bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway
Authors: Liu Na , Fu Dejie , Yang Junjun , Liu Pingju , Song Xiongbo , Wang Xin , Li Rui , Fu Zhenlan , Chen Jiajia , Gong Xiaoyuan , Chen Cheng , Yang Liu 
Published: May 2020

AbstractBackgroundOsteoarthritis (OA), the most common joint disorder, is characterized by a progressive degradation of articular cartilage. Increasing evidence suggests that OA is closely associated with cartilage pathologies including chondrocyte hypertrophy and fibrosis.MethodsIn this study, we showed that asiatic acid (AA) treatment reduced chondrocyte hypertrophy and fibrosis. First, the cytotoxicity of AA (0, 5, 10, and 20 μM) to chondrocytes was evaluated, and 5 μM was selected for subsequent experiments. Then, we detected the gene and protein level of chondrocyte hypertrophic markers including type X collagen (COL-X), matrix metalloproteinase-13 (MMP-13), alkaline phosphatase (ALP), and runt-related transcription factor 2 (Runx2); chondrocyte fibrosis markers including type I collagen (COL-Ι) and alpha-smooth muscle actin (α-SMA); and chondrogenic markers including SRY-related HMG box 9 (SOX9), type II collagen (COL-II), and aggrecan (ACAN). Further, we tested the mechanism of AA on inhibiting chondrocyte hypertrophy and fibrosis. Finally, we verified the results in an anterior cruciate ligament transection (ACLT) rat OA model.ResultsWe found that AA treatment inhibited the hypertrophic and fibrotic phenotype of chondrocytes, without affecting the chondrogenic phenotype. Moreover, we found that AA treatment activated AMP-activated protein kinase (AMPK) and inhibited phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) signaling pathway in vitro. The results in an ACLT rat OA model also indicated that AA significantly attenuated chondrocyte hypertrophy and fibrosis.ConclusionAA treatment could reduce hypertrophic and fibrotic differentiation and maintain the chondrogenic phenotype of articular chondrocytes by targeting the AMPK/PI3K/AKT signaling pathway. Our study suggested that AA might be a prospective drug component that targets hypertrophic and fibrotic chondrocytes for OA treatment.
Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis
Authors: Yin Yufeng , Wang Mingjun , Liu Mengru , Zhou Erye , Ren Tian , Chang Xin , He Michun , Zeng Keqin , Guo Yufan , Wu Jian 
Published: May 2020

Abstract
Objectives
To systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis.

Methods
A systematic review of the literature was performed for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. Meta-analyses were used to determine the efficacy and safety of the IL-17 inhibitors in the treatment of these patients. The primary endpoint was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary endpoint was defined as ASAS40 at week 16.

Results
Six phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR = 1.63, 95% CI 1.45 to 1.84, p = 0.00) and the secondary endpoint ASAS40 response rate (RR = 2.12, 95% CI 1.75 to 2.56, p = 0.00) versus those for the placebo. With respect to the safety profile, more treatment-emergent adverse events (RR = 1.11, 95% CI 1.01 to 1.22, p = 0.03) and non-severe infections (RR = 1.82, 95% CI 1.40 to 2.37, p < 0.001) were described after treatment with IL-17 inhibitors than after treatment with placebo, while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including death, discontinuation due to adverse events, or serious adverse events.

Conclusions
IL-17 inhibitors produced favorable response rates but an increased risk of non-severe infections in the treatment of active ankylosing spondylitis.
Immunohistochemistry of advanced glycation end product Nε-(carboxymethyl)lysine in coronary arteries in relation to cardiac fibrosis and serum N-terminal-pro basic natriuretic peptide in forensic autopsy cases
Authors: Nogami Makoto , Hoshi Tomoaki , Toukairin Yoko , Arai Tomomi , Nishio Tadashi 
Published: May 2020

Abstract
Objective
Advanced glycation end products (AGEs) are known to play important roles in the development of diabetes mellitus and atherosclerosis.　Nε-(carboxymethyl)lysine (CML) is the major AGE, and is found in the arterial walls in the heart. The CML involvement in myocardial ischemia has been reported. We studied the immunohistochemical localization of CML in the hearts from forensic autopsies in relation to the age, serum N-terminal-pro basic natriuretic peptide (NT-proBNP), heart weights, and the degree of peri-myocardial fibrous tissues reflecting coronary microvascular infarction and myocardial remodeling.

Results
The CML immunoreactivity in the endothelial cells and intima of arterial walls in the interstitium of ventricular muscles was significantly stronger in the aged group, compatible with the progression of atherosclerosis. The blood level of NT-proBNP, a known useful marker for heart failure, had the positive correlation with the CML immunoreactivity. The degree of fibrosis, heart weights and the histories of hypertension and hyperlipidemia showed positive correlations with the CML immunoreactivity. Our results show the novel positive correlation between the CML immunohistochemistry in the heart vessels and heart conditions, and its future usefulness in the cardiovascular evaluation in histopathology.
Bio-banding in junior soccer players: a pilot study
Authors: Romann Michael , Lüdin Dennis , Born Dennis-Peter 
Published: May 2020

Abstract
Objective
Bio-banding (BB) has been introduced to account for varying maturity and to improve the talent development of junior soccer players. To date, research that investigated the physiological and technical effects of BB is sparse. Therefore, the aim of the study was to compare effects of BB with CA on selected technical and tactical parameters in U13 and U14 soccer players.

Results
BB significantly increased the number of duels (p = 0.024) and set pieces (p = 0.025) compared to chronological age. The mean time of ball possession per action was reduced (p = 0.021) and the rate of successful passes was lower with BB (p = 0.001). Meanwhile, the total number of passes was unaffected (p = 0.796), and there was a trend towards a lower difference in ball possession between BB teams (p = 0.058). In addition, BB reduced the distances covered while jogging (p = 0.001), running (p = 0.038) and high-speed running (p = 0.035). With BB, an increased number of duels, unsuccessful passes and set pieces resulted in a quicker change of match play situations between teams. While physical demand was reduced, BB seems to result in a more technically and tactically challenging game. Benefits in long-term player development, however, require further investigation.
Transcriptional analysis of the multiple Sry genes and developmental program at the onset of testis differentiation in the rat
Authors: Prokop Jeremy W. , Chhetri Surya B. , van Veen J. Edward , Chen Xuqi , Underwood Adam C. , Uhl Katie , Dwinell Melinda R. , Geurts Aron M. , Correa Stephanie M. , Arnold Arthur P. 
Published: May 2020

AbstractBackgroundThe commonly used laboratory rat,Rattus norvegicus, is unique in having multipleSrygene copies found on the Y chromosome, with different copies encoding amino acid variations that influence the resulting protein function. It is not clear whichSrygenes are expressed at the onset of testis differentiation or how their expression correlates with that of other genes in testis-determination pathways.MethodsHere, two independent E11–E14 developmental RNAseq datasets show that multipleSrygenes are expressed at E12–E13.ResultsThe identified copies expressed during testis initiation includeSry4A,Sry1, andSry3C, which are conserved in every strain ofRattus norvegicuswith genomes sequenced to date.ConclusionsThis work represents a first step in defining the complex environment of rat testis differentiation that can open the door for generating sex reversal model systems using embryo manipulation techniques that have been available in the mouse but not the rat.
kGCN: a graph-based deep learning framework for chemical structures
Authors: Kojima Ryosuke , Ishida Shoichi , Ohta Masateru , Iwata Hiroaki , Honma Teruki , Okuno Yasushi 
Published: May 2020

AbstractDeep learning is developing as an important technology to perform various tasks in cheminformatics. In particular, graph convolutional neural networks (GCNs) have been reported to perform well in many types of prediction tasks related to molecules. Although GCN exhibits considerable potential in various applications, appropriate utilization of this resource for obtaining reasonable and reliable prediction results requires thorough understanding of GCN and programming. To leverage the power of GCN to benefit various users from chemists to cheminformaticians, an open-source GCN tool, kGCN, is introduced. To support the users with various levels of programming skills, kGCN includes three interfaces: a graphical user interface (GUI) employing KNIME for users with limited programming skills such as chemists, as well as command-line and Python library interfaces for users with advanced programming skills such as cheminformaticians. To support the three steps required for building a prediction model, i.e., pre-processing, model tuning, and interpretation of results, kGCN includes functions of typical pre-processing, Bayesian optimization for automatic model tuning, and visualization of the atomic contribution to prediction for interpretation of results. kGCN supports three types of approaches, single-task, multi-task, and multi-modal predictions. The prediction of compound-protein interaction for four matrixmetalloproteases, MMP-3, -9, -12 and -13, in the inhibition assays is performed as a representative case study using kGCN. Additionally, kGCN provides the visualization of atomic contributions to the prediction. Such visualization is useful for the validation of the prediction models and the design of molecules based on the prediction model, realizing “explainable AI” for understanding the factors affecting AI prediction. kGCN is available at https://github.com/clinfo.
VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs
Authors: Johnson Lynne L. , Johnson Jordan , Ali Ziad , Tekabe Yared , Ober Rebecca , Geist Gail , McLuckie Alicia , Safarov Aram , Holland April , Zhang Geping , Backer Marina , Backer Joseph 
Published: May 2020

Abstract
Background
New therapies to treat diabetic peripheral artery disease (PAD) require target-specific non-invasive imaging modalities to follow efficacy. As a translational study, we performed targeted imaging of receptors for vascular endothelial growth factor (VEGF) in response to anterior femoral artery occlusion (FAO) in Yucatan minipigs and compare the normal response to response in diabetic Yucatan minipigs.

Methods
Eleven Yucatan minipigs, 6 non-diabetic (non-D) and 5 purpose bred diabetic (D) (Sinclair, Auxvasse MO), underwent intravascular total occlusion of the anterior femoral artery (FA). At days 1 and 28, pigs underwent SPECT/CT 201Tl hindlimb perfusion imaging and at day 7 were injected with [99mTc]DOTA-PEG-scVEGF (scV/Tc) tracer targeting VEGF receptor, and underwent biopsies of the hindlimb muscles for gamma counting and histology, followed by imaging. One day after the final scan, pigs underwent contrast angiography of the lower extremities. Counts from scans were converted to percentage injected activity (%IA).

Results
Perfusion was lower in the occluded hindlimb compared to non-occluded on day 1 in both the D and non-D pigs. At day 7, scV/Tc count ratio of counts from ROIs drawn in proximal gastrocnemius muscle for the occluded over non-occluded limb was significantly higher in non-D vs. D pigs (1.32 ± 0.06 vs. 1.04 ± 0.13, P = 0.02) reflecting higher level of angiogenesis. Perfusion increased between days 1 and 28 in the muscles in the occluded limb for the non-diabetic pigs while the diabetic pig showed no increase (+ 0.13 ± 0.08 %IA vs. − 0.13 ± 0.11, P = 0.003). The anterior FA showed poor contrast filling beyond occluder and qualitatively fewer bridging collaterals compared to non-D pigs at 28 days.

Conclusion
VEGF receptor targeted imaging showed the effects of diabetes to suppress angiogenesis in response to occlusion of the anterior femoral artery of purpose bred diabetic Yucatan minipigs and indicates potential applicability as a marker to follow efficacy of novel therapies to improve blood flow by stimulating angiogenesis in diabetic PAD.
RNA-Seq analysis of European sea bass (Dicentrarchus labrax L.) infected with nodavirus reveals powerful modulation of the stress response
Authors: Lama Raquel , Pereiro Patricia , Valenzuela-Muñoz Valentina , Gallardo-Escárate Cristian , Tort Lluis , Figueras Antonio , Novoa Beatriz 
Published: May 2020

AbstractNodavirus, or nervous necrosis virus (NNV), is the causative agent of viral encephalopathy and retinopathy (VER), a severe disease affecting numerous fish species worldwide. European sea bass, a cultured species of great economic importance, is highly susceptible to the disease. To better understand the response of this organism to NNV, we conducted RNA-Seq analysis of the brain and head kidney from experimentally infected and uninfected sea bass juveniles at 24 and 72 hours post-infection (hpi). Contrary to what was expected, we observed modest modulation of immune-related genes in the brain, the target organ of this virus, and some of these genes were even downregulated. However, genes involved in the stress response showed extremely high modulation. Accordingly, the genes encoding the enzymes implicated in the synthesis of cortisol were almost the only overexpressed genes in the head kidney at 24 hpi. This stress response was attenuated after 72 h in both tissues, and a progressive immune response against the virus was mounted. Moreover, experiments were conducted to determine how stress activation could impact NNV replication. Our results show the complex interplay between viral activity, the stress reaction and the immune response.
Estimation of f-divergence and Shannon entropy by using Levinson type inequalities for higher order convex functions via Hermite interpolating polynomial
Authors: Adeel Muhammad , Khan Khuram Ali , Pečarić Ðilda , Pečarić Josip 
Published: May 2020

AbstractLevinson type inequalities are generalized by using Hermite interpolating polynomial for the class of $\mathfrak{n}$n-convex functions. In seek of application to information theory, some estimates for new functional are obtained based on f divergence. Inequalities involving Shannon entropies are also discussed.
Existence and monotone iteration of unique solution for tempered fractional differential equations Riemann–Stieltjes integral boundary value problems
Authors: Zhou Bibo , Zhang Lingling , Zhang Nan , Addai Emmanuel 
Published: May 2020

AbstractThe primary objective of this research paper is to investigate two kinds of high-order tempered fractional differential equations integral boundary value problems. By means of the mixed monotone operators fixed point theorems with perturbation and the increasing$\varphi -(h,\sigma )$φ−(h,σ)-concave operators fixed point theorems, we can not only guarantee the existence-uniqueness of solution, but also construct successively sequences for approximating the unique solution. In addition, we demonstrate the effectiveness of the main result by using two examples.
COVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission
Authors: Godri Pollitt Krystal J. , Peccia Jordan , Ko Albert I. , Kaminski Naftali , Dela Cruz Charles S. , Nebert Daniel W. , Reichardt Juergen K.V. , Thompson David C. , Vasiliou Vasilis 
Published: May 2020

AbstractThe recent coronavirus disease (COVID-19), caused by SARS-CoV-2, is inarguably the most challenging coronavirus outbreak relative to the previous outbreaks involving SARS-CoV and MERS-CoV. With the number of COVID-19 cases now exceeding 2 million worldwide, it is apparent that (i) transmission of SARS-CoV-2 is very high and (ii) there are large variations in disease severity, one component of which may be genetic variability in the response to the virus. Controlling current rates of infection and combating future waves require a better understanding of the routes of exposure to SARS-CoV-2 and the underlying genomic susceptibility to this disease. In this mini-review, we highlight possible genetic determinants of COVID-19 and the contribution of aerosol exposure as a potentially important transmission route of SARS-CoV-2.
Factors associated with drug use in prison – results from the Norwegian offender mental health and addiction (NorMA) study
Authors: Bukten Anne , Lund Ingunn Olea , Kinner Stuart A. , Rognli Eline Borger , Havnes Ingrid Amalia , Muller Ashley Elizabeth , Stavseth Marianne Riksheim 
Published: May 2020

Abstract
Background
Remarkably little is known about drug use during imprisonment, including whether it represents a continuation of pre-incarceration drug use, or whether prison is also a setting for drug use initiation. This paper aims to describe drug use among people in prison in Norway and investigate risk factors associated with in-prison drug use.

Methods
We used data from the Norwegian Offender Mental Health and Addiction (NorMA) Study, a cross-sectional survey of 1499 individuals in Norwegian prisons. Respondents reported on drug use (narcotics and non-prescribed medications) both before and during imprisonment. We used multivariate logistic regression to investigate the associations between drug use in prison and demographics, previous drug use, mental health, and criminal activity.

Results
Sixty-five percent of respondents reported lifetime drug use, and about 50% reported daily use of drugs during the 6 months before incarceration. Thirty-five percent reported ever using drugs in prison, but initiation of drug used during incarceration was uncommon. In a multivariate model, factors independently associated with drug use in prison included lifetime number of drugs used (adjusted odds ratio [aOR] = 1.17; 95% confidence interval [CI] 1.12–1.23; p <  0.001), daily drug use in the 6 months before imprisonment (aOR = 7.12; 95%CI 3.99–12.70; p <  0.001), and being intoxicated while committing the crime related to current imprisonment (aOR = 2.13; 95%CI 1.13–4.03; p = 0.020).

Conclusions
In-prison drug use is independently associated with high-risk drug use before imprisonment. To reduce drug use in prison, correctional services must systematically screen for pre-prison drug use and offer effective drug treatment for those in need.
How anxious is too anxious? State and trait physiological arousal predict anxious youth’s treatment response to brief cognitive behavioral therapy
Authors: McCormack Caitlyn C. , Mennies Rebekah J. , Silk Jennifer S. , Stone Lindsey B. 
Published: May 2020

Abstract
Background
Exposure therapy is the gold standard for treating childhood anxiety, yet not all youth improve. Children do not always have insight on their distress, which can limit the utility of self-reported units of distress (SUDS) during exposures. Physiological assessment provides an objective means of monitoring emotional arousal. Electrodermal activity (EDA) in particular indexes sympathetic nervous system arousal which is heavily linked to anxiety. The aim of the current study was to examine the feasibility and utility of incorporating EDA assessment in an in-session exposure. We examined concordance between EDA and SUDS, and whether either predicted treatment response.

Methods
Thirty-four youth who met DSM-5 criteria for generalized, separation, and/or social anxiety disorder completed brief CBT (8 sessions) and completed a survey on trait physiological arousal. EDA and SUDS were collected from 18 youth (9 female, ages 9–14) during a mid-treatment exposure. Changes in anxiety severity were examined post-treatment.

Results
SUDS were not correlated with trait or state physiological arousal. There was a large association between heightened sympathetic arousal and poorer post-treatment response. Similarly, SUDS indices of greater fear activation and habituation were associated with poorer post-treatment response with a small to moderate effect size. Supplemental analyses among the full sample aligned: trait physiological arousal predicted poorer treatment response.

Conclusions
The lack of concordance between sympathetic arousal and SUDS indices highlights the limitations of relying solely on SUDS with pediatric populations. EDA provided unique data on youth’s distress during exposures. Thus, results indicate that physiological assessment may exhibit clinical utility for aiding clinicians in monitoring youth’s progress in exposure therapy.

Trial Registration
ClinicalTrials.gov Identifier: NCT02259036.
Evaluation of geochemical records as a paleoenvironmental proxy in the hypercalcified demosponge Astrosclera willeyana
Authors: Asami Ryuji , Kinjo Akira , Ohshiro Daiki , Naruse Tohru , Mizuyama Masaru , Uemura Ryu , Shinjo Ryuichi , Ise Yuji , Fujita Yoshihisa , Sakamaki Takashi 
Published: May 2020

AbstractThe geochemistry of the calcium carbonates of marine organisms is an excellent proxy for reconstruction of the paleoceanographic history. However, previous studies of hypercalcified demosponges (sclerosponges) are considerably fewer than those of corals, foraminifers, and bivalves. Here, we investigated stable oxygen (δ18O) and carbon (δ13C) isotopes and minor and trace element (Mg, Sr, Ba, Pb, and U) to Ca ratios of 36 living sclerosponges (Astrosclera willeyana) collected from Kume Island in the Ryukyu Islands, southwestern Japan, to evaluate the utility of geochemistry as a paleoenvironmental proxy. The δ18O, δ13C, and Sr/Ca deviations of the coevally precipitated skeleton were extremely small and almost constant at all skeletal portions, strongly suggesting that within-skeletal variations in the chemical components are negligibly small for non-symbiotic sclerosponges. Mean δ18O, δ13C, and Sr/Ca values (N = 36), falling within a quite narrow range, showed no significant evidence for intraspecific (inter-specimen) variations in the sclerosponges. The sclerosponges δ18O and δ13C were consistent with those of the aragonites precipitated in isotopic equilibrium with seawater at the growth site. The sclerosponge Sr/Ca was close to that of inorganically precipitated aragonite, and the estimated partition coefficient of 1.1 (almost unity) is identical to previously reported values for different species (Ceratoporella nicholsoni). Consequently, these results suggest that A. willeyana sclerosponge, having little vital effects on the geochemistry, is a robust indicator of paleocean environments (seawater δ18O, temperature, and dissolved inorganic carbon δ13C). Further, our evaluation study documents that sclerosponges living in deeper ocean environments can support the reconstruction of spatial and vertical paleoceanographic changes in conjunction with coral proxy records. The sclerosponge U/Ca showed little within-skeletal and intraspecific variations, but the heterogeneity and individual difference of the Mg/Ca, Ba/Ca, and Pb/Ca were relatively large, the reasons of which still remain unresolved.