bluuebunny/crossref_metadata_2025 huggingface dataset:
Dimensionality-reduction Procedure for the Capacitated p-Median Transportation Inventory Problem
Authors: Carmona-Benítez Rafael Bernardo
Published: April 2020

The capacitated p-median transportation inventory problem with heterogeneous fleet (CLITraP-HTF) aims to determine an optimal solution to a transportation problem subject to location-allocation, inventory management and transportation decisions. The novelty of CLITraP-HTF is to design a supply chain that solves all these decisions at the same time. Optimizing the CLITraP-HTF is a challenge because of the high dimension of the decision variables that lead to a large and complex search space. The contribution of this paper is to develop a dimensionality-reduction procedure (DRP) to reduce the CLITraP-HTF complexity and help to solve it. The proposed DRP is a mathematical proof to demonstrate that the inventory management and transportation decisions can be solved before the optimization procedure, thus reducing the complexity of the CLITraP-HTF by greatly narrowing its number of decision variables such that the remaining problem to solve is the well-known capacitated p-median problem (CPMP). The conclusion is that the proposed DRP helps to solve the CLITraP-HTF because the CPMP can be and has been solved by applying different algorithms and heuristic methods.
Magnifiers in Some Generalization of the Full Transformation Semigroups
Authors: Kaewnoi Thananya , Petapirak Montakarn , Chinram Ronnason
Published: April 2020

An element a of a semigroup S is called a left [right] magnifier if there exists a proper subset M of S such that a M = S ( M a = S ) . Let T ( X ) denote the semigroup of all transformations on a nonempty set X under the composition of functions, P = { X i ∣ i ∈ Λ } be a partition, and ρ be an equivalence relation on the set X. In this paper, we focus on the properties of magnifiers of the set T ρ ( X , P ) = { f ∈ T ( X ) ∣ ∀ ( x , y ) ∈ ρ , ( x f , y f ) ∈ ρ and X i f ⊆ X i for all i ∈ Λ } , which is a subsemigroup of T ( X ) , and provide the necessary and sufficient conditions for elements in T ρ ( X , P ) to be left or right magnifiers.
Generalized 5-Point Approximating Subdivision Scheme of Varying Arity
Authors: Hussain Sardar Muhammad , Rehman Aziz Ur , Baleanu Dumitru , Nisar Kottakkaran Sooppy , Ghaffar Abdul , Abdul Karim Samsul Ariffin
Published: April 2020

The Subdivision Schemes (SSs) have been the heart of Computer Aided Geometric Design (CAGD) almost from its origin, and various analyses of SSs have been conducted. SSs are commonly used in CAGD and several methods have been invented to design curves/surfaces produced by SSs to applied geometry. In this article, we consider an algorithm that generates the 5-point approximating subdivision scheme with varying arity. By applying the algorithm, we further discuss several properties: continuity, Hölder regularity, limit stencils, error bound, and shape of limit curves. The efficiency of the scheme is also depicted with assuming different values of shape parameter along with its application.
Existence of Weak Solutions for a New Class of Fractional p-Laplacian Boundary Value Systems
Authors: Kamache Fares , Guefaifia Rafik , Boulaaras Salah , Alharbi Asma
Published: April 2020

In this paper, at least three weak solutions were obtained for a new class of dual non-linear dual-Laplace systems according to two parameters by using variational methods combined with a critical point theory due to Bonano and Marano. Two examples are given to illustrate our main results applications.
On the Nonlocal Fractional Delta-Nabla Sum Boundary Value Problem for Sequential Fractional Delta-Nabla Sum-Difference Equations
Authors: Reunsumrit Jiraporn , Sitthiwirattham Thanin
Published: April 2020

In this paper, we propose sequential fractional delta-nabla sum-difference equations with nonlocal fractional delta-nabla sum boundary conditions. The Banach contraction principle and the Schauder’s fixed point theorem are used to prove the existence and uniqueness results of the problem. The different orders in one fractional delta differences, one fractional nabla differences, two fractional delta sum, and two fractional nabla sum are considered. Finally, we present an illustrative example.
Computer Simulation and Iterative Algorithm for Approximate Solving of Initial Value Problem for Riemann-Liouville Fractional Delay Differential Equations
Authors: Hristova Snezhana , Stefanova Kremena , Golev Angel
Published: April 2020

The main aim of this paper is to suggest an algorithm for constructing two monotone sequences of mild lower and upper solutions which are convergent to the mild solution of the initial value problem for Riemann-Liouville fractional delay differential equation. The iterative scheme is based on a monotone iterative technique. The suggested scheme is computerized and applied to solve approximately the initial value problem for scalar nonlinear Riemann-Liouville fractional differential equations with a constant delay on a finite interval. The suggested and well-grounded algorithm is applied to a particular problem and the practical usefulness is illustrated.
δ(2,2)-Invariant for Lagrangian Submanifolds in Quaternionic Space Forms
Authors: Macsim Gabriel , Mihai Adela , Mihai Ion
Published: April 2020

In the geometry of submanifolds, Chen inequalities represent one of the most important tool to find relationships between intrinsic and extrinsic invariants; the aim is to find sharp such inequalities. In this paper we establish an optimal inequality for the Chen invariant δ ( 2 , 2 ) on Lagrangian submanifolds in quaternionic space forms, regarded as a problem of constrained maxima.
Pattern Recognition in Epileptic EEG Signals via Dynamic Mode Decomposition
Authors: Seo Jong-Hyeon , Tsuda Ichiro , Lee Young Ju , Ikeda Akio , Matsuhashi Masao , Matsumoto Riki , Kikuchi Takayuki , Kang Hunseok
Published: April 2020

In this paper, we propose a new method based on the dynamic mode decomposition (DMD) to find a distinctive contrast between the ictal and interictal patterns in epileptic electroencephalography (EEG) data. The features extracted from the method of DMD clearly capture the phase transition of a specific frequency among the channels corresponding to the ictal state and the channel corresponding to the interictal state, such as direct current shift (DC-shift or ictal slow shifts) and high-frequency oscillation (HFO). By performing classification tests with Electrocorticography (ECoG) recordings of one patient measured at different timings, it is shown that the captured phenomenon is the unique pattern that occurs in the ictal onset zone of the patient. We eventually explain how advantageously the DMD captures some specific characteristics to distinguish the ictal state and the interictal state. The method presented in this study allows simultaneous interpretation of changes in the channel correlation and particular information for activity related to an epileptic seizure so that it can be applied to identification and prediction of the ictal state and analysis of the mechanism on its dynamics.
A Study on Cubic H-Relations in a Topological Universe Viewpoint
Authors: Lee Jeong-Gon , Hur Kul , Chen Xueyou
Published: April 2020

We introduce the concrete category CRel P ( H ) [resp. CRel R ( H ) ] of cubic H-relational spaces and P-preserving [resp. R-preserving] mappings between them and study it in a topological universe viewpoint. In addition, we prove that it is Cartesian closed over Set . Next, we introduce the subcategory CRel P , R ( H ) [resp. CRel R , R ( H ) ] of CRel P ( H ) [resp. CRel R ( H ) ] and investigate it in the sense of a topological universe. In particular, we obtain exponential objects in CRel P , R ( H ) [resp. CRel R , R ( H ) ] quite different from those in CRel P ( H ) [resp. CRel R ( H ) ].
Multi-Term Fractional Degenerate Evolution Equations and Optimal Control Problems
Authors: Plekhanova Marina , Baybulatova Guzel
Published: April 2020

A theorem on unique solvability in the sense of the strong solutions is proved for a class of degenerate multi-term fractional equations in Banach spaces. It applies to the deriving of the conditions on unique solution existence for an optimal control problem to the corresponding equation. Obtained results are used to an optimal control problem study for a model system which is described by an initial-boundary value problem for a partial differential equation.
Computation of the Cutoff Wavenumbers of Metallic Waveguides with Symmetries by Using a Nonlinear Eigenproblem Formulation: A Group Theoretical Approach
Authors: Angiulli Giovanni , Versaci Mario , Calcagno Salvatore
Published: April 2020

The evaluation of the cutoff wavenumbers of metallic waveguides can be related to the numerical resolution of a suitable nonlinear eigenproblem defined on the domain C described by the contour of its transverse cross section. In this work, we show that the symmetries of C can be exploited to obtain a block diagonal matrix representation of the nonlinear eigenproblem, which enables a remarkable reduction in the computational effort involved in its resolution.
Stability of the Fréchet Equation in Quasi-Banach Spaces
Authors: Kim Sang Og
Published: April 2020

We investigate the Hyers–Ulam stability of the well-known Fréchet functional equation that comes from a characterization of inner product spaces. We also show its hyperstability on a restricted domain. We work in the framework of quasi-Banach spaces. In the proof, a fixed point theorem due to Dung and Hang, which is an extension of a fixed point theorem in Banach spaces, plays a main role.
On Coefficient Functionals for Functions with Coefficients Bounded by 1
Authors: Zaprawa Paweł , Futa Anna , Jastrzębska Magdalena
Published: April 2020

In this paper, we discuss two well-known coefficient functionals a 2 a 4 − a 3 2 and a 4 − a 2 a 3 . The first one is called the Hankel determinant of order 2. The second one is a special case of Zalcman functional. We consider them for functions in the class Q R ( 1 2 ) of analytic functions with real coefficients which satisfy the condition Re f ( z ) z > 1 2 for z in the unit disk Δ . It is known that all coefficients of f ∈ Q R ( 1 2 ) are bounded by 1. We find the upper bound of a 2 a 4 − a 3 2 and the bound of | a 4 − a 2 a 3 | . We also consider a few subclasses of Q R ( 1 2 ) and we estimate the above mentioned functionals. In our research two different methods are applied. The first method connects the coefficients of a function in a given class with coefficients of a corresponding Schwarz function or a function with positive real part. The second method is based on the theorem of formulated by Szapiel. According to this theorem, we can point out the extremal functions in this problem, that is, functions for which equalities in the estimates hold. The obtained estimates significantly extend the results previously established for the discussed classes. They allow to compare the behavior of the coefficient functionals considered in the case of real coefficients and arbitrary coefficients.
Existence of Solutions for a System of Integral Equations Using a Generalization of Darbo’s Fixed Point Theorem
Authors: Mohammadi Babak , Shole Haghighi Ali Asghar , Khorshidi Maryam , De la Sen Manuel , Parvaneh Vahid
Published: April 2020

In this paper, an extension of Darbo’s fixed point theorem via θ -F-contractions in a Banach space has been presented. Measure of noncompactness approach is the main tool in the presentation of our proofs. As an application, we study the existence of solutions for a system of integral equations. Finally, we present a concrete example to support the effectiveness of our results.
Effects of Cyclization on Activity and Stability of α-Conotoxin TxIB
Authors: Li Xincan , Wang Shuai , Zhu Xiaopeng , Zhangsun Dongting , Wu Yong , Luo Sulan
Published: April 2020

α-Conotoxin TxIB specifically blocked α6/α3β2β3 acetylcholine receptors (nAChRs), and it could be a potential probe for studying addiction and other diseases related to α6/α3β2β3 nAChRs. However, as a peptide, TxIB may suffer from low stability, short half-life, and poor bioavailability. In this study, cyclization of TxIB was used to improve its stability. Four cyclic mutants of TxIB (cTxIB) were synthesized, and the inhibition of these analogues on α6/α3β2β3 nAChRs as well as their stability in human serum were measured. All cyclized analogues had similar activity compared to wild-type TxIB, which indicated that backbone cyclization of TxIB had no significant effect on its activity. Cyclization of TxIB with a seven-residue linker improved its stability significantly in human serum. Besides this, the results showed that cyclization maintained the activity of α-conotoxin TxIB, which is conducive to its future application.
Adaptation of a Health Education Program for Improving the Uptake of HIV Self-Testing by Men in Rwanda: A Study Protocol
Authors: Dzinamarira Tafadzwa , Mashamba-Thompson Tivani Phosa
Published: April 2020

Background and objectives: Available evidence shows a low uptake of HIV services among men in Rwanda. HIV self-testing (HIVST), a new intervention, may have the potential to improve the uptake of HIV testing services among men. The current study aims to adapt a health education program (HEP) for improving the uptake of HIVST among men in Rwanda. Materials and Methods: We propose a mixed method study, which will be conducted in four phases. In Phase 1, we will conduct a scoping review to map the available evidence on health education programs for men in low- and middle-income countries (LMICs). In Phase 2, we will conduct interviews with stakeholders in the Rwanda HIV response and healthcare providers to determine their perspectives on implementation of HIVST in Rwanda. In Phase 3, a cross-sectional survey will be used to assess HIVST awareness and acceptability among men in Rwanda. Guided by findings from Phases 1, 2, and 3, we will employ the nominal group technique to develop and optimize the HEP for improving the uptake of HIVST among men in Rwanda. In Phase 4, we will use a pragmatic pilot randomized controlled trial to assess the preliminary impact of the HEP for men in Rwanda and assess the feasibility of a later, larger study. We will employ the Stata version 16 statistical package and NVivo version 12 for the analysis of quantitative and qualitative data, respectively. We anticipate that the findings of this study will inform implementers and policy makers to guide strategies on the implementation of HIVST in Rwanda and ultimately accomplish goals set forth in the Rwanda 2019–2024 Fourth Health Sector Strategic Plan on scaling up the number of men who know their HIV status. Conclusion: It is anticipated that this study will proffer solutions and strategies that are applicable not only in Rwanda but also in similar settings of LMICs.
Comparison of Subjective Workout Intensities between Aquatic and Land-based Running in Healthy Young Males: A Pilot Study
Authors: Lee Chang-Hyung , Choi Jun Hwan , Kim Soo-Yeon
Published: April 2020

Background and objectives: Aquatic exercises have demonstrated several advantages over land-based exercise, but only a few studies have compared the workout intensities and efficiencies in a stage-specific manner. This study aimed to investigate workout intensity during aquatic and land-based running, based on the rating of perceived exertion (RPE). Materials and Methods: Twenty healthy young male subjects underwent a land-based running test (LRT) and an aquatic running test (ART), in the form of a cardiopulmonary exercise treadmill test and a shallow-water running test. The seven stages of the ART were composed of 3 minutes each of the Bruce protocol performed during the LRT. In the ART, the participants were instructed to run in a swimming pool with matching RPE to that obtained at each stage of the LRT. Results: Heart rate (HR) during both LRT and ART exhibited a linear relationship (r = 0.997 and 0.996, respectively; p < 0.001). During the initial and middle period, HR was higher in the ART than in the LRT. However, in the final period, HR was higher in the LRT than in the ART. Conclusions: In aquatic exercises based on the RPE obtained from the LRT, HR exhibited a linear relationship in both the ART and the LRT. The ART appears to increase cardiac loading more efficiently in the initial period and does not increase cardiac loading abruptly at a later period. Although there is no precise, objective, controlled parameter to compare the ART and the LRT, the RPE may be used as a convenient measurement for workout intensity in aquatic running.
EMS-effect of Exercises with Music on Fatness and Biomarkers of Obese Elderly Women
Authors: Kim Jiyoun , Jee Yongseok
Published: April 2020

Background and objectives: Electromyostimulation (EMS) has been shown to improve body composition, but what biomarkers it affects has not been investigated. The purpose of this study was to compare the EMS-effect of exercises with music on fatness and biomarker levels in obese elderly. Materials and Methods: Twenty-five women were randomly classified into a control group (CON) and EMS group (EMSG). EMS suits used in this study enabled the simultaneous activation of eight pairs with selectable intensities. Program sessions of EMS were combined with exercises of listening to music three times a week for eight weeks. Although both groups received the same program, CON did not receive electrical stimuli. Results: Compared with CON, a significant effect of the EMS intervention concerning decreased fatness, as well as an increased skeletal muscle mass and basal metabolic rate, were evident. Tumor necrosis factor-a, C-reactive protein, resistin, and carcinoembryonic antigen of biomarkers were significantly different in the groups by time interaction. Similarly, the positive changes caused by EMS were represented in lipoprotein-cholesterols. Conclusions: The results indicate that a significant effect due to the EMS intervention was found concerning body composition and biomarkers in obese elderly women.
Pseudomonas PS01 Isolated from Maize Rhizosphere Alters Root System Architecture and Promotes Plant Growth
Authors: Chu Thanh Nguyen , Bui Le Van , Hoang Minh Thi Thanh
Published: April 2020

The objectives of this study were to evaluate the plant growth promoting effects on Arabidopsis by Pseudomonas sp. strains associated with rhizosphere of crop plants grown in Mekong Delta, Vietnam. Out of all the screened isolates, Pseudomonas PS01 isolated from maize rhizosphere showed the most prominent plant growth promoting effects on Arabidopsis and maize (Zea mays). We also found that PS01 altered root system architecture (RSA). The full genome of PS01 was resolved using high-throughput sequencing. Phylogenetic analysis identified PS01 as a member of the Pseudomonas putida subclade, which is closely related to Pseudomonas taiwanensis. PS01 genome size is 5.3 Mb, assembled in 71 scaffolds comprising of 4820 putative coding sequence. PS01 encodes genes for the indole-3-acetic acid (IAA), acetoin and 2,3-butanediol biosynthesis pathways. PS01 promoted the growth of Arabidopsis and altered the root system architecture by inhibiting primary root elongation and promoting lateral root and root hair formation. By employing gene expression analysis, genetic screening and pharmacological approaches, we suggested that the plant-growth promoting effects of PS01 and the alteration of RSA might be independent of bacterial auxin and could be caused by a combination of different diffusible compounds and volatile organic compounds (VOCs). Taken together, our results suggest that PS01 is a potential candidate to be used as bio-fertilizer agent for enhancing plant growth.
High-Throughput Screening of the ReFRAME Library Identifies Potential Drug Repurposing Candidates for Trypanosoma cruzi
Authors: Bernatchez Jean A. , Chen Emily , Hull Mitchell V. , McNamara Case W. , McKerrow James H. , Siqueira-Neto Jair L.
Published: April 2020

Chagas disease, caused by the kinetoplastid parasite Trypanosoma cruzi, affects between 6 and 7 million people worldwide, with an estimated 300,000 to 1 million of these cases in the United States. In the chronic phase of infection, T. cruzi can cause severe gastrointestinal and cardiac disease, which can be fatal. Currently, only benznidazole is clinically approved by the FDA for pediatric use to treat this infection in the USA. Toxicity associated with this compound has driven the search for new anti-Chagas agents. Drug repurposing is a particularly attractive strategy for neglected diseases, as pharmacological parameters and toxicity are already known for these compounds, reducing costs and saving time in the drug development pipeline. Here, we screened 7680 compounds from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library, a collection of drugs or compounds with confirmed clinical safety, against T. cruzi. We identified seven compounds of interest with potent in vitro activity against the parasite with a therapeutic index of 10 or greater, including the previously unreported activity of the antiherpetic compound 348U87. These results provide the framework for further development of new T. cruzi leads that can potentially move quickly to the clinic.
New Insights into the Microbial Degradation of D-Cyphenothrin in Contaminated Water/Soil Environments
Authors: Huang Yaohua , Lin Ziqiu , Zhang Wenping , Pang Shimei , Bhatt Pankaj , Rene Eldon , Kumar Alagarasan , Chen Shaohua
Published: April 2020

Persistent use of the insecticide D-cyphenothrin has resulted in heavy environmental contamination and public concern. However, microbial degradation of D-cyphenothrin has never been investigated and the mechanism remains unknown. During this study, for the first time, an efficient D-cyphenothrin-degrading bacterial strain Staphylococcus succinus HLJ-10 was identified. Response surface methodology was successfully employed by using Box-Behnken design to optimize the culture conditions. At optimized conditions, over 90% degradation of D-cyphenothrin (50 mg·L−1) was achieved in a mineral salt medium within 7 d. Kinetics analysis revealed that its half-life was reduced by 61.2 d, in comparison with the uninoculated control. Eight intermediate metabolites were detected in the biodegradation pathway of D-cyphenothrin including cis-D-cyphenothrin, trans-D-cyphenothrin, 3-phenoxybenzaldehyde, α-hydroxy-3-phenoxy-benzeneacetonitrile, trans-2,2-dimethyl-3-propenyl-cyclopropanol, 2,2-dimethyl-3-propenyl-cyclopropionic acid, trans-2,2-dimethyl-3-propenyl-cyclopropionaldehyde, and 1,2-benzenedicarboxylic acid, dipropyl ester. This is the first report about the degradation of D-cyphenothrin through cleavage of carboxylester linkage and diaryl bond. In addition to degradation of D-cyphenothrin, strain HLJ-10 effectively degraded a wide range of synthetic pyrethroids including permethrin, tetramethrin, bifenthrin, allethrin, and chlorempenthrin, which are also widely used insecticides with environmental contamination problems. Bioaugmentation of D-cyphenothrin-contaminated soils with strain HLJ-10 substantially enhanced its degradation and over 72% of D-cyphenothrin was removed from soils within 40 d. These findings unveil the biochemical basis of a highly efficient D-cyphenothrin-degrading bacterial isolate and provide potent agents for eliminating environmental residues of pyrethroids.
Adaptive Development of Soil Bacterial Communities to Ecological Processes Caused by Mining Activities in the Loess Plateau, China
Authors: Luo Zhanbin , Ma Jing , Chen Fu , Li Xiaoxiao , Zhang Qi , Yang Yongjun
Published: April 2020

Microorganisms are the driving force behind the circulation and transformation of the soil substance. The development of soil bacterial communities is critical for ecosystem restoration and evolution. In the Loess Plateau, coal mining activities have aggravated the deterioration of the fragile local ecological environment. The adaptive development of soil bacterial communities in response to different ecological processes caused by coal mining activities was explored through high-throughput sequencing technology and an ecological network analysis of the mining subsidence area of the Daliuta Coal Mine and vegetation rehabilitation area of the Heidaigou Coal Mine in the Loess Plateau. The results showed that while mining subsidence was inhibited, vegetation rehabilitation promoted the soil physicochemical properties. Soil organic matter, available phosphorus and available potassium in the subsidence area decreased significantly (P < 0.05), while soil organic matter, soil water, pH and EC in the vegetation rehabilitation area increased significantly (P < 0.05). The diversity index in the subsidence area decreased by about 20%, while that in the vegetation rehabilitation area increased by 63%. Mining subsidence and vegetation rehabilitation had a distinct influence on the molecular ecological networks of the soil bacteria, which tended to be more complex after the mining subsidence, and the number of connections in the network increased otherwise significantly enhanced interactive relationships. After the vegetation rehabilitation, the number of modules in the ecological network increased, but the contents of modules tended to be simpler. Soil bacterial communities adapted to the changes by changing the relationships between bacteria in response to different ecological processes. This study provides new insights into the monitoring and abatement of the damaged ecological environment in mines.
The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection
Authors: Garcia-Castillo Valeria , Marcial Guillermo , Albarracín Leonardo , Tomokiyo Mikado , Clua Patricia , Takahashi Hideki , Kitazawa Haruki , Garcia-Cancino Apolinaria , Villena Julio
Published: April 2020

Lactobacillus fermentum UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages after Helicobacter pylori infection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection against H. pylori infection in mice by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of H. pylori-infected mice. The differential cytokine profile induced by Lf979C in H. pylori-infected mice correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected mice, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance against H. pylori infection by modulating the gastric innate immune response. In addition, we advanced knowledge of the mechanisms involved in the beneficial effects of Lf979C by demonstrating that its EPS is partially responsible for its immunomodulatory effect.
Novel Clinical Campylobacter jejuni Infection Models Based on Sensitization of Mice to Lipooligosaccharide, a Major Bacterial Factor Triggering Innate Immune Responses in Human Campylobacteriosis
Authors: Mousavi Soraya , Bereswill Stefan , Heimesaat Markus M.
Published: April 2020

Human Campylobacter jejuni infections inducing campylobacteriosis including post-infectious sequelae such as Guillain-Barré syndrome and reactive arthritis are rising worldwide and progress into a global burden of high socioeconomic impact. Intestinal immunopathology underlying campylobacteriosis is a classical response of the innate immune system characterized by the accumulation of neutrophils and macrophages which cause tissue destruction, barrier defects and malabsorption leading to bloody diarrhea. Clinical studies revealed that enteritis and post-infectious morbidities of human C. jejuni infections are strongly dependent on the structure of pathogenic lipooligosaccharides (LOS) triggering the innate immune system via Toll-like-receptor (TLR)-4 signaling. Compared to humans, mice display an approximately 10,000 times weaker TLR-4 response and a pronounced colonization resistance (CR) against C. jejuni maintained by the murine gut microbiota. In consequence, investigations of campylobacteriosis have been hampered by the lack of experimental animal models. We here summarize recent progress made in the development of murine C. jejuni infection models that are based on the abolishment of CR by modulating the murine gut microbiota and by sensitization of mice to LOS. These advances support the major role of LOS driven innate immunity in pathogenesis of campylobacteriosis including post-infectious autoimmune diseases and promote the preclinical evaluation of novel pharmaceutical strategies for prophylaxis and treatment.
Characterization of the Duodenal Mucosal Microbiome in Obese Adult Subjects by 16S rRNA Sequencing
Authors: Nardelli Carmela , Granata Ilaria , D'Argenio Valeria , Tramontano Salvatore , Compare Debora , Guarracino Mario Rosario , Nardone Gerardo , Pilone Vincenzo , Sacchetti Lucia
Published: April 2020

The gut microbiota may have an impact on obesity. To date, the majority of studies in obese patients reported microbiota composition in stool samples. The aim of this study was to investigate the duodenal mucosa dysbiosis in adult obese individuals from Campania, a region in Italy with a very high percentage of obese people, to highlight microbial taxa likely associated with obesity. Duodenum biopsies were taken during upper gastrointestinal endoscopy in 19 obese (OB) and 16 lean control subjects (CO) and microbiome studied by 16S rRNA gene sequencing. Duodenal microbiome in our groups consisted of six phyla: Proteobacteria, Firmicutes, Actinobacteria, Fusobacteria, Bacteroidetes and Acidobacteria. Proteobacteria (51.1% vs. 40.1%) and Firmicutes (33.6% vs. 44.9%) were significantly (p < 0.05) more and less abundant in OB compared with CO, respectively. Oribacterium asaccharolyticum, Atopobium parvulum and Fusobacterium nucleatum were reduced (p < 0.01) and Pseudomonadales were increased (p < 0.05) in OB compared with CO. Receiver operating characteristic curve analysis showed Atopobium and Oribacterium genera able to discriminate with accuracy (power = 75% and 78%, respectively) OB from CO. In conclusion, increased Proteobacteria and decreased Firmicutes (Lachnospiraceae) characterized the duodenal microbiome of obese subjects. These data direct to further studies to evaluate the functional role of the dysbiotic-obese-associated signature.
Soybean Oil Modulates the Gut Microbiota Associated with Atherogenic Biomarkers
Authors: Korach-Rechtman Hila , Rom Oren , Mazouz Lirane , Freilich Shay , Jeries Helana , Hayek Tony , Aviram Michael , Kashi Yechezkel
Published: April 2020

During the last few decades there has been a staggering rise in human consumption of soybean-oil (SO). The microbiome and specific taxa composing it are dramatically affected by diet; specifically, by high-fat diets. Increasing evidence indicates the association between dysbiosis and health or disease state, including cardiovascular diseases (CVD) and atherosclerosis pathogenesis in human and animal models. To investigate the effects of high SO intake, C57BL/6 mice were orally supplemented with SO-based emulsion (SOE) for one month, followed by analyses of atherosclerosis-related biomarkers and microbiota profiling by 16S rRNA gene sequencing of fecal DNA. SOE-supplementation caused compositional changes to 64 taxa, including enrichment in Bacteroidetes, Mucispirillum, Prevotella and Ruminococcus, and decreased Firmicutes. These changes were previously associated with atherosclerosis in numerous studies. Among the shifted taxa, 40 significantly correlated with at least one atherosclerosis-related biomarker (FDR < 0.05), while 13 taxa positively correlated with the average of all biomarkers. These microbial alterations also caused a microbial-derived metabolic-pathways shift, including enrichment in different amino-acid metabolic-pathways known to be implicated in CVD. In conclusion, our results demonstrate dysbiosis following SOE supplementation associated with atherosclerosis-related biomarkers. These findings point to the microbiome as a possible mediator to CVD, and it may be implemented into non-invasive diagnostic tools or as potential therapeutic strategies.
Epichloë Endophyte Infection Rates and Alkaloid Content in Commercially Available Grass Seed Mixtures in Europe
Authors: Krauss Jochen , Vikuk Veronika , Young Carolyn A. , Krischke Markus , Mueller Martin J. , Baerenfaller Katja
Published: April 2020

Fungal endophytes of the genus Epichloë live symbiotically in cool season grass species and can produce alkaloids toxic to insects and vertebrates, yet reports of intoxication of grazing animals have been rare in Europe in contrast to overseas. However, due to the beneficial resistance traits observed in Epichloë infected grasses, the inclusion of Epichloë in seed mixtures might become increasingly advantageous. Despite the toxicity of fungal alkaloids, European seed mixtures are rarely tested for Epichloë infection and their infection status is unknown for consumers. In this study, we tested 24 commercially available seed mixtures for their infection rates with Epichloë endophytes and measured the concentrations of the alkaloids ergovaline, lolitrem B, paxilline, and peramine. We detected Epichloë infections in six seed mixtures, and four contained vertebrate and insect toxic alkaloids typical for Epichloë festucae var. lolii infecting Lolium perenne. As Epichloë infected seed mixtures can harm livestock, when infected grasses become dominant in the seeded grasslands, we recommend seed producers to test and communicate Epichloë infection status or avoiding Epichloë infected seed mixtures.
Viruses of Respiratory Tract: an Observational Retrospective Study on Hospitalized Patients in Rome, Italy
Authors: Ciotti Marco , Maurici Massimo , Santoro Viviana , Coppola Luigi , Sarmati Loredana , De Carolis Gerardo , De Filippis Patrizia , Pica Francesca
Published: April 2020

Respiratory tract infections account for high morbidity and mortality around the world. Fragile patients are at high risk of developing complications such as pneumonia and may die from it. Limited information is available on the extent of the circulation of respiratory viruses in the hospital setting. Most knowledge relates to influenza viruses (FLU) but several other viruses produce flu-like illness. The study was conducted at the University Hospital Policlinico Tor Vergata, Rome, Italy. Clinical and laboratory data from hospitalized patients with respiratory tract infections during the period October 2016–March 2019 were analysed. The retrospective analysis included 17 viral agents detected by FilmArray test and clinical data from medical records and hospital discharge sheets. Models were adjusted for relevant confounders such as clinical severity and risk of death, socio-demographic characteristics and surgical procedures. From a total of 539 specimens analysed, 180 (33.39%) were positive for one or more respiratory viruses. Among them, 83 (46.1 %) were positive for influenza viruses (FLU), 36 (20%) rhino/enteroviruses (RHV/EV), 17 (9.44%) human coronaviruses (HCOV-229E, -HKU1, -NL63, and -OC43), 17 (9.44%) respiratory syncytial virus, 15 (8.33%) human metapneumovirus (HMPV), 8 (4.44%) parainfluenza viruses (PIV) and 4 (2.22%) adenoviruses (ADV). The distribution of viral agents varied across age groups and month of detection. The positive specimens were from 168 patients [102 M, 66 F; median age (range): 64 years (19−93)]. Overall, 40% of them had a high-grade clinical severity and a 27% risk of death; 27 patients died and 22 of them (81.5%) had received a clinical diagnosis of pneumonia. Respiratory viral infections may have a severe course and a poor prognosis in hospitalized patients, due to underlying comorbidities. Monitoring the circulation of respiratory viruses in hospital settings is important to improve diagnosis, prevention and treatment.
Biochar and Rhizobacteria Amendments Improve Several Soil Properties and Bacterial Diversity
Authors: Ren Han , Huang Baoling , Fernández-García Víctor , Miesel Jessica , Yan Li , Lv Chengqun
Published: April 2020

In the current context, there is a growing interest in reducing the use of chemical fertilizers and pesticides to promote ecological agriculture. The use of biochar and plant growth-promoting rhizobacteria (PGPR) is an environmentally friendly alternative that can improve soil conditions and increase ecosystem productivity. However, the effects of biochar and PGPR amendments on forest plantations are not well known. The aim of this study is to investigate the effects of biochar and PGPR applications on soil nutrients and bacterial community. To achieve this goal, we applied amendments of (i) biochar at 20 t hm−2, (ii) PGPR at 5 × 1010 CFU mL−1, and (iii) biochar at 20 t hm−2 + PGPR at 5 × 1010 CFU mL−1 in a eucalyptus seedling plantation in Guangxi, China. Three months after applying the amendments, we collected six soil samples from each treatment and from control plots. From each soil sample, we analyzed several physicochemical properties (pH, electrical conductivity, total N, inorganic N, NO3−-N, NH4+-N, total P, total K, and soil water content), and we determined the bacterial community composition by sequencing the ribosomal 16S rRNA. Results indicated that co-application of biochar and PGPR amendments significantly decreased concentrations of soil total P and NH4+-N, whereas they increased NO3-N, total K, and soil water content. Biochar and PGPR treatments increased the richness and diversity of soil bacteria and the relative abundance of specific bacterial taxa such as Actinobacteria, Gemmatimonadetes, and Cyanobacteria. In general, the microbial composition was similar in the two treatments with PGPR. We also found that soil physicochemical properties had no significant influence on the soil composition of bacterial phyla, but soil NH4+-N was significantly related to the soil community composition of dominant bacterial genus. Thus, our findings suggest that biochar and PGPR amendments could be useful to maintain soil sustainability in eucalyptus plantations.
Small Molecule Inhibitors of the Response Regulator ArsR Exhibit Bactericidal Activity against Helicobacter pylori
Authors: González Andrés , Casado Javier , Chueca Eduardo , Salillas Sandra , Velázquez-Campoy Adrián , Sancho Javier , Lanas Ángel
Published: April 2020

Helicobacter pylori is considered the most prevalent bacterial pathogen in humans. The increasing antibiotic resistance evolved by this microorganism has raised alarm bells worldwide due to the significant reduction in the eradication rates of traditional standard therapies. A major challenge in this antibiotic resistance crisis is the identification of novel microbial targets whose inhibitors can overcome the currently circulating resistome. In the present study, we have validated the use of the essential response regulator ArsR as a novel and promising therapeutic target against H. pylori infections. A high-throughput screening of a repurposing chemical library using a fluorescence-based thermal shift assay identified several ArsR binders. At least four of these low-molecular weight compounds noticeably inhibited the DNA binding activity of ArsR and showed bactericidal effects against antibiotic-resistant strains of H. pylori. Among the ArsR inhibitors, a human secondary bile acid, lithocholic acid, quickly destroyed H. pylori cells and exhibited partial synergistic action in combination with clarithromycin or levofloxacin, while the antimicrobial effect of this compound against representative members of the normal human microbiota such as Escherichia coli and Staphylococcus epidermidis appeared irrelevant. Our results enhance the battery of novel therapeutic tools against refractory infections caused by multidrug-resistant H. pylori strains.
Spheres of Influence: Insights into Salmonella Pathogenesis from Intestinal Organoids
Authors: Verma Smriti , Senger Stefania , Cherayil Bobby J. , Faherty Christina S.
Published: April 2020

The molecular complexity of host-pathogen interactions remains poorly understood in many infectious diseases, particularly in humans due to the limited availability of reliable and specific experimental models. To bridge the gap between classical two-dimensional culture systems, which often involve transformed cell lines that may not have all the physiologic properties of primary cells, and in vivo animal studies, researchers have developed the organoid model system. Organoids are complex three-dimensional structures that are generated in vitro from primary cells and can recapitulate key in vivo properties of an organ such as structural organization, multicellularity, and function. In this review, we discuss how organoids have been deployed in exploring Salmonella infection in mice and humans. In addition, we summarize the recent advancements that hold promise to elevate our understanding of the interactions and crosstalk between multiple cell types and the microbiota with Salmonella. These models have the potential for improving clinical outcomes and future prophylactic and therapeutic intervention strategies.
Enhancing Pharmaceutical Packaging through a Technology Ecosystem to Facilitate the Reuse of Medicines and Reduce Medicinal Waste
Authors: Hui Terence K. L. , Mohammed Bilal , Donyai Parastou , McCrindle Rachel , Sherratt R. Simon
Published: April 2020

Background: The idea of reusing dispensed medicines is appealing to the general public provided its benefits are illustrated, its risks minimized, and the logistics resolved. For example, medicine reuse could help reduce medicinal waste, protect the environment and improve public health. However, the associated technologies and legislation facilitating medicine reuse are generally not available. The availability of suitable technologies could arguably help shape stakeholders’ beliefs and in turn, uptake of a future medicine reuse scheme by tackling the risks and facilitating the practicalities. A literature survey is undertaken to lay down the groundwork for implementing technologies on and around pharmaceutical packaging in order to meet stakeholders’ previously expressed misgivings about medicine reuse (’stakeholder requirements’), and propose a novel ecosystem for, in effect, reusing returned medicines. Methods: A structured literature search examining the application of existing technologies on pharmaceutical packaging to enable medicine reuse was conducted and presented as a narrative review. Results: Reviewed technologies are classified according to different stakeholders’ requirements, and a novel ecosystem from a technology perspective is suggested as a solution to reusing medicines. Conclusion: Active sensing technologies applying to pharmaceutical packaging using printed electronics enlist medicines to be part of the Internet of Things network. Validating the quality and safety of returned medicines through this network seems to be the most effective way for reusing medicines and the correct application of technologies may be the key enabler.
Contrasting PTH Response of Denosumab Use in Dialysis Patients: A Report of 2 Cases
Authors: Jang Soo Min , Anam Smitha , Pringle Tara , Lahren Paul , Infante Sergio
Published: April 2020

A common complication of end-stage renal disease (ESRD) is mineral and bone disorder. Yet, many anti-osteoporotic drugs are contraindicated in ESRD patients. Denosumab, a monoclonal antibody, does not require renal dose adjustment. However, its use is uncertain due to a lack of safety and efficacy of data in this population. Two hemodialysis patient cases of contrasting responses in parathyroid hormone (PTH) after denosumab administration were observed. Patient 1, a 62-years-old male received denosumab 60 mg at Day 0. His calcium decreased from 8.8 mg/dL to 6.8 mg/dL on Day 30. The PTH level increased from 265 pg/mL to 372 pg/mL after 30 days. Calcium and PTH levels approached normal range after increasing doses of vitamin D/calcium supplements, and calcitriol. Patient 2, a 72-years-old male on hemodialysis also received denosumab 60 mg on Day 0. His baseline calcium and PTH were 9.2 mg/dL and 420 pg/mL, respectively. On Day 30, his calcium level decreased (6.8 mg/dL) but, PTH level drastically increased (>5000 pg/mL). Denosumab commonly causes hypocalcemia and hyperparathyroidism since it inhibits osteoclast activation, reduces calcium release from bone and increases PTH levels as a compensatory mechanism. With a wait-and-watch approach, Patient 2’s levels approached the normal range (calcium 9.6 mg/dL and PTH 274 pg/mL at Day 90).
Seasonal and Interannual Variability of the Indo-Pacific Warm Pool and its Associated Climate Factors Based on Remote Sensing
Authors: Yin Zi , Dong Qing , Kong Fanping , Cao Dan , Long Shuang
Published: April 2020

With satellite observed Sea Surface Temperature (SST) accumulated for multiple decades, multi-time scale variabilities of the Indo-Pacific Warm Pool are examined and contrasted in this study by separating it into the Indian Ocean sector and the Pacific Ocean sector. Surface size, zonal center, meridional center, maximum SST and mean SST as the practical warm pool properties are chosen to investigate the warm pool variations for the period 1982–2018. On the seasonal time scale, the oscillation of the Indian Warm Pool is found much more vigorous than the Pacific Warm Pool on size and intensity, yet the interannual variabilities of the Indian Warm Pool and the Pacific Warm Pool are comparable. The Indian Warm Pool has weak interannual variations (3–5 years) and the Pacific Warm Pool has mighty interdecadal variations. The size, zonal movement and mean SST of the Indian Ocean Warm Pool (IW) are more accurate to depict the seasonal variability, and for the Pacific Ocean Warm Pool (PW), the size, zonal and meridional movements and maximum SST are more suitable. On the interannual scale, except for the meridional movements, all the other properties of the same basin have similar interannual variation signals. Following the correlation analysis, it turns out that the Indian Ocean basin-wide index (IOBW) is the most important contributor to the variabilities of both sectors. Lead-lag correlation results show that variation of the Pacific Ocean Warm Pool leads the IOBW and variation of the Indian Ocean Warm Pool is synchronous with the IOBW. This indicates that both sectors of the Indo-Pacific Warm Pool are significantly correlated with basin-wide warming or cooling.