bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet miRNA bio-signature discriminates between dementia with Lewy bodies and Alzheimer disease: A cross-sectional study.
Authors: Gámez-Valero Ana , Campdelacreu Jaume , Vilas Dolores , Ispierto Lourdes , Samaniego Daniela , Gascón-Bayarri Jordi , Reñé Ramón , Álvarez Ramiro , Armengol Maria P , Borràs Francesc E. , Beyer Katrin 
Published: May 2020

Abstract
Background

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets have been previously related to neurodegeneration. They contain microRNAs (miRNAs), and their analysis may provide disease biomarkers.
Methods

Small RNAs from platelets of DLB patients and controls were analyzed by Next Generation Sequencing (NGS), and miRNAs deregulated in DLB were selected. Expression of these miRNAs was then determined and validated by LNA-based qRT-PCR in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Their predictive diagnostic potential was calculated by ROC curve analysis. miRTarbase and miRGate were used for target prediction.
Results

We profiled the whole platelet miRNA transcriptome from 7 DLB patients and 7 controls using NGS. Twenty-two selected miRNAs were further validated in independent studies (2017–2019) including DLB (n = 59), AD (n = 28), and PD (n = 24) patients, and control individuals (n = 51). Our results demonstrated downregulated expression levels for hsa-let-7d-5p (fold change 0.14; p = 0.006), hsa-miR-132-5p (0.12; p = 0.0015), hsa-miR-142-3p (0.07; p = 0.00047), hsa-miR-146a-5p (0.07; p = 0.00035), hsa-miR-150-5p (0.10; p = 0.0098), hsa-miR-25-3p (0.13; p = 0.0019) and hsa-miR-26b-5p (0.09; p = 0.0014) in DLB compared to AD. ROC curve for this seven-miRNA biosignature yielded an area under the curve (AUC) of 1. Both hsa-miR-142-3p and hsa-miR-150-5p, were down-regulated in DLB compared to controls (AUC = 0.85). Comparing AD and controls, miRNAs hsa-miR-132-5p, hsa-miR-146a-5p, hsa-miR-25-3p, and hsa-miR-6747-3p were up-regulated in AD (AUC = 0.94); and hsa-miR-128-3p and hsa-miR-139-5p were down-regulated in PD compared to controls (AUC = 0.81). Predictive target analysis identified three disease-specific pathway clusters as a result of platelet-miRNA deregulation. In DLB, pathways related to gene expression and small RNA metabolism; in AD, pathways related to stress response and RNA stress granules; and in PD pathways related to protein phosphorylation, metabolism and degradation were identified.
Conclusion

A platelet-associated bio-signature composed of 7 miRNAs is highly specific and sensitive for distinguishing DLB from AD.
The incidence of in-stent restenosis after drug-eluting stent implantation in patients on chronic hemodialysis
Authors: Motohiro Masayuki , Sugita Hiroshi , Shibutani Hiroki , Morishita Syun , Tanaka Masami , Tsujimoto Satoshi , Shiojima Ichiro 
Published: May 2020

Abstract
Background: Recently, drug-eluting stents have been widely adopted rather than bare-metal stents in patients on chronic hemodialysis (HD) based on the extrapolation of data from patients on non-HD. However, whether DES implantation is associated with a reduced rate of in-stent restenosis (ISR) is unclear. We investigated the incidence of ISR and its predictors in patients on HD after drug-eluting stent implantation.Methods and Results: We analyzed 194 consecutive patients (331 lesions) on HD who underwent follow-up angiography after drug-eluting stent implantation. ISR was observed in 74 lesions (22.4%). Angiographically, the relative incidence of AHA/ACC type C lesion was increased (47% vs. 32%; P=0.043), the minimal lumen diameter (MLD) before DES implantation was smaller (0.82±0.49 vs. 0.97±0.45mm; P<0.01) and the lesion length (LL) was increased (30.2±16.1 vs. 24.4±12.1mm; P=0.023) in lesions with ISR compared to those without ISR. The rate of rotational atherectomy use was also increased in lesions with ISR compared to those without ISR (50% vs. 25%; P<0.01). In a multivariate analysis, the MLD before drug-eluting stent implantation (odds ratio [OR] =0.50, 95% confidence interval [CI] 0.27-0.91, P=0.024), LL (OR=1.02, 95% CI 1.00-1.04, P=0.030) and the use of rotational atherectomy (OR=2.71, 95% CI 1.55-4.72, P<0.01) were independent predictors of ISR. The incidence of ISR was similar between lesions treated with the first-generation (25.8%) and the second-generation DESs (20.4%).Conclusion: ISR was observed in 74 lesions (22.4%). A small MLD, long LL and the use of rotational atherectomy were independent predictors of ISR after drug-eluting stent implantation in patients on HD. There was no significant difference in ISR rate between the first- and the second-generation drug-eluting stents.
Clinical characteristics of non-small cell lung cancer patients with EGFR mutations and ALK&amp;ROS1 fusions
Authors: Liu Qinghua , Wu Heming , Wu Hailing , Rao Hui , Yu Zhikang , Huang Qingyan , Zhong Zhixiong 
Published: May 2020

Abstract
Background
The purpose of this study was to study the relationship between ALK&ROS1 gene rearrangement, EGFR mutation, non-ALK&ROS1/EGFR and their clinical characteristics in non-small cell lung cancer (NSCLC) patients to distinguish these different types.
Methods
Both ALK&ROS1 gene rearrangements and EGFR mutations testing were performed in 461 NSCLC patients. The clinical characteristics and associated pulmonary abnormalities were investigated.
Results
Of the 461 patients studied, we identified 175 cases with EGFR mutations (38.0%, 175/461). ALK gene fusions were identified in 33 cases (33/461, 7.2%) and ROS1 gene fusions were identified in 9 cases (9/461, 1.9%). In the EGFR-positive group, the majority were female (50.9%, P < 0.001), non-smoking (76.6%, P < 0.001), adenocarcinoma (90.9%, P < 0.001) patients. Compared with the non-ALK&ROS1/EGFR group, the significant differences in ALK&ROS1-positive group were: younger (P < 0.001), the majority were female (52.4%, P < 0.001), non-smoking (66.7%, P = 0.001), adenocarcinoma (90.5%, P = 0.002) patients, appeared lymphangitic was more (23.8%, P = 0.044) and emphysema was less (9.5%, P < 0.001). The NSCLC patients with exon 19 deletion (74.7%) and L858R (86.4%) most were non-smokers, while patients with L861Q (62.5%) and G719 × (66.7%) most were smokers.
Conclusions
NSCLC with EGFR mutation and ALK&ROS1 gene rearrangement were more likely to occur in young, non-smoking women. Patients with ALK&ROS1 gene rearrangements and EGFR mutations were less likely to develop emphysema.
Iron metabolism in patients with rheumatoid arthritis
Authors: Tański Wojciech , Chabowski Mariusz , Jankowska-Polańska Beata , Jankowska Ewa Anita 
Published: May 2020

Abstract
Background. The most common haematological manifestation in RA is anaemia (30-60%). The aim of the study was the assessment of the prevalence of iron deficiency in RA patients using standard parameters and new biomarkers.Material and methods. The study was conducted on 62 RA patients, aged 52±15, treated at the Department of Internal Medicine of the 4th Military Teaching Hospital in Wrocław between 2016 and 2017. The control group comprised 58 healthy individuals, aged 56±9. The following tests were carried out: DAS-28, complete blood count, creatinine, uric acid, AspAT, ALAT, GGT, bilirubin, TSH, lipid profile, iron, TIBC, transferrin saturation, ferritin, soluble transferrin receptor, hepcidin, and IL-6.Results. A higher percentage of RA patients compared with the control group had TSAT values below 20%, ferritin levels below the reference range, soluble transferrin receptor levels above 1.59mg/l and hepcidin levels below 14.5 ng/ml. 60% of RA patients had iron deficiency. The correlations between reduced ferritin levels and younger age, female gender, lower GGT levels and increased platelet counts was shown. The correlations were found between iron deficiency and younger age, female gender, reduced haemoglobin levels, increased platelet counts, increased GFR, reduced GGT levels, lower disease activity and less frequent use of sulfasalazineConclusions. Iron deficiency is common in RA patients with high disease activity. RA patients had lower transferrin saturation, lower ferritin and hepcidin levels and higher serum sTfR levels. The increased DAS-28 scores and reduced haemoglobin levels were the two strongest determinants of iron deficiency in RA patients.
High-Cadence Cycling for Parkinson Disease: A Single-Arm Hybrid Implementation and Effectiveness Clinical Trial in the Community Setting
Authors: McKee Kathleen , Johnson Remy K , Chan James , Wills Anne-Marie 
Published: May 2020

Abstract
BACKGROUND Efficacy of exercise to improve motor symptoms in Parkinson Disease (PD) has been established in multiple clinical trials. The Pedaling for Parkinson’s ™ (PFP) program is an existing community-based cycling intervention for individuals with PD. Although the program design was informed by efficacy studies, the implementation and effectiveness of the program have not been studied. We used a hybrid trial, which blends the study of implementation and effectiveness, to study the implementation of PFP in community gyms in the greater Boston area. METHODS This was a single-arm open-label pragmatic hybrid type 3 clinical trial designed to test implementation and observe clinical effectiveness. The implementation strategy consisted of enhanced multi-modal training and support for community-based gyms to implement the PFP protocol. Individuals with Hoehn and Yahr stage I-III idiopathic PD were recruited to participate. Primary implementation outcomes included adoption, gym fidelity, participant adherence, implementation cost, sustainability, acceptability, and safety. Secondary effectiveness outcomes included disease and quality of life measures. RESULTS 34 gyms were invited to participate. 4 gyms agreed to participate and implemented the PFP protocol. 24 individuals with idiopathic PD agreed to participate in the study and started classes. The program was implemented safely and sustainably across all sites but with high fidelity at only one of four gyms. 58% of individuals who started classes completed at least 80% of classes. 96% of participants who started classes enjoyed the program and 87% wished to continue. No effectiveness outcomes demonstrated a significant change from pre to post. CONCLUSION Our implementation strategy of additional multi-modal training and support in starting a PFP class was insufficient to achieve wide adoption of and high fidelity and adherence to the PFP protocol. However, participating gyms’ modifications of the PFP protocol in this study suggests such protocol modification may be necessary for effective implementation in the community setting. Future studies should first establish effectiveness of a revised PFP protocol. Implementation could then be achieved through a participatory approach in which barriers to gym participation are identified and mitigated early in the implementation process.
Crack propagation characteristics and mechanism of energy evolution in intermittent externally fissured sandstone
Authors: Yu Hui , Liu Shaowei , Jia Housheng , Zheng Huaichang , Liu Zhihe 
Published: May 2020

Abstract
Geostress environment and fracture distribution both exert important influences on the mechanical properties and failure modes of fissured rock masses. Laboratory test results are presented here to simulate particle flow code (PFC) in externally double-fissured sandstone samples. Mechanical responses of confining pressure and rock bridge angle on stress-strain curves as well as macroscopic damage and fracture propagation in these samples were studied in order to elucidate energy dissipation mechanisms. The results of this analysis show that fissured sandstone peak strength and elastic modulus as well as peak axial and lateral strain increase significantly as rock bridge angle decreases while peak strength increases slightly in concert with confining pressure. Rock bridge angle exerts an important influence on macro fracturing patterns; when β = 0°, wing cracks from two pre-existing external fissures propagate in opposite directions, but when β = 60°, the inner tips of two external fissures become directly connected. The evolution of specimen fracturing passes through four main stages, elastic compression deformation, stable crack development, unstable crack development, and post-peak accelerated crack development. Internal contact forces reach maximum values at the peak stress point, while cracks are mainly tensile and shear examples are mostly distributed at orientations between 80° and 100°. Shear cracks are mainly generated along the direction of main stress, σ 1 , while pre-peak dissipated energy is small, and increases rapidly at the post-peak. As rock bridge angle decreases, peak strain and boundary energies both increase significantly. Data show that energy and rock bridge angle are approximately linearly positively correlated.
Is it feasible to predict lymph node metastasis intraoperatively or postoperatively in early-stage lung adenocarcinoma: the application of machine learning algorithms?
Authors: Wu Yijun , Chong Yuming , Liu Jianghao , Wu Pancheng , Wang Yanyu , Han Chang , Gong Liang , Liu Xinyu , Wang Zhile , Liang Naixin , Li Shanqing 
Published: May 2020

Abstract
BackgroundLymph node metastasis (LNM) status can be a critical decisive factor for clinical management of lung cancer. Accurately evaluating the risk of LNM during or after the surgery can be helpful for making clinical decisions. This study aims to incorporate clinicopathological characteristics to develop reliable machine learning (ML)-based models for predicting LNM in patients with early-stage lung adenocarcinoma.MethodsA total of 709 lung adenocarcinoma patients with tumor size ≤ 2 cm were enrolled for analysis and modeling by multiple ML algorithms. The receiver operating characteristic (ROC) curve and decision curve were used for evaluating model’s predictive performance and clinical usefulness. Feature selection based on potential models was performed to identify most-contributed predictive factors.ResultsLNM occurred in 11.3% (80/709) of patients with lung adenocarcinoma. Most models reached high areas under the ROC curve (AUCs) > 0.9. In the decision curve, all models performed better than the treat-all and treat-none lines. The random forest classifier (RFC) model, with a minimal number of 5 variables introduced (including carcinoembryonic antigen, solid component, micropapillary component, lymphovascular invasion and pleural invasion), was identified as the optimal model for predicting LNM, because of its excellent performance in both ROC and decision curves. The cost-efficient application of RFC model could precisely predict LNM during or after the operation of early-stage adenocarcinomas (sensitivity: 87.5%; specificity: 82.2%).ConclusionsIncorporating clinicopathological characteristics, it is feasible to predict LNM intraoperatively or postoperatively by ML algorithms.Trial registration: NA
Analgecine inhibits NF-kB to regulate microglia polarization by TLR4 MyD88-dependent and MyD88-independent pathways in ischemic stroke
Authors: Yang Cuicui , Gong Shili , Chen Xiaoping , Wang Mingyang , Zhang Li , Li Lin , Zhang Dongqing , Zhang Lan , Hu Chaoying 
Published: May 2020

Abstract
Background: Microglia polarization plays an important role in poststroke recovery. Inhibition of proinflammatory (M1) polarization and promotion of anti-inflammatory (M2) polarization of microglia are potential therapeutic strategies for inflammation reduction and neuronal recovery after stroke. Analgecine (AGC), the extracts of Vaccin a variola-inoculated rabbit skin, is used to treat patients with chronic low back pain due to degenerative vertebral disorders. Here, we evaluated the neuroprotective effect of AGC in stroke and investigate anti-inflammatory mechanism of AGC on microglia-mediated neural damage.Methods: Sprague-Dawley (SD) rats underwent 120 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. We injected AGC intravenously into rats starting 3 h after the onset of MCAO. Then we investigated the effect of AGC on neurological impairment, neuronal loss and inflammatory cytokines. For in vitro study, we examined the effect of AGC on microglial polarization in oxygen-glucose deprivation/reperfusion (OGD/R) or LPS/IFN-γ induced microglia cells and further investigated neuroprotective effect of ACG in microglia-mediated neural damage based on the direct or indirect co-culture systems. Finally, TLR4/Myd88/ NF-κB pathway was detected in OGD/R-induced microglia cells with or without Myd88 siRNA transfection.Results: AGC treatment reduced the neurological deficits and suppressed neuronal loss. In terms of inflammatory cytokines, AGC inhibited the release of pro-inflammatory cytokines and elevated the content of anti-inflammatory cytokines in vivo (SD rats) and in vitro (microglia). We further showed that AGC promoted M1 to M2 phenotypic transition of microglia in OGD/R or LPS/IFN-γ induced microglia cells. Based on the direct or indirect co-culture systems, we found AGC indirectly inhibits LPS/IFN-γ-induced neuronal damage by modulating microglial polarization. Moreover, AGC suppressed the nuclear translocation of the phosphorylation of NF-κB p65 by inhibiting the TLR4/Myd88/TRAF6 but not TLR9 signaling. We also confirmed that AGC-regulated TLR4 inhibition partly dependent on Myd88 in a Myd88 depletion cell line.Conclusion: Our findings provide a new understanding of AGC in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing TLR4 MyD88-dependent and MyD88-independent pathways. Thus, AGC treatment may represent a novel approach in inflammation reduction or poststroke recovery.
SILEX: A fast and inexpensive high-quality DNA extraction method suitable for multiple sequencing platforms and recalcitrant plant species
Authors: vilanova santiago , Alonso David , Gramazio Pietro , Plazas Mariola , Ferrante Paola , Schmidt Maximilian , Diez-Niclós María J. , Usadel Björn , Giuliano Giovanni , Prohens Jaime 
Published: May 2020

Abstract
Background: The use of sequencing and genotyping platforms has undergone dramatic improvements, enabling the generation of a wealth of genomic information. Despite this progress, the availability of high-quality genomic DNA (gDNA) in sufficient concentrations is often a main limitation, especially for third-generation sequencing platforms. A variety of DNA extraction methods and commercial kits are available. However, many of these are costly and frequently give either low yield or low-quality DNA, inappropriate for next generation sequencing (NGS) platforms. Here, we describe a fast and inexpensive DNA extraction method (SILEX) applicable to a wide range of plant species and tissues. Results: SILEX is a high-throughput DNA extraction protocol, based on the standard CTAB method with a DNA silica matrix recovery, which allows obtaining NGS-quality high molecular weight genomic plant DNA free of inhibitory compounds. SILEX was compared with a standard CTAB extraction protocol and a common commercial extraction kit in a variety of species, including recalcitrant ones, from different families. In comparison with the other methods, SILEX yielded DNA in higher concentrations and of higher quality. Manual extraction of 48 samples can be done in 96 min by one person at a cost of 0.12 €/sample of reagents and consumables. Hundreds of tomato gDNA samples obtained with either SILEX or the commercial kit were successfully genotyped with Single Primer Enrichment Technology (SPET) with the Illumina HiSeq 2500 platform. Furthermore, DNA extracted from Solanum elaeagnifolium using this protocol was assessed by Pulsed-field gel electrophoresis (PFGE), obtaining a suitable size ranges for most sequencing platforms that required high-molecular-weight DNA such as Nanopore or PacBio. Conclusions: A high-throughput, fast and inexpensive DNA extraction protocol was developed and validated for a wide variety of plants and tissues. SILEX offers an easy, scalable, efficient and inexpensive way to extract DNA for various next-generation sequencing applications including SPET and Nanopore among others.
The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study
Authors: Wang Zhuo , Yang Fangkun , Ma Menghuai , Bao Qinyi , Shen Jinlian , Ye Feiming , xie xiaojie 
Published: May 2020

Abstract
Background: Growth differentiation factor 15(GDF-15) concentration is apparently associated with cardiovascular disease, but whether there is a causal relationship has not been testified. Methods: We utilized Mendelian randomization to assess the function of GDF-15 in incidence of cardiovascular disease. The single-nucleotide polymorphism- GDF-15 association evaluations came from meta-analysis of genome-wide association study (GWAS). Besides inverse-variance weighted, MR-Egger test and weighted median method were applied to examine sensitivity. Results: Base on the instruments, GDF-15 level linked to increased risk of cardioembolic stroke (1.06, OR 1.09 per SD increase, 95% CI 1.01, 1.19) and atrial fibrillation (OR 1.03 per SD increase, 95% CI 1.0, 1.06). However, the significant causal relationship between GDF-15 and the other cardiovascular diseases was not found in our work. Conclusions: The result suggested that GDF-15 is causally associated with the risk of cardioembolic stroke and atrial fibrillation, providing conceivable strategies to alleviate the burden of cardiovascular disease.
COVID-19: Impact of early decision and type of lock-down over the spread of the virus
Authors: Humaid Jehan Al , Khan Soban Qadir , Farooqi Faraz , Alhareky Muhanad , Alonaizan Faisal , Harbi Fahad Al 
Published: May 2020

Abstract
Objectives: Aim of the present study was to analyze the (1) partial vs complete lock down effects over the spread of COVID-19, (2) time taken for complete lock down decision in relation with the spread of disease. Method: COVID-19 data for the current observational study was taken up to 14th April since the outbreak of the virus. There were 28 countries which passed through the inclusion criteria and included for analysis.Results: Average number of reported cases during 1st, 2nd and 3rd week of lockdown (complete vs partial) were 6872.9 vs 8990, 13431 vs 20032 and 19005 vs 26859.5 respectively. However, differences were not statistically significant. Days taken to announce complete lockdown was found significantly correlated with number of cases reported during 1st and 2nd after lockdown announced. Similarly, number of reported cases when lockdown announced had direct and strong correlation with number of weekly reported cases after lockdown.Conclusion: Number of weekly reported cases among partially lockdown countries was found higher compare to complete lockdown countries. Furthermore, early decision of lockdown was extremely important as it had grave impact over the spread of disease.