bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bile acid sequestrants: a review of mechanism and design
Authors: Feng Yumiao , Li Qian , Ou Ge , Yang Meiyan , Du Lina 
Published: April 2021

Abstract

Objective
Bile acid sequestrants (BAS) are used extensively in the treatment of hypercholesterolaemia. This brief review aimed to describe the design and evaluation of three types of BAS: amphiphilic copolymers, cyclodextrin/poly-cyclodextrin and molecular imprinted polymers. The mechanisms underlying the action of BAS are also discussed.

Key findings
BAS could lower plasma cholesterol, improve glycemic control in patients with type 2 diabetes and regulate balance energy metabolism via receptors or receptor-independent mediated mechanisms. Different types of BAS have different levels of ability to bind to bile acids, different stability and different in-vivo activity.

Conclusions
A growing amount of evidence suggests that bile acids play important roles not only in lipid metabolism but also in glucose metabolism. The higher selectivity, specificity, stability and in-vivo activity of BAS show considerable potential for lipid-lowering therapy.
Pepper E3 ligase CaAIRE1 promotes ABA sensitivity and drought tolerance by degradation of protein phosphatase CaAITP1
Authors: Baek Woonhee , Lim Chae Woo , Lee Sung Chul 
Published: April 2021

Abstract
Plants have developed defense mechanisms to survive in extreme environmental conditions. Abscisic acid (ABA) is a key phytohormone associated with plant adaptation to environmental stress. In this study, we isolated and functionally characterized the pepper RING-type E3 ligase CaAIRE1 (Capsicum annuum ABA Induced RING-type E3 ligase 1) containing the C3HC4-type RING domain. CaAIRE1 was induced by ABA and drought, and CaAIRE1 had E3 ligase activity. CaAIRE1-silenced pepper and CaAIRE1-overexpressing Arabidopsis presented drought-sensitive and drought-tolerant phenotypes, respectively, which were accompanied by altered transpiration water loss and ABA sensitivity. Moreover, we found that CaAIRE1 interacts with and ubiquitinates the pepper type 2C protein phosphatase, CaAITP1 (Capsicum annuum CaAIRE1 Interacting Target Phosphatase 1). A cell-free degradation assay with CaAIRE1-silenced peppers and CaAIRE1-overexpressing Arabidopsis plants revealed that the CaAITP1 protein level was negatively modulated by the expression level of CaAIRE1. In contrast to CaAIRE1, CaAITP1-silenced pepper showed ABA-sensitivity phenotypes. CaAITP1-overexpressing Arabidopsis plants were the most insensitive phenotypes to ABA compared with the wild type and other pepper PP2C-overexpressing plants. Taken together, our data indicate that CaAITP1 plays a major role as a negative modulator in ABA signaling, and CaAIRE1 regulates the ABA signaling and drought response through modulation of CaAITP1 stability.
MiR-150 Expression in Chronic Myeloid Leukemia: Relation to Imatinib Response
Authors: Habib Eman M , Nosiar Nahla A , Eid Manal A , Taha Atef M , Sherief Dalia E , Hassan Asmaa E , Abdel Ghafar Muhammad T 
Published: April 2021

Abstract

Objective
To assess the circulating micro-RNA-150 (miR-150) expression in patients with chronic myeloid leukemia (CML) in relation to imatinib response.

Methods
Sixty patients with CML and 20 age- and sex-matched control subjects were enrolled. Circulating miR-150 levels were assessed by quantitative real-time polymerase chain reaction on days 0, 14, and 90 of imatinib therapy for patients and once for control subjects.

Results
The baseline miR-150 expression was significantly lower in patients with CML than in control subjects with subsequent elevation at 14 and 90 days after the start of imatinib treatment. Early treatment response (ETR) at 90 days was the main study outcome. The miR-150 expression had a significantly higher level in patients with CML with ETR. On multivariate analysis, miR-150 on day 14 was significantly related to ETR in patients with CML with predictive efficacy (area under the curve = 0.838, 72.9% sensitivity, and 84.2% specificity).

Conclusion
We found that miR-150 expression on day 14 of imatinib treatment is a useful early predictive candidate for imatinib response in patients with CML.
Fundamental mechanism of the creation of chemical bimodality in the Milky Way disc in the cold accretion theory
Authors: Noguchi Masafumi 
Published: April 2021

ABSTRACT
Chemical bimodality of the Milky Way (MW) disc stars constitutes one of the most remarkable properties of MW. The cold accretion theory for the cosmological gas accretion provides one viable explanation to this phenomenon. In this scenario, the rapid cold-mode accretion in the early epoch creates the first generation stars relatively rich in α-elements (O, Mg, Si, S, Ca, etc) and later cooling flow produces iron-rich second generation stars, creating the bimodality in the [α/Fe] ratio. We employ a cosmologically motivated chemical evolution model for disc galaxies to elucidate the role played by type Ia supernovae (SN Ia), which serve as the major source of iron, in the creation of the bimodality. To this end, we divide SN Ia into two groups, those formed from the 1st generation stars (the first SN Ia) and those formed from the 2nd generation stars (the second SN Ia). The model with the first SN Ia suppressed during the second star formation stage produces stars having high [α/Fe] in the early phase of this stage, whereas the model which prohibits the second SN Ia produces high [α/Fe] stars in the late phase. Both models fail to create a well-defined bimodality. We, thus, conclude that the cooperation of the first and the second SN Ia plays a crucial role in creating the bimodality by maintaining rich iron content in the interstellar gas throughout the second star formation stage.
Unraveling the inner substructure of new candidate hub-filament system in the H ii region G25.4NW
Authors: Dewangan L K 
Published: April 2021

ABSTRACT
We present multiscale and multiwavelength data of the Galactic H ii region G25.4−0.14 (hereafter G25.4NW, distance ∼5.7 kpc). The SHARC-II 350-μm continuum map displays a hub-filament configuration containing five parsec-scale filaments and a central compact hub. Through the 5-GHz radio continuum map, four ionized clumps (i.e. Ia–Id) are identified towards the central hub, and are powered by massive OB-stars. The Herschel temperature map depicts the warm dust emission (i.e. T$_{\rm d}\, \sim$23–39 K) towards the hub. High-resolution Atacama Large Millimeter/submillimeter Array (ALMA) 1.3-mm continuum map (resolution ∼0.82 × 0.58 arcsec2) reveals three cores (c1–c3; mass ∼80–130 M⊙) towards the ionized clumps Ia, and another one (c4; mass ∼70 M⊙) towards the ionized clump Ib. A compact near-infrared (NIR) emission feature (extent ∼0.2 pc) is investigated towards the ionized clump Ia excited by an O8V-type star, and contains at least three embedded K-band stars. In the direction of the ionized clump Ia, the ALMA map also shows an elongated feature (extent ∼0.2 pc) hosting the cores c1–c3. All these findings together illustrate the existence of a small cluster of massive stars in the central hub. Considering the detection of the hub-filament morphology and the spatial locations of the mm cores, a global non-isotropic collapse (GNIC) scenario appears to be applicable in G25.4NW, which includes the basic ingredients of the global hierarchical collapse and clump-fed accretion models. Overall, the GNIC scenario explains the birth of massive stars in G25.4NW.
A generative model of galactic dust emission using variational autoencoders
Authors: Thorne Ben , Knox Lloyd , Prabhu Karthik 
Published: April 2021

ABSTRACT
Emission from the interstellar medium can be a significant contaminant of measurements of the intensity and polarization of the cosmic microwave background (CMB). For planning CMB observations, and for optimizing foreground-cleaning algorithms, a description of the statistical properties of such emission can be helpful. Here, we examine a machine learning approach to inferring the statistical properties of dust from observational data. In particular, we apply a type of neural network called a variational autoencoder (VAE) to maps of the intensity of emission from interstellar dust as inferred from Planck sky maps and demonstrate its ability to (i) simulate new samples with similar summary statistics as the training set, (ii) provide fits to emission maps withheld from the training set, and (iii) produce constrained realizations. We find VAEs are easier to train than another popular architecture: that of generative adversarial networks, and are better suited for use in Bayesian inference.
Temporal evolution of prompt GRB polarization
Authors: Gill Ramandeep , Granot Jonathan 
Published: April 2021

ABSTRACT
The dominant radiation mechanism that produces the prompt emission in gamma-ray bursts (GRBs) remains a major open question. Spectral information alone has proven insufficient in elucidating its nature. Time-resolved linear polarization has the potential to distinguish between popular emission mechanisms, e.g. synchrotron radiation from electrons with a power-law energy distribution or inverse Compton scattering of soft seed thermal photons, which can yield the typical GRB spectrum but produce different levels of polarization. Furthermore, it can be used to learn about the outflow’s composition (i.e. whether it is kinetic-energy-dominated or Poynting-flux-dominated) and angular structure. For synchrotron emission, it is a powerful probe of the magnetic field geometry. Here, we consider synchrotron emission from a thin ultrarelativistic outflow, with bulk Lorentz factor Γ(R) = Γ0(R/R0)−m/2 ≫ 1, that radiates a Band-function spectrum in a single (multiple) pulse(s) over a range of radii, R0 ≤ R ≤ R0 + ΔR. Pulse profiles and polarization evolution at a given energy are presented for a coasting (m = 0) and accelerating (m = −2/3) thin spherical shell and for different viewing angles for a top-hat jet with sharp as well as smooth edges in emissivity. Four different magnetic field configurations are considered, such as a locally ordered field coherent over angular scales θB ≳ 1/Γ, a tangled field (B⊥) in the plane transverse to the radial direction, an ordered field (B∥) aligned in the radial direction, and a globally ordered toroidal field (Btor). All field configurations produce distinct polarization evolution with single (for B⊥ and B∥) and double (for Btor) 90○ changes in the polarization position angle.
Analysis of Genetic Diversity and Antibiotic Options for Clinical Listeria monocytogenes Infections in China
Authors: Yu Wei , Huang Yicheng , Ying Chaoqun , Zhou Yanzi , Zhang Li , Zhang Jiajie , Chen Yingsha , Qiu Yunqing 
Published: April 2021

Abstract

Background
The aim of this study was to investigate the mechanism of Listeria monocytogenes (Lm) pathogenicity and resistance. In addition, the effect of existing treatment options against Lm were systematically evaluated.

Methods
Six Lm isolates were collected and antimicrobial susceptibility testing of 15 antibiotics were done. Subsequently, whole genome sequencing and bioinformatics analysis were performed. Biofilm formation was evaluated by crystal violet staining. Furthermore, the effect of meropenem, linezolid, penicillin, vancomycin, and trimethoprim/sulfamethoxazole were determined using the time-kill assay.

Results
Four sequence types (STs) were identified (ST1, ST3, ST87, ST451). Multivirulence-locus sequence typing results classified ST87 isolates into cluster. All isolates were resistant to fosfomycin and daptomycin with fosX and mprF. In addition, a total of 80 virulence genes were detected and 72 genes were found in all 6 isolates. Seven genes associated with hemolysin were found in 26530 and 115423. However, due to lack of one genomic island including virulence genes related to flagellar synthesis, isolate 115423 produced less biofilm than 5 other isolates. Although all isolates were susceptible to vancomycin, the in vitro time-kill assay showed that vancomycin monotherapy resulted in less than 2 log10 cerebrospinal fluid (CFU)/mL compared with the initial count. Trimethoprim/sulfamethoxazole at serum or CFU concentrations had bactericidal effect against tested Lm strains at 24 hours.

Conclusions
ST87 clone was a typical prevalent ST in clinical Lm isolates in China. Trimethoprim/sulfamethoxazole might be greater potential therapeutic option against Lm infections.
Major components of the KARRIKIN INSENSITIVE2-dependent signaling pathway are conserved in the liverwortMarchantia polymorpha
Authors: Mizuno Yohei , Komatsu Aino , Shimazaki Shota , Naramoto Satoshi , Inoue Keisuke , Xie Xiaonan , Ishizaki Kimitsune , Kohchi Takayuki , Kyozuka Junko 
Published: April 2021

AbstractKARRIKIN INSENSITIVE2 (KAI2) was first identified as a receptor of karrikins, smoke-derived germination stimulants. KAI2 is also considered a receptor of an unidentified endogenous molecule called the KAI2 ligand. Upon KAI2 activation, signals are transmitted through the degradation of D53/SMXL proteins via MAX2-dependent ubiquitination. Although components in the KAI2-dependent signaling pathway, namely MpKAI2A and MpKAI2B, MpMAX2, and MpSMXL, exist in the genome of the liverwort Marchantia polymorpha, their functions remain unknown. Here, we show that early thallus growth is retarded and gemma dormancy in the dark is suppressed in Mpkai2a and Mpmax2 loss-of-function mutants. These defects are counteracted in Mpkai2a Mpsmxl and Mpmax2 Mpsmxl double mutants indicating that MpKAI2A, MpMAX2, and MpSMXL act in the same genetic pathway. Introduction of MpSMXLd53, in which a domain required for degradation is mutated, into wild-type plants mimicks Mpkai2a and Mpmax2 plants. In addition, the detection of citrine fluorescence in Nicotiana benthamiana cells transiently expressing a SMXL-Citrine fusion protein requires treatment with MG132, a proteasome inhibitor. These findings imply that MpSMXL is subjected to degradation, and that the degradation of MpSMXL is crucial for MpKAI2A-dependent signaling in M. polymorpha. Therefore, we claim that the basic mechanisms in the KAI2-dependent signaling pathway are conserved in M. polymorpha.
The Efficacy, Adverse Events, and Withdrawal Rates of the Pharmacological Management of Chronic Spinal Cord Injury Pain: A Systematic Review and Meta-Analysis
Authors: Canavan Clare , Inoue Takayoshi , McMahon Sinead , Doody Catherine , Blake Catherine , Fullen Brona M 
Published: April 2021

Abstract

Objective
To establish the efficacy of medications, incidence of adverse events (AEs), and withdrawal rates associated with the pharmacological management of chronic spinal cord injury pain.

Methodology
PubMed, MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and PsycINFO were searched (November 2017) and updated (January 2020). Two independent review authors screened and identified papers for inclusion.

Results
Twenty-one studies met inclusion requirements for efficacy analysis and 17 for AE and withdrawal rate analysis; no additional papers were included from the updated 2020 search. Treatments were divided into six categories: anticonvulsants (n = 6), antidepressants (n = 3), analgesics (n = 8), anti-spasticity medications (n = 2), cannabinoids (n = 1), and other (n = 2). Trials of anticonvulsants, antidepressants, and cannabinoids included long-term follow-up trials (2 weeks to 4 months), and trials of analgesics and anti-spasticity medications, among others, were short-term trials (0–2 days). Effectiveness for neuropathic pain was found for pregabalin (3/3 studies) and lidocaine (2/3 studies). Studies using ketamine also reported effectiveness (2/2), but the quality of these papers was rated as poor. The most frequently reported AEs included dizziness, dry mouth, nausea, and constipation. Pregabalin was associated with a higher risk of somnolence (risk ratio [RR] 3.15, 95% confidence interval [CI]: 2.00–4.98) and dizziness (RR 2.9, 95% CI: 1.58–5.30). Ketamine was associated with a higher risk of reduced vision (RR 9.00, 95% CI: 0.05–146.11), dizziness (RR 8.33, 95% CI: 1.73–40.10), and somnolence (RR 7.00, 95% CI: 1.73–40.1). Withdrawal rates ranged from 18.4% for antidepressants to 0–30% for anticonvulsants, 0–10% for anti-spasticity medications, 0–48% for analgesics, 28.6% for cannabinoids, and 0–22.2% for other medications.

Conclusion
Pregabalin was found to be effective for neuropathic pain vs placebo. Cannabinoids were ineffective for neuropathic pain. AEs are a common cause for withdrawal. The nature of AEs was poorly reported, and AE reporting should be improved in future randomized controlled trials.
Private Information, Securities Lending, and Asset Prices
Authors: Nezafat Mahdi , Schroder Mark 
Published: April 2021

Abstract
We study the role of private information in the equity lending market in a rational expectations model with endogenous loan fees. When all investors are privately informed, an increase in information precision reduces the fee by increasing trade aggressiveness and decreasing demand dispersion. However, when some investors are uninformed, the information asymmetry tends to increase the fee, and, thus, the overall effect of an increase in precision is ambiguous. We show that the fee can be incrementally informative given the stock price and that fee opaqueness tends to increase the fee but has an ambiguous effect on the stock price.
SODIUM ACETATE ATTENUATES MYOCARDIAL TRIGLYCERIDE ACCUMULATION IN COMBINED ORAL CONTRACEPTIVE-TREATED RATS BY SUPPRESSING ADENOSINE DEAMINASE/XANTHINE OXIDASE-DEPENDENT PATHWAY
Authors: Omolekulo Tolulope , Olatunji Lawrence Aderemi 
Published: April 2021

Objective:
Myocardial triglyceride accumulation characterizes many cardiovascular disorders. Cardiovascular disorders are the leading cause of mortality and morbidity worldwide. Continuous usage of Combined Oral Contraceptive (COC) has been associated with disrupted lipid metabolism, however, the exact mechanism is not clear. Adenosine Deaminase (ADA) and Xanthine Oxidase (XO) are reportedly involved in cardiometabolic derangement, particularly lipid dysmetabolism. We, therefore hypothesized that increased ADA and XO activities and elevated uric acid level are involved in COC-induced myocardial triglyceride accumulation. This study also aimed at investigating the ameliorative effects of sodium acetate on COC-induced myocardial lipid accumulation in female Wistar rats.

Design and method:
Female Wistar rats received vehicle per ostium (p.o.) and COC (1.0 microgram of ethinylestradiol plus 5.0 microgram of levonorgestrel; p.o.) with or without sodium acetate (ACE; 200 miligram/kilogram; p.o.) for 8 weeks (n = 6/group). Insulin resistance was estimated by homeostatic model of assessment whereas glucose tolerance was determined by oral glucose tolerance test. Other biochemical variables were evaluated using standard methods. Data were analysed using one-way analysis of variance followed by Bonferroni's post hoc test. Significant differences were accepted at p < 0.05.

Results:
Treatment with COC led to increased 1-h postload glucose response, plasma insulin, triglyceride-glucose index, insulin resistance and impaired glucose tolerance. COC treatment also resulted in increased plasma and cardiac free fatty acid, triglyceride, triglyceride/high density lipoprotein-cholesterol ratio, malondialdehyde, uric acid, ADA and XO activities. On the other hand, COC led to reduction in nitric oxide level. However, sodium acetate significantly ameliorated the alterations induced by COC treatment, but XO activity remains elevated during COC treatment.

Conclusions:
Therefore, sodium acetate would impact positively on myocardial lipid accumulation-related cardiovascular disorders, at least in part, by suppression of adenosine deaminase/xanthine oxidase/uric acid-dependent pathway.
PREDICTIVE POWER OF 24-HOUR AMBULATORY PULSE PRESSURE AND ITS COMPONENTS FOR MORTALITY AND CARDIOVASCULAR OUTCOMES IN 11,848 PARTICIPANTS RECRUITED FROM 13 POPULATIONS
Authors: Gavish Benjamin , Bursztyn Michael , Yang Wen Yi , Thijs Lutgrade , Zhang Zhen-Yu , Boggia José , Hansen Tine W. , Asayama Kei , Ohkubo Takayoshi , Kikuya Masahiro , Imai Yutaka , Stolarz-Skrzypek Katarzyna , Li Yan , Wang Ji -Guang , Casiglia Edoardo , Malyutina Sofia , Staessen Jan 
Published: April 2021

Objective:
The role of pulse pressure ’widening’ at older age, as a cardiovascular risk factor is still controversial. 24-hour ambulatory pulse pressure (PP) was previously expressed as a sum of two components: ’elastic’ PP (elPP) and 'stiffening’ PP (stPP) associated, respectively, with arterial stiffness at diastole and the change in stiffness during systole. We investigated the association of PP, elPP and stPP (’PP variables’) with mortality and composite cardiovascular (CV) events in different age classes.

Design and method:
Longitudinal population-based cohort study of adults from Europe, Asia, and South America with baseline observations, including 24-hour ambulatory BP. Age classes were age < 50, 50–60, 60–70, and > 70 year. Co-primary endpoints were total mortality and composite CV events. Hazard ratios (HRs) per 1-SD increase in the PP variables were calculated from multivariable adjusted Cox regression models.

Results:
The 11,848 participants from 13 cohorts (age 53 ± 16, 50% males) were followed up for 13.4 ± 6.9 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or non-fatal cardiovascular event (12.9 per 1000 person-years). PP components were uncorrelated (r = -0.07), and the ratio stPP/elPP was 0.143. PP and elPP showed a curvilinear relationship with age reaching a nadir around middle-age, whereas stPP steadily increased from age 30 years onwards. In persons ?50 years of age, but not in those < 50 years, both PP and elPP were associated with increased risk for the primary endpoints. For total mortality and cardiovascular events hazard ratios for PP decreased from 50–60 years old participants to those aged > 70 years (P < 0.02); from 1.29[95%CI: 1.13–1.46] to 1.11[1.05–1.15], and from 1.40[1.24–1.58] to 1.16[1.10–1.23], respectively, and for elPP for cardiovascular events; from 1.29[1.14–1.45] to 1.16[1.09–1.23]. On the other hand, stPP was associated with increased risk for the primary endpoints in subjects 50 to 60 years of age but not in the older age groups.

Conclusions:
The age-related increase in PP variables is not reflected in a corresponding PP-associated increase in cardiovascular risk. Results support the view that normal ageing weakens the association of PP variables with CV risk.