bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors of Anti-Vascular Endothelial Growth Factor Therapy Withdrawal in Patients with Neovascular Age-Related Macular Degeneration: Implications for Improving Patient Adherence
Authors: Gomi Fumi , Toyoda Reiko , Yoon Annabelle Hein , Imai Kota
Published: July 2021

We investigated the factors associated with the discontinuation of anti-vascular endothelial growth factor (VEGF) therapies in patients with neovascular age-related macular degeneration (AMD). Japanese patients with AMD aged ≥50 years, reporting at least one prior injection of an anti-VEGF drug, completed an online survey covering reasons for discontinuation or dissatisfaction with therapy, quality of life (EQ-5D-5L) and patient activation (PAM-13). The respondents were divided into two cohorts: Cohort 1—patients who discontinued anti-VEGF therapy (n = 207); Cohort 2—patients continuing anti-VEGF therapy (n = 65). The most common reason for discontinuing therapy was the “doctor’s decision” in 89.4% (Cohort 1-1). In the other 22 (10.6%) patients in Cohort 1 (Cohort 1-2), reasons included “no deterioration in vision”, “financial burden” and “ineffective treatment”. Patients in Cohort 2 were dissatisfied with “long waiting times” (77%), “financial burden” and “ineffective treatment”. Pain/discomfort posed the greatest impact on quality of life. Only 5% of patients in Cohorts 1-1 and 2 and none in Cohort 1-2 were considered advocates for their own health. In conclusion, most patients who discontinued anti-VEGF therapy did so at their doctor’s decision. Addressing the reasons associated with discontinuation or dissatisfaction with anti-VEGF therapies might help improve their continuation.
Oral Candidosis: Pathophysiology and Best Practice for Diagnosis, Classification, and Successful Management
Authors: Lu Shin-Yu
Published: July 2021

Oral candidosis is the most common fungal infection that frequently occurs in patients debilitated by other diseases or conditions. No candidosis happens without a cause; hence oral candidosis has been branded as a disease of the diseased. Prior research has identified oral candidosis as a mark of systemic diseases, such as hematinic deficiency, diabetes mellitus, leukopenia, HIV/AIDS, malignancies, and carbohydrate-rich diet, drugs, or immunosuppressive conditions. An array of interaction between Candida and the host is dynamic and complex. Candida exhibits multifaceted strategies for growth, proliferation, evasion of host defenses, and survival within the host to induce fungal infection. Oral candidosis presents a variety of clinical forms, including pseudomembranous candidosis, erythematous candidosis, angular cheilitis, median rhomboid glossitis, cheilocandidosis, juxtavermillion candidosis, mucocutaneous candidosis, hyperplastic candidosis, oropharyngeal candidosis, and rare suppurative candidosis. The prognosis is usually favorable, but treatment failure or recurrence is common due to either incorrect diagnosis, missing other pathology, inability to address underlying risk factors, or inaccurate prescription of antifungal agents. In immunocompromised patients, oropharyngeal candidosis can spread to the bloodstream or upper gastrointestinal tract, leading to potentially lethal systemic candidosis. This review therefore describes oral candidosis with regard to its pathophysiology and best practice for diagnosis, practical classification, and successful management.
Genome-Wide Expression Profiling of Small RNAs in Indian Strain of Rhizoctonia solani AG1-1A Reveals Differential Regulation of milRNAs during Pathogenesis and Crosstalk of Gene Regulation
Authors: Prathi Naresh Babu , Durga Rani Chagamreddy Venkata , Balachandran Sena Munuswamy , Prakasam Vellaisamy , Chandra Mohan Yeshala , Nagalakshmi Sanivarapu , Srivastava Sunil K. , Sundaram Raman Meenakshi , Mangrauthia Satendra K.
Published: July 2021

Rhizoctonia solani AG1-1A is a necrotrophic fungus that causes sheath blight disease in rice. The reliable resistant source against this phytopathogenic fungus is not available in the gene pool of rice. Better understanding of pathogen genomics and gene regulatory networks are critical to devise alternate strategies for developing resistance against this noxious pathogen. In this study, miRNA-like RNAs (milRNAs) of an Indian strain of R. solani were identified by deep sequencing of small RNAs. We identified 128 known and 22 novel milRNAs from 20,963,123 sequence reads. These milRNAs showed 1725 target genes in the fungal genome which include genes associated with growth, development, pathogenesis and virulence of R. solani. Notably, these fungal milRNAs showed their target genes in host (rice) genome also which were later verified by qRT-PCR. The host target genes are associated with auxin metabolism, hypersensitive response, defense genes, and genes related to growth and development of rice. Osa-vacuolar-sorting receptor precursor: Rhi-milR-13, Osa-KANADI1:Rhi-milR-124, Osa-isoflavone reductase: Rhi-milR-135, Osa-nuclear transcription factor Y:Rhi-milR-131, Osa-NB-ARC domain containing protein: Rhi-milR-18, and Osa-OsFBX438: Rhi-milR-142 are notable potential regulons of host target genes: fungal milRNAs that need to be investigated for better understanding of the crosstalk of RNAi pathways between R. solani and rice. The detailed expression analysis of 17 milRNAs by qRT-PCR was analysed during infection at different time points of inoculation, at different growth stages of the host, in four different genotypes of the host, and also in four different strains of fungi which revealed differential regulation of milRNAs associated with pathogenesis and virulence. This study highlights several important findings on fungal milRNAs which need to be further studied and characterized to decipher the gene expression and regulation of this economically important phytopathogen.
Phylogenetic Position of Shiraia-Like Endophytes on Bamboos and the Diverse Biosynthesis of Hypocrellin and Hypocrellin Derivatives
Authors: Tong Xin , Wang Qiu-Tong , Shen Xiao-Ye , Hou Cheng-Lin , Cannon Paul F.
Published: July 2021

The main active ingredients of the fruiting bodies of Shiraia bambusicola and Rubroshiraia bambusae are Hypocrellins, belonging perylenequinones with potential photodynamic activity against cancer and microbial diseases. However, the strains of S. bambusicola and R. bambusae do not produce hypocrellins in culture, so resource exploitation of natural products was seriously restricted. In this study, a series of novel Shiraia-like fungal endophyte strains, with varying sporulation ability and synthesizing diverse secondary metabolites, was isolated from different bamboos. Based on phylogenetic analyses and morphological characteristics of the endophytes, Pseudoshiraia conidialis gen. et sp. nov. is proposed. The secondary metabolites of different fruiting bodies and strains have been comprehensively analyzed for the first time, finding that the endophytic strains are shown not only to produce hypocrellins, but also other perylenequinonoid compounds. It was noteworthy that the highest yield of total perylenequinone production and hypocrellin A appeared in P. conidialis CNUCC 1353PR (1410.13 mg/L), which was significantly higher than any other wild type P. conidialis strains in published reports. In view of these results, the identification of Shiraia-like endophytes not only confirm the phylogenetic status of similar strains, but will further assist in developing the production of valuable natural products.
Characteristics of Fake News and Misinformation in Greece: The Rise of New Crowdsourcing-Based Journalistic Fact-Checking Models
Authors: Lamprou Evangelos , Antonopoulos Nikos , Anomeritou Iouliani , Apostolou Chrysoula
Published: July 2021

Fake news and misinformation are a menace to the public sphere, democracy, and society with sometimes irreversible consequences. Journalists in the new era seem not to be able or willing to play their traditional role of gatekeeper and social media have made the problem even more intense. The need for truth is unnegotiable in modern democracies. Nevertheless, non-true stories and misinformation dominate media outlets with severe consequences and negative impacts on societies all over the world. Fact-checking platforms based on crowdsourcing strategies or automated digital websites might be the answer to a problem that is escalating. Initially, in order to tackle such a severe problem, researchers and experts have to monitor its characteristics. Very few research attempts have been conducted in Greece on fake news, its characteristics, origin, and impact. This dissertation scopes to map the characteristics of fake news and misinformation in an EU country such as Greece, based on the findings of “Ellinika Hoaxes” a fact-checking platform that uses in combination professional fact-checkers and crowdsourcing strategies in collaboration with Facebook. The findings shape new perspectives on the nature of misinformation and fake news in Greece and focus on new communication and fact-checking models.
Quantitative Measurement of Breast Tumors Using Intravoxel Incoherent Motion (IVIM) MR Images
Authors: Chan Si-Wa , Hu Wei-Hsuan , Ouyang Yen-Chieh , Su Hsien-Chi , Lin Chin-Yao , Chang Yung-Chieh , Hsu Chia-Chun , Chen Kuan-Wen , Liu Chia-Chen , Chien Sou-Hsin
Published: July 2021

Breast magnetic resonance imaging (MRI) is currently a widely used clinical examination tool. Recently, MR diffusion-related technologies, such as intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI), have been extensively studied by breast cancer researchers and gradually adopted in clinical practice. In this study, we explored automatic tumor detection by IVIM-DWI. We considered the acquired IVIM-DWI data as a hyperspectral image cube and used a well-known hyperspectral subpixel target detection technique: constrained energy minimization (CEM). Two extended CEM methods—kernel CEM (K-CEM) and iterative CEM (I-CEM)—were employed to detect breast tumors. The K-means and fuzzy C-means clustering algorithms were also evaluated. The quantitative measurement results were compared to dynamic contrast-enhanced T1-MR imaging as ground truth. All four methods were successful in detecting tumors for all the patients studied. The clustering methods were found to be faster, but the CEM methods demonstrated better performance according to both the Dice and Jaccard metrics. These unsupervised tumor detection methods have the advantage of potentially eliminating operator variability. The quantitative results can be measured by using ADC, signal attenuation slope, D*, D, and PF parameters to classify tumors of mass, non-mass, cyst, and fibroadenoma types.
Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma
Authors: Ilcus Cristina , Silaghi Horatiu , Georgescu Carmen Emanuela , Georgiu Carmen , Ciurea Anca Ileana , Nicoara Simona Delia , Silaghi Cristina Alina
Published: July 2021

Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis. Germinomas are highly radiosensitive tumours, with survival rates >90% in the context of chemoradiotherapy. However, patients with resistant disease have limited therapeutic options and poor survival. The aim of this review is to highlight the genetic, epigenetic, and immunologic features, which could provide the basis for targeted therapy. Intracranial germinomas present genetic and epigenetic alterations (chromosomal aberrations, KIT, MAPK and PI3K pathways mutations, DNA hypomethylation, miRNA dysregulation) that may represent targets for therapy. Tyrosine kinase and mTOR inhibitors warrant further investigation in these cases. Immune markers, PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1), are expressed in germinomas, representing potential targets for immune checkpoint inhibitors. Resistant cases should benefit from a personalized management: genetic and immunological testing and enrolment in trials evaluating targeted therapies in intracranial germinomas.
Sustainable Landscape Planning to Mitigate Wildlife–Vehicle Collisions
Authors: Fedorca Ancuta , Fedorca Mihai , Ionescu Ovidiu , Jurj Ramon , Ionescu Georgeta , Popa Marius
Published: July 2021

Road development, traffic intensification, and collisions with wildlife represent a danger both for road safety and species conservation. For planners, deciding which mitigation methods to apply is often problematic. Through a kernel density estimate, we analyzed 715 crossing locations and wildlife–vehicle collisions (WVCs) involving brown bears, lynx, wolf, red deer, roe deer, and wild boar in the Southeastern Carpathian Mountains. We identified 25 WVC hotspots, of which eight require urgent mitigation of existing infrastructure. Moreover, many of these hotspots are in Natura 2000 sites, along road sections where vegetation is in close proximity, animal movement is the highest, and driver visibility is low. Our study is the first in Romania to recommend practical solutions to remediate WVC hotspots and benefit sustainable landscape management.
Inverse Problem for the Sobolev Type Equation of Higher Order
Authors: Zamyshlyaeva Alyona , Lut Aleksandr
Published: July 2021

The article investigates the inverse problem for a complete, inhomogeneous, higher-order Sobolev type equation, together with the Cauchy and overdetermination conditions. This problem was reduced to two equivalent problems in the aggregate: regular and singular. For these problems, the theory of polynomially bounded operator pencils is used. The unknown coefficient of the original equation is restored using the method of successive approximations. The main result of this work is a theorem on the unique solvability of the original problem. This study continues and generalizes the authors’ previous research in this area. All the obtained results can be applied to the mathematical modeling of various processes and phenomena that fit the problem under study.
3D Model Identification of a Soft Robotic Neck
Authors: Quevedo Fernando , Muñoz Jorge , Castano Pena Juan Alejandro , Monje Concepción A.
Published: July 2021

Soft robotics is becoming an emerging solution to many of the problems in robotics, such as weight, cost and human interaction. In order to overcome such problems, bio-inspired designs have introduced new actuators, links and architectures. However, the complexity of the required models for control has increased dramatically and geometrical model approaches, widely used to model rigid dynamics, are not enough to model these new hardware types. In this paper, different linear and non-linear models will be used to model a soft neck consisting of a central soft link actuated by three motor-driven tendons. By combining the force on the different tendons, the neck is able to perform a motion similar to that of a human neck. In order to simplify the modeling, first a system input–output redefinition is proposed, considering the neck pitch and roll angles as outputs and the tendon lengths as inputs. Later, two identification strategies are selected and adapted to our case: set membership, a data-driven, nonlinear and non-parametric identification strategy which needs no input redefinition; and Recursive least-squares (RLS), a widely recognized identification technique. The first method offers the possibility of modeling complex dynamics without specific knowledge of its mathematical representation. The selection of this method was done considering its possible extension to more complex dynamics and the fact that its impact in soft robotics is yet to be studied according to the current literature. On the other hand, RLS shows the implication of using a parametric and linear identification in a nonlinear plant, and also helps to evaluate the degree of nonlinearity of the system by comparing the different performances. In addition to these methods, a neural network identification is used for comparison purposes. The obtained results validate the modeling approaches proposed.
An Operational Characterization of Soft Topologies by Crisp Topologies
Authors: Alcantud José Carlos R.
Published: July 2021

This paper contributes to the expanding literature on soft topology. We first prove that soft topologies can be characterized by crisp topologies. This takes advantage of two connected constructions that produce soft topologies from crisp topologies and vice versa. Both constructions are explicit and amenable to mathematical manipulations. Various consequences demonstrate that our theory has far-reaching implications for the development of soft topology and its extensions.
Nonlinear Compartment Models with Time-Dependent Parameters
Authors: Merker Jochen , Kunsch Benjamin , Schuldt Gregor
Published: July 2021

A nonlinear compartment model generates a semi-process on a simplex and may have an arbitrarily complex dynamical behaviour in the interior of the simplex. Nonetheless, in applications nonlinear compartment models often have a unique asymptotically stable equilibrium attracting all interior points. Further, the convergence to this equilibrium is often wave-like and related to slow dynamics near a second hyperbolic equilibrium on the boundary. We discuss a generic two-parameter bifurcation of this equilibrium at a corner of the simplex, which leads to such dynamics, and explain the wave-like convergence as an artifact of a non-smooth nearby system in C0-topology, where the second equilibrium on the boundary attracts an open interior set of the simplex. As such nearby idealized systems have two disjoint basins of attraction, they are able to show rate-induced tipping in the non-autonomous case of time-dependent parameters, and induce phenomena in the original systems like, e.g., avoiding a wave by quickly varying parameters. Thus, this article reports a quite unexpected path, how rate-induced tipping can occur in nonlinear compartment models.
Multi-Time Generalized Nash Equilibria with Dynamic Flow Applications
Authors: Singh Shipra , Gibali Aviv , Reich Simeon
Published: July 2021

We propose a multi-time generalized Nash equilibrium problem and prove its equivalence with a multi-time quasi-variational inequality problem. Then, we establish the existence of equilibria. Furthermore, we demonstrate that our multi-time generalized Nash equilibrium problem can be applied to solving traffic network problems, the aim of which is to minimize the traffic cost of each route and to solving a river basin pollution problem. Moreover, we also study the proposed multi-time generalized Nash equilibrium problem as a projected dynamical system and numerically illustrate our theoretical results.
Important Criteria for Asymptotic Properties of Nonlinear Differential Equations
Authors: AlGhamdi Ahmed , Bazighifan Omar , El-Nabulsi Rami Ahmad
Published: July 2021

In this article, we prove some new oscillation theorems for fourth-order differential equations. New oscillation results are established that complement related contributions to the subject. We use the Riccati technique and the integral averaging technique to prove our results. As proof of the effectiveness of the new criteria, we offer more than one practical example.
Robot-Assisted Gait Training in Patients with Multiple Sclerosis: A Randomized Controlled Crossover Trial
Authors: Sconza Cristiano , Negrini Francesco , Di Matteo Berardo , Borboni Alberto , Boccia Gennaro , Petrikonis Ignas , Stankevičius Edgaras , Casale Roberto
Published: July 2021

Background and Objectives: Gait disorders represent one of the most disabling aspects in multiple sclerosis (MS) that strongly influence patient quality of life. The improvement of walking ability is a primary goal for rehabilitation treatment. The aim of this study is to evaluate the effectiveness of robot-assisted gait training (RAGT) in association with physiotherapy treatment in patients affected by MS in comparison with ground conventional gait training. Study design: Randomized controlled crossover trial. Materials and Methods: Twenty-seven participants affected by MS with EDSS scores between 3.5 and 7 were enrolled, of whom seventeen completed the study. They received five training sessions per week over five weeks of conventional gait training with (experimental group) or without (control group) the inclusion of RAGT. The patients were prospectively evaluated before and after the first treatment session and, after the crossover phase, before and after the second treatment session. The evaluation was based on the 25-foot walk test (25FW, main outcome), 6 min walk test (6MWT), Tinetti Test, Modified Ashworth Scale, and modified Motricity Index for lower limbs. We also measured disability parameters using Functional Independence Measure and Quality of Life Index, and instrumental kinematic and gait parameters: knee extensor strength, double-time support, step length ratio; 17 patients reached the final evaluation. Results: Both groups significantly improved on gait parameters, motor abilities, and autonomy recovery in daily living activities with generally better results of RAGT over control treatment. In particular, the RAGT group improved more than control group in the 25FW (p = 0.004) and the 6MWT (p = 0.022). Conclusions: RAGT is a valid treatment option that in association with physiotherapy could induce positive effects in MS-correlated gait disorders. Our results showed greater effectiveness in recovering gait speed and resistance than conventional gait training.
CM-Dil Staining and SEC of Plasma as an Approach to Increase Sensitivity of Extracellular Nanovesicles Quantification by Bead-Assisted Flow Cytometry
Authors: Nikiforova Nadezhda , Chumachenko Maria , Nazarova Inga , Zabegina Lidia , Slyusarenko Maria , Sidina Elena , Malek Anastasia
Published: July 2021

The quantification of the specific disease-associated populations of circulating extracellular membrane nanovesicles (ENVs) has opened up new opportunities for liquid biopsy in cancer and other chronic diseases. However, the sensitivity of such methods is mediated by an optimal combination of the isolation and labeling approaches, and is not yet sufficient for routine clinical application. The presented study aimed to develop, characterize, and explore a new approach to non-specific ENV staining, followed by size-exclusive chromatography (SEC), which allows us to increase the sensitivity of bead-assisted flow cytometry. Plasma from healthy donors was purified from large components, stained with lipophilic CM-Dil dye, and fractionated by means of SEC. The obtained fractions were analyzed in terms of particle size and concentration using NTA, as well as vesicular markers and plasma protein content via dot-blotting. We characterized the process of CM-Dil-stained plasma fractionation in detail and indicated the fractions with optimal characteristics. Finally, we explored the sensitivity of on-bead flow cytometry for the analysis of specific populations of plasma ENVs and demonstrated the advantages and limitations of the proposed technique.
Fabrication of Cementitious Microfiltration Membrane and Its Catalytic Ozonation for the Removal of Small Molecule Organic Pollutants
Authors: Sun Jingyi , Liu Shan , Kang Jing , Chen Zhonglin , Cai Liming , Guo Yuhao , Shen Jimin , Wang Zhe
Published: July 2021

In this study, a low-cost cementitious microfiltration membrane (CM) with a catalytic ozone oxidation function for the removal of organic pollutants was fabricated by using cementitious and C-10 μm silica powders at a certain silica–cementitious particle ratio (s/c). The effect of the s/c on the pore size distribution and mechanical strength of the membrane was investigated. The membrane pore size showed a bimodal distribution, and the higher the s/c, the closer the second peak was to the accumulated average particle size of silica. The increase in the s/c led to a decrease in the bending strength of the membrane. The cross-sectional morphology by SEM and crystal structure by XRD of CMs confirmed that a calcium silicate hydrate gel was generated around the silica powder to improve the mechanical strength of the CM. Considering the bending strength and pore size distribution of CMs, s/c = 0.5 was selected as the optimal membrane fabrication condition. The FT-IR results characterizing the surface functional groups of CMs were rich in surface hydroxyl groups with the ability to catalyze ozone oxidation for organic pollutant removal. Six small molecule organic pollutants were selected as model compounds for the efficiency experiments via a CM–ozone coupling process to prove the catalytic property of the CM. The CM has an alkaline buffering effect and can stabilize the initial pH of the solution in the catalytic ozonation process. The reuse experiments of the CM–ozone coupling process demonstrated the broad spectrum of the CM catalytic performance and self-cleaning properties. The results of this study provide the basis and experimental support to expand the practical application of CMs.
Plasma Bile Acid Profile in Patients with and without Type 2 Diabetes
Authors: Mantovani Alessandro , Dalbeni Andrea , Peserico Denise , Cattazzo Filippo , Bevilacqua Michele , Salvagno Gian Luca , Lippi Giuseppe , Targher Giovanni , Danese Elisa , Fava Cristiano
Published: July 2021

A paucity of information currently exists on plasma bile acid (BA) profiles in patients with and without type 2 diabetes mellitus (T2DM). We assayed 14 plasma BA species in 224 patients with T2DM and in 102 nondiabetic individuals with metabolic syndrome. Plasma BA levels were measured with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) technique. Multivariable linear regression analyses were undertaken to assess associations between measured plasma BA species and T2DM status after adjustment for confounding factors. The presence of T2DM was significantly associated with higher plasma concentrations of both primary BAs (adjusted-standardized β coefficient: 0.279, p = 0.005) and secondary BAs (standardized β coefficient: 0.508, p < 0.001) after adjustment for age, sex, adiposity measures, serum alanine aminotransferase and use of statins or metformin. More specifically, the presence of T2DM was significantly associated with higher levels of plasma taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid, hyodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid and glycodeoxycholic acid (adjusted-standardized β coefficients ranging from 0.315 to 0.600; p < 0.01 or less), as well as with lower plasma levels of cholic acid (adjusted-standardized β coefficient: −0.250, p = 0.013) and taurocholic acid (adjusted-standardized β coefficient: −0.309, p = 0.001). This study shows that there are marked differences in plasma BA profiles between patients with and without T2DM. Further research will be needed to better understand how these differences in plasma BA profiles may interplay with the pathophysiology of T2DM.
Plant Growth Promoting Rhizobacteria, Arbuscular Mycorrhizal Fungi and Their Synergistic Interactions to Counteract the Negative Effects of Saline Soil on Agriculture: Key Macromolecules and Mechanisms
Authors: Sagar Alka , Rathore Parikshita , Ramteke Pramod W. , Ramakrishna Wusirika , Reddy Munagala S. , Pecoraro Lorenzo
Published: July 2021

Soil saltiness is a noteworthy issue as it results in loss of profitability and development of agrarian harvests and decline in soil health. Microorganisms associated with plants contribute to their growth promotion and salinity tolerance by employing a multitude of macromolecules and pathways. Plant growth promoting rhizobacteria (PGPR) have an immediate impact on improving profitability based on higher crop yield. Some PGPR produce 1-aminocyclopropane-1-carboxylic (ACC) deaminase (EC 4.1.99.4), which controls ethylene production by diverting ACC into α-ketobutyrate and ammonia. ACC deaminase enhances germination rate and growth parameters of root and shoot in different harvests with and without salt stress. Arbuscular mycorrhizal fungi (AMF) show a symbiotic relationship with plants, which helps in efficient uptake of mineral nutrients and water by the plants and also provide protection to the plants against pathogens and various abiotic stresses. The dual inoculation of PGPR and AMF enhances nutrient uptake and productivity of several crops compared to a single inoculation in both normal and stressed environments. Positively interacting PGPR + AMF combination is an efficient and cost-effective recipe for improving plant tolerance against salinity stress, which can be an extremely useful approach for sustainable agriculture.
Candida albicans Biofilm Inhibition by Two Vaccinium macrocarpon (Cranberry) Urinary Metabolites: 5-(3′,4′-DihydroxyPhenyl)-γ-Valerolactone and 4-Hydroxybenzoic Acid
Authors: Ottaviano Emerenziana , Baron Giovanna , Fumagalli Laura , Leite Jessica , Colombo Elisa Adele , Artasensi Angelica , Aldini Giancarlo , Borghi Elisa
Published: July 2021

Candida spp. are pathobionts, as they can switch from commensals to pathogens, responsible for a variety of pathological processes. Adhesion to surfaces, morphological switch and biofilm-forming ability are the recognized virulence factors promoting yeast virulence. Sessile lifestyle also favors fungal persistence and antifungal tolerance. In this study, we investigated, in vitro, the efficacy of two urinary cranberry metabolites, 5-(3′,4′-dihydroxy phenyl)-γ-valerolactone (VAL) and 4-hydroxybenzoic acid (4-HBA), in inhibiting C. albicans adhesion and biofilm formation. Both the reference strain SC5314 and clinical isolates were used. We evaluated biomass reduction, by confocal microscopy and crystal violet assay, and the possible mechanisms mediating their inhibitory effects. Both VAL and 4-HBA were able to interfere with the yeast adhesion, by modulating the expression of key genes, HWP1 and ALS3. A significant dose-dependent reduction in biofilm biomass and metabolic activity was also recorded. Our data showed that the two cranberry metabolites VAL and 4-HBA could pave the way for drug development, for targeting the very early phases of biofilm formation and for preventing genitourinary Candida infections.
Analysis of Bacterial Communities on North Sea Macroalgae and Characterization of the Isolated Planctomycetes Adhaeretor mobilis gen. nov., sp. nov., Roseimaritima multifibrata sp. nov., Rosistilla ulvae sp. nov. and Rubripirellula lacrimiformis sp. nov.
Authors: Wiegand Sandra , Rast Patrick , Kallscheuer Nicolai , Jogler Mareike , Heuer Anja , Boedeker Christian , Jeske Olga , Kohn Timo , Vollmers John , Kaster Anne-Kristin , Quast Christian , Glöckner Frank Oliver , Rohde Manfred , Jogler Christian
Published: July 2021

Planctomycetes are bacteria that were long thought to be unculturable, of low abundance, and therefore neglectable in the environment. This view changed in recent years, after it was shown that members of the phylum Planctomycetes can be abundant in many aquatic environments, e.g., in the epiphytic communities on macroalgae surfaces. Here, we analyzed three different macroalgae from the North Sea and show that Planctomycetes is the most abundant bacterial phylum on the alga Fucus sp., while it represents a minor fraction of the surface-associated bacterial community of Ulva sp. and Laminaria sp. Especially dominant within the phylum Planctomycetes were Blastopirellula sp., followed by Rhodopirellula sp., Rubripirellula sp., as well as other Pirellulaceae and Lacipirellulaceae, but also members of the OM190 lineage. Motivated by the observed abundance, we isolated four novel planctomycetal strains to expand the collection of species available as axenic cultures since access to different strains is a prerequisite to investigate the success of planctomycetes in marine environments. The isolated strains constitute four novel species belonging to one novel and three previously described genera in the order Pirellulales, class Planctomycetia, phylum Planctomycetes.
Resilience of Microbial Communities after Hydrogen Peroxide Treatment of a Eutrophic Lake to Suppress Harmful Cyanobacterial Blooms
Authors: Piel Tim , Sandrini Giovanni , Muyzer Gerard , Brussaard Corina P. D. , Slot Pieter C. , van Herk Maria J. , Huisman Jef , Visser Petra M.
Published: July 2021

Applying low concentrations of hydrogen peroxide (H2O2) to lakes is an emerging method to mitigate harmful cyanobacterial blooms. While cyanobacteria are very sensitive to H2O2, little is known about the impacts of these H2O2 treatments on other members of the microbial community. In this study, we investigated changes in microbial community composition during two lake treatments with low H2O2 concentrations (target: 2.5 mg L−1) and in two series of controlled lake incubations. The results show that the H2O2 treatments effectively suppressed the dominant cyanobacteria Aphanizomenon klebahnii, Dolichospermum sp. and, to a lesser extent, Planktothrix agardhii. Microbial community analysis revealed that several Proteobacteria (e.g., Alteromonadales, Pseudomonadales, Rhodobacterales) profited from the treatments, whereas some bacterial taxa declined (e.g., Verrucomicrobia). In particular, the taxa known to be resistant to oxidative stress (e.g., Rheinheimera) strongly increased in relative abundance during the first 24 h after H2O2 addition, but subsequently declined again. Alpha and beta diversity showed a temporary decline but recovered within a few days, demonstrating resilience of the microbial community. The predicted functionality of the microbial community revealed a temporary increase of anti-ROS defenses and glycoside hydrolases but otherwise remained stable throughout the treatments. We conclude that the use of low concentrations of H2O2 to suppress cyanobacterial blooms provides a short-term pulse disturbance but is not detrimental to lake microbial communities and their ecosystem functioning.
Engineering the Steroid Hydroxylating System from Cochliobolus lunatus in Mycolicibacterium smegmatis
Authors: Felpeto-Santero Carmen , Galán Beatriz , García José Luis
Published: July 2021

14α-hydroxylated steroids are starting materials for the synthesis of contraceptive and anti-inflammatory compounds in the steroid industry. A synthetic bacterial operon containing the cytochrome P450 CYP103168 and the reductase CPR64795 of the fungus Cochlioboluslunatus able to hydroxylate steroids has been engineered into a shuttle plasmid named pMVFAN. This plasmid was used to transform two mutants of Mycolicibacterium smegmatis named MS6039-5941 and MS6039 that accumulate 4-androstene-3,17-dione (AD), and 1,4-androstadiene-3,17-dione (ADD), respectively. The recombinant mutants MS6039-5941 (pMVFAN) and MS6039 (pMVFAN) were able to efficiently express the hydroxylating CYP system of C.lunatus and produced in high yields 14αOH-AD and 14αOH-ADD, respectively, directly from cholesterol and phytosterols in a single fermentation step. These results open a new avenue for producing at industrial scale these and other hydroxylated steroidal synthons by transforming with this synthetic operon other Mycolicibacterium strains currently used for the commercial production of steroidal synthons from phytosterols as feedstock.
Persulfate Oxidation Coupled with Biodegradation by Pseudomonas fluorescens Enhances Naphthenic Acid Remediation and Toxicity Reduction
Authors: Balaberda Amy-lynne , Ulrich Ania C.
Published: July 2021

The extraction of bitumen from the Albertan oilsands produces large amounts of oil sands process-affected water (OSPW) that requires remediation. Classical naphthenic acids (NAs), a complex mixture of organic compounds containing O2− species, are present in the acid extractable organic fraction of OSPW and are a primary cause of acute toxicity. A potential remediation strategy is combining chemical oxidation and biodegradation. Persulfate as an oxidant is advantageous, as it is powerful, economical, and less harmful towards microorganisms. This is the first study to examine persulfate oxidation coupled to biodegradation for NA remediation. Merichem NAs were reacted with 100, 250, 500, and 1000 mg/L of unactivated persulfate at 21 °C and 500 and 1000 mg/L of activated persulfate at 30 °C, then inoculated with Pseudomonas fluorescens LP6a after 2 months. At 21 °C, the coupled treatment removed 52.8–98.9% of Merichem NAs, while 30 °C saw increased removals of 99.4–99.7%. Coupling persulfate oxidation with biodegradation improved removal of Merichem NAs and chemical oxidation demand by up to 1.8× and 6.7×, respectively, and microbial viability was enhanced up to 4.6×. Acute toxicity towards Vibrio fischeri was negatively impacted by synergistic interactions between the persulfate and Merichem NAs; however, it was ultimately reduced by 74.5–100%. This study supports that persulfate oxidation coupled to biodegradation is an effective and feasible treatment to remove NAs and reduce toxicity.
Metagenomic Insight of a Full Scale Eco-Friendly Treatment System of Textile Dye Wastewater Using Bioaugmentation of the Composite Culture CES-1
Authors: Santhanarajan Aalfin Emmanuel , Sul Woo-Jun , Yoo Keun-Je , Seong Hoon-Je , Kim Hong-Gi , Koh Sung-Cheol
Published: July 2021

Effects of bioaugmentation of the composite microbial culture CES-1 on a full scale textile dye wastewater treatment process were investigated in terms of water quality, sludge reduction, dynamics of microbial community structures and their functional genes responsible for degradation of azo dye, and other chemicals. The removal efficiencies for Chemical Oxygen Demand (COD), Total Nitrogen (T-N), Total Phosphorus (T-P), Suspended Solids (SS), and color intensity (96.4%, 78.4, 83.1, 84.4, and 92.0, respectively) 300–531 days after the augmentation were generally improved after bioaugmentation. The denitrification linked to T-N removal appeared to contribute to the concomitant COD removal that triggered a reduction of sludge (up to 22%) in the same period of augmentation. Azo dye and aromatic compound degradation and other downstream pathways were highly metabolically interrelated. Augmentation of CES-1 increased microbial diversity in the later stages of augmentation when a strong microbial community selection of Acinetobacterparvus, Acinetobacterjohnsonii, Marinobacter manganoxydans, Verminephrobacter sp., and Arcobacter sp. occurred. Herein, there might be a possibility that the CES-1 augmentation could facilitate the indigenous microbial community successions so that the selected communities made the augmentation successful. The metagenomic analysis turned out to be a reasonable and powerful tool to provide with new insights and useful biomarkers for the complex environmental conditions, such as the full scale dye wastewater treatment system undergoing bioaugmentation.
Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance
Authors: Ferreira Mariana , Gameiro Paula
Published: July 2021

Fluoroquinolones (FQs) are antibiotics widely used in the clinical practice due to their large spectrum of action against Gram-negative and some Gram-positive bacteria. Nevertheless, the misuse and overuse of these antibiotics has triggered the development of bacterial resistance mechanisms. One of the strategies to circumvent this problem is the complexation of FQs with transition metal ions, known as metalloantibiotics, which can promote different activity and enhanced pharmacological behaviour. Here, we discuss the stability of FQ metalloantibiotics and their possible translocation pathways. The main goal of the present review is to frame the present knowledge on the conjunction of biophysical and biological tools that can help to unravel the antibacterial action of FQ metalloantibiotics. An additional goal is to shed light on the studies that must be accomplished to ensure stability and viability of such metalloantibiotics. Potentiometric, spectroscopic, microscopic, microbiological, and computational techniques are surveyed. Stability and partition constants, interaction with membrane porins and elucidation of their role in the influx, determination of the antimicrobial activity against multidrug-resistant (MDR) clinical isolates, elucidation of the mechanism of action, and toxicity assays are described for FQ metalloantibiotics.
2019 Survey of Antimicrobial Drug Use and Stewardship Practices in Adult Cows on California Dairies: Post Senate Bill 27
Authors: Abdelfattah Essam M. , Ekong Pius S. , Okello Emmanuel , Williams Deniece R. , Karle Betsy M. , Rowe Joan D. , Marshall Edith S. , Lehenbauer Terry W. , Aly Sharif S.
Published: July 2021

Antimicrobial resistance (AMR) is a global issue for both human and animal health. Antimicrobial drug (AMD) use in animals can contribute to the emergence of AMR. In January 2018, California (CA) implemented legislation (Senate Bill 27; SB 27) requiring veterinary prescriptions for medically important AMD use in food animals. The objective of our survey was to characterize AMD use, health management, and AMD stewardship practices of adult cows on CA dairies since the implementation of SB 27. In 2019, we mailed a questionnaire to 1282 California dairies. We received a total of 131 (10.2%) survey responses from 19 counties in CA. Our results showed that 45.6% of respondents included a veterinarian in their decision on which injectable AMD to purchase. Additionally, 48.8% of dairy producers included a veterinarian in their decision on which AMDs were used to treat sick cows. The majority (96.8%) of dairy producers were aware that all uses of medically important AMDs require a prescription. Approximately 49% of respondents agreed or strongly agreed that AMD use in livestock does not cause problems in humans. The survey documents antimicrobial use and stewardship practices in CA’s dairy industry and focus areas for future research and education.
Ex and In Situ Reactivity and Sorption of Selenium in Opalinus Clay in the Presence of a Selenium Reducing Microbial Community
Authors: Bleyen Nele , Small Joe S. , Mijnendonckx Kristel , Hendrix Katrien , Albrecht Achim , De Cannière Pierre , Surkova Maryna , Wittebroodt Charles , Valcke Elie
Published: July 2021

79Se is a critical radionuclide concerning the safety of deep geological disposal of certain radioactive wastes in clay-rich formations. To study the fate of selenium oxyanions in clayey rocks in the presence of a selenium reducing microbial community, in situ tests were performed in the Opalinus Clay at the Mont Terri Rock Laboratory (Switzerland). Furthermore, biotic and abiotic batch tests were performed to assess Se(VI) and Se(IV) reactivity in the presence of Opalinus Clay and/or stainless steel, in order to support the interpretation of the in situ tests. Geochemical modeling was applied to simulate Se(VI) reduction, Se(IV) sorption and solubility, and diffusion processes. This study shows that microbial activity is required to transform Se(VI) into more reduced and sorbing Se species in the Opalinus Clay, while in abiotic conditions, Se(VI) remains unreactive. On the other hand, Se(IV) can be reduced by microorganisms but can also sorb in the presence of clay without microorganisms. In situ microbial reduction of Se oxyanions can occur with electron donors provided by the clay itself. If microorganisms would be active in the clay surrounding a disposal facility, microbial reduction of leached Se could thus contribute to the overall retention of Se in clayey host rocks.
Editorial for the Special Issue “Modularity and Twinning in Mineral Crystal Structures”
Authors: Ferraris Giovanni
Published: July 2021

Ferraris et al [...]
High Surface Area Mesoporous Silica Nanoparticles with Tunable Size in the Sub-Micrometer Regime: Insights on the Size and Porosity Control Mechanisms
Authors: Rizzi Federica , Castaldo Rachele , Latronico Tiziana , Lasala Pierluigi , Gentile Gennaro , Lavorgna Marino , Striccoli Marinella , Agostiano Angela , Comparelli Roberto , Depalo Nicoletta , Curri Maria Lucia , Fanizza Elisabetta
Published: July 2021

Mesoporous silica nanostructures (MSNs) attract high interest due to their unique and tunable physical chemical features, including high specific surface area and large pore volume, that hold a great potential in a variety of fields, i.e., adsorption, catalysis, and biomedicine. An essential feature for biomedical application of MSNs is limiting MSN size in the sub-micrometer regime to control uptake and cell viability. However, careful size tuning in such a regime remains still challenging. We aim to tackling this issue by developing two synthetic procedures for MSN size modulation, performed in homogenous aqueous/ethanol solution or two-phase aqueous/ethyl acetate system. Both approaches make use of tetraethyl orthosilicate as precursor, in the presence of cetyltrimethylammonium bromide, as structure-directing agent, and NaOH, as base-catalyst. NaOH catalyzed syntheses usually require high temperature (>80 °C) and large reaction medium volume to trigger MSN formation and limit aggregation. Here, a successful modulation of MSNs size from 40 up to 150 nm is demonstrated to be achieved by purposely balancing synthesis conditions, being able, in addition, to keep reaction temperature not higher than 50 °C (30 °C and 50 °C, respectively) and reaction mixture volume low. Through a comprehensive and in-depth systematic morphological and structural investigation, the mechanism and kinetics that sustain the control of MSNs size in such low dimensional regime are defined, highlighting that modulation of size and pores of the structures are mainly mediated by base concentration, reaction time and temperature and ageing, for the homogenous phase approach, and by temperature for the two-phase synthesis. Finally, an in vitro study is performed on bEnd.3 cells to investigate on the cytotoxicity of the MNSs.
Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy
Authors: Pang Xiao-Jing , Liu Xiu-Juan , Liu Yuan , Liu Wen-Bo , Li Yin-Ru , Yu Guang-Xi , Tian Xin-Yi , Zhang Yan-Bing , Song Jian , Jin Cheng-Yun , Zhang Sai-Yang
Published: July 2021

FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human cancer cell lines, which promotes tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising cancer therapy with small molecules. Many FAK inhibitors have been reported as anticancer agents with various mechanisms. Currently, six FAK inhibitors, including GSK-2256098 (Phase I), VS-6063 (Phase II), CEP-37440 (Phase I), VS-6062 (Phase I), VS-4718 (Phase I), and BI-853520 (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through “proteolysis targeting chimera” (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new anticancer agents.