bluuebunny/crossref_metadata_2025_split huggingface dataset:
The magnitude of neonatal mortality and its predictors in Ethiopia: a systematic review and meta-analysis
Authors: Asmare Yared , Shibabaw Wondimeneh , Yirga Tadesse , Dargie Abate , Hab-tewold Tesfa Dejenie 
Published: May 2019

AbstractsBackgroundAlthough neonatal death is a global burden, it is the highest in Sub Saharan Africa countries such as Ethiopia. This study was aimed to provide pooled national prevalence and predictors of neonatal mortality in Ethiopia.ObjectiveTo assess the pooled prevalence and predictors of neonatal mortality in Ethiopia.Search Strategyglobal databases were systematically explored. Systematically searched using the following databases: Boolean operator, Cochrane library, PubMed, EMBASE, HINARI, and Google Scholar. Selection, screening, reviewing and data extraction was done by two reviewers independently using Microsoft excel spread sheet. The modified Newcastle–Ottawa Scale (NOS) and the Joanna Briggs Institute Prevalence Critical Appraisal tools were used to assess the quality of evidenceSelection criteriaAll studies conducted in Ethiopia and reporting the prevalence and predictors of neonatal mortality were includedData Collection and AnalysisData were extracted using a Microsoft Excel spreadsheet software and imported into STATA Version 14 s for further analysis. The pooled effect size with 95% confidence interval of neonatal mortality rate was determined using a weighted inverse variance random-effects model. Publication bias was checked using funnel plots, Egger’s and bagger’s regression test. Heterogeneity also checked by Higgins’s method. A random effects meta-analysis model was computed to estimate the pooled effect size (i.e. prevalence and odds ratio). Moreover, subgroup analysis based on region, sample size and study design were done.ResultsAfter reviewing 88 studies, 12 studies fulfilled the inclusion criteria and were included in the meta-analysis. The pooled national prevalence of neonatal mortality in Ethiopia was 16.3% (95% CI: 11.9, 20.7, I2 =88.6%). The subgroup analysis indicated that the highest prevalence was observed in Amhara region with a prevalence of 20.3% (95% CI: 9.6, 31.1, I2 =98.8) followed by Oromia, 18.8% (95%CI: 11.9,49.4, I2=99.5). Gestational age AOR,1.14 (95% CI: 0.94, 1.3), neonatal sepsis (OR:1.2(95% CI: 0.8, 1.5), respiratory distros (OR: 1.2(95% CI: 0.8, 1.5) and place of residency (OR:1.93 (95% CI:1.1,2.7) were the most important predictor.Conclusionsneonatal mortality in Ethiopia was significantly decreased than the national report. There was evidence that neonatal sepsis, gestational age, respiratory distress were the significant predictors. We strongly recommended that health care workers should give a priority for the identified predictors.
Correlation of IL-17 level in gingival crevicular fluid of orthodontically induced inflammatory root resorption
Authors: Zhou Hua , Liang Xiao , Liu Aipeng , Nong Dongmei , Qin Yaqing , Chen Lianxiang , Kang Na 
Published: May 2019

ABSTRACTObjectiveTo investigate IL-17 expression in orthodontic tooth movement and orthodontic nickel-titanium spring-induced inflammatory root resorption.MethodsOrthodontic nickel-titanium springs were ligated between the bilateral maxillary first molar and the incisors of the rats to establish a rat model of orthodontic tooth movement (OTM), each rat was subjected to two cycles of near-GCF and peripheral blood serum collection before and after force application, and IL-17 levels in GCF and serum were measured quantitatively by ELISA. Morphological changes in periodontal tissue and root of the experimental dentine were evaluated by hematoxylin and eosin staining. Tartrate-resistant acid phosphatase staining and immunohistochemistry were used to determine the osteoclast number and expression changes in IL-17, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) in the periodontal tissues, respectively, on the pressure side of the experimental tooth.ResultsIL-17 was detected in GCF and serum. The pressure area exhibited alveolar bone resorption only at a force of 20g. Additionally, a force of 60g led to root resorption. IL-17, RANKL/OPG and osteoclast number showed similar trend that all expressed increasing high level at early stage, then significantly decreased from days 5 to 14, and revealed 60g group the highest expression level while 0g group the lowest.The change in the IL-17 level in the GCF was strongly correlated with IL-17 and RANKL/OPG expression levels and osteoclast numbers in the periodontal ligament.ConclusionsThe results indicated that measuring IL-17 level in GCF can predict the risk of alveolar bone and root resorption induced by orthodontic treatment.
Integration of eQTL and Parkinson’s disease GWAS data implicates 11 disease genes
Authors: Kia Demis A. , Zhang David , Guelfi Sebastian , Manzoni Claudia , Hubbard Leon ,   United Kingdom Brain Expression Consortium (UKBEC),   International Parkinson’s Disease Genomics Consortium (IPDGC), Reynolds Regina H. , Botía Juan , Ryten Mina , Ferrari Raffaele , Lewis Patrick A. , Williams Nigel , Trabzuni Daniah , Hardy John , Wood Nicholas W. 
Published: May 2019

AbstractSubstantial genome-wide association study (GWAS) work in Parkinson’s disease (PD) has led to an increasing number of loci shown reliably and robustly to be associated with the increased risk of the disease. Prioritising causative genes and pathways from these studies has proven problematic. Here, we present a comprehensive analysis of PD GWAS data with expression and methylation quantitative trait loci (eQTL/mQTL) using Colocalisation analysis (Coloc) and transcriptome-wide association analysis (TWAS) to uncover putative gene expression and splicing mechanisms driving PD GWAS signals. Candidate genes were further characterised by determining cell-type specificity, weighted gene co-expression (WGNCA) and protein-protein interaction (PPI) networks.Gene-level analysis of expression revealed 5 genes (WDR6, CD38, GPNMB, RAB29, TMEM163) that replicated using both Coloc and TWAS analyses in both GTEx and Braineac expression datasets. A further 6 genes (ZRANB3, PCGF3, NEK1, NUPL2, GALC, CTSB) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell-types compared to neurons. The WGNCA analysis showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes related with protein ubiquitination (protein ubiquitination (p=7.47e-10) and ubiquitin-dependent protein catabolic process (p = 2.57e-17) in nucleus accumbens, caudate and putamen, while TMEM163 and ZRANB3 were both important in modules indicating regulation of signalling (p=1.33e-65] and cell communication (p=7.55e-35) in the frontal cortex and caudate respectively. PPI analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known Mendelian PD and parkinsonism proteins than would be expected by chance. The proteins core proteins this network were enriched for regulation of the ERBB receptor tyrosine protein kinase signalling pathways.Together, these results point to a number of candidate genes and pathways that are driving the associations observed in PD GWAS studies.
Bdellovibrio and Like Organisms are Predictors of Microbiome Diversity in distinct Host Groups
Authors: Johnke Julia , Fraune Sebastian , Bosch Thomas , Hentschel Ute , Schulenburg Hinrich 
Published: May 2019

AbstractBiodiversity is generally believed to be a main determinant of ecosystem functioning. This principle also applies to the microbiome and could consequently contribute to host health. According to ecological theory, communities are shaped by top predators whose direct and indirect interactions with community members cause stability and diversity. Bdellovibrio and like organisms (BALOs) are a neglected group of predatory bacteria that feed on Gram-negative bacteria and can thereby influence microbiome composition. We asked whether BALOs can predict biodiversity levels in microbiomes from distinct host groups and environments. We demonstrate that genetic signatures of BALOs are commonly found within the 16S rRNA reads from diverse host taxa. In many cases, their presence, abundance, and especially richness are positively correlated with overall microbiome diversity. Our findings suggest that BALOs can act as drivers of microbial alpha-diversity and should therefore be considered as candidates for the restoration of microbiomes and the prevention of dysbiosis.
A cellular and spatial map of the choroid plexus across brain ventricles and ages
Authors: Dani Neil , Herbst Rebecca H. , Habib Naomi , Head Joshua , Dionne Danielle , Nguyen Lan , McCabe Cristin , Cui Jin , Shipley Frederick B. , Jang Ahram , Rodman Christopher , Riesenfeld Samantha J. , Zhang Feng , Rozenblatt-Rosen Orit , Regev Aviv , Lehtinen Maria K. 
Published: May 2019

AbstractThe choroid plexus (ChP), located in each brain ventricle, produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier, but is under-characterized. Here, we combine single cell RNA-Seq and spatial mapping of RNA and proteins to construct an atlas of each ChP in the developing and adult mouse brain. Each ChP comprises of epithelial, endothelial, mesenchymal, immune, neuronal, and glial cells, with distinct subtypes, differentiation states and anatomical locations. Epithelial, fibroblast, and macrophage populations had ventricle-specific, regionalized gene expression programs across the developing brain. Key cell types are retained in adult, with loss of developmental signatures and maturation of ventricle-specific regionalization in the epithelial cells. Expression of cognate ligand-receptor pairs across cell subtypes suggests substantial cell-cell interactions within the ChP. Our atlas sheds new light on the development and function of the ChP brain barrier system, and will facilitate future studies on its role in brain development, homeostasis and disease.
Impaired tumor death receptor signaling drives resistance to CAR T cell therapy
Authors: Singh Nathan , Shestova Olga , Ravikumar Pranali , Hayer Katharina E. , Hong Seok Jae , Orlando Elena J. , Mueller Karen Thudium , Good Charly R. , Berger Shelley L. , Shalem Ophir , Weitzman Matthew D. , Grupp Stephan A. , June Carl H. , Gill Saar , Ruella Marco 
Published: May 2019

AbstractCellular immunotherapy using T cells engineered to express chimeric antigen receptors targeting CD19 (CART19) leads to long-term remission in patients with B-cell malignancies1–5. Unfortunately, a significant fraction of patients demonstrate primary resistance to CART19 or experience relapse after achieving remission. Beyond loss of target antigen, the molecular pathways governing CART19 failure are unknown. Here we demonstrate that death receptors, cell surface signaling molecules that induce target cell apoptosis, are key mediators of leukemic resistance and CART19 failure. Using a functional CRISPR/Cas9-based genome-wide knockout screen6 in B-cell acute lymphoblastic leukemia (ALL), we identified the death receptor signaling pathway as a central regulator of sensitivity to CART19-induced cell death. In the absence of the pro-apoptotic death receptor signaling molecules BID or FADD, ALL cells were resistant to CART19 cytotoxicity, resulting in rapid disease progression in mice. We found that this initial resistance to cytotoxicity led to persistence of tumor cells, which drove the development of T cell dysfunction that further compromised anti-tumor immunity and permitted tumor outgrowth. We validated these findings using clinical samples collected from patients with ALL treated with CD19-targeted CAR T cells and found that expression of pro-apoptotic death receptor pathway genes in pre-treatment tumor samples correlated with CAR T cell expansion and persistence, as well as patient response and overall survival. Our findings indicate that tumor-intrinsic death receptor signaling directly contributes to CAR T cell failure.
Fat SIRAH: Coarse-grained phospholipids to explore membrane-protein dynamics
Authors: Barrera Exequiel E. , Machado Matías R. , Pantano Sergio 
Published: May 2019

ABSTRACTTne capability to handle highly heterogeneous molecular assemblies in a consistent manner is among the greatest challenges faced when deriving simulation parameters. This is particularly the case for coarse-grained simulations in which chemical functional groups are lumped into effective interaction centers for which transferability between different chemical environments is not guaranteed. Here we introduce the parameterization of a set of CG phospholipids compatible with the latest version of the SIRAH force field for proteins. The newly introduced lipid species include different acylic chain lengths, partial unsaturation, as well as polar and acidic head groups that show a very good reproduction of structural membrane determinants, as areas per lipid, thickness, order parameter, etc., and their dependence with temperature. Simulation of membrane proteins showed unprecedented accuracy in the unbiased description of the thickness-dependent membrane-protein orientation in systems where this information is experimentally available (namely, the SarcoEndoplasmic Reticulum Calcium –SERCA-pump and its regulator Phospholamban). The interactions that lead to this faithful reproduction can be traced down to single amino acid-lipid interaction level and show full agreement with biochemical data present in the literature. Finally, the present parameterization is implemented in the GROMACS and AMBER simulation packages facilitating its use to a wide portion of the Biocomputing community.
Circadian regulation of light-evoked attraction/avoidance in day- vs. night-biting mosquitoes
Authors: Baik Lisa Soyeon , Nave Ceazar , Au David D. , Guda Tom , Chevez Joshua A. , Ray Anandasankar , Holmes Todd C. 
Published: May 2019

AbstractMosquitoes pose widespread threats to humans and other animals as disease vectors. Day- vs. night-biting mosquitoes occupy distinct time-of-day niches and exhibit very different innate temporal attraction/avoidance behavioral responses to light, yet little is known about their circuit or molecular mechanisms. Day-biting diurnal mosquitoesAedes aegyptiare attracted to light during the day regardless of spectra. In contrast, night-biting nocturnal mosquitoesAnopheles coluzziiavoid short, but not long wavelength light. Attraction/avoidance behavioral responses to light in both species change with time-of-day and show distinct sex and circuit differences. The basis of diurnal versus nocturnal behavior is driven by clock timing, which cycle anti-phase between day-biting versus night-biting mosquito species. Disruption of the circadian molecular clock severely interferes with light-evoked attraction/avoidance behavior in mosquitoes. In summary, attraction/avoidance mosquito behaviors are circadian and light regulated, which may be applied towards species specific control of harmful mosquitoes.
Identification of the pathway of Rhodoquinone biosynthesis inC.elegans
Authors: Del Borrello Samantha , Lautens Margot , Dolan Kathleen , Tan June H. , Spensley Mark A. , Caudy Amy A. , Fraser Andrew G. 
Published: May 2019

AbstractParasitic helminths infect over a billion humans. To survive in the low oxygen environment of their hosts, these parasites use unusual anaerobic metabolism. This requires Rhodoquinone (RQ), an electron carrier that is made by very few animal species — crucially it is not present in any parasitic hosts. RQ synthesis is thus an ideal target for anthelmintics but little is known about how RQ is made and no drugs are known to block RQ synthesis.C.elegansmakes RQ and can use RQ-dependent metabolic pathways — here, we useC.elegansgenetics to identify the pathway for RQ synthesis and show thatC.elegansrequires RQ for survival in hypoxic conditions. Finally, we establish a robust assay for drugs that block RQ-dependent metabolism. This study identifies for the first time how RQ is made in any animal and establishes a novel assay that can drive the development of a new class of anthelmintic drugs.
Transformation and Integration of Microenvironment Microarray Data Improves Discovery of Latent Effects
Authors: Hunt Gregory J. , Dane Mark A. , Korkola James E. , Heiser Laura M. , Gagnon-Bartsch Johann A. 
Published: May 2019

SummaryThe immediate physical and bio-chemical surroundings of a cell, the cellular microenvironment, is an important component of many fundamental cell and tissue level processes and is implicated in many diseases and dysfunctions. Thus understanding the interaction of cells with their microenvironment can further both basic research and aid the discovery of therapeutic agents. To study perturbations of cellular microenvironments a novel image-based cell-profiling technology called the microenvironment microarray (MEMA) has been recently employed. In this paper we explore the effect of preprocessing transformations for MEMA data on the discovery of biological and technical latent effects. We find that Gaussianizing the data and carefully removing outliers can enhance discovery of important biological effects. In particular, these transformations help reveal a relationship between cell morphological features and the extra-cellular-matrix protein THBS1 in MCF10A breast tissue. More broadly, MEMAs are part of a recent and wide-spread adoption of image-based cell-profiling technologies in the quantification of phenotypic differences among cell populations (Caicedo et al., 2017). Thus we anticipate that the advantages of the proposed preprocessing transformations will likely also be realized in the analysis of data from other highly-multiplexed technologies like Cyclic Immunofluorescence. All code and supplementary analysis for this paper is available at gjhunt.github.io/rr.
Differential effects of Doxorubicin and Actinomycin D on the stability of RNA binding proteins, RBM10 and RBM5: Actinomycin D promotes the nuclear speckles targeting of RBM10 and RBM5 through the novel structural elements
Authors: Nishio Koji , Qiao Shanlou , Chang Kung Sang 
Published: May 2019

AbstractBackgroundRNA binding motif (RBM) proteins, RBM10v1, RBM10v2 and RBM5 share a high degree of the conserved domains. So far, the drug-sensitivities of the RBMs in tumor cells have not been fully examined.ObjectiveThe expression profiles of RBM10 and RBM5 in several virus-transformed tumor cells, and the effect of the most established antitumor agents, actinomycin D and doxorubicin, were investigated.Methods and ResultsDoxorubicin and actinomycin D differentially reduced RBM10 and RBM5 protein, respectively in both of HeLa and COS-7 cells. RBM10 protein was highly sensitive to doxorubicin in HeLa, COS-7 and A549 cells. In silico analysis revealed the several sumoylation sites of RBM10 and its sumoylated form could be targeted for the activated ubiquitin proteasome system. Actinomycin D affected the nuclear speckles localization of RBM10 and RBM5 in COS-7 and A549 lung carcinoma cells. Addition of actinomycin D in the culture medium and following culture for 3〜4 hours promoted the prominent nuclear speckles of RBM10v2-GFP and RBM5. Hence, we explored the subnuclear localization of the full length RBM10v2 (852aa) and the amino terminally truncated forms and the responsible structural elements. The amino terminally truncated RBM10v2 [#486-852, #642-852], RBM10v2 [#648-852], RBM10v2 [#681-759, #681-852], and RBM10v2 [#660-852] retained the targeting elements for the nuclear speckles, nucleoplasm, nucleoli and whole nuclei, respectively.ConclusionRBM10 is highly sensitive to doxorubicin. Actinomycin D affects the structural elements of RBM10 and promotes the nuclear speckles targeting. The C-terminal regions: RBM10v2 [#642-647], [#642-659], and [#660-680] play critical roles in the targeting to the subnuclear compartments. SIM and sumoylation sits of RBM10 and PML4 are important for molecular interaction of RBM10 and PML.
No evidence for accelerated brain aging in patients with chronic non-cancer pain
Authors: Sörös Peter , Bantel Carsten 
Published: May 2019

AbstractChronic pain is often associated with changes in brain structure and function, and also cognitive deficits. It has been noted that these chronic pain-related alterations may resemble changes found in healthy aging, and thus may represent accelerated or pre-mature aging of the brain. Here we test the hypothesis that patients with chronic non-cancer pain demonstrate accelerated brain aging compared to healthy control subjects. The predicted brain age of 59 patients with chronic pain (mean chronological age ± standard deviation: 53.0 ± 9.0 years; 43 women) and 60 pain-free healthy controls (52.6 ± 9.0 years; 44 women) was determined using the softwarebrainageR. This software segments the individual T1-weighted structural MR images into gray and white matter and compares gray and white matter images to a large (n = 2001) training set of structural images, using machine learning. Finally, brain age delta, which is the predicted brain age minus chronological age, was calculated and compared across groups. This study provided no evidence for the hypothesis that chronic pain is associated with accelerated brain aging (Welch’s t-test, p = 0.74, Cohen’s d = 0.061). A Bayesian independent samples t-test indicated moderate evidence in favor of the null hypothesis (BF01 = 4.875, i.e. group means were equal). Our results provide indirect support for recent models of pain related-changes of brain structure, brain function, and cognitive functions. These models postulate network-specific maladaptive plasticity, rather than wide-spread or global neural degeneration, leading to synaptic, dendritic, and neuronal remodeling.
A Nature-based solution in practice: ecological and economic modelling shows pollinators outperform agrochemicals in oilseed crop production
Authors: Catarino Rui , Bretagnolle Vincent , Perrot Thomas , Vialloux Fabien , Gaba Sabrina 
Published: May 2019

AbstratNature-based agriculture, reducing dependency on chemical inputs, requires using ecological principles for sustainable agro-ecosystems, balancing ecology, economics and social justice. There is growing evidence that pollinator-dependent crops with high insect pollination service can give higher yields. However, the interacting effects between insect pollination and agricultural inputs on crop yields and farm economics remain to be established to reconcile food production with biodiversity conservation. We investigated the effects of insect pollination and agricultural inputs on oilseed rape (Brassica napusL.). We show that not only yield but also gross margins are 16-40% higher in fields with higher pollinator abundance than in fields with reduced pollinator abundance. This effect is however strongly reduced by pesticides use. Higher yields may be achieved by either increasing agrochemicals (reducing pests) or increasing bee abundance, but crop economic returns was only increased by the latter, because pesticides did not increase yields while their costs reduced gross margins.