bluuebunny/crossref_metadata_2025_split huggingface dataset:
Th2 cells promote eosinophil‐independent pathology in a murine model of allergic bronchopulmonary aspergillosis
Authors: Dietschmann Axel , Schruefer Sebastian , Krappmann Sven , Voehringer David 
Published: February 2020

AbstractRepeated inhalation of airborne conidia derived from the fungus Aspergillus fumigatus (Af) can lead to a severe eosinophil‐dominated inflammatory condition of the lung termed allergic bronchopulmonary aspergillosis (ABPA). ABPA affects about 5 million individuals worldwide and the mechanisms regulating lung pathology in ABPA are poorly understood. Here, we used a mouse model of ABPA to investigate the role of eosinophils and T cell‐derived IL‐4/IL‐13 for induction of allergic lung inflammation. Selective deletion of IL‐4/IL‐13 in T cells blunted the Af‐induced lung eosinophilia and further resulted in lower expression of STAT6‐regulated chemokines and effector proteins such as Arginase 1, Relm‐α, Relm‐β, and Muc5a/c. Eosinophil‐deficient ΔdblGata mice showed lower IL‐4 expression in the lung and the number of Th2 cells in the lung parenchyma was reduced. However, expression of the goblet cell markers Clca1 and Muc5a/c, abundance of mucin‐positive cells, as well as weight gain of lungs were comparable between Af‐challenged ΔdblGata and WT mice. Based on these results, we conclude that T cell‐derived IL‐4/IL‐13 is essential for Af‐induced lung eosinophilia and inflammation while eosinophils may play a more subtle immunomodulatory role and should not simply be regarded as pro‐inflammatory effector cells in ABPA.
Electrochemical Conversion of Magnetic Nanoparticles Using Disposable Working Electrode in a 3D‐Printed Electrochemical Cell
Authors: He Yawen , Jia Fei , Guan Junfei , Fu Yingchun , Li Yanbin 
Published: February 2020

AbstractExploration of new property/function of nanomaterials is always a strong impetus in the nanoscience field. Here, a new method of electrochemical conversion (ECC) of magnetic nanoparticles (MNPs) is proposed to endow MNPs with signal generation ability for sensing. Briefly, high potential was applied to split H2O to generate acid, while Fe3O4 MNPs reacted with H+ and produce ferric/ferrous ions, which further reacted with K4Fe(CN)6 to yield Prussian blue (PB) through potential cycling. The ECC method worked well on both home‐made and commercial MNPs with different sizes. The generated PB possessed strong electrochemical activity for further applications. Interestingly, an uneven deposition of PB on working electrode and undesired contamination of the reference and counter electrodes were found when using commercial integrated three‐electrode chip. A 3D‐printed electrochemical cell was designed to facilitate the ECC and avoid drawbacks of commercial integrated electrode. The 3D‐printed electrochemical cell was proven to solve the problem above through spatial separation of electrodes and thus facilitated the ECC process. An electrochemical sensor for H2O2 detection based on the catalysis ability of ECC‐based PB exhibited a linear response from 5 μM to 1 mM, a high sensitivity of 269 μA mM−1 cm−2 and a low detection limit of 0.16 μM (S/N=3), which suggests its promising application prospect in electrochemistry‐related analysis.
Application of deep eutectic solvents for the extraction of phenolic compounds from extra‐virgin olive oil
Authors: Fanali Chiara , Posta Susanna Della , Dugo Laura , Russo Marina , Gentili Alessandra , Mondello Luigi , De Gara Laura 
Published: February 2020

AbstractA HPLC–DAD/ESI–MS method has been developed and validated for the analysis of the most representative phenolic compounds in extra‐virgin olive oil (EVOO) samples using a green extraction approach based on deep eutectic solvents (DESs) at room temperature. We examined ten DESs based on choline chloride and betaine in combination with different hydrogen bond donors comprising six alcohols, two organic acids, and one urea. Five phenolic compounds, belonging to the classes of secoiridoids and phenolic alcohols, were selected for the evaluation of extraction efficiency. A betaine‐based DES with glycerol (molar ratio 1:2) was found to be the most effective for extracting phenolic compounds as compared to a conventional solvent. The optimization of the extraction method involved the study of the quantity of water to be added to the DES and evaluation of the sample‐to‐solvent ratio optimal condition. Thirty percent of water added to DES and sample to solvent ratio 1:1 (w/v) were selected as the best conditions. The chromatographic method was validated by studying LOD, LOQ, intraday and interday retention time precision, and linearity range. Recovery values obtained spiking seed oil sample aliquots with standard compounds at 5 and 100 μg/g concentration were in the range between 75.2% and 98.7%.
Aspartate: An interesting model for analyzing dipole‐ion and ion pair interactions through its oppositely charged amine and acid groups
Authors: Hernández Belén , Pflüger Fernando , Ghomi Mahmoud 
Published: February 2020

AbstractAnionic species of aspartic acid, Asp−, having a zwitterionic backbone and a deprotonated side chain, appears to be a good example for analyzing dipole‐ion and ion pair interactions. Density functional theory calculations were herein performed to investigate the low energy conformers of Asp− embedded in a dielectric continuum modeling an aqueous environment, through a scan of the potential energy as a function of the side chain (χ1, χ2) torsion angles. The most energetically favorable conformers having g+g− and g−g+ side chain orientations are found to be stabilized by charge‐enhanced intramolecular H‐bonding involving the positively charged () and the two negatively charged (COO−) groups. These conformers were further used to analyze Asp− + nW clusters (W: water, n = 1 or 3), and Asp−/Asp− pair formation. COO− groups were found to be the most attractive sites for hosting a water molecule (binding energy: −6.0 ± 1.5 kcal/mol), compared to groups (binding energy: −4.7 ± 1.1 kcal/mol). Energy separation between g+g− and g−g+ conformers increases upon explicit hydration. Asp−/Asp− ion pairs, stabilized by the interaction between the group of a partner and the COO− group of the other, shows a quite constant binding energy (−8.1 ± 0.2 kcal/mol), whatever the pair type, and the relative orientation of the two interacting partners. This study suggests a first step to achieve a more realistic image of intermolecular interactions in aqueous environment, especially upon increasing concentration. It can also be considered as a preliminary attempt to assess the interactions of the Lys+…Asp−/Glu− ion pairs stabilizing intra‐ and interchain interactions in proteins.
Multicomponent reactions and supramolecular catalyst: A perfect synergy for eco‐compatible synthesis of pyrido[2,3‐d]pyrimidines in water
Authors: Chate Asha V. , Kulkarni Ankita S. , Jadhav Chetan K. , Nipte Amol S. , Bondle Girabala M. 
Published: February 2020

AbstractIn this article, we have developed a straightforward, easy and exceedingly competent approach for the synthesis of 5‐phenyl‐5,6‐dihydropyrido[2,3‐d]pyrimidine‐2,4,7(1H,3H,8H)‐triones obtain in superior yields in a sole reaction pace with an air and humidity steady catalyst in water as a green solvent at 100°C. The present procedure paves the approach for the synthesis of biologically fascinating molecular frameworks and has reward in conditions of little catalyst loading with palpable ambiguous and straightforward‐to‐do reaction circumstances with easy purification process. The used β‐cyclodextrin catalyst was recuperated and repeated several times devoid of noteworthy loss of catalytic activity, which is a crucial parameter of green synthesis.
Implementation of an active case management network to identify HIV‐positive infants and accelerate the initiation of antiretroviral therapy, Thailand 2015 to 2018
Authors: Lolekha Rangsima , Pavaputanon Patcharaporn , Puthanakit Thanyawee , Martin Michael , Kosalaraksa Pope , Petdachai Witaya , Borkird Thitiporn , Hansudewechakul Rawiwan , Rojanawiwat Archawin , Boonsuk Sarawut , Samleerat Tanawan , Ongwandee Sumet ,   on behalf of the ACC working group
Published: February 2020

AbstractIntroductionEarly initiation of antiretroviral therapy (ART) can reduce HIV‐related morbidity and mortality in HIV‐positive infants. We implemented an Active Case Management Network to promote early ART initiation Aiming for Cure (ACC) in August 2014. We describe ACC implementation, early infant diagnosis (EID) coverage and ART initiation during August 2014 to July 2018 compared with a national EID survey during October 2007 to September 2011 (pre‐ACC).MethodsThailand's 2014 HIV Treatment Guidelines recommend that HIV‐exposed infants have HIV polymerase chain reaction (PCR) testing at birth, one month and at two to four months. Testing is done at 14 national HIV PCR laboratories. When an HIV‐positive infant (HIV PCR+) is identified, PCR laboratory staff send the result to the hospital staff responsible for the infant's care and to the national laboratory case manager (CM). As part of ACC, the national laboratory CM alerts a regional CM who contacts the hospital staff caring for the infant to offer technical support with ART initiation and ART adherence. CMs enter clinical, demographic and laboratory data into the national ACC database. We analysed the ACC data from August 2014 to July 2018 to assess the ACC's impact on EID coverage, ART initiation and time‐to‐ART initiation.ResultsThe uptake of EID increased from 64% (pre‐ACC) to >95% in 2018 (ACC). The number of HIV‐positive infants born declined from 429 cases (pre‐ACC) to 267 cases (ACC). Median age at the first‐positive PCR declined from 75 days (pre‐ACC) to 60 days (ACC); P < 0.001. Among 429 infants diagnosed before ACC was started, 241 (56%) received ART; during ACC, 235 (88%) of 267 HIV‐positive infants received ART. The median age at ART initiation declined from 282 days before ACC to 83 days during ACC (P < 0.001) and the median time from blood collection to ART initiation declined from 168 days before ACC to 23 days during ACC (P < 0.001).ConclusionsAn innovative case management network (ACC) has been established in Thailand and results suggest that the network is promoting EID and early ART initiation. The ACC model, using case‐managed PCR notification and follow‐up, may speed ART initiation in other settings.
TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation
Authors: Watson Colton J.F. , Maguire Aindriu R.R. , Rouillard Melissa M. , Crozier Robert W.E. , Yousef Michael , Bruton Kelly M. , Fajardo Val A. , MacNeil Adam J. 
Published: February 2020

Abstract
Mast cells drive the inappropriate immune response characteristic of allergic inflammatory disorders via release of pro-inflammatory mediators in response to environmental cues detected by the IgE-FcεRI complex. The role of TGF-β-activated kinase 1 (TAK1), a participant in related signaling in other contexts, remains unknown in allergy. We detect novel activation of TAK1 at Ser412 in response to IgE-mediated activation under SCF-c-kit potentiation in a mast cell-driven response characteristic of allergic inflammation, which is potently blocked by TAK1 inhibitor 5Z-7-oxozeaenol (OZ). We, therefore, interrogated the role of TAK1 in a series of mast cell-mediated responses using IgE-sensitized murine bone marrow-derived mast cells, stimulated with allergen under several TAK1 inhibition strategies. TAK1 inhibition by OZ resulted in significant impairment in the phosphorylation of MAPKs p38, ERK, and JNK; and mediation of the NF-κB pathway via IκBα. Impaired gene expression and near abrogation in release of pro-inflammatory cytokines TNF, IL-6, IL-13, and chemokines CCL1, and CCL2 was detected. Finally, a significant inhibition of mast cell degranulation, accompanied by an impairment in calcium mobilization, was observed in TAK1-inhibited cells. These results suggest that TAK1 acts as a signaling node, not only linking the MAPK and NF-κB pathways in driving the late-phase response, but also initiation of the degranulation mechanism of the mast cell early-phase response following allergen recognition and may warrant consideration in future therapeutic development.
Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases
Authors: Sugita Kazunari , Kabashima Kenji 
Published: February 2020

AbstractThis review focuses on recent developments related to asthma, chronic rhinosinusitis, atopic dermatitis (AD), eosinophilic esophagitis, and inflammatory bowel diseases (IBD), with a particular focus on tight junctions (TJs) and their role in the pathogenetic mechanisms of these diseases. Lung, skin, and intestinal surfaces are lined by epithelial cells that interact with environmental factors and immune cells. Therefore, together with the cellular immune system, the epithelium performs a pivotal role as the first line physical barrier against external antigens. Paracellular space is almost exclusively sealed by TJs and is maintained by complex protein-protein interactions. Thus, TJ dysfunction increases paracellular permeability, resulting in enhanced flux across TJs. Epithelial TJ dysfunction also causes immune cell activation and contributes to the pathogenesis of chronic lung, skin, and intestinal inflammation. Characterization of TJ protein alteration is one of the key factors for enhancing our understanding of allergic diseases as well as IBDs. Furthermore, TJ-based epithelial disturbance can promote immune cell behaviors, such as those in dendritic cells, Th2 cells, Th17 cells, and innate lymphoid cells (ILCs), thereby offering new insights into TJ-based targets. The purpose of this review is to illustrate how TJ dysfunction can lead to the disruption of the immune homeostasis in barrier tissues and subsequent inflammation. This review also highlights the various TJ barrier dysfunctions across different organ sites, which would help to develop future drugs to target allergic diseases and IBD.
Simulation of monsoon intra‐seasonal oscillations in Geophysical Fluid Dynamics Laboratory models from Atmospheric Model Intercomparison Project integrations of Coupled Model Intercomparison Project phase 5
Authors: Mandke Sujata K. , Pillai Prasanth A. , Sahai Atul Kumar 
Published: February 2020

AbstractThe simulation of the intra‐seasonal variability (ISV), especially the fidelity of monsoon intra‐seasonal oscillations (MISO) over the South Asian summer monsoon (SASM), has been evaluated in Atmospheric Model Intercomparison Project run of three Geophysical Fluid Dynamics Laboratory (GFDL) atmospheric general circulation models (AGCM), participating in Coupled Model Intercomparison Project phase 5. Two of the models, namely, “GFDL‐HIRAM‐C180” and “GFDL‐HIRAM‐C360” are global high‐resolution atmospheric models (HIRAMs), which are same but at different horizontal resolutions. Third model “GFDL‐CM3” is at moderate horizontal resolution, whose atmospheric component differs from HIRAMs. Results have led to the conclusion that simulation of ISV over SASM remains poor in GFDL AGCMs at higher horizontal resolution, except northwards propagation of 30–60‐day mode of MISO by HIRAMs. Our diagnostics revealed resemblance in key characteristics of ISV simulated in two HIRAMs, except spectral peak at lower frequencies (30–60 day), which is captured only by “GFDL‐HIRAM‐C180” over equatorial Indian Ocean. Based on these results, it is conjectured that although high horizontal resolution is crucial for AGCMs to reproduce observed northwards propagation of 30–60‐day mode of MISO, the simulation of nature of ISV over SASM is not influenced by the difference of horizontal resolution in two HIRAMs. Analysis implicates that a reasonable representation of meridional migration of horizontal moisture advection, the meridional gradient of low‐level specific humidity over Indian longitudes and precipitation–SST relationship over north Indian Ocean, the northwestern tropical Pacific Ocean and tropical Indian Ocean assures the northwards propagation of 30–60‐day mode of MISO in HIRAMs.
Evaluation of CT‐MR image registration methodologies for 3D preoperative planning of forearm surgeries
Authors: Gerber Nicolas , Carrillo Fabio , Abegg Daniel , Sutter Reto , Zheng Guoyan , Fürnstahl Philipp 
Published: February 2020

AbstractComputerized surgical planning for forearm procedures that considers both soft and bony tissue, requires alignment of preoperatively acquired computed tomography (CT) and magnetic resonance (MR) images by image registration. Normalized mutual information (NMI) registration techniques have been researched to improve efficiency and to eliminate the user dependency associated with manual alignment. While successfully applied in various medical fields, the application of NMI registration to images of the forearm, for which the relative pose of the radius and ulna likely differs between CT and MR acquisitions, is yet to be described. To enable the alignment of CT and MR forearm data, we propose an NMI‐based registration pipeline, which allows manual steering of the registration algorithm to the desired image subregion and is, thus, applicable to the forearm. Successive automated registration is proposed to enable planning incorporating multiple target anatomical structures such as the radius and ulna. With respect to gold‐standard manual registration, the proposed registration methodology achieved mean accuracies of 0.08 ± 0.09 mm (0.01‐0.41 mm range) in comparison with 0.28 ± 0.23 mm (0.03‐0.99 mm range) associated with a landmark‐based registration when tested on 40 patient data sets. Application of the proposed registration pipeline required less than 10 minutes on average compared with 20 minutes required by the landmark‐based registration. The clinical feasibility and relevance of the method were tested on two different clinical applications, a forearm tumor resection and radioulnar joint instability analysis, obtaining accurate and robust CT‐MR image alignment for both cases.
Contemporary conditional cancer‐specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract
Authors: Rosiello Giuseppe , Palumbo Carlotta , Knipper Sophie , Pecoraro Angela , Luzzago Stefano , Deuker Marina , Mistretta Francesco A. , Tian Zhe , Fossati Nicola , Gallina Andrea , Montorsi Francesco , Shariat Shahrokh F. , Saad Fred , Briganti Alberto , Karakiewicz Pierre I. 
Published: February 2020

AbstractBackground and ObjectivesTo examine the effect of conditional survival on 5‐year cancer‐specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non‐metastatic urothelial carcinoma of the upper urinary tract (UTUC).MethodsWithin the Surveillance, Epidemiology and End Results database (2004‐2015), 6826 patients were identified. Conditional 5‐year CSS estimates were assessed after event‐free follow‐up duration. Multivariable Cox regression (MCR) models predicted cancer‐specific mortality (CSM) according to event‐free follow‐up length.ResultsOverall, 956 (14.0%) were T1low grade(LG)N0, 1305 (19.1%) T1high grade(HG)N0, 1215 (17.8%) T2N0, 2249 (32.9%) T3N0 and 1101 (16.1%) T4N0/TanyN1‐3. From baseline, 93.4% to 94.2% in T1LGN0 provided 5‐year CSS and, respectively, 86.2% to 95.3% in T1HGN0, 77.5% to 87.8% in T2N0, 63.0% to 91.1% in T3N0, and 38.8% to 88.2% in T4N0/TanyN1‐3. In MCR models, relative to T1LGN0, T1HGN0 (Hazard ratio [HR] 1.7), T2N0 (HR 3.0), T3N0 (HR: 5.2), and T4N0/TanyN1‐3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1LGN0 at 3 years vs 5 years of event‐free survival for T1HGN0 and all other groups, respectively.ConclusionsA direct relationship exists between event‐free follow‐up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.
Using Machine Learning Methods and Structural Alerts for Prediction of Mitochondrial Toxicity
Authors: Hemmerich Jennifer , Troger Florentina , Füzi Barbara , F.Ecker Gerhard 
Published: February 2020

AbstractOver the last few years more and more organ and idiosyncratic toxicities were linked to mitochondrial toxicity. Despite well‐established assays, such as the seahorse and Glucose/Galactose assay, an in silico approach to mitochondrial toxicity is still feasible, particularly when it comes to the assessment of large compound libraries. Therefore, in silico approaches could be very beneficial to indicate hazards early in the drug development pipeline. By combining multiple endpoints, we derived the largest so far published dataset on mitochondrial toxicity. A thorough data analysis shows that molecules causing mitochondrial toxicity can be distinguished by physicochemical properties. Finally, the combination of machine learning and structural alerts highlights the suitability for in silico risk assessment of mitochondrial toxicity.
Multisection tandem couplers with coupled‐line sections having unequal lengths
Authors: Staszek Kamil , Sorocki Jakub , Gruszczynski Slawomir , Wincza Krzysztof 
Published: February 2020

AbstractA novel concept of multisection tandem couplers composed of 2 quarter wavelength coupled‐line sections in between which a 270°‐long section is inserted has been proposed. The presented couplers feature relaxed coupling coefficients' requirements and a shorter overall electrical length with respect to the classic multisection tandem couplers, preserving simultaneously similar frequency characteristics to the ones obtainable in classic solutions. The proposed concept has been verified by the design and measurements of the developed tandem coupler operating at the center frequency 2 GHz with amplitude characteristics of a three‐section directional coupler.
Recombinant human insulin‐like growth factor‐1 therapy for 6 months improves growth but not motor function in boys with Duchenne muscular dystrophy
Authors: Rutter Meilan M. , Wong Brenda L. , Collins James J. , Sawnani Hemant , Taylor Michael D. , Horn Paul S. , Backeljauw Philippe F. 
Published: February 2020

AbstractIntroductionRecombinant human insulin‐like growth factor‐1 (rhIGF‐1) is a growth factor and has anabolic effects on muscle. We investigated whether rhIGF‐1 therapy: 1) improves or preserves muscle function; and 2) improves growth in boys with Duchenne muscular dystrophy (DMD).MethodsIn this study we compared prepubescent, ambulatory, glucocorticoid‐treated boys with DMD (n = 17) vs controls (glucocorticoid therapy only, n = 21) in a 6‐month‐long, prospective, randomized, controlled trial of subcutaneous rhIGF‐1 therapy. The primary outcome was 6‐minute walk distance (6MWD). Secondary outcomes included height velocity (HV), change in height standard deviation score (ΔHtSDS), motor function, cardiopulmonary function, body composition, insulin sensitivity, quality of life, and safety.ResultsChange in 6MWD was similar between groups (rhIGF‐1 vs controls [mean ± SD]: 3.4 ± 32.4 vs −5.1 ± 50.2 meters, P = .53). Treated subjects grew more than controls (HV: 6.5 ± 1.7 vs 3.3 ± 1.3 cm/year, P < .0001; 6‐month ΔHtSDS: 0.25, P < .0001). Lean mass and insulin sensitivity increased in treated subjects.DiscussionIn boys with DMD, 6 months of rhIGF‐1 therapy did not change motor function, but it improved linear growth.