bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining user fee reductions in public primary healthcare facilities in Kenya, 1997–2012: effects on the use and content of antenatal care
Authors: Dennis Mardieh L. , Benova Lenka , Goodman Catherine , Barasa Edwine , Abuya Timothy , Campbell Oona M. R. 
Published: March 2020

Abstract
Background
In 2004, The Kenyan government removed user fees in public dispensaries and health centers and replaced them with registration charges of 10 and 20 Kenyan shillings (2004 $US 0.13 and $0.25), respectively. This was termed the 10/20 policy. We examined the effect of this policy on the coverage, timing, source, and content of antenatal care (ANC), and the equity in these outcomes.

Methods
Data from the 2003, 2008/9 and 2014 Kenya Demographic and Health Surveys were pooled to investigate women’s ANC care-seeking. We conducted an interrupted time series analysis to assess the impact of the 10/20 policy on the levels of and trends in coverage for 4+ ANC contacts among all women; early ANC initiation and use of public facility-based care among 1+ ANC users; and use of public primary care facilities and receipt of good content, or quality, of ANC among users of public facilities. All analyses were conducted at the population level and separately for women with higher and lower household wealth.

Results
The policy had positive effects on use of 4+ ANC among both better-off and worse-off women. Among users of 1+ ANC, the 10/20 policy had positive effects on early ANC initiation at the population-level and among better-off women, but not among the worse-off. The policy was associated with reduced use of public facility-based ANC among better-off women. Among worse-off users of public facility-based ANC, the 10/20 policy was associated with reduced use of primary care facilities and increased content of ANC.

Conclusions
This study highlights mixed findings on the impact of the 10/20 policy on ANC service-seeking and content of care. Given the reduced use of public facilities among the better-off and of primary care facilities among the worse-off, this research also brings into question the mechanisms through which the policy achieved any benefits and whether reducing user fees is sufficient for equitably increasing healthcare access.
Associations between perfluoroalkyl substances and serum lipids in a Swedish adult population with contaminated drinking water
Authors: Li Ying , Barregard Lars , Xu Yiyi , Scott Kristin , Pineda Daniela , Lindh Christian H. , Jakobsson Kristina , Fletcher Tony 
Published: March 2020

Abstract
Background
Exposures to perfluoroalkyl substances (PFAS) have shown positive associations with serum lipids in previous studies. While many studies on lipids investigated associations with perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), there are only a few studies regarding other PFAS, such as perfluorohexane sulfonic acid (PFHxS). The purpose of the current study is to investigate if associations with serum lipids were present, not only for serum PFOS and PFOA, but also for PFHxS, and if the associations with PFAS remained also in a comparison based only on residency in areas with contrasting exposure to PFAS.

Methods
1945 adults aged 20–60 were included from Ronneby, Sweden, a municipality where one out of two waterworks had been heavily contaminated from aqueous fire-fighting foams, and from a nearby control area. The exposure was categorized based on either been living in areas with contrasting PFAS exposure or based on the actual serum PFAS measurements. Regression analyses of serum lipids were fitted against serum PFAS levels, percentile groups, smooth splines and between exposed and reference areas, adjusting for age, sex and BMI.

Results
Drinking water contamination caused high serum levels of PFOS (median 157 ng/ml) and PFHxS (median 136 ng/ml) and PFOA (median 8.6 ng/ml). These serum PFAS levels in the exposed groups were 5 to 100-fold higher than in the controls. In this population with mixed PFAS exposure, predominantly PFOS and PFHxS, PFAS exposure were positively associated with serum lipids. This was observed both when quantifying exposure as contrast between exposed and controls, and in terms of serum PFAS. Due to high correlations between each PFAS, we cannot separate them.

Conclusions
In conclusion, the present study provides further evidence of a causal association between PFAS and serum lipids, especially for PFHxS.
Dysregulated serum lipid profile and its correlation to disease activity in young female adults diagnosed with systemic lupus erythematosus: a cross-sectional study
Authors: Zhou Bo , Xia Yulong , She Jianqing 
Published: March 2020

Abstract
Background
Recent studies showed that dyslipidemia could be a critical factor in the progression of cardiovascular disease in systemic lupus erythematosus (SLE). The aim of the present study was to describe the relationship between serum lipid profile and SLE disease activity in young female adults with SLE.

Methods
Seventy-one female subjects diagnosed with SLE aged 20~30 years were enrolled. Serum lipid profile including TC, TG, HDL-C, LDL-C, VLDL-C, Apo A, Apo B, and Apo E were evaluated between control and young female SLE patients. Univariate correlation analyses were performed to explore the correlation between serum lipid levels and SLE disease activity.

Results
Our results showed that TG and VLDL-C levels were significantly increased in young female SLE as compared to control, with TC, HDL-C, LDL-C, Apo A, and Apo B significantly reduced. Meanwhile, univariate correlation analyses showed negative correlations between SLE disease activity index and HDL-C, LDL-C, Apo A, and Apo B; with positive correlations between SLE disease activity index and TG and VLDL-C.

Conclusion
Serum lipid profile was significantly dysregulated in young female SLE patients. Moreover, SLE disease activity was correlated to the serum lipid levels, supporting the notion that the young patients with SLE might also have a higher risk of cardiovascular disease.
Quality of life in elderly people after a hip fracture: a prospective study
Authors: Amarilla-Donoso Francisco Javier , López-Espuela Fidel , Roncero-Martín Raúl , Leal-Hernandez Olga , Puerto-Parejo Luis Manuel , Aliaga-Vera Ignacio , Toribio-Felipe Rosaura , Lavado-García Jesús María 
Published: March 2020

Abstract
Background
Hip fracture is an important social and medical problem due to its increasing prevalence, the consequences for health and the economic impact on the health care system, but there is no doubt that it also has repercussions on health-related quality of life (HRQoL). Hence the importance of understanding and determining the impact of the condition on everyday life from the perspective of the patient’s physical, emotional and social well-being.

Purpose
To determine the impact of hip fracture on HRQoL of people over the age of 65 1 month after surgery, related factors and the effects on functional ability and mood.

Methods
Prospective observational study conducted in the traumatology units of two university hospitals in the province of Cáceres with consecutive sampling of all patients over the age of 65 admitted for hip fracture surgery during the study period. Sociodemographic and clinical data were recorded at the time of admission and prospectively at the follow-up visit 1 month later. Clinical, social, quality of life (EQ-5D-), basic functional and instrumental capacity (Barthel Index (BI) and Lawton & Brody Scale), and geriatric depression (Yesavage) variables were collected.

Results
The study included 224 patients with a median age of 84.6 years (SD ± 6.1), 76.3% were female. Charlson’s comorbidity was 5.3 (SD ± 1.2). The EQ-5D index decreased from 0.62 (SD ± 0.35) to 0.16 at 1 month follow up (SD ± 0.20) p <  0.001. The mean Visual Analog Scale (VAS) score of EQ-5D decreased from 72.8 (SD ±15.8) to 48.3 (SD ± 17.2) p <  0.001. All dimensions of EQ-5D showed a significant reduction from the time of pre-fracture status to 1 month after surgery. Independent factors associated with HRQoL 1 month after surgery were pre-fracture status Barthel Index score, Lawton and Brody scale, presence of depression, and type of surgery.

Conclusions
After a hip fracture, patients experience considerable deterioration in their HRQoL, especially in self-care, daily activities, and mobility. There is also a significant decline in functional capacity for both the basic and instrumental activities of daily living. One month after surgery, HRQoL is a long way from pre-fracture levels.
Bisphenol A: an emerging threat to female fertility
Authors: Pivonello Claudia , Muscogiuri Giovanna , Nardone Antonio , Garifalos Francesco , Provvisiero Donatella Paola , Verde Nunzia , de Angelis Cristina , Conforti Alessandro , Piscopo Mariangela , Auriemma Renata Simona , Colao Annamaria , Pivonello Rosario 
Published: March 2020

AbstractBisphenol-A (BPA) has been reported to be associated to female infertility. Indeed, BPA has been found to be more frequently detected in infertile women thus leading to hypothesize a possible effect of BPA on natural conception and spontaneous fecundity. In addition, in procedures of medically assisted reproduction BPA exposure has been found to be negatively associated with peak serum estradiol levels during gonadotropin stimulation, number of retrieved oocytes, number of normally fertilized oocytes and implantation. BPA deleterious effects are more critical during perinatal exposure, causing dysregulation of hypothalamic-pituitary-ovarian axis in pups and adults, with a precocious maturation of the axis through a damage of GnRH pulsatility, gonadotropin signaling and sex steroid hormone production. Further, BPA exposure during early lifestage may have a transgenerational effect predisposing the subsequent generations to the risk of developing BPA related disease. Experimental studies suggested that prenatal, perinatal and postnatal exposure to BPA can impair several steps of ovarian development, induce ovarian morphology rearrangement and impair ovarian function, particularly folliculogenesis, as well as can impair uterus morphology and function, in female adult animal and offspring. Finally, studies carried out in animal models have been reported the occurrence of endometriosis-like lesions after BPA exposure. Moreover, BPA exposure has been described to encourage the genesis of PCOS-like abnormalities through the impairment of the secretion of sex hormones affecting ovarian morphology and functions, particularly folliculogenesis. The current manuscript summarizes the evidence regarding the association between BPA exposure and female infertility, reviewing both clinical and preclinical studies.
Angiopoietin-2 induces angiogenesis via exosomes in human hepatocellular carcinoma
Authors: Xie Ji-yan , Wei Jin-xing , Lv Li-hong , Han Qing-fang , Yang Wei-bang , Li Guo-lin , Wang Pan-xia , Wu Shao-bin , Duan Jin-xin , Zhuo Wen-feng , Liu Pei-qing , Min Jun 
Published: March 2020

Abstract
Background
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is a highly vascularized solid tumor. Angiopoietin-2 (ANGPT2) has been described as an attractive target for antiangiogenic therapy. Exosomes are small extracellular vesicles secreted by most cell types and contribute to cell-to-cell communication by delivering functional cargo to recipient cells. The expression of ANGPT2 in tumor-derived exosomes remains unknown.

Methods
We detected the ANGPT2 expression in HCC-derived exosomes by immunoblotting, enzyme-linked immunosorbent assay and immunogold labeling, then observed exosomal ANGPT2 internalization and recycling by confocal laser scanning microscopy, co-immunoprecipitation and immunoblotting. We used two HCC cell lines (Hep3B and MHCC97H) to overexpress ANGPT2 by lentivirus infection or knockdown ANGPT2 by the CRISPR/Cas system, then isolated exosomes to coculture with human umbilical vein endothelial cells (HUVECs) and observed the angiogenesis by Matrigel microtubule formation assay, transwell migration assay, wound healing assay, cell counting kit-8 assay, immunoblotting and in vivo tumorigenesis assay.

Results
We found that HCC-derived exosomes carried ANGPT2 and delivered it into HUVECs by exosome endocytosis, this delivery led to a notable increase in angiogenesis by a Tie2-independent pathway. Concomitantly, we observed that HCC cell-secreted exosomal ANGPT2 was recycled by recipient HUVECs and might be reused. In addition, the CRISPR-Cas systems to knock down ANGPT2 significantly inhibited the angiogenesis induced by HCC cell-secreted exosomal ANGPT2, and obviously suppressed the epithelial-mesenchymal transition activation in HCC.

Conclusions
Taken together, these results reveal a novel pathway of tumor angiogenesis induced by HCC cell-secreted exosomal ANGPT2 that is different from the classic ANGPT2/Tie2 pathway. This way may be a potential therapeutic target for antiangiogenic therapy.
Copper induce zebrafish retinal developmental defects via triggering stresses and apoptosis
Authors: Zhao Guang , Sun HaoJie , Zhang Ting , Liu Jing-Xia 
Published: March 2020

AbstractBackgroundThe disorder of copper homeostasis is linked with disease and developmental defects, and excess copper_nanoparticles (CuNPs) and ion (Cu2+) will induce developmental malformation and disease in organisms. However, little knowledge is available regarding its potential regulation mechanisms, and little study links excess copper with retinal developmental malformation and disease.MethodsEmbryos were stressed with copper (CuNPs and Cu2+), and cell proliferation and apoptosis assays, reactive oxygen species (ROS) and endoplasmic reticulum (ER) signaling detections, and genetic mutantscox17−/−andatp7a−/−application, were used to evaluate copper induced retinal developmental malformation and the underlying genetic and biological regulating mechanisms.ResultsCopper reduced retinal cells and down-regulated expression of retinal genes, damaged the structures of ER and mitochondria in retinal cells, up-regulated unfold protein responses (UPR) and ROS, and increased apoptosis in copper-stressed retinal cells. The copper induced retinal defects could be significantly neutralized by ROS scavengers reduced Glutathione (GSH) & N-acetylcysteine (NAC) and ER stress inhibitor 4- phenylbutyric acid (PBA). Blocking the transportation of copper to mitochondria, or to trans-Golgi network and to be exported into plasma, by deleting genecox17oratp7a, could alleviate retinal developmental defects in embryos under copper stresses.ConclusionsThis is probably the first report to reveal that copper nanoparticles and ions induce retinal developmental defects via upregulating UPR and ROS, leading to apoptosis in zebrafish embryonic retinal cells. Integrated function of copper transporter (Cox17 and Atp7a) is necessary for copper induced retinal defects.Graphical abstract
Profiling the Salivary microbiome of the Qatari population
Authors: Murugesan Selvasankar , Al Ahmad Sara Fahad , Singh Parul , Saadaoui Marwa , Kumar Manoj , Al Khodor Souhaila 
Published: March 2020

Abstract
Background
The role of the human microbiome in human health and disease has been studied in various body sites. However, compared to the gut microbiome, where most of the research focus is, the salivary microbiome still bears a vast amount of information that needs to be revealed. This study aims to characterize the salivary microbiome composition in the Qatari population, and to explore specific microbial signatures that can be associated with various lifestyles and different oral conditions.

Materials and methods
We characterized the salivary microbiome of 997 Qatari adults using high-throughput sequencing of the V1–V3 region of the 16S rRNA gene.

Results
In this study, we have characterized the salivary microbiome of 997 Qatari participants. Our data show that Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria are the common phyla isolated from the saliva samples, with Bacteroidetes being the most predominant phylum. Bacteroidetes was also more predominant in males versus females in the study cohort, although differences in the microbial diversity were not statistically significant. We also show that, a lower diversity of the salivary microbiome is observed in the elderly participants, with Prevotella and Treponema being the most significant genera. In participants with oral conditions such as mouth ulcers, bleeding or painful gum, our data show that Prevotella and Capnocytophaga are the most dominant genera as compared to the controls. Similar patterns were observed in participants with various smoking habits as compared to the non-smoking participants. Our data show that Streptococcus and Neisseria are more dominant among denture users, as compared to the non-denture users. Our data also show that, abnormal oral conditions are associated with a reduced microbial diversity and microbial richness. Moreover, in this study we show that frequent coffee drinkers have higher microbial diversity compared to the non-drinkers, indicating that coffee may cause changes to the salivary microbiome. Furthermore, tea drinkers show higher microbial richness as compared to the non-tea drinkers.

Conclusion
This is the first study to assess the salivary microbiome in an Arab population, and one of the largest population-based studies aiming to the characterize the salivary microbiome composition and its association with age, oral health, denture use, smoking and coffee-tea consumption.
Pellino1 regulates neuropathic pain as well as microglial activation through the regulation of MAPK/NF-κB signaling in the spinal cord
Authors: Wang Lijuan , Yin Cui , Liu Tianya , Abdul Mannan , Zhou Yan , Cao Jun-Li , Lu Chen 
Published: March 2020

Abstract
Background
Spinal cord microglia plays a crucial role in the pathogenesis of neuropathic pain. However, the mechanisms underlying spinal microglial activation during neuropathic pain remain incompletely determined. Here, we investigated the role of Pellino1 (Peli1) and its interplay with spinal microglial activation in neuropathic pain.

Methods
In this study, we examined the effects of Peli1 on pain hypersensitivity and spinal microglial activation after chronic constriction injury (CCI) of the sciatic nerve in mice. The molecular mechanisms involved in Peli1-mediated hyperalgesia were determined by western blot, immunofluorescence, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). We utilized immunoprecipitation to examine the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6) following CCI. In addition, we explored the effect of Peli1 on BV2 microglial cells in response to lipopolysaccharide (LPS) challenge.

Results
We found that CCI induced a significant increase in the levels of Peli1, which was present in the great majority of microglia in the spinal dorsal horn. Our results showed that spinal Peli1 contributed to the induction and maintenance of CCI-induced neuropathic pain. The biochemical data revealed that CCI-induced Peli1 in the spinal cord significantly increased mitogen-activated protein kinase (MAPK) phosphorylation, activated nuclear factor kappa B (NF-κB), and enhanced the production of proinflammatory cytokines, accompanied by spinal microglial activation. Peli1 additionally was able to promote K63-linked ubiquitination of TRAF6 in the ipsilateral spinal cord following CCI. Furthermore, we demonstrated that Peli1 in microglial cells significantly enhanced inflammatory reactions after LPS treatment.

Conclusion
These results suggest that the upregulation of spinal Peli1 is essential for the pathogenesis of neuropathic pain via Peli1-dependent mobilization of spinal cord microglia, activation of MAPK/NF-κB signaling, and production of proinflammatory cytokines. Modulation of Peli1 may serve as a potential approach for the treatment of neuropathic pain.
Longitudinal examination of changing fertility intentions and behaviors over a four-year period in urban Senegal
Authors: Speizer Ilene S. , Escamilla Veronica , Lance Peter M. , Guilkey David K. 
Published: March 2020

AbstractBackgroundFertility intentions and contraceptive use are often used to demonstrate gaps in programs and policies to meet the contraceptive needs of women and couples. Prior work demonstrated that fertility intentions are fluid and change over a woman’s (or couple’s) life course with changing marital status, childbearing, and education/employment opportunities. This study uses longitudinal data to better examine the fluidity of women’s fertility intentions and disentangle the complex interrelationships between fertility and contraceptive use.MethodsUsing survey data from three time points and three urban sites in Senegal, this study examines how women’s fertility intentions and contraceptive use in an earlier period affect pregnancy experience and the intentionality of experienced pregnancies among a sample of 1050 women who were in union at all three time points. We apply correlated random effect longitudinal regression methods to predict a subsequent birth by fertility intentions and modern contraceptive use at an earlier period addressing endogeneity concerns of earlier analyses that only include two time periods.ResultsDescriptive results demonstrate some change in fertility desires over time such that 6–8% of women who reported their pregnancy as intended (i.e., wanted to get pregnant at time of pregnancy) reported earlier that they did not want any(more) children. Multivariate analyses demonstrate that women who want to delay or avoid a pregnancy and are using modern contraception are the least likely to get pregnant. Among women who became pregnant, the only factor differentiating whether the pregnancy is reported as intended or unintended (mistimed or unwanted) was prior fertility intention. Women who wanted to delay a pregnancy previously were more likely to report the pregnancy as unintended compared to women who wanted to get pregnant soon.ConclusionsThese results suggest some post-hoc rationalization among women who are getting pregnant. Women who say they do not want to get pregnant may be choosing not to use a contraceptive method in this urban Senegal context of high fertility. Programs seeking to reach these women need to consider their complex situations including their fertility intentions, family planning use, and the community norms within which they are reporting these intentions and behaviors.
Isobavachalcone inhibits Pseudorabies virus by impairing virus-induced cell-to-cell fusion
Authors: Wang Yu , Liu Tian-Xin , Wang Tong-Yun , Tang Yan-Dong , Wei Ping 
Published: March 2020

AbstractPseudorabies virus (PRV) is an important pathogen that threatens the global swine industry. Currently, there is no effective drug that can clinically prevent or treat PRV infections. Isobavachalcone (IBC), a natural chalcone compound derived from Psoralea corylifolia, displays multiple biological activities, such as antibacterial, antifungal, and anticancer activities. Recently, it was found that IBC exhibited antiviral activity against an RNA virus, porcine reproductive and respiratory syndrome virus (PRRSV), in vitro. In the current study, we further demonstrated for the first time that IBC has a strong inhibitory effect on PRV. Through a viral luciferase expression assay, we showed that the inhibition step occurs mainly in the late stage of viral replication. Finally, via a cell-to-cell fusion assay, we demonstrated that IBC inhibits PRV by blocking virus-mediated cell fusion. Thus, IBC may be a candidate for further therapeutic evaluation against PRV infection in vivo.