bluuebunny/crossref_metadata_2025 huggingface dataset:
¿Compartir contenidos en línea o no? Un análisis del artículo 17 de la Directiva sobre ropiedad intelectual en el mercado único digital = To upload or not – an analysis of art. 17 of the Directive on copyright in the digital single market
Authors: Spindler Gerald
Published: March 2020

Resumen: El “filtro de carga” para las plataformas de intercambio en línea ha sido uno de los temas más candentes en relación con la nueva Directiva 2019/790 sobre derechos de autor y derechos afines en el Mercado Único Digital (DCMUD). La batalla continúa en el ámbito nacional a la hora de afrontar la correcta y equilibrada transposición del art. 17 DCMUD, en particular en lo que respecta a garantizar la libertad de expresión. Este ensayo explora el sistema de responsabilidad del citado art. 17 y analiza su potencial contradicción con los derechos fundamentales de la Unión Europea, tal y como han sido ponderados por el TJUE en el asunto SABAM Netlog y otros recientes, en particular, con la pro­hibición de deberes generales de control y supervisión. Aunque sería posible argumentar que el art. 17 DCMUD podría superar ese examen de contraste, el precepto articula varias opciones de transposición que podrían emplearse para garantizar los derechos de los usuarios y la libertad de expresión.Palabras clave: propiedad intelectual, derechos de autor, plataformas de intermediación, puertos seguros, filtros de carga, contenidos digitales, contenidos generados por los usuarios, derechos funda­mentales, libertad de expresión, liability, e-commerce.Abstract: The “upload-filter” for online sharing platforms have been one of the hot issues regar­ding the new DSM-directive on copyright. The battle continues at the national level concerning the correct and balanced implementation of Art. 17 DSM-D, in particular regarding the guarantee of free­dom of speech. The article explores the liability system of Art. 17 DSM-D and analyzes its potential contradiction to fundamental EU rights which has been laid down by the CJEU in the SABAM Netlog case, in particular the prohibition of general monitoring duties. Even though one might argue that Art. 17 DSM-D could pass that test the article develops several implementation options in order to safeguard user rights and freedom of speech.Keywords: copyright, intermediary platforms, safe harbours, upload filters, digital contents, user generated contents, fundamental rights, right of free speech, responsabilidad, comercio electrónico.
Investigating Self-Regulated Learning Differences Based on Gender, Scholarship, and Student’s Housing
Authors: Nurdian Susilowati  , Sari Lestari  , Dela Yuniarsih  , Deviana Hardining Maharani
Published: March 2020

This study aims to determine the differences students’ self-regulated learning (SRL) based on gender, scholarship, and student’s housing. Referring to Roscoe, our sample of the study is 36 students by using purposive sampling technique.. Analysis of the data are quantitative descriptive and hypothesis testing using independent sample t-test. The results showed that there is no significant difference in self-regulated learning based on gender. Self-regulated learning of female is higher than male students. Based on scholarships, there is no significant difference in self-regulated learning but students as scholarship recipients have higher self-regulated learning.Then, there is no significant difference based on house hold but students who live at home have highest self-regulated learning than students who live in boarding schools and boarding house. This research gives implication theoretically and practically. The finding proves that students who have self-regulated learning higher than others is due to good habit and intrinsic motivation. Thus; this research suggestsfor the university to establish good environment for students to develop themselves.
Comparison of the Methods for Analyzing Rate- and Pressure-Transient Data from Multistage Hydraulically Fractured Unconventional Gas Reservoirs
Authors: Atadeger Aykut , Batur Ela , Onur Mustafa , Thompson Leslie G.
Published: March 2020

In this study, we provide a detailed review and comparison of the various graphical methods, available in the literature, to interpret/analyze rate- and pressure-transient data acquired from multistage hydraulically fractured horizontal wells (MHFHWs) completed in unconventional gas reservoirs. The methods reviewed in this study do not address complex transport mechanisms and complex fracture networks, but do address transient matrix linear flow (Ibrahim and Wattenbarger 2006; Nobakht and Clarkson 2012a, 2012b; Chen and Raghavan 2013) and boundary-dominated flow (BDF). The methods for BDF are the contacted-volume methods based on the ending times of linear flow (Wattenbarger et al. 1998; Behmanesh et al. 2015) and the flowing material-balance (FMB) methods. The Agarwal-Gardner FMB method (Agarwal et al. 1999) and the conventional FMB method involve plotting rate-normalized pseudopressure vs. material-balance pseudotime. We delineate the advantages and limitations associated with each method and identify the best methods of interpretation and analysis. Three different production modes—constant rate (CR), constant bottomhole pressure (BHP) (CBHP), and variable-rate BHP—are considered. For comparison, various synthetic test data sets generated from a high-resolution spectral gas simulator, which treats nonlinear gas flow rigorously and accurately to simulate rate-transient data, is used. Both synthetic noise-free and noisy-rate pressure-data sets considering wide ranges of initial reservoir pressure and BHP, as well as real-field data sets, are used to compare the methods. For linear flow, the Nobakht-Clarkson method (Nobakht and Clarkson 2012a, 2012b) yields the best results, although its use is tedious because it requires an iterative procedure. The Chen and Raghavan (2013) method for linear flow seems to provide results that are comparable with the Nobakht-Clarkson method (Nobakht and Clarkson 2012b) but does not require an iterative procedure. The Ibrahim-Wattenbarger method (Ibrahim and Wattenbarger 2006) for linear-flow analysis always overestimates flow capacity compared with the other methods. Among the methods that discuss the ending time of linear flow, it was found that the unit-impulse method from Behmanesh et al. (2015) provides the best results for predicting gas in place. For BDF, the results show that the Agarwal-Gardner FMB method (Agarwal et al. 1999) is quite vulnerable to the error in rate/pressure data, whereas the conventional FMB method is more robust to noise and provides more accurate estimates of gas in place.
Multiresolution Grid Connectivity-Based Transform for Efficient History Matching of Unconventional Reservoirs
Authors: Kim Hyunmin , Datta-Gupta Akhil
Published: March 2020

Proper characterization of heterogeneous rock properties and hydraulic fracture parameters is essential for optimization of well spacing and reliable estimation of estimated ultimate recovery (EUR) in unconventional reservoirs. High resolution characterization of matrix properties and complex fracture parameters require efficient history matching of well production and pressure response. We propose a novel reservoir model parameterization method to reduce the number of unknowns, regularize the ill-posed problem, and enhance the efficiency of history matching of unconventional reservoirs.

The proposed method makes a low-rank approximation of the spatial distribution of reservoir properties taking into account the varying model resolution of the matrix and hydraulic fractures. Typically, hydraulic fractures are represented with much higher resolution through local grid refinements compared to the matrix properties. In our approach, the spatial property distribution of both matrix and fractures is represented using a few parameters via a linear transformation with multiresolution basis functions. The parameters in transform domain are then updated during model calibrations, substantially reducing the number of unknowns. The multiresolution basis functions are constructed by using Eigen-decomposition of an adaptively coarsened grid Laplacian corresponding to the data resolution. Higher property resolution at the area of interest through the adaptive resolution control while keeping the original grid structure improves quality of history matching, reduces simulation runtime, and improves the efficiency of history matching.

We demonstrate the power and efficacy of our method using synthetic and field examples. First, we illustrate the effectiveness of the proposed multiresolution parameterization by comparing it with traditional methods. For the field application, an unconventional tight oil reservoir model with a multistage hydraulic fractured well is calibrated using bottomhole pressure and water cut history data. The hydraulic fractures as well as the stimulated reservoir volume (SRV) near the well are represented with higher grid resolution. In addition to matrix and fracture properties, the extent of the SRV and hydraulic fractures are also adjusted through history matching using a multiobjective genetic algorithm. The calibrated ensemble of models are used to obtain bounds of production forecast.

Our proposed method is designed to calibrate reservoir and fracture properties with higher resolution in regions that have improved data resolution and higher sensitivity to the well performance data, for example the SRV region and the hydraulic fractures. This leads to a fast and efficient history matching workflow and enables us to make optimal development/completion plans in a reasonable time frame.
The effect of dot size in random-dot stereograms on the results of stereoacuity measurements
Authors: Zhao Lingzhi , Wu Huang
Published: March 2020

Background The aim of this study was to evaluate the effect of the size of the dots in random-dot stereograms on the results of stereoacuity measurements. Methods A stereopsis measurement system was created using a phoropter and two 4K smartphones. Three dot sizes, including 1×1 pixel, 6×6 pixels, and 10×10 pixels (equivalent to 0.17min arc, 1 min arc and 1.68 min arc arc, respectively), were used to form random-dot arrays, and each test pattern had one Lea symbol hidden within it. The resulting stereograms were tested on 30 subjects with normal acuity and stereoacuity. Results Stereoacuity measured with the 1-pixel dots was significantly worse than that measured with the 6-pixel dots (Wilcoxon signed ranks test, Z=-4.903, P <0.001) and the 10-pixel dots ( Z =-4.941, P <0.001). No significant difference was found between 6-pixel dot and 10-pixel dot stereograms ( Z =-1.000, P =0.317). Conclusion The size of the dots in random-dot stereograms affects the test results significantly when the dots are too small for the eye to resolve.
Potential value of serum Aspergillus IgG antibody detection in the diagnosis of invasive and chronic pulmonary aspergillosis in non-agranulocytic patients
Authors: Yu Qihong , He Jingdong , Xing Bin , Li Xin , Qian Hongyu , Zhang Hong , Xu Meilin , Peng Haiying
Published: March 2020

Background: At present, serum Aspergillus IgG and IgM antibody detection is mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but its value in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. IgM can be used as a marker of acute infection to help diagnose acute infection-related diseases. IgG is a marker of long-term infection and is used to assist in the diagnosis of pre-existing or chronic infection-related diseases. The aim of this study was to investigate and compare the value of serum Aspergillus IgG and IgM antibody detection in the diagnosis of IPA and CPA in non-agranulocytic patients.Methods: Fifty-eight cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of community-acquired bacterial pneumonia and 50 cases in the healthy control group were collected. The serum (1,3)-β-D-glucan test (G test) was performed with a chromogenic method, and the galactomannan test (GM test) and Aspergillus IgG and IgM antibody detection were performed by commercial enzyme-linked immunosorbent assay (ELISA) in all patients. The sensitivity and specificity, cut-off value and area under the curve (AUC) of Aspergillus IgG and IgM antibodies were further obtained by receiver operating characteristic (ROC) curves.Results: The positive rate of the G test, Aspergillus IgG antibody detection and the GM test also showed notable differences among the IPA, CPA, community-acquired bacterial pneumonia and healthy groups (P = 0.006, P < 0.001 and P = 0.217, respectively). Only the positive rate of the GM test showed a significant difference between the IPA and CPA groups (P = 0.04). ROC curves indicated that Aspergillus IgG antibody detection had a higher specificity in the IPA group than in the CPA group (0.952). The detection of Aspergillus IgG antibody can preferably distinguish IPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.923, specificity = 0.459, cut-off value = 134.46, AUC = 0.727). It can also distinguish CPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut-off value = 75.46, AUC = 0.873).Conclusions: Serum Aspergillus IgG antibody detection may have certain clinical value in the diagnosis of IPA and CPA in non-agranulocytic patients.
Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma
Authors: Zhou Minwen , Lu Bing , Tan Wei , Fu Mingshui
Published: March 2020

Background: Primary open angle glaucoma (POAG) is a multifactorial disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear. Methods: Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network. Results: During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched. Conclusion: This study provides novel insights into the lncRNA‑related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.
Functional parameters indicative of Mild Cognitive Impairment: a Systematic Review using Instrumented Kinematic Assessment
Authors: Fuentes-Abolafio Iván José , Stubbs Brendon , Pérez-Belmonte Luis Miguel , Bernal-López María Rosa , Gómez-Huelgas Ricardo , Cuesta-Vargas Antonio I
Published: March 2020

Background People with mild cognitive impairment (MCI) experience alterations of functional parameters, such as impaired balance or gait. The current systematic review set out to investigate whether functional objective performance may predict a future risk of MCI; to compare functional objective parameters in people with MCI and a control group; and to assess changes in these parameters after different physical activity interventions. Methods A systematic review of relevant literature was conducted. Literature were searched in PubMed, AMED, CINAHL, EMBASE, PEDro and Web of Science as well as grey literature databases. Cohort studies and Randomized Controlled Trials (RCTs) were included. Quality of reviewed studies were assessed independently by reviewers using quality assessment checklists. Results Seventeen studies met inclusion criteria including people with MCI. Results from RCTs suggested that gait speed, gait variability and balance may be improved by different physical activity interventions. Cohort studies showed that gait speed,especially in Dual Task (DT) conditions, was the parameter impaired in people with MCI in comparison with a Control Gorup. Furthermore, cohort studies suggested that gait variability could be a predictor of MCI. However, RCTs showed an unclear risk of bias and all studies included in this systematic review reported a low quality of evidence. Conclusions Studies suggest that gait variability may predict incident MCI, moreover different gait parameters, especially during DT conditions, could be impaired in MCI. These parameters could be improved by some physical activity interventions. Further studies are required to refute our findings. PROSPERO: CRD42019119180.
A multiplex guide RNA expression system and its efficacy for plant genome engineering
Authors: Oh Youngbin , Lee Bora , Kim Hyeonjin , Kim Sang-Gyu
Published: March 2020

Background: The Streptococcus pyogenes CRISPR system is composed of a Cas9 endonuclease (SpCas9) and a single-stranded guide RNA (gRNA) harboring a target-specific sequence. Theoretically, SpCas9 proteins could cleave as many targeted loci as gRNAs bind in a genome.Results: We introduce a PCR-free multiple gRNA cloning system for editing plant genomes. This method consists of two steps: (1) cloning the annealed products of two single-stranded oligonucleotide fragments harboring a complimentary target-binding sequence on each strand between tRNA and gRNA scaffold sequences in a pGRNA vector; and (2) assembling tRNA-gRNA units from several pGRNA vectors with a plant binary vector containing a SpCas9 expression cassette using the Golden Gate assembly method. We validated the editing efficiency and patterns of the multiplex gRNA expression system in wild tobacco (Nicotiana attenuata) protoplasts and in transformed plants by performing targeted deep sequencing. Two proximal cleavages by SpCas9-gRNA largely increased the editing efficiency and induced large deletions between two cleavage sites.Conclusions: This multiplex gRNA expression system enables high-throughput production of a single binary vector and increases the efficiency of plant genome editing.
Lung injury induced by short-term mechanical ventilation with hyperoxia and its mitigation by deferoxamine in rats
Authors: Wang Xiao-Xia , Sha Xiao-Lan , Li Yulan , Li Chun-Lan , Chen Su-Heng , Wang Jing-Jing , Xia ZhengYuan
Published: March 2020

Background: Long-term mechanical ventilation with hyperoxia can induce lung injury. General anesthesia is associated with a very high incidence of hyperoxaemia, despite it usually lasts for a relatively short period of time. It remains unclear whether short-term mechanical ventilation with hyperoxia has an adverse impact on or cause injury to the lungs. The present study aimed to assess whether short-term mechanical ventilation with hyperoxia may cause lung injury in rats and whether deferoxamine (DFO), a ferrous ion chelator, could mitigate such injury to the lungs and explore the possible mechanism. Methods: Twenty-four SD rats were randomly divided into 3 groups (n=8/group): mechanical ventilated with normoxia group (MV group, FiO2=21%), with hyperoxia group (HMV group, FiO2=90%), or with hyperoxia + DFO group (HMV+DFO group, FiO2=90%). Mechanical ventilation under different oxygen concentrations was given for 4 hours.The HMV+DFO group received continuous intravenous infusion of DFO at 200mg•kg-1•d-1, while the MV and HMV groups received an equal volume of normal saline. Carotid artery cannulation was carried out to monitor the blood gas parameters under mechanical ventilation for 2 hours and 4 hours, respectively, and the PaO2/FiO2 ratio was calculated. After 4 hours ventilation, the right anterior lobe of the lung and BALF from the right lung was sampled for pathological and biochemical assays. Results: PaO2 in the HMV and HMV+DFO groups were significantly higher, but the PaO2/FiO2 ratio were significantly lower than those of the MV group (all p<0.01). The lung pathological scores and the wet-to-dry weight ratio (W/D) in the HMV and HMV+DFO groups were significantly higher than those of the MV group, but score and the W/D ratio were reduced by DFO (p<0.05). Biochemically, HMV resulted in significant reductions in SP-C, SP-D, and GR levels and elevation of XOD in both the Bronchoalveolar lavage fluid and the lung tissue homogenate, and all these changes were prevented or significantly reverted by DFO. Conclusions: Mechanical ventilation with hyperoxia for 4 hours induced oxidative injury of the lungs, accompanied by a dramatic reduction in the concentrations of SP-C and SP-D. DFO could mitigate such injury by lowering XOD activity and elevating GR activity.
Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice
Authors: Liu Yinlu , Chen Qi-Yu , Lee Jung Hyun , Li Xu-Hui , Yu Shengyuan , Zhuo Min
Published: March 2020

Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dose-dependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP8-37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.
Clinical impact of advance chronic kidney disease in patients with non-HIV pulmonary cryptococcosis
Authors: Tashiro Hiroki , Haraguchi Tetsuro , Takahashi Koichiro , Sadamatsu Hironori , Tajiri Ryo , Takamori Ayako , Kimura Shinya , Aragane Naoko
Published: March 2020

Background: Pulmonary cryptococcosis is an uncommon infectious disease that can develop in both immunocompromised and immunocompetent patients. Severity of chronic kidney disease (CKD) was reported to be one of the risk factors for pulmonary cryptococcosis, but its clinical characteristics have not been fully assessed. The purpose of this study is to clarify clinical characteristics of advance CKD in patients with pulmonary cryptococcosis.Methods: The present study retrospectively investigated 56 patients who had pulmonary cryptococcosis with non-human immunodeficiency virus (HIV) infection and were treated at Saga University Hospital between 2005 and 2018. The clinical characteristics were evaluated and compared between patients with estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m2 (n = 42) (early CKD) and those with eGFR <45 mL/min/1.73m2 (n = 14) (advance CKD).Results: Compared with patients with early CKD, those with advance CKD had significantly higher rate of disseminated cryptococcosis (21.4% vs 2.4%, p = 0.03); lower percentage of patients who recovered after treatment (63.6% vs 92.5%, p = 0.02); and more frequent clinical features of fever (57.1% vs 19.0%, p < 0.01), pleural effusion (21.4% vs 2.4%, p = 0.03), high white blood cell count (8550/ml vs 6150/ml, p = 0.01) and C-reactive protein (2.1 mg/dl vs 0.2 mg/dl, p = 0.02), and low level of serum albumin (3.0 g/dl vs 3.8 g/dl, p <0.01). Multivariate analysis adjusted by immunosuppressive drug use indicated significant differences of fever (odds ratio or β value [95% confidence interval] 6.4 [1.65 – 20.09], p <0.01), high white blood cell count (1293.2 [110.2 – 2476.2], p = 0.03), C-reactive protein (0.89 [0.18 – 1.59], p = 0.01) and low level of serum albumin (- 0.34 [-0.54 – -0.14], p <0.01) in patients with eGFR <45 mL/min/1.73m2.Conclusion: Advance CKD is associated with poor clinical characteristics and outcomes in patients with non-HIV pulmonary cryptococcosis.
ABCD2 and ABCD3-I scores in a TIA population with low stroke risk
Authors: Ildstad Fredrik , Ellekjær Hanne , Wethal Torgeir , Lydersen Stian , Fjærtoft Hild , Indredavik Bent
Published: March 2020

Background Several clinical risk scores have been developed to predict stroke risk after transient ischemic attack (TIA). We aimed to evaluate the ABCD3-I score and compare it with the ABCD2 score in short and long-term stroke risk prediction in our post TIA stroke risk study, MIDNOR TIA. Methods We performed a prospective, multicenter study in Central Norway from October, 2012, to July, 2015, enrolling 577 patients with TIA. In a subset of patients (n=305) we calculated the AUC statistics of the ABCD3-I score and compared this with the ABCD2 score at 1 week, 3 months and 1 year. To assess stroke occurrences, data obtained by telephone follow-up and registry data from the Norwegian Stroke Register was used. Results Three hundred and five patients had complete data for both ABCD3-I and ABCD2 scores. Within 1 week, 3 months and 1 year, 1.0% (n=3), 3.3% (n=10) and 5.2% (n=16) experienced a stroke, respectively. The AUCs for the ABCD3-I score were 0.72 (95% CI, 0.54 to 0.89) at 1 week (compared with ABCD2 score p =0.019), 0.66 (95% CI, 0.53 to 0.80) at 3 months ( p =0.11), and 0.68 (0.95% CI, 0.56 to 0.79) at 1 year ( p =0.39). Conclusions The ABCD3-I score had limited value in short term prediction of subsequent stroke after TIA and did not reliably discriminate between low and high-risk patients in long-term follow-up. The ABCD2 score did not predict subsequent stroke accurately at any time point. Since modern treatment regimens and a decrease in risk factors in the population have contributed to a generally lower stroke risk after TIA during the last years, the benefit of these clinical risk scores and their role in TIA management seems limited.
Difference in osteogenic ability of bone marrow mesenchymal stem cells in patients with hemifacial microsomia on the healthy side versus affected side of the mandible
Authors: huang nan , Li Tianya , Chen Wei , ZHANG Qun , CHAI Gang
Published: March 2020

Background: This study was conducted to examine the differences in the osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) in patients with hemifacial microsomia on the healthy side versus on the affected side of the mandible. Methods: Patients with hemifacial microsomia admitted to Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine received bone marrow blood from the healthy and affected sides of the mandible, and BMSCs were cultured to evaluate their osteogenic induction and differentiation activities. Alizarin red (AR) staining was performed to observe the mineralization nodule formation ability of BMSCs. Alkaline phosphatase (ALP) staining was used to measure alkaline phosphatase activity, and the gene expression of the osteogenic-related indicators osteocalcin, osteopontin, Runx-related transcription factor 2, and ALP was detected by real-time fluorescent quantitative PCR. Differences in osteogenic capacity were also explored. Results: Osteogenesis related staining and Quantitative real-time PCR were performed，the results showed:in AR staining, osteogenesis on the healthy side was significantly better than that on the affected side (P＜0.001) ;in ALP staing, ALP activity of the affected side was significantly lower than that of the healthy side(P＜0.001);in the Quantitative real-time PCR,the osteogenesis-related genes ALP, OCN, OPN, and RUNX2 showed high expression on the healthy side and low expression on the affected side(P＜0.05). Conclusions: The osteogenesis ability of BMSCs differed on the healthy and affected mandibular bone in patients with hemifacial microsomia; the osteogenesis ability on the affected side was significantly lower than that on the healthy side. Keywords: hemifacial microsomia; bone marrow-derived mesenchymal stem cells; osteogenesis
The (cost-)effectiveness and cost-utility of a novel integrative care initiative for patients with chronic musculoskeletal pain: the pragmatic trial protocol of Network Pain Rehabilitation Limburg
Authors: Lamper Cynthia , Huijnen Ivan PJ , Goossens Mariëlle EJB , Winkens Bjorn , Ruwaard Dirk , Verbunt Jeanine AMCF , Kroese Mariëlle E
Published: March 2020

Background: Rehabilitation care for patients with chronic musculoskeletal pain (CMP) is not optimally organized. The Network Pain Rehabilitation Limburg 2.0 (NPRL2.0) provides integrated care with a biopsychosocial approach and strives to improve the Quadruple Aim outcomes: pain-related disability of patients with CMP; experiences of care of patients with CMP; meaning in the work of healthcare professionals; and healthcare costs. Firstly, in this study, the effectiveness (with regard to the functioning and participation of patients) of primary care for patients with CMP will be assessed, comparing care organized following the NPRL2.0 procedure with usual care. Secondly, the cost-effectiveness and cost-utility with regard to health-related quality of life and healthcare costs will be assessed. And thirdly, the effect of duration of participation in a local network in primary care will be studied. Methods: In this pragmatic study, it is expected that two local networks with 105 patients will participate in the prospective cohort study and six local networks with 184 patients in the stepped-wedge based design. Healthcare professionals in the local networks will recruit patients. Inclusion criteria: age ≥ 18 years; having CMP; willing to improve functioning despite pain; and adequate Dutch literacy. Exclusion criteria: pregnancy; and having a treatable medical or psychiatric disease. Patients will complete questionnaires at baseline (T1), 3 months (T2), 6 months (T3), and 9 months (T4). Questionnaires at T1 and T4 will include the Pain Disability Index and Short Form Health Survey. Questionnaires at T1, T2, T3, and T4 will include the EQ-5D-5L, and iMTA Medical Consumption and Productivity Cost Questionnaires. Outcomes will be compared using linear mixed-model analysis and costs will be compared using bootstrapping methods. Discussion: NPRL2.0 is a multidimensional, complex intervention, executed in daily practice, and therefore needing a pragmatic study design. The current study will assess the NPRL2.0 with respect to the Quadruple Aim’s outcomes of effectiveness of healthcare and economic consequences. The other two Quadruple Aim outcomes will be examined alongside this study, providing a broad scope of the performance of NPRL2.0. Trial registration: Netherlands Trial Register: NL7643; Registered 5 April 2019. https://www.trialregister.nl/trial/7643
Epigenetic regulation of osteopontin splicing isoform c defines its role as a microenvironmental factor to promote the survival of colon cancer cells from 5-FU treatment
Authors: Chang Siyuan , Huang Jing , Niu Huan , Wang Jing , Si Yang , Bai Zhigang , Cheng Shan , Ding Wei
Published: March 2020

Background: Drug resistance to 5-fluorouracil (5-FU) and recurrence after chemotherapy in colorectal cancer remain a challenge to be resolved for the improvement of patient outcomes. It is recognized that a variety of secretory proteins released from the tumor cells exposed to chemo-drugsinto the tumor microenvironment (TME) contributedto the cell-to-cell communication, and altered the drug sensitivity.One of these important factors is osteopontin (OPN), which exists in several functional forms from alternative splicing and post-translational processing. In colon cancer cells, increased total OPN expression was observed during the progression of tumors, however, the exact role and regulation of the OPN splicing isoforms was not well understood. Methods: We assayed precisely the abundance of majorOPN splicing isoformsunder5-FU treatmentsincolon cancer cell lineswith different sensitivities to 5-FU, and also evaluated the effects of the condition medium from OPNsplicing isoforms overexpressed cells on cell functions. The methods of nuclear calcium reporter assays and ChIP (chromatin immunoprecipitation) assays were used to investigate the molecular mechanism underlining the production of OPN isoforms.Results: We discovered that OPNc was a most increased splicing isoform to a significant abundance following 5-FU treatment of colon cancer cells. OPNc as a secretory protein in the conditioned medium exerted a more potent effect to promote cell survival in 5-FU than other OPN isoforms. The kinetic response of nuclear calcium signalscouldbe used to indicate an immediate effect of the conditioned medium containing OPNc and other isoforms. MeCP2 was identified to regulate the splicing of opn gene, where the phosphorylation of MeCP2 at S421 site, possibly by CAMKII, was required. Conclusions: The results demonstrated that the production of OPNc was highly controlled under epigenetic regulations, where MeCP2 and the activation of nuclear calcium signaling were involved. It was also suggested that OPNc could transmit the stress signal of cells upon chemotherapy in TME and promoted the survival of adjacent colon cancer cells.
Determinants of health facilities to provide newborn care services in Ethiopia: Finding from service Availability and Readiness Assessment 2018
Authors: Tesema Tefera Taddele
Published: March 2020

Background : Almost 50% of under-five mortality happens during the neonatal period. Sub-Saharan Africa has the highest rates of neonatal mortality. In this study we assessed the availability and readiness of health facility for newborn care service, its variations by health facility type, managing authority, location and regions in Ethiopia. Method: Data were used from the 2018 Ethiopian Service Availability and Readiness Assessment (SARA) from 9 regions and two city administration of the country. The overall newborn care services readiness score was calculated using ten tracer items and its mean availability was created for measuring health facilities overall capacity to provide newborn care services. A multiple linear regression model was used to determine factors associated with the newborn health readiness score. The analysis was done using SPSS version 20 and STATA version 14. Result : A total of 632 health facilities were included in the analysis. The mean availability of newborn care services at a national level was 63%. Only 7% of clinics provided neonatal resuscitation. A higher proportion of public facilities provided all signal functions compared with others facility types. Availability of newborn care services in overall facilities found in Tigray region were higher than facilities found in other regions. The overall newborn readiness score for health centres and clinics were lower than hospitals respectively. The expected value of newborn care readiness to provide the service was lower in health facilities found in Oromiya, Somali and Gambella than health facilities in Tigray. Conclusion : The availability of neonatal resuscitation, corticosteroids, antibiotic for preterm or prolonged premature rupture of membrane and injectable antibiotics for sepsis signal functions and the capacity of health facilities in terms of the mean availability of ten tracer items to provide newborn care services were low in clinics compared with health centres and hospitals. There was regional variation on the availability of the services. So, in the future focus should be given on clinics and the regions whose readiness score was low to ensure equity in distribution and its newborn care service capacity.
An e-registry for household contacts exposed to multidrug resistant TB in Mongolia
Authors: Naker Kush , Gaskell Katherine M , Dorjravdan Munhjargal , Daamba Naranzul , Roberts Chrissy h , Moore David AJ
Published: March 2020

Background: The WHO recommends that individuals exposed to persons with multidrug resistant tuberculosis (MDRTB) should be screened for active TB and followed up for two years to detect and treat secondary cases early. Resource prioritisation means this is rarely undertaken and where it is performed it is usually using a paper-based record, without collation of data. Electronic data collection into a web-based registry offers the opportunity for simplified and systematic TB contact surveillance with automatic synthesis of data at local, regional and national level. This pilot study was designed to explore the feasibility of usage of a novel e-registry tool and explore obstacles and facilitating factors to implementation. Methods: In parallel with their paper records, seven dispensaries in Ulaanbaatar, Mongolia collected standardized data electronically using Open Data Kit (ODK). Patients with MDRTB and their contacts were recruited during a single clinic visit. Staff and patients were interviewed to gain insights into acceptability and to identify areas for improvement. Results: 70 household contacts of 32 MDR-TB index patients were recruited. 7/70 contacts (10%) traced had active TB at the time they were recruited to the e-registry. Paper registry satisfaction was low; 88% of staff preferred the e-registry as it was perceived as faster and more secure. Patients and their contacts were generally supportive of the e-registry; however, a significant minority 10/42 (24%) of index cases who were invited, declined to participate in the e-registry, with data security cited as their top concern. Conclusion: E-registries are a promising tool for MDRTB contact tracing, but their acceptability amongst patients should not be taken for granted.
SET domain-containing protein 4: biological functions and role in genomic methylation profiles of bone marrow mesenchymal stem cells
Authors: Liao Xiao-min , Wu Cai-xia , Shao Zhong-ming , Zhang Shu-ya , Zou Yuan , Yuan Jian-ling , Feng Mu-yin , Ha Yan-ping , Li Ru-jia , Xing Jing-ci , Zheng A-xiu , Shen Zhi-hua , Guo Jun-li , Zheng Shao-Jiang , Jie Wei
Published: March 2020

Background: Epigenetic modification is a crucial mechanism affecting the biological function of stem cells. SETD4 is a histone methyltransferase, and its biological role in bone marrow mesenchymal stem cells (BMSCs) is currently unknown. This work was aimed to reveal the SETD4 biological role as well as its impacts on the genomic methylation profiles in BMSCs. Methods: BMSCs were isolated form SETD4 knockout (KO) and wild type (WT) mice that established by CRISPR/Cas9 technology. The cell proliferation, migration, myogenic differentiation and angiogenesis were tested according to appropriate biology techniques. And the Reduced Representation Bisulfite Sequencing (RRBS) method was adopted to analyze the global genomic methylation profiles of BMSCs, following bioinformatics analysis of GO functions and KEGG signaling of differential methylated CpG sites and differential methylation regions (DMRs). Finally, validation experiments were conducted to examine the expression of histone lysine methyltransferase and some representative genes. Results: SETD4 KO significantly promoted BMSCs proliferation, which was characterized by enhanced cell viability and increased expression of PCNA, Cyclin A2, Cyclin E1, CDK2, CDK6, Bcl2 and decreased the expression of P16, P21 and Caspase3. SETD4 deficiency impaired BMSCs migration and myogenic differentiation potentials, and even the angiogenesis via paracrine of VEGF. Compared with WT control, the overall genomic methylation of BMSCs in the SETD4 KO group only was decreased by 0.47%. However, the changed genomic methylation covers a total of 96,331 differential methylated CpG sites and 8692 DMR, with part of them settled in promoter regions. GO and KEGG analysis revealed that differential CpG islands and DMRs in promotes impacted 270 GO functions and 34 KEGG signaling pathways, with some closely related to stem cell biology. SETD4 KO inhibited sets of monomethylases and dimethylases for histone lysine, along with significant changes in some factors including Nkx2.5, Gata4, Gli2, Grem2, E2f7, Map7, Nr2f2 and Shox2 that associated with stem cell biology. Conclusions: These results are the first to reveal that even though SETD4 changes the genome’s overall methylation to a limited extent in BMSCs, it still affects the numerous cellular functions and signaling pathways, implying SETD4-altered genomic methylation serves a crucial molecular role in BMSCs’ biological functions.
Engaging stakeholders to identify implementation strategies for a faith-based physical activity program
Authors: Haughton Jessica , Takemoto Michelle L. , Schneider Jennifer , Hooker Steven P. , Rabin Borsika , Brownson Ross C. , Arredondo Elva M.
Published: March 2020

Background: Stakeholder engagement is critical to the acceleration of evidence-based interventions into community settings. Harnessing the knowledge and opinions of community stakeholders increases the likelihood of successful implementation, scale up, and sustainment of evidence-based interventions. Faith in Action ( Fe en Acción ) is an evidence-based promotora -led physical activity program designed to increase moderate-to-vigorous physical activity among churchgoing Latina women.Methods: We conducted in-depth interviews using a semi-structured interview guide based on the Consolidated Framework for Implementation Research (CFIR) at various Catholic and Protestant churches with large Latino membership in San Diego County, California to explore barriers and facilitators to implementation of a Faith in Action and to identify promising implementation strategies for program scale-up and dissemination. We interviewed 22 pastors and church staff and analyzed transcripts using an iterative-deductive team approach.Results: Stakeholders described barriers and facilitators to implementation within three domains of CFIR: characteristics of individuals (lack of self-efficacy for and knowledge of PA; influence on churchgoers’ behaviors), inner setting (church culture and norms, alignment with mission and values, competing priorities, lack of resources), and outer setting (need for buy-in from senior leadership). From the interviews, we identified four promising implementation strategies for the scale-up of faith-based health promotion programs: 1) health behavior change training for pastors and staff; 2) tailored messaging; 3) developing community collaborations; and 4) gaining denominational support.Conclusions: While churches can serve as valuable partners in health promotion, specific barriers and facilitators to implementation must be recognized and understood. Addressing these barriers through targeted implementation strategies at the adopter and organizational level can facilitate improved program implementation and lead the way for scale-up and dissemination.
Oxycodone reduced postoperative catheter-related bladder discomfort undergoing transurethral resection prostate. A prospective, double -blind randomized study
Authors: li jian
Published: March 2020

Background: Catheter-related bladder discomfort (CRBD) is a common and distressing complication that often occurs caused by urinary bladder catheterization and urethral mucosa injury postoperatively. Oxycodone is a semi-synthetic opioids prepared from opium alkaloid the baine plant derivative. Its μ and κ dual-receptor agonism has a unique effect in the treatment of visceral pain. The aim of this study to observe the efficacy of oxycodone for the treatment of CRBD undergo trans-urethral resection prostate (TURP). Methods: Patients with ASA I-III received trans-urethral resection prostate under general anesthesia were enrolled. Patients who complained CRBD were randomized allocated to the control group (n=42) received placebo and the observed group (n=41) received 0.03mg/kg of oxycodone. The severity of CRBD assessed by NRS were assessed at 0, 5min, 1/2h, and 2h after administration of the study agents. VAS scores were used to assess pain intensity during the same period. Postoperative PCA analgesic sufentanil dose during of PACU times and the incidences of agitation, nausea, vomiting, dizziness, over sedation were recorded in these patients. Results: Compared with the control group, the incidence of CRBD was significantly lower in the oxycodone group at 5min and 1/2h. Compared with the controlled group, VAS scores and incidences of agitation were lower in oxycodone group and significantly decreased sufentanil dosage within 6h (P<0.01). There were no significant differences in the incidence of postoperative adverse effects and during of PACU between two groups(P＜0.05). Conclusion: Oxycodone 0.03mg/kg effectively reduced patients with CRBD after TURP without incurring serious adverse effects.Trial registration: Chinese Clinical Trial Registry, ChiCTR-IPR-16008814.
Psychiatric comorbidities among cancer survivors in South Korea: A nationwide, population-based, longitudinal study
Authors: Heo Jaesung , Noh O Kyu
Published: March 2020

Background: This longitudinal study aimed to analyze the incidence of mental disorders in cancer survivors using claims data in South Korea. Methods: We confirmed the presence of mental disorders in a nationwide cohort of 555,776 patients diagnosed with stomach, breast, colorectal, or prostate cancer between January 1, 2010 and December 31, 2016. We analyzed the incidence of mental disorders based on age and time of diagnosis. Results: Analysis of the data revealed 36,526 (6.5%) cancer survivors were diagnosed with a mental disorder 1 year prior to cancer diagnosis. Of these patients with mental disorders, 16,035 were diagnosed with anxiety (43.9%), 13,848 with depression (37.9%), 3,998 with stress reaction/adjustment disorders (10.9%), and 2,645 (7.2%) with substance abuse during their first visit. The incidence of depression was relatively high in the breast-cancer group and that of anxiety was high in the prostate-cancer group. The incidence of anxiety was high in females and that of substance abuse was high in males. Further, the incidence of depression was relatively high in the young age group and that of anxiety was high in the elderly group. The overall frequency of mental disorders peaked 2 months after cancer diagnosis. The highest rate of increase after diagnosis was noted among those with stress reaction/adjustment disorders. Conclusion: Mental disorders in cancer survivors showed different patterns of incidence depending on the nature of the disease, sex, age, and primary cancer. Considering individual factors, timely diagnosis and intervention for psychological distress may increase these patients’ quality of life.