bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in health inequalities for patients with diabetes among middle-aged and elderly in China from 2011 to 2015
Authors: Cao Guizhen , Cui Zhizhen , Ma Qinghua , Wang Congju , Xu Yong , Sun Hongpeng , Ma Yana 
Published: August 2020

Abstract
Background
The purpose of this paper is to measure income-related health inequality among middle-aged and elderly patients with diabetes in China from 2011 to 2015 and to investigate factors that might be related to this inequality.

Methods
The data for this study were obtained from the China Health and Retirement Longitudinal Study that was carried out in 2011, 2013 and 2015. In total, 48,519 Chinese middle-aged and elderly population were included (15,457 in 2011, 16,576 in 2013 and 16,486 in 2015). A principal component analysis was performed to measure asset-based economic status. The concentration index was used to measure income-related inequality in patients with diabetes. Additionally, by used generalized linear model, we decomposed the concentration index to identify factors that explained wealth-related inequality in patients with diabetes.

Results
The prevalence of self-reported diabetes among middle-aged and elderly Chinese was 5.61, 7.49 and 8.99% in 2011, 2013 and 2015, respectively. The concentration indices and 95% confidence intervals for diabetes were 0.1359 (0.0525–0.0597), 0.1207 (0.0709–0.0789), 0.1021 (0.0855–0.0942) in 2011, 2013, and 2015, respectively, which are indicative of inequality that favors the rich. The decomposition of the concentration index showed that residence (39.38%), BMI (31.16%), education (7.28%), and region (6.09%) had positive contributions to the measured inequality in diabetes in China in 2015. Age (− 29.93%) had a negative contribution to inequality.

Conclusion
The findings confirm a health inequality in diabetes that favor the rich. Furthermore, the inequality declined from 2011 to 2015. We suggest that policy and intervention strategies should be developed to alleviate this health inequality, such as narrow the gap between urban and rural areas by improving the urban-rural medical insurance scheme, implementing strategies to enhance hygiene health education, control obesity rate.
LncRNA DLX6-AS1 aggravates the development of ovarian cancer via modulating FHL2 by sponging miR-195-5p
Authors: Kong Lijun , Zhang Chengyan 
Published: August 2020

Abstract
Background
Ovarian cancer (OC) is a huge burden on women’s lives. Recently, the implication of long non-coding RNAs (lncRNAs) in cancers, including OC, has aroused much attention. The objective of this study was to explore the role and functional mechanism of lncRNA distal-less homeobox 6 antisense 1 (DLX6-AS1) in OC.

Methods
The expression of DLX6-AS1, miR-195-5p, and four and a half LIM domains protein 2 (FHL2) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation, apoptosis, migration, and invasion were assessed by cell count kit 8 (CCK-8), flow cytometry and transwell assays, respectively. The protein levels of proliferating cell nuclear antigen (PCNA), cleaved-caspase-3 (C-caspase 3), N-cadherin, Vimentin, E-cadherin and FHL2 were quantified by western blot. The relationship between miR-195-5p and DLX6-AS1 or FHL2 was predicted by bioinformatics tool starBase and verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft tumor model was established to observe the role of DLX6-AS1 in vivo.

Results
DLX6-AS1 and FHL2 were up-regulated in OC tissues and cells, while miR-195-5p was down-regulated. DLX6-AS1 knockdown inhibited proliferation, migration, and invasion but induced apoptosis of OC cells. However, miR-195-5p inhibition reversed these effects. Overexpression of miR-195-5p also depleted proliferation, migration, and invasion but promoted apoptosis of OC cells, while FHL2 overexpression overturned these influences. DLX6-AS1 knockdown blocked tumor growth in vivo.

Conclusion
DLX6-AS1, as an oncogene in OC, accelerated tumor progression by up-regulating FHL2 via mediating miR-195-5p, suggesting that DLX6-AS1 was a hopeful target for the lncRNA-targeted therapy in OC.
The combination of Biochanin A and SB590885 potentiates the inhibition of tumour progression in hepatocellular carcinoma
Authors: Xiao Yi , Gong Qiang , Wang Wenhong , Liu Fang , Kong Qinghong , Pan Feng , Zhang Xiaoke , Yu Changyan , Hu Shanshan , Fan Fang , Li Sanhua , Liu Yun 
Published: August 2020

Abstract
Background
Hepatocellular carcinoma (HCC) is the most aggressive and frequently diagnosed malignancy of the liver. Despite aggressive therapy, life expectancy of many patients in these cases is extended by only a few months. Hepatocellular carcinoma (HCC) has a particularly poor prognosis and would greatly benefit from more effective therapies.

Methods
The CCK-8 assay and colony formation assays were used to test the cell proliferation and viability. The effects of combination Biochanin A and SB590885 on apoptosis and cell cycle arrest of HCC cells were analysed by flow cytometry. The expression of ERK MAPK and PI3K/AKT/mTOR signalling as well as apoptosis and cell cycle-related proteins in HCC cells were tested by western blotting. The HCC cell xenograft model was established to test the tumor proliferation. Serum and plasma were tested for liver and kidney safety markers (ALP, ALT, AST, total bilirubin, creatinine, urea nitrogen) by using SpectraMax i3X.

Results
The combination of natural product Biochanin A with the BRAF inhibitor SB590885 synergistically suppressed proliferation, and promoted cell cycle arrest and apoptosis in vitro. Furthermore, we demonstrated that the combination of Biochanin A and SB590885 led to increased impairment of proliferation and HCC tumour inhibition through disrupting of the ERK MAPK and the PI3K/AKT pathways in vitro. The volumes tumors and the weights of tumours were significantly reduced by the combination treatment compared to the control or single treatments in vivo. In addition, we found that there was no significant hepatorenal toxicity with the drug combination, as indicated by the hepatorenal toxicity test.

Conclusion
The results identify an effective combination therapy for the most aggressive form of HCC and provide the possibility of therapeutic improvement for patients with advanced HCC.
A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression
Authors: Luo Lingli , Wang Min , Li Xianping , Luo Can , Tan Shan , Yin Sheng , Liu Lei , Zhu Xiaolin 
Published: August 2020

Abstract
Background
Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a role in the development of cervical cancer (CC) and the exact mechanism of its role has not been elucidated.

Methods
Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of messenger RNA of ACTA2-AS1, miR-143-3p and SMAD3 in tumor tissues and cells. Additionally, SMAD3 protein expression by western blots in cells. Small interference RNA against ACTA2‐AS1 or SMAD3 and miR‐143‐3p mimic/inhibitor was designed and transfected into CC cell lines to investigate their correlations and potential impacts on cell function. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell cycle assay, transwell assay and flow cytometry analysis were performed to detect the specific effects on cell line proliferation, metastasis and apoptosis.

Results
ACTA2-AS1 was significantly increased in CC tissues and cells and miR‐143‐3p was down-regulated. Clinically, the higher expression of ACTA2-AS1 was significantly correlated with higher FIGO stage. Loss-of-function assay revealed that silencing of ACTA2-AS1 inhibited cell proliferation, colony formation, migration and promoted apoptosis in CC. Additionally, Pearson correlation analysis showed that the expression of ACTA2-AS1 and miR-143-3p were negatively correlated. Dual-luciferase reporter assay and further mechanistic experiments confirmed that ACTA2-AS1 could sponge and regulate the expression of miR-143-3p. Furthermore, SMAD3 was the target gene of miR-143-3p and ACTA2-AS1 could upregulate SMAD3 through acting as a competitive endogenous RNA (ceRNA) of miR-143-3p. Finally, rescue assay demonstrated that the ACTA2-AS1/miR-143-3p/SMAD3 axis played an important role in the proliferation, migration and apoptosis of CC cells.

Conclusions
In summary, our study revealed that ACTA2-AS1 upregulates SMAD3 by competitively binding miR-143-3p, thereby accelerating CC progression. The ACTA2-AS1/miR-143-3p/SMAD3 axis can play a crucial role in cervical carcinogenesis, providing new clues for the early diagnosis and treatment of CC.
Gravidity-dependent associations between interferon response and birth weight in placental malaria
Authors: Quanquin Natalie M. , Barres Lauren G. , Aliyari Saba R. , Day Nathan T. , Gerami Hoda , Fisher Susan J. , Kakuru Abel , Kamya Moses R. , Havlir Diane V. , Feeney Margaret , Dorsey Grant , Cheng Genhong , Gaw Stephanie L. 
Published: August 2020

Abstract
Background
Maternal malarial infection leads to poor perinatal outcomes, including low birth weight from preterm delivery and/or fetal growth restriction, particularly in primigravidas. In placental malaria, Plasmodium falciparum-infected red blood cells cause an inflammatory response that can interfere with maternal–fetal exchange, leading to poor growth. The type I interferon (IFN-I) pathway plays an immunomodulatory role in viral and bacterial infections, usually by suppressing inflammatory responses. However, its role in placental malaria is unknown. This study examines the cytokine responses in placental tissue from subsets of malaria-infected and uninfected women, and attempts to correlate them with particular birth outcomes.

Methods
40 whole placental biopsy samples were obtained from pregnant women at least 16 years of age recruited to a larger prospective chemoprevention trial against malaria. These were patients at Tororo District Hospital in Uganda, an area of high malaria endemicity where approximately 40% of women have evidence of malaria infection at delivery. They were regularly followed at a local clinic and monitored for fever, with blood smears performed then and at time of delivery to diagnose malaria infection. Placenta biopsies were taken for histological diagnosis of placental malaria, as well as quantitative PCR analysis of genes in the IFN-I pathway (IFN-β, IL-10 and MX-1). Parameters such as infant birth weight and gestational age were also recorded.

Results
Histological analysis revealed placental malaria in 18 samples, while 22 were found to be uninfected. RT-PCR analysis showed a four-fold increase in IFN-β and IL-10 expression in multigravidas with placental malaria when compared to gravidity-matched, uninfected controls. This effect was not observed in primigravidas. Interestingly, linear regression analysis showed a positive association between IFN-β levels and higher birth weights (β = 101.2 g per log2-fold increase in IFN-β expression, p = 0.042). This association was strongest in primigravidas with placental malaria (β = 339.0, p = 0.006).

Conclusions
These results demonstrate differential regulation of the IFN-I pathway in placental malaria according to gravidity, with the greatest anti-inflammatory response seen in multigravidas. The association between IFN-β levels and higher birth weight also suggests a protective role for IFN-I against fetal growth restriction in placental malaria.
Disability inclusiveness of government responses to COVID-19 in South America: a framework analysis study
Authors: Sakellariou Dikaios , Malfitano Ana Paula Serrata , Rotarou Elena S. 
Published: August 2020

Abstract
Background
Disabled people are particularly exposed to the risks of COVID-19, as well as to the measures taken to address it, and their impact. The aim of the study was to examine the disability-inclusiveness of government responses to COVID-19 in four South American Countries: Argentina, Brazil, Chile, and Peru.

Methods
We conducted documentary research, using framework analysis to analyse reports, legislation, decrees, and other official documents that communicated measures taken in response to the pandemic, published from February 1st until May 22nd, 2020. We included documents reporting measures that affected disabled people either directly (measures specifically designed for disabled people) or indirectly (measures for the general population). We developed an analytical framework based on recommendations for disability-inclusive response to COVID-19 published by the Economic Commission for Latin America and the Carribean, the World Health Organisation, and other international organisations.

Results
We analysed 72 documents. The findings highlight that while some positive measures were taken, the needs of disabled people were not fully considered. Several countries published recommendations for a disability-inclusive response to COVID-19, without ensuring their translation to practice. All countries took at least some steps to ensure access to financial support, health, and education for disabled people, but at the same time they also implemented policies that had a detrimental impact on disabled people. The populations that are most exposed to the impacts of COVID-19, including disabled people living in institutional care, were protected in several cases only by recommendations rather by legislation.

Conclusions
This study illustrates how the official government responses taken by four countries in the region – while positive, in several aspects – do not fully address the needs of disabled people, thus further disadvantaging them. In order to ensure response to COVID − 19 is disability inclusive, it is necessary to translate recommendations to practice, consider disabled people both in mainstream policy and in disability-specific measures, and focus on the long-term reconstruction phase.
Quercetin attenuates reduced uterine perfusion pressure -induced hypertension in pregnant rats through regulation of endothelin-1 and endothelin-1 type A receptor
Authors: Sun Xia , Zhang Shuping , Song Haitao 
Published: August 2020

Abstract
Background
Quercetin was reported to be crucial for a broad range of activities, including attenuating inflammation, platelet aggregation, capillary permeability, and lipid peroxidation. However, the effect of quercetin in hypertension during pregnancy, was not fully understood.

Methods
The model of hypertension in pregnancy was established in rats by reduced uterine perfusion pressure (RUPP). Quercetin was administrated by gavage. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using the CODA 6 BP system. Plasma concentrations of Endothelin-1 (ET-1), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF) were detected using enzyme-linked immunosorbent assay kits. The mRNA and protein levels of ET-1 and endothelin-1 type A receptor (ETAR) were determined by RT-PCR and Western blotting. The ETAR antagonist BQ-123 was performed by osmotic minipumps.

Results
In RUPP induced rats, quercetin treatment decreased SBP and DBP, fetal resorptions percentage, plasma ET-1 and sFlt-1 concentrations, ET-1 and ETAR levels, but increased fetal body weight and VEGF expression. BQ-123 administration attenuated SBP and DBP, suppressed fatal resorptions percentage, and increased fetal body weight of RUPP rats.

Conclusion
Quercetin attenuates RUPP induced hypertension in pregnant rats through the regulation of ET-1 and ETAR.
Spatial distribution of the “Mais Médicos (More Doctors) Program” and social vulnerability: an analysis of the Brazilian metropolitan regions
Authors: Oliveira Aimê , Barreto Jorge Otávio Maia , de Araújo Sidclei Queiroga , Santos Leonor Maria Pacheco 
Published: August 2020

Abstract
Background
The “Mais Médicos (More Doctors) Program” established in 2013 by the Brazilian Government aimed to reduce inequalities by means of an emergency provision of physicians, the improvement of medical care service in the Brazilian Unified Health System, and the expansion of medical education training in Brazil. In this context, equity should be considered when defining priorities and allocating resources. This study describes the distribution of physicians for the Program in five Brazilian metropolitan regions (MRs) and analyses whether the most vulnerable areas within each one of these regions had been prioritized in compliance with the legislation framework of the program.

Methods
This is a quantitative cross-sectional study. Official secondary data was analyzed to verify the relationship between the Index of Social Vulnerability, set up by the Institute of Applied Economic Research, and the physician allocation provided by the Program. The data were organized into categories and quintiles. For spatialization purposes, the QGIS 3.4 Madeira software was used.

Results
There are 2592 primary health care units, (in Portuguese, UBS), within the five MRs studied; 981 of these hosted at least one physician from the Program. In the Manaus, Recife, and the DF MRs, the 4th and 5th quintiles (the most vulnerable ones) hosted physicians in more significant proportions than the other quintiles, namely, 71.4%, 71.4%, and 52.2%, respectively, exceeding the national average (51.7%). It is worth mentioning that in the São Paulo MR, the units located in the most vulnerable quintiles (4th and 5th) also hosted physicians in proportions significantly higher than others (45.8%); however, this proportion did not reach 50%. There was no significant difference in the allocation of physicians in the Porto Alegre MR, indicating that there was no prioritization of the UBS according to vulnerability.

Conclusions
These results appoint to the enormous gaps of vulnerability existing both between the analyzed MRs and internally in each one of them. It emphasizes the need for criteria for the allocation of physicians so as not to increase inequities. It also highlights the importance of the continuity of the “Mais Médicos (More Doctors) Program” in the metropolitan regions, above all, in areas of extreme vulnerabilities. On the other hand, they contribute to the national debate about the importance of public policies regarding constitutional rights related to access to health care and the relevance of primary care and the “Mais Médicos (More Doctors) Program” for the reduction of disparities regarding access to health care, especially for the citizens who live in regions of greater vulnerability, whether it is inside or outside large metropolitan regions.
Therapeutic perspectives in food allergy
Authors: Marcucci Francesco , Isidori Chiara , Argentiero Alberto , Neglia Cosimo , Esposito Susanna 
Published: August 2020

Abstract
Background
In the last twenty years, several studies have been conducted in the search for new therapeutic strategies in patients with food allergy; in particular, after the failure of injection immunotherapy, three different routes of administration, oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT), have been tested. The aim of this manuscript is to review OIT, SLIT, and EPIT clinical trials on food allergies and to suggest advantages and limits of the different routes of immunotherapy administration.

Main body
Of the three different routes of immunotherapy used in the treatment of food allergy, OIT is, at present, the only one actually able to induce an increase in tolerance in the majority of patients. However, its use is affected by serious secondary effects, such as major abdominal symptoms and anaphylaxis. The combination with omalizumab reduces the percentage of serious side effects. There are not many studies with SLIT for food allergy, but they have nevertheless shown that it is possible to obtain an increase in tolerance; however, this increase is modest in comparison with that obtained by OIT. EPIT, performed through the diffusion of allergens on intact skin, is the most recent form of immunotherapy. Although there are many works on EPIT carried out in laboratory animals, only few clinical studies have been published in humans. EPIT, unlike OIT and SLIT, is not responsible for systemic secondary effects such as anaphylaxis and eosinophilic oesophagitis but only for local and mild effects in areas where the devices are applied. Moreover, EPIT is characterized by high patient adherence.

Conclusion
OIT seems to have a prevalent application in patients who do not report previous symptoms of systemic or gastroenteric anaphylaxis, while SLIT and EPIT, in particular, could be more preferentially used in patients with a risk of anaphylaxis.
Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury by inhibiting alveolar macrophage pyroptosis via the Keap1/Nrf2/HO-1 signaling pathway
Authors: Fei Lin , Jingyuan Xiao , Fangte Liang , Huijun Dai , Liu Ye , Ren Jing , Jinyuan Lin , Linghui Pan 
Published: August 2020

Abstract
Background
Lung ischemia–reperfusion injury (LIRI) is a complex pathophysiological process that can lead to poor patient outcomes. Inflammasome-dependent macrophage pyroptosis contributes to organ damage caused by ischemia/reperfusion injury. Oxidative stress and antioxidant enzymes also play an important role in LIRI. In this study, we conducted experiments to investigate whether and how preconditioning with rHMGB1 could ameliorate LIRI in a mouse model.

Methods
Adult male BALB/c mice were anesthetized, the left hilus pulmonis was clamped, and reperfusion was performed. rHMGB1 was administered via intraperitoneal injection before anesthesia, and brusatol was given intraperitoneally every other day before surgery. We measured pathohistological lung tissue damage, wet/dry mass ratios of pulmonary tissue, and levels of inflammatory mediators to assess the extent of lung injury. Alveolar macrophage pyroptosis was evaluated by measuring release of lactate dehydrogenase, caspase-1 expression was assessed using flow cytometry, and gasdermin-D expression was analyzed using immunofluorescent staining. Levels of oxidative stress markers and antioxidant enzymes were also analyzed.

Results
Preconditioning with rHMGB1 significantly ameliorated lung injury induced by ischemia–reperfusion, based on measurements of morphology, wet/dry mass ratios, as well as expression of IL-1β, IL-6, NF-κB, and HMGB1 in lung tissues. It also alleviated alveolar macrophage pyroptosis, reduced oxidative stress and restored the activity of antioxidant enzymes. These beneficial effects were mediated at least in part by the Keap1/Nrf2/HO-1 pathway, since they were reversed by the pathway inhibitor brusatol.

Conclusions
Preconditioning with rHMGB1 may protect against LIRI by suppressing alveolar macrophage pyroptosis. This appears to involve reduction of oxidative stress and promotion of antioxidant enzyme activity via the Keap1/Nrf2/HO-1 pathway.