Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced expression of circ_0000267 in hepatocellular carcinoma indicates poor prognosis and facilitates cell progression by sponging miR‐646

Hepatocellular carcinoma (HCC) is a highly aggressive carcinoma worldwide. Circular RNAs (circRNAs) have been proved to be involved in the pathogenesis of several carcinomas. circ_0000267 was reported to be elevated in HCC tissue samples by circRNA microarray. In this study, quantitative reverse‐transcription polymerase chain reaction was induced to further detect the expression of circ_0000267 in HCC tissues and cells. The clinical significance was also explored by Fisher’s exact test, Kaplan‐Meier curves and Cox regression analysis. Cell counting kit‐8, colony formation, flow cytometry and transwell experiments were conducted on HCC cells to elucidate the functions of circ_0000267. Dual‐luciferase reporter assay was induced to explore the mechanism of circ_0000267. Moreover, rescue experiments were also performed on HCC cells. As a result, circ_0000267 was enhanced in HCC tissues and cell lines. This upregulation is associated with patients’ clinical severity and poor prognosis. Functionally, circ_0000267 could facilitate cell growth, migration and invasion and attenuate cell apoptosis in HCC cells. Mechanistically, circ_0000267 could directly sponge miR‐646 to exert its oncogenic properties. In summary, we identified a novel HCC‐associated circRNA in the progression of this fatal disease.
Animal models of ischemic stroke and their impact on drug discovery

ABSTRACT Introduction: Representing the leading cause of long-term disability, ischemic stroke urgently needs further research and drug development. This review summarizes current animal models of ischemic stroke that can be used for drug discovery. Areas covered: Several reproducible models of permanent and transient focal cerebral ischemia have been established in a variety of animal species including rats and mice, in which a brain-supplying artery, often the middle cerebral artery, is occluded by mechanical devices including sutures, clips and hooks, pharmacological agents or delivery of blot clots. The authors review existing literature about these models, outlining their utility for evaluating acute and post-acute stroke treatments. Since stroke is an age-related disease that strongly affects humans with vascular risk factors and co-morbidities, the authors give focus to strategies replicating risk factors in ischemic stroke models. Furthermore, the authors present models of spontaneous stroke. Expert opinion: It is important that animal models mimic clinical conditions in a reliable and clinically relevant way, so here, they should replicate the pathophysiology of human stroke, stroke-associated risk factors and doses, times and modes of drug treatment. We propose that risk factor models should more widely be used in early drug discovery, if possible already during the identification of treatment targets.
The Mycobacterium tuberculosis Pup-proteasome system regulates nitrate metabolism through an essential protein quality control pathway

Significance The proteasome is required for the full virulence of Mycobacterium tuberculosis. However, the extent of its role as a regulator of bacterial physiology remains unclear. In this work, we demonstrate a function of the proteasome system in maintaining the expression of essential chaperonin genes. This activity by the proteasome is required for M. tuberculosis to use nitrate as a nitrogen source. Furthermore, we identified a specific growth condition that robustly decreases the abundance of pupylated proteins. This observation strongly suggests the presence of a yet-to-be-determined mechanism of control over the Pup-proteasome system in M. tuberculosis that is induced in nitrate. The human pathogen Mycobacterium tuberculosis encodes a proteasome that carries out regulated degradation of bacterial proteins. It has been proposed that the proteasome contributes to nitrogen metabolism in M. tuberculosis, although this hypothesis had not been tested. Upon assessing M. tuberculosis growth in several nitrogen sources, we found that a mutant strain lacking the Mycobacterium proteasomal activator Mpa was unable to use nitrate as a sole nitrogen source due to a specific failure in the pathway of nitrate reduction to ammonium. We found that the robust activity of the nitrite reductase complex NirBD depended on expression of the groEL/groES chaperonin genes, which are regulated by the repressor HrcA. We identified HrcA as a likely proteasome substrate, and propose that the degradation of HrcA is required for the full expression of chaperonin genes. Furthermore, our data suggest that degradation of HrcA, along with numerous other proteasome substrates, is enhanced during growth in nitrate to facilitate the derepression of the chaperonin genes. Importantly, growth in nitrate is an example of a specific condition that reduces the steady-state levels of numerous proteasome substrates in M. tuberculosis.
Improved Object Proposals with Geometrical Features for Autonomous Driving

This paper aims at generating high-quality object proposals for object detection in autonomous driving. Most existing proposal generation methods are designed for the general object detection, which may not perform well in a particular scene. We propose several geometrical features suited for autonomous driving and integrate them into state-of-the-art general proposal generation methods. In particular, we formulate the integration as a feature fusion problem by fusing the geometrical features with existing proposal generation methods in a Bayesian framework. Experiments on the challenging KITTI benchmark demonstrate that our approach improves the existing methods significantly. Combined with a convolutional neural net detector, our approach achieves state-of-the-art performance on all three KITTI object classes.
MiR-374b reduces cell proliferation and cell invasion of cervical cancer through regulating FOXM1.

OBJECTIVE Deregulation of microRNAs (miRNAs) has been identified as critical event in tumor initiation and progression. We aimed to explore the role of miR-374b in cervical cancer progression. PATIENTS AND METHODS MiR-374b expression was detected using qRT-PCR in cervical cancer tissues compared with normal counterparts. Cell proliferation and invasion ability were detected using Cell Counting Kit-8 (CCK8) cell proliferation and transwell invasion assay. Dual luciferase reporter assay, qRT-PCR, and Western blot analysis were used to demonstrate that FOXM1 was a target of miR-374b. RESULTS We demonstrated that downregulation of miR-374b was frequently examined in cervical cancer tissues compared with normal counterparts. Furthermore, we showed the lower miR-374b expression associated with lymph node metastasis and advanced FIGO stage in patients with cervical cancer. Furthermore, ectopic expression of miR-374b could significantly decrease cell proliferation and invasion ability. However, inhibition of miR-374b had opposite effects. Dual luciferase reporter assay, qRT-PCR, and Western blot analysis revealed that miR-374b overexpression suppressed cell proliferation and invasion ability via affecting FOXM1 expression. CONCLUSIONS These results indicated that miR-374b acted as tumor suppressor and may serve as a potential target for cervical cancer treatment.
Cardiac output measurement during exercise in COPD: A comparison of dye dilution and impedance cardiography

Impedance cardiography (IC) derived from morphological analysis of the thoracic impedance signal is now commonly used for noninvasive assessment of cardiac output (CO) at rest and during exercise. However, in Chronic Obstructive Pulmonary Disease (COPD), conflicting findings put its accuracy into question.
Turning Observed Founder Alleles into Expected Relationships in an Intercross Population

Pedigree-derived relationships for individuals from an intercross of several lines cannot easily account for the segregation variance that is mainly caused by loci with alternative alleles fixed in different lines. However, when all founders are genotyped for a large number of markers, such relationships can be derived for descendants as expected genomic relationships conditional on the observed founder allele frequencies. A tabular method was derived in detail for autosomes and the X-chromosome. As a case study, we analyzed litter size and body weights at three different ages in an advanced mouse intercross (29 generations, total pedigree size 19,266) between a line selected for high litter size (FL1) and a highly inbred control line (DUKsi). Approximately 60% of the total genetic variance was due to segregation variance. Estimated heritability values were 0.20 (0.03), 0.34 (0.04), 0.23 (0.03), 0.41 (0.03) and 0.47 (0.02) for litter size, litter weight and body weight at ages of 21, 42 and 63 days, respectively (standard errors in brackets). These values were between 12% and 65% higher than observed in analyses that treated founders as unrelated. Fields of applications include experimental populations (selection experiments or advanced intercross lines) with a limited number of founders, which can be genotyped at a reasonable cost. In principle any number of founder lines can be treated. Additional genotypes from individuals in later generations can be combined into a joint relationship matrix by capitalizing on previously published approaches.
Stereoscopic Viewing Enhances Visually Induced Motion Sickness but Sound Does Not

Optic flow in visual displays or virtual environments often induces motion sickness (MS). We conducted two studies to analyze the effects of stereopsis, background sound, and realism (video vs. simulation) on the severity of MS and related feelings of immersion and vection. In Experiment 1, 79 participants watched either a 15-min-long video clip taken during a real roller coaster ride, or a precise simulation of the same ride. Additionally, half of the participants watched the movie in 2D, and the other half in 3D. MS was measured using the Simulator Sickness Questionnaire (SSQ) and the Fast Motion Sickness Scale (FMS). Results showed a significant interaction for both variables, indicating highest sickness scores for the real roller coaster video presented in 3D, while all other videos provoked less MS and did not differ among one another. In Experiment 2, 69 subjects were exposed to a video captured during a bicycle ride. Viewing mode (3D vs. 2D) and sound (on vs. off) were varied between subjects. Response measures were the same as in Experiment 1. Results showed a significant effect of stereopsis; MS was more severe for 3D presentation. Sound did not have a significant effect. Taken together, stereoscopic viewing played a crucial role in MS in both experiments. Our findings imply that stereoscopic videos can amplify visual discomfort and should be handled with care.
Diffusion Tensor Imaging to Aid Subgenual Cingulum Target Selection for Deep Brain Stimulation in Depression

Background: The most investigated target for deep brain stimulation in depression is the subgenual cingulate gyrus (Cg25) which has been shown to be a critical hub for signalling in the condition. Diffusion tensor imaging (DTI) is a form of MR sequence that can visualise white matter connections and potentially aid target selection. Objectives: To assess whether targets selected using DTI to find the area of maximal tract crossover (maximal isotropy) underlying the subgenual cingulum differ significantly in location from those selected using standard T2 sequences. Methods: Fifty-nine non-depressed adult volunteers underwent MR imaging using T1, T2 and DTI sequences of the brain. Each patient had targets selected for both hemispheres using both T2 and DTI sequences. The significance of the differences in coordinates in all three dimensions was tested using the paired t test. Results: There was a significant difference in the mediolateral (x) and dorsoventral (z) coordinates of DTI targets when compared with T2 targets (p < 0.001). Conclusions: Targets within Cg25 selected using DTI are significantly different in location from those selected using T2 sequences and have the potential to enhance treatment outcome by reducing the impact of interindividual variability.
Conductive films based on sandwich structures of carbon nanotubes/silver nanowires for stretchable interconnects

A variety of conductive films made of a hybrid of two conductive nanomaterials have been used as stretchable electrodes or interconnectors, desirable for stretchable electronic devices. Their intrinsic stretchability of electrical conductivity allows for accommodating mechanical strain to a certain extent under various deformations. However, few efforts have been made to enhance the interactions between two conductive components in a hybrid system. Herein, we reported new conductive films with tri-layer sandwich structures based on carbon nanotubes (CNTs) and Ag nanowires (NWs), encapsulated in silicone rubber, exhibited high stretchability along with insignificant piezoresistivity. They are suitable to be stretchable interconnectors. A successive vacuum filtration method was used to stack the conductive components layer by layer. The effects of the stacking sequence and the interactions between layers on the stretchability and stability of the electrical properties under mechanical deformations were studied. In the case of a tri-layer conductive film comprising two CNT outer layers and one AgNW central layer in the presence of enhanced interfacial interactions, it showed exceptionally durability in withstanding repetitive deformations.
Role of low field MRI in detecting knee lesions

Objective: The aim of this work is to evaluate the diagnostic accuracy of 0.3T sectoral MR imaging, compared with arthroscopy, for meniscal, cruciate ligaments and chondral knee lesions. Materials and Methods: We conducted a retrospective study analyzing all the consecutive knees subjected to arthroscopy at our institution between January 2014 and June 2017 and preceded within 3 months by knee MR examination at our institution with 0.3 T equipment. Patients with history of a new trauma in the time interval between MR exam and arthroscopy were excluded from the study. Two independent experienced radiologists evaluated in double blind the MR findings of menisci, cruciate ligaments and articular cartilage. Both radiological findings were independently compared with those of the arthroscopic report considered as gold standard. For each of the examined targets we calculated the following parameters: sensitivity, specificity, accuracy, positive and negative predictive value; interobserver concordance statistically calculated using Cohen’s Kappa test. Results: 214 knees (95R/119L) of 214 patients (143M/71F) aged from 18 to 72 years (mean 44) were included and analyzed. We found a good diagnostic accuracy of the low field MR in identifying the injuries of the menisci (93%) and the crossed ligaments (96%), but a lower accuracy for the articular cartilage (85%). Sensitivity resulted 90% for menisci, 73% for ligaments and 58% for cartilage. Specificity was 91% for menisci, 97% for ligaments and 92% for cartilage. Inter-observer concordance resulted to be excellent for cruciate ligaments (K of Cohen’s test = 0.832), good (K = 0.768) for menisci, modest to moderate for articular cartilage (K from 0.236 to 0.389) with worse concordance for tibial cartilage. Conclusions: Low-field MR sectoral device with dedicated joint equipment confirms its diagnostic reliability for the evaluation of meniscal and cruciate ligaments lesions but is weak in evaluating low grade chondral lesions. (www.actabiomedica.it)
Grade Retention Risk among Children with Asthma and Other Chronic Health Conditions in a Large Urban School District

Abstract Asthma accounts for 12.8 million missed school days for children nationwide. Whether this excess absenteeism contributes to poor outcomes such as grade retention is of interest. The Clark County School District in Las Vegas, NV has incorporated the Federal “No Child Left Behind Act,” which states that absences per individual in excess of 10 per school year are considered unapproved and may put a child at risk for repeating a grade. The purpose of this study was to determine if children with asthma are at increased risk for absenteeism associated with grade retention. Secondary data were obtained for students in attendance for the 2006-2007 school year. Days absent were weighted for enrollment time. Frequencies were obtained using descriptive statistics, and multivariate logistic regression was used to model the odds of absenteeism > 10 days per year. Of 300 881 students, 27 299 (9.1%) reported having asthma, as determined by school health records. The population was 52% male, 37% white, and 39% Hispanic. Significant predictors of missing > 10 days per school year included ethnicity, gender, grade, and health status (P < 0.0001). Students with asthma (adjusted odds ratio [aOR], 1.5) or asthma plus another health condition (aOR, 1.6) were at significantly increased odds of missing > 10 school days per year compared with healthy students or those with a medical condition other than asthma (P < 0.0001). Lastly, some disparities were found in current grade point average by race, gender, and asthma status. Children with asthma have a greater risk of absenteeism associated with grade retention. Therefore, improved asthma management and tailored education is necessary to identify and eliminate asthma triggers in the home and school setting for school-aged children.
Polymethoxylated Flavones Target Cancer Stemness and Improve the Antiproliferative Effect of 5-Fluorouracil in a 3D Cell Model of Colorectal Cancer

Polymethoxylated flavones (PMFs) from citrus fruits are reported to present anticancer potential. However, there is a lack of information regarding their effect on cancer stem cell (CSC) populations, which has been recognized as responsible for tumor initiation, relapse, and chemoresistance. In this study, we evaluated the effect of an orange peel extract (OPE) and its main PMFs, namely, nobiletin, sinensetin, tangeretin, and scutellarein tetramethylether in targeting cell proliferation and stemness using a 3D cell model of colorectal cancer composed of HT29 cell spheroids cultured for 7 days in stirred conditions. Soft agar assay, ALDH1 activity, and relative quantitative gene expression analysis of specific biomarkers were carried out to characterize the stemness, self-renewal, and mesenchymal features of HT29 cell spheroids. Then, the impact of OPE and PMFs in reducing cell proliferation and modulating cancer stemness and self-renewal was assessed. Results showed that, when compared with monolayer cultures, HT29 cell spheroids presented higher ALDH1 activity (81.97% ± 5.27% compared to 63.55% ± 17.49% for 2D), upregulation of CD44, PROM1, SOX9, and SNAI1 genes (1.83 ± 0.34, 2.54 ± 0.51, 2.03 ± 0.15, and 6.12 ± 1.59 times) and high self-renewal capability (352 ± 55 colonies compared to 253 ± 42 for 2D). Incubation with OPE (1 mg/mL) significantly inhibited cell proliferation and modulated cancer stemness and self-renewal ability: colony formation, ALDH1 activity, and the expression of cancer stemness biomarkers PROM1 and LGR5 were significantly reduced (0.66 ± 0.15 and 0.51 ± 0.14 times, respectively). Among all PMFs, tangeretin was the most efficient in targeting the CSC population by decreasing colony formation and the expression of PROM1 and LGR5. Scutellarein tetramethylether was shown to modulate markers of mesenchymal/metastatic transition (increasing CDH1 and reducing ZEB1 and SNAI1) and nobiletin was capable of downregulating PROM1 and SNAI1 expression. Importantly, all PMFs and OPE were shown to synergistically interact with 5-fluorouracil, improving the antiproliferative response of this drug.
Curcumin regulates the miR-21/PTEN/Akt pathway and acts in synergy with PD98059 to induce apoptosis of human gastric cancer MGC-803 cells

Objective PD98059 is a potent and selective inhibitor of mitogen-activated protein kinase. Substantial preclinical evidence has shown an anti-tumor effect of curcumin on various solid tumors. This study aimed to investigate whether curcumin synergistically acts with PD98059 in exerting anti-gastric cancer effects. Methods The cell counting kit-8 assay was used to detect cell proliferation of the human gastric cancer MGC-803 cell line. Flow cytometry was performed to detect apoptosis. Western blotting was used to detect phosphatase and tensin homolog (PTEN) and phosphorylated Akt (p-Akt) expression levels. Quantitative reverse transcription-polymerase chain reaction was used to determine microRNA-21 (miR-21). Results A dose of 5 to 40 µM curcumin inhibited proliferation of MGC-803 cells in a dose- and time-dependent manner. A high dose of curcumin strongly inhibited p-Akt protein expression. With increasing curcumin levels, PTEN expression increased and miR-21 levels decreased. These results suggest that curcumin negatively modulated the miR-21/PTEN/Akt pathway. Moreover, after pretreatment with PD98059, cell apoptosis induced by curcumin was significantly increased. Additionally, the inhibitory effects of curcumin on the miR-21/PTEN/Akt pathway were significantly enhanced. Conclusion PD98059 combined with curcumin may be a potential strategy for managing gastric cancer.
Critical Care Nurse Work Environments 2018: Findings and Implications

BACKGROUND The health of critical care nurse work environments affects patient and nurse outcomes. The results of the 2018 Critical Care Nurse Work Environment Study are reported here with comparisons to previous studies and recommendations for continued improvement. OBJECTIVE To evaluate the current state of critical care nurse work environments. METHODS An online survey was used to collect quantitative and qualitative data for this mixed‐methods study. A total of 8080 American Association of Critical‐Care Nurses (AACN) members and constituents responded to the survey. RESULTS The health of critical care nurse work environments has improved since the previous study in 2013; however, there are still areas of concern and opportunities for improvement. Key findings include documented absence of appropriate staffing by more than 60% of participants; an alarming number of physical and mental well‐being issues (198 340 incidents reported by 6017 participants); one‐third of the participants expressed intent to leave their current positions in the next 12 months; and evidence of the positive outcomes of implementing the AACN Healthy Work Environment standards. CONCLUSION Evidence of the relationship between healthy nurse work environments and patient and nurse outcomes continues to increase. The results of this study provide evidence of the positive relationship between implementation of the AACN Healthy Work Environment standards and the health of critical care nurse work environments, between the health of critical care nurse work environments and job satisfaction, and between job satisfaction and the intent of critical care nurses to leave their current positions or stay.