bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extent of and trends in inequalities in child stunting in Sierra-Leone from 2005 to 2013: evidence from demographic and health surveys and multiple indicator cluster surveys
Authors: Shibre Gebretsadik , Zegeye Betregiorigis , Haidar Jemal 
Published: June 2020

Abstract
Background
Comprehensive assessment of stunting disparity in Sierra-Leone has not been done so far. We aimed to document extent and over time dynamics of inequality in stunting in Sierra-Leone using approaches that facilitate implementation of interventions aim to eliminate non-justified stunting disparity in the country.

Methods
The data for the study were derived from two rounds of the Sierra Leone Demographic and Health Survey conducted in 2008 and 2013, and two rounds of the Sierra Leone Multiple Indicator Cluster Survey done in 2005 and 2010. We used the 2019 update WHO Health Equity Assessment Toolkit (HEAT) to do the analysis. The toolkit makes use of data stored in the WHO Health Equity Monitor database. We analyzed stunting inequality using summary measures: Population Attributable Risk, Population Attributable Fraction, Difference and Ratio. The summary measures were computed for five equity stratifers: wealth, education, child’s sex, place of residence and subnational region. We computed 95% Confidence Interval (CI) for each point estimate to show whether or not observed stunting inequalities are statistically significant, and whether or not the disparity changed over time statistically significantly.

Results
The findings demonstrated stark inequalities in stunting in all the studied dimensions of inequality. While residence and subnational regional related inequalities remain unchanged over time, wealth and educational inequality had seen slight improvement during the same time period. Large sex related stunting inequality remained during the first three surveys time points, but it disappeared in 2013.

Conclusions
Huge stunting disparities occurred in Sierra Leone, and the disparity disproportionately affects disadvantaged subpopulations and male children. Nutrition interventions that specifically target the subgroups which suffer more from the burden of stunting are required.
Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology
Authors: Hu Wei , Liu Cong , Bi Zhuo-Yue , Zhou Qun , Zhang Han , Li Lin-Lin , Zhang Jian , Zhu Wei , Song Yang-Yi-Yan , Zhang Feng , Yang Hui-Min , Bi Yong-Yi , He Qi-Qiang , Tan Gong-Jun , Sun Cheng-Cao , Li De-Jia 
Published: June 2020

AbstractExtracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.
Association between nonalcoholic fatty liver disease and extrahepatic cancers: a systematic review and meta-analysis
Authors: Liu Shou-Sheng , Ma Xue-Feng , Zhao Jie , Du Shui-Xian , Zhang Jie , Dong Meng-Zhen , Xin Yong-Ning 
Published: May 2020

Abstract
Background
NAFLD is tightly associated with various diseases such as diabetes, cardiovascular disease, kidney disease, and cancer. Previous studies had investigated the association between NAFLD and various extrahepatic cancers, but the available data to date is not conclusive. The aim of this study was to investigate the association between NAFLD and various extrahepatic cancers comprehensively.

Methods
Searches were conducted of various electronic databases (PubMed, EMBASE, Medline, and the Cochrane Library) to identify observational studies published between 1996 and January 2020 which investigated the association between NAFLD and extrahepatic cancers. The pooled OR/HR/IRR of the association between NAFLD and various extrahepatic cancers were analyzed.

Results
A total of 26 studies were included to investigate the association between NAFLD and various extrahepatic cancers. As the results shown, the pooled OR values of the risk of colorectal cancer and adenomas in patients with NAFLD were 1.72 (95%CI: 1.40–2.11) and 1.37 (95%CI: 1.29–1.46), respectively. The pooled OR values of the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in patients with NAFLD were 2.46 (95%CI: 1.77–3.44) and 2.24 (95%CI: 1.58–3.17), respectively. The pooled OR value of the risk of breast cancer in patients with NAFLD was 1.69 (95%CI: 1.44–1.99). In addition, NAFLD was also tightly associatied with the risk of gastric cancer, pancreatic cancer, prostate cancer, and esophageal cancer.

Conclusions
NAFLD could significantly increase the development risk of colorectal adenomas and cancer, intrahepatic and extrahepatic cholangiocarcinoma, breast, gastric, pancreatic, prostate, and esophageal cancer. NAFLD could be considered as one of the influencing factors during the clinical diagnosis and treatment for the extrahepatic cancers.
MiR-9-5p promotes rabbit preadipocyte differentiation by suppressing leptin gene expression
Authors: Luo Gang , Hu Shenqiang , Lai Tianfu , Wang Jie , Wang Li , Lai Songjia 
Published: June 2020

Abstract
Background
MicroRNAs (miRNAs) are a class of small non-coding RNAs, which participate in the regulation of cell differentiation. Previous studies have demonstrated that miR-9-5p plays a key role in cancer cell development, but the mechanisms by which miR-9-5p regulates adipogenesis remain poorly understood. The present study intended to investigate its significance in producing rabbits with high-quality meat by observing the regulatory effect of miR-9-5p in preadipocytes and finding the related targets.

Methods
In this study, a dual-luciferase reporter assay was employed to validate the targeting relationship between miR-9-5p and leptin gene. We also utilized quantitative reverse transcription PCR (qRT-PCR), western blot, oil red-O staining assay, and determination of triglyceride content to analyze the regulation of miR-9-5p and leptin gene during adipocyte differentiation.

Results
The analysis demonstrated that during preadipocyte differentiation, miR-9-5p was up-regulated and the fat formation related biomarkers, i.e., fatty acid-binding protein 4 (FABP4), CCAAT-enhancer binding protein α (C/EBPα), and peroxisome proliferator activated receptor γ (PPARγ) were also up-regulated. Meanwhile, the oil red-O staining assay revealed that the accumulation of lipid droplets increased. We also explored the expression pattern and role of miR-9-5p in adipogenesis using white pre-adipocytes. The results showed that miR-9-5p was up-regulated during preadipocyte differentiation, and overexpression of miR-9-5p enhanced lipid accumulation. Furthermore, we found that the overexpression of miR-9-5p significantly up- regulated the expression of marker genes, PPARγ, C/EBPα and FABP4, and increased the protein levels of PPARγ and triglyceride content. The results suggest that miR-9-5p might be involved in the regulation of rabbit preadipocyte differentiation. We predicted that leptin is the target gene of miR-9-5p, by using bioinformatics tools and the conclusion was validated by a luciferase reporter assay. Finally, we verified that the knock-down of leptin by si-leptin promoted preadipocyte differentiation in rabbits.

Conclusion
The results of the present study indicate that miR-9-5p regulates white preadipocyte differentiation in rabbits by targeting the leptin gene.
808 nm-activable core@multishell upconverting nanoparticles with enhanced stability for efficient photodynamic therapy
Authors: Martínez Raquel , Polo Ester , Barbosa Silvia , Taboada Pablo , del Pino Pablo , Pelaz Beatriz 
Published: June 2020

Abstract
Background
The unique upconversion properties of rare-earth-doped nanoparticles offers exciting opportunities for biomedical applications, in which near-IR remote activation of biological processes is desired, including in vivo bioimaging, optogenetics, and light-based therapies. Tuning of upconversion in purposely designed core–shell nanoparticles gives access to biological windows in biological tissue. In recent years there have been several reports on NIR-excitable upconverting nanoparticles capable of working in biological mixtures and cellular settings. Unfortunately, most of these nanosystems are based on ytterbium’s upconversion at 980 nm, concurrent with water’s absorption within the first biological window. Thus, methods to produce robust upconverting nanoplatforms that can be efficiently excited with other than 980 nm NIR sources, such as 808 nm and 1064 nm, are required for biomedical applications.

Results
Herein, we report a synthetic method to produce aqueous stable upconverting nanoparticles that can be activated with 808 nm excitation sources, thus avoiding unwanted heating processes due to water absorbance at 980 nm. Importantly, these nanoparticles, once transferred to an aqueous environment using an amphiphilic polymer, remain colloidally stable for long periods of time in relevant biological media, while keeping their photoluminescence properties. The selected polymer was covalently modified by click chemistry with two FDA-approved photosensitizers (Rose Bengal and Chlorin e6), which can be efficiently and simultaneously excited by the light emission of our upconverting nanoparticles. Thus, our polymer-functionalization strategy allows producing an 808 nm-activable photodynamic nanoplatform. These upconverting nanocomposites are preferentially stored in acidic lysosomal compartments, which does not negatively affect their performance as photodynamic agents. Upon 808 nm excitation, the production of reactive oxidative species (ROS) and their effect in mitochondrial integrity were demonstrated.

Conclusions
In summary, we have demonstrated the feasibility of using photosensitizer-polymer-modified upconverting nanoplatforms that can be activated by 808 nm light excitation sources for application in photodynamic therapy. Our nanoplatforms remain photoactive after internalization by living cells, allowing for 808 nm-activated ROS generation. The versatility of our polymer-stabilization strategy promises a straightforward access to other derivatizations (for instance, by integrating other photosensitizers or homing ligands), which could synergistically operate as multifunctional photodynamic platforms nanoreactors for in vivo applications.
Development and use of health outcome descriptors: a guideline development case study
Authors: Baldeh Tejan , Saz-Parkinson Zuleika , Muti Paola , Santesso Nancy , Morgano Gian Paolo , Wiercioch Wojtek , Nieuwlaat Robby , Gräwingholt Axel , Broeders Mireille , Duffy Stephen , Hofvind Solveig , Nystrom Lennarth , Ioannidou-Mouzaka Lydia , Warman Sue , McGarrigle Helen , Knox Susan , Fitzpatrick Patricia , Rossi Paolo Giorgi , Quinn Cecily , Borisch Bettina , Lebeau Annette , de Wolf Chris , Langendam Miranda , Piggott Thomas , Giordano Livia , van Landsveld-Verhoeven Cary , Bernier Jacques , Rabe Peter , Schünemann Holger J. 
Published: June 2020

Abstract
Background
During healthcare guideline development, panel members often have implicit, different definitions of health outcomes that can lead to misunderstandings about how important these outcomes are and how to balance benefits and harms. McMaster GRADE Centre researchers developed ‘health outcome descriptors’ for standardizing descriptions of health outcomes and overcoming these problems to support the European Commission Initiative on Breast Cancer (ECIBC) Guideline Development Group (GDG). We aimed to determine which aspects of the development, content, and use of health outcome descriptors were valuable to guideline developers.

Methods
We developed 24 health outcome descriptors related to breast cancer screening and diagnosis for the European Commission Breast Guideline Development Group (GDG). Eighteen GDG members provided feedback in written format or in interviews. We then evaluated the process and conducted two health utility rating surveys.

Results
Feedback from GDG members revealed that health outcome descriptors are probably useful for developing recommendations and improving transparency of guideline methods. Time commitment, methodology training, and need for multidisciplinary expertise throughout development were considered important determinants of the process. Comparison of the two health utility surveys showed a decrease in standard deviation in the second survey across 21 (88%) of the outcomes.

Conclusions
Health outcome descriptors are feasible and should be developed prior to the outcome prioritization step in the guideline development process. Guideline developers should involve a subgroup of multidisciplinary experts in all stages of development and ensure all guideline panel members are trained in guideline methodology that includes understanding the importance of defining and understanding the outcomes of interest.
Health-related quality of life in Norwegian adolescents living with chronic fatigue syndrome
Authors: Similä Wenche Ann , Halsteinli Vidar , Helland Ingrid B. , Suvatne Christer , Elmi Hanna , Rø Torstein Baade 
Published: June 2020

Abstract
Purpose
The primary aim was to measure health related quality of life (HRQoL) in a Norwegian cohort of adolescents with Chronic Fatigue Syndrome (CFS/ME). A secondary aim was to identify factors before diagnosis, at time of diagnosis and after diagnosis that were associated with HRQoL.

Methods
In this cross-sectional population-based study, HRQoL was measured by Pediatric Quality of Life Inventory™ Generic Core scale version 4.0 (PedsQL4.0) in 63 adolescents with CFS/ME. In addition, fatigue was measured by PedsQL Multidimensional Fatigue scale (PedsQL-MFS), depressive symptoms were measured by the Short Mood and Feelings Questionnaire (SMFQ), and disruption in school activities was measured by The De Paul Pediatric Health Questionnaire (DPHQ-N). Data were also collected from medical records and patient interviews.

Results
Age at diagnosis was 15 (2) years (mean (SD)), and four out of five participants were female. Time from diagnosis to reply was 39 (22) months. Adolescents with CFS/ME reported PedsQL4.0 score 50 (17), and boys reported a better score than girls (64 vs 47, 95% Confidence Interval (CI) for difference (− 27; − 6)). There were positive associations between overall HRQoL and support from a schoolteacher, school attendance or participation in leisure activities. There were negative associations between overall HRQoL and delayed school progression, having been to rehabilitation stay and depressive symptoms.

Conclusion
HRQoL in adolescents diagnosed with CFS/ME was low. The associations between reported HRQoL, healthcare previously provided, support from a schoolteacher, school attendance and participation in leisure activity may provide information of value when developing refined strategies for healthcare among adolescents with CFS/ME. Possible causal relationships must however be explored in future studies.
MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma
Authors: Hohmann Tim , Hohmann Urszula , Kolbe Marc R. , Dahlmann Mathias , Kobelt Dennis , Stein Ulrike , Dehghani Faramarz 
Published: June 2020

AbstractBackgroundMetastasis-associated in colon cancer 1 (MACC1) is an established marker for metastasis and tumor cell migration in a multitude of tumor entities, including glioblastoma (GBM). Nevertheless, the mechanism underlying the increased migratory capacity in GBM is not comprehensively explored.MethodsWe performed live cell and atomic force microscopy measurements to assess cell migration and mechanical properties ofMACC1overexpressing GBM cells. We quantifiedMACC1dependent dynamics of 3D aggregate formation. For mechanistic studies we measured the expression of key adhesion molecules using qRT-PCR, and MACC1 dependent changes in short term adhesion to fibronectin and laminin. We then determined changes in sub-cellular distribution of integrins and actin in dependence ofMACC1, but also in microtubule and intermediate filament organization.ResultsMACC1increased the migratory speed and elastic modulus of GBM cells, but decreased cell-cell adhesion and inhibited the formation of 3D aggregates. These effects were not associated with altered mRNA expression of several key adhesion molecules or altered short-term affinity to laminin and fibronectin.MACC1did neither change the organization of the microtubule nor intermediate filament cytoskeleton, but resulted in increased amounts of protrusive actin on laminin.ConclusionMACC1overexpression increases elastic modulus and migration and reduces adhesion of GBM cells thereby impeding 3D aggregate formation. The underlying molecular mechanism is independent on the organization of microtubules, intermediate filaments and several key adhesion molecules, but depends on adhesion to laminin. Thus, targeting re-organization of the cytoskeleton and cell motility via MACC1 may offer a treatment option to impede GBM spreading.
A prognostic nomogram integrating novel biomarkers identified by machine learning for cervical squamous cell carcinoma
Authors: Li Yimin , Lu Shun , Lan Mei , Peng Xinhao , Zhang Zijian , Lang Jinyi 
Published: June 2020

Abstract
Background
Cervical cancer (CC) represents the fourth most frequently diagnosed malignancy affecting women all over the world. However, effective prognostic biomarkers are still limited for accurately identifying high-risk patients. Here, we provided a combination machine learning algorithm-based signature to predict the prognosis of cervical squamous cell carcinoma (CSCC).

Methods and materials
After utilizing RNA sequencing (RNA-seq) data from 36 formalin-fixed and paraffin-embedded (FFPE) samples, the most significant modules were highlighted by the weighted gene co-expression network analysis (WGCNA). A candidate genes-based prognostic classifier was constructed by the least absolute shrinkage and selection operator (LASSO) and then validated in an independent validation set. Finally, based on the multivariate analysis, a nomogram including the FIGO stage, therapy outcome, and risk score level was built to predict progression-free survival (PFS) probability.

Results
A mRNA-based signature was developed to classify patients into high- and low-risk groups with significantly different PFS and overall survival (OS) rate (training set: p < 0.001 for PFS, p = 0.016 for OS; validation set: p = 0.002 for PFS, p = 0.028 for OS). The prognostic classifier was an independent and powerful prognostic biomarker for PFS in both cohorts (training set: hazard ratio [HR] = 0.13, 95% CI 0.05–0.33, p < 0.001; validation set: HR = 0.02, 95% CI 0.01–0.04, p < 0.001). A nomogram that integrated the independent prognostic factors was constructed for clinical application. The calibration curve showed that the nomogram was able to predict 1-, 3-, and 5-year PFS accurately, and it performed well in the external validation cohorts (concordance index: 0.828 and 0.864, respectively).

Conclusion
The mRNA-based biomarker is a powerful and independent prognostic factor. Furthermore, the nomogram comprising our prognostic classifier is a promising predictor in identifying the progression risk of CSCC patients.
Big data from small tissues: extraction of high-quality RNA for RNA-sequencing from different oilseed Brassica seed tissues during seed development
Authors: Siles Laura , Eastmond Peter , Kurup Smita 
Published: June 2020

Abstract
Background
Obtaining high-quality RNA for gene expression analyses from different seed tissues is challenging due to the presence of various contaminants, such as polyphenols, polysaccharides and lipids which interfere with RNA extraction methods. At present, the available protocols for extracting RNA from seeds require high amounts of tissue and are mainly focused on extracting RNA from whole seeds. However, extracting RNA at the tissue level enables more detailed studies regarding tissue specific transcriptomes during seed development.

Results
Seeds from heart stage embryo to mature developmental stages of Brassica napus and B. oleracea were sampled for isolation of the embryo, endosperm and seed coat tissues. Ovules and ovary wall tissue were also collected from pre-fertilized buds. Subsequent to testing several RNA extraction methods, modifications applied to E.Z.N.A. Plant RNA and Picopure RNA Isolation kit extraction methods resulted in RNA with high yield and quality. Furthermore, the use of polyvinylpolypyrrolidone for seed coats and endosperm at green stages resulted in high-quality RNA. As a result of the introduced modifications to established RNA extraction methods, the RNA from all the above-mentioned tissues presented clear 28S and 18S bands and high RIN values, ranging from 7.0 to 10.0. The protocols reported in this study are not only suitable for different and challenging seed tissue types, but also enable the extraction of high-quality RNA using only 2 to 3 mg of starting tissue.

Conclusions
Here, we present efficient, reproducible and reliable high-quality RNA extraction methods for diverse oilseed Brassica spp reproductive tissue types including pre-fertilization and developing seed tissues for diploid and polyploid species. The high-quality RNA obtained is suitable for RNA-Sequencing and subsequent gene expression analysis.