bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of glutamate release by complexes of adenosine and cannabinoid receptors
Authors: Köfalvi Attila , Moreno Estefanía , Cordomí Arnau , Cai Ning-Sheng , Fernández-Dueñas Victor , Ferreira Samira G. , Guixà-González Ramón , Sánchez-Soto Marta , Yano Hideaki , Casadó-Anguera Verònica , Cunha Rodrigo A. , Sebastião Ana Maria , Ciruela Francisco , Pardo Leonardo , Casadó Vicent , Ferré Sergi 
Published: January 2020

Abstract
Background
It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 receptors (CB1R) localized in glutamatergic nerve terminals mediate the integration of adenosine and endocannabinoid signaling involved in the modulation of striatal excitatory neurotransmission. Previous studies have demonstrated the existence of A2AR-CB1R heteromers in artificial cell systems. A dependence of A2AR signaling for the Gi protein-mediated CB1R signaling was described as one of its main biochemical characteristics. However, recent studies have questioned the localization of functionally significant A2AR-CB1R heteromers in striatal glutamatergic terminals.

Results
Using a peptide-interfering approach combined with biophysical and biochemical techniques in mammalian transfected cells and computational modeling, we could establish a tetrameric quaternary structure of the A2AR-CB1R heterotetramer. This quaternary structure was different to the also tetrameric structure of heteromers of A2AR with adenosine A1 receptors or dopamine D2 receptors, with different heteromeric or homomeric interfaces. The specific quaternary structure of the A2A-CB1R, which depended on intermolecular interactions involving the long C-terminus of the A2AR, determined a significant A2AR and Gs protein-mediated constitutive activation of adenylyl cyclase. Using heteromer-interfering peptides in experiments with striatal glutamatergic terminals, we could then demonstrate the presence of functionally significant A2AR-CB1R heteromers with the same biochemical characteristics of those studied in mammalian transfected cells. First, either an A2AR agonist or an A2AR antagonist allosterically counteracted Gi-mediated CB1R agonist-induced inhibition of depolarization-induced glutamate release. Second, co-application of both an A2AR agonist and an antagonist cancelled each other effects. Finally, a CB1R agonist inhibited glutamate release dependent on a constitutive activation of A2AR by a canonical Gs-Gi antagonistic interaction at the adenylyl cyclase level.

Conclusions
We demonstrate that the well-established cannabinoid-induced inhibition of striatal glutamate release can mostly be explained by a CB1R-mediated counteraction of the A2AR-mediated constitutive activation of adenylyl cyclase in the A2AR-CB1R heteromer.
SP1 induced long non-coding RNA LINC00958 overexpression facilitate cell proliferation, migration and invasion in lung adenocarcinoma via mediating miR-625-5p/CPSF7 axis
Authors: Yang Longhai , Li Lili , Zhou Zizi , Liu Yi , Sun Jinyuan , Zhang Xiaoming , Pan Huiyu , Liu Song 
Published: January 2020

Abstract
Background
Increasing evidences have underlined the importance of long non-coding RNAs (lncRNAs) in human malignancies. LINC00958 has been found involved in some cancers. However, the underlying mechanical performance of LINC00958 in lung adenocarcinoma (LAD) has not been explored yet.

Methods
The expression of relevant mRNA and protein were measured by qRT-PCR and western blot assays. EdU, colony formation, TUNEL and transwell assays were performed to investigate the function of LINC00958 on LAD progression. Luciferase reporter, RNA pull down and RIP assays were conducted to investigate the molecular mechanism of relevant RNAs.

Results
LINC00958 was found notably overexpressed in LAD, which was associated with the stimulation of its promoter activity induced by SP1. LINC00958 depletion dramatically inhibited LAD cell proliferation, migration and invasion capacities by acting as a miR-625-5p sponge. MiR-625-5p curbed LAD progression via targeting CPSF7 and down-regulating its expression. Mechanically, LINC00958 was identified as a competing endogenous RNA (ceRNA) and positively regulated the expression of CPSF7 via sponging miR-625-5p.

Conclusions
LINC00958 might drive LAD progression via mediating miR-625-5p/CPSF7 axis, indicating the potential of targeting LINC00958 for the treatment of LAD.
Health gains and financial risk protection afforded by public financing of selected malaria interventions in Ethiopia: an extended cost-effectiveness analysis
Authors: Assebe Lelisa Fekadu , Kwete Xiaoxiao Jiang , Wang Dan , Liu Lingrui , Norheim Ole Frithjof , Jbaily Abdulrahman , Verguet Stéphane , Johansson Kjell Arne , Tolla Mieraf Taddesse 
Published: January 2020

Abstract
Background
Malaria is a public health burden and a major cause for morbidity and mortality in Ethiopia. Malaria also places a substantial financial burden on families and Ethiopia’s national economy. Economic evaluations, with evidence on equity and financial risk protection (FRP), are therefore essential to support decision-making for policymakers to identify best buys amongst possible malaria interventions. The aim of this study is to estimate the expected health and FRP benefits of universal public financing of key malaria interventions in Ethiopia.

Methods
Using extended cost-effectiveness analysis (ECEA), the potential health and FRP benefits were estimated, and their distributions across socio-economic groups, of publicly financing a 10% coverage increase in artemisinin-based combination therapy (ACT), long-lasting insecticide-treated bed nets (LLIN), indoor residual spraying (IRS), and malaria vaccine (hypothetical).

Results
ACT, LLIN, IRS, and vaccine would avert 358, 188, 107 and 38 deaths, respectively, each year at a net government cost of $5.7, 16.5, 32.6, and 5.1 million, respectively. The annual cost of implementing IRS would be two times higher than that of the LLIN interventions, and would be the main driver of the total costs. The averted deaths would be mainly concentrated in the poorest two income quintiles. The four interventions would eliminate about $4,627,800 of private health expenditures, and the poorest income quintiles would see the greatest FRP benefits. ACT and LLINs would have the largest impact on malaria-related deaths averted and FRP benefits.

Conclusions
ACT, LLIN, IRS, and vaccine interventions would bring large health and financial benefits to the poorest households in Ethiopia.
Evaluation of DawaPlus 3.0 and DawaPlus 4.0, deltamethrin–PBO combination nets against pyrethroid-resistant Anopheles culicifacies in experimental huts in India
Authors: Gunasekaran Kasinathan , Sahu Sudhansu Sekhar , Vijayakumar Tharmalingam , Subramanian Swaminathan , Rahi Manju , Jambulingam Purushothaman 
Published: January 2020

Abstract
Background
The development of resistance in vectors is one of the major impediments for malaria control. Adding synergists to insecticides has proven to be an alternative choice for controlling resistant mosquitoes. DawaPlus 3.0 and DawaPlus 4.0 are new long-lasting insecticidal nets (LLINs) in which deltamethrin and a synergist, piperonyl butoxide (PBO) are added into filaments and their efficacy was tested against resistant malaria vector, Anopheles culicifacies in experimental huts in India.

Methods
The performance of two trial nets in terms of deterrence induced exiting, blood-feeding inhibition and mortality of An. culicifacies was compared with DawaPlus 2.0 and untreated net.

Results
There was a significant reduction in entry, blood feeding and mortality (p < 0.05) and increase in exit rates of An. culicifacies in the treatment arms compared to untreated arm. But, both candidate LNs washed 20 times could not perform better than the washed reference net (DawaPlus 2.0). Cone bioassay results showed that all the treatment arms (both washed and unwashed) produced < 80% mortality of An. culicifacies before and after hut evaluation.

Conclusions
DawaPlus 3.0 and DawaPlus 4.0 with their current specification may not be as effective as required to control the resistant vector, An. culicifacies, in east-central India.
Core–shell polymeric nanoparticles co-loaded with photosensitizer and organic dye for photodynamic therapy guided by fluorescence imaging in near and short-wave infrared spectral regions
Authors: Chepurna O. M. , Yakovliev A. , Ziniuk R. , Nikolaeva O. A. , Levchenko S. M. , Xu H. , Losytskyy M. Y. , Bricks J. L. , Slominskii Yu. L. , Vretik L. O. , Qu J. , Ohulchanskyy T. Y. 
Published: January 2020

Abstract
Background
Biodistribution of photosensitizer (PS) in photodynamic therapy (PDT) can be assessed by fluorescence imaging that visualizes the accumulation of PS in malignant tissue prior to PDT. At the same time, excitation of the PS during an assessment of its biodistribution results in premature photobleaching and can cause toxicity to healthy tissues. Combination of PS with a separate fluorescent moiety, which can be excited apart from PS activation, provides a possibility for fluorescence imaging (FI) guided delivery of PS to cancer site, followed by PDT.

Results
In this work, we report nanoformulations (NFs) of core–shell polymeric nanoparticles (NPs) co-loaded with PS [2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a, HPPH] and near infrared fluorescent organic dyes (NIRFDs) that can be excited in the first or second near-infrared windows of tissue optical transparency (NIR-I, ~ 700–950 nm and NIR-II, ~ 1000–1350 nm), where HPPH does not absorb and emit. After addition to nanoparticle suspensions, PS and NIRFDs are entrapped by the nanoparticle shell of co-polymer of N-isopropylacrylamide and acrylamide [poly(NIPAM-co-AA)], while do not bind with the polystyrene (polySt) core alone. Loading of the NIRFD and PS to the NPs shell precludes aggregation of these hydrophobic molecules in water, preventing fluorescence quenching and reduction of singlet oxygen generation. Moreover, shift of the absorption of NIRFD to longer wavelengths was found to strongly reduce an efficiency of the electronic excitation energy transfer between PS and NIRFD, increasing the efficacy of PDT with PS-NIRFD combination. As a result, use of the NFs of PS and NIR-II NIRFD enables fluorescence imaging guided PDT, as it was shown by confocal microscopy and PDT of the cancer cells in vitro. In vivo studies with subcutaneously tumored mice demonstrated a possibility to image biodistribution of tumor targeted NFs both using HPPH fluorescence with conventional imaging camera sensitive in visible and NIR-I ranges (~ 400–750 nm) and imaging camera for short-wave infrared (SWIR) region (~ 1000–1700 nm), which was recently shown to be beneficial for in vivo optical imaging.

Conclusions
A combination of PS with fluorescence in visible and NIR-I spectral ranges and, NIR-II fluorescent dye allowed us to obtain PS nanoformulation promising for see-and-treat PDT guided with visible-NIR-SWIR fluorescence imaging.
Recent sylvatic yellow fever virus transmission in Brazil: the news from an old disease
Authors: Silva Natalia Ingrid Oliveira , Sacchetto Lívia , de Rezende Izabela Maurício , Trindade Giliane de Souza , LaBeaud Angelle Desiree , de Thoisy Benoit , Drumond Betânia Paiva 
Published: January 2020

AbstractYellow fever (YF) is an acute viral disease, affecting humans and non-human primates (NHP), caused by the yellow fever virus (YFV). Despite the existence of a safe vaccine, YF continues to cause morbidity and mortality in thousands of people in Africa and South America. Since 2016, massive YF outbreaks have taken place in Brazil, reaching YF–free zones, causing thousands of deaths of humans and NHP. Here we reviewed the main epidemiological aspects, new clinical findings in humans, and issues regarding YFV infection in vectors and NHP in Brazil. The 2016–2019 YF epidemics have been considered the most significant outbreaks of the last 70 years in the country, and the number of human cases was 2.8 times higher than total cases in the previous 36 years. A new YFV lineage was associated with the recent outbreaks, with persistent circulation in Southeast Brazil until 2019. Due to the high number of infected patients, it was possible to evaluate severity and death predictors and new clinical features of YF.Haemagogus janthinomysandHaemagogus leucocelaenuswere considered the primary vectors during the outbreaks, and no human case suggested the occurrence of the urban transmission cycle. YFV was detected in a variety of NHP specimens presenting viscerotropic disease, similar to that described experimentally. Further studies regarding NHP sensitivity to YFV, YF pathogenesis, and the duration of the immune response in NHP could contribute to YF surveillance, control, and future strategies for NHP conservation.
Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis
Authors: Huang Xiu-Yan , Huang Zi-Li , Huang Jin , Xu Bin , Huang Xin-Yu , Xu Yong-Hua , Zhou Jian , Tang Zhao-You 
Published: January 2020

Abstract
Background
Exosomes play crucial roles in regulating the crosstalk between normal and cancer cells in the tumor microenvironment, and in regulating cancer proliferation, migration and invasion through their cargo molecules.

Methods
We analyzed the pro-invasiveness of exosomal circRNA-100,338 in HCC using the transwell invasion assay. The co-culture of human umbilical vein endothelial cells (HUVEC) and exosomes derived from HCC cell lines were used to evaluate the impact of HCC derived exosomes on HUVEC. Nude mice models were used to validate the findings in vitro. Clinically, quantitative RT-PCR was used to quantify the expression of serum exosomal circRNA-100,338 in HCC patients at both pre-surgery within one week and post-surgery within three weeks.

Results
We aim to investigate the pro-invasive role of exosomal circRNA-100,338 in HCC metastasis. We for the first time demonstrated that circRNA-100,338 was highly expressed in both highly metastatic HCC cells and their secreted exosomes. The transwell invasion assay showed that the overexpression or knockdown of exosomal circRNA-100,338 significantly enhanced or reduced the invasive abilities of HCC cells. Subsequently, in vitro and in vivo assays showed that exosomal circRNA-100,338 affected the cell proliferation, angiogenesis, permeability, and vasculogenic mimicry (VM) formation ability of human umbilical vein endothelial cells (HUVEC), and tumor metastasis. Furthermore, we also observed that the persistent high expression of exosomal circRNA-100,338 in serum of HCC patients who underwent curative hepatectomy may be a risk indicator of pulmonary metastasis and poor survival.

Conclusions
Our findings indicated that metastatic ability of HCC cells could be enhanced by transferring exosomal circRNA-100,338 to recipient HUVECs, which could affect proangiogenic activity by regulating angiogenesis.
Symptomatic pes planus in children: a synthesis of allied health professional practices
Authors: Morrison Stewart C. , Tait Madeleine , Bong Elaine , Kane Kyra J. , Nester Chris 
Published: January 2020

AbstractBackgroundThis study sought to explore professional perspectives on the assessment and management of symptomatic pes planus in children.MethodsData was collected from three professional groups (podiatrists, physiotherapists, and orthotists) with experience of managing foot problems in children. The survey was undertaken in the United Kingdom via a self‐administered, online survey. Data was captured over a four‐month period in 2018.ResultsFifty‐five health professionals completed the survey and the results highlighted that assessment techniques varied between professions, with standing tip‐toe and joint range of motion being the most common. Treatment options for children were diverse and professionals were adopting different strategies as their first line intervention. All professions used orthoses.ConclusionsThere were inconsistencies in how the health professionals assessed children presenting with foot symptoms, variation in how the condition was managed and differences in outcome measurement. These findings might be explained by the lack of robust evidence and suggests that more effort is needed to harmonise assessment and treatment approaches between professions. Addressing discrepancies in practice could help prioritise professional roles in this area, and better support the management of children with foot pain.
Improving risk perception and uptake of voluntary medical male circumcision with peer-education sessions and incentives, in Manicaland, East Zimbabwe: study protocol for a pilot randomised trial
Authors: Thomas Ranjeeta , Skovdal Morten , Galizzi Matteo M. , Schaefer Robin , Moorhouse Louisa , Nyamukapa Constance , Maswera Rufurwokuda , Mandizvidza Phyllis , Hallett Timothy B. , Gregson Simon 
Published: January 2020

Abstract
Background
Voluntary medical male circumcision (VMMC) is a key component of combination HIV-prevention programmes. Several high-HIV-prevalence countries in sub-Saharan Africa, including Zimbabwe, are looking to scale up VMMC activities. There is limited evidence on how a combination of social learning from peer education by a role model with different behavioural incentives influences demand for VMMC in such settings.

Methods/Design
This matched-cluster randomised controlled trial with 1740 participants will compare two behavioural incentives against a control with no intervention. In the intervention clusters, participants will participate in an education session delivered by a circumcised young male (“role model”) on the risks of HIV infection and the benefits from medical male circumcision. All participants will receive contributions towards transport costs to access medical male circumcision at participating clinics. Via blocked randomisation, in the intervention clusters participants will be randomly assigned to receive one of two types of incentives – fixed cash payment or lottery payment – both conditional on undergoing surgical VMMC. In two sites, a community-led intervention will also be implemented to address social obstacles and to increase support from peers, families and social structures. Baseline measures of endpoints will be gathered in surveys. Follow-up assessment at 6 months will include self-reported uptake of VMMC triangulated with clinic data.

Discussion
This is the first trial to pilot-test social learning to improve risk perception and self-efficacy and to address the fear of pain associated with VMMC and possible present-biased preferences with front-loaded compensations as well as fixed or lottery-based cash payments. This study will generate important knowledge to inform HIV-prevention policies about the effectiveness of behavioural interventions and incentives, which could be easily scaled-up.

Trial registration
This trial has been registered on ClinicalTrials.gov (identifier: NCT03565588). Registered on 21 June 2018.
The role of point-of-care ultrasound in the diagnosis and management of necrotizing soft tissue infections
Authors: Magalhães Luís , Martins Sara Raquel Pereira , Nogué Ramon 
Published: January 2020

AbstractBackgroundNecrotizing soft tissue infections are associated with high morbidity and mortality, even when the correct treatment is initiated. The diagnosis of these conditions is hard and the most sensitive methods are time-consuming, expensive and not readily available. Point-of-care ultrasound can complement clinical evaluation to increase the diagnostic accuracy.Case presentationWe bring a case of a woman, without comorbidities, who presented to the emergency department with signs of soft tissue infection. Bedside ultrasound showed subcutaneous tissue thickening, with fluid accumulation, and subcutaneous gas in the affected area. Based on the clinical suspicion and the ultrasound findings, the patient underwent prompt medical treatment and surgical debridement.ConclusionsThis case shows the utility of bedside ultrasound for the decision-making process in a disease where an early diagnosis is important. This information should always be used together with the clinical judgement, as it has a relative low sensitivity.
Reduced culture temperature attenuates oxidative stress and inflammatory response facilitating expansion and differentiation of adipose-derived stem cells
Authors: Tirza Gal , Solodeev Inna , Sela Meirav , Greenberg Ilanit , Pasmanik-Chor Metsada , Gur Eyal , Shani Nir 
Published: January 2020

Abstract
Background
Adipose-derived stem cell (ASC) expansion under atmospheric oxygen levels (21%) was previously shown to cause increased reactive oxygen species (ROS) accumulation and genetic instability compared to cells cultured under physiological oxygen levels (2–8%). However, since culture under physiological oxygen levels is costly and complicated, a simpler method to reduce ROS accumulation is desirable. The current study aimed to determine whether lower culture temperature can reduce ROS production in ASCs without impairing their culture expansion.

Methods
Proliferation, differentiation, ROS accumulation, and gene expression were compared between ASC cultures at 35 °C and 37 °C. ASCs isolated either from rat fat depots or from human lipoaspirates were examined in the study.

Results
Rat visceral ASCs (vASCs) cultured at 35 °C demonstrated reduced ROS production and apoptosis and enhanced expansion and adipogenic differentiation compared to vASCs cultured at 37 °C. Similarly, the culture of human ASCs (hASCs) at 35 °C led to reduced ROS accumulation and apoptosis, with no effect on the proliferation rate, compared to hASCs cultured at 37 °C. Comparison of gene expression profiles of 35 °C versus 37 °C vASCs uncovered the development of a pro-inflammatory phenotype in 37 °C vASCs in correlation with culture temperature and ROS overproduction. This correlation was reaffirmed in both hASCs and subcutaneous rat ASCs.

Conclusions
This is the first evidence of the effect of culture temperature on ASC growth and differentiation properties. Reduced temperatures may result in superior ASC cultures with enhanced expansion capacities in vitro and effectiveness in vivo.
Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate IL-6-induced acute liver injury through miR-455-3p
Authors: Shao Mingyang , Xu Qing , Wu Zhenru , Chen Yuwei , Shu Yuke , Cao Xiaoyue , Chen Menglin , Zhang Bo , Zhou Yongjie , Yao Rong , Shi Yujun , Bu Hong 
Published: January 2020

Abstract
Background
Using a toxin-induced nonhuman primate model of acute liver failure (ALF), we previously reported that peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) strongly suppresses the activation of circulating monocytes and interleukin-6 (IL-6) production, thereby disrupting the development of a cytokine storm and improving the prognosis of monkeys. MSCs are considered to play a therapeutic role under different stresses by adaptively producing specific factors, prompting us to investigate the factors that hUC-MSCs produce in response to high serum levels of IL-6, which plays a critical role in initiating and accelerating ALF.

Methods
We stimulated hUC-MSCs with IL-6, and the hUC-MSC-derived exosomes were deeply sequenced. The miRNAs in the exosomes that have potential to suppress IL-6-associated signaling pathway were screened, and the role of one of the most possible miRNAs was tested in the mouse model of inflammatory liver injury.

Result
We determined that miR-455-3p, which is secreted through exosomes and potentially targets PI3K signaling, was highly produced by hUC-MSCs with IL-6 stimulation. The miR-455-3p-enriched exosomes could inhibit the activation and cytokine production of macrophages challenged with lipopolysaccharide (LPS) both in vivo and in vitro. In a chemical liver injury mouse model, enforced expression of miR-455-3p could attenuate macrophage infiltration and local liver damage and reduce the serum levels of inflammatory factors, thereby improving liver histology and systemic disorder.

Conclusions
miR-455-3p-enriched exosomes derived from hUC-MSCs are a promising therapy for acute inflammatory liver injury.