bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tranexamic acid suppresses the release of mitochondrial DNA, protects the endothelial monolayer and enhances oxidative phosphorylation
Authors: Prudovsky Igor , Carter Damien , Kacer Doreen , Palmeri Monica , Soul Tee , Kumpel Chloe , Pyburn Kathleen , Barrett Karyn , DeMambro Victoria , Alexandrov Ilya , Brandina Irina , Kramer Robert , Rappold Joseph 
Published: April 2019

AbstractDamage‐associated molecular patterns, including mitochondrial DNA (mtDNA) are released during hemorrhage resulting in the development of endotheliopathy. Tranexamic acid (TXA), an antifibrinolytic drug used in hemorrhaging patients, enhances their survival despite the lack of a comprehensive understanding of its cellular mechanisms of action. The present study is aimed to elucidate these mechanisms, with a focus on mitochondria. We found that TXA inhibits the release of endogenous mtDNA from granulocytes and endothelial cells. Furthermore, TXA attenuates the loss of the endothelial monolayer integrity induced by exogenous mtDNA. Using the Seahorse XF technology, it was demonstrated that TXA strongly stimulates mitochondrial respiration. Studies using Mitotracker dye, cells derived from mito‐QC mice, and the ActivSignal IPAD assay, indicate that TXA stimulates biogenesis of mitochondria and inhibits mitophagy. These findings open the potential for improvement of the strategies of TXA applications in trauma patients and the development of more efficient TXA derivatives.
On the Field Strength Dependence of Bi‐ and Triexponential Intravoxel Incoherent Motion (IVIM) Parameters in the Liver
Authors: Riexinger Andreas Julian , Martin Jan , Rauh Susanne , Wetscherek Andreas , Pistel Mona , Kuder Tristan Anselm , Nagel Armin Michael , Uder Michael , Hensel Bernhard , Müller Lars , Laun Frederik Bernd 
Published: April 2019

BackgroundStudies on intravoxel incoherent motion (IVIM) imaging are carried out with different acquisition protocols.PurposeTo investigate the dependence of IVIM parameters on the B0 field strength when using a bi‐ or triexponential model.Study TypeProspective.Study Population20 healthy volunteers (age: 19–28 years).Field Strength/SequenceVolunteers were examined at two field strengths (1.5 and 3T). Diffusion‐weighted images of the abdomen were acquired at 24 b‐values ranging from 0.2 to 500 s/mm2.AssessmentROIs were manually drawn in the liver. Data were fitted with a bi‐ and a triexponential IVIM model. The resulting parameters were compared between both field strengths.Statistical TestsOne‐way analysis of variance (ANOVA) and Kruskal–Wallis test were used to test the obtained IVIM parameters for a significant field strength dependency.ResultsAt b‐values below 6 s/mm2, the triexponential model provided better agreement with the data than the biexponential model. The average tissue diffusivity was D = 1.22/1.00 μm2/msec at 1.5/3T. The average pseudodiffusion coefficients for the biexponential model were D* = 308/260 μm2/msec at 1.5/3T; and for the triexponential model = 81.3/65.9 μm2/msec, = 2453/2333 μm2/msec at 1.5/3T. The average perfusion fractions for the biexponential model were f = 0.286/0.303 at 1.5/3T; and for the triexponential model f1 = 0.161/0.174 and f2 = 0.152/0.159 at 1.5/3T. A significant B0 dependence was only found for the biexponential pseudodiffusion coefficient (ANOVA/KW P = 0.037/0.0453) and tissue diffusivity (ANOVA/KW: P < 0.001).Data ConclusionOur experimental results suggest that triexponential pseudodiffusion coefficients and perfusion fractions obtained at different field strengths could be compared across different studies using different B0. However, it is recommended to take the field strength into account when comparing tissue diffusivities or using the biexponential IVIM model. Considering published values for oxygenation‐dependent transversal relaxation times of blood, it is unlikely that the two blood compartments of the triexponential model represent venous and arterial blood.Level of Evidence: 1Technical Efficacy Stage: 2J. Magn. Reson. Imaging 2019;50:1883–1892.
Distinct expression and clinical value of aquaporin 4 in children with hand, foot and mouth disease caused by enterovirus 71
Authors: Zhu Lei , Yin Hong , Qian Tong , Qi Gong‐jian , Ren Jin‐song , Wang Yin , Qi Bo‐xiang 
Published: April 2019

AbstractBrain dysfunction is a prerequisite for critical complications in children with hand, foot, and mouth disease (HFMD). Aquaporin 4 (AQP‐4) may be involved in the pathological process of cerebral oedema and injury in children with severe and critical HFMD. This study aimed to assess the association of AQP‐4 with the severity of enterovirus 71 (EV71)–associated HFMD. Children with EV71‐infected HFMD were divided into a common group (clinical stage 1), a severe group (clinical stage 2), and a critical group (clinical stage 3) according to Chinese guidelines. The levels of AQP‐4, interleukin‐6 (IL‐6), norepinephrine (NE), and neuron‐specific enolase (NSE) before and after treatment were tested. Serum AQP‐4, IL‐6, NE, and NSE levels showed significant differences among the critical, severe, and common groups before and after treatment (P < 0.01). No significant differences in AQP‐4 levels in cerebrospinal fluid (CSF) were observed between the critical and severe groups before and after treatment, but the CSF AQP‐4 levels in these two groups were higher than those in the common group before treatment (P < 0.01). Serum AQP‐4 levels, but not CSF AQP‐4 levels, closely correlated with serum IL‐6, NE, and NSE levels. These results suggest that the level of AQP‐4 in serum, but not in CSF, is a candidate biomarker for evaluating the severity and prognosis of EV71‐associated HFMD.
Microglial phagocytosis in aging and Alzheimer's disease
Authors: Gabandé‐Rodríguez Enrique , Keane Lily , Capasso Melania 
Published: April 2019

AbstractMicroglia are the innate immune cells of the brain, which maintain homeostasis by constantly scanning and surveying the environment with their highly ramified processes. In order to exert this function, they need to phagocytose synapses as well as debris and dead cells, a process that is further amplified in pathological conditions. Importantly, it has been shown that microglia phagocytic capacity is altered in the course of neurodegenerative disease, for which aging is one of the highest risk factors. Thus, understanding how phagocytosis is impaired during aging is a priority for future research. Advances in this area are expected to significantly contribute to our understanding of normal cognition during aging, as well as changes that take place in age‐associated neurodegenerative diseases. In this review, we will summarize the current knowledge on how phagocytosis is executed and affected by aging or in age‐associated neurological disorders, such as Alzheimer's disease (AD). Furthermore, we will summarize both protective and deleterious consequences of altered phagocytosis in AD and where relevant in other neurodegenerative diseases.
Limitations of univariate linear bias correction in yielding cross‐correlation between monthly precipitation and temperature
Authors: Bhowmik R. Das , Sankarasubramanian A. 
Published: April 2019

AbstractStatistical bias correction techniques are commonly used in climate model projections to reduce systematic biases. Among the several bias correction techniques, univariate linear bias correction (e.g., quantile mapping) is the most popular, given its simplicity. Univariate linear bias correction can accurately reproduce the observed mean of a given climate variable. However, when performed separately on multiple variables, it does not yield the observed multivariate cross‐correlation structure. In the current study, we consider the intrinsic properties of two candidate univariate linear bias‐correction approaches (simple linear regression and asynchronous regression) in estimating the observed cross‐correlation between precipitation and temperature. Two linear regression models are applied separately on both the observed and the projected variables. The analytical solution suggests that two candidate approaches simply reproduce the cross‐correlation from the general circulation models (GCMs) in the bias‐corrected data set because of their linearity. Our study adopts two frameworks, based on the Fisher z‐transformation and bootstrapping, to provide 95% lower and upper confidence limits (referred as the permissible bound) for the GCM cross‐correlation. Beyond the permissible bound, raw/bias‐corrected GCM cross‐correlation significantly differs from those observed. Two frameworks are applied on three GCMs from the CMIP5 multimodel ensemble over the coterminous United States. We found that (a) the univariate linear techniques fail to reproduce the observed cross‐correlation in the bias‐corrected data set over 90% (30–50%) of the grid points where the multivariate skewness coefficient values are substantial (small) and statistically significant (statistically insignificant) from zero; (b) the performance of the univariate linear techniques under bootstrapping (Fisher z‐transformation) remains uniform (non‐uniform) across climate regions, months, and GCMs; (c) grid points, where the observed cross‐correlation is statistically significant, witness a failure fraction of around 0.2 (0.8) under the Fisher z‐transformation (bootstrapping). The importance of reproducing cross‐correlations is also discussed along with an enquiry into the multivariate approaches that can potentially address the bias in yielding cross‐correlations.
Comprehensive characterization and quantification of multiple components in Dan‐Huang‐Qu‐Yu capsule using a multivariate data processing approach based on microwave‐assisted extraction with UHPLC and Q Exactive quadrupole‐orbitrap high‐resolution mass spectrometry
Authors: Yang Bo , Ying Yin , Zou Jie , Ge Shuyu , Zuo Lihua 
Published: April 2019

AbstractDan‐Huang‐Qu‐Yu capsule, a Chinese herbal medicine compound preparation, is widely used for chronic pelvic inflammatory disease. In this study, a rapid, selective, and sensitive microwave‐assisted extraction ultra‐high‐performance liquid chromatography‐Q Exactive quadrupole‐orbitrap high‐resolution mass spectrometry method was developed for analyzing its chemical compositions. A total of 85 compounds, including 22 flavonoids, 8 terpenoids, 5 quinones, 5 phthaleolactone, 23 organic acids, and 22 other compounds were identified from Dan‐Huang‐Qu‐Yu capsule. Among them, 35 major compounds were unambiguously detected by comparing them with reference standards and selected as quality control markers, which were simultaneously determined in Dan‐Huang‐Qu‐Yu capsule. The established method was successfully validated and applied for simultaneous determination of 35 bioactive compounds in Dan‐Huang‐Qu‐Yu capsule from ten sample batches. The quantitative data of the analytes were analyzed by principal component analysis for quality assessment of Dan‐Huang‐Qu‐Yu capsule. Six compounds (e.g., astragaloside IV, salvianolic acid B, ellagic acid, chlorogenic acid, N‐butylidenephthalide, and luteolin) were screened out and regarded as chemical markers for quality control of Dan‐Huang‐Qu‐Yu capsule. The established method has been proved to be a novel and useful tool for rapid research of Dan‐Huang‐Qu‐Yu capsule. This research will provide reference for the scientific research of traditional Chinese medicines.
Enhanced Bone Defect Repair by Polymeric Substitute Fillers of MultiArm Polyethylene Glycol‐Crosslinked Hyaluronic Acid Hydrogels
Authors: Yuan Jishan , Maturavongsadit Panita , Metavarayuth Kamolrat , Luckanagul Jittima Amie , Wang Qian 
Published: April 2019

AbstractBone regeneration is still one of the greatest challenges for the treatment of bone defects since no current clinical approach has been proven effective. To develop an alternative biodegradable bone graft material, multiarm polyethylene glycol (PEG) crosslinked hyaluronic acid (HA) hydrogels are synthesized and applied to promote osteogenesis of mesenchymal stem cells (MSCs) with the ultimate goal for bone defect repair. The multiarm PEG‐HA hydrogels provide a significant improvement of alkaline phosphatase (ALP) activity and calcium mineralization of the in vitro encapsulated MSCs under osteogenic condition after 3, 7, and 28 days. In addition, the multiarm PEG‐HA hydrogels also facilitate healing of the cranial bone defects more effectively in a Sprague Dawley rat model after 10 weeks of implantation based on histological evaluations and microcomputed tomography analysis. These promising results set the stage for the development of innovative biodegradable hydrogels to provide a more effective and versatile treatment option for bone regeneration.
Synthesis and Gas Permeability of Chemically Cross‐Linked Polynorbornene Dicarboximides Bearing Fluorinated Moieties
Authors: Aranda‐Suárez Ivette , Corona‐García Carlos , Santiago Arlette A. , López Morales Salvador , Abatal Mohamed , López‐González Mar , Vargas Joel 
Published: April 2019

AbstractThis work reports on the synthesis of a novel bifunctional norbornene dicarboximide monomer (HFDA) based on 4,4′‐(hexafluoroisopropylidene)bis(p‐phenyleneoxy)dianiline and its application as a cross‐linking agent in the ring‐opening metathesis polymerization (ROMP) with N‐3‐trifluoromethylphenyl‐exo,endo‐norbornene‐5,6‐dicarboximide (mCF3) employing the Grubbs 2nd generation catalyst (I) and cis‐1,4‐diacetoxy‐2‐butene as a chain transfer agent (CTA) to yield a series of soluble nonlinear highly branched chains polymers with increasing degree of cross‐linking. A comparative study of gas transport in membranes based on these cross‐linked polynorbornene dicarboximides is performed and the gases studied are hydrogen, oxygen, nitrogen, carbon dioxide, methane, ethylene, and propylene. It is found that cross‐linking increases the gas permeability, leads to the highest separation factor reported to date for the H2/C3H6 mixture in this kind of polymers, and also enhances the CO2 plasticization resistance up to 14 atm upstream pressure. The chemical cross‐linking approach employed in this research is an effective tool to enhance gas transport properties for dense polynorbornene dicarboximide membranes.
A review of the molecular design and biological activities of RXR agonists
Authors: de Almeida Nathalia Rodrigues , Conda‐Sheridan Martin 
Published: April 2019

AbstractAn attractive approach to combat disease is to target theregulation of cell function. At the heart of this task are nuclear receptors (NRs); which control functions such as gene transcription. Arguably, the key player in this regulatory machinery is the retinoid X receptor (RXR). This NR associates with a third of the NRs found in humans. Scientists have hypothesized that controlling the activity of RXR is an attractive approach to control cellular functions that modulate diseases such as cancer, diabetes, Alzheimer's disease and Parkinson's disease. In this review, we will describe the key features of the RXR, present a historic perspective of the first RXR agonists, and discuss various templates that have been reported to activate RXR with a focus on their molecular structure, biological activity, and limitations. Finally, we will present an outlook of the field and future directions and considerations to synthesize or modulate RXR agonists to make these compounds a clinical reality.
Reduction of expression of IL‐18, IL‐1β genes in the articular joint by sumac fruit extract (Rhus coriaria L.)
Authors: Momeni Amin , Maghsoodi Hossein , Rezapour Sadegh , Shiravand Mostafa , Mardani Mahnaz 
Published: April 2019

AbstractBackgroundOsteoarthritis is the most common malignant disease in the world. The disease is caused by changes in the metabolism, the structure and function of multiple joints, and joint tissues. Sumac is one of the indigenous plants of Iran and has traditionally been used as a spice in Iran. The aim of this study was to investigate the reduction of expression of IL‐18, IL‐1β genes in the articular joint by sumac fruit extract (Rhus coriaria L.).MethodsThe alcoholic extract of sumac fruit (E.E.R.C.L) was prepared from the Genetic Reserve Center. Bleeding was used to provide synoviocyte cells from the joint and fluid of the anatomical metacarpal limb of the 8‐month‐old Holstein healthy calf without any signs of inflammation. Using cell‐hemocytometer count, their viability was evaluated by trypan blue and after lipopolysaccharide (LPS) proliferation and injection to enhance the level of cytokines. After isolating the RNA and preparing the cDNA, RT‐PCR and PCR were performed and then, using the real‐time PCR method, the expression of the desired genes was investigated.ResultsIn this study, after the expression of IL‐18 cytokines, IL‐1β increased to 100%, and following the treatment with alcoholic extract, the reduction of expression of these cytokines was 33.61% and 29.01%, respectively. The results of anti‐inflammatory effects showed that the alcoholic extract of sumac reduced the IL‐1β, IL‐18 expression in LPS‐stimulated cells.ConclusionSumac fruit extract can be an effective medication for reducing pain.
Quantitative muscle ultrasound in upper extremity mononeuropathies
Authors: Wang Yun , Gutierrez Hilda , Martucci Maria , Poussaint Alison , Qi Kristin , Sanchez Benjamin , Rutkove Seward B. 
Published: April 2019

ABSTRACTIntroductionWe assessed the potential use of quantitative ultrasound (QUS) in the evaluation hand muscles affected by upper extremity mononeuropathies.MethodsThe gray scale levels (GSLs) of abductor pollicis brevis (APB), abductor digiti minimi (ADM), and first dorsal interosseous (FDI) of 30 healthy and 30 upper extremity mononeuropathy patients were measured and compared with standard electrophysiological values.ResultsMean GSL was elevated in 34 APBs of carpal tunnel syndrome patients and 18 FDIs of ulnar neuropathy patients (e.g., FDI mean GSL (interquartile range) 31.5 (27.3~43.8) arbitrary units for patients and 24.0(23.0~29.0) for healthy subjects (P = 0.020)). GSL correlated with motor response amplitudes (Spearman's rho (ρ) = ‐0.39, P = 0.002 in APB, ρ = ‐0.72, P = 0.002 in FDI, and ρ = ‐0.43, P = 0.013 in ADM). The APB GSL correlated with electromyographic severity and disease duration (ρ = 0.46, P < 0.001 and ρ = 0.45, P = 0.003).ConclusionsMuscle QUS may serve as a useful tool in upper extremity mononeuropathy evaluation. Further study of this concept is recommended.
Aerobic exercise and consecutive task‐specific training (AExaCTT) for upper limb recovery after stroke: A randomized controlled pilot study
Authors: Valkenborghs Sarah R. , van Vliet Paulette , Nilsson Michael , Zalewska Katarzyna , Visser Milanka M. , Erickson Kirk I. , Callister Robin 
Published: April 2019

AbstractObjectiveThis study examined the feasibility of a parallel‐group assessor‐blinded randomized controlled trial investigating whether task‐specific training preceded by aerobic exercise (AEX + TST) improves upper limb function more than task‐specific training (TST) alone.MethodsPeople with upper limb motor dysfunction after stroke were allocated to TST or AEX + TST. Both groups were prescribed 60 hr of TST over 10 weeks (3 × 1‐hr sessions with a therapist per week and 3 × 1 hr of home‐based self‐practice per week). The AEX + TST group performed 30 minutes of aerobic exercise immediately prior to the 1 hr of TST with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events were recorded. Clinical measures were performed prerandomization at baseline, on completion of the intervention, and at 1‐ and 6‐month follow‐up.ResultsFifty‐nine persons after stroke were screened, 42 met the eligibility criteria, and 20 (11 male; mean [SD] age: 55.4 [16.0] years; time since stroke: 71.7 [91.2] months) were recruited over 17 months. The mean Wolf Motor Function Test Functional Ability Score at baseline was 27.4 (max = 75) and the mean Action Research Arm Test score was 11.2 (max = 57). Nine were randomized to AEX + TST and 11 to TST. There were no adverse events, but there was one drop out. Retention at 1‐ and 6‐month follow‐up was 80% and 85%, respectively. Attendance was 93% (6) for the AEX + TST group, and 89% (9) for the TST group. AEX + TST was perceived as acceptable (100%) and beneficial (87.5%). Exertional fatigue (visual analogue scale) prior to TST was worse in the AEX + TST group (3.5 [0.7] out of 10) than the TST group (1.7 [1.4] out of 10). The TST group performed 31% more repetitions per session than the AEX + TST group.ConclusionA subsequent Phase III study is feasible, but modifications to eligibility criteria, outcome measures, and intervention delivery are recommended.
Bismaleimide cross‐linked anthrax toxin forms functional octamers with high specificity in tumor targeting
Authors: Fischer Elyse S. , Campbell Warren A. , Liu Shihui , Ghirlando Rodolfo , Fattah Rasem J. , Bugge Thomas H. , Leppla Stephen H. 
Published: April 2019

AbstractIn recent years, anthrax toxin has been reengineered to act as a highly specific antiangiogenic cancer therapeutic, shown to kill tumors in animal models. This has been achieved by modifying protective antigen (PA) so that its activation and toxicity require the presence of two proteases, matrix metalloproteinase (MMP) and urokinase plasminogen activator (uPA), which are upregulated in tumor microenvironments. These therapeutics consist of intercomplementing PA variants, which are individually nontoxic, but form functional toxins upon complementary oligomerization. Here, we have created a dual‐protease requiring PA targeting system which utilizes bismaleimide cross‐linked PA (CLPA) rather than the intercomplementing PA variants. Three different CLPA agents were tested and, as expected, found to exclusively form octamers. Two of the CLPA agents have in vitro toxicities equal to those of previous intercomplementing agents, while the third CLPA agent had compromised in vitro cleavage and was significantly less cytotoxic. We hypothesize this difference was due to steric hindrance caused by cross‐linking two PA monomers in close proximity to the PA cleavage site. Overall, this work advances the development and use of the PA and LF tumor‐targeting system as a practical cancer therapeutic, as it provides a way to reduce the drug components of the anthrax toxin drug delivery system from three to two, which may lower the cost and simplify testing in clinical trials.HIGHLIGHTPreviously, anthrax toxin has been reengineered to act as a highly specific antiangiogenic cancer therapeutic. Here, we present a version, which utilizes bismaleimide cross‐linked protective antigen (PA) rather than intercomplementing PA variants. This advances the development of anthrax toxin as a practical cancer therapeutic as it reduces the components of the drug delivery system to two, which may lower the cost and simplify testing in clinical trials.