bluuebunny/crossref_metadata_2025_split huggingface dataset:
Falls and fear of falling in older adults with total joint arthroplasty: a scoping review
Authors: Chen Serena Kuangyi , Voaklander Don , Perry Danielle , Jones C. Allyson 
Published: December 2019

AbstractBackgroundPatients waiting or recovering from total joint arthroplasty (TJA) are at risk for falls which can lead to restriction of activity and negatively impact recovery. The objective of this scoping review is to critically appraise and synthesize the evidence in the reported number of falls, fear of falling, and risk factors associated with falls in older patients waiting for or recovering from TJA.MethodsSeven electronic databases were searched with no date limits and using language restriction (English). The inclusion criteria were 1) cohorts that included older adults 60+ years of age, 2) reported prevalence of falls, fear of falling, and/or risk factors for falls in patients who were waiting or recovering from TJA and 3) cross-sectional studies, cohort studies, and case control study designs. The quality assessment of selected articles was assessed using the SIGN Guidelines Checklist.ResultsOf the 866 citations identified, 12 studies met the inclusion criteria and were reviewed. Prevalence of falls in pre-operative TJA patients and post-operative TJA patients ranged from 23 to 63%, and 13 to 42%, respectively. Of those five studies that examined fear of falling, pre-operative TJA patients reported greater fear of falling than post-operative patients. Modifiable risk factors for falls included fear of falling, joint range of motion, and depression.ConclusionsAn increased risk of falls in patients with TJA was reported both for patients waiting for and recovering from surgery. A number of modifiable risk factors were identified including fear of falling that could be targeted in fall prevention programs for TJA.
Systematic computational identification of prognostic cytogenetic markers in neuroblastoma
Authors: Qin Chao , He Xiaoyan , Zhao Yanding , Tong Chun-Yip , Zhu Kenneth Y. , Sun Yongqi , Cheng Chao 
Published: December 2019

Abstract
Background
Neuroblastoma (NB) is the most common extracranial solid tumor found in children. The frequent gain/loss of many chromosome bands in tumor cells and absence of mutations found at diagnosis suggests that NB is a copy number-driven cancer. Despite the previous work, a systematic analysis that investigates the relationship between such frequent gain/loss of chromosome bands and patient prognosis has yet to be implemented.

Methods
First, we analyzed two NB CNV datasets to select chromosomal bands with a high frequency of gain or loss. Second, we applied a computational approach to infer sample-specific CNVs for each chromosomal band selected in step 1 based on gene expression data. Third, we applied univariate Cox proportional hazards models to examine the association between the resulting inferred copy number values (iCNVs) and patient survival. Finally, we applied multivariate Cox proportional hazards models to select chromosomal bands that remained significantly associated with prognosis after adjusting for critical clinical variables, including age, stage, gender, and MYCN amplification status.

Results
Here, we used a computational method to infer the copy number variations (CNVs) of sample-specific chromosome bands from NB patient gene expression profiles. The resulting inferred CNVs (iCNVs) were highly correlated with the experimentally determined CNVs, demonstrating CNVs can be accurately inferred from gene expression profiles. Using this iCNV metric, we identified 58 frequent gain/loss chromosome bands that were significantly associated with patient survival. Furthermore, we found that 7 chromosome bands were still significantly associated with patient survival even when clinical factors, such as MYCN status, were considered. Particularly, we found that the chromosome band chr11p14 has high potential as a novel candidate cytogenetic biomarker for clinical use.

Conclusion
Our analysis resulted in a comprehensive list of prognostic chromosome bands supported by strong statistical evidence. In particular, the chr11p14 gain event provided additional prognostic value in addition to well-established clinical factors, including MYCN status, and thereby represents a novel candidate cytogenetic biomarker with high clinical potential. Additionally, this computational framework could be readily extended to other cancer types, such as leukemia.
Process engineering of pH tolerant Ustilago cynodontis for efficient itaconic acid production
Authors: Hosseinpour Tehrani Hamed , Saur Katharina , Tharmasothirajan Apilaasha , Blank Lars M. , Wierckx Nick 
Published: December 2019

Abstract
Background
Ustilago cynodontis ranks among the relatively unknown itaconate production organisms. In comparison to the well-known and established organisms like Aspergillus terreus and Ustilago maydis, genetic engineering and first optimizations for itaconate production were only recently developed for U. cynodontis, enabling metabolic and morphological engineering of this acid-tolerant organism for efficient itaconate production. These engineered strains were so far mostly characterized in small scale shaken cultures.

Results
In pH-controlled fed-batch experiments an optimum pH of 3.6 could be determined for itaconate production in the morphology-engineered U. cynodontis Δfuz7. With U. cynodontis ∆fuz7r∆cyp3rPetefmttA Pria1ria1, optimized for itaconate production through the deletion of an itaconate oxidase and overexpression of rate-limiting production steps, titers up to 82.9 ± 0.8 g L−1 were reached in a high-density pulsed fed-batch fermentation at this pH. The use of a constant glucose feed controlled by in-line glucose analysis increased the yield in the production phase to 0.61 gITA gGLC−1, which is 84% of the maximum theoretical pathway yield. Productivity could be improved to a maximum of 1.44 g L−1 h−1 and cell recycling was achieved by repeated-batch application.

Conclusions
Here, we characterize engineered U. cynodontis strains in controlled bioreactors and optimize the fermentation process for itaconate production. The results obtained are discussed in a biotechnological context and show the great potential of U. cynodontis as an itaconate producing host.
Co-designing obesity prevention interventions together with children: intervention mapping meets youth-led participatory action research
Authors: Anselma Manou , Altenburg Teatske M. , Emke Helga , van Nassau Femke , Jurg Merlin , Ruiter Robert A. C. , Jurkowski Janine M. , Chinapaw Mai J. M. 
Published: December 2019

AbstractBackgroundYouth-led Participatory Action Research (YPAR) involves children throughout the process of developing and implementing interventions. Combining YPAR with a structural approach for designing and planning interventions, such as Intervention Mapping (IM), may further improve implementation and effectiveness of interventions. This paper describes how YPAR and IM were combined in the Kids in Action study.MethodsThe Kids in Action study aims to improve health behaviors of 9–12-year old children living in a low socioeconomic neighborhood in Amsterdam, by co-designing interventions with these children. At each of four schools 6–8 children (N = 18–24 total per year) and two academic researchers formed participatory groups that met weekly or every fortnight during two school years. An IM expert panel advised the participatory groups on the application of IM.ResultsFollowing the IM protocol, we conducted a participatory needs assessment with children, parents and professionals, in IM-step 1. In IM-step 2, the IM expert panel constructed matrices of program objectives, and the children provided feedback. In collaboration with children programs were designed and produced using an iterative process during IM-steps 3–4. In IM-step 5, the participatory groups and professional community partners designed the implementation plan. Finally, in IM-step 6, the protocol of the process and effect evaluation – executed by academic researchers with input from children – was developed.ConclusionsBy combining YPAR and IM, several interventions have been developed and implemented, varying from a school water policy to extracurricular sports activities. Sharing responsibility with children was challenging when combining IM with YPAR. In YPAR children are given as much autonomy as possible, while traditional IM development work is primarily done by academic researchers. Strengths in combining IM and YPAR include the involvement of the end-users - children - throughout the process while at the same time developing interventions based on existing evidence. Time-management, a multidisciplinary team, and flexibility are important conditions when combining IM with YPAR. A strong community project group, with professionals who were willing to help children develop and execute their ideas, was an important success factor. This study can serve as an example to other YPAR studies developing interventions using the IM protocol.
Modelling the effects of glucagon during glucose tolerance testing
Authors: Kelly Ross A. , Fitches Molly J. , Webb Steven D. , Pop S. R. , Chidlow Stewart J. 
Published: December 2019

Abstract
Background
Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship.

Results
Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ).

Conclusions
The models are used to investigate how different degrees of pax‘tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted.
The regulatory mechanism of p38/MAPK in the chondrogenic differentiation from bone marrow mesenchymal stem cells
Authors: Ma Ning , Teng Xiao , Zheng Qi , Chen Peng 
Published: December 2019

Abstract
Background
Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and joint inflammation, in which growth factors are significantly involved. The extracellular signal-regulated p38 MAPK pathways play important roles in the regulation of osteogenic and chondrogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). However, the exact mechanism remains unclear.

Methods
In this study, the chondrogenic differentiation of human BMSCs was initiated in micromass culture in the presence of TGF-β1 for 14 days. Quantitative RT-PCR and Western blot were performed to detect the transfection effect of shRNA-p38 interfering plasmid in BMSCs. The protein expressions of p/t-p38, SOX9, collagen II, Aggrecan, p/t-Smad1, and p/t-Smad4, as well as the kinase activities of p38/ERK/JNK pathway, were investigated using Western blot analysis. Additionally, the level of chondroitin sulfate and glycosaminoglycans (GAG) expression were measured by Alcian blue staining and GAG assay kit via qualitative and quantitative methods, respectively.

Results
The results demonstrated that p38 pathway was activated in the chondrogenic differentiation of BMSCs induced by TGF-β1. Cartilage-specific genes and chondrogenic regulators, such as SOX9, collagen II, Aggrecan, and GAG, were upregulated by TGF-β1, which could be reversed by predisposed with shRNA-p38 interfering plasmid and p38-MAPK inhibitors (SB203580). Moreover, the activation of p38/ERK/JNK pathways in the presence of TGF-β1 was suppressed by shRNA-p38 and SB203580 treatment.

Conclusion
Collectively, the activation of p38/ERK/JNK/Smad pathways plays a facilitated role in the chondrogenic differentiation induced by TGF-β1. After suppressing the p38 pathway, the chondrogenesis can be inhibited, which can be used to guide the treatment of osteoarthritis.
Nucleotide composition of transposable elements likely contributes to AT/GC compositional homogeneity of teleost fish genomes
Authors: Symonová Radka , Suh Alexander 
Published: December 2019

Abstract
Background
Teleost fish genome size has been repeatedly demonstrated to positively correlate with the proportion of transposable elements (TEs). This finding might have far-reaching implications for our understanding of the evolution of nucleotide composition across vertebrates. Genomes of fish and amphibians are GC homogenous, with non-teleost gars being the single exception identified to date, whereas birds and mammals are AT/GC heterogeneous. The exact reason for this phenomenon remains controversial. Since TEs make up significant proportions of genomes and can quickly accumulate across genomes, they can potentially influence the host genome with their own GC content (GC%). However, the GC% of fish TEs has so far been neglected.

Results
The genomic proportion of TEs indeed correlates with genome size, although not as linearly as previously shown with fewer genomes, and GC% negatively correlates with genome size in the 33 fish genome assemblies analysed here (excluding salmonids). GC% of fish TE consensus sequences positively correlates with the corresponding genomic GC% in 29 species tested. Likewise, the GC contents of the entire repetitive vs. non-repetitive genomic fractions correlate positively in 54 fish species in Ensembl. However, among these fish species, there is also a wide variation in GC% between the main groups of TEs. Class II DNA transposons, predominant TEs in fish genomes, are significantly GC-poorer than Class I retrotransposons. The AT/GC heterogeneous gar genome contains fewer Class II TEs, a situation similar to fugu with its extremely compact and also GC-enriched but AT/GC homogenous genome.

Conclusion
Our results reveal a previously overlooked correlation between GC% of fish genomes and their TEs. This applies to both TE consensus sequences as well as the entire repetitive genomic fraction. On the other hand, there is a wide variation in GC% across fish TE groups. These results raise the question whether GC% of TEs evolves independently of GC% of the host genome or whether it is driven by TE localization in the host genome. Answering these questions will help to understand how genomic GC% is shaped over time. Long-term accumulation of GC-poor(er) Class II DNA transposons might indeed have influenced AT/GC homogenization of fish genomes and requires further investigation.
Methods and efficacy of extracellular vesicles derived from mesenchymal stromal cells in animal models of disease: a preclinical systematic review protocol
Authors: Tieu Alvin , Slobodian Mitchell , Fergusson Dean A. , Montroy Joshua , Burger Dylan , Stewart Duncan J. , Shorr Risa , Allan David S. , Lalu Manoj M. 
Published: December 2019

AbstractBackgroundOver the past decade, mesenchymal stromal cells have been increasingly investigated for their therapeutic potential in several different illnesses. However, cell therapy can be limited by potentially serious adverse events including cell embolus formation and tumorigenesis. Importantly, the protective effects of mesenchymal stromal cells are largely mediated by paracrine mechanisms including release of extracellular vesicles. This systematic review intends to synthesize the current knowledge of mesenchymal stromal cell-derived extracellular vesicles as a therapeutic option for preclinical models of disease, inflammation, or injury.MethodsA systematic literature search of MEDLINE, Embase, and BIOSIS databases will be conducted. Interventional preclinical in vivo studies using extracellular vesicles derived from any tissue source of mesenchymal stromal cells will be included. Studies will be screened by abstract, and full-text by two independent reviewers. Eligible studies will undergo data extraction with subcategorization into domains based on disease. Methods utilized for extracellular vesicle characterization and isolation will be collected, as well as information on interventional traits, such as tissue source of mesenchymal stromal cells, dosage regimen, and vesicle modifications. Reported outcomes will be collected to determine which diseases studied may be impacted most from treatment with mesenchymal stromal cell-derived extracellular vesicles.DiscussionThis systematic review will summarize preclinical studies investigating the therapeutic efficacy of both small and large extracellular vesicles derived by mesenchymal stromal cells. Extracellular vesicles represent a possibility to harness the benefits of mesenchymal stromal cells with added benefits of reduced manufacturing costs and an improved safety profile. Hence, there has been an exponential increase in interest for developing this cell-free therapy with hundreds of preclinical studies published to date. However, a vast amount of heterogeneity between groups relates to methods of extracellular vesicle isolation, characterization, and study design. This review will capture this heterogeneity and identify the most commonly used and optimal approaches to evaluate mesenchymal stromal cell-derived extracellular vesicle treatment. A meta-analysis of outcomes within each disease domain will help elucidate which fields of research demonstrate promise for developing extracellular vesicles as a novel cell-free therapy. Summarizing this robust information on extracellular vesicles as an intervention can provide guidance for designing preclinical studies with hopes of future clinical translation.
Analyzing long-term empirical interactions between renewable energy generation, energy use, human capital, and economic performance in Pakistan
Authors: Fatima Nousheen , Li Yanbin , Ahmad Munir , Jabeen Gul , Li Xiaoyu 
Published: December 2019

Abstract
Background
The current research attempts to systematically investigate the causal interactions between renewable energy generation, aggregated energy use, human capital, and economic performance in Pakistan both in a short-term and long-term test for the period of 1990–2016.

Methods
As a primary step, a unit root analysis was conducted employing, among others, an augmented Dickey-Fuller-generalized least squares (ADF-GLS) test. Based on the order of integration I(1), the Johansen and Juselius (JJ) co-integration testing was employed to confirm a long-term causality analysis, which was followed by a vector error correction model (VECM) to calculate the short-run Granger causality analysis. Furthermore, the vector autoregressive (VAR)-based Cholesky test allowed the standard deviation impulse response functions to be generated to explain the responses of variables to arbitrary shocks in the data series under analysis.

Results
The empirical findings unearthed the bilateral causal connection between aggregated energy use and economic performance, renewable energy generation and economic performance, and human capital and economic performance. Thus, it confirmed the existence of feedback effects for aggregated energy use, renewable energy generation, and human capital in their relation to economic performance. Likewise, a unilateral positive causal connection was revealed running from renewable energy generation and human capital to aggregated energy use, and from human capital to renewable energy generation in both a long-term and short-term test. Additionally, the causal association running from aggregated energy use and renewable energy generation to economic performance was exposed in a long-term as well as short-term test, hence supporting the growth hypothesis.

Conclusions
The findings signified the importance of an enhanced generation of renewable energy along with the promotion of an aggregated energy use for the economic performance in Pakistan.
Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer’s disease related pathology
Authors: Joshi Amit U. , Van Wassenhove Lauren D. , Logas Kelsey R. , Minhas Paras S. , Andreasson Katrin I. , Weinberg Kenneth I. , Chen Che-Hong , Mochly-Rosen Daria 
Published: December 2019

AbstractAldehyde dehydrogenase 2 deficiency (ALDH2*2) causes facial flushing in response to alcohol consumption in approximately 560 million East Asians. Recent meta-analysis demonstrated the potential link between ALDH2*2 mutation and Alzheimer’s Disease (AD). Other studies have linked chronic alcohol consumption as a risk factor for AD. In the present study, we show that fibroblasts of an AD patient that also has an ALDH2*2 mutation or overexpression of ALDH2*2 in fibroblasts derived from AD patients harboring ApoE ε4 allele exhibited increased aldehydic load, oxidative stress, and increased mitochondrial dysfunction relative to healthy subjects and exposure to ethanol exacerbated these dysfunctions. In an in vivo model, daily exposure of WT mice to ethanol for 11 weeks resulted in mitochondrial dysfunction, oxidative stress and increased aldehyde levels in their brains and these pathologies were greater in ALDH2*2/*2 (homozygous) mice. Following chronic ethanol exposure, the levels of the AD-associated protein, amyloid-β, and neuroinflammation were higher in the brains of the ALDH2*2/*2 mice relative to WT. Cultured primary cortical neurons of ALDH2*2/*2 mice showed increased sensitivity to ethanol and there was a greater activation of their primary astrocytes relative to the responses of neurons or astrocytes from the WT mice. Importantly, an activator of ALDH2 and ALDH2*2, Alda-1, blunted the ethanol-induced increases in Aβ, and the neuroinflammation in vitro and in vivo. These data indicate that impairment in the metabolism of aldehydes, and specifically ethanol-derived acetaldehyde, is a contributor to AD associated pathology and highlights the likely risk of alcohol consumption in the general population and especially in East Asians that carry ALDH2*2 mutation.