bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring antibody avidity to Plasmodium falciparum merozoite antigens using a multiplex immunoassay approach
Authors: Taylor Diane Wallace , Bobbili Naveen , Kayatani Alex , Tassi Yunga Samuel , Kidima Winifrida , Leke Rose F. G. 
Published: May 2020

Abstract
Background
Antibodies (Ab) play a significant role in immunity to Plasmodium falciparum malaria. Usually, following repeated exposure to pathogens, affinity maturation and clonal selection take place, resulting in increased antibody avidity. However, some studies suggest affinity maturation may not occur to malaria antigens in endemic areas. Information on development of antibody avidity is confusing and conflicting, in part, because different techniques have been used to measure avidity. Today, bead-based multiplex immunoassays (MIA) are routinely used to simultaneously quantitate antibody levels to multiple antigens. This study evaluated the feasibility of developing an avidity MIA with 5 merozoite antigens (AMA1, EBA-175, MSP1-42, MSP2, MSP3) that uses a single chaotropic concentration.

Methods
The most common ELISA protocols that used the chaotropic reagents guanidine HCl (GdHCl), urea, and ammonium thiocyanate (NH4SCN) were adapted to a multiplex MIA format. Then, different concentrations of chaotropes and incubation times were compared and results were expressed as an Avidity Index (AI), i.e., percentage of antibody remaining bound in the presence of chaotrope. Experiments were conducted to (i) identify the assay with the widest range of AI (discriminatory power), (ii) determine the amount of chaotrope needed to release 50% of bound Ab using plasma from adults and infants, and (iii) evaluate assay repeatability.

Results
Overall, 4 M GdHCl and 8 M urea were weaker chaotropes than 3 M NH4SCN. For example, they failed to release significant amounts of Ab bound to MSP1-42 in adult plasma samples; whereas, a range of AI values was obtained with NH4SCN. Titration of NH4SCN revealed that 2 M NH4SCN gave the widest range of AI for the 5 antigens. Binding studies using plasma from 40 adults and 57 1-year old infants in Cameroon showed that 2.1 M ± 0.32 (mean ± SD) NH4SCN (adults) and 1.8 M ± 0.23 M (infants) released 50% of bound Ab from the merozoite antigens.

Conclusions
An avidity MIA is feasible for the 5 merozoite antigens that uses a single concentration (2 M) of NH4SCN. The assay provides a simple method to quickly obtain information about Ab quantity and quality in the acquisition of immunity to malaria in endemic populations.
Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity
Authors: Stieb David M. , Zheng Carine , Salama Dina , Berjawi Rania , Emode Monica , Hocking Robyn , Lyrette Ninon , Matz Carlyn , Lavigne Eric , Shin Hwashin H. 
Published: May 2020

Abstract
Background
Nitrogen dioxide (NO2) is a pervasive urban pollutant originating primarily from vehicle emissions. Ischemic heart disease (IHD) is associated with a considerable public health burden worldwide, but whether NO2 exposure is causally related to IHD morbidity remains in question. Our objective was to determine whether short term exposure to outdoor NO2 is causally associated with IHD-related morbidity based on a synthesis of findings from case-crossover and time-series studies.

Methods
MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts between reviewers were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran’s Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined using Leave One Out analysis and publication bias was evaluated using Funnel plots, Begg’s and Egger’s tests, and trim and fill.

Results
Thirty-eight case-crossover studies and 48 time-series studies were included in our analysis. NO2 was significantly associated with IHD morbidity (pooled odds ratio from case-crossover studies: 1.074 95% CI 1.052–1.097; pooled relative risk from time-series studies: 1.022 95% CI 1.016–1.029 per 10 ppb). Pooled estimates for case-crossover studies from Europe and North America were significantly lower than for studies conducted elsewhere. The high degree of heterogeneity among studies was only partially accounted for in meta-regression. There was evidence of publication bias, particularly for case-crossover studies. For both case-crossover and time-series studies, pooled estimates based on multi-pollutant models were smaller than those from single pollutant models, and those based on older populations were larger than those based on younger populations, but these differences were not statistically significant.

Conclusions
We concluded that there is a likely causal relationship between short term NO2 exposure and IHD-related morbidity, but important uncertainties remain, particularly related to the contribution of co-pollutants or other concomitant exposures, and the lack of supporting evidence from toxicological and controlled human studies.
MiR-363 suppresses cell migration, invasion, and epithelial-mesenchymal transition of osteosarcoma by binding to NOB1
Authors: Zhang Yongtao , Wang Fang , Wang Lina , Zhang Quanbin 
Published: May 2020

Abstract
Background
Osteosarcoma (OS) is a primary malignant bone tumor with a high rate of metastasis and a short 5-year survival rate. MiR-363 was downregulated in a variety of tumors and played a role in suppressing tumors. However, the roles of miR-363 in osteosarcoma remain unknown; thus, the purpose of this study was to explore the functions of miR-363 in osteosarcoma.

Methods
CCK-8 and transwell assays were performed to evaluate the proliferation, migration, and invasion abilities of MG63 cells. The epithelial-mesenchymal transition (EMT) and apoptosis-associated proteins were measured by using Western blot assay. Luciferase reporter assay was utilized to verify whether miR-363 directly bound to the 3′-UTR of NOB1 mRNA.

Results
MiR-363 was downregulated while NOB1 was upregulated in osteosarcoma clinical tissue specimens and cell lines as compared with the adjacent normal tissue specimens and normal cell line. The miR-363 is reversely correlated with the expression of NOB1 in osteosarcoma tissues. Overexpression of miR-363 suppressed the ability of cell migration, invasion, and EMT, whereas low expression of miR-363 promoted this ability. In addition, miR-363 inhibited osteosarcoma proliferation both in vitro and in vivo and inhibited the apoptosis in MG63 cells. Interference of NOB1 could inhibit the migration, invasion, and EMT of osteosarcoma cell line MG63. NOB1 was verified to be a direct target of miR-363 and its expression was mediated by miR-363. Re-expression of NOB1 could partially reverse the inhibitory effect of miR-363 on cell migration and invasion. In addition, low expression of miR-363 or overexpression of NOB1 predicted poor prognosis of osteosarcoma patients.

Conclusion
MiR-363 inhibited osteosarcoma the proliferation, migration, invasion, and EMT and induced the apoptosis by directly targeting NOB1 in MG63 cells. The newly identified miR-363/NOB1 axis provides novel insights into the pathogenesis of osteosarcoma.
Retinoic acid inducible gene-I mediated detection of bacterial nucleic acids in human microglial cells
Authors: Johnson M. Brittany , Halman Justin R. , Burmeister Amanda R. , Currin Saralynn , Khisamutdinov Emil F. , Afonin Kirill A. , Marriott Ian 
Published: May 2020

Abstract
Background
Bacterial meningitis and meningoencephalitis are associated with devastating neuroinflammation. We and others have demonstrated the importance of glial cells in the initiation of immune responses to pathogens invading the central nervous system (CNS). These cells use a variety of pattern recognition receptors (PRRs) to identify common pathogen motifs and the cytosolic sensor retinoic acid inducible gene-1 (RIG-I) is known to serve as a viral PRR and initiator of interferon (IFN) responses. Intriguingly, recent evidence indicates that RIG-I also has an important role in the detection of bacterial nucleic acids, but such a role has not been investigated in glia.

Methods
In this study, we have assessed whether primary or immortalized human and murine glia express RIG-I either constitutively or following stimulation with bacteria or their products by immunoblot analysis. We have used capture ELISAs and immunoblot analysis to assess human microglial interferon regulatory factor 3 (IRF3) activation and IFN production elicited by bacterial nucleic acids and novel engineered nucleic acid nanoparticles. Furthermore, we have utilized a pharmacological inhibitor of RIG-I signaling and siRNA-mediated knockdown approaches to assess the relative importance of RIG-I in such responses.

Results
We demonstrate that RIG-I is constitutively expressed by human and murine microglia and astrocytes, and is elevated following bacterial infection in a pathogen and cell type-specific manner. Additionally, surface and cytosolic PRR ligands are also sufficient to enhance RIG-I expression. Importantly, our data demonstrate that bacterial RNA and DNA both trigger RIG-I-dependent IRF3 phosphorylation and subsequent type I IFN production in human microglia. This ability has been confirmed using our nucleic acid nanoparticles where we demonstrate that both RNA- and DNA-based nanoparticles can stimulate RIG-I-dependent IFN responses in these cells.

Conclusions
The constitutive and bacteria-induced expression of RIG-I by human glia and its ability to mediate IFN responses to bacterial RNA and DNA and nucleic acid nanoparticles raises the intriguing possibility that RIG-I may be a potential target for therapeutic intervention during bacterial infections of the CNS, and that the use of engineered nucleic acid nanoparticles that engage this sensor might be a method to achieve this goal.
DiSCount: computer vision for automated quantification of Striga seed germination
Authors: Masteling Raul , Voorhoeve Lodewijk , IJsselmuiden Joris , Dini-Andreote Francisco , de Boer Wietse , Raaijmakers Jos M. 
Published: May 2020

Abstract
Background
Plant parasitic weeds belonging to the genus Striga are a major threat for food production in Sub-Saharan Africa and Southeast Asia. The parasite’s life cycle starts with the induction of seed germination by host plant-derived signals, followed by parasite attachment, infection, outgrowth, flowering, reproduction, seed set and dispersal. Given the small seed size of the parasite (< 200 μm), quantification of the impact of new control measures that interfere with seed germination relies on manual, labour-intensive counting of seed batches under the microscope. Hence, there is a need for high-throughput assays that allow for large-scale screening of compounds or microorganisms that adversely affect Striga seed germination.

Results
Here, we introduce DiSCount (Digital Striga Counter): a computer vision tool for automated quantification of total and germinated Striga seed numbers in standard glass fibre filter assays. We developed the software using a machine learning approach trained with a dataset of 98 manually annotated images. Then, we validated and tested the model against a total dataset of 188 manually counted images. The results showed that DiSCount has an average error of 3.38 percentage points per image compared to the manually counted dataset. Most importantly, DiSCount achieves a 100 to 3000-fold speed increase in image analysis when compared to manual analysis, with an inference time of approximately 3 s per image on a single CPU and 0.1 s on a GPU.

Conclusions
DiSCount is accurate and efficient in quantifying total and germinated Striga seeds in a standardized germination assay. This automated computer vision tool enables for high-throughput, large-scale screening of chemical compound libraries and biological control agents of this devastating parasitic weed. The complete software and manual are hosted at https://gitlab.com/lodewijk-track32/discount_paper and the archived version is available at Zenodo with the DOI 10.5281/zenodo.3627138. The dataset used for testing is available at Zenodo with the DOI 10.5281/zenodo.3403956.
Analysis of microRNA expression in peripheral blood monocytes of three Traditional Chinese Medicine (TCM) syndrome types in psoriasis patients
Authors: Lu Yue , Qi Yao , Yan Yuhong , Yao Danni , Deng Hao , Deng Jingwen , Ye Shuyan , Chen Haiming , Chen Qubo , Gao Hengjun , Han Ling , Lu Chuanjian 
Published: May 2020

Abstract
Background
To analyze the expression of miRNA (microRNA) in peripheral blood mononuclear cells in patients with Psoriasis vulgaris with different TCM syndromes by miRNA chip. It further revealed the micromaterial basis of different syndrome types of psoriasis at the miRNA level.

Methods
Peripheral blood monocytes were collected and prepared from 30 patients with Psoriasis vulgaris (including 9 patients of blood heat syndrome, 8 patients of blood stasis syndrome, and 13 patients of blood dry syndrome) and 9 healthy controls. The miRNA expression profile of peripheral blood monocytes was detected by Agilent Hum miRNA chip.

Results
Compared to the healthy control group, 156 upregulated and 242 downregulated miRNAs were detected in all psoriasis patients. Compared to the healthy control group, 40 miRNAs were upregulated and 44 were downregulated in the blood heat syndrome group. Furthermore, there were 49 upregulated miRNAs and 44 downregulated miRNAs in the dry syndrome group as compared to the healthy control group. Also, 67 miRNAs were upregulated and 154 miRNAs were downregulated in the blood stasis syndrome group as compared to the healthy control group.

Conclusions
There are common different miRNAs and pathways, as well as specific miRNAs between the psoriasis and the healthy control groups.
Trial registration ChiCTR-TRC-14005185 registered on August 8, 2014.
Management guidelines of penile cancer- a contemporary review of sub-Saharan Africa
Authors: Cassell Ayun , Yunusa Bashir , Manobah Burgess , Wambo Desire 
Published: May 2020

Abstract
Background
Penile cancer is a rare malignancy with prevalence higher in areas of high Human Papilloma Virus (HPV) such as Africa, Asia and South America. In middle- and low-income countries where circumcision is not routinely practiced, the rate of penile cancer could be ten times higher.

Main body of the abstract
A literature review was conducted from 1992 to 2019 using PubMed, Google Scholar, African Journal Online and Google with inclusion of 27 publications with emphasis on the Sub-Saharan literature. Findings revealed that most men with penile cancer in Sub-Saharan Africa (SSA) present with locally advanced to advanced disease with devastating consequences. The option of penile sparing procedure is reduced with most treatment option directed to mutilating surgeries. The lack of appropriate chemotherapy and radiotherapy worsens the prognosis in the region.

Short conclusion
Human Papilloma Virus (HPV) vaccination may not be cost-effective for most regions in SSA. Therefore, early childhood circumcision might be the best advocated alternative for prevention.
The development of a Consensus Conference on Pediatric Procedural Sedation in the Emergency Department in Italy: from here where to?
Authors:   on behalf of the Procedural Sedation Analgesia Consensus working group, Sforzi Idanna , Bressan Silvia , Saffirio Claudia , De Masi Salvatore , Bussolin Leonardo , Da Dalt Liviana , De Iaco Fabio , Shavit Itai , Krauss Baruch , Barbi Egidio 
Published: May 2020

Abstract
Background
In Italy, as in many European countries, Pediatric Emergency Medicine is not formally recognized as a pediatric subspecialty, hindering nation-wide adoption of standards of care, especially in the field of procedural sedation and analgesia (PSA) in the Emergency Department (ED). For this reason PSA in Italy is mostly neglected or performed very heterogeneously and by different providers, with no reference standard. We aimed to describe the procedures and results of the first multidisciplinary and multi-professional Consensus Conference in Italy on safe and effective pediatric PSA in Italian EDs.

Methods
The preparation, organization and conduct of the Consensus Conference, held in Florence in 2017, followed the recommended National methodological standards. Professionals from different specialties across the country were invited to participate.

Results
Overall 86 recommendations covering 8 themes (pre-sedation evaluation, pharmacologic agents, monitoring, equipment and discharge checklists, training, non-pharmacologic techniques, the adult ED setting, impact on hospitalizations) were developed, taking into account the Italian training system and healthcare organization characteristics.

Conclusion
The results of the first multidisciplinary and multi-professional Consensus Conference in Italy are meant to provide up-to-date national guidance to improve the standard of care of children undergoing painful and stressful procedures in the ED. The recommendations will be periodically updated as new relevant evidence is published.
Glucocorticoid receptors are required effectors of TGFβ1-induced p38 MAPK signaling to advanced cancer phenotypes in triple-negative breast cancer
Authors: Perez Kerkvliet Carlos , Dwyer Amy R. , Diep Caroline H. , Oakley Robert H. , Liddle Christopher , Cidlowski John A. , Lange Carol A. 
Published: May 2020

Abstract
Background
Altered signaling pathways typify breast cancer and serve as direct inputs to steroid hormone receptor sensors. We previously reported that phospho-Ser134-GR (pS134-GR) species are elevated in triple-negative breast cancer (TNBC) and cooperate with hypoxia-inducible factors, providing a novel avenue for activation of GR in response to local or cellular stress.

Methods
We probed GR regulation by factors (cytokines, growth factors) that are rich within the tumor microenvironment (TME). TNBC cells harboring endogenous wild-type (wt) or S134A-GR species were created by CRISPR/Cas knock-in and subjected to transwell migration, invasion, soft-agar colony formation, and tumorsphere assays. RNA-seq was employed to identify pS134-GR target genes that are regulated both basally (intrinsic) or by TGFβ1 in the absence of exogenously added GR ligands. Regulation of selected basal and TGFβ1-induced pS134-GR target genes was validated by qRT-PCR and chromatin immunoprecipitation assays. Bioinformatics tools were used to probe public data sets for expression of pS134-GR 24-gene signatures.

Results
In the absence of GR ligands, GR is transcriptionally activated via p38-dependent phosphorylation of Ser134 as a mechanism of homeostatic stress-sensing and regulated upon exposure of TNBC cells to TME-derived agents. The ligand-independent pS134-GR transcriptome encompasses TGFβ1 and MAPK signaling gene sets associated with TNBC cell survival and migration/invasion. Accordingly, pS134-GR was essential for TNBC cell anchorage-independent growth in soft-agar, migration, invasion, and tumorsphere formation, an in vitro readout of cancer stemness properties. Both pS134-GR and expression of the MAPK-scaffolding molecule 14-3-3ζ were essential for a functionally intact p38 MAPK signaling pathway downstream of MAP3K5/ASK1, indicative of a feedforward signaling loop wherein self-perpetuated GR phosphorylation enables cancer cell autonomy. A 24-gene pS134-GR-dependent signature induced by TGFβ1 predicts shortened overall survival in breast cancer patients.

Conclusions
Phospho-S134-GR is a critical downstream effector of p38 MAPK signaling and TNBC migration/invasion, survival, and stemness properties. Our studies define a ligand-independent role for GR as a homeostatic “sensor” of intrinsic stimuli as well as extrinsic factors rich within the TME (TGFβ1) that enable potent activation of the p38 MAPK stress-sensing pathway and nominate pS134-GR as a therapeutic target in aggressive TNBC.
Effects of perioperative enhanced recovery after surgery pathway management versus traditional management on the clinical outcomes of laparoscopic-assisted radical resection of distal gastric cancer: study protocol for a randomized controlled trial
Authors: Tian Yulong , Cao Shougen , Li Leping , He Qingsi , Xia Lijian , Jiang Lixin , Ding Yinlu , Wang Xinjian , Wang Hao , Mao Weizheng , Hui Xizeng , Shi Yiran , Zhang Huanhu , Chu Xianqun , Kehlet Henrik , Zhou Yanbing 
Published: May 2020

Abstract
Background
The incidence of gastric cancer in East Asia is much higher than the international average. Therefore, improving the prognosis of patients and establishing effective clinical pathways are important topics for the prevention and treatment of gastric cancer. At present, the enhanced recovery after surgery (ERAS) pathway is widely used in the field of gastric surgery. Many randomized controlled trial (RCT) studies have proven that the ERAS regimen can improve the short-term clinical outcomes of patients with gastric cancer. However, a prospective study on the effect of the ERAS pathway on the prognosis of patients with gastric cancer has not yet been reported. This trial aims to confirm whether the ERAS pathway can improve the disease-free survival and overall survival of patients undergoing laparoscopic-assisted radical resection for distal gastric cancer.

Methods/design
This study is a prospective, multicentre RCT. This experiment will consist of two groups – an experimental group and a control group – randomly divided in a 1:1 ratio. The perioperative period of the experimental group will be managed according to the ERAS pathway and that of the control group will be managed according to the traditional management mode. An estimated 400 patients will be enrolled. The main endpoint for comparison is the 3-year overall survival and disease-free survival between the two groups.

Discussion
The results of this RCT should clarify whether the ERAS pathway is superior to traditional treatment on inflammatory indexes, short-term clinical outcome and survival for laparoscopic-assisted radical resection of distal gastric cancer. It is hoped that our data will provide evidence that the ERAS pathway improves survival in patients with gastric cancer.

Trial registration
Chinese Clinical Trial Registry, CHiCTR1900022438. Registered on 11 April 2019.