bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA OGFRP1 acts as an oncogene in NSCLC via miR-4640-5p/eIF5A axis
Authors: Liu Xiaojing , Niu Na , Li Pibao , Zhai Liping , Xiao Ke , Chen Wendan , Zhuang Xuewei 
Published: August 2021

AbstractBackgroundLong noncoding RNAs (lncRNAs) OGFRP1 is up-regulated in endometrial cancer and cervical carcinoma, and OGFRP1 suppression inhibits the malignant behavior of cancer cells. Here, we evaluated the expression pattern, biological function and potential mechanism of OGFRP1 in non-small cell lung cancer (NSCLC).MethodsThe expression of target genes in 25 pairs of clinically collected NSCLC and normal lung tissue samples was detected by qRT-PCR or western blot. We screened the siRNA (siOGFRP1) to down-regulate the expression of OGFRP1 in A549 and H1299 cells. The biological function of A549 and H1299 cells were examined by CCK8, wound healing and transwell assays. The molecular mechanism of OGFRP1 was further explored.ResultsThe expression of OGFRP1 in NSCLC tissues were higher than that in normal lung tissue. siOGFRP1 inhibited the proliferation, migration and invasion of A549 and H1299 cells. In addition, the expression of EMT-related and apoptosis-related proteins was changed by siOGFRP1 transfection. OGFRP1 can directly interact with miR-4640-5p, and siOGFRP1 increased the level of miR-4640-5p. Moreover, miR-4640-5p could directly bind to the 3’ UTR region of eIF5A mRNA. eIF5A was highly expressed in NSCLC tissues, and predicted a poor prognosis. In addition, the expression of miR-4640-5p and eIF5A in NSCLC tissues were negatively correlated, while the expression of OGFRP1 and eIF5A were positively correlated. Knockdown of OGFRP1 inhibited the expression of eIF5A, while transfection of miR-4640-5p inhibitor up-regulated the expression of eIF5A.ConclusionsTaken together, we demonstrated that down-regulation of OGFRP1 inhibited the progression of NSCLC through miR-4640-5p/eIF5A axis.
Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria
Authors: Ali Fawad , Wali Hira , Jan Saadia , Zia Asad , Aslam Muneeba , Ahmad Imtiaz , Afridi Sahib Gul , Shams Sulaiman , Khan Asifullah 
Published: August 2021

AbstractBackgroundPlasmodium falciparumis an obligate intracellular parasite of humans that causes malaria. Falciparum malaria is a major public health threat to human life responsible for high mortality. Currently, the risk of multi-drug resistance ofP. falciparumis rapidly increasing. There is a need to address new anti-malarial therapeutics strategies to combat the drug-resistance threat.MethodsTheP. falciparumessential proteins were retrieved from the recently published studies.These proteins were initially scanned against human host and its gut microbiome proteome sets by comparative proteomics analyses. The human host non-homologs essential proteins ofP. falciparumwere additionally analysed for druggability potential via in silico methods to possibly identify novel therapeutic targets. Finally, the PfAp4AH target was prioritized for pharmacophore modelling based virtual screening and molecular docking analyses to identify potent inhibitors from drug-like compounds databases.ResultsThe analyses identified sixP. falciparumessential and human host non-homolog proteins that follow the key druggability features. These druggable targets have not been catalogued so far in the Drugbank repository. These prioritized proteins seem novel and promising drug targets againstP. falciparumdue to their key protein–protein interactions features in pathogen-specific biological pathways and to hold appropriate drug-like molecule binding pockets. The pharmacophore features based virtual screening of Pharmit resource predicted a lead compound i.e. MolPort-045–917-542 as a promising inhibitor of PfAp4AH among prioritized targets.ConclusionThe prioritized protein targets may worthy to test in malarial drug discovery programme to overcome the anti-malarial resistance issues. Thein-vitroandin-vivostudies might be promising for additional validation of these prioritized lists of drug targets against malaria.
High-dose intravenous hydromorphone for patients who use opioids in the hospital setting: time to reduce the barriers
Authors: Labonté Laura E. , Young Samantha 
Published: August 2021

AbstractIndividuals who use opioids have higher rates of hospitalization compared to the general population. Insufficiently treated withdrawal and pain are major factors contributing to high rates of self-initiated hospital discharges (also referred to as leaving against medical advice) in this population. While injectable opioid agonist therapy is limited or unavailable in the majority of Canadian communities, intravenous hydromorphone (IV HM) is widely available in the hospital setting and high-dose IV HM may be a useful treatment adjunct to improve comfort and engagement in inpatient care for some individuals who use opioids. However, major barriers to its use exist including lack of comfort amongst healthcare providers and hospital policies restricting administration. In this commentary, we highlight the potential usefulness of high-dose IV HM as a treatment adjunct for individuals who use opioids in the hospital setting and advocate for expanded hospital policies to facilitate its use.
Validity and reliability of the Norwegian version of the Musculoskeletal Health Questionnaire in people on sick leave
Authors: Tingulstad Alexander , Van Tulder Maurits W. , Rysstad Tarjei , Tveter Anne Therese , Hill Jonathan C. , Grotle Margreth 
Published: August 2021

AbstractBackgroundThe Musculoskeletal Health Questionnaire (MSK-HQ) is a recently developed generic questionnaire that consists of 14 items assessing health status in people with musculoskeletal disorders. The objective was to translate and cross-culturally adapt the MSK-HQ into Norwegian and to examine its construct validity and reliability in people on sick leave with musculoskeletal disorders.MethodsA prospective cohort study was carried out in Norway on people between 18 and 67 years of age and sick leave due to a musculoskeletal disorder. The participants were recruited through the Norwegian Labour and Welfare Administration during November 2018–January 2019 and responded to the MSK-HQ at inclusion and after four weeks. Internal consistency was assessed by Cronbach’s alpha, and structural validity with a factor analysis. Construct validity was assessed by eight “a priori” defined hypotheses regarding correlations between the MSK-HQ and other reference scales. Correlations were analyzed by Spearman’s- or Pearson’s correlation coefficient and interpreted as high with values ≥ 0.50, moderate between 0.30–0.49, and low < 0.29. Reliability was tested with test–retest, standard error of measurement (SEM) and smallest detectable change (SDC).ResultsA total of 549 patients, mean age (SD) 48.6 (10.7), 309 women (56.3%), were included. The mean (SD) MSK-HQ sum scores (min–max 3–56) were 27.7 (8.2). Internal consistency was 0.86 and a three-factor structure was determined by factor analysis. Construct validity was supported by the confirmation of all hypotheses; high correlation with HRQOL, psychosocial risk profile, and self-perceived health; moderate correlation with physical activity, self-perceived work ability, and work presenteeism; and low correlation with the number of sick days. The test–retest reliability was good with an intraclass correlation coefficient of 0.83 (95% CI, 0.74–0.89), SEM was 2.3 and SDC 6.5.ConclusionsThe Norwegian version of the MSK-HQ demonstrated high internal consistency, a three-factor structure,good construct validity and good test–retest reliability when used among people on sick leave due to musculoskeletal disorders.
N6-methyladenosine (m6A) RNA methylation regulator SNRPC is a prognostic biomarker and is correlated with immunotherapy in hepatocellular carcinoma
Authors: Cai Jihao , Zhou Minglei , Xu Jianxin 
Published: August 2021

AbstractBackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and due to its complex pathogenic factors, its prognosis is poor. N6-methyladenosine (m6A) RNA methylation plays an important role in the tumorigenesis, progression, and prognosis of many tumors. The m6A RNA methylation regulator small nuclear ribonucleoprotein polypeptide C (SNRPC), which encodes one of the specific protein components of the U1 small nuclear ribonucleoprotein (snRNP) particle, has been proven to be related to the prognosis of patients with HCC. However, the effect ofSNRPCon the tumor microenvironment and immunotherapy in HCC remains unclear.Case presentationThe HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI-JP samples, respectively, were used in this study. Both the expression ofSNRPCin HCC was upregulated in the TCGA and ICGC databases compared to normal tissues. Next, the expression ofSNRPCwas validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By gene set variation (GSVA) analysis and gene set enrichment (GSEA) analysis, we found thatSNRPCwas mainly related to protein metabolism and the immune process. Furthermore, the estimation of stromal and immune cells in malignant tumor tissues using expression (ESTIMATE), microenvironment cell population counter (MCP-counter), and single sample GSEA (ssGSEA) algorithms revealed that the high-SNRPCgroup had a lower stromal score, lower abundance of endothelial cells and fibroblasts, and lower immune infiltration. Ultimately, a tumor immune dysfunction and exclusion (TIDE) analysis revealed that patients in the low-SNRPCgroup may be more sensitive to immune checkpoint inhibitor therapy.ConclusionSNRPCcould serve as a promising prognostic and immunotherapeutic marker in HCC and might contribute to new directions and strategies for HCC treatment.
What is the impact of granulocyte colony-stimulating factor (G-CSF) in subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles on recurrent implantation failure: a systematic review and meta-analysis?
Authors: Hou Zhijin , Jiang Fangjie , Yang Jie , Liu Yang , Zha Hao , Yang Xiaoling , Bie Jia , Meng Yushi 
Published: August 2021

Abstract
Background
Among recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors. Effective treatments are urgently needed to improve the outcomes of embryo transfer for RIF patients. In recent years, many researchers have focused on immunotherapy using granulocyte colony-stimulating factor (G-CSF) to regulate the immune environment. However, the study of the G-CSF for RIF patients has reached conflicting conclusions. The aim of this systematic review and meta-analysis was performed to further explore the effects of G-CSF according to embryo transfer cycle (fresh or frozen) and administration route (subcutaneous injection or intrauterine infusion) among RIF patients.

Method
The PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for literature published from the initial to October 2020. The meta-analysis, random-effects model and heterogeneity of the studies with I2 index were analyzed. Stata 15 was used for statistical analysis.

Results
A total of 684 studies were obtained through the databases mentioned above. Nine RCTs included 976 RIF patients were enrolled in this meta-analysis. Subgroup analysis indicated that G-CSF improved the clinical pregnancy rate for both the fresh and frozen embryo transfer cycles (fresh RR: 1.74, 95% CI: 1.27–2.37, I2 = 0.0%, n = 410; frozen RR: 1.44, 95% CI: 1.14–1.81, I2 = 0.0.%, n = 366), and for both subcutaneous injection and intrauterine infusion (subcutaneous RR: 1.73, 95% CI: 1.33–2.23, I2 = 0.0%, n = 497; intrauterine RR: 1.39, 95% CI: 1.09–1.78, I2 = 0.0%, n = 479), but the biochemical pregnancy rate of the RIF group was also higher than that of the control group (RR: 1.85, 95% CI: 1.28–2.68; I2 = 20.1%, n = 469). There were no significant differences in the miscarriage rate (RR: 1.13, 95% CI: 0.25–5.21: I2 = 63.2%, n = 472) and live birth rate (RR: 1.43, 95% CI: 0.86–2.36; I2 = 52.5%; n = 372) when a random-effects model was employed.

Conclusion
The administration of G-CSF via either subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles for RIF patients can improve the clinical pregnancy rate. However, whether G-CSF is effective in improving livebirth rates of RIF patients is still uncertain, continued research on the utilization and effectiveness of G-CSF is recommended before G-CSF can be considered mainstream treatment for RIF patients.
Multi-omics network characterization reveals novel microRNA biomarkers and mechanisms for diagnosis and subtyping of kidney transplant rejection
Authors: Lin Yuxin , Wang Liangliang , Ge Wenqing , Hui Yu , Zhou Zheng , Hu Linkun , Pan Hao , Huang Yuhua , Shen Bairong 
Published: August 2021

Abstract
Background
Kidney transplantation is an optimal method for treatment of end-stage kidney failure. However, kidney transplant rejection (KTR) is commonly observed to have negative effects on allograft function. MicroRNAs (miRNAs) are small non-coding RNAs with regulatory role in KTR genesis, the identification of miRNA biomarkers for accurate diagnosis and subtyping of KTR is therefore of clinical significance for active intervention and personalized therapy.

Methods
In this study, an integrative bioinformatics model was developed based on multi-omics network characterization for miRNA biomarker discovery in KTR. Compared with existed methods, the topological importance of miRNA targets was prioritized based on cross-level miRNA-mRNA and protein–protein interaction network analyses. The biomarker potential of identified miRNAs was computationally validated and explored by receiver-operating characteristic (ROC) evaluation and integrated “miRNA-gene-pathway” pathogenic survey.

Results
Three miRNAs, i.e., miR-145-5p, miR-155-5p, and miR-23b-3p, were screened as putative biomarkers for KTR monitoring. Among them, miR-155-5p was a previously reported signature in KTR, whereas the remaining two were novel candidates both for KTR diagnosis and subtyping. The ROC analysis convinced the power of identified miRNAs as single and combined biomarkers for KTR prediction in kidney tissue and blood samples. Functional analyses, including the latent crosstalk among HLA-related genes, immune signaling pathways and identified miRNAs, provided new insights of these miRNAs in KTR pathogenesis.

Conclusions
A network-based bioinformatics approach was proposed and applied to identify candidate miRNA biomarkers for KTR study. Biological and clinical validations are further needed for translational applications of the findings.
Quantification of spatial metal accumulation patterns in Noccaea caerulescens by X-ray fluorescence image processing for genetic studies
Authors: van der Zee Lucas , Corzo Remigio Amelia , Casey Lachlan W. , Purwadi Imam , Yamjabok Jitpanu , van der Ent Antony , Kootstra Gert , Aarts Mark G. M. 
Published: August 2021

AbstractBackgroundHyperaccumulation of trace elements is a rare trait among plants which is being investigated to advance our understanding of the regulation of metal accumulation and applications in phytotechnologies.Noccaea caerulescens(Brassicaceae) is an intensively studied hyperaccumulator model plant capable of attaining extremely high tissue concentrations of zinc and nickel with substantial genetic variation at the population-level. Micro-X-ray Fluorescence spectroscopy (µXRF) mapping is a sensitive high-resolution technique to obtain information of the spatial distribution of the plant metallome in hydrated samples. We used laboratory-based µXRF to characterize a collection of 86 genetically diverseNoccaea caerulescensaccessions from across Europe. We developed an image-processing method to segment different plant substructures in the µXRF images. We introduced the concentration quotient (CQ) to quantify spatial patterns of metal accumulation and linked that to genetic variation.ResultsImage processing resulted in automated segmentation of µXRF plant images into petiole, leaf margin, leaf interveinal and leaf vasculature substructures. The harmonic means of recall and precision (F1 score) were 0.79, 0.80, 0.67, and 0.68, respectively. Spatial metal accumulation as determined by CQ is highly heritable inNoccaea caerulescensfor all substructures, with broad-sense heritability (H2) ranging from 76 to 92%, and correlates only weakly with other heritable traits. Insertion of noise into the image segmentation algorithm barely decreases heritability scores of CQ for the segmented substructures, illustrating the robustness of the trait and the quantification method. Very low heritability was found for CQ if randomly generated substructures were compared, validating the approach.ConclusionsA strategy for segmenting µXRF images ofNoccaea caerulescensis proposed and the concentration quotient is developed to provide a quantitative measure of metal accumulation pattern, which can be used to determine genetic variation for such pattern. The metric is robust to segmentation error and provides reliable H2estimates. This strategy provides an avenue for quantifying XRF data for analysis of the genetics of metal distribution patterns in plants and the subsequent discovery of new genes that regulate metal homeostasis and sequestration in plants.
Disc measurement and nucleus calibration in a smoothened lumbar model increases the accuracy and efficiency of in-silico study
Authors: Li Jingchi , Xu Chen , Zhang Xiaoyu , Xi Zhipeng , Sun Shenglu , Zhang Ke , Fang Xiaoyang , Xie Lin , Liu Yang , Song Yueming 
Published: August 2021

Abstract
Backgrounds
Finite element analysis (FEA) is an important tool during the spinal biomechanical study. Irregular surfaces in FEA models directly reconstructed based on imaging data may increase the computational burden and decrease the computational credibility. Definitions of the relative nucleus position and its cross-sectional area ratio do not conform to a uniform standard in FEA.

Methods
To increase the accuracy and efficiency of FEA, nucleus position and cross-sectional area ratio were measured from imaging data. A FEA model with smoothened surfaces was constructed using measured values. Nucleus position was calibrated by estimating the differences in the range of motion (RoM) between the FEA model and that of an in-vitro study. Then, the differences were re-estimated by comparing the RoM, the intradiscal pressure, the facet contact force, and the disc compression to validate the measured and calibrated indicators. The computational time in different models was also recorded to evaluate the efficiency.

Results
Computational results indicated that 99% of accuracy was attained when measured and calibrated indicators were set in the FEA model, with a model validation of greater than 90% attained under almost all of the loading conditions. Computational time decreased by around 70% in the fitted model with smoothened surfaces compared with that of the reconstructed model.

Conclusions
The computational accuracy and efficiency of in-silico study can be improved in the lumbar FEA model constructed using smoothened surfaces with measured and calibrated relative nucleus position and its cross-sectional area ratio.
Prevalence and management of driveline infections in mechanical circulatory support - a single center analysis
Authors: Juraszek Andrzej , Smólski Mikołaj , Kołsut Piotr , Szymański Jarosław , Litwiński Paweł , Kuśmierski Krzysztof , Zakrzewska-Koperska Joanna , Sterliński Maciej , Dziodzio Tomasz , Kuśmierczyk Mariusz 
Published: August 2021

Abstract
Background
Driveline infections in continuous-flow left ventricular assist devices (cf-LVAD) remain the most common adverse event. This single-center retrospective study investigated the risk factors, prevalence and management of driveline infections.

Methods
Patients treated after cf-LVAD implantation from December 2014 to January 2020 were enrolled. Baseline data were collected and potential risk factors were elaborated. The multi-modal treatment was based on antibiotic therapy, daily wound care, surgical driveline reposition, and heart transplantation. Time of infection development, freedom of reinfection, freedom of heart transplantation, and death in the follow-up time were investigated.

Results
Of 75 observed patients, 26 (34.7%) developed a driveline infection. The mean time from implantation to infection diagnosis was 463 (±399; range, 35–1400) days. The most common pathogen was Staphylococcus aureus (n = 15, 60%). First-line therapy was based on antibiotics, with a primary success rate of 27%. The majority of patients (n = 19; 73.1%) were treated with surgical reposition after initial antibiotic therapy. During the follow-up time of 569 (±506; range 32–2093) days, the reinfection freedom after surgical transposition was 57.9%. Heart transplantation was performed in eight patients due to resistant infection. The overall mortality for driveline infection was 11.5%.

Conclusions
Driveline infections are frequent in patients with implanted cf-LVAD, and treatment does not efficiently avoid reinfection, leading to moderate mortality rates. Only about a quarter of the infected patients were cured with antibiotics alone. Surgical driveline reposition is a reasonable treatment option and does not preclude subsequent heart transplantation due to limited reinfection freedom.
Epidemiological investigation of hemophagocytic lymphohistiocytosis in China
Authors: Yao Shuyan , Wang Yini , Sun Yuan , Liu Li , Zhang Rui , Fang Jianpei , Jin Runming , Yu Jie , Li Fei , Bai Jie , Zeng Yun , Zhang Cheng , Tan Huo , Zhou Fan , Chen Yan , Zhang Qiaohua , Wang Zhao 
Published: August 2021

Abstract
Background
Currently, most research on hemophagocytic lymphohistiocytosis (HLH) have focused on etiology and therapy, leaving few epidemiological reports. The published studies of China are mainly regional investigations. We aimed to present the overall epidemiological status of HLH in China, and provide Chinese data for the international HLH epidemiological investigation.

Methods
The data of HLH cases in China in 2019 were collected and statistically analyzed.

Findings
Epstein-Barr virus accounted for 44.01% of the 1445 cases in 31 regions and was the most common cause. Lymphoma-associated HLH patients were more often male (P < 0.05) while rheumatic and immune-associated HLH were more often female (P < 0.001). Primary HLH and Epstein-Barr Virus-associated HLH were predominant in children (P < 0.001) while tumor-associated HLH was predominant in adults. Lymphoma-associated HLH was positively correlated with the age of onset (P < 0.01). The diagnosis rate of 29 areas had a significant correlation with per capita Gross domestic product (P < 0.05).

Conclusion
The different distribution of HLH etiology by age and gender contributes to the diagnosis of HLH by clinicians; The suboptimal diagnosis rate in regions with a high incidence of HLH in China is a result of the effect of the local economic level indicating the importance of improving the regional medical level.