bluuebunny/crossref_metadata_2025_split huggingface dataset:
Career mobility of maternal care providers in Mali: a mixed method study on midwives and obstetric nurses
Authors: Sidibé Cheick Sidya , Touré Ousmane , Codjia Laurence , Keïta Assa Sidibé , Broerse Jacqueline E. W. , Dieleman Marjolein 
Published: December 2019

Abstract
Background
An important strategy to reduce maternal and child mortality in Mali is to increase the number of deliveries assisted by qualified personnel in primary care facilities, especially in rural areas. However, placements and retention of healthcare professionals in rural areas are a major problem, not only in Mali but worldwide, and are a challenge to the health sector. The purpose of this study was to map the mobility of midwives and obstetric nurses during their work lives, in order to better understand their career paths and the role that working in rural areas plays. This article contributes to the understanding of career mobility as a determinant of the retention of rural health professionals.

Methods
A mixed method study was conducted on 2005, 2010, and 2015 cohorts of midwives and obstetric nurses. The cohorts have been defined by their year of graduation.
Quantitative data were collected from 268 midwives and obstetric nurses through questionnaires. Qualitative data had been gathered through semi-structured interviews from 25 midwives and stakeholders. A content analysis was conducted for the qualitative data.

Results
Unemployment rate was high among the respondents: 39.4% for midwives and 59.4% for obstetric nurses. Most of these unemployed nurses and midwives are working, but unpaid. About 80% of the employed midwives were working in urban facilities compared to 64.52% for obstetric nurses. Midwives were employed in community health centers (CSCom) (43%), referral health centers (CSRef) (20%), and private clinics and non-governmental organizations (NGO) (15%). The majority of midwives and obstetric nurses were working in the public sector (75.35%) and as civil servants (65.5%). The employment status of midwives and obstetric nurses evolved from private to public sector, from rural to urban areas, and from volunteer/unpaid to civil servants through recruitment competitions. Qualitative data supported the finding that midwives and obstetric nurses prefer to work as civil servant and preferably in urban areas and CSRef.

Conclusion
The current mobility pattern of midwives and obstetric nurses that brings them from rural to urban areas and towards a civil servant status in CSRef shows that it is not likely to increase their numbers in the short term in places where qualified midwives are most needed.
Analysing how physical activity competes: a cross-disciplinary application of the Duplication of Behaviour Law
Authors: Wilson Amy L. , Nguyen Cathy , Bogomolova Svetlana , Sharp Byron , Olds Timothy 
Published: December 2019

Abstract
Background
Despite the ongoing promotion of physical activity, the rates of physical inactivity remain high. Drawing on established methods of analysing consumer behaviour, this study seeks to understand how physical activity competes for finite time in a day – how Exercise and Sport compete with other everyday behaviours, and how engagement in physical activity is shared across Exercise and Sport activities. As targeted efforts are common in physical activity intervention and promotion, the existence of segmentation is also explored.

Methods
Time-use recall data (n = 2307 adults) is analysed using the Duplication of Behaviour Law, and tested against expected values, to document what proportion of the population that engage in one activity, also engage in another competing activity. Additionally, a Mean Absolute Deviation approach is used to test for segmentation.

Results
The Duplication of Behaviour Law is evident for everyday activities, and Exercise and Sport activities – all activities ‘compete’ with each other, and the prevalence of the competing activity determines the extent of competition. However, some activities compete more or less than expected, suggesting the combinations of activities that should be used or avoided in promotion efforts. Competition between everyday activities is predictable, and there are no specific activities that are sacrificed to engage in Exercise and Sport. How people share their physical activity across different Exercise and Sport activities is less predictable – Males and younger people (under 20 years) are more likely to engage in Exercise and Sport, and those who engage in Exercise and Sport are slightly more likely to Work and Study. High competition between Team Sports and Non-Team Sports suggests strong preferences for sports of different varieties. Finally, gender and age-based segmentation does not exist for Exercise and Sport relative to other everyday activities; however, segmentation does exist for Team Sports, Games, Active Play and Dance.

Conclusions
The Duplication of Behaviour Law demonstrates that population-level patterns of behaviour can yield insight into the competition between different activities, and how engagement in physical activity is shared across different Exercise and Sport activities. Such insights can be used to describe and predict physical activity behaviour and may be used to inform and evaluate promotion and intervention.
Proteomic analysis of cerebrospinal fluid extracellular vesicles reveals synaptic injury, inflammation, and stress response markers in HIV patients with cognitive impairment
Authors: Guha Debjani , Lorenz David R. , Misra Vikas , Chettimada Sukrutha , Morgello Susan , Gabuzda Dana 
Published: December 2019

AbstractBackgroundExtracellular vesicles (EVs) are nano-sized particles present in most body fluids including cerebrospinal fluid (CSF). Little is known about CSF EV proteins in HIV+ individuals. Here, we characterize the CSF EV proteome in HIV+ subjects and its relationship to neuroinflammation, stress responses, and HIV-associated neurocognitive disorders (HAND).MethodsCSF EVs isolated from 20 HIV+ subjects with (n = 10) or without (n = 10) cognitive impairment were characterized by electron microscopy, nanoparticle tracking analysis, immunoblotting, and untargeted LC/MS/MS mass spectrometry. Functional annotation was performed by gene ontology (GO) mapping and expression annotation using Biobase Transfac and PANTHER software. Cultured astrocytic U87 cells were treated with hydrogen peroxide for 4 h to induce oxidative stress and EVs isolated by ultracentrifugation. Selected markers of astrocytes (GFAP, GLUL), inflammation (CRP), and stress responses (PRDX2, PARK7, HSP70) were evaluated in EVs released by U87 cells following induction of oxidative stress and in CSF EVs from HIV+ patients by immunoblotting.ResultsMass spectrometry identified 2727 and 1626 proteins in EV fractions and EV-depleted CSF samples, respectively. CSF EV fractions were enriched with exosomal markers including Alix, syntenin, tetraspanins, and heat-shock proteins and a subset of neuronal, astrocyte, oligodendrocyte, and choroid plexus markers, in comparison to EV-depleted CSF. Proteins related to synapses, immune/inflammatory responses, stress responses, metabolic processes, mitochondrial functions, and blood-brain barrier were also identified in CSF EV fractions by GO mapping. HAND subjects had higher abundance of CSF EVs and proteins mapping to GO terms for synapses, glial cells, inflammation, and stress responses compared to those without HAND. GFAP, GLUL, CRP, PRDX2, PARK7, and HSP70 were confirmed by immunoblotting of CSF EVs from subjects with HAND and were also detected in EVs released by U87 cells under oxidative stress.ConclusionsThese findings suggest that CSF EVs derived from neurons, glial cells, and choroid plexus carry synaptic, immune/inflammation-related, and stress response proteins in HIV+ individuals with cognitive impairment, representing a valuable source for biomarker discovery.
The pentose phosphate pathway regulates chronic neuroinflammation and dopaminergic neurodegeneration
Authors: Tu Dezhen , Gao Yun , Yang Ru , Guan Tian , Hong Jau-Shyong , Gao Hui-Ming 
Published: December 2019

Abstract
Background
Metabolic dysfunction and neuroinflammation are increasingly implicated in Parkinson’s disease (PD). The pentose phosphate pathway (PPP, a metabolic pathway parallel to glycolysis) converts glucose-6-phosphate into pentoses and generates ribose-5-phosphate and NADPH thereby governing anabolic biosynthesis and redox homeostasis. Brains and immune cells display high activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP. A postmortem study reveals dysregulation of G6PD enzyme in brains of PD patients. However, spatial and temporal changes in activity/expression of G6PD in PD remain undetermined. More importantly, it is unclear how dysfunction of G6PD and the PPP affects neuroinflammation and neurodegeneration in PD.

Methods
We examined expression/activity of G6PD and its association with microglial activation and dopaminergic neurodegeneration in multiple chronic PD models generated by an intranigral/intraperitoneal injection of LPS, daily subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 6 days, or transgenic expression of A53T α-synuclein. Primary microglia were transfected with G6PD siRNAs and treated with lipopolysaccharide (LPS) to examine effects of G6PD knockdown on microglial activation and death of co-cultured neurons. LPS alone or with G6PD inhibitor(s) was administrated to mouse substantia nigra or midbrain neuron-glia cultures. While histological and biochemical analyses were conducted to examine microglial activation and dopaminergic neurodegeneration in vitro and in vivo, rotarod behavior test was performed to evaluate locomotor impairment in mice.

Results
Expression and activity of G6PD were elevated in LPS-treated midbrain neuron-glia cultures (an in vitro PD model) and the substantia nigra of four in vivo PD models. Such elevation was positively associated with microglial activation and dopaminergic neurodegeneration. Furthermore, inhibition of G6PD by 6-aminonicotinamide and dehydroepiandrosterone and knockdown of microglial G6PD attenuated LPS-elicited chronic dopaminergic neurodegeneration. Mechanistically, microglia with elevated G6PD activity/expression produced excessive NADPH and provided abundant substrate to over-activated NADPH oxidase (NOX2) leading to production of excessive reactive oxygen species (ROS). Knockdown and inhibition of G6PD ameliorated LPS-triggered production of ROS and activation of NF-кB thereby dampening microglial activation.

Conclusions
Our findings indicated that G6PD-mediated PPP dysfunction and neuroinflammation exacerbated each other mediating chronic dopaminergic neurodegeneration and locomotor impairment. Insight into metabolic-inflammatory interface suggests that G6PD and NOX2 are potential therapeutic targets for PD.
Response of membrane tension to gravity in an approximate cell model
Authors: Wang Lili , Chen Weiyi , Guo Hongmei , Qian Airong 
Published: December 2019

Abstract
Background
Gravity, especially hypergravity, can affect the morphology of membranes, and further influence most biological processes. Since vesicle structures are relatively simple, the vesicle can be treated as a vital model to study the mechanical properties of membranes in most cases. Basic research on membrane tension has become a vital research topic in cellular biomechanics.

Methods
In this study, a new vesicle model is proposed to quantitatively investigate the response of membrane tension to gravity. In the model, the aqueous lumen inside the vesicle is represented by water, and the vesicle membrane is simplified as a closed, thin, linear elastic shell. Then, the corresponding static equilibrium differential equations of membrane tension are established, and the analytical expression is obtained by the semi-inverse method. The model parameters of the equations are accurately obtained by fitting the reported data, and the values calculated by the model agree well with the reported results.

Results
The results are as follows: First, both the pseudo-ellipsoidal cap and the pseudo-spherical cap can be used to describe the deformed vesicle model; however, the former can better represent the deformation of the vesicle model because the variance of the pseudo-ellipsoidal cap is smaller. Second, the value of membrane tension is no longer a constant for both models. Interestingly, it varies with the vesicle height under the action of gravity. The closer it is to the substrate, the greater the membrane tension. Finally, the inclination between the tangent and the radial lines at a certain point is nearly proportional to the radius of the cross section in both models.

Conclusion
These findings may be helpful to study the vesicle model spreading more accurately by taking into account the influence of gravity because it could affect the distribution of membrane tension. Furthermore, it may also provide some guidance for cell spreading and may have some implications for membrane tension-related mechanobiology studies, especially in the hypergravity conditions.
Low rates of prior HIV testing among HIV-positive adults accessing outpatient services in Eswatini
Authors: Nuwagaba-Biribonwoha Harriet , Wu Yingfeng , Gachuhi Averie Baird , McNairy Margaret L. , Madau Veli , Lamb Mathew , Mazibuko Sikhathele , Mnisi Zandile , Burke Sean , Philip Neena , Sahabo Ruben , El Sadr Wafaa M. 
Published: December 2019

AbstractPrior HIV testing and awareness of HIV-positive status were assessed among HIV-positive adults at 20 clinics in Eswatini. Of 2196 HIV-positive adults, 1183 (53.8%) reported no prior HIV testing, and 1948 (88.7%) were unaware of their HIV-positive status. Males [adjusted odds ratio, AOR, (95% confidence interval): 0.7 (0.5–0.9)], youth 18–25 years [AOR 0.6 (0.4–0.95)], adults ≥ 50 years [AOR 0.5 (0.3–0.9)], those needing family support [AOR 0.6 (0.5–0.8)], and those living ≥ 45 min from clinic [AOR 0.5 (0.4–0.8)] were less likely to know their HIV-positive status. More HIV testing is needed to achieve 95-95-95 targets, with targeted strategies for those less likely to test for HIV.
A second puncture and injection technique for treating osteoporotic vertebral compression fractures
Authors: Zhang Zhaofei , Jiao Feng , Huang He , Feng Yonghui , Xie Chunliang , Liu Donghua , Qin Fengwei , Zhang Sineng , Wu Peiyu , Tan Weiguang , Tang Wang 
Published: December 2019

Abstract
Objective
To evaluate the clinical effect of the second puncture and injection technique during a percutaneous vertebroplasty (PVP) procedure.

Methods
Patients treated with a second puncture and injection (group A) or a single puncture and injection (group B) during PVP at our institution during 2010–2017 were reviewed. Vertebral height loss, visual analogue scale (VAS) score, Oswestry disability index (ODI), adjacent vertebral fractures, and cement leakage were compared between the groups.

Results
A total of 193 patients were enrolled (86 cases in group A, 107 cases in group B). The follow-up period was 15.64 (12–20) months. The loss of anterior (group A 0.01 ± 0.03; group B 0.14 ± 0.17) and middle (group A 0.13 ± 0.12; group B 0.16 ± 0.11) vertebral height in group B was significantly higher than that in group A (P < 0.05). The VAS score and ODI were also significantly higher in group B than in group A at the final follow-up; the VAS score and ODI in group B were 1.65 ± 0.70 and 14.50 ± 4.16, respectively, and those in group A were 1.00 ± 0.74 and 12.81 ± 4.02, respectively (P < 0.05). Three patients in group A and two in group B experienced adjacent vertebral fractures. Regarding mild, moderate, and severe cement leakage, there were 25 (29%), 5 (5%), and 0 cases, respectively, in group A and 28 (26%), 3 (2.8%), and 1 (0.009%) case, respectively, in group B (P > 0.05).

Conclusions
The second puncture and injection technique may effectively increase the dispersion of cement, thus preventing recompression of the cemented vertebral body, and it does not increase the risk of cement leakage or adjacent vertebral fracture.
Evolutionarily novel genes are expressed in transgenic fish tumors and their orthologs are involved in development of progressive traits in humans
Authors: Matyunina E. A. , Emelyanov A. V. , Kurbatova T. V. , Makashov A. A. , Mizgirev I. V. , Kozlov A. P. 
Published: December 2019

Abstract
Earlier we suggested a new hypothesis of the possible evolutionary role of hereditary tumors (Kozlov, Evolution by tumor Neofunctionalization, 2014), and described a new class of genes – tumor specifically expressed, evolutionarily novel (TSEEN) genes - that are predicted by this hypothesis (Kozlov, Infect Agents Cancer 11:34, 2016). In this paper we studied evolutionarily novel genes expressed in fish tumors after regression, as a model of evolving organs. As evolutionarily novel genes may not yet have organismal functions, we studied the acquisition of new gene functions by comparing fish evolutionarily novel genes with their human orthologs. We found that many genes involved in development of progressive traits in humans (lung, mammary gland, placenta, ventricular septum, etc.) originated in fish and are expressed in fish tumors and tumors after regression. These findings support a possible evolutionary role of hereditary tumors, and in particular the hypothesis of evolution by tumor neofunctionalization.

Research highlights
Earlier we described a new class of genes that are tumor-specifically expressed and evolutionarily novel (TSEEN). As the functions of TSEEN genes are often uncertain, we decided to study TSEEN genes of fishes so that we could trace the appearance of their new functions in higher vertebrates. We found that many human genes which are involved in development of progressive traits (placenta development, mammary gland and lung development etc.,) originated in fishes and are expressed in fish tumors.
Simultaneously inactivating Src and AKT by saracatinib/capivasertib co-delivery nanoparticles to improve the efficacy of anti-Src therapy in head and neck squamous cell carcinoma
Authors: Lang Liwei , Shay Chloe , Zhao Xiangdong , Xiong Yuanping , Wang Xuli , Teng Yong 
Published: December 2019

Abstract
Background
Src, an oncoprotein that drives progression of head and neck squamous cell carcinoma (HNSCC), is commonly hyperactivated in this disease. Unfortunately, the clinical benefit of targeting Src is significantly dampened in HNSCC patients, because the cytotoxic effects of anti-Src therapy and tumor resistance to it are less predictable. Thus, understanding the mechanism of tumor resistance to Src inhibition and seeking a way to overcome it are warranted.

Methods
Dual drug-loaded nanoparticles (NPs) were developed to co-deliver Src inhibitor saracatinib (AZD0530) and AKT inhibitor capivasertib (AZD5363) into the same population of tumor cells. An orthotopic tongue tumor model was generated to evaluate the in vivo therapeutic effects. Cell growth was determined by CellTiter-Glo® Luminescent Cell Viability Kit, colony formation, and 3D culture, and tumor growth was determined by bioluminescence and tumor size. The molecular changes induced by the treatments were assessed by Western blotting and immunohistochemistry.

Results
Capivasertib inactivated the AKT-S6 signaling and re-sensitized saracatinib-resistant HNSCC cells to saracatinib. Combination of capivasertib with saracatinib suppressed HNSCC growth more efficiently than either drug alone. Cathepsin B-sensitive NPs for co-delivering saracatinib and capivasertib significantly improved the efficacy of tumor repression without increasing side effects, which were due to highly specific tumor-targeting drug delivery system and synergistic anticancer effects by co-inactivation of AKT and Src in HNSCC cells.

Conclusions
Addition of AKT blockade improves anti-HNSCC efficacy of anti-Src therapy, and co-delivery of capivasertib and saracatinib by tumor-targeting NPs has the potential to achieve better treatment outcomes than the free drug combination.
NOS1 inhibits the interferon response of cancer cells by S-nitrosylation of HDAC2
Authors: Xu Pengfei , Ye Shuangyan , Li Keyi , Huang Mengqiu , Wang Qianli , Zeng Sisi , Chen Xi , Gao Wenwen , Chen Jianping , Zhang Qianbing , Zhong Zhuo , Lin Ying , Rong Zhili , Xu Yang , Hao Bingtao , Peng Anghui , Ouyang Manzhao , Liu Qiuzhen 
Published: December 2019

AbstractBackgroundThe dysfunction of type I interferon (IFN) signaling is an important mechanism of immune escape and metastasis in tumors. Increased NOS1 expression has been detected in melanoma, which correlated with dysfunctional IFN signaling and poor response to immunotherapy, but the specific mechanism has not been determined. In this study, we investigated the regulation of NOS1 on the interferon response and clarified the relevant molecular mechanisms.MethodsAfter stable transfection of A375 cells with NOS1 expression plasmids, the transcription and expression of IFNα-stimulated genes (ISGs) were assessed using pISRE luciferase reporter gene analysis, RT-PCR, and western blotting, respectively. The effect of NOS1 on lung metastasis was assessed in melanoma mouse models. A biotin-switch assay was performed to detect the S-nitrosylation of HDAC2 by NOS1. ChIP-qPCR was conducted to measure the binding of HDAC2, H4K16ac, H4K5ac, H3ac, and RNA polymerase II in the promoters of ISGs after IFNα stimulation. This effect was further evaluated by altering the expression level of HDAC2 or by transfecting the HDAC2-C262A/C274A site mutant plasmids into cells. The coimmunoprecipitation assay was performed to detect the interaction of HDAC2 with STAT1 and STAT2. Loss-of-function and gain-of-function approaches were used to examine the effect of HDAC2-C262A/C274A on lung metastasis. Tumor infiltrating lymphocytes were analyzed by flow cytometry.ResultsHDAC2 is recruited to the promoter of ISGs and deacetylates H4K16 for the optimal expression of ISGs in response to IFNα treatment. Overexpression of NOS1 in melanoma cells decreases IFNα-responsiveness and induces the S-nitrosylation of HDAC2-C262/C274. This modification decreases the binding of HDAC2 with STAT1, thereby reducing the recruitment of HDAC2 to the ISG promoter and the deacetylation of H4K16. Moreover, expression of a mutant form of HDAC2, which cannot be nitrosylated, reverses the inhibition of ISG expression by NOS1 in vitro and decreases NOS1-induced lung metastasis and inhibition of tumor infiltrating lymphocytes in a melanoma mouse model.ConclusionsThis study provides evidence that NOS1 induces dysfunctional IFN signaling to promote lung metastasis in melanoma, highlighting NOS1-induced S-nitrosylation of HDAC2 in the regulation of IFN signaling via histone modification.