bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs
Authors: George Blessy , Wen Xia , Jaimes Edgar A. , Joy Melanie S. , Aleksunes Lauren M.
Published: June 2021

The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that ondansetron, a 5-HT3 antagonist drug used to prevent nausea and vomiting, can inhibit OCT2- and MATE1-mediated transport. The purpose of this study was to test the ability of five 5-HT3 antagonist drugs to inhibit the OCT2 and MATE1 transporters. The transport of the OCT2/MATE1 probe substrate ASP+ was assessed using two models: (1) HEK293 kidney cells overexpressing human OCT2 or MATE1, and (2) MDCK cells transfected with human OCT2 and MATE1. In HEK293 cells, the inhibition of ASP+ uptake by OCT2 listed in order of potency was palonosetron (IC50: 2.6 μM) > ondansetron > granisetron > tropisetron > dolasetron (IC50: 85.4 μM) and the inhibition of ASP+ uptake by MATE1 in order of potency was ondansetron (IC50: 0.1 μM) > palonosetron = tropisetron > granisetron > dolasetron (IC50: 27.4 μM). Ondansetron (0.5–20 μM) inhibited the basolateral-to-apical transcellular transport of ASP+ up to 64%. Higher concentrations (10 and 20 μM) of palonosetron, tropisetron, and dolasetron similarly reduced the transcellular transport of ASP+. In double-transfected OCT2-MATE1 MDCK cells, ondansetron at concentrations of 0.5 and 2.5 μM caused significant intracellular accumulation of ASP+. Taken together, these data suggest that 5-HT3 antagonist drugs may inhibit the renal secretion of cationic drugs by interfering with OCT2 and/or MATE1 function.
Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan
Authors: Salazar Sebastián , Yutronic Nicolás , Kogan Marcelo J. , Jara Paul
Published: June 2021

This article describes the synthesis and characterization of β-cyclodextrin-based nano-sponges (NS) inclusion compounds (IC) with the anti-tumor drugs melphalan (MPH) and cytoxan (CYT), and the addition of gold nanoparticles (AuNPs) onto both systems, for the potential release of the drugs by means of laser irradiation. The NS-MPH and NS-CYT inclusion compounds were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), UV–Vis, and proton nuclear magnetic resonance (1H-NMR). Thus, the inclusion of MPH and CYT inside the cavities of NSs was confirmed. The association of AuNPs with the ICs was confirmed by SEM, EDS, TEM, and UV–Vis. Drug release studies using NSs synthesized with different molar ratios of β-cyclodextrin and diphenylcarbonate (1:4 and 1:8) demonstrated that the ability of NSs to entrap and release the drug molecules depends on the crosslinking between the cyclodextrin monomers. Finally, irradiation assays using a continuous laser of 532 nm showed that photothermal drug release of both MPH and CYT from the cavities of NSs via plasmonic heating of AuNPs is possible.
Developing a Glyoxal-Crosslinked Chitosan/Gelatin Hydrogel for Sustained Release of Human Platelet Lysate to Promote Tissue Regeneration
Authors: Tsai Ching-Cheng , Young Tai-Horng , Chen Guang-Shih , Cheng Nai-Chen
Published: June 2021

The clinical application of human platelet lysate (HPL) holds promise for tissue regeneration, and the development of an efficient vehicle for its delivery is desired. Chitosan-based hydrogels are potential candidates, but they often exhibit weak mechanical properties. In this study, a chitosan/gelatin (CS-GE) hydrogel crosslinked by glyoxal was fabricated for sustained release of HPL. The influence of HPL on Hs68 fibroblast and human umbilical vein endothelial cell (HUVEC) culture was evaluated, and we found that supplementing 5% HPL in the medium could significantly improve cell proliferation relative to supplementing 10% fetal bovine serum (FBS). Moreover, HPL accelerated the in vitro wound closure of Hs68 cells and facilitated the tube formation of HUVECs. Subsequently, we fabricated CS-GE hydrogels crosslinked with different concentrations of glyoxal, and the release pattern of FITC-dextrans (4, 40 and 500 kDa) from the hydrogels was assessed. After an ideal glyoxal concentration was determined, we further characterized the crosslinked CS-GE hydrogels encapsulated with different amounts of HPL. The HPL-incorporated hydrogel was shown to significantly promote the proliferation of Hs68 cells and the migration of HUVECs. Moreover, the release pattern of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB) from hydrogel was examined in vitro, demonstrating a sustained release profile of the growth factors. Finally, the chick chorioallantoic membrane assay revealed that HPL encapsulation in the hydrogel significantly stimulated angiogenesis in ovo. These results demonstrate the great potential of the crosslinked CS-GE hydrogel to serve as an effective delivery system for HPL to promote tissue regeneration.
Hydrogen Sulfide Metabolite, Sodium Thiosulfate: Clinical Applications and Underlying Molecular Mechanisms
Authors: Zhang Max Y. , Dugbartey George J. , Juriasingani Smriti , Sener Alp
Published: June 2021

Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (H2S), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review discusses the biochemical and molecular pathways in the generation of STS from H2S, its clinical usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these clinical applications and a future perspective in kidney transplantation.
Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases
Authors: Degtyareva Arina O. , Antontseva Elena V. , Merkulova Tatiana I.
Published: June 2021

The vast majority of the genetic variants (mainly SNPs) associated with various human traits and diseases map to a noncoding part of the genome and are enriched in its regulatory compartment, suggesting that many causal variants may affect gene expression. The leading mechanism of action of these SNPs consists in the alterations in the transcription factor binding via creation or disruption of transcription factor binding sites (TFBSs) or some change in the affinity of these regulatory proteins to their cognate sites. In this review, we first focus on the history of the discovery of regulatory SNPs (rSNPs) and systematized description of the existing methodical approaches to their study. Then, we brief the recent comprehensive examples of rSNPs studied from the discovery of the changes in the TFBS sequence as a result of a nucleotide substitution to identification of its effect on the target gene expression and, eventually, to phenotype. We also describe state-of-the-art genome-wide approaches to identification of regulatory variants, including both making molecular sense of genome-wide association studies (GWAS) and the alternative approaches the primary goal of which is to determine the functionality of genetic variants. Among these approaches, special attention is paid to expression quantitative trait loci (eQTLs) analysis and the search for allele-specific events in RNA-seq (ASE events) as well as in ChIP-seq, DNase-seq, and ATAC-seq (ASB events) data.
The Role of the Disulfide Bridge in the Copper (II) Binding by the Cyclic His4-Peptide
Authors: Pieniężna Aleksandra , Witak Weronika , Szymańska Aneta , Brasuń Justyna
Published: June 2021

In this paper, we present studies on the influence of the disulfide bridge on the copper (II) ions’ binding abilities by the cyclic His4-peptide. The studied ligand HKHPHRHC-S-S-C consists of nine amino acids. The cyclic structure was obtained through a disulfide bridge between two cysteinyl groups. Moreover, this peptide is characterized by the presence of four His residues in the sequence, which makes it an interesting ligand for transition metal ions. The potentiometric and spectroscopic (UV-Vis spectroscopy and circular dichroism spectroscopy (CD)) studies were carried out in various molar ligand to metal ratios: 2:1, 1:1, and 1:2, in the pH range of 2.5–11 at 25 °C. The results showed that the cyclic His4-peptide promotes dinuclear complexes in each of these systems and forms the final dinuclear species with the {NIm, 3N-amide}{NIm, 3N-amide} coordination mode. The obtained data shows that cyclization by the formation of the disulfide bond has an impact on the peptide chain flexibility and appearance of additional potential donors for metal ions and influences the copper (II) ions’ coordination.
Selective Antimicrobial Therapies for Periodontitis: Win the “Battle and the War”
Authors: Elashiry Mahmoud , Morandini Ana Carolina , Cornelius Timothius Celine Joyce , Ghaly Mira , Cutler Christopher W.
Published: June 2021

Traditional antimicrobial therapies for periodontitis (PD) have long focused on non-selective and direct approaches. Professional cleaning of the subgingival biofilm by instrumentation of dental root surfaces, known as scaling and root planning (SRP), is the mainstay of periodontal therapy and is indisputably effective. Non-physical approaches used as adjuncts to SRP, such as chemical and biological agents, will be the focus of this review. In this regard, traditional agents such as oral antiseptics and antibiotics, delivered either locally or systemically, were briefly reviewed as a backdrop. While generally effective in winning the “battle” against PD in the short term, by reducing its signs and symptoms, patients receiving such therapies are more susceptible to recurrence of PD. Moreover, the long-term consequences of such therapies are still in question. In particular, concern about chronic use of systemic antibiotics and their influence on the oral and gut microbiota is warranted, considering antibiotic resistance plasmids, and potential transfer between oral and non-oral microbes. In the interest of winning the “battle and the war”, new more selective and targeted antimicrobials and biologics for PD are being studied. These are principally indirect, blocking pathways involved in bacterial colonization, nutrient acquisition, inflammation or cellular invasion without directly killing the pathogens. This review will focus on current and prospective antimicrobial therapies for PD, emphasizing therapies that act indirectly on the microbiota, with clearly defined cellular and molecular targets.
User Interface Pattern for AR in Industrial Applications
Authors: Koreng Regina , Krömker Heidi
Published: June 2021

The background of the paper is that there are currently no specifications or guidelines for the design of a user interface for an augmented reality system in an industrial context. In this area, special requirements apply for the perception and recognition of content, which are given by the framework conditions of the industrial environment, the human–technology interaction, and the work task. This paper addresses the software-technical design of augmented reality surfaces in the industrial environment. The aim is to give first design examples for software tasks by means of sample solutions. For a user-oriented implementation, the methods of personas and an empirical investigation were used. Personas are a stereotypical representation of end users that reflect their characteristics and requirements. For the subsequent development of the pattern catalog, different prototypes with layout and interaction variants were tested in an empirical study with 50 participants. By observing the current realizations, these can be examined more closely in terms of their specific use in an industrial environment. The result is a pattern catalog with 26 solutions for layout and interaction variants. For the layout variants, no direct favorite of the testers could be ascertained; the existing solutions already offer a wide spectrum, which are chosen according to personal preferences. For interaction, on the other hand, it is important to enable fast input. During the study, gesture control revealed weaknesses in this regard. This can be supportive in the development of an industrial augmented reality system regarding a user-oriented representation of the interface.
Rapid Isothermal Amplification for the Buccal Detection SARS-CoV-2 in the Context of Out-Patient COVID-19 Screening
Authors: Bouam Amar , Vincent Jean-Jacques , Le Glass Elisabeth , Almeras Lionel , Levy Pierre-Yves , Tissot-Dupont Hervé , Lagier Jean-Christophe , Fournier Pierre-Edward , Raoult Didier , Drancourt Michel
Published: June 2021

A commercially available isothermal amplification of SARS-CoV-2 RNA was applied to self-collected saliva samples using dry dental cotton rolls, which were held in the mouth for two minutes. Of 212 tests, isothermal amplification yielded three (0.14%) invalid results, 120 (56.6%) positive results and 89 (42%) negative results. Compared to reference RT-PCR assays routinely performed simultaneously on nasopharyngeal swabs, excluding the three invalid isothermal amplification assays and one RT-PCR invalid assay, these figures indicated that 119/123 (96.7%) samples were positive in both methods and 85/85 samples were negative in both methods. Four positive buccal swabs which were missed by the isothermal amplification, exhibited Ct values of 26–34 in reference RT-PCR assays. Positive isothermal amplification detection was achieved in less than 10 min. Supervision of the self-sampling procedure was key to achieve these performances. These data support the proposal to use the protocol reported in this paper, including supervised buccal self-sampling, to screen people suspected of having COVID-19 at the point of care.
Utility of Acute Physiology and Chronic Health Evaluation (APACHE II) in Predicting Mortality in Patients with Pyogenic Liver Abscess: A Retrospective Study
Authors: Lee Yuan-Ti , Wang Chi-Chih , Li Chien-Feng , Chen Hsuan-Yi , Liao Hsien-Hua , Lin Chia-Chun
Published: June 2021

Pyogenic liver abscess (PLA) is a major life-threatening disease with varied clinical features. This study aimed to determine predictors of mortality in patients with PLA using criteria determined upon admission. We retrospectively examined the data of 324 hospitalized adults in whom liver abscesses were confirmed using abdominal ultrasound and/or computed tomography. The relationship between various risk factors was assessed using multivariate analysis. A total of 109 (33.6%) patients were admitted to the intensive care unit (ICU). The overall mortality rate was 7.4% and was higher among ICU patients than non-ICU patients (21.1% vs. 0.5%, p < 0.001). PLA patients with an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥18 had a 19.31-fold increased risk, and those with concomitant infections had a 34.33-fold increased risk of 30-day mortality according to multivariate analysis. The estimated area under the receiver operating characteristic curve for predicting 30-day mortality revealed that APACHE II score ≥18 (sensitivity of 75% and specificity of 84%, p < 0.0001) had better discriminative power than Sequential Organ Failure Assessment (SOFA) ≥6 (sensitivity of 81% and specificity of 66%, p < 0.0001). APACHE II has shown better discrimination ability than SOFA in predicting mortality in PLA patients. To improve outcomes in patients with PLA, future management strategies should focus on high-risk patients.
Combined Mutational and Clonality Analyses Support the Existence of Intra-Tumor Heterogeneity in Papillary Thyroid Cancer
Authors: Muzza Marina , Pogliaghi Gabriele , Persani Luca , Fugazzola Laura , Colombo Carla
Published: June 2021

Despite its potential clinical impact, intra-tumor genetic heterogeneity (ITH) has been scantly investigated in papillary thyroid cancer (PTC). We studied ITH in PTC by combining, for the first time, data derived from the evaluation of the normalized allelic frequencies (NAF) of the mutation/s, using a customized MassARRAY panel, and those obtained by the HUMARA clonality assay. Among tumors with a single mutation, 80% of cases with NAF 50 ± 5% were clonal, consistent with the presence of a single mutated clone, while 20% of cases showed a polyclonal pattern, suggesting the presence of the same mutation in two or more clones. Differently, all cases with NAF < 45% were polyclonal. Among tumors with double mutation, cases with both mutations showing NAF 50 ± 5% were monoclonal, consistent with the presence of a single clone harboring both mutations. On the other hand, all cases with double mutation at NAF < 45% were polyclonal, indicating the presence of two clones with different mutations. Finally, no significant differences in the clinico-pathological characteristics were found between monoclonal and polyclonal tumors. In conclusion, the present study adds insights into the concept of ITH in PTC, which warrants attention because the occurrence of this phenomenon is likely to affect the response to targeted drugs.
Tracheostomy Timing and Outcome in Severe COVID-19: The WeanTrach Multicenter Study
Authors: Battaglini Denise , Missale Francesco , Schiavetti Irene , Filauro Marta , Iannuzzi Francesca , Ascoli Alessandro , Bertazzoli Alberto , Pascucci Federico , Grasso Salvatore , Murgolo Francesco , Binda Simone , Maraggia Davide , Montrucchio Giorgia , Sales Gabriele , Pascarella Giuseppe , Agrò Felice Eugenio , Faccio Gaia , Ferraris Sandra , Spadaro Savino , Falò Giulia , Mereto Nadia , Uva Alessandro , Maugeri Jessica Giuseppina , Agrippino Bellissima , Vargas Maria , Servillo Giuseppe , Robba Chiara , Ball Lorenzo , Mora Francesco , Signori Alessio , Torres Antoni , Giacobbe Daniele Roberto , Vena Antonio , Bassetti Matteo , Peretti Giorgio , Rocco Patricia R. M. , Pelosi Paolo
Published: June 2021

Background: Tracheostomy can be performed safely in patients with coronavirus disease 2019 (COVID-19). However, little is known about the optimal timing, effects on outcome, and complications. Methods: A multicenter, retrospective, observational study. This study included 153 tracheostomized COVID-19 patients from 11 intensive care units (ICUs). The primary endpoint was the median time to tracheostomy in critically ill COVID-19 patients. Secondary endpoints were survival rate, length of ICU stay, and post-tracheostomy complications, stratified by tracheostomy timing (early versus late) and technique (surgical versus percutaneous). Results: The median time to tracheostomy was 15 (1–64) days. There was no significant difference in survival between critically ill COVID-19 patients who received tracheostomy before versus after day 15, nor between surgical and percutaneous techniques. ICU length of stay was shorter with early compared to late tracheostomy (p < 0.001) and percutaneous compared to surgical tracheostomy (p = 0.050). The rate of lower respiratory tract infections was higher with surgical versus percutaneous technique (p = 0.007). Conclusions: Among critically ill patients with COVID-19, neither early nor percutaneous tracheostomy improved outcomes, but did shorten ICU stay. Infectious complications were less frequent with percutaneous than surgical tracheostomy.
Predictive Value of Comorbid Conditions for COVID-19 Mortality
Authors: Marincu Iosif , Bratosin Felix , Vidican Iulia , Bostanaru Andra-Cristina , Frent Stefan , Cerbu Bianca , Turaiche Mirela , Tirnea Livius , Timircan Madalina
Published: June 2021

In this paper, we aim at understanding the broad spectrum of factors influencing the survival of infected patients and the correlations between these factors to create a predictive probabilistic score for surviving the COVID-19 disease. Initially, 510 hospital admissions were counted in the study, out of which 310 patients did not survive. A prediction model was developed based on this data by using a Bayesian approach. Following the data collection process for the development study, the second cohort of patients totaling 541 was built to validate the risk matrix previously created. The final model has an area under the curve of 0.773 and predicts the mortality risk of SARS-CoV-2 infection based on nine disease groups while considering the gender and age of the patient as distinct risk groups. To ease medical workers’ assessment of patients, we created a visual risk matrix based on a probabilistic model, ranging from a score of 1 (very low mortality risk) to 5 (very high mortality risk). Each score comprises a correlation between existing comorbid conditions, the number of comorbid conditions, gender, and age group category. This clinical model can be generalized in a hospital context and can be used to identify patients at high risk for whom immediate intervention might be required.
Management of Intraoperative Mechanical Ventilation to Prevent Postoperative Complications after General Anesthesia: A Narrative Review
Authors: Fogagnolo Alberto , Montanaro Federica , Al-Husinat Lou’i , Turrini Cecilia , Rauseo Michela , Mirabella Lucia , Ragazzi Riccardo , Ottaviani Irene , Cinnella Gilda , Volta Carlo Alberto , Spadaro Savino
Published: June 2021

Mechanical ventilation (MV) is still necessary in many surgical procedures; nonetheless, intraoperative MV is not free from harmful effects. Protective ventilation strategies, which include the combination of low tidal volume and adequate positive end expiratory pressure (PEEP) levels, are usually adopted to minimize the ventilation-induced lung injury and to avoid post-operative pulmonary complications (PPCs). Even so, volutrauma and atelectrauma may co-exist at different levels of tidal volume and PEEP, and therefore, the physiological response to the MV settings should be monitored in each patient. A personalized perioperative approach is gaining relevance in the field of intraoperative MV; in particular, many efforts have been made to individualize PEEP, giving more emphasis on physiological and functional status to the whole body. In this review, we summarized the latest findings about the optimization of PEEP and intraoperative MV in different surgical settings. Starting from a physiological point of view, we described how to approach the individualized MV and monitor the effects of MV on lung function.
The Energy Balance in Aluminum–Copper High-Speed Collision Welding
Authors: Groche Peter , Niessen Benedikt
Published: June 2021

Collision welding is a joining technology that is based on the high-speed collision and the resulting plastic deformation of at least one joining partner. The ability to form a high-strength substance-to-substance bond between joining partners of dissimilar metals allows us to design a new generation of joints. However, the occurrence of process-specific phenomena during the high-speed collision, such as a so-called jet or wave formation in the interface, complicates the prediction of bond formation and the resulting bond properties. In this paper, the collision welding of aluminum and copper was investigated at the lower limits of the process. The experiments were performed on a model test rig and observed by high-speed imaging to determine the welding window, which was compared to the ones of similar material parings from former investigation. This allowed to deepen the understanding of the decisive mechanisms at the welding window boundaries. Furthermore, an optical and a scanning electron microscope with energy dispersive X-ray analysis were used to analyze the weld interface. The results showed the important and to date neglected role of the jet and/or the cloud of particles to extract energy from the collision zone, allowing bond formation without melting and intermetallic phases.
Wave-Modified Ekman Current Solutions for the Time-Dependent Vertical Eddy Viscosity
Authors: Chen Hui , Li Shaofeng , Song Jinbao , He Hailun
Published: June 2021

This study aimed to highlight a general lack of clarity regarding the scale of the temporal averaging implicit in Ekman-type models. Under the assumption of time and depth-dependent eddy viscosity, we present an analytical Fourier series solution for a wave-modified Ekman model. The depth dependence of eddy viscosity is based on the K-Profile Parameterization (KPP) scheme. The solution reproduces major characteristics of diurnal variation in ocean velocity and shear. Results show that the time variability in eddy viscosity leads to an enhanced mean current near-surface and a decrease in the effective eddy viscosity, which finally results in an intensified near-surface shear and wakes a low-level jet flow. Rectification values are dominated by the strength of diurnal mixing, and partly due to the nonlinear depth dependence of the eddy viscosity.
Assessment of the Manoeuvrability Characteristics of a Twin Shaft Naval Vessel Using an Open-Source CFD Code
Authors: Franceschi Andrea , Piaggio Benedetto , Tonelli Roberto , Villa Diego , Viviani Michele
Published: June 2021

The purpose of this study is to assess the quality of the manoeuvre prediction of a twin-shaft naval vessel by means of a time-domain simulator based on Computational Fluid Dynamics (CFD) hydrodynamic coefficients. The simulator uses a modular approach in which the hull, rudders, appendices and propellers are based on different mathematical models. The hydrodynamic coefficients of the hull in the bare and appended configurations are computed using virtual captive tests performed with an open-source CFD code: OpenFoam. This paper demonstrates that the application of the CFD hydrodynamic coefficients led to a good estimate of the macroscopic characteristics of the main IMO manoeuvres with respect to the experimental measures. The adopted test case is the DTMB 5415M frigate both with and without appendages. This test case has been investigated in several research studies and international benchmark workshops, such as SIMMAN 2008, SIMMAN 2014 and many CFD workgroups.
Conception and Evolution of the Probabilistic Methods for Ship Damage Stability and Flooding Risk Assessment
Authors: Vassalos Dracos , Mujeeb-Ahmed M. P.
Published: June 2021

The paper provides a full description and explanation of the probabilistic method for ship damage stability assessment from its conception to date with focus on the probability of survival (s-factor), explaining pertinent assumptions and limitations and describing its evolution for specific application to passenger ships, using contemporary numerical and experimental tools and data. It also provides comparisons in results between statistical and direct approaches and makes recommendations on how these can be reconciled with better understanding of the implicit assumptions in the approach for use in ship design and operation. Evolution over the latter years to support pertinent regulatory developments relating to flooding risk (safety level) assessment as well as research in this direction with a focus on passenger ships, have created a new focus that combines all flooding hazards (collision, bottom and side groundings) to assess potential loss of life as a means of guiding further research and developments on damage stability for this ship type. The paper concludes by providing recommendations on the way forward for ship damage stability and flooding risk assessment.
Drivers, Impacts and Mitigation of Increased Sedimentation in the Hydropower Reservoirs of East Africa
Authors: Amasi Aloyce , Wynants Maarten , Blake William , Mtei Kelvin
Published: June 2021

Hydropower reservoirs are essential for the climate-neutral development of East Africa. Hydropower production, however, is threatened by human activities that lead to a decrease in water storage capacity of reservoirs. Land use/land cover and climatic changes are driving accelerated soil erosion in semi-arid East Africa, which ultimately increases reservoir sedimentation and decreases energy production. Sediment delivery dynamics at the catchment scale are complex, involving the interaction of multiple factors and processes on different spatial and temporal scales. A lack of understanding of these processes and their interactions may impede the efficiency of sediment mitigation and control strategies. A deep understanding of the processes of erosion and connectivity of the land to river channel, as well as storage of eroded material within hillslopes and floodplains, and sediment accumulation in the reservoirs supports selection of future dam locations and sustainable management of reservoirs. The sediment budget approach can provide such a holistic perspective by accounting for the various sediment sources, transport, sinks, and redistribution when the sediment is routed through that catchment. Constructing sediment budgets is challenging, but the potential for integrating a number of different techniques offers new opportunities to collect the required information. In East Africa, the spatial planning of dams is mainly dominated by political and financial motives, and impacts of land use and climate on the sediment transport dynamics are not adequately considered. Production of sediment budgets under different scenarios of land use and climate change should be an essential step when deciding the location and management strategies for dams. Selection of new hydroelectric reservoir sites must consider long-term scientific data on climate change, and the sediment budget components for sustainable land management planning, hydropower sustainability.
The Imprint of Built-Up Land Expansion on Cropland Distribution and Productivity in Shandong Province
Authors: Wang Meng , Xu Qingchen , Fan Zemeng , Sun Xiaofang
Published: June 2021

Grain self-sufficiency is a national food security target of China. The way that built-up land expansion impacts upon cropland loss and food provision needs to be explored in the major grain producing areas. Shandong Province is an important agricultural food production region, which is also experiencing rapidly urbanizing. Here we assessed the spatiotemporal distribution of cropland loss due to built-up land expansion and landscape dynamics of cropland during 2000–2020, by using 30 m resolution land cover data. We also analyzed the potential yield change influenced by cropland loss. The results showed that the area of built-up land expanded by 5199 km2 from 2000–2010, and 11,949 km2 from 2010–2020. Approximately 95% of the new built-up land was from cropland during the two stages, and the primary mode of built-up land expansion was the edge expansion. The patch density and the patch size of cropland kept increasing and decreasing, respectively, and the aggregation index kept decreasing from 2000 to 2020, indicating increased cropland fragmentation. The proportion of occupied cropland with potential yield greater than 7500 kg/ha was 25% and 37% during the former and the latter period. Thus, higher quality cropland was encroached in the recent period. The findings could provide meaningful implications for making sustainable land use development strategies in the study area and other similar regions.
New Grain Formation Mechanisms during Powder Bed Fusion
Authors: Rausch Alexander M. , Pistor Julian , Breuning Christoph , Markl Matthias , Körner Carolin
Published: June 2021

Tailoring the mechanical properties of parts by influencing the solidification conditions is a key topic of powder bed fusion. Depending on the application, single crystalline, columnar, or equiaxed microstructures are desirable. To produce single crystals or equiaxed microstructures, the control of nucleation is of outstanding importance. Either it should be avoided or provoked. There are also applications, such as turbine blades, where both microstructures at different locations are required. Here, we investigate nucleation at the melt-pool border during the remelting of CMSX-4® samples built using powder bed fusion. We studied the difference between remelting as-built and homogenized microstructures. We identified two new mechanisms that led to grain formation at the beginning of solidification. Both mechanisms involved a change in the solidification microstructure from the former remelted and newly forming material. For the as-built samples, a discrepancy between the former and new dendrite arm spacing led to increased interdentritic undercooling at the beginning of solidification. For the heat-treated samples, the collapse of a planar front led to new grains. To identify these mechanisms, we conducted experimental and numerical investigations. The identification of such mechanisms during powder bed fusion is a fundamental prerequisite to controlling the solidification conditions to produce single crystalline and equiaxed microstructures.
Matching-Type Image-Labelings of Trees
Authors: Su Jing , Wang Hongyu , Yao Bing
Published: June 2021

A variety of labelings on trees have emerged in order to attack the Graceful Tree Conjecture, but lack showing the connections between two labelings. In this paper, we propose two new labelings: vertex image-labeling and edge image-labeling, and combine new labelings to form matching-type image-labeling with multiple restrictions. The research starts from the set-ordered graceful labeling of the trees, and we give several generation methods and relationships for well-known labelings and two new labelings on trees.
Study of Synergistic Effects in Complex Stochastic Systems
Authors: Tsitsiashvili Gurami
Published: June 2021

In this paper, a method for detecting synergistic effects of the interaction of elements in multi-element stochastic systems of separate redundancy, multi-server queuing, and statistical estimates of nonlinear recurrent relations parameters has been developed. The detected effects are quite strong and manifest themselves even with rough estimates. This allows studying them with mathematical methods of relatively low complexity and thereby expand the set of possible applications. These methods are based on special techniques of the structural analysis of multi-element stochastic models in combination with majorant asymptotic estimates of their performance indicators. They allow moving to more accurate and rather economical numerical calculations, as they indicate in which direction it is most convenient to perform these calculations.
Orbital Stability of Solitary Waves to Double Dispersion Equations with Combined Power-Type Nonlinearity
Authors: Kolkovska Natalia , Dimova Milena , Kutev Nikolai
Published: June 2021

We consider the orbital stability of solitary waves to the double dispersion equation utt−uxx+h1uxxxx−h2uttxx+f(u)xx=0,h1>0,h2>0 with combined power-type nonlinearity f(u)=a|u|pu+b|u|2pu,p>0,a∈R,b∈R,b≠0. The stability of solitary waves with velocity c, c2<1 is proved by means of the Grillakis, Shatah, and Strauss abstract theory and the convexity of the function d(c), related to some conservation laws. We derive explicit analytical formulas for the function d(c) and its second derivative for quadratic-cubic nonlinearity f(u)=au2+bu3 and parameters b>0, c2∈0,min1,h1h2. As a consequence, the orbital stability of solitary waves is analyzed depending on the parameters of the problem. Well-known results are generalized in the case of a single cubic nonlinearity f(u)=bu3.
An Analysis of Usage of a Multi-Criteria Approach in an Athlete Evaluation: An Evidence of NHL Attackers
Authors: Vavrek Roman
Published: June 2021

The presented research focuses on the commonly used Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), which is applied to an evaluation of a basic set of 581 national hockey league (NHL) players in the 2018/2019 season. This is used in combination with a number of objective methods for weighting indicators for identifying differences in their usage. A total of 11 indicators with their own testimonial values, including points, hits, blocked shots and more, are selected for this purpose. The selection of a method for weighting indicators has a major influence on the results obtained and the differences between them, and maintains the internal links within the ranked set of players. Of the evaluated methods, we prefer the Mean Weight method, and we recommend that the input indicators be considered equivalent when evaluating athletes.
Bacterial Communities in Alkaline Saline Soils Amended with Young Maize Plants or Its (Hemi)Cellulose Fraction
Authors: Pérez-Hernández Valentín , Hernández-Guzmán Mario , Luna-Guido Marco , Navarro-Noya Yendi E. , Romero-Tepal Elda M. , Dendooven Luc
Published: June 2021

We studied three soils of the former lake Texcoco with different electrolytic conductivity (1.9 dS m−1, 17.3 dS m−1, and 33.4 dS m−1) and pH (9.3, 10.4, and 10.3) amended with young maize plants and their neutral detergent fibre (NDF) fraction and aerobically incubated in the laboratory for 14 days while the soil bacterial community structure was monitored by means of 454-pyrosequencing of their 16S rRNA marker gene. We identified specific bacterial groups that showed adaptability to soil salinity, i.e., Prauseria in soil amended with young maize plants and Marinobacter in soil amended with NDF. An increase in soil salinity (17.3 dS m−1, 33.4 dS m−1) showed more bacterial genera enriched than soil with low salinity (1.9 dS m−1). Functional prediction showed that members of Alfa-, Gamma-, and Deltaproteobacteria, which are known to adapt to extreme conditions, such as salinity and low nutrient soil content, were involved in the lignocellulose degradation, e.g., Marinimicrobium and Pseudomonas as cellulose degraders, and Halomonas and Methylobacterium as lignin degraders. This research showed that the taxonomic annotation and their functional prediction both highlighted keystone bacterial groups with the ability to degrade complex C-compounds, such as lignin and (hemi)cellulose, in the extreme saline-alkaline soil of the former Lake of Texcoco.
Oral Lactobacillus Species in Systemic Sclerosis
Authors: Melchiorre Daniela , Ceccherini Maria Teresa , Romano Eloisa , Cometi Laura , El-Aoufy Khadija , Bellando-Randone Silvia , Roccotelli Angela , Bruni Cosimo , Moggi-Pignone Alberto , Carboni Davide , Guiducci Serena , Lepri Gemma , Tofani Lorenzo , Pietramellara Giacomo , Matucci-Cerinic Marco
Published: June 2021

In systemic sclerosis (SSc), the gastrointestinal tract (GIT) plays a central role in the patient’s quality of life. The microbiome populates the GIT, where a relationship between the Lactobacillus and gastrointestinal motility has been suggested. In this study, the analysis of oral Lactobacillus species in SSc patients and healthy subjects using culture-independent molecular techniques, together with a review of the literature on microbiota and lactobacilli in SSc, has been carried out. Twenty-nine SSc female patients (mean age 62) and twenty-three female healthy subjects (HS, mean age 57.6) were enrolled and underwent tongue and gum swab sampling. Quantitative PCR was conducted in triplicate using Lactobacillus specific primers rpoB1, rpoB1o and rpoB2 for the RNA-polymerase β subunit gene. Our data show significantly (p = 0.0211) lower LactobacillusspprpoB sequences on the tongue of patients with SSc compared to HS. The mean value of the amount of Lactobacillus ssprpoB gene on the gumsofSSc patients was minor compared to HS. A significant difference between tongue and gums (p = 0.0421) was found in HS but not in SSc patients. In conclusion, our results show a lower presence of Lactobacillus in the oral cavity of SSc patients. This strengthens the hypothesis that Lactobacillus may have both a protective and therapeutic role in SSc patients.
Pathogen Moonlighting Proteins: From Ancestral Key Metabolic Enzymes to Virulence Factors
Authors: Franco-Serrano Luis , Sánchez-Redondo David , Nájar-García Araceli , Hernández Sergio , Amela Isaac , Perez-Pons Josep Antoni , Piñol Jaume , Mozo-Villarias Angel , Cedano Juan , Querol Enrique
Published: June 2021

Moonlighting and multitasking proteins refer to proteins with two or more functions performed by a single polypeptide chain. An amazing example of the Gain of Function (GoF) phenomenon of these proteins is that 25% of the moonlighting functions of our Multitasking Proteins Database (MultitaskProtDB-II) are related to pathogen virulence activity. Moreover, they usually have a canonical function belonging to highly conserved ancestral key functions, and their moonlighting functions are often involved in inducing extracellular matrix (ECM) protein remodeling. There are three main questions in the context of moonlighting proteins in pathogen virulence: (A) Why are a high percentage of pathogen moonlighting proteins involved in virulence? (B) Why do most of the canonical functions of these moonlighting proteins belong to primary metabolism? Moreover, why are they common in many pathogen species? (C) How are these different protein sequences and structures able to bind the same set of host ECM protein targets, mainly plasminogen (PLG), and colonize host tissues? By means of an extensive bioinformatics analysis, we suggest answers and approaches to these questions. There are three main ideas derived from the work: first, moonlighting proteins are not good candidates for vaccines. Second, several motifs that might be important in the adhesion to the ECM were identified. Third, an overrepresentation of GO codes related with virulence in moonlighting proteins were seen.
Bacterial Extracellular DNA Promotes β-Amyloid Aggregation
Authors: Tetz George , Tetz Victor
Published: June 2021

Alzheimer’s disease is associated with prion-like aggregation of the amyloid β (Aβ) peptide and the subsequent accumulation of misfolded neurotoxic aggregates in the brain. Therefore, it is critical to clearly identify the factors that trigger the cascade of Aβ misfolding and aggregation. Numerous studies have pointed out the association between microorganisms and their virulence factors and Alzheimer’s disease; however, their exact mechanisms of action remain unclear. Recently, we discovered a new pathogenic role of bacterial extracellular DNA, triggering the formation of misfolded Tau aggregates. In this study, we investigated the possible role of DNA extracted from different bacterial and eukaryotic cells in triggering Aβ aggregation in vitro. Interestingly, we found that the extracellular DNA of some, but not all, bacteria is an effective trigger of Aβ aggregation. Furthermore, the acceleration of Aβ nucleation and elongation can vary based on the concentration of the bacterial DNA and the bacterial strain from which this DNA had originated. Our findings suggest that bacterial extracellular DNA might play a previously overlooked role in the Aβ protein misfolding associated with Alzheimer’s disease pathogenesis. Moreover, it highlights a new mechanism of how distantly localized bacteria can remotely contribute to protein misfolding and diseases associated with this process. These findings might lead to the use of bacterial DNA as a novel therapeutic target for the prevention and treatment of Alzheimer’s disease.
Gut Microbiota and Host Metabolism: From Proof of Concept to Therapeutic Intervention
Authors: Cani Patrice D. , Moens de Hase Emilie , Van Hul Matthias
Published: June 2021

The field of the gut microbiota is still a relatively young science area, yet many studies have already highlighted the translational potential of microbiome research in the context of human health and disease. However, like in many new fields, discoveries are occurring at a fast pace and have provided new hope for the development of novel clinical applications in many different medical conditions, not in the least in metabolic disorders. This rapid progress has left the field vulnerable to premature claims, misconceptions and criticism, both from within and outside the sector. Tackling these issues requires a broad collaborative effort within the research field and is only possible by acknowledging the difficulties and challenges that are faced and that are currently hindering clinical implementation. These issues include: the primarily descriptive nature of evidence, methodological concerns, disagreements in analysis techniques, lack of causality, and a rather limited molecular-based understanding of underlying mechanisms. In this review, we discuss various studies and models that helped identifying the microbiota as an attractive tool or target for developing various translational applications. We also discuss some of the limitations and try to clarify some common misconceptions that are still prevalent in the field.
Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review
Authors: Ríos-Barnés María , Fortuny Clàudia , Alarcón Ana , Noguera-Julian Antoni
Published: June 2021

Background: Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients. Objective: We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels. Methods: A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible. Results: Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established. Conclusions: Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.
Dengue Virus Induces the Expression and Release of Endocan from Endothelial Cells by an NS1–TLR4-Dependent Mechanism
Authors: Domínguez-Alemán Carlos Alonso , Sánchez-Vargas Luis Alberto , Hernández-Flores Karina Guadalupe , Torres-Zugaide Andrea Isabel , Reyes-Sandoval Arturo , Cedillo-Barrón Leticia , Remes-Ruiz Ricardo , Vivanco-Cid Héctor
Published: June 2021

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.