bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved utilization of soybean meal through fermentation with commensal Shewanella sp. MR-7 in turbot (Scophthalmus maximus L.)
Authors: Li Chaoqun , Zhang Beili , Wang Xin , Pi Xionge , Wang Xuan , Zhou Huihui , Mai Kangsen , He Gen
Published: December 2019

Background

Increased inclusion of plant proteins in aquafeeds has become a common practice due to the high cost and limited supply of fish meal but generally leads to inferior growth performance and health problems of fish. Effective method is needed to improve the plant proteins utilization and eliminate their negative effects on fish. This study took a unique approach to improve the utilization of soybean meal (SBM) by fish through autochthonous plant-degrading microbe isolation and subsequent fermentation.

Results

A strain of Shewanella sp. MR-7 was isolated and identified as the leading microbe that could utilize SBM in the intestine of turbot. It was further optimized for SBM fermentation and able to improve the protein availability and degrade multiple anti-nutritional factors of SBM. The fishmeal was able to be replaced up to 45% by Shewanella sp. MR-7 fermented SBM compared to only up to 30% by SBM in experimental diets without adverse effects on growth and feed utilization of turbot after feeding trials. Further analyses showed that Shewanella sp. MR-7 fermentation significantly counteracted the SBM-induced adverse effects by increasing digestive enzymes activities, suppressing inflammatory responses, and alleviating microbiota dysbiosis in the intestine of turbot.

Conclusions

This study demonstrated that plant protein utilization by fish could be significantly improved through pre-digestion with isolated plant-degrading host microbes. Further exploitation of autochthonous bacterial activities should be valuable for better performances of plant-based diets in aquaculture.
Monitoring of efficacy, tolerability and safety of artemether–lumefantrine and artesunate–amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Lambaréné, Gabon: an open-label clinical trial
Authors: Adegbite Bayode R. , Edoa Jean R. , Honkpehedji Yabo J. , Zinsou Frejus J. , Dejon-Agobe Jean C. , Mbong-Ngwese Mirabeau , Lotola-Mougueni Fabrice , Koehne Erik , Lalremruata Albert , Kreidenweiss Andrea , Nguyen The T. , Kun Jutta , Agnandji Selidji T. , Lell Bertrand , Safiou Abdou R. , Obone Atome Fridia A. , Mombo-Ngoma Ghyslain , Ramharter Michael , Velavan Thirumalaisamy P. , Mordmüller Benjamin , Kremsner Peter G. , Adegnika Ayola A.
Published: December 2019

Background

Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (AS–AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon.

Methods

A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS–AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti‑malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened.

Results

Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86–100) and 95% (95% CI 84–99) for AL and AS–AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment.

Conclusion

This study showed that AL and AS–AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential.

Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True
Assessing the impact of the addition of pyriproxyfen on the durability of permethrin-treated bed nets in Burkina Faso: a compound-randomized controlled trial
Authors: Toé Kobié H. , Mechan Frank , Tangena Julie-Anne A. , Morris Marion , Solino Joanna , Tchicaya Emile F. S. , Traoré Alphonse , Ismail Hanafy , Maas James , Lissenden Natalie , Pinder Margaret , Lindsay Steve W. , Tiono Alfred B. , Ranson Hilary , Sagnon N’Falé
Published: December 2019

Background

Long-lasting insecticidal nets (LLINs) treated with pyrethroids are the foundation of malaria control in sub-Saharan Africa. Rising pyrethroid resistance in vectors, however, has driven the development of alternative net formulations. Here the durability of polyethylene nets with a novel combination of a pyrethroid, permethrin, and the insect juvenile hormone mimic, pyriproxyfen (PPF), compared to a standard permethrin LLIN, was assessed in rural Burkina Faso.

Methods

A compound-randomized controlled trial was completed in two villages. In one village 326 of the PPF-permethrin nets (Olyset Duo) and 327 standard LLINs (Olyset) were distributed to assess bioefficacy. In a second village, 170 PPF-permethrin nets and 376 LLINs were distributed to assess survivorship. Nets were followed at 6-monthly intervals for 3 years. Bioefficacy was assessed by exposing permethrin-susceptible and resistant Anopheles gambiae sensu lato mosquito strains to standard World Health Organization (WHO) cone and tunnel tests with impacts on fertility measured in the resistant strain. Insecticide content was measured using high-performance liquid chromatography. LLIN survivorship was recorded with a questionnaire and assessed by comparing the physical integrity using the proportionate hole index (pHI).

Results

The PPF-permethrin net met WHO bioefficacy criteria (≥ 80% mortality or ≥ 95% knockdown) for the first 18 months, compared to 6 months for the standard LLIN. Mean mosquito mortality for PPF-permethrin nets, across all time points, was 8.6% (CI 2.6–14.6%) higher than the standard LLIN. Fertility rates were reduced after PPF-permethrin net exposure at 1-month post distribution, but not later. Permethrin content of both types of nets remained within the target range of 20 g/kg ± 25% for 242/248 nets tested. The pyriproxyfen content of PPF-permethrin nets declined by 54%, from 10.4 g/kg (CI 10.2–10.6) to 4.7 g/kg (CI 3.5–6.0, p < 0.001) over 36 months. Net survivorship was poor, with only 13% of PPF-permethrin nets and 12% of LLINs still present in the original household after 36 months. There was no difference in the fabric integrity or survivorship between the two net types.

Conclusion

The PPF-permethrin net, Olyset Duo, met or exceeded the performance of the WHO-recommended standard LLIN (Olyset) in the current study but both net types failed the 3-year WHO bioefficacy criteria.
Antibody responses within two leading Plasmodium vivax vaccine candidate antigens in three geographically diverse malaria-endemic regions of India
Authors: Kale Sonal , Yadav Chander P. , Rao Pavitra N. , Shalini Sneh , Eapen Alex , Srivasatava Harish C. , Sharma Surya K. , Pande Veena , Carlton Jane M. , Singh Om P. , Mallick Prashant K.
Published: December 2019

Background

Identifying highly immunogenic blood stage antigens which can work as target for naturally acquired antibodies in different eco-epidemiological settings is an important step for designing malaria vaccine. Blood stage proteins ofPlasmodium vivax, apical membrane antigen-1 (PvAMA-1) and 19 kDa fragment of merozoite surface protein (PvMSP-119) are such promising vaccine candidate antigens. This study determined the naturally-acquired antibody response to PvAMA-1 and PvMSP-119antigens in individuals living in three geographically diverse malaria endemic regions of India.

Methods

A total of 234 blood samples were collected from individuals living in three different eco-epidemiological settings, Chennai, Nadiad, and Rourkela of India. Indirect ELISA was performed to measure human IgG antibodies against recombinant PvAMA-1 and PvMSP-119antigens. The difference in seroprevalence and factors associated with antibody responses at each site was statistically analysed.

Results

The overall seroprevalence was 40.6% for PvAMA-1 and 62.4% for PvMSP-119. Seroprevalence to PvAMA-1 was higher in Chennai (47%) followed by Nadiad (46.7%) and Rourkela (27.6%). For PvMSP-119, seroprevalence was higher in Chennai (80.3%) as compared to Nadiad (53.3%) and Rourkela (57.9%). Seroprevalence for both the antigens were found to be higher in Chennai whereP. vivaxis the dominant malaria species. In addition, heterogeneous antibody response was observed for PvAMA-1 and PvMSP-119antigens at each of the study sites. Two factors, age and malaria positivity were significantly associated with seropositivity for both the antigens PvAMA-1 and PvMSP-119.

Conclusion

These data suggest that natural acquired antibody response is higher for PvMSP-119antigen as compared to PvAMA-1 antigen in individuals living in three geographically diverse malaria endemic regions in India. PvMSP-119appears to be highly immunogenic in Indian population and has great potential as a malaria vaccine candidate. The differences in immune response against vaccine candidate antigens in different endemic settings should be taken into account for development of asexual stage basedP. vivaxmalaria vaccine, which in turn can enhance malaria control efforts.
Strategies to support culturally safe health and wellbeing evaluations in Indigenous settings in Australia and New Zealand: a concept mapping study
Authors: Cargo Margaret , Potaka-Osborne Gill , Cvitanovic Lynley , Warner Lisa , Clarke Sharon , Judd Jenni , Chakraborty Amal , Boulton Amohia
Published: December 2019

Background

In recent decades, financial investment has been made in health-related programs and services to overcome inequities and improve Indigenous people’s wellbeing in Australia and New Zealand. Despite policies aiming to ‘close the gap’, limited evaluation evidence has informed evidence-based policy and practice. Indigenous leaders have called for evaluation stakeholders to align their practices with Indigenous approaches.

Methods

This study aimed to strengthen culturally safe evaluation practice in Indigenous settings by engaging evaluation stakeholders, in both countries, in a participatory concept mapping study. Concept maps for each country were generated from multi-dimensional scaling and hierarchical cluster analysis.

Results

The 12-cluster Australia map identifies four cluster regions: An Evaluation Approach that Honours Community; Respect and Reciprocity; Core Heart of the Evaluation; and Cultural Integrity of the Evaluation. The 11-cluster New Zealand map identifies four cluster regions: Authentic Evaluation Practice; Building Māori Evaluation Expertise; Integrity in Māori Evaluation; and Putting Community First. Both maps highlight the importance of cultural integrity in evaluation. Differences include the distinctiveness of the ‘Respecting Language Protocols’ concept in the Australia map in contrast to language being embedded within the cluster of ‘Knowing Yourself as an Evaluator in a Māori Evaluation Context’ in the New Zealand map. Participant ratings highlight the importance of all clusters with some relatively more difficult to achieve, in practice. Notably, the ‘Funding Responsive to Community Needs and Priorities’ and ‘Translating Evaluation Findings to Benefit Community’ clusters were rated the least achievable, in Australia. The ‘Conduct of the Evaluation’ and the ‘Prioritising Māori Interests’ clusters were rated as least achievable in New Zealand. In both countries, clusters of strategies related to commissioning were deemed least achievable.

Conclusions

The results suggest that the commissioning of evaluation is crucial as it sets the stage for whether evaluations: reflect Indigenous interests, are planned in ways that align with Indigenous ways of working and are translated to benefit Indigenous communities Identified strategies align with health promotion principles and relational accountability values of Indigenous approaches to research. These findings may be relevant to the commissioning and conduct of Indigenous health program evaluations in developed nations.
Comparative analysis of computer-vision and BLE technology based indoor navigation systems for people with visual impairments
Authors: Kunhoth Jayakanth , Karkar AbdelGhani , Al-Maadeed Somaya , Al-Attiyah Asma
Published: December 2019

Background

Considerable number of indoor navigation systems has been proposed to augment people with visual impairments (VI) about their surroundings. These systems leverage several technologies, such as computer-vision, Bluetooth low energy (BLE), and other techniques to estimate the position of a user in indoor areas. Computer-vision based systems use several techniques including matching pictures, classifying captured images, recognizing visual objects or visual markers. BLE based system utilizes BLE beacons attached in the indoor areas as the source of the radio frequency signal to localize the position of the user.

Methods

In this paper, we examine the performance and usability of two computer-vision based systems and BLE-based system. The first system is computer-vision based system, called CamNav that uses a trained deep learning model to recognize locations, and the second system, called QRNav, that utilizes visual markers (QR codes) to determine locations. A field test with 10 blindfolded users has been conducted while using the three navigation systems.

Results

The obtained results from navigation experiment and feedback from blindfolded users show that QRNav and CamNav system is more efficient than BLE based system in terms of accuracy and usability. The error occurred in BLE based application is more than 30% compared to computer vision based systems including CamNav and QRNav.

Conclusions

The developed navigation systems are able to provide reliable assistance for the participants during real time experiments. Some of the participants took minimal external assistance while moving through the junctions in the corridor areas. Computer vision technology demonstrated its superiority over BLE technology in assistive systems for people with visual impairments.
Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis
Authors: Zhang Tianhua , Chen Jin , Tang Xiaoyu , Luo Qin , Xu Danyan , Yu Bilian
Published: December 2019

Obesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction.
The double edge of anti-CD40 siRNA therapy: It increases renal microcapillar density but favours the generation of an inflammatory milieu in the kidneys of ApoE−/− mice
Authors: Hueso Miguel , Casas Angela , Mallén Adrian , de Ramón Laura , Bolaños Nuria , Varela Cristian , Cruzado Josep M. , Torras Joan , Navarro Estanislao
Published: December 2019

Background

Chronic kidney disease (CKD) is associated with endothelial dysfunctions thus prompting links between microcirculation (MC), inflammation and major cardiovascular risk factors.

Purpose of the study

We have previously reported that siRNA-silencing of CD40 (siCD40) reduced atherosclerosis (ATH) progression. Here, we have deepened on the effects of the siCD40 treatment by evaluating retrospectively, in stored kidneys from the siCD40 treated ApoE−/− mice, the renal microcirculation (measured as the density of peritubular capillaries), macrophage infiltration and NF-κB activation.

Methods

Kidneys were isolated after 16 weeks of treatment with the anti-CD40 siRNA (siCD40), with a scrambled control siRNA (siSC) or with PBS (Veh. group). Renal endothelium, infiltrating macrophages and activated NF-κB in endothelium were identified by immunohistochemistry, while the density of stained peritubular capillaries was quantified by image analysis.

Results

ATH was associated with a reduction in renal MC, an effect reversed by the anti-CD40 siRNA treatment (3.8 ± 2.7% in siCD40; vs. 1.8 ± 0.1% in siSC; or 1.9 ± 1.6% in Veh.; p < 0.0001). Furthermore, siCD40 treatment reduced the number of infiltrating macrophages compared to the SC group (14.1 ± 5.9 cells/field in siCD40; vs. 37.1 ± 17.8 cells/field in siSC; and 1.3 ± 1.7 cells/field in Veh.; p = 0.001). NF-κB activation also peaked in the siSC group, showing lower levels in the siCD40 and Veh. groups (63 ± 60 positive cells/section in siCD40; vs. 152 ± 44 positive cells/section in siSC; or 26 ± 29 positive cells/section in veh.; p = 0.014). Lastly, serum creatinine was also increased in the siCD40 (3.4 ± 3.3 mg/dL) and siSC (4.6 ± 3.0 mg/dL) groups when compared with Veh. (1.1 ± 0.9 mg/dL, p = 0.1).

Conclusions

Anti-CD40 siRNA therapy significantly increased the density of peritubular capillaries and decreased renal inflammation in the ATH model. These data provide a physiological basis for the development of renal diseases in patients with ATH. Furthermore, our results also highligth renal off-target effects of the siRNA treatment which are discussed.

Graphical abstract
BCL2 and hsa-miR-181a-5p are potential biomarkers associated with papillary thyroid cancer based on bioinformatics analysis
Authors: Zhang Cong , Bo Chunrui , Guo Lunhua , Yu Pingyang , Miao Susheng , Gu Xin
Published: December 2019

Background

The morbidity of thyroid carcinoma has been rising worldwide and increasing faster than any other cancer type. The most common subtype with the best prognosis is papillary thyroid cancer (PTC); however, the exact molecular pathogenesis of PTC is still not completely understood.

Methods

In the current study, 3 gene expression datasets (GSE3678, GSE3467, and GSE33630) and 2 miRNA expression datasets (GSE113629 and GSE73182) of PTC were selected from the Gene Expression Omnibus (GEO) database and were further used to identify differentially expressed genes (DEGs) and deregulated miRNAs between normal thyroid tissue samples and PTC samples. Then, Gene Ontology (GO) and pathway enrichment analyses were conducted, and a protein-protein interaction (PPI) network was constructed to explore the potential mechanism of PTC carcinogenesis. The hub gene detection was performed using the CentiScaPe v2.0 plugin, and significant modules were discovered using the MCODE plugin for Cytoscape. In addition, a miRNA-gene regulatory network in PTC was constructed using common deregulated miRNAs and DEGs.

Results

A total of 263 common DEGs and 12 common deregulated miRNAs were identified. Then, 6 significant KEGG pathways (P < 0.05) and 82 significant GO terms were found to be enriched, indicating that PTC was closely related to amino acid metabolism, development, immune system, and endocrine system. In addition, by constructing a PPI network and miRNA-gene regulatory network, we found that hsa-miR-181a-5p regulated the most DEGs, while BCL2 was targeted by the most miRNAs.

Conclusions

The results of this study suggested that hsa-miR-181a-5p and BCL2 and their regulatory networks may play important roles in the pathogenesis of PTC.
Analysis of the Health Product Profile Directory — a new tool to inform priority-setting in global public health
Authors: Terry R. F. , Plasència A. , Reeder J. C.
Published: December 2019

Background

The Health Product Profile Directory (HPPD) is an online database describing 8–10 key characteristics (such as target population, measures of efficacy and dosage) of product profiles for medicines, vaccines, diagnostics and other products that are intended to be accessed by populations in low- and middle-income countries. The HPPD was developed by TDR on behalf of WHO and launched on 15 May 2019.

Methods

The contents of the HPPD were downloaded into an Excel™ spreadsheet via the open access interface and analysed to identify the number of health product profiles by type, disease, year of publication, status, author organization and safety information.

Results

The HPPD contains summaries of 215 health product profiles published between 2008 and May 2019, 117 (54%) of which provide a hyperlink to the detailed publication from which the summary was extracted, and the remaining 98 provide an email contact for further information. A total of 55 target disease or health conditions are covered, with 210 profiles describing a product with an infectious disease as the target. Only 5 product profiles in the HPPD describe a product for a non-communicable disease. Four diseases account for 40% of product profiles in the HPPD; these are tuberculosis (33 profiles, 15%), malaria (31 profiles, 14%), HIV (13 profiles, 6%) and Chagas (10 profiles, 5%).

Conclusion

The HPPD provides a new tool to inform priority-setting in global health — it includes all product profiles authored by WHO (n = 51). There is a need to standardise nomenclature to more clearly distinguish between strategic publications (describing research and development (R&D) priorities or preferred characteristics) compared to target product profiles to guide a specific candidate product undergoing R&D. It is recommended that all profiles published in the HPPD define more clearly what affordability means in the context where the product is intended to be used and all profiles should include a statement of safety. Combining the analysis from HPPD to a mapping of funds available for R&D and those products in the R&D pipeline would create a better overview of global health priorities and how they are supported. Such analysis and increased transparency should take us a step closer to measuring and improving coordination of efforts in global health R&D.
Bystander effects of ionizing radiation: conditioned media from X-ray irradiated MCF-7 cells increases the angiogenic ability of endothelial cells
Authors: Jabbari Nasrollah , Nawaz Muhammad , Rezaie Jafar
Published: December 2019

Background

Non-targeting effects of radiotherapy have become as clinical concern due to secondary tumorigenesis in the patients receiving radiotherapy. Radiotherapy also affects non-tumoral cells present in the tumor microenvironment and surrounding tissues. As such, the irradiated cells are thought to communicate the signals that promote secondary tumorigenesis by affecting the function and fate of non-irradiated cells in the vicinity including endothelial cells. This may include up-regulation of genes in irradiated cells, secretion of paracrine factors and induction of gene expression in surrounding non-irradiated cells, which favor cell survival and secondary tumorigenesis. In the current study, we aimed to investigate whether the conditioned media from X-ray irradiated MCF-7 cells contribute to induction of gene expression in human umbilical vein endothelial cells (HUVECs) in vitro and modulate their angiogenic capability and migration.

Methods

Following the co-culturing of X-ray irradiated MCF-7 media with HUVECs, the migration and wound healing rate of HUVECs was monitored using Transwell plate and scratch wound healing assay, respectively. The levels of angiogenic protein i.e. vascular endothelial growth factor (VEGF-A) in the conditioned media of MCF-7 cells was measured using ELISA. Additionally, we quantified mRNA levels of VEGFR-2, HSP-70, Ang-2, and Ang-1 genes in HUVECs by real time-PCR. Tubulogenesis capacity of endothelial cells was measured by growth factor reduced Matrigel matrix, whereas expression of CD34 (a marker of angiogenic tip cells) was detected by flow cytometry.

Results

Data showed that VEGF-A protein content of conditioned media of irradiated MCF-7 cells was increased (P < 0.05) with increase in dose. Data showed that irradiated conditioned media from MCF-7 cells, when incubated with HUVECs, significantly enhanced the cell migration and wound healing rate of HUVECs in a dose-dependent manner (P < 0.05). The mRNA levels of VEGFR-2, HSP-70, Ang-2, and Ang-1 were dose-dependently enhanced in HUVECs incubated with irradiated conditioned media (P < 0.05). Importantly, HUVECs treated with irradiated conditioned media showed a marked increase in the tube formation capability as well as in expression of CD34 marker (P < 0.05).

Conclusions

Our findings indicate that conditioned media from irradiated MCF-7 cells induce angiogenic responses in endothelial cells in vitro, which could be due to transfer of overexpressed VEGF-A and possibly other factors secreted from irradiated MCF-7 cells to endothelial cells, and induction of intrinsic genes (VEGFR-2, HSP-70, Ang-2, and Ang-1) in endothelial cells.

Graphical abstract
Health-related quality of life during early aggressive treatment in patients with polyarticular juvenile idiopathic arthritis: results from randomized controlled trial
Authors: Tarkiainen Maarit , Tynjälä Pirjo , Vähäsalo Paula , Kröger Liisa , Aalto Kristiina , Lahdenne Pekka
Published: December 2019

Background

Juvenile Idiopathic Arthritis (JIA) may cause significant impairment in health-related quality of life (HrQoL), despite effective therapies. The aim of this study was to assess HrQoL during first-year treatment in patients with new-onset polyarticular JIA, and to compare treatment strategies.

Methods

In ACUTE-JIA Study, 60 patients with new-onset JIA were randomized to receive either infliximab with methotrexate (IFX+MTX); a triple therapy of methotrexate, hydroxychloroquine, and sulfasalazine (Triple); or methotrexate monotherapy (MTX). Efficacy was measured with American College of Rheumatology pediatric (ACRp) score, and juvenile arthritis disease activity score (JADAS). HrQoL was evaluated with Child Health Questionnaire (CHQ), which includes physical and psychosocial summary scores (PhS and PsS). Linear mixed models were utilized to compare groups over time.

Results

In the whole group of 60 patients, mean physical summary score (PhS) improved from 26.2 (SD 8.7) at week 0 to 49.7 (SD 13.2) at week 54 (p=0.046). Mean improvement of PhS was 20.3 (95% CI -15.5 to 56.2); 22.6 (-19.5 to 64.7); and 26.6 (-12.1 to 65.3) in IFX+MTX, Triple, and MTX, respectively. Changes in psychosocial summary score (PsS) were smaller: from 51.0 (SD 8.5) to 54.7 (6.3) (p=0.019) in all patients. No differences between the three treatment groups were detected in either of the measures. In multivariate analyses, Child Health Assessment Questionnaire (CHAQ), pain VAS, and time spent in inactive disease contributed to improvement in PhS; gender and CHAQ to PsS.

Conclusions

HrQol improved during the first year on therapy for JIA irrespective of the treatment strategy. The timing of change in the different dimensions of HrQoL varied; improvement occurred earlier in physical than psychosocial domains of HrQol.

Trial registration

This study was registered within the Hospital District of Helsinki and Uusimaa (http://www.hus.fi) clinical trials, number 211864 in October 2002, and later on with ClinicalTrials.gov, number NCT01015547.
Cardiovascular disease risk in an urban African population: a cross-sectional analysis on the role of HIV and antiretroviral treatment
Authors: Vos Alinda G. , Hoeve Klariska , Barth Roos E. , Peper Joyce , Moorhouse Michelle , Crowther Nigel J. , Venter Willem D. F. , Grobbee Diederick E. , Bots Michiel L. , Klipstein-Grobusch Kerstin
Published: December 2019

Background

Life expectancy is increasing in the HIV-positive population and age-related non-communicable diseases, such as cardiovascular disease, (CVD) are seen more frequently. This study investigated to what extent HIV and antiretroviral therapy (ART) is associated with CVD risk in an urban African population.

Methods

A cross-sectional study was performed in Johannesburg, South Africa, between July 2016 and November 2017. Both HIV-positive adults (ART-naïve, or on first- or second-line ART), as well as age and sex matched HIV-negative controls who were family or friends of the HIV-positive participants were included. Data were collected on demographics, cardiovascular risk factors, HIV-related characteristics, carotid intima-media thickness (CIMT) and carotid distensibility. The association between HIV, ART and CIMT and distensibility was analysed with linear regression models, adjusting for age, gender and CVD risk factors.

Results

The study included 548 participants, 337 (62%) females, age 38.3 ± 9.5 years of whom 104 (19.0%) were HIV-positive, ART-naïve; 94 (17.2%) were on first-line ART; 197 (35.9%) were on second-line ART; and 153 (27.9%) were HIV-negative. Participants on second-line ART had higher CIMT and lower distensibility compared to the other groups (p < 0.001). After adjustment for age, these outcomes were similar between groups. Further adjustment for CVD and HIV-related factors did not alter the findings.

Conclusion

Neither HIV nor ART was associated with CIMT or carotid distensibility in this urban African population. Longitudinal studies are needed to fully understand the relationship between HIV and CVD across different populations.
STLV-1 as a model for studying HTLV-1 infection
Authors: Jégado Brice , Kashanchi Fatah , Dutartre Hélène , Mahieux Renaud
Published: December 2019

Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all simian species. Subsequent molecular epidemiology studies demonstrated that, apart from HTLV-1 subtype A, all human subtypes have a simian homolog. As HTLV-1, STLV-1 is the etiological agent of ATL, while no case of TSP/HAM has been described. Given its similarities with HTLV-1, STLV-1 represents a unique tool used for performing clinical studies, vaccine studies as well as basic science.
HIV-1 Rev interacts with HERV-K RcREs present in the human genome and promotes export of unspliced HERV-K proviral RNA
Authors: Gray Laurie R. , Jackson Rachel E. , Jackson Patrick E. H. , Bekiranov Stefan , Rekosh David , Hammarskjöld Marie-Louise
Published: December 2019

Background

The HERV-K (HML-2) viruses are the youngest of the human endogenous retroviruses. They are present as several almost complete proviral copies and numerous fragments in the human genome. Many HERV-K proviruses express a regulatory protein Rec, which binds to an element present in HERV-K mRNAs called the RcRE. This interaction is necessary for the nucleo-cytoplasmic export and expression of HERV-K mRNAs that retain introns and plays a role analogous to that of Rev and the RRE in HIV replication. There are over 900 HERV-K RcREs distributed throughout the human genome. Thus, it was of interest to determine if Rev could functionally interact with selected RcRE elements that map either to HERV-K proviruses or human gene regions. This interaction would have the potential to alter the expression of both HERV-K mRNAs and cellular mRNAs during HIV-1 infection.

Results

In this study we employed a combination of RNAseq, bioinformatics and cell-based functional assays. Potential RcREs were identified through a number of bioinformatic approaches. They were then tested for their ability to promote export and translation of a reporter mRNA with a retained intron in conjunction with Rev or Rec. Some of the selected elements functioned well with either Rev, Rec or both, whereas some showed little or no function. Rev function on individual RcREs varied and was also dependent on the Rev sequence. We also performed RNAseq on total and cytoplasmic RNA isolated from SupT1 cells expressing HIV Rev, with or without Tat, or HERV-K Rec. Proviral mRNA from three HERV-K loci (4p16.1b, 22q11.23 and most significantly 3q12.3) accumulated in the cytoplasm in the presence of Rev or Tat and Rev, but not Rec. Consistent with this, the 3′ RcRE from 3q12.3 functioned well with HIV-Rev in our reporter assay. In contrast, this RcRE showed little or no function with Rec.

Conclusions

The HIV Rev protein can functionally interact with many RcREs present in the human genome, depending on the RcRE sequence, as well as the Rev sequence. This leads to export of some of the HERV-K proviral mRNAs and also has the potential to change the expression of non-viral genes.
Melatonin is responsible for rice resistance to rice stripe virus infection through a nitric oxide-dependent pathway
Authors: Lu Rongfei , Liu Zhiyang , Shao Yudong , Sun Feng , Zhang Yali , Cui Jin , Zhou Yijun , Shen Wenbiao , Zhou Tong
Published: December 2019

Rice stripe virus (RSV) causes one of the most important rice virus diseases of plants in East Asia. However, the molecular mechanisms controlling rice resistance to RSV infection are largely unknown. Recently, several studies presented a novel model that melatonin (MT) and nitric oxide (NO) participate in the plant-pathogen interaction in a synergetic manner. In this study, there was a difference in MT content between two rice varieties that correlated with one being susceptible and one being resistant to RSV, which suggested that MT is related to RSV resistance. In addition, a test with two NO biosynthesis inhibitors revealed that NO inhibitor were able to increase the disease incidence of RSV. A pharmacological experiment with exogenous MT and NO showed that increased MT and NO in the MT-pretreated plants led to lower disease incidences; however, only NO increased in a NO-releasing reagent [sodium nitroprusside (SNP)] pretreated plants. The expressions level of OsPR1b and OsWRKY 45 were significantly induced by MT and NO. These results suggest that rice resistance to RSV can be improved by increased MT through a NO-dependent pathway.
Endothelial IL-8 induced by porcine circovirus type 2 affects dendritic cell maturation and antigen-presenting function
Authors: Liu Shiyu , Li Qiuming , Qiao Jinzeng , Wang Jianfang , Cui Defeng , Gu Kewei , Zhou Shuanghai , Li Huanrong
Published: December 2019

Background

Porcine circovirus (PCV) disease caused by PCV type 2 (PCV2) is mainly attributed to immunosuppression and immune damage. PCV2 can infect vascular endothelial cells and induce high expression of endothelial IL-8. Dendritic cells (DCs), as professional antigen-presenting cells, can not only present antigens but also activate naïve T-cells, causing an immune response.

Methods

To demonstrate whether endothelial IL-8 is the main factor inhibiting the maturation and related functions of dendritic cells during PCV2 infection, monocyte-derived DCs (MoDCs) and porcine iliac artery endothelial cells (PIECs) processed by different methods were co-cultured in two ways. Flow cytometry, molecular probe labeling, fluorescence quantitative PCR, and the MTS assay were used to detect the changes in related functions and molecules of MoDCs.

Results

Compared to those in the PIEC-DC group, the endothelial IL-8 upregulation co-culture group showed significantly lower double-positive rates for CD80/86 and MHC-II of MoDCs and significantly increased endocytosis of MoDCs. Meanwhile, the adhesion rate and average fluorescence intensity of MoDCs were significantly downregulated in migration and adhesion experiments. Furthermore, the MHC-I and LAMP7 mRNA levels in MoDCs and the proliferation of MoDC-stimulated T-cells were markedly reduced. However, the changes in MoDCs of the endothelial IL-8 downregulation co-culture group were the opposite.

Conclusions

PCV2-induced endothelial IL-8 reduces the adhesion and migration ability of MoDCs, resulting in a decreased maturation rate of MoDCs, and further inhibits antigen presentation by DCs. These results may explain the immunosuppressive mechanism of PCV2 from the perspective of the interaction between endothelial cells and DCs in vitro.
Mapping of CD4+ T-cell epitopes in bovine leukemia virus from five cattle with differential susceptibilities to bovine leukemia virus disease progression
Authors: Bai Lanlan , Takeshima Shin-nosuke , Sato Masaaki , Davis William C. , Wada Satoshi , Kohara Junko , Aida Yoko
Published: December 2019

Background

Bovine leukemia virus (BLV), which is closely related to human T-cell leukemia virus, is the etiological agent of enzootic bovine leukosis, a disease characterized by a highly prolonged course involving persistent lymphocytosis and B-cell lymphoma. The bovine major histocompatibility complex class II region plays a key role in the subclinical progression of BLV infection. In this study, we aimed to evaluate the roles of CD4+T-cell epitopes in disease progression in cattle.

Methods

We examined five Japanese Black cattle, including three disease-susceptible animals, one disease-resistant animal, and one normal animal, classified according to genotyping of bovine leukocyte antigen (BoLA)-DRB3andBoLA-DQA1alleles using polymerase chain reaction sequence-based typing methods. All cattle were inoculated with BLV-infected blood collected from BLV experimentally infected cattle and then subjected to CD4+T-cell epitope mapping by cell proliferation assays.

Results

Five Japanese Black cattle were successfully infected with BLV, and CD4+T-cell epitope mapping was then conducted. Disease-resistant and normal cattle showed low and moderate proviral loads and harbored six or five types of CD4+T-cell epitopes, respectively. In contrast, the one of three disease-susceptible cattle with the highest proviral load did not harbor CD4+T-cell epitopes, and two of three other cattle with high proviral loads each had only one epitope. Thus, the CD4+T-cell epitope repertoire was less frequent in disease-susceptible cattle than in other cattle.

Conclusion

Although only a few cattle were included in this study, our results showed that CD4+T-cell epitopes may be associated withBoLA-DRB3-DQA1haplotypes, which conferred differential susceptibilities to BLV proviral loads. These CD4+T-cell epitopes could be useful for the design of anti-BLV vaccines targeting disease-susceptible Japanese Black cattle. Further studies of CD4+T-cell epitopes in other breeds and using larger numbers of cattle with differential susceptibilities are required to confirm these findings.
Women’s advice to healthcare professionals regarding breastfeeding: “offer sensitive individualized breastfeeding support”- an interview study
Authors: Blixt Ingrid , Johansson Margareta , Hildingsson Ingegerd , Papoutsi Zoi , Rubertsson Christine
Published: December 2019

Background

The World Health Organization recommends exclusive breastfeeding for 6 months followed by continued breastfeeding with complementary food up to 2 years of age or beyond. Few women achieve this recommendation in Sweden, and they often stop breastfeeding earlier than they would like. Investigating women’s advice to healthcare professionals is important for the provision of optimal breastfeeding support. The aim of this study was to explore women’s advice to healthcare professionals regarding support for continuing to breastfeed for at least 6 months.

Methods

This investigation used an exploratory study design, and a purposive sample of women was recruited between 2015 and 2016 through social media platforms. The work is a follow-up of an earlier study exploring women’s perceptions of the factors that assisted them in breastfeeding for at least 6 months. Telephone interviews were conducted with 139 Swedish women who reported that they had breastfed for at least 6 months. Women were asked the question, “Do you have any advice that you would like to give to healthcare professionals regarding breastfeeding support?”. The data were analysed using content analysis.

Results

The theme, “Professionals need to offer women sensitive, individualized breastfeeding support to promote a positive breastfeeding experience”, describes the women’s advice based on five categories: 1) providing evidence-based care, 2) preparing expectant parents during pregnancy, 3) creating a respectful and mutual dialogue, 4) offering individual solutions to breastfeeding problems, and 5) offering practical support.

Conclusions

This study highlights the importance of professionals providing evidence-based breastfeeding support in a sensitive and individualized manner. This consideration is an important prerequisite to strengthening women’s self-confidence and assisting them in reaching their breastfeeding goals, which may enhance the positive nature of their breastfeeding experience.
A protocol for laser microdissection (LMD) followed by transcriptome analysis of plant reproductive tissue in phylogenetically distant angiosperms
Authors: Kivivirta Kimmo , Herbert Denise , Lange Matthias , Beuerlein Knut , Altmüller Janine , Becker Annette
Published: December 2019

Background

Plant development is controlled by the action of many, often connected gene regulatory networks. Differential gene expression controlled by internal and external cues is a major driver of growth and time specific differentiation in plants. Transcriptome analysis is the state-of-the-art method to detect spatio-temporal changes in gene expression during development. Monitoring changes in gene expression at early stages or in small plant organs and tissues requires an accurate technique of tissue isolation, which subsequently results in RNA of sufficient quality and quantity. Laser-microdissection enables such accurate dissection and collection of desired tissue from sectioned material at a microscopic level for RNA extraction and subsequent downstream analyses, such as transcriptome, proteome, genome or miRNA.

Results

A protocol for laser-microdissection, RNA extraction and RNA-seq was optimized and verified for three distant angiosperm species:Arabidopsis thaliana(Brassicaceae),Oryza sativa(Poaceae) andEschscholzia californica(Papaveraceae). Previously published protocols were improved in processing speed by reducing the vacuum intensity and incubation time during tissue fixation and incubation time and cryoprotection and by applying adhesive tape. The sample preparation and sectioning of complex and heterogenous flowers produced adequate histological quality and subsequent RNA extraction from micro-dissected gynoecia reliably generated samples of sufficient quality and quantity on all species for RNA-seq. Expression analysis of growth stage specificA. thalianaandO. sativatranscriptomes showed distinct patterns of expression of chromatin remodelers on different time points of gynoecium morphogenesis from the initiation of development to post-meiotic stages.

Conclusion

Here we describe a protocol for plant tissue preparation, cryoprotection, cryo-sectioning, laser microdissection and RNA sample preparation for Illumina sequencing of complex plant organs from three phyletically distant plant species. We are confident that this approach is widely applicable to other plant species to enable transcriptome analysis with high spatial resolution in non-model plant species. The protocol is rapid, produces high quality sections of complex organs and results in RNA of adequate quality well suited for RNA-seq approaches. We provide detailed description of each stage of sample preparation with the quality and quantity measurements as well as an analysis of generated transcriptomes.
Application of data mining techniques and logistic regression to model drug use transition to injection: a case study in drug use treatment centers in Kermanshah Province, Iran
Authors: Najafi-Ghobadi Somayeh , Najafi-Ghobadi Khadijeh , Tapak Lily , Aghaei Abbas
Published: December 2019

Background

Drug injection has been increasing over the past decades all over the world. Hepatitis B and C viruses (HBV and HCV) are two common infections among people who inject drugs (PWID) and more than 60% of new human immunodeficiency virus (HIV) cases are PWID. Thus, investigating risk factors associated with drug use transition to injection is essential and was the aim of this research.

Methods

We used a database from drug use treatment centers in Kermanshah Province (Iran) in 2013 that included 2098 records of people who use drugs (PWUD). The information of 29 potential risk factors that are commonly used in the literature on drug use was selected. We employed four classification methods (decision tree, neural network, support vector machine, and logistic regression) to determine factors affecting the decision of PWUD to transition to injection.

Results

The average specificity of all models was over 84%. Support vector machine produced the highest specificity (0.9). Also, this model showed the highest total accuracy (0.91), sensitivity (0.94), positive likelihood ratio [1] and Kappa (0.94) and the smallest negative likelihood ratio (0). Therefore, important factors according to the support vector machine model were used for further interpretation.

Conclusions

Based on the support vector machine model, the use of heroin, cocaine, and hallucinogens were identified as the three most important factors associated with drug use transition injection. The results further indicated that PWUD with the history of prison or using drug due to curiosity and unemployment are at higher risks. Unemployment and unreliable sources of income were other suggested factors of transition in this research.
The effect of robot-navigation-assisted core decompression on early stage osteonecrosis of the femoral head
Authors: Bi Benjun , Zhang Shudong , Zhao Yuchi
Published: December 2019

Background

The aim of the current paper is to evaluate the effects of robot-navigation-assisted core decompression compared with conventional core decompression surgery for early-stage osteonecrosis of the femoral head.

Methods

Twenty patients with a total of 36 hips who were diagnosed with Association Research Circulation Osseous stage 2 avascular necrosis of the femoral head and who received core decompression with or without robotic assistance were reviewed. The Harris hip score and visual analog scale score were used to assess clinical function. Intraoperative radiation exposure and operation time were used to evaluate the effectiveness of the robot-assisted system.

Results

At a mean follow-up of 26.4 months (24–36 months), the Harris hip score, visual analog scale score, and survival rate of the patients were similar between the conventional and robot-assisted groups. The guidewire insertion time, number of guidewire attempts, and radiation exposure during guidewire insertion were all significantly lower in the robot-assisted group than in the conventional group.

Conclusions

Robot-assisted core decompression of the femoral head is as safe and effective as a conventional core decompression surgery. It can reduce operation time and decrease intraoperative radiation exposure.