bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infrapatellar Fat Pad-derived Mesenchymal Stem Cell-based Spheroids Enhance Their Therapeutic Efficacy to Reverse Synovitis and Fat Pad Fibrosis
Authors: Kouroupis Dimitrios , Willman Melissa A , Best Thomas M , Kaplan Lee D , Correa Diego 
Published: October 2020

Abstract
Background: To investigate the in vitro and in vivo anti-inflammatory/anti-fibrotic capacity of IFP-MSC manufactured as 3D spheroids. According to our hypothesis, IFP-MSC do not require prior cell priming to acquire a robust immunomodulatory phenotype in vitro in order to efficiently reverse synovitis and IFP fibrosis and secondarily delay articular cartilage damage in vivo.Methods: Human IFP-MSC immunophenotype, tri-potentiality, and transcriptional profiles were assessed in 3D settings. Multiplex secretomes were assessed in IFP-MSC spheroids [Crude (non-immunoselected), CD146+ or CD146- immunoselected cells] and compared with 2D cultures with and without prior inflammatory/fibrotic cell priming. Functionally, immunopotency limiting human PBMCs proliferation and effect on stimulated synoviocytes with inflammation and fibrotic cues. Finally, spheroids were tested in vivo in a rat model of acute synovitis/fat pad fibrosis.Results: Spheroids enhanced IFP-MSC phenotypic, transcriptional and secretory immunomodulatory profiles compared to 2D cultures. Further, CD146+ IFP-MSC spheroids showed enhanced secretory and transcriptional profiles, however, not reflected in a superior capacity to suppress activated PBMC suggesting 3D environment sufficient to induce an immunomodulatory phenotype. Crude IFP-MSC spheroids modulated the molecular response of synoviocytes previously exposed to inflammatory cues. Therapeutically, IFP-MSC spheroids retained Substance P degradation potential in vivo, while effectively induced resolution of inflammation/fibrosis of synovium and fat pad, halting the articular cartilage degradation in a rat model of progressive synovitis, fat pad fibrosis and osteoarthritis.Conclusions: 3D spheroids confer IFP-MSC a reproducible and enhanced immunomodulatory effect in vitro and in vivo, circumventing the requirement of non-compliant cell priming or selection before administration, thus streamlining cell products manufacturing protocols.
Gene Engineered Mesenchymal Stem Cells:&nbsp;Greater Transgene Expression and Efficacy With Minicircle Vs. Plasmid DNA&nbsp;Vectors in a Mouse Model of Acute Lung Injury
Authors: Florian Maria , Wang Jia-Pey , Deng Yupu , Souza-Moreira Luciana , Stewart Duncan John , Mei Shirley Hsin-Ju 
Published: October 2020

Abstract
Background: Acute lung injury (ALI), and in its severe form the Acute respiratory distress syndrome (ARDS), results in increased pulmonary vascular inflammation and permeability, and is a major cause of mortality in many critically ill patients. Although cell-based therapies have shown promise in experimental ALI, strategies are needed to enhance potency of mesenchymal stem cells (MSC) to develop more effective treatments. Genetic modification of MSC has been demonstrated to significantly improve therapeutic benefits of these cells; however, the optimal vector for gene transfer is not clear. Given the acute nature of ARDS, transient transfection is desirable to avoid off target effects of long-term transgene expression, as well as the potential adverse consequences of genomic integration. Methods: Here, we explored whether a minicircle DNA (MC) DNA vector containing human angiopoietin 1 (MC-ANGPT-1) can provide more effective platform for gene-enhanced MSC therapy of ALI/ARDS. Results: At 24 hours after transfection, nuclear-targeted electroporation using a MC-ANGPT1 vector resulted in a 3,7 fold greater increase in human ANGPT1 protein in MSC conditioned media compared to the use of a plasmid ANGPT1 (pANGPT1) vector (2048±567pg/mL vs. 552.1±33.5pg/mL). In the lipopolysaccharide (LPS)-induced ALI model, administration of pANGPT1 transfected MSC significantly reduced bronchoalveolar lavage (BAL) neutrophil counts by 57%, while MC-ANGPT1 transfected MSC reduced it by 71% (p<0.001) by Holm-Sidak’s multiple comparison test. Moreover, compared to pANGPT1, the MC-ANGPT1 transfected MSC significantly reduced pulmonary inflammation, as observed in decreased levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interferron gamma (IFN-γ), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2). pANGPT1 transfected MSC significantly reduced BAL albumin levels by 71% , while MC-ANGPT1 transfected MSC reduced it by 85%. Coclusions: Overall, using a minicircle vector, we demonstrated an efficient and sustained expression of the ANGPT1 transgene in MSC and enhanced therapeutic effect on ALI model compared to plasmid. These results support the potential benefits of the MC-ANGPT1 gene enhancement of MSC therapy to treat ARDS.
Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking
Authors: Alizadehmohajer Negin , Sadeghi Bahman , Najafgholian Simin , Moradi Shabnam , Mohammadi Forogh , Nedaeinia Reza , javanmard Shaghayegh haghjooy , Sohrabi Ehsan , Salehi Rasoul , A.Ferns Gordon , Manian Mostafa , Nejad Asieh Emami 
Published: October 2020

Abstract
Background: 2019-nCoV (COVID-19) is a pandemic disease with a high infectivity and mortality. The prevention and treatment of COVID-19 have become urgent matters for consideration. It often takes several years to develop new drugs, or vaccines, based on the usual clinical trial process. This dwell-time can be shortened by repurposing previously approved drugs.Methods: We have designed and evaluated a bacterial biosensor expressing a luciferase We aimed to assess several available small-molecule; Abl kinase inhibitors, Janus kinase inhibitor, Dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papin-like Protease inhibitors, using binding simulation with proteins that might prove to be effective in inhibiting COVID-19 infection. The efficiency of inhibitors was evaluated based on docking scores using auto dock vina software.Results: Strong ligand-protein interactions were predicted among some of these drugs, such as Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control (directly and indirectly) or in viral proteins attenuation. It is worth to highlight the powerful immunomodulatory role of Abivertinib that inhibits pro-inflammatory cytokine production that are associated with cytokine release syndrome (CRS) or cytokine storm and progression of COVID-19 infection.Conclusions: COVID-19 is similar to SARS-CoV, the potential role of Abl kinase inhibitors such as Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS) may indicate that these drugs may be useful for COVID-19. Moreover, Remdesivir, and Telaprevir have the most efficiency with their docked proteins in-silico as well although clinical trials are needed to confirm the effect of these drugs.
Prevalence and Antimicrobial Resistance Profiles of Salmonella Species and Escherichia coli Isolates from Poultry Feeds in Ruiru Sub - County, Kenya
Authors: Ngai Dorica Gakii , Nyamache Anthony Kebira , Ombori Omwoyo 
Published: October 2020

Abstract
Objectives: Contaminated poultry feeds can be a major source of E. coli and Salmonella infections in poultry. This study aimed at determining the microbial quality, prevalence and antimicrobial resistance and associated resistance genes to Salmonella and E. coli isolates from poultry feeds.Results: A total of 150 samples of different poultry feed types were randomly collected from selected sites within Ruiru Sub-County. A microbial load was determined, Salmonella and Escherichia coli were isolated and antimicrobial susceptibility test accomplished. Antimicrobial resistance genes; TEM, SHV, strB and Dfr were established. Out of analyzed samples, 58% contained Escherichia coli and 28% Salmonella. Bacterial load ranged between 3.1 x105 cfug to 3.0 x106 cfu/g. The highest resistance was found with ampicillin (41%) for Salmonella and (62%) for E. coli isolates. All the Ampicilin resistant isolates carried TEM and SHV genes. In addition, strB and Dfr drug resistance genes associated with streptomycin and Cotri-moxazole were analysed. All isolates were susceptible to chloramphenicol and ciprofloxacin. The study reveals high bacterial contamination, presence of beta-lactamase, aminoglycoside and sulphonamide resistance genes across isolates from poultry feeds. Therefore, contaminated poultry feeds with bacteria are likely to lead to increase and spread of antimicrobial resistant strains across the community.
Resveratrol induces H3 and H4K16 de-acetylation and H2A.X phosphorylation in Toxoplasma gondii
Authors: Contreras Susana Marisol , Ganuza Agustina , Corvi Maria Martha , Angel Sergio 
Published: October 2020

Abstract
Objective: Objective: Resveratrol (RSV) is a multi-target drug that has demonstrated activity against Toxoplasma gondii in macrophage and HFF cell line infection models. However, its mechanism of action has not been determined yet. With the aim of determining a possible mechanism of anti-T. gondii action, we analyzed the effect of RSV on histones H3 and H4 lysine 16 acetylation (H4K16). RSV-induced DNA damage of intracellular tachyzoites was assessed as well by using the DNA damage marker phosphorylated histone H2A.X (gH2AX).Results: RSV inhibited intracellular T. gondii tachyzoite growth at concentrations below the toxic effect on host cells. The IC50 value in a 24-hours treatment was 53 mM. RSV induced a reduction in H4K16 acetylation (H4K16ac), a mark associated to transcription, DNA replication and homologous recombination repair. The same deacetylating effect was observed on histone H3. RSV also enhanced the SQE motif phosphorylation on T. gondii H2A.X (termed γH2A.X), a DNA damage associated PTM. Our findings suggest a possible link between RSV and DNA damage or DNA repair process maybe associated to DNA replication stress.
Promising Acyclovir and its derivatives to inhibit the protease of SARS-CoV-2: Molecular Docking and Molecular Dynamics simulations
Authors: Kumar Durgesh , Kumari Kamlesh , Bahadur Indra , Singh Prashant 
Published: October 2020

Abstract
Till date, more than 40 million people are affected throughout the world due to the COVID-19. Therefore, there is an urgency to find a solution to cure this infection. It is is due to the SARS-CoV-2 infection and the authors have targetted the protease of the SARS-CoV-2 so the infection will not spread. Herein, the authors have selected the antiviral drug, acyclovir for the inhibition of protease of the SARS-CoV-2. Acyclovir is a popular and selective antiherpes agent and started a new beginning for the viral infection. The other name of acyclovir is aciclovir and is being used in the treatment of chickenpox, and shingles. Further, it can be used in avoidance of cytomegalovirus infections. Even, acyclovir can used to cure the patients suffering from cold scores, shingles and also decreases the pain.In the present work, acyclovir (CMPD1) and its two derivatives, the first derivative is Ganciclovir (CMPD2) and the second derivative is (CMPD3). These three molecules were used to inhibit the protease of SARS-CoV-2. It was studied through the molecular docking, molecular dynamics simulations etc. Herein, simulations method were used to calculate relative change in binding free energy under the influence of Amber force field through MM-GBSA. The structural behavior of complex system with acyclovir and its derivatives were observed in term of RMSD and RMSF for all residues. Authors observed that complex of CMPD3 with the protease is stable and has less fluctuation than the native protease. Further, CMPD3 follow the creteria of all drug likeness term and it showed good activity against SARS-CoV-2. It was suggested that CMPD3 may be used as a inhibitor for coronavirus activity to protect life of human being in world.
Dopaminergic Neuron Lesion at the Area of the Biological Clock Pacemaker, Suprachiasmatic Nuclei (SCN) Induces Metabolic Syndrome in Rats
Authors: Luo Shuqin , Ezrokhi Michael , Cominos Nicholas , Tsai Tsung-Huang , Stoelzel Carl R. , Trubitsyna Yelena , Cincotta Anthony H. 
Published: October 2020

Abstract
Background: The daily peak in dopaminergic neuronal activity at the area of the biological clock (hypothalamic suprachiasmatic nuclei [SCN]) is diminished in obese/insulin resistant vs lean/insulin sensitive animals. The impact of targeted lesioning of dopamine (DA) neurons specifically at the area surrounding (and that communicate with) the SCN (but not within the SCN itself) upon glucose metabolism, adipose and liver lipid gene expression, and cardiovascular biology in normal laboratory animals has not been investigated and was the focus of this study. Methods: Female Sprague-Dawley rats received either DA neuron neurotoxic lesion by bilateral intra-cannula injection of 6-hydroxydopamine (2-4 μg/side) or vehicle treatment at the area surrounding the SCN at 20 minutes post protriptyline ip injection (20 mg/kg) to protect against damage to noradrenergic and serotonergic neurons. Results: At 16 weeks post-lesion relative to vehicle treatment, peri-SCN area DA neuron lesioning increased weight gain (34.8%, P<0.005), parametrial and retroperitoneal fat weight (45% and 90% respectively, P<0.05), fasting plasma insulin, leptin and norepinephrine levels (180%, 71%, and 40% respectively, P<0.05), glucose tolerance test area under the curve (AUC) insulin (112.5%, P<0.05), and insulin resistance (44% - Matsuda Index, p<0.05) without altering food consumption during the test period. Such lesion also induced the expression of several lipid synthesis genes in adipose and liver and the adipose lipolytic gene, hormone sensitive lipase in adipose (P<0.05 for all). Liver monocyte chemoattractant protein 1 (a proinflammatory protein associated with metabolic syndrome) gene expression was also significantly elevated in peri-SCN area dopaminergic lesioned rats. Peri-SCN area dopaminergic neuron lesioned rats were also hypertensive (systolic BP rose from 157±5 to 175±5 mmHg, P<0.01; diastolic BP rose from 109±4 to 120±3 mmHg, P<0.05 and heart rate increase from 368±12 to 406±12 BPM, P<0.05) and had elevated plasma norepinephrine levels (40% increased, P < 0.05) relative to controls. Conclusions: These findings suggest that reduced dopaminergic neuronal activity in neurons at the area of and communicating with the SCN contributes significantly to increased sympathetic tone and the development of metabolic syndrome, without effect on feeding.
Optimizing for taxonomic coverage: a comparison of methods to recover mesofauna from soil
Authors: Dritsoulas Alexandros , Duncan Larry W. 
Published: October 2020

Abstract
Manipulating soil properties to modify the dynamics between nematodes and their natural enemies has been proposed to conserve services such as the biological control of insect pests by entomopathogenic nematodes. Many soil microarthropods including acari mites and collembola are natural enemies of nematodes; however, little is known about the naturally occurring assemblages of these two soil dwelling groups and how they might be influenced by soil conditions. A method to efficiently recover both nematodes and microarthropods from environmental samples would be helpful to characterize communities of these two groups in different habitats. Because samples of nematodes extracted from soil by sucrose centrifugation (SC) also contain soil mites, collembola, protozoans, and fungal and bacterial propagules, the efficiency of SC to recover microarthropods was compared to more conventional methods of microarthropod recovery such as heptane flotation (HF), Berlese funnels (BF), and a modified flotation Berlese method (FBF). Microarthropods were identified using an inverted microscope to class in one experiment and to order in a second. Significantly more microarthropods of all taxa were recovered by SC than with either Berlese method (BF or FBF). In total, 40% more microarthropods comprising seven orders were recovered by HF compared to SC, but the difference was not significant. Ecological indices (diversity, richness, and evenness) derived from HF and SC were congruent and significantly higher than those derived from BF. Excessive organic matter in the HF extractions, compared to those of SC, BF, and FBF, made mite detection and identification difficult and time consuming. Moreover, unlike SC, neither HF nor any Berlese method recovered nematodes. Accordingly, we found SC to be the most efficient method for microarthropod extraction, making it an ideal method for studies of communities of nematodes and many of their natural enemies in the soil.
Religión, Identidad y Seguridad: el Estado Islámico y las minorías en Irak y Siria.
Authors: Morales Guillermo Ospina 
Published: October 2020

El artículo analiza la amenaza existencial que ha representado el Estado Islámico para las comunidades minoritarias de Irak y Siria. Para lo cual, hace uso de los conceptos de seguridad societal y securitización. Señala que las acciones del Estado Islámico buscaron erradicar la presencia de las minorías, principalmente yazidíes y cristianos, como parte de un proceso de securitización de la religión que se fundamenta en el discurso del salafismo-yihadista, que establece la necesidad de eliminar y perseguir toda representación del politeísmo (shirk) e infidelidad (kafir) para hacer frente al enemigo en una aparente guerra en contra del Islam.
Palabras Clave:
Estado Islámico, Irak, minorías, salafismo-yihadista, securitización, seguridad societal, Siria.
Effectiveness of pathogenetic therapy for infectious diarrhea in children with COVID-19
Authors: Khavkina D. A. , Ruzhentsova T. A. , Popova R. V. , Chukhliaev P. V. , Garbuzov A. A. , Meshkova N. A. 
Published: October 2020

Introduction. The article presents basic information on approaches to pathogenetic therapy of acute intestinal infections. Data from our own research on the diagnosis and treatment of gastrointestinal manifestations of COVID-19 in children aged 3 months to 18 years are presented. The aim of the study was to evaluate the effectiveness of complex rehydration, cytomucoprotective and probiotic therapy for infectious diarrhea of various etiologies, including those developing with a new coronavirus infection.Materials and methods. We analyzed data from our own observations of patients aged 3 months to 18 years with diarrhea against the background of acute intestinal infections of various etiologies (120 children)), as well as with a new coronavirus infection caused by the SARS-CoV-2 virus (32 children). The children were treated in accordance with current standards and treatment recommendations. Clinical examples are presented.Results and discussion. Diarrhea was observed in 64% of patients with a new coronavirus infection. Clinical cases confirm the effectiveness of rehydration, cytomucoprotective and probiotic therapy for infectious diarrhea, regardless of the etiology, including COVID-19.Conclusions. Diarrhoea and other symptoms of gastrointestinal disorders in COVID-19 are stopped when pathogenetic therapy is recommended for patients with acute intestinal infections.
A case study on the effect of smart meter sampling intervals and gap-filling approaches on water distribution network simulations
Authors: Kirstein Jonas Kjeld , Høgh Klavs , Rygaard Martin , Borup Morten 
Published: October 2020

Abstract
Water usage data collected from smart meters at the end user can improve the accuracy and applicability of water distribution network models. Collecting and storing large amounts of data across hundreds or more smart meters is costly, which makes it important to consider what constitutes a sufficient sampling interval. This paper explores the effect of varying sampling intervals in smart meter data on model performance in regard to flow, pressure and water age simulations. Furthermore, the effect of using linear interpolation, a demand pattern or a network-inflow-weighted approach to fill gaps when data are sampled coarsely, is investigated. The study was based on real data from 525 smart meters in a district metered area in Denmark. The results show that smart meter data can improve modelling results, and if the sampling intervals are coarser than 2 h, then a weighted gap-filling approach markedly outperforms linear interpolation and models with coarse bi-annual demand data.
Implementation of point-of-use water treatment methods in a rural Tanzanian community: a case study
Authors: Ngasala T. M. , Masten S. J. , Cohen C. , Ravitz D. , Mwita E. J. 
Published: October 2020

Abstract
This study was conducted in an agro-pastoral community in Northern Tanzania, where water sources are contaminated, and point-of-use water treatment is rarely used. The objectives of the study were to determine the quality of drinking water at the household level and to assess the perception and attitude towards the treatment methods that were introduced to community members. The three treatment methods evaluated were chlorine tablets, silver-infused ceramic tablets, and solar water disinfection (SODIS). These methods were selected due to their availability, ease of use, cost, and effectiveness in water with high levels of coliform bacteria. Each home within the study area was provided with one of three treatment methods. The use, performance, and acceptability of the new water treatment methods were assessed over a three-week period. Prior to the introduction of the methods, 40% of households reported that they treated water regularly. However, 80% of the household water samples tested positive for Escherichia coli. After introducing the new methods, 60% of households increased their water consumption, and all water samples tested negative for E. coli during the final week of testing. The work demonstrates the need to provide access to cost-effective household water treatment methods, especially in rural communities that lack access to potable water.
Evaluation of integrated impacts of climate and land use change on the river flow regime in Wamkurumadzi River, Shire Basin in Malawi
Authors: Nkhoma Lusungu , Ngongondo Cosmo , Dulanya Zuze , Monjerezi Maurice 
Published: October 2020

Abstract
Climate and land use change (CC and LUC hereafter) are interlinked factors that can lead to river flow regime changes, as well as affecting hydrological extremes such as floods and drought. There is now considerable evidence of CC and LUC in many catchments in Malawi but without corresponding evaluations of their impacts on river flow regimes. Therefore, this study assessed how both factors affect the flow regime of Wamkurumadzi River, a key tributary of the major Shire River in southern Malawi. Land use and hydroclimatic data for the basin were first analyzed for spatial–temporal trends in the historical period between the years 1984 and 2015. The Soil and Water Assessment Tool (SWAT) model was then applied with different LUC and CC scenarios in order to assess their sole and combined impacts on the river flow regime. The model was calibrated and validated using the split sample method from the year 1984 to 1999 and from the year 2000 to 2015. Model performance was acceptable according to the selected evaluation criteria, with the Nash–Sutcliffe (NSE) coefficient of 0.78 and coefficient of determination (R2) of 0.96 during calibration and NSE of 0.93 and R2 of 0.98 during validation. Results of the integrated impacts of LUC and CC suggest a slight increase in river discharge of 0.05 m3/s for the period between the 1980s and 2000s. During the 1980s–1990s, both CC through rainfall decreased and LUC resulted in decreases in the mean river discharges by 1.58 and 0.37 m3/s, respectively. The study also found that CC through increased rainfall in the 1990s–2000s decades saw an overall increase of 1.39 m3/s in mean river discharge, while LUC shows the increase of mean river discharge by 0.25 m3/s. However, the study observed that reforestation efforts in the basin were greatly responsible for the alteration of the river flow regime in the later period.