bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translating academic research into guidance to support healthcare improvement: how should guidance development be reported?
Authors: Turner Simon , Sharp Charlotte A. , Sheringham Jessica , Leamon Shaun , Fulop Naomi J. 
Published: December 2019

Abstract
Background
There is interest internationally in improving the uptake of research evidence to inform health care quality and safety. This article focusses on guidance development from research studies as one method for improving research uptake. While we recognise that implementation strategies on the ´demand´ side for encouraging the uptake of research are important, e.g. knowledge brokers and university-practice collaborations, this article focusses on the ´production´ aspect of how guidance development is reported and the consequent influence this may have on end-users´ receptivity to evidence, in addition to other demand-side processes.

Main text
The article considers the following question: how is guidance developed and what are the implications for reporting? We address this question by reviewing examples of guidance development reporting from applied health research studies, then describe how we produced guidance for a national study of evidence use in decision-making on adopting innovations. The starting point for reflecting on our experiences is a vignette of the guidance ´launch´ event at a national conference.

Conclusions
Implications for reporting guidance development and supporting improvement are discussed. These include the need to (a) produce reporting standards for the production of guidance to match reporting standards for other research methods, (b) acknowledge the ´informal´ or emergent aspects of producing guidance and its role within a wider knowledge mobilization strategy, (c) consider guidance development from projects as part of a wider knowledge mobilization strategy, and (d) encourage a receptive environment for guidance development and use, including researcher training, durable funding to support impact, and closer relations between research and practice.
Prevalence and phylogenetic analysis of porcine diarrhea associated viruses in southern China from 2012 to 2018
Authors: Zhang Fanfan , Luo Suxian , Gu Jun , Li Zhiquan , Li Kai , Yuan Weifeng , Ye Yu , Li Hao , Ding Zhen , Song Deping , Tang Yuxin 
Published: December 2019

AbstractBackgroundIn China, large-scale outbreaks of severe diarrhea caused by viruses have occurred in pigs since late 2010. To investigate the prevalence and genetic evolution of diarrhea-associated viruses responsible for the outbreaks, a total of 2987 field diarrheal samples collected from 168 pig farms in five provinces in Southern China during 2012–2018 were tested.ResultsPorcine epidemic diarrhea virus (PEDV) was most frequently detected virus with prevalence rates between 50.21 and 62.10% in samples, and 96.43% (162/168) in premises, respectively. Porcine deltacoronavirus (PDCoV) was the second prevalent virus with prevalence rates ranging from 19.62 to 29.19% in samples, and 70.24% (118/168) in premises, respectively. Both transmissible gastroenteritis virus (TGEV) and porcine rotavirus (PoRV) were detected at low prevalence rates of < 3% in samples and 10.12% in premises. In this study, we identified a newly emerged swine acute diarrhea syndrome coronavirus (SADS-CoV) in diarrheal samples of piglets from Fujian province in Southern China, and the prevalence rate of SADS-CoV was 10.29% (7/68). Co-infections of these diarrhea-associated viruses were common. The most frequent co-infection was PEDV with PDCoV, with an average detection rate of 12.72% (380/2987, ranging from 8.26–17.33%). Phylogenetic analysis revealed that PEDVs circulating in Southern China during the last 7 years were clustered with the variant strains of PEDV in genotype IIa. The most frequent mutations were present in the collagenase equivalent (COE) and epitope regions of the spike gene of the PEDVs currently circulating in the field. Genetic relationships of PDCoVs were closely related with Chinese strains, other than those present in the USA, South Korea, Thailand and Lao’s public.ConclusionsThe findings of this study indicated that variant PEDV, PDCoV, and SADS-CoV were leading etiologic agents of porcine diarrhea, and either mono-infections or co-infections of pathogenic enteric CoVs were common in pigs in Southern China during 2012–2018. Thus, significant attention should be paid in order to effectively prevent and control porcine viral diarrhea.
Comparative metabolome analysis of serum changes in sheep under overgrazing or light grazing conditions
Authors: Zhang Jize , Gao Yang , Guo Huiqin , Ding Yong , Ren Weibo 
Published: December 2019

Abstract
Background
Overgrazing is a primary contributor to severe reduction in forage quality and production in Inner Mongolia, leading to extensive ecosystem degradation, sheep health impairment and growth performance reduction. Further studies to identify serum biomarkers that reflect changes in sheep health and nutritional status following overgrazing would be beneficial. We hereby hypothesize that reduced sheep growth performance under overgrazing conditions would be associated with metabolic and immune response alterations. This study used an untargeted metabolomics analysis by conducting ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) of sheep serum under overgrazing and light grazing conditions to identify metabolic disruptions in response to overgrazing.

Results
The sheep body weight gains as well as serum biochemical variables associated with immune responses and nutritional metabolism (immunoglobulin G, albumin, glucose, and nonesterified fatty acids) were significantly decreased with overgrazing compared with light grazing condition. In contrast, other serum parameters such as alanine and aspartate aminotransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen, and interleukin-8 were markedly higher in the overgrazing group. Principal component analysis discriminated the metabolomes of the light grazing from the overgrazing group. Multivariate and univariate analyses revealed changes in the serum concentrations of 15 metabolites (9 metabolites exhibited a marked increase, whereas 6 metabolites showed a significant decrease) in the overgrazing group. Major changes of fatty acid oxidation, bile acid biosynthesis, and purine and protein metabolism were observed.

Conclusions
These findings offer metabolic evidence for putative biomarkers for overgrazing-induced changes in serum metabolism. Target-identification of these particular metabolites may potentially increase our knowledge of the molecular mechanisms of altered immune responses, nutritional metabolism, and reduced sheep growth performance under overgrazing conditions.
Synchronous and metachronous liver metastases in patients with colorectal cancer—towards a clinically relevant definition
Authors: Engstrand Jennie , Strömberg Cecilia , Nilsson Henrik , Freedman Jacob , Jonas Eduard 
Published: December 2019

AbstractBackgroundApproximately 25% of patients with colorectal cancer (CRC) will have liver metastases classified as synchronous or metachronous. There is no consensus on the defining time point for synchronous/metachronous, and the prognostic implications thereof remain unclear. The aim of the study was to assess the prognostic value of differential detection at various defining time points in a population-based patient cohort and conduct a literature review of the topic.MethodsAll patients diagnosed with CRC in the counties of Stockholm and Gotland, Sweden, during 2008 were included in the study and followed for 5 years or until death to identify patients diagnosed with liver metastases. Patients with liver metastases were followed from time of diagnosis of liver metastases for at least 5 years or until death. Different time points defining synchronous/metachronous detection, as reported in the literature and identified in a literature search of databases (PubMed, Embase, Cochrane library), were applied to the cohort, and overall survival was calculated using Kaplan-Meier curves and compared with log-rank test. The influence of synchronously or metachronously detected liver metastases on disease-free and overall survival as reported in articles forthcoming from the literature search was also assessed.ResultsLiver metastases were diagnosed in 272/1026 patients with CRC (26.5%). No statistically significant difference in overall survival for synchronous vs. metachronous detection at any of the defining time points (CRC diagnosis/surgery and 3, 6 and 12 months post-diagnosis/surgery) was demonstrated for operated or non-operated patients. In the literature search, 41 publications met the inclusion criteria. No clear pattern emerged regarding the prognostic significance of synchronous vs. metachronous detection.ConclusionSynchronous vs. metachronous detection of CRC liver metastases lacks prognostic value. Using primary tumour diagnosis/operation as standardized cut-off point to define synchronous/metachronous detection is semantically correct. In synchronous detection, it defines a clinically relevant group of patients where individualized multimodality treatment protocols will apply.
The relationship between physical activity, mental wellbeing and symptoms of mental health disorder in adolescents: a cohort study
Authors: Bell Sarah Louise , Audrey Suzanne , Gunnell David , Cooper Ashley , Campbell Rona 
Published: December 2019

AbstractBackgroundMental illness is a worldwide public health concern. In the UK, there is a high prevalence of mental illness and poor mental wellbeing among young people. The aim of this study was to investigate whether physical activity is associated with better mental wellbeing and reduced symptoms of mental health disorder in adolescents.MethodsA cohort of 928 12–13 year olds (Year 8) from six secondary schools in England, who had participated in the AHEAD trial, ‘Activity and Healthy Eating in Adolescence’, were followed up three years later (when 15–16 years old, Year 11). At baseline, physical activity was measured using accelerometers. At follow-up, mental wellbeing was measured using the ‘Warwick Edinburgh Mental Wellbeing Scale’ (WEMWBS) and symptoms of mental health disorder using the ‘Strengths and Difficulties Questionnaire’ (SDQ). Multivariable linear regression analyses were used to investigate associations between physical activity and both mental wellbeing and symptoms of mental health disorder.Results794 (86%) of the eligible 928 young people provided valid accelerometer data at baseline. 668 (72%) provided complete mental wellbeing data and 673 (73%) provided complete symptoms of mental health disorder data at follow-up. The multivariable analyses showed no evidence of an association between physical activity volume (counts per minute (cpm)) or intensity (Moderate to Vigorous Physical Activity (MVPA)) and mental wellbeing (WEMWBS overall score) or overall symptoms of mental health disorder (SDQ Total Difficulties Score). However, higher levels of physical activity volume at age 12–13 years were associated with lower scores on the emotional problems subscale of the SDQ at age 15–16 years.ConclusionsThis cohort study found no strong evidence that physical activity is associated with better mental wellbeing or reduced symptoms of mental health disorder in adolescents. However, a protective association between physical activity and the emotional problems subscale of the SDQ was found. This suggests that physical activity has the potential to reduce symptoms of depression and anxiety in adolescents. Future cohort study designs should allow for repeated measures to fully explore the temporal nature of any relationship.
Palmitoylethanolamide counteracts substance P-induced mast cell activation in vitro by stimulating diacylglycerol lipase activity
Authors: Petrosino Stefania , Schiano Moriello Aniello , Verde Roberta , Allarà Marco , Imperatore Roberta , Ligresti Alessia , Mahmoud Ali Mokhtar , Peritore Alessio Filippo , Iannotti Fabio Arturo , Di Marzo Vincenzo 
Published: December 2019

Abstract
Background
Palmitoylethanolamide (PEA) is a pleiotropic endogenous lipid mediator currently used as a “dietary food for special medical purposes” against neuropathic pain and neuro-inflammatory conditions. Several mechanisms underlie PEA actions, among which the “entourage” effect, consisting of PEA potentiation of endocannabinoid signaling at either cannabinoid receptors or transient receptor potential vanilloid type-1 (TRPV1) channels. Here, we report novel molecular mechanisms through which PEA controls mast cell degranulation and substance P (SP)-induced histamine release in rat basophilic leukemia (RBL-2H3) cells, a mast cell model.

Methods
RBL-2H3 cells stimulated with SP were treated with PEA in the presence and absence of a cannabinoid type-2 (CB2) receptor antagonist (AM630), or a diacylglycerol lipase (DAGL) enzyme inhibitor (OMDM188) to inhibit the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). The release of histamine was measured by ELISA and β-hexosaminidase release and toluidine blue staining were used as indices of degranulation. 2-AG levels were measured by LC-MS. The mRNA expression of proposed PEA targets (Cnr1, Cnr2, Trpv1, Ppara and Gpr55), and of PEA and endocannabinoid biosynthetic (Napepld, Dagla and Daglb) and catabolic (Faah, Naaa and Mgl) enzymes were also measured. The effects of PEA on the activity of DAGL-α or -β enzymes were assessed in COS-7 cells overexpressing the human recombinant enzyme or in RBL-2H3 cells, respectively.

Results
SP increased the number of degranulated RBL-2H3 cells and triggered the release of histamine. PEA counteracted these effects in a manner antagonized by AM630. PEA concomitantly increased the levels of 2-AG in SP-stimulated RBL-2H3 cells, and this effect was reversed by OMDM188. PEA significantly stimulated DAGL-α and -β activity and, consequently, 2-AG biosynthesis in cell-free systems. Co-treatment with PEA and 2-AG at per se ineffective concentrations downmodulated SP-induced release of histamine and degranulation, and this effect was reversed by OMDM188.

Conclusions
Activation of CB2 underlies the inhibitory effects on SP-induced RBL-2H3 cell degranulation by PEA alone. We demonstrate for the first time that the effects in RBL-2H3 cells of PEA are due to the stimulation of 2-AG biosynthesis by DAGLs.
Increased gait variability during robot-assisted walking is accompanied by increased sensorimotor brain activity in healthy people
Authors: Berger Alisa , Horst Fabian , Steinberg Fabian , Thomas Fabian , Müller-Eising Claudia , Schöllhorn Wolfgang I. , Doppelmayr Michael 
Published: December 2019

Abstract
Background
Gait disorders are major symptoms of neurological diseases affecting the quality of life. Interventions that restore walking and allow patients to maintain safe and independent mobility are essential. Robot-assisted gait training (RAGT) proved to be a promising treatment for restoring and improving the ability to walk. Due to heterogenuous study designs and fragmentary knowlegde about the neural correlates associated with RAGT and the relation to motor recovery, guidelines for an individually optimized therapy can hardly be derived. To optimize robotic rehabilitation, it is crucial to understand how robotic assistance affect locomotor control and its underlying brain activity. Thus, this study aimed to investigate the effects of robotic assistance (RA) during treadmill walking (TW) on cortical activity and the relationship between RA-related changes of cortical activity and biomechanical gait characteristics.

Methods
Twelve healthy, right-handed volunteers (9 females; M = 25 ± 4 years) performed unassisted walking (UAW) and robot-assisted walking (RAW) trials on a treadmill, at 2.8 km/h, in a randomized, within-subject design. Ground reaction forces (GRFs) provided information regarding the individual gait patterns, while brain activity was examined by measuring cerebral hemodynamic changes in brain regions associated with the cortical locomotor network, including the sensorimotor cortex (SMC), premotor cortex (PMC) and supplementary motor area (SMA), using functional near-infrared spectroscopy (fNIRS).

Results
A statistically significant increase in brain activity was observed in the SMC compared with the PMC and SMA (p < 0.05), and a classical double bump in the vertical GRF was observed during both UAW and RAW throughout the stance phase. However, intraindividual gait variability increased significantly with RA and was correlated with increased brain activity in the SMC (p = 0.05; r = 0.57).

Conclusions
On the one hand, robotic guidance could generate sensory feedback that promotes active participation, leading to increased gait variability and somatosensory brain activity. On the other hand, changes in brain activity and biomechanical gait characteristics may also be due to the sensory feedback of the robot, which disrupts the cortical network of automated walking in healthy individuals. More comprehensive neurophysiological studies both in laboratory and in clinical settings are necessary to investigate the entire brain network associated with RAW.
Genetic perturbations of disease risk genes in mice capture transcriptomic signatures of late-onset Alzheimer’s disease
Authors: Pandey Ravi S. , Graham Leah , Uyar Asli , Preuss Christoph , Howell Gareth R. , Carter Gregory W. 
Published: December 2019

Abstract
Background
New genetic and genomic resources have identified multiple genetic risk factors for late-onset Alzheimer’s disease (LOAD) and characterized this common dementia at the molecular level. Experimental studies in model organisms can validate these associations and elucidate the links between specific genetic factors and transcriptomic signatures. Animal models based on LOAD-associated genes can potentially connect common genetic variation with LOAD transcriptomes, thereby providing novel insights into basic biological mechanisms underlying the disease.

Methods
We performed RNA-Seq on whole brain samples from a panel of six-month-old female mice, each carrying one of the following mutations: homozygous deletions of Apoe and Clu; hemizygous deletions of Bin1 and Cd2ap; and a transgenic APOEε4. Similar data from a transgenic APP/PS1 model was included for comparison to early-onset variant effects. Weighted gene co-expression network analysis (WGCNA) was used to identify modules of correlated genes and each module was tested for differential expression by strain. We then compared mouse modules with human postmortem brain modules from the Accelerating Medicine’s Partnership for AD (AMP-AD) to determine the LOAD-related processes affected by each genetic risk factor.

Results
Mouse modules were significantly enriched in multiple AD-related processes, including immune response, inflammation, lipid processing, endocytosis, and synaptic cell function. WGCNA modules were significantly associated with Apoe−/−, APOEε4, Clu−/−, and APP/PS1 mouse models. Apoe−/−, GFAP-driven APOEε4, and APP/PS1 driven modules overlapped with AMP-AD inflammation and microglial modules; Clu−/− driven modules overlapped with synaptic modules; and APP/PS1 modules separately overlapped with lipid-processing and metabolism modules.

Conclusions
This study of genetic mouse models provides a basis to dissect the role of AD risk genes in relevant AD pathologies. We determined that different genetic perturbations affect different molecular mechanisms comprising AD, and mapped specific effects to each risk gene. Our approach provides a platform for further exploration into the causes and progression of AD by assessing animal models at different ages and/or with different combinations of LOAD risk variants.
Open-chest cardiopulmonary resuscitation versus closed-chest cardiopulmonary resuscitation in patients with cardiac arrest: a systematic review and meta-analysis
Authors: Wang Mao , Lu Xiaoguang , Gong Ping , Zhong Yilong , Gong Dianbo , Song Yi 
Published: December 2019

AbstractBackgroundCardiopulmonary resuscitation is the most urgent and critical step in the rescue of patients with cardiac arrest. However, only about 10% of patients with out-of-hospital cardiac arrest survive to discharge. Surprisingly, there is growing evidence that open-chest cardiopulmonary resuscitation is superior to closed-chest cardiopulmonary resuscitation. Meanwhile, The Western Trauma Association and The European Resuscitation Council encouraged thoracotomy in certain circumstances for trauma patients. But whether open-chest cardiopulmonary resuscitation is superior to closed-chest cardiopulmonary resuscitation remains undetermined. Therefore, the aim of this study was to summarize current studies on open-chest cardiopulmonary resuscitation in a systematic review, comparing it to closed-chest cardiopulmonary resuscitation, in a meta-analysis.MethodsIn this systematic review and meta-analysis, we searched the PubMed, EmBase, Web of Science, and Cochrane Library databases from inception to May 2019 investigating the effect of open-chest cardiopulmonary resuscitation and closed-chest cardiopulmonary resuscitation in patients with cardiac arrest, without language restrictions. Statistical analysis was performed using Stata 12.0 software. The primary outcome was return of spontaneous circulation. The secondary outcome was survival to discharge.ResultsSeven observational studies were eligible for inclusion in this meta-analysis involving 8548 patients. No comparative randomized clinical trial was reported in the literature. There was no significant difference in return of spontaneous circulation and survival to discharge between open-chest cardiopulmonary resuscitation and closed-chest cardiopulmonary resuscitation in cardiac arrest patients. The odds ratio (OR) were 0.92 (95%CI 0.36–2.31,P > 0.05) and 0.54 (95%CI 0.17–1.78,P > 0.05) for return of spontaneous circulation and survival to discharge, respectively. Subgroup analysis of cardiac arrest patients with trauma showed that closed-chest cardiopulmonary resuscitation was associated with higher return of spontaneous circulation compared with open-chest cardiopulmonary resuscitation (OR = 0.59 95%CI 0.37–0.94,P < 0.05). And subgroup analysis of cardiac arrest patients with non-trauma showed that open-chest cardiopulmonary resuscitation was associated with higher ROSC compared with closed-chest cardiopulmonary resuscitation (OR = 3.12 95%CI 1.23–7.91,P < 0.05).ConclusionsIn conclusion, for patients with cardiac arrest, we should implement closed-chest cardiopulmonary resuscitation as soon as possible. However, for cardiac arrest patients with chest trauma who cannot perform closed-chest cardiopulmonary resuscitation, open-chest cardiopulmonary resuscitation should be implemented as soon as possible.