bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Dietary Indole-3-Acetate Sodium on Laying Performance, Egg Quality, Serum Hormone Levels and Biochemical Parameters of Danzhou Chickens
Authors: Chen Linlin , Xia Jun , Wang Lei , Wang Zhaobin , Mou Qi , Zhong Yan , Li Yali , Wang Qiye , Huang Jing , Huang Pengfei , Yang Huansheng
Published: February 2021

This study was conducted to investigate the effects of indole-3-acetate sodium (IAA-Na) inclusion in diets on the egg production performance, egg quality, intestinal tissue morphology, serum hormone levels and biochemical parameters of Danzhou chickens to preliminarily explore the efficacy of IAA-Na as a feed additive. A total of 192 Danzhou chickens (50 weeks old) were randomly assigned to 2 groups of 96. The diets for the treatment group consisted of the basal diets, supplemented with IAA-Na (200 mg/kg). The formal feeding trial lasted for four weeks. The results showed that the feed supplemented with IAA-Na not only increased the laying rate (p < 0.05) and egg yolk ratio (0.05 < p < 0.1), but also significantly reduced the feed:egg ratio (p < 0.05). In addition, the dietary supplementation of IAA-Na significantly increased the serum estradiol levels (p < 0.05) and decreased serum alkaline phosphatase activity (p < 0.05). Compared with the control group, the addition of IAA-Na to the diet had no significant effect on the intestinal tissue morphology or serum antioxidant capacity of Danzhou chickens. This study preliminarily provides evidence that dietary IAA-Na can improve laying performance, indicating that IAA-Na is a potentially effective feed additive for laying hens, but further studies are required before arriving at definite conclusions.
The Reported Use of Tongue-Ties and Nosebands in Thoroughbred and Standardbred Horse Racing—A Pilot Study
Authors: Weller Dominic , Franklin Samantha , White Peter , Shea Glenn , Fenner Kate , Wilson Bethany , Wilkins Cristina , McGreevy Paul
Published: February 2021

This article reports on the results of a survey of racehorse trainers (n = 112) outlining the reasons for tongue-tie (TT) and noseband (NB) use by Thoroughbred trainers (TBTs) (n = 72) and Standardbred trainers (SBTs) (n = 40). The study also investigated the reported effectiveness of TTs and possible complications arising from their use. Tongue-tie use was reported by 62.5% (n = 70) of racehorse trainers. The reasons for TT use varied between TBTs and SBTs. For TBTs, the most common reason for TT use was to prevent or reduce airway obstruction (72.3%, n = 34), followed closely by to prevent or reduce airway noise (55.3%, n = 16). Standardbred trainers assigned equal importance for TT use [to prevent or reduce airway obstruction (69.6%, n = 16) and to prevent the horse from moving its tongue over the bit (69.6%, n = 16)]. Tongue-ties were considered significantly less effective at improving performance than at reducing airway obstruction and preventing the tongue from moving over the bit (t = −2.700, p = 0.0007). For respondents who used both TTs and NBs, there was a mild to moderate positive association between the reasons for using TTs and NBs. Of the 70 TT-using respondents, 51.4% (n = 36) recorded having encountered either a physical or behavioural complication due to TT use, with redness/bruising of the tongue (20.0%, n = 14) being the most common physical complication reported. Duration of use influenced the risk of observing complications. The likelihood of a respondent reporting a behavioural complication due to TT use increased with every minute of reported application and a nine-minute increment in application period doubled the odds of a respondent reporting a complication. Tightness was a risk factor for physical complications: Checking TT tightness by noting the tongue as not moving was associated with increased reporting of physical complications (OR = 6.59; CI 1.1–67.5). This pilot study provides some insight into how and why TTs are applied by some racehorse trainers, and the potential risks associated with their use. A further study of a larger cohort is recommended because these results are valid for only the 112 trainers who responded and cannot be generalized to the equine industry.
Relationship between Bone Quality, Egg Production and Eggshell Quality in Laying Hens at the End of an Extended Production Cycle (105 Weeks)
Authors: Alfonso-Carrillo Clara , Benavides-Reyes Cristina , de los Mozos Jon , Dominguez-Gasca Nazaret , Sanchez-Rodríguez Estefanía , Garcia-Ruiz Ana Isabel , Rodriguez-Navarro Alejandro B.
Published: February 2021

(1) Background: Nowadays the industry aims to improve lay persistency for extended cycles (100 weeks or longer) to make egg production more sustainable. However, intensive egg production challenges hen health, inducing severe osteoporosis and the incidence of bone fractures. In this study, the relationship between bone quality and egg production, and/or eggshell quality, was evaluated at the end of an extended laying cycle of 100 weeks, comparing groups of hens with different production and eggshell quality parameters; (2) Methods: Quality parameters of egg (as weight, egg white height), eggshell (as thickness, weight, breaking strength, elasticity and microstructure) and tibiae bone (weight, diameter, cortical thickness, ash weight, breaking strength, medullary bone) were determined; (3) Results: Hens from groups with a high egg production and good eggshell quality have poorer bone quality (lower ash weight and lesser amount of medullary bone). However, Pearson’s correlation analysis shows no clear relationship between bone and egg/eggshell parameters. (4) Conclusions: Bone and egg production/eggshell quality are independent and can be improved separately. Medullary bone has an important contribution to bone mechanical properties, being important to accumulate enough bone medullary bone early in life to maintain skeletal integrity and eggshell quality in old hens.
Comparative Transcriptome Profile between Iberian Pig Varieties Provides New Insights into Their Distinct Fat Deposition and Fatty Acids Content
Authors: Villaplana-Velasco Ana , Noguera Jose Luis , Pena Ramona Natacha , Ballester Maria , Muñoz Lourdes , González Elena , Tejeda Juan Florencio , Ibáñez-Escriche Noelia
Published: February 2021

The high deposition of intramuscular fat and the content of oleic fatty acid are characteristic of the Iberian pig. These two parameters present great variability and are differentiated amongst the varieties that make up the Iberian pig population. Although previous studies generated evidence for causal genes and polymorphisms associated to the adipogenic potential of the Iberian pig, there is little information about how genetic expression influences this trait’s variability. The aim of this study was to analyses the expression profile between two varieties of Iberian pig (Torbiscal and Retinto) and their reciprocal crosses differentiated in their intramuscular fat (IMF) content and fatty acid (FA) composition in the Longissimus thoracis muscle using an RNA-seq approach. Our results corroborate that the Retinto variety is the fattiest amongst all studied varieties as its upregulated genes, such as FABP3 and FABP5, SLC27A1 and VEGFA among others, contribute to increasing adiposity. In its turn, Torbiscal pigs showed an upregulation of genes associated with the inhibition of fat deposition such as ADIPOQ and CPT1A. Further genetic variation analysis in these Iberian varieties showed relevant associations for SNP located within the differentially expressed genes with IMF and FA content. Thus, the differences found in the genetic architecture and the muscle transcriptome of these Iberian varieties might explain the variability in their fat content and composition and hence, their meat quality.
Effects of Resistance Training on the Redox Status of Skeletal Muscle in Older Adults
Authors: Mesquita Paulo H. C. , Lamb Donald A. , Godwin Joshua S. , Osburn Shelby C. , Ruple Bradley A. , Moore Johnathon H. , Vann Christopher G. , Huggins Kevin W. , Fruge Andrew D. , Young Kaelin C. , Kavazis Andreas N. , Roberts Michael D.
Published: February 2021

The aim of this study was to investigate the effects of resistance training (RT) on the redox status of skeletal muscle in older adults. Thirteen males aged 64 ± 9 years performed full-body RT 2x/week for 6 weeks. Muscle biopsies were obtained from the vastus lateralis prior to and following RT. The mRNA, protein, and enzymatic activity levels of various endogenous antioxidants were determined. In addition, skeletal muscle 4-hydroxynonenal and protein carbonyls were determined as markers of oxidative damage. Protein levels of heat shock proteins (HSPs) were also quantified. RT increased mRNA levels of all assayed antioxidant genes, albeit protein levels either did not change or decreased. RT increased total antioxidant capacity, catalase, and glutathione reductase activities, and decreased glutathione peroxidase activity. Lipid peroxidation also decreased and HSP60 protein increased following RT. In summary, 6 weeks of RT decreased oxidative damage and increased antioxidant enzyme activities. Our results suggest the older adult responses to RT involve multi-level (transcriptional, post-transcriptional, and post-translational) control of the redox status of skeletal muscle.
Physiological and Biochemical Dissection Reveals a Trade-Off between Antioxidant Capacity and Heat Tolerance in Bread Wheat (Triticum aestivum L.)
Authors: Mohi-Ud-Din Mohammed , Siddiqui Nurealam , Rohman Motiar , Jagadish S. V. Krishna , Ahmed Jalal Uddin , Hassan Mohamed M. , Hossain Akbar , Islam Tofazzal
Published: February 2021

Heat stress alters photosynthetic components and the antioxidant scavenging system, negatively affecting plant growth and development. Plants overcome heat stress damage through an integrated network involving enzymatic and non-enzymatic antioxidants. This study aimed to assess physiological and biochemical responses in contrasting thermo-tolerant wheat varieties exposed to 25 °C (control) and 35 °C (heat stress), during the seedling stage. Our results revealed a substantial decrease in the photosynthetic pigments, carotenoids, anthocyanin content, and increased membrane injury index, malondialdehyde, methylglyoxal (MG), H2O2 contents and lipoxygenase activity compared to non-stress wheat seedlings. The heat-tolerant variety BARI Gom 26 (“BG26”) maintained higher cellular homeostasis compared to the heat susceptible variety Pavon 76 (“Pavon”), perpetuated by higher accumulation of proline, glycine betaine, ascorbate-glutathione cycle associated enzymes, reduced glutathione and ascorbate concentration in plant cells. Significantly lower levels of MG detoxification and antioxidant activities and ascorbate-glutathione cycle-related enzymatic activities lead to increased susceptibility in variety “Pavon”. Hierarchical clustering and principal component analysis revealed that variety “BG26” possess a combination of biochemical responses tailoring antioxidant activities that induced a higher level of tolerance. Taken together, our results provide a pipeline for establishing a trade-off between antioxidant capacity and heat tolerance to facilitate functional genomics and translational research to unravel underlying mechanisms to better adapt wheat to heat stress.
Antiproliferative and Antimicrobial Activity of Anthocyanins from Berry Fruits after Their Isolation and Freeze-Drying
Authors: Salamon Ivan , Şimşek Sezer Ela Nur , Kryvtsova Maryna , Labun Pavol
Published: February 2021

Natural phytonutrients in foods, including anthocyanins, can play an important role in human health. Anthocyanins have been reported to cause many various useful effects, such as reducing cancer cell proliferation, regulating blood pressure, preventing tumor formation, and preventing diabetes. In this study, we aimed to reveal the qualitative anthocyanin content, antiproliferative and antimicrobial effects of different extracts derived from Vaccinium myrtillus, Vaccinium corymbosum, Sambucus nigra and Aronia melanocarpa. The anthocyanin content of the plants mentioned in the study was characterized after the freeze-drying process. MTT assay was chosen to determine the antiproliferative effect of extracts on colorectal cancer cells. Antimicrobial effects of extracts were studied on typical and clinical strains of five different bacteria. As a result, it was determined that the anthocyanin content in the extracts obtained by the freeze-drying method was acceptable, and some extracts were found to have a strong antiproliferative effect on colorectal cancer cells and have an antibacterial effect on typical and clinical strains. Conclusionally, it has been shown that anthocyanins, which are reported to have many beneficial effects, are very promising when prepared with a relatively new method, and this study is a pioneer study for possible future pharmacological and in vivo studies.
Approximation of the Fixed Point for Unified Three-Step Iterative Algorithm with Convergence Analysis in Busemann Spaces
Authors: Almusawa Hassan , Hammad Hasanen A. , Sharma Nisha
Published: February 2021

In this manuscript, a new three-step iterative scheme to approximate fixed points in the setting of Busemann spaces is introduced. The proposed algorithms unify and extend most of the existing iterative schemes. Thereafter, by making consequent use of this method, strong and Δ-convergence results of mappings that satisfy the condition (Eμ) in the framework of uniformly convex Busemann space are obtained. Our results generalize several existing results in the same direction.
Peptidylarginine Deiminase (PAD) and Post-Translational Protein Deimination—Novel Insights into Alveolata Metabolism, Epigenetic Regulation and Host–Pathogen Interactions
Authors: Kristmundsson Árni , Erlingsdóttir Ásthildur , Lange Sigrun
Published: February 2021

The alveolates (Superphylum Alveolata) comprise a group of primarily single-celled eukaryotes that have adopted extremely diverse modes of nutrition, such as predation, photoautotrophy and parasitism. The alveolates consists of several major phyla including the apicomplexans, a large group of unicellular, spore forming obligate intracellular parasites, and chromerids, which are believed to be the phototrophic ancestors of the parasitic apicomplexans. Molecular pathways involved in Alveolata host–pathogen interactions, epigenetic regulation and metabolism in parasite development remain to be fully understood. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination, affecting protein function through the conversion of arginine to citrulline in a wide range of target proteins, contributing to protein moonlighting in physiological and pathological processes. The identification of deiminated protein targets in alveolate parasites may therefore provide novel insight into pathogen survival and host-pathogen interactions. The current study assessed PAD homologues and deiminated protein profiles of two alveolate parasites, Piridium sociabile (Chromerida) and Merocystis kathae (Apicomplexa). Histological analysis verified strong cytoplasmic PAD expression in both Alveolates, detected deiminated proteins in nuclear and cytoplasmic compartments of the alveolate parasites and verified the presence of citrullinated histone H3 in Alveolata nucleus, indicating roles in epigenetic regulation. Histone H3 citrullination was also found significantly elevated in the host tissue, indicative of neutrophil extracellular trap formation, a host-defence mechanism against a range of pathogens, particularly those that are too large for phagocytosis. Proteomic analysis of deiminated proteins from both Alveolata identified GO and KEGG pathways strongly relating to metabolic and genetic regulation, with some species-specific differences between the apicomplexan and the chromerid. Our findings provide novel insights into roles for the conserved PAD/ADI enzyme family in the regulation of metabolic and epigenetic pathways in alveolate parasites, possibly also relating to their life cycle and host–pathogen interactions.
The Role of Surface Chemistry and Polyethylenimine Grafting in the Removal of Cr (VI) by Activated Carbons from Cashew Nut Shells
Authors: Smith Victoria A. , Rivera Juster F. A. , Bello Ruby , Rodríguez-Aguado Elena , Elshaer Mohammed R. , Wodzinski Rebecca L. , Bashkova Svetlana
Published: February 2021

Activated carbons prepared from cashew nut shells and modified by grafting polyethylenimine onto the surface were tested for removal of Cr (VI). The removal efficiency of carbons without and with polyethylenimine decreased with an increase in pH, with maximum efficiency found at pH 2. The average maximum adsorption capacities of carbons were calculated to be 340 ± 20 mg/g and 320 ± 20 mg/g for unmodified and modified carbons, respectively. Surface characterization of carbons revealed that C–O functionalities are actively involved in both polyethylenimine grafting and Cr (VI) removal. Moreover, lactone groups and amides, formed by polyethylenimine grafting, seemingly undergo acid hydrolysis with formation of phenol and carboxylic groups. Considering that Cr (III) is the only form of chromium found on the surface of both carbons, the reduction mechanism is deduced as the predominant one. Here Cr (VI), majorly present as HCrO4¯, is attracted to the positively charged carbon surface, reduced to Cr (III) by phenol groups, and adsorbed inside the pores. The mechanism of Cr (VI) removal appears to be similar for unmodified and modified carbons, where the smaller adsorption capacity of the latter one can be related to steric hindrance and pore inaccessibility.
Cancer-Associated Fibroblasts as a Common Orchestrator of Therapy Resistance in Lung and Pancreatic Cancer
Authors: Domen Andreas , Quatannens Delphine , Zanivan Sara , Deben Christophe , Van Audenaerde Jonas , Smits Evelien , Wouters An , Lardon Filip , Roeyen Geert , Verhoeven Yannick , Janssens Annelies , Vandamme Timon , van Dam Peter , Peeters Marc , Prenen Hans
Published: February 2021

Cancer arises from mutations accruing within cancer cells, but the tumor microenvironment (TME) is believed to be a major, often neglected, factor involved in therapy resistance and disease progression. Cancer-associated fibroblasts (CAFs) are prominent and key components of the TME in most types of solid tumors. Extensive research over the past decade revealed their ability to modulate cancer metastasis, angiogenesis, tumor mechanics, immunosuppression, and drug access through synthesis and remodeling of the extracellular matrix and production of growth factors. Thus, they are considered to impede the response to current clinical cancer therapies. Therefore, targeting CAFs to counteract these protumorigenic effects, and overcome the resistance to current therapeutic options, is an appealing and emerging strategy. In this review, we discuss how CAFs affect prognosis and response to clinical therapy and provide an overview of novel therapies involving CAF-targeting agents in lung and pancreatic cancer.
HIF-Prolyl Hydroxylase Domain Proteins (PHDs) in Cancer—Potential Targets for Anti-Tumor Therapy?
Authors: Gaete Diana , Rodriguez Diego , Watts Deepika , Sormendi Sundary , Chavakis Triantafyllos , Wielockx Ben
Published: February 2021

Solid tumors are typically associated with unbridled proliferation of malignant cells, accompanied by an immature and dysfunctional tumor-associated vascular network. Consequent impairment in transport of nutrients and oxygen eventually leads to a hypoxic environment wherein cells must adapt to survive and overcome these stresses. Hypoxia inducible factors (HIFs) are central transcription factors in the hypoxia response and drive the expression of a vast number of survival genes in cancer cells and in cells in the tumor microenvironment. HIFs are tightly controlled by a class of oxygen sensors, the HIF-prolyl hydroxylase domain proteins (PHDs), which hydroxylate HIFs, thereby marking them for proteasomal degradation. Remarkable and intense research during the past decade has revealed that, contrary to expectations, PHDs are often overexpressed in many tumor types, and that inhibition of PHDs can lead to decreased tumor growth, impaired metastasis, and diminished tumor-associated immune-tolerance. Therefore, PHDs represent an attractive therapeutic target in cancer research. Multiple PHD inhibitors have been developed that were either recently accepted in China as erythropoiesis stimulating agents (ESA) or are currently in phase III trials. We review here the function of HIFs and PHDs in cancer and related therapeutic opportunities.
Generation and Breeding of EGFP-Transgenic Marmoset Monkeys: Cell Chimerism and Implications for Disease Modeling
Authors: Drummer Charis , Vogt Edgar-John , Heistermann Michael , Roshani Berit , Becker Tamara , Mätz-Rensing Kerstin , Kues Wilfried A. , Kügler Sebastian , Behr Rüdiger
Published: February 2021

Genetic modification of non-human primates (NHP) paves the way for realistic disease models. The common marmoset is a NHP species increasingly used in biomedical research. Despite the invention of RNA-guided nucleases, one strategy for protein overexpression in NHP is still lentiviral transduction. We generated three male and one female enhanced green fluorescent protein (EGFP)-transgenic founder marmosets via lentiviral transduction of natural preimplantation embryos. All founders accomplished germline transmission of the transgene by natural mating, yielding 20 transgenic offspring together (in total, 45 pups; 44% transgenic). This demonstrates that the transgenic gametes are capable of natural fertilization even when in competition with wildtype gametes. Importantly, 90% of the transgenic offspring showed transgene silencing, which is in sharp contrast to rodents, where the identical transgene facilitated robust EGFP expression. Furthermore, we consistently discovered somatic, but so far, no germ cell chimerism in mixed wildtype/transgenic litters. Somatic cell chimerism resulted in false-positive genotyping of the respective wildtype littermates. For the discrimination of transgenic from transgene-chimeric animals by polymerase chain reaction on skin samples, a chimeric cell depletion protocol was established. In summary, it is possible to establish a cohort of genetically modified marmosets by natural mating, but specific requirements including careful promoter selection are essential.
Upregulation of the Renin–Angiotensin System Pathways and SARS-CoV-2 Infection: The Rationale for the Administration of Zinc-Chelating Agents in COVID-19 Patients
Authors: Zamai Loris
Published: February 2021

The article describes the rationale for the administration of zinc-chelating agents in COVID-19 patients. In a previous work I have highlighted that the binding of the SARS-CoV spike proteins to the zinc-metalloprotease ACE2 has been shown to induce ACE2 shedding by activating the zinc-metalloprotease ADAM17, which ultimately leads to systemic upregulation of ACE2 activity. Moreover, based on experimental models, it was also shown the detrimental effect of the excessive systemic activity of ACE2 through its downstream pathways, which leads to “clinical” manifestations resembling COVID-19. In this regard, strong upregulation of circulating ACE2 activity was recently reported in COVID-19 patients, thus supporting the previous hypothesis that COVID-19 may derive from upregulation of ACE2 activity. Based on this, a reasonable hypothesis of using inhibitors that curb the upregulation of both ACE2 and ADAM17 zinc-metalloprotease activities and consequent positive feedback-loops (initially triggered by SARS-CoV-2 and subsequently sustained independently on viral trigger) is proposed as therapy for COVID-19. In particular, zinc-chelating agents such as citrate and ethylenediaminetetraacetic acid (EDTA) alone or in combination are expected to act in protecting from COVID-19 at different levels thanks to their both anticoagulant properties and inhibitory activity on zinc-metalloproteases. Several arguments are presented in support of this hypothesis and based on the current knowledge of both beneficial/harmful effects and cost/effectiveness, the use of chelating agents in the prevention and therapy of COVID-19 is proposed. In this regard, clinical trials (currently absent) employing citrate/EDTA in COVID-19 are urgently needed in order to shed more light on the efficacy of zinc chelators against SARS-CoV-2 infection in vivo.
Toward Management of Uncertainty in Self-Adaptive Software Systems: IoT Case Study
Authors: Ismail Shereen , Shah Kruti , Reza Hassan , Marsh Ronald , Grant Emanuel
Published: February 2021

Adaptivity is the ability of the system to change its behavior whenever it does not achieve the system requirements. Self-adaptive software systems (SASS) are considered a milestone in software development in many modern complex scientific and engineering fields. Employing self-adaptation into a system can accomplish better functionality or performance; however, it may lead to unexpected system behavior and consequently to uncertainty. The uncertainty that results from using SASS needs to be tackled from different perspectives. The Internet of Things (IoT) that utilizes the attributes of SASS presents great development opportunities. Because IoT is a relatively new domain, it carries a high level of uncertainty. The goal of this work is to highlight more details about self-adaptivity in software systems, describe all possible sources of uncertainty, and illustrate its effect on the ability of the system to fulfill its objectives. We provide a survey of state-of-the-art approaches coping with uncertainty in SASS and discuss their performance. We classify the different sources of uncertainty based on their location and nature in SASS. Moreover, we present IoT as a case study to define uncertainty at different layers of the IoT stack. We use this case study to identify the sources of uncertainty, categorize the sources according to IoT stack layers, demonstrate the effect of uncertainty on the ability of the system to fulfill its objectives, and discuss the state-of-the-art approaches to mitigate the sources of uncertainty. We conclude with a set of challenges that provide a guide for future study.
Epicardial Adiposity in Relation to Metabolic Abnormality, Circulating Adipocyte FABP, and Preserved Ejection Fraction Heart Failure
Authors: Lin Jiun-Lu , Sung Kuo-Tzu , Lai Yau-Huei , Yen Chih-Hsuan , Yun Chun-Ho , Su Cheng-Huang , Kuo Jen-Yuan , Liu Chia-Yuan , Chien Chen-Yen , Cury Ricardo C. , Bezerra Hiram G. , Hung Chung-Lieh
Published: February 2021

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p < 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (pinteraction for all > 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p < 0.05). Higher A-FABP levels were associated with greater EAT thickness (pinteraction > 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF.
Is Blood Eosinophil Count a Biomarker for Chronic Obstructive Pulmonary Disease in a Real-World Clinical Setting? Predictive Property and Longitudinal Stability in Japanese Patients
Authors: Nishimura Koichi , Kusunose Masaaki , Sanda Ryo , Mori Mio , Shibayama Ayumi , Nakayasu Kazuhito
Published: February 2021

The authors examined predictive properties and the longitudinal stability of blood eosinophil count (BEC) or three strata (<100 cells/mm3, 100–299 cells/mm3 and ≥300 cells/mm3) in patients with chronic obstructive pulmonary disease (COPD) for up to six and a half years as part of a hospital-based cohort study. Of the 135 patients enrolled, 21 (15.6%) were confirmed to have died during the follow-up period. Episodes of acute exacerbation of COPD (AECOPD) were identified in 74 out of 130 available patients (56.9%), and admission due to AECOPD in 35 out of 132 (26.5%). Univariate Cox proportional hazards analyses revealed that almost all the age, forced expiratory volume in 1 s (FEV1) and health status measures using St. George’s Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) Score were significantly related to these types of events, but the relationship between age and AECOPD did not reach statistical significance (p = 0.05). Neither BEC nor the three different groups stratified by BEC were significant predictors of any subsequent events. There were no significant differences in the BEC between Visits 1–3 (p = 0.127, Friedman test). The ICC value was 0.755 using log-transformed data, indicating excellent repeatability. In the case of assigning to strata, Fleiss’ kappa was calculated to be 0.464, indicating moderate agreement. The predictive properties of BEC may be limited in a real-world Japanese clinical setting. Attention must be paid to the fact that the longitudinal stability of the three strata is regarded as moderate.
A Software Tool for Calculating the Uncertainty of Diagnostic Accuracy Measures
Authors: Chatzimichail Theodora , Hatjimihail Aristides T.
Published: February 2021

Screening and diagnostic tests are applied for the classification of people into diseased and non-diseased populations. Although diagnostic accuracy measures are used to evaluate the correctness of classification in clinical research and practice, there has been limited research on their uncertainty. The objective for this work was to develop a tool for calculating the uncertainty of diagnostic accuracy measures, as diagnostic accuracy is fundamental to clinical decision-making. For this reason, the freely available interactive program Diagnostic Uncertainty has been developed in the Wolfram Language. The program provides six modules with nine submodules for calculating and plotting the standard combined, measurement and sampling uncertainty and the resultant confidence intervals of various diagnostic accuracy measures of screening or diagnostic tests, which measure a normally distributed measurand, applied at a single point in time to samples of non-diseased and diseased populations. This is done for differing sample sizes, mean and standard deviation of the measurand, diagnostic threshold and standard measurement uncertainty of the test. The application of the program is demonstrated with an illustrative example of glucose measurements in samples of diabetic and non-diabetic populations, that shows the calculation of the uncertainty of diagnostic accuracy measures. The presented interactive program is user-friendly and can be used as a flexible educational and research tool in medical decision-making, to calculate and explore the uncertainty of diagnostic accuracy measures.
Diagnosis of Biofilm-Associated Peri-Implant Disease Using a Fluorescence-Based Approach
Authors: Hwang Geelsu , Blatz Markus B. , Wolff Mark S. , Steier Liviu
Published: February 2021

Dental implants have become a routine component of daily dental practice and the demand for dental implants is expected to increase significantly in the future. Despite the high success rates of dental implants, failures do occur, resulting in discomfort, rampant destruction of the oral health, or painful and costly surgical replacement of a failed implant. Peri-implant diseases are inflammatory conditions affecting the soft/hard tissues surrounding a functional dental implant. Plenty of experimental evidence indicates that the accumulation of dental plaque at the soft tissue–implant interface and the subsequent local inflammatory response seems to be key in the pathogenesis of the peri-implant mucositis. Such peri-implant–soft tissue interface is less effective than natural teeth in resisting bacterial invasion, enhancing vulnerability to subsequent peri-implant disease. Furthermore, in certain individuals, it will progress to peri-implantitis, resulting in alveolar bone loss and implant failure. Although early diagnosis and accurate identification of risk factors are extremely important to effectively prevent peri-implant diseases, current systematic reviews revealed that a uniform classification and diagnostic methodology for peri-implantitis are lacking. Recent progress on fluorescence-based technology enabled rapid diagnosis of the disease and effective removal of plaques. Here, we briefly review biofilm-associated peri-implant diseases and propose a fluorescence-based approach for more accurate and objective diagnoses. A fluorescence-based diagnosis tool through headlights combined with special-filtered dental loupes may serve as a hands-free solution for both precise diagnosis and effective removal of plaque-biofilms.
Deep Residual Dense Network for Single Image Super-Resolution
Authors: Musunuri Yogendra Rao , Kwon Oh-Seol
Published: February 2021

In this paper, we propose a deep residual dense network (DRDN) for single image super- resolution. Based on human perceptual characteristics, the residual in residual dense block strategy (RRDB) is exploited to implement various depths in network architectures. The proposed model exhibits a simple sequential structure comprising residual and dense blocks with skip connections. It improves the stability and computational complexity of the network, as well as the perceptual quality. We adopt a perceptual metric to learn and assess the quality of the reconstructed images. The proposed model is trained with the Diverse2k dataset, and the performance is evaluated using standard datasets. The experimental results confirm that the proposed model exhibits superior performance, with better reconstruction results and perceptual quality than conventional methods.
Machine Learning Methods for Histopathological Image Analysis: A Review
Authors: de Matos Jonathan , Ataky Steve , de Souza Britto Alceu , Soares de Oliveira Luiz , Lameiras Koerich Alessandro
Published: February 2021

Histopathological images (HIs) are the gold standard for evaluating some types of tumors for cancer diagnosis. The analysis of such images is time and resource-consuming and very challenging even for experienced pathologists, resulting in inter-observer and intra-observer disagreements. One of the ways of accelerating such an analysis is to use computer-aided diagnosis (CAD) systems. This paper presents a review on machine learning methods for histopathological image analysis, including shallow and deep learning methods. We also cover the most common tasks in HI analysis, such as segmentation and feature extraction. Besides, we present a list of publicly available and private datasets that have been used in HI research.
1.0 V-0.18 µm CMOS Tunable Low Pass Filters with 73 dB DR for On-Chip Sensing Acquisition Systems
Authors: Pérez-Bailón Jorge , Calvo Belén , Medrano Nicolás
Published: February 2021

This paper presents a new approach based on the use of a Current Steering (CS) technique for the design of fully integrated Gm–C Low Pass Filters (LPF) with sub-Hz to kHz tunable cut-off frequencies and an enhanced power-area-dynamic range trade-off. The proposed approach has been experimentally validated by two different first-order single-ended LPFs designed in a 0.18 µm CMOS technology powered by a 1.0 V single supply: a folded-OTA based LPF and a mirrored-OTA based LPF. The first one exhibits a constant power consumption of 180 nW at 100 nA bias current with an active area of 0.00135 mm2 and a tunable cutoff frequency that spans over 4 orders of magnitude (~100 mHz–152 Hz @ CL = 50 pF) preserving dynamic figures greater than 78 dB. The second one exhibits a power consumption of 1.75 µW at 500 nA with an active area of 0.0137 mm2 and a tunable cutoff frequency that spans over 5 orders of magnitude (~80 mHz–~1.2 kHz @ CL = 50 pF) preserving a dynamic range greater than 73 dB. Compared with previously reported filters, this proposal is a competitive solution while satisfying the low-voltage low-power on-chip constraints, becoming a preferable choice for general-purpose reconfigurable front-end sensor interfaces.
Real-Time Minimization of Mechanical Specific Energy with Multivariable Extremum Seeking
Authors: Nystad Magnus , Aadnøy Bernt Sigve , Pavlov Alexey
Published: February 2021

Drilling more efficiently and with less non-productive time (NPT) is one of the key enablers to reduce field development costs. In this work, we investigate the application of a data-driven optimization method called extremum seeking (ES) to achieve more efficient and safe drilling through automatic real-time minimization of the mechanical specific energy (MSE). The ES algorithm gathers information about the current downhole conditions by performing small tests with the applied weight on bit (WOB) and drill string rotational rate (RPM) while drilling and automatically implements optimization actions based on the test results. The ES method does not require an a priori model of the drilling process and can thus be applied even in instances when sufficiently accurate drilling models are not available. The proposed algorithm can handle various drilling constraints related to drilling dysfunctions and hardware limitations. The algorithm’s performance is demonstrated by simulations, where the algorithm successfully finds and maintains the optimal WOB and RPM while adhering to drilling constraints in various settings. The simulations show that the ES method is able to track changes in the optimal WOB and RPM corresponding to changes in the drilled formation. As demonstrated in the simulation scenarios, the overall improvements in rate of penetration (ROP) can be up to 20–170%, depending on the initial guess of the optimal WOB and RPM obtained from e.g., a drill-off test or a potentially inaccurate model. The presented algorithm is supplied with specific design choices and tuning considerations that facilitate its simple and efficient use in drilling applications.
Considering Life Cycle Greenhouse Gas Emissions in Power System Expansion Planning for Europe and North Africa Using Multi-Objective Optimization
Authors: Junne Tobias , Cao Karl-Kiên , Miskiw Kim Kira , Hottenroth Heidi , Naegler Tobias
Published: February 2021

We integrate life cycle indicators for various technologies of an energy system model with high spatiotemporal detail and a focus on Europe and North Africa. Using multi-objective optimization, we calculate a pareto front that allows us to assess the trade-offs between system costs and life cycle greenhouse gas (GHG) emissions of future power systems. Furthermore, we perform environmental ex-post assessments of selected solutions using a broad set of life cycle impact categories. In a system with the least life cycle GHG emissions, the costs would increase by ~63%, thereby reducing life cycle GHG emissions by ~82% compared to the cost-optimal solution. Power systems mitigating a substantial part of life cycle GHG emissions with small increases in system costs show a trend towards a deployment of wind onshore, electricity grid and a decline in photovoltaic plants and Li-ion storage. Further reductions are achieved by the deployment of concentrated solar power, wind offshore and nuclear power but lead to considerably higher costs compared to the cost-optimal solution. Power systems that mitigate life cycle GHG emissions also perform better for most impact categories but have higher ionizing radiation, water use and increased fossil fuel demand driven by nuclear power. This study shows that it is crucial to consider upstream GHG emissions in future assessments, as they represent an inheritable part of total emissions in ambitious energy scenarios that, so far, mainly aim to reduce direct CO2 emissions.
Design Space Optimization of a Three-Phase LCL Filter for Electric Vehicle Ultra-Fast Battery Charging
Authors: Cittanti Davide , Mandrile Fabio , Gregorio Matteo , Bojoi Radu
Published: February 2021

State-of-the-art ultra-fast battery chargers for electric vehicles simultaneously require high efficiency and high power density, leading to a challenging power converter design. In particular, the grid-side filter, which ensures sinusoidal current absorption with low pulse-width modulation (PWM) harmonic content, can be a major contributor to the overall converter size and losses. Therefore, this paper proposes a complete analysis, design and optimization procedure of a three-phase LCL filter for a modular DC fast charger. First, an overview of the basic LCL filter modeling is provided and the most significant system transfer functions are identified. Then, the optimal ratio between grid-side and converter-side inductance is discussed, aiming for the maximum filtering performance. A novel design methodology, based on a graphical representation of the filter design space, is thus proposed. Specifically, several constraints on the LCL filtering elements are enforced, such that all feasible design parameter combinations are identified. Therefore, since in low-voltage high-power applications the inductive components typically dominate the overall filter volume, loss and cost, the viable LCL filter design that minimizes the total required inductance is selected. The proposed design procedure is applied to a 30 kW, 20 kHz 3-level unidirectional rectifier, employed in a modular DC fast charger. The performance of the selected optimal design, featuring equal grid-side and converter-side 175 μμH inductors and 15 μμF capacitors, is verified experimentally on an active front-end prototype, both in terms of harmonic attenuation capability and current control dynamics. A current total harmonic distortion (THD) of 1.2% is achieved at full load and all generated current harmonics comply with the applicable harmonic standard. Moreover, separate tests are performed with different values of grid inner impedance, verifying the converter control stability in various operating conditions and supporting the general validity of the proposed design methodology.
Editorial: Lactic Acid Fermentation and the Colours of Biotechnology 2.0
Authors: Capozzi Vittorio , Grieco Francesco
Published: February 2021

Lactic acid bacteria (LAB) belong to an assorted cluster of bacteria that are protagonists of fermentative processes and bio-based solutions of interest in the different fields of biotechnological sciences, from the agri-food sector (green) up to the industrial (white), throughout the pharmaceutical (red) [...]
Learning How to Separate Fake from Real News: Scalable Digital Tutorials Promoting Students’ Civic Online Reasoning
Authors: Axelsson Carl-Anton Werner , Guath Mona , Nygren Thomas
Published: February 2021

With the rise of misinformation, there is a great need for scalable educational interventions supporting students’ abilities to determine the trustworthiness of digital news. We address this challenge in our study by developing an online intervention tool based on tutorials in civic online reasoning that aims to teach adolescents how to critically assess online information comprising text, videos and images. Our findings from an online intervention with 209 upper secondary students highlight how observational learning and feedback support their ability to read laterally and improve their performance in determining the credibility of digital news and social media posts.
Glycemic Index of Gluten-Free Bread and Their Main Ingredients: A Systematic Review and Meta-Analysis
Authors: Romão Bernardo , Falcomer Ana Luísa , Palos Gabriela , Cavalcante Sandra , Botelho Raquel Braz Assunção , Nakano Eduardo Yoshio , Raposo António , Shakeel Faiyaz , Alshehri Sultan , Mahdi Wael A. , Zandonadi Renata Puppin
Published: February 2021

This study aimed to perform a systematic review and meta-analysis of the glycemic index (GI) of gluten-free bread (GFB) and its main ingredients. The systematic review followed PRISMA guidelines, using seven electronic databases (PubMed, EMBASE, Scopus, Science Direct, Web of Science, gray literature research with Google Scholar, and patents with Google Patent tool), from inception to November 2020. Eighteen studies met the inclusion criteria evaluating 132 GFB samples. Five articles tested GI in vivo, eleven in vitro; and two studies tested both methods. The analysis showed that 60.7% (95% CI: 40.2–78.1%) of the samples presented high glycemic indexes, evidencing a high glycemic profile for GFB. Only 18.2% (95% CI: 11.7–27.2%) of the bread samples presented in the studies were classified as a low GI. Meta-analysis presented moderate/low heterogenicity between studies (I2 = 61% and <1% for both high and low GIs) and reinforced the proportion of high GIs. Lower GIs were found in formulations based on Colocasia esculenta flour or enriched with fiber, yogurt and curd cheese, sourdough, psyllium, hydrocolloids, enzymes, fructans, and resistant starch, highlighting the efficacy of these ingredients to lower GFBs’ GI. GFB tends to present high GI, impacting the development of chronic diseases when consumed.
Simulation of Folding Kinetics for Aligned RNAs
Authors: Huang Jiabin , Voß Björn
Published: February 2021

Studying the folding kinetics of an RNA can provide insight into its function and is thus a valuable method for RNA analyses. Computational approaches to the simulation of folding kinetics suffer from the exponentially large folding space that needs to be evaluated. Here, we present a new approach that combines structure abstraction with evolutionary conservation to restrict the analysis to common parts of folding spaces of related RNAs. The resulting algorithm can recapitulate the folding kinetics known for single RNAs and is able to analyse even long RNAs in reasonable time. Our program RNAliHiKinetics is the first algorithm for the simulation of consensus folding kinetics and addresses a long-standing problem in a new and unique way.
miRNAture—Computational Detection of microRNA Candidates
Authors: Velandia-Huerto Cristian A. , Fallmann Jörg , Stadler Peter F.
Published: February 2021

Homology-based annotation of short RNAs, including microRNAs, is a difficult problem because their inherently small size limits the available information. Highly sensitive methods, including parameter optimized blast, nhmmer, or cmsearch runs designed to increase sensitivity inevitable lead to large numbers of false positives, which can be detected only by detailed analysis of specific features typical for a RNA family and/or the analysis of conservation patterns in structure-annotated multiple sequence alignments. The miRNAture pipeline implements a workflow specific to animal microRNAs that automatizes homology search and validation steps. The miRNAture pipeline yields very good results for a large number of “typical” miRBase families. However, it also highlights difficulties with atypical cases, in particular microRNAs deriving from repetitive elements and microRNAs with unusual, branched precursor structures and atypical locations of the mature product, which require specific curation by domain experts.