Here, we have used the Co-writer scenario in which a child is asked to teach a robot how to write via demonstration on a tablet, combined with a series of games we developed to train specifically pressure, tilt, speed, and letter liaison controls. This setup was proposed to a 10-year-old boy with a complex neurodevelopmental disorder combining phonological disorder, attention deficit/hyperactivity disorder, dyslexia, and developmental coordination disorder with severe dysgraphia. Writing impairments were severe and limited his participation in classroom activities despite 2 years of specific support in school and professional speech and motor remediation. We implemented the setup during his occupational therapy for 20 consecutive weekly sessions. We found that his motivation was restored; avoidance behaviors disappeared both during sessions and at school; handwriting quality and posture improved dramatically. In conclusion, treating dysgraphia using child–robot interaction is feasible and improves writing. Larger clinical studies are required to confirm that children with dysgraphia could benefit from this setup.
A Potential Autophagy-Related Competing Endogenous RNA Network and Corresponding Diagnostic Efficacy in Schizophrenia
Authors: Li Rongjie , Wang Qiaoye , Qiu Yufen , Meng Youshi , Wei Lei , Wang Hao , Mo Ruikang , Zou Donghua , Liu Chunbin
Published: February 2021

Competing endogenous RNA (ceRNA) and autophagy were related to neurological diseases. But the relationship among ceRNA, autophagy and Schizophrenia (SZ) was not clear. In this study, we obtained gene expression profile of SZ patients (GSE38484, GSE54578, and GSE16930) from Gene Expression Omnibus (GEO) database. Then we screened the autophagy-related differentially expressed lncRNA, miRNA, and mRNA (DElncRNA, DEmiRNA, and DEmRNA) combined with Gene database from The National Center for Biotechnology Information (NCBI). In addition, we performed enrichment analysis. The result showed that biological processes (BPs) mainly were associated with cellular responses to oxygen concentration. The enriched pathways mainly included ErbB, AMPK, mTOR signaling pathway and cell cycle. Furthermore, we constructed autophagy-related ceRNA network based on the TargetScan database. Moreover, we explored the diagnostic efficiency of lncRNA, miRNA and mRNA in ceRNA, through gene set variation analysis (GSVA). The result showed that the diagnostic efficiency was robust, especially miRNA (AUC = 0.884). The miRNA included hsa-miR-423-5p, hsa-miR-4532, hsa-miR-593-3p, hsa-miR-618, hsa-miR-4723-3p, hsa-miR-4640-3p, hsa-miR-296-5p, and hsa-miR-3943. The result of this study may be helpful for deepening the pathophysiology of SZ. In addition, our finding may provide a guideline for the clinical diagnosis of SZ.
Root Tonics and Resilience: Building Strength, Health, and Heritage in Jamaica
Authors: Vandebroek Ina , Picking David , Tretina Jessica , West Jason , Grizzle Michael , Sweil Denton , Green Ucal , Lindsay Devon
Published: February 2021

Jamaican root tonics are fermented beverages made with the roots, bark, vines (and dried leaves) of several plant species, many of which are wild-harvested in forest areas of this Caribbean island. These tonics are popular across Jamaica, and also appreciated among the Jamaican diaspora in the United States, Canada, and the United Kingdom. Although plants are the focal point of the ethnobotany of root tonics, interviews with 99 knowledgeable Jamaicans across five parishes of the island, with the goal of documenting their knowledge, perceptions, beliefs, and oral histories, showed that studying these tonics solely from a natural sciences perspective would serve as an injustice to the important sociocultural dimensions and symbolism that surround their use. Jamaican explanations about root tonics are filled with metaphorical expressions about the reciprocity between the qualities of “nature” and the strength of the human body. Furthermore, testimonies about the perceived cultural origins, and reasons for using root tonics, provided valuable insights into the extent of human hardship endured historically during slavery, and the continued struggle experienced by many Jamaicans living a subsistence lifestyle today. On the other hand, the popularity of root tonics is also indicative of the resilience of hard-working Jamaicans, and their quest for bodily and mental strength and health in dealing with socioeconomic and other societal challenges. Half of all study participants considered Rastafari the present-day knowledge holders of Jamaican root tonics. Even though these tonics represent a powerful informal symbol of Jamaican biocultural heritage, they lack official recognition and development for the benefit of local producers and vendors. We therefore used a sustainable development conceptual framework consisting of social, cultural, economic, and ecological pillars, to design a road map for a cottage industry for these artisanal producers. The four steps of this road map (growing production, growing alliances, transitioning into the formal economy, and safeguarding ecological sustainability) provide a starting point for future research and applied projects to promote this biocultural heritage product prepared with Neglected and Underutilized Species (NUS) of plants.
Intraoperative Fascia Tension as an Alternative to Component Separation. A Prospective Observational Study
Authors: Niebuhr Henning , Aufenberg Thomas , Dag Halil , Reinpold Wolfgang , Peiper Christian , Schardey Hans Martin , Renter Marc Alexander , Aly Mohamed , Eucker Dietmar , Köckerling Ferdinand , Eichelter Jakob
Published: February 2021

Incisional hernias are common late complications of abdominal surgery, with a 1-year post-laparotomy incidence of about 20%. A giant hernia is often preceded by severe peritonitis of various causes. The Fasciotens® Abdomen device is used to stretch the fascia in a measurably controlled manner during surgery to achieve primary tension-free abdominal closure. This prospective observational study aims to clarify the extent to which this traction method can function as an alternative to component separation (CS) methods.

Methods: We included data of 21 patients treated with intraoperative fascia stretching in seven specialized hernia centers between November 2019 and August 2020.

Results: Intraoperatively-measured fascial distance averaged 17.3 cm (range 8.5–44 cm). After application of diagonal-anterior traction >10 kg for an average duration of 32.3 min (range 30–40 min), the fascial distance decreased by 9.8 cm (1–26 cm) to an average 7.5 cm (range 2–19 cm), which is a large effect (r = 0.62). The fascial length increase (average 9.8 cm) after applied traction was highly significant. All hernias were closed under moderate tension after the traction phase. In 19 patients, this closure was reinforced with mesh using a sublay technique.

Conclusion: This method allows primary closure of complex (LOD) hernias and is potentially less prone to complications than component separation (CS) methods.
Bovine Abortions Revisited—Enhancing Abortion Diagnostics by 16S rDNA Amplicon Sequencing and Fluorescence in situ Hybridization
Authors: Wolf-Jäckel Godelind Alma , Strube Mikael Lenz , Schou Kirstine Klitgaard , Schnee Christiane , Agerholm Jørgen S. , Jensen Tim Kåre
Published: February 2021

Abortion in cattle causes significant economic losses for cattle farmers worldwide. The diversity of abortifacients makes abortion diagnostics a complex and challenging discipline that additionally is restrained by time and economy. Microbial culture has traditionally been an important method for the identification of bacterial and mycotic abortifacients. However, it comes with the inherent bias of favoring the easy-to-culture species, e.g., those that do not require cell culture, pre-enrichment, a variety of selective growth media, or different oxygen levels for in vitro growth. Molecular methods such as polymerase chain reaction (PCR) and next-generation sequencing have been established as alternatives to traditional microbial culturing methods in several diagnostic fields including abortion diagnostics. Fluorescence in situ hybridization (FISH), a bridging microscopy technique that combines molecular accuracy with culture independence, and spatial resolution of the pathogen-lesion relation, is also gaining influence in several diagnostic fields. In this study, real-time quantitative PCR (qPCR), 16S rDNA amplicon sequencing, and FISH were applied separately and in combination in order to (i) identify potentially abortifacient bacteria without the bias of culturability, (ii) increase the diagnostic rate using combined molecular methods, (iii) investigate the presence of the difficult-to-culture zoonotic agents Coxiella burnetii, Chlamydia spp., and Leptospira spp. in bovine abortions in Denmark. Tissues from 162 aborted or stillborn bovine fetuses and placentas submitted for routine diagnostics were screened for pathogenic bacteria using 16S rDNA amplicon sequencing. Lesion association of fungal elements, as well as of selection of bacterial abortifacients, was assessed using specific FISH assays. The presence of Chlamydia spp. and chlamydia-like organisms was assessed using qPCR. The study focused on bacterial and fungal abortifacients, because Danish cattle is free from most viral abortifacients. The 16S rDNA amplicon sequencing–guided FISH approach was suitable for enhancing abortion diagnostics, i.e., the diagnostic rate for cases with tissue lesions (n = 115) was increased from 46 to 53% when compared to routine diagnostic methods. Identification of Bacillus licheniformis, Escherichia coli, and Trueperella pyogenes accounted for the majority of additional cases with an established etiology. No evidence for emerging or epizootic bacterial pathogens was found. The difficult-to-culture abortifacients were either not detected or not identified as abortifacients.
Oral Immunization of Recombinant Lactococcus lactis and Enterococcus faecalis Expressing Dendritic Cell Targeting Peptide and Hexon Protein of Fowl Adenovirus 4 Induces Protective Immunity Against Homologous Infection
Authors: Jia Zhipeng , Ma Chunli , Yang Xuelian , Pan Xinghui , Li Guangxing , Ma Dexing
Published: February 2021

Hepatitis-hydropericardium syndrome (HPS) causes severe economic losses in the global poultry industry. The present study aims to explore oral immunization of recombinant Lactococcus lactis and Enterococcus faecalis expressing Hexon protein of fowl adenovirus 4 (FAdV-4). The bacteria L. lactis NZ9000 and E. faecalis MDXEF-1 were, respectively, modified as host strain to deliver truncated Hexon protein (ΔHexon) or ΔHexon protein fusing with dendritic cell (DC) targeting peptide (DC-ΔHexon) on the surface of bacteria. The expression of target protein in L. lactis NZ9000 and E. faecalis MDXEF-1 were detected by western blot. To evaluate the immune responses and protective efficacies provided by the live recombinant bacteria, chickens were immunized with the constructed ΔHexon-expressing bacteria three times at 2-week intervals, then experimentally challenged with hypervirulent FAdV-4/GX01. The results showed that oral immunizations with the four ΔHexon-expressing bacteria (NZ9000/ΔHexon-CWA, NZ9000/DC-ΔHexon-CWA, MDXEF-1/ΔHexon-CWA, and MDXEF-1/DC-ΔHexon-CWA), especially the two bacteria carrying DC-targeting peptide, stimulated higher levels of ΔHexon-specific sera IgG and secretory IgA (sIgA) in jejunal lavage fluid, higher proliferation of peripheral blood lymphocytes (PBLs) and higher levels of Th1/Th2-type cytokines, along with significantly decreased virus loads in liver and more offered protective efficacies against FAdV infection compared with PBS and empty vector control groups (p < 0.01). For chickens in the group MDXEF-1/DC-ΔHexon-CWA, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in sera, and the virus loads in livers were significantly decreased vs. the other three ΔHexon-expressing bacteria (p < 0.01). The pathological changes in the hearts, livers, spleens and kidneys of chickens in MDXEF-1/DC-ΔHexon-CWA group were relatively slight compared to infection control group and other three ΔHexon-expressing bacteria groups. The rate of protection in MDXEF-1/DC-ΔHexon-CWA group was 90%. The present work demonstrated that cell surface-displayed target protein and immune enhancers in L. lactis and E. faecalis might be a promising approach to enhance immunity and immune efficacy against pathogen FAdV-4 infection.
A Multi-Disciplinary Approach to Assess the Welfare Impacts of a New Virtual Fencing Technology
Authors: Lee Caroline , Campbell Dana L. M.
Published: February 2021

Virtual fencing involving the application of audio cues and electrical stimuli is being commercially developed for cattle. Virtual fencing has the potential to improve productivity through optimized pasture management and utilization by grazing animals. The application of virtual fencing initiates public concern for the potential welfare impacts on animals due the aversive nature of using an electrical stimulus. It is therefore important to provide welfare assurance of the impacts of virtual fencing on livestock. In this paper, we provide an overview of the welfare assessment and validation stages for virtual fencing which could be applied to other new technologies utilizing novel systems. An understanding of stress measures and their suitability for use in specific contexts is discussed, including the use of glucocorticoids to measure both acute and chronic stress, and behavioral responses and patterns to indicate welfare states. The importance of individual differences in relation to learning and cognition are also highlighted. Together, this multi-disciplinary approach to welfare assessment provides a tool kit that may be applied for welfare assurance of some new technologies and systems for farm animals.
Oil Palm Tree Detection and Health Classification on High-Resolution Imagery Using Deep Learning
Authors: Yarak Kanitta , Witayangkurn Apichon , Kritiyutanont Kunnaree , Arunplod Chomchanok , Shibasaki Ryosuke
Published: February 2021

Combining modern technology and agriculture is an important consideration for the effective management of oil palm trees. In this study, an alternative method for oil palm tree management is proposed by applying high-resolution imagery, combined with Faster-RCNN, for automatic detection and health classification of oil palm trees. This study used a total of 4172 bounding boxes of healthy and unhealthy palm trees, constructed from 2000 pixel × 2000 pixel images. Of the total dataset, 90% was used for training and 10% was prepared for testing using Resnet-50 and VGG-16. Three techniques were used to assess the models’ performance: model training evaluation, evaluation using visual interpretation, and ground sampling inspections. The study identified three characteristics needed for detection and health classification: crown size, color, and density. The optimal altitude to capture images for detection and classification was determined to be 100 m, although the model showed satisfactory performance up to 140 m. For oil palm tree detection, healthy tree identification, and unhealthy tree identification, Resnet-50 obtained F1-scores of 95.09%, 92.07%, and 86.96%, respectively, with respect to visual interpretation ground truth and 97.67%, 95.30%, and 57.14%, respectively, with respect to ground sampling inspection ground truth. Resnet-50 yielded better F1-scores than VGG-16 in both evaluations. Therefore, the proposed method is well suited for the effective management of crops.
Insufficient Stability of Clavulanic Acid in Widely Used Child-Appropriate Formulations
Authors: Mack Ines , Sharland Mike , Brussee Janneke M. , Rehm Sophia , Rentsch Katharina , Bielicki Julia
Published: February 2021

Amoxicillin-clavulanic acid (AMC) belongs to the WHO Essential Medicines List for children, but for optimal antimicrobial effectiveness, reconstituted dry powder suspensions need to be stored in a refrigerated environment. Many patients in low- and middle-income countries who are sold AMC suspensions would be expected not to keep to the specified storage conditions. We aimed to assess the stability of both ingredients in liquid formulations and dispersible tablets, combined with nationally representative data on access to appropriate storage. Degradation of amoxicillin (AMX) and clavulanic-acid (CLA) was measured in suspensions and dispersible tablets commercially available in Switzerland at different ambient temperatures (8 °C vs. 28 °C over 7 days, and 23 °C vs. 28 °C over 24 h, respectively). Data on access to refrigeration and electricity were assessed from the USAID-funded Demographic and Health Survey program. In suspensions, CLA degraded to a maximum of 12.9% (95% CI −55.7%, +29.9%) at 8°C and 72.3% (95% CI −82.8%, −61.8%) at a 28 °C ambient temperature during an observation period of 7 days. Dispersible tablets were observed during 24 h and CLA degraded to 15.4% (95% CI −51.9%, +21.2%) at 23 °C and 21.7% (−28.2%, −15.1%) at a 28 °C ambient temperature. There is relevant degradation of CLA in suspensions during a 7-day course. To overcome the stability challenges for all active components, durable child-appropriate formulations are needed. Until then, prescribers of AMC suspensions or pharmacists who sell the drug need to create awareness for the importance of proper storage conditions regarding effectiveness of both antibiotics and this recommendation should be reflected in the WHO Essential Medicines List for children.
Oxidatively Modified LDL Suppresses Lymphangiogenesis via CD36 Signaling
Authors: Singla Bhupesh , Lin Hui-Ping , Ahn WonMo , White Joseph , Csányi Gábor
Published: February 2021

Arterial accumulation of plasma-derived LDL and its subsequent oxidation contributes to atherosclerosis. Lymphatic vessel (LV)-mediated removal of arterial cholesterol has been shown to reduce atherosclerotic lesion formation. However, the precise mechanisms that regulate LV density and function in atherosclerotic vessels remain to be identified. The aim of this study was to investigate the role of native LDL (nLDL) and oxidized LDL (oxLDL) in modulating lymphangiogenesis and underlying molecular mechanisms. Western blotting and immunostaining experiments demonstrated increased oxLDL expression in human atherosclerotic arteries. Furthermore, elevated oxLDL levels were detected in the adventitial layer, where LV are primarily present. Treatment of human lymphatic endothelial cells (LEC) with oxLDL inhibited in vitro tube formation, while nLDL stimulated it. Similar results were observed with Matrigel plug assay in vivo. CD36 deletion in mice and its siRNA-mediated knockdown in LEC prevented oxLDL-induced inhibition of lymphangiogenesis. In addition, oxLDL via CD36 receptor suppressed cell cycle, downregulated AKT and eNOS expression, and increased levels of p27 in LEC. Collectively, these results indicate that oxLDL inhibits lymphangiogenesis via CD36-mediated regulation of AKT/eNOS pathway and cell cycle. These findings suggest that therapeutic blockade of LEC CD36 may promote arterial lymphangiogenesis, leading to increased cholesterol removal from the arterial wall and reduced atherosclerosis.
The Changes of Leaf Reflectance Spectrum and Leaf Functional Traits of Osmanthus fragrans Are Related to the Parasitism of Cuscuta japonica
Authors: Zhu Jiyou , Xu Qing , Yao Jiangming , Zhang Xinna , Xu Chengyang
Published: February 2021

Studies on the influence of parasitism on plants based on hyperspectral analysis have not been reported so far. To fully understand the variation characteristics and laws of leaf reflectance spectrum and functional traits after the urban plant parasitized by Cuscuta japonica Choisy. Osmanthus fragrans (Thunb.) Lour. was taken as the research object to analyze the spectral reflectance and functional traits characteristics at different parasitical stages. Results showed that the spectral reflectance was higher than those being parasitized in the visible and near-infrared range. The spectral reflectance in 750~1400 nm was the sensitive range of spectral response of host plant to parasitic infection, which is universal at different parasitic stages. We established a chlorophyll inversion model (y = −65913.323x + 9.783, R2 = 0.6888) based on the reflectance of red valley, which can be used for chlorophyll content of the parasitic Osmanthus fragrans. There was a significant correlation between spectral parameters and chlorophyll content index. Through the change of spectral parameters, we can predict the chlorophyll content of Osmanthus fragrans under different parasitic degrees. After being parasitized, the leaf functional traits of host plant were generally characterized by large leaf thickness, small leaf area, small specific leaf area, low relative chlorophyll content, high leaf dry matter content and high leaf tissue density. These findings indicate that the host plant have adopted a certain trade-off strategy to maintain their growth in the invasion environment of parasitic plants. Therefore, we suspect that the leaf economics spectrum may also exist in the parasitic environment, and there was a general trend toward the “slow investment-return” type in the global leaf economics spectrum.
In Silico Validation of MCID Platform for Monte Carlo-Based Voxel Dosimetry Applied to 90Y-Radioembolization of Liver Malignancies
Authors: Milano Alessia , Gil Alex Vergara , Fabrizi Enrico , Cremonesi Marta , Veronese Ivan , Gallo Salvatore , Lanconelli Nico , Faccini Riccardo , Pacilio Massimiliano
Published: February 2021

The aim was the validation of a platform for internal dosimetry, named MCID, based on patient-specific images and direct Monte Carlo (MC) simulations, for radioembolization of liver tumors with 90Y-labeled microspheres. CT of real patients were used to create voxelized phantoms with different density and activity maps. SPECT acquisitions were simulated by the SIMIND MC code. Input macros for the GATE/Geant4 code were generated by MCID, loading coregistered morphological and functional images and performing image segmentation. The dosimetric results obtained from the direct MC simulations and from conventional MIRD approach at both organ and voxel level, in condition of homogeneous tissues, were compared, obtaining differences of about 0.3% and within 3%, respectively, whereas differences increased (up to 14%) introducing tissue heterogeneities in phantoms. Mean absorbed dose for spherical regions of different sizes (10 mm ≤ r ≤ 30 mm) from MC code and from OLINDA/EXM were also compared obtaining differences varying in the range 7–69%, which decreased to 2–9% after correcting for partial volume effects (PVEs) from imaging, confirming that differences were mostly due to PVEs, even though a still high difference for the smallest sphere suggested possible source description mismatching. This study validated the MCID platform, which allows the fast implementation of a patient-specific GATE simulation, avoiding complex and time-consuming manual coding. It also points out the relevance of personalized dosimetry, accounting for inhomogeneities, in order to avoid absorbed dose misestimations.
DMSO Improves the Ski-Slope Effect in Direct PCR
Authors: Kim Joo-Young , Jung Ju Yeon , Kim Da-Hye , Moon Seohyun , Lee Won-Hae , Chun Byung-Won , Choi Dong-Ho
Published: February 2021

Analytical techniques such as DNA profiling are widely used in various fields, including forensic science, and novel technologies such as direct polymerase chain reaction (PCR) amplification are continuously being developed in order to acquire DNA profiles efficiently. However, non-specific amplification may occur depending on the quality of the crime scene evidence and amplification methods employed. In particular, the ski-slope effect observed in direct PCR amplification has led to inaccurate interpretations of the DNA profile results. In this study, we aimed to reduce the ski-slope effect by using dimethyl sulfoxide (DMSO) in direct PCR. We confirmed that DMSO (3.75%, v/v) increased the amplification yield of large-sized DNA sequences more than that of small-sized ones. Using 50 Korean buccal samples, we further demonstrated that DMSO reduced the ski-slope effect in direct PCR. These results suggest that the experimental method developed in this study is suitable for direct PCR and may help to successfully obtain DNA profiles from various types of evidence at crime scenes.
Category-Theoretic Formulation of the Model-Based Systems Architecting Cognitive-Computational Cycle
Authors: Mordecai Yaniv , Fairbanks James P. , Crawley Edward F.
Published: February 2021

We introduce the Concept→Model→Graph→View Cycle (CMGVC). The CMGVC facilitates coherent architecture analysis, reasoning, insight, and decision making based on conceptual models that are transformed into a generic, robust graph data structure (GDS). The GDS is then transformed into multiple views of the model, which inform stakeholders in various ways. This GDS-based approach decouples the view from the model and constitutes a powerful enhancement of model-based systems engineering (MBSE). The CMGVC applies the rigorous foundations of Category Theory, a mathematical framework of representations and transformations. We show that modeling languages are categories, drawing an analogy to programming languages. The CMGVC architecture is superior to direct transformations and language-coupled common representations. We demonstrate the CMGVC to transform a conceptual system architecture model built with the Object Process Modeling Language (OPM) into dual graphs and a stakeholder-informing matrix that stimulates system architecture insight.
Optimizing a Reverse Supply Chain Network for Electronic Waste under Risk and Uncertain Factors
Authors: Doan Linh Thi Truc , Amer Yousef , Lee Sang-Heon , Phuc Phan Nguyen Ky , Tran Tham Thi
Published: February 2021

Minimizing the impact of electronic waste (e-waste) on the environment through designing an effective reverse supply chain (RSC) is attracting the attention of both industry and academia. To obtain this goal, this study strives to develop an e-waste RSC model where the input parameters are fuzzy and risk factors are considered. The problem is then solved through crisp transformation and decision-makers are given the right to choose solutions based on their satisfaction. The result shows that the proposed model provides a practical and satisfactory solution to compromise between the level of satisfaction of constraints and the objective value. This solution includes strategic and operational decisions such as the optimal locations of facilities (i.e., disassembly, repairing, recycling facilities) and the flow quantities in the RSC.
Robust Long-Term Visual Object Tracking via Low-Rank Sparse Learning for Re-Detection
Authors: Luo Shanshan , Li Baoqing , Yuan Xiaobing , Liu Huawei
Published: February 2021

The Discriminative Correlation Filter (DCF) has been universally recognized in visual object tracking, thanks to its excellent accuracy and high speed. Nevertheless, these DCF-based trackers perform poorly in long-term tracking. The reasons include the following aspects—first, they have low adaptability to significant appearance changes in long-term tracking and are prone to tracking failure; second, these trackers lack a practical re-detection module to find the target again after tracking failure. In our work, we propose a new long-term tracking strategy to solve these issues. First, we make the best of the static and dynamic information of the target by introducing the motion features to our long-term tracker and obtain a more robust tracker. Second, we introduce a low-rank sparse dictionary learning method for re-detection. This re-detection module can exploit a correlation among these training samples and alleviate the impact of occlusion and noise. Third, we propose a new reliability evaluation method to model an adaptive update, which can switch expediently between the tracking module and the re-detection module. Massive experiments demonstrate that our proposed approach has an obvious improvement in precision and success rate over these state-of-the-art trackers.
Effects of Tooth Surface Crack Propagation on Meshing Stiffness and Vibration Characteristic of Spur Gear System
Authors: Yang Lan-tao , Shao Yi-min , Jiang Wei-wei , Zhang Lu-ke , Wang Li-ming , Xu Jin
Published: February 2021

Tooth surface cracks are considered as the early stage of the development of tooth surface spalling failure. Understanding the excitation mechanism of surface cracks has a great significance in the early diagnosis of spalling faults. However, there are few studies on the dynamic modelling of surface cracks, and the influence mechanism of surface cracking on the dynamic characteristics of a gear system is also not yet clear during its propagation process. Thus, an analytical calculation model of the meshing stiffness of gear with tooth surface crack is developed. Then, a dynamic model of a spur gear system with six degrees of freedom (DOF) is established based on the proposed surface crack calculation model. The effects of surface crack propagation on the meshing stiffness and dynamic characteristics of gear system are investigated. The results show that the side frequencies of dynamic transmission error (DTE) are more sensitive than those of the acceleration responses during the surface crack propagation, which is more favorable to the surface crack fault diagnosis. Compared to the traditional spalling fault model, the proposed model can accurately characterize the dynamic characteristics of a gear system with the early spalling defect.