bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil-selective deletion of Cxcr2 protects against CNS neurodegeneration in a mouse model of multiple sclerosis
Authors: Khaw Yee Ming , Cunningham Claire , Tierney Abigail , Sivaguru Mayandi , Inoue Makoto 
Published: February 2020

AbstractBackgroundMultiple sclerosis (MS) is a chronic debilitating immune-mediated disease of the central nervous system (CNS) driven by demyelination and gray matter neurodegeneration. We previously reported an experimental autoimmune encephalomyelitis (EAE) MS mouse model with elevated serum CXCL1 that developed severe and prolonged neuron damage. Our findings suggested that CXCR2 signaling may be important in neuronal damage, thus implicating neutrophils, which express CXCR2 in abundance, as a potential cell type involved. The goals of this study were to determine if CXCR2 signaling in neutrophils mediate neuronal damage and to identify potential mechanisms of damage.MethodsEAE was induced in wild-type control and neutrophil-specificCxcr2knockout (Cxcr2cKO) mice by repeated high-dose injections of heat-killedMycobacterium tuberculosisand MOG35–55peptide. Mice were examined daily for motor deficit. Serum CXCL1 level was determined at different time points throughout disease development. Neuronal morphology in Golgi-Cox stained lumbar spinal cord ventral horn was assessed using recently developed confocal reflection super-resolution technique. Immune cells from CNS and lymphoid organs were quantified by flow cytometry. CNS-derived neutrophils were co-cultured with neuronal crest cells and neuronal cell death was measured. Neutrophils isolated from lymphoid organs were examined for expression of reactive oxygen species (ROS) and ROS-related genes. Thioglycolate-activated neutrophils were isolated, treated with recombinant CXCL1, and measured for ROS production.ResultsCxcr2cKO mice had less severe disease symptoms at peak and late phase when compared to control mice with similar levels of CNS-infiltrating neutrophils and other immune cells despite high levels of circulating CXCL1. Additionally,Cxcr2cKO mice had significantly reduced CNS neuronal damage in the ventral horn of the spinal cord. Neutrophils isolated from control EAE mice induced vast neuronal cell death in vitro when compared with neutrophils isolated fromCxcr2cKO EAE mice. Neutrophils isolated from control EAE mice, but notCxcr2cKO mice, exhibited elevated ROS generation, in addition to heightenedNcf1andIl1btranscription. Furthermore, recombinant CXCL1 was sufficient to significantly increase neutrophils ROS production.ConclusionsCXCR2 signal in neutrophils is critical in triggering CNS neuronal damage via ROS generation, which leads to prolonged EAE disease. These findings emphasize that CXCR2 signaling in neutrophils may be a viable target for therapeutic intervention against CNS neuronal damage.
Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model
Authors: Luo Li , Sun Ting , Yang Le , Liu An , Liu Qing-qing , Tian Qin-qin , Wang Yan , Zhao Ming-gao , Yang Qi 
Published: February 2020

AbstractAnxiety disorder is highly prevalent worldwide and represents a chronic and functionally disabling condition, with high levels of psychological stress characterized by cognitive and physiological symptoms. Scopoletin (SP), a main active compound in Angelica dahurica, is traditionally used for the treatment of headache, rhinitis, pain, and other conditions. Here, we evaluated the effects of SP in a mouse model of complete Freund’s adjuvant (CFA)-induced chronic inflammation anxiety. SP (2.0, 10.0, 50.0 mg/kg) administration for 2 weeks dose-dependently ameliorated CFA-induced anxiety-like behaviors in the open field test and elevated plus maze test. Moreover, we found that SP treatment inhibited microglia activation and decreased both peripheral and central IL-1β, IL-6, and TNF-α levels in a dose-dependent manner. Additionally, the imbalance in excitatory/inhibitory receptors and neurotransmitters in the basolateral nucleus after CFA injection was also modulated by SP administration. Our findings indicate that the inhibition of the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways involving anti-inflammatory activities and regulation of the excitatory/inhibitory balance can be attributed to the anxiolytic effects of SP. Moreover, our molecular docking analyses show that SP also has good affinity for gamma-aminobutyric acid (GABA) transaminase and GABAA receptors. Therefore, these results suggest that SP could be a candidate compound for anxiolytic therapy and for use as a structural base for developing new drugs.
Intravenous versus subcutaneous route pharmacokinetics of paracetamol (acetaminophen) in palliative care patients: study protocol for a randomized trial (ParaSCIVPallia)
Authors: Vernant Marine , Lepoupet Marie , Creveuil Christian , Alix Antoine , Gourio Charlotte , Peyro-Saint-Paul Laure , Lelong-Boulouard Veronique , Guillaumé Cyril 
Published: February 2020

Abstract
Background
Among palliative care (PC) patients who are administered paracetamol, the subcutaneous (SC) route is often an alternative to the intravenous (IV) route. Yet pharmacological and clinical data on whether these are equivalent pharmacokinetically are lacking. Many French palliative teams are now empirically using paracetamol by the SC route, but there are no data to support this practice. This trial aims to compare the pharmacokinetic (PK) parameters of paracetomol between the IV and SC routes in PC patients.

Methods/design
This is a randomized, open, crossover study in two PC centers. The primary endpoints are AUC0-t, AUC0-∞, Cmax, Vd, and t1/2. All adverse events will be reported for a safety analysis. Twenty adult PC patients with an IV device having spontaneous pain not related to care, with a numeric pain rate scale > 3/10, or having a systematic prescription of paracetamol as the usual treatment will be included. All patients also have to meet all eligibility criteria.

Conclusion
This is the first study comparing PK parameters for IV paracetamol versus SC paracetamol in PC patients.

Trial registration
ClinicalTrials.gov, NCT03944044. Registered on 4 June 2019.
Committee for the protection of persons (CPP) 18.09.05.58206 approval 4 October 2018.
National Drug Safety Agency (ANSM; Agence Nationale de Sécurité Médicament) MEDAECNAT-2018-09-00009 approval 29 November 2018.
LUMI-PCR: an Illumina platform ligation-mediated PCR protocol for integration site cloning, provides molecular quantitation of integration sites
Authors: Dawes Joanna C. , Webster Philip , Iadarola Barbara , Garcia-Diaz Claudia , Dore Marian , Bolt Bruce J. , Dewchand Hamlata , Dharmalingam Gopuraja , McLatchie Alex P. , Kaczor Jakub , Caceres Juan J. , Paccanaro Alberto , Game Laurence , Parrinello Simona , Uren Anthony G. 
Published: February 2020

AbstractBackgroundLigation-mediated PCR protocols have diverse uses including the identification of integration sites of insertional mutagens, integrating vectors and naturally occurring mobile genetic elements. For approaches that employ NGS sequencing, the relative abundance of integrations within a complex mixture is typically determined through the use of read counts or unique fragment lengths from a ligation of sheared DNA; however, these estimates may be skewed by PCR amplification biases and saturation of sequencing coverage.ResultsHere we describe a modification of our previous splinkerette based ligation-mediated PCR using a novel Illumina-compatible adapter design that prevents amplification of non-target DNA and incorporates unique molecular identifiers. This design reduces the number of PCR cycles required and improves relative quantitation of integration abundance for saturating sequencing coverage. By inverting the forked adapter strands from a standard orientation, the integration-genome junction can be sequenced without affecting the sequence diversity required for cluster generation on the flow cell. Replicate libraries of murine leukemia virus-infected spleen samples yielded highly reproducible quantitation of clonal integrations as well as a deep coverage of subclonal integrations. A dilution series of DNAs bearing integrations of MuLV or piggyBac transposon shows linearity of the quantitation over a range of concentrations.ConclusionsMerging ligation and library generation steps can reduce total PCR amplification cycles without sacrificing coverage or fidelity. The protocol is robust enough for use in a 96 well format using an automated liquid handler and we include programs for use of a Beckman Biomek liquid handling workstation. We also include an informatics pipeline that maps reads, builds integration contigs and quantitates integration abundance using both fragment lengths and unique molecular identifiers. Suggestions for optimizing the protocol to other target DNA sequences are included. The reproducible distinction of clonal and subclonal integration sites from each other allows for analysis of populations of cells undergoing selection, such as those found in insertional mutagenesis screens.
Integrating transposable elements in the 3D genome
Authors: Bousios Alexandros , Nützmann Hans-Wilhelm , Buck Dorothy , Michieletto Davide 
Published: February 2020

AbstractChromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or “topography”) of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome.
Stability of neuropsychological test performance in older adults serving as normative controls for a study on postoperative cognitive dysfunction
Authors: Feinkohl Insa , Borchers Friedrich , Burkhardt Sarah , Krampe Henning , Kraft Antje , Speidel Saya , Kant Ilse M. J. , van Montfort Simone J. T. , Aarts Ellen , Kruppa Jochen , Slooter Arjen , Winterer Georg , Pischon Tobias , Spies Claudia 
Published: February 2020

Abstract
Objective
Studies of postoperative cognitive dysfunction (POCD) rely on repeat neuropsychological testing. The stability of the applied instruments, which are affected by natural variability in performance and measurement imprecision, is often unclear. We determined the stability of a neuropsychological test battery using a sample of older adults from the general population. Forty-five participants aged 65 to 89 years performed six computerized and non-computerized neuropsychological tests at baseline and again at 7 day and 3 months follow-up sessions. Mean scores on each test were compared across time points using repeated measures analyses of variance (ANOVA) with pairwise comparison. Two-way mixed effects, absolute agreement analyses of variance intra-class correlation coefficients (ICC) determined test–retest reliability.

Results
All tests had moderate to excellent test–retest reliability during 7-day (ICC range 0.63 to 0.94; all p < 0.01) and 3-month intervals (ICC range 0.60 to 0.92; all p < 0.01) though confidence intervals of ICC estimates were large throughout. Practice effects apparent at 7 days eased off by 3 months. No substantial differences between computerized and non-computerized tests were observed. We conclude that the present six-test neuropsychological test battery is appropriate for use in POCD research though small sample size of our study needs to be recognized as a limitation.
Trial registration ClinicalTrials.gov Identifier NCT02265263 (15th October 2014)
Classification of Andrographis paniculata extracts by solvent extraction using HPLC fingerprint and chemometric analysis
Authors: Rafi M. , Devi A. F. , Syafitri U. D. , Heryanto R. , Suparto I. H. , Amran M. B. , Rohman A. , Prajogo B. , Lim L. W. 
Published: February 2020

Abstract
Objective
Andrographis paniculata, widely used as an antidiabetic in Indonesian traditional medicines (jamu), contains chemical compounds whose concentration is related to its therapeutic effects. The concentration of solvents used for extraction will also affect the number of compounds extracted. Therefore, a quality control method is needed to ensure consistency in quantifying these compounds in A. paniculata to improve its therapeutic application. High-performance liquid chromatography fingerprint analysis combined with chemometrics was used to evaluate extracts from different solvent extraction treatments. The content of andrographolide, the main bioactive compound in A. paniculata, and the level of α-glucosidase inhibition activity, an indicator of its antidiabetic activity, were also determined.

Results
Fingerprint chromatograms of A. paniculata extracts from different treatments exhibited a similar pattern with several peaks in common, only differing in area and intensity value. The A. paniculata extracts were classified using HPLC fingerprint and principal component analysis to allow grouping according to their respective solvent extraction treatments. The highest andrographolide content and α-glucosidase inhibition activity occurred in the 50% ethanol extract and the lowest in the water extract. HPLC fingerprint analysis could be used for identifying A. paniculata extracts based on solvent extraction, thus improving quality control for their therapeutic application.
Assessment of levels of asthma control among adult patients with asthma at Chitungwiza Central Hospital, Zimbabwe
Authors: Ndarukwa Pisirai , Chimbari Moses John , Sibanda Elopy 
Published: February 2020

Abstract
Background
The management of the reversible airways obstruction forms the cornerstone of quality asthma management. The aim of this study was to assess the level of control for asthma in adult patients, using a cross sectional study design. The assessment of control for asthma was based on the ACQ.

Methods
We conducted a cross-sectional study to measure the level of control for asthma among patients with asthma who volunteered and were reporting to Chitungwiza Central Hospital. We interviewed and conducted spirometry (lung function testing) on 400 adult patients with asthma. We used the ACQ questions to interview patients. A trained health care provider performed spirometry using the Koko Legend spirometer after meeting all the ambient conditions as outlined in the American Thoracic Society guidelines.

Results
Our study assessed levels of asthma control among 400 adult patients with physician-diagnosed asthma. The results showed that 248 (62%) participants had uncontrolled asthma. The median age of the adult patients who had uncontrolled asthma was 35 years (IQR: 27–44). Using the clinical practice cut-point of 0.75 for controlled asthma, only 152 (38%) were controlled, while 72 (18.8%), 50 (12.5%) and 123 (30.7%) were mildly uncontrolled, moderately uncontrolled and very uncontrolled respectively. Among participants who were widowed had uncontrolled asthma (p = 0.003) while most of the married 103 (67.8%) had controlled asthma (p = 0.018). The findings of the study showed that all the items on the ACQ were significantly different in asthma mean scores (p ≤ 0.0001).

Conclusion
We concluded that most asthma patients that participated in the study were uncontrolled. We therefore, recommend an evaluation of factors associated with poor asthma control in order to improve asthma care and achieve good asthma control outcomes.
A randomized, double-blind, placebo-controlled, parallel-group study of once-daily inhaled fluticasone furoate on the hypothalamic–pituitary–adrenocortical axis of children with asthma
Authors: Bareille Philippe , Tomkins Susan , Imber Varsha , Tayob Mohammed , Dunn Karen , Mehta Rashmi , Khindri Sanjeev 
Published: February 2020

Abstract
Background
To evaluate the effects of fluticasone furoate on the hypothalamic–pituitary–adrenocortical axis, and the safety and tolerability of fluticasone furoate treatment in children with asthma.

Methods
This was a randomized, double-blind, placebo-controlled, multicenter, stratified, parallel-group, non-inferiority study of fluticasone furoate 50 µg inhalation powder administered once daily. The study enrolled children (aged 5–11 years inclusive) with a documented diagnosis of asthma for ≥ 6 months and a Childhood Asthma Control Test score of > 19. After a 7–14-day run-in period, eligible subjects were stratified by age and randomized to fluticasone furoate 50 µg once daily or placebo once daily via ELLIPTA for 6 weeks. The primary endpoint was the change from baseline (expressed as a ratio) in 0–24-h weighted mean serum cortisol at the end of the treatment period.

Results
Fifty-six randomized subjects received fluticasone furoate 50 µg once daily and 55 received placebo. The primary analysis was performed in the serum cortisol population (n = 104) and demonstrated that fluticasone furoate 50 µg once daily was non-inferior to placebo (ratio = 0.93; 95% confidence interval 0.8096, 1.0620), as the lower limit of the 95% confidence interval for the geometric mean treatment ratio of fluticasone furoate 50 µg once daily versus placebo was greater than 0.80. Findings from the intent-to-treat population (n = 111) were similar.

Conclusions
Six weeks of treatment with inhaled fluticasone furoate 50 µg once daily had no clinically relevant effect on the hypothalamic–pituitary–adrenocortical axis function of children, as measured by 24-h serum cortisol profiles. The primary analysis showed that fluticasone furoate 50 µg once daily was non-inferior to placebo. Fluticasone furoate 50 µg once daily was well tolerated and no new safety concerns emerged during the study.

Trial registration
This study is registered in ClinicalTrials.gov (NCT02483975). Date of submission: 25 June 2015.
CEUS LI-RADS: a pictorial review
Authors: Bartolotta Tommaso Vincenzo , Terranova Maria Chiara , Gagliardo Cesare , Taibbi Adele 
Published: February 2020

AbstractContrast-enhanced ultrasound (CEUS) greatly improved the diagnostic accuracy of US in the detection and characterization of focal liver lesions (FLLs), and it is suggested and often included in many international guidelines as an important diagnostic tool in the imaging work-up of cirrhotic patients at risk for developing hepatocellular carcinoma (HCC). In particular, CEUS Liver Imaging Reporting and Data System (LI-RADS) provides standardized terminology, interpretation, and reporting for the diagnosis of HCC. The aim of this pictorial essay is to illustrate CEUS features of nodules discovered at US in cirrhotic liver according to LI-RADS categorization.
Efficacy of mesenchymal stem cells in animal models of lupus nephritis: a meta-analysis
Authors: Zhou Tianbiao , Liao Chunling , Li Hong-Yan , Lin Wenshan , Lin Shujun , Zhong Hongzhen 
Published: February 2020

Abstract
Background
Lupus nephritis is usually manifested by proteinuria, active urinary sediment, hypertension, and renal failure and is a serious complication with more than 50% occurrence in systemic lupus erythematosus patients. Mesenchymal stem cells (MSC) present remarkable immunomodulatory ability, and these cells are potential therapeutic agents for autoimmune disorders. In clinical trials, the effectiveness of MSC in the treatment of lupus nephritis is still controversial. A meta-analysis was performed to assess whether MSC can achieve good efficacy in the treatment of lupus nephritis in mice.

Methods
A comprehensive literature search was performed in Cochrane Library, ISI Web of Science, PubMed, and EMBASE from inception to Oct 1, 2019. Two authors independently extracted the data, which were pooled and calculated using RevMan 5.3.

Results
A total of 28 studies met the inclusion criteria. MSC treatment resulted in lower levels of ds-DNA (OR = − 29.58, 95% CI − 29.58, − 17.99; P < 0.00001), ANA (OR = − 70.93, 95% CI − 104.55, − 37.32; P < 0.0001), Scr (OR = − 8.20, 95% CI − 12.71, − 3.69; P = 0.0004), BUN (OR = − 14.57, 95% CI − 20.50, − 8.64; P < 0.00001), proteinuria (OR = − 4.26, 95% CI − 5.15 to − 3.37; P < 0.00001), and renal sclerosis score (OR = − 1.92, 95% CI − 2.66 to − 1.18; P < 0.00001), and MSC treatment could get higher levels of albumin. To detect the potential, the cytokines were also assessed, and the MSC treatment group had lower levels of IL-2, IL-12, IL-17, and IFN-γ when compared with the control group. However, the difference was not notable for IL-4, IL-6, IL-10, TGF-β, MCP-1, TNF-α, Th1, Th17, Foxp3, or Tregs.

Conclusion
Our study confirmed that MSC treatment in an animal model for lupus nephritis in the studies included in the meta-analysis resulted in lower levels of ds-DNA, ANA, Scr, BUN, proteinuria, and renal sclerosis score, and MSC treatment could get higher levels of albumin.
Ventilatory support and mechanical properties of the fibrotic lung acting as a “squishy ball”
Authors: Marchioni Alessandro , Tonelli Roberto , Rossi Giulio , Spagnolo Paolo , Luppi Fabrizio , Cerri Stefania , Cocconcelli Elisabetta , Pellegrino Maria Rosaria , Fantini Riccardo , Tabbì Luca , Castaniere Ivana , Ball Lorenzo , Malbrain Manu L. N. G. , Pelosi Paolo , Clini Enrico 
Published: February 2020

AbstractProtective ventilation is the cornerstone of treatment of patients with the acute respiratory distress syndrome (ARDS); however, no studies have yet established the best ventilatory strategy to adopt when patients with acute exacerbation of interstitial lung disease (AE-ILD) are admitted to the intensive care unit. Due to the severe impairment of the respiratory mechanics, the fibrotic lung is at high risk of developing ventilator-induced lung injury, regardless of the lung fibrosis etiology. The purpose of this review is to analyze the effects of mechanical ventilation in AE-ILD and to increase the knowledge on the characteristics of fibrotic lung during artificial ventilation, introducing the concept of “squishy ball lung”. The role of positive end-expiratory pressure is discussed, proposing a “lung resting strategy” as opposed to the “open lung approach”. The review also discusses the practical management of AE-ILD patients discussing illustrative clinical cases.