Miracle-dz/UniFAR-FTUs huggingface dataset:
Upregulated exosomal miR-221/222 promotes cervical cancer via repressing methyl-CpG-binding domain protein 2.

OBJECTIVE Methyl-CpG-binding domain protein 2, a target gene of miR-221and miR-222, plays a crucial role in a large body of human cancers. In this study, we aim to explore the mechanism by which miR-221/222 promotes cervical cancer. MATERIALS AND METHODS We have analyzed mRNA expression of MeCP2 and MBD2 in cervical cancer tissues by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and examined the expression of miR-221/222 in C33A, HeLa, and CaSki cells by Western blot. RESULTS We found that the expression levels of MBD2 and MeCP2 were significantly reduced in cervical cancer samples as detected by the analysis of MeCP2 in matched tumor-normal samples of patients with cervical cancer, indicating a reduction in a significant percentage of patients. At the same time, we found that miR-221 and miR-222, which targeted MBD2, were upregulated in cervical cancer samples. To further elucidate the relation between miR-221/222 and MBD2, we used a lot of cell lines such as C33A, HeLa, and CaSki. Surprisingly, we found that the expression levels of MBD2 and MeCP2 were significantly lower in HeLa and CaSki than in C33A, as detected by qRT-PCR. Western blot analysis of MeCP2 of HeLa and CaSki was significantly lower than in C33A. MiR-221/222 was significantly higher in HeLa and CaSki than in C33A by qRT-PCR. The knockdown of miR-221/222 in HeLa and CaSki resulted in the downregulation of miR-221/222 levels, which rescued the expression levels of MBD2 and MeCP2 in HeLa and CaSki. However, transfection of miR-221/222 on C33A could upregulate the expression levels of miR-221/222 and decrease the expression levels of MBD2 and MeCP2. CONCLUSIONS Our results demonstrate that the upregulated miR-221/222 promotes cervical cancer by repressing MBD2 and MeCP2.
The effect of luteolin in prevention of periodontal disease in Wistar rats.

BACKGROUND Periodontal disease is the chronic infectious disease of the periodontium. Because of irreversibility, prevention of disease is one of the most important goals of periodontal treatment. The aim of this study was to evaluate the effect of luteolin, a powerful anti-inflammatory agent, on the prevention of experimental periodontitis by determining morphological and histological tissue alterations. METHODS This study consisted of 28 rats and 4 experimental groups: Healthy control group (C, n = 6); Periodontitis group (P, n = 6); Periodontitis and 50 mg/kg luteolin administered group (L-50, n = 8); Periodontitis and 100 mg/kg luteolin administered group (L-100, n = 8). Experimental periodontitis was induced via ligature method around lower right first molar teeth. All rats were euthanized 11 days after. The severity of periodontal destruction was determined by measuring alveolar bone loss under a stereomicroscope. Osteoblast and inflammatory cell counts were counted on hematoxylin-eosin stained slides and osteoclasts were counted on tartrate resistant acid phosphatase-stained slides. The levels of inducible nitric oxide synthase (iNOS), bone morphogenetic protein (BMP) -2, matrix metallo proteinase (MMP)-8, tissue inhibitor of MMP (TIMP)-1, Receptor activator of nuclear factor κB ligand (RANKL), and osteoprotegerin (OPG) were determined by immunohistochemistry. RESULTS The highest alveolar bone loss was observed in the periodontitis group and the luteolin administration decreased bone loss in both groups. Osteoblast cell number was higher and osteoclast and inflammatory cell numbers were lower in the P group compared to C, L-50 and L-100 groups. Luteolin, dose-dependently increased osteoblast cell counts. Luteolin attenuated periodontal inflammation in both L-50 and L-100 groups. Like osteoblast cell numbers, BMP-2 expressions were also elevated in luteolin groups. Both doses of luteolin significantly increased TIMP-1 and BMP-2 expressions and decreased MMP-8 levels. iNOS expressions increased in P group and L-100 significantly decreased iNOS levels. RANKL increased and OPG decreased in P group and 100 mg/kg luteolin increased OPG and decreased RANKL levels significantly. CONCLUSIONS As a conclusion, within the limits of present experimental study, luteolin successfully improved periodontal health in a ligature-induced experimental periodontitis model in Wistar rats. The decrease in inflammation, osteoclastic and collagenase activity and increase in osteoblastic activity are possibly involved in this process. This article is protected by copyright. All rights reserved.
Neuronal Targeting of Cardiotrophin-1 by Coupling with Tetanus Toxin C Fragment

Cardiotrophin-1 (CT-1) is a potent neurotrophic factor for motoneurons but its clinical use in motor neuron diseases is precluded by side effects on the heart and liver. We explored the possibility of targeting CT-1 to neurons by coupling with the tetanus toxin fragment TTC. Genetic fusion proteins between CT-1 or GFP and TTC were produced in Escherichia coli and assayed in vitro. In contrast to uncoupled CT-1 or GFP, TTC-coupled proteins bound with high affinity to cerebral neurons and spinal cord motoneurons and were rapidly internalized. Glia, hepatocytes, or cardiomyocytes did not show detectable binding or uptake of TTC-coupled proteins. Similar to CT-1, TTC-coupled CT-1 induced IL-6 secretion by KB cells, activated Reg-2 gene expression, and promoted motoneuron survival in a dose-dependent manner. In vivo studies will test whether TTC-coupled CT-1 might be targeted to degenerating spinal cord or brain-stem motoneurons and migrate trans-synaptically to cortical motoneurons, which are also affected in amyotrophic lateral sclerosis.
Robust Stoichiometry of FliW-CsrA Governs Flagellin Homeostasis and Cytoplasmic Organization in Bacillus subtilis

The intracellular concentration of flagellar filament protein Hag is restricted by the Hag-FliW-CsrA system in B. subtilis. Here we show that the Hag-FliW-CsrAdimer system functions at nearly 1:1:1 stoichiometry and that the system is both robust with respect to perturbation and hypersensitive to the Hag intracellular concentration. Moreover, restriction of cytoplasmic Hag levels is important for maintaining proper intracellular architecture, as artificial Hag hyperaccumulation led to generalized spatial defects and a high frequency of minicell production. The Hag-FliW-CsrA system is conserved in the deeper branches of bacterial phylogeny, and we note that the Hag-FliW-CsrA “homeostasis module” resembles a toxin-antitoxin system where, by analogy, CsrA is the “toxin,” FliW is the “antitoxin,” and Hag is the target. ABSTRACT Flagellin (Hag) is one of the most abundant proteins in Bacillus subtilis. Here we show that each flagellar filament is assembled from ∼12,000 Hag monomers and that there is a cytoplasmic pool of Hag that is restricted to 5% of the total. Hag is thought to be restricted at the level of translation by a partner-switching mechanism involving FliW and the homodimeric RNA-binding protein CsrA (CsrAdimer). We further show that the mechanism of translation inhibition is hypersensitive due to a 1:1 ratio of Hag to FliW, a 1:1 inhibitory ratio of FliW to CsrAdimer, and a nearly 1:1 ratio of CsrAdimer to hag transcripts. Equimolarity of all components couples single-molecule detection of Hag export to compensatory translation and causes cytoplasmic Hag concentrations to oscillate around the level of FliW. We found that stoichiometry is ensured by genetic architecture, translational coupling, and the ability of CsrAdimer to restrict hag transcript accumulation. We further show that homeostasis prevents Hag hyperaccumulation that would otherwise cause severe defects in intracellular architecture, perhaps due to increased molecular crowding. We note that FliW-CsrA-mediated structural homeostasis has similarities to that seen with some toxin-antitoxin systems. IMPORTANCE The intracellular concentration of flagellar filament protein Hag is restricted by the Hag-FliW-CsrA system in B. subtilis. Here we show that the Hag-FliW-CsrAdimer system functions at nearly 1:1:1 stoichiometry and that the system is both robust with respect to perturbation and hypersensitive to the Hag intracellular concentration. Moreover, restriction of cytoplasmic Hag levels is important for maintaining proper intracellular architecture, as artificial Hag hyperaccumulation led to generalized spatial defects and a high frequency of minicell production. The Hag-FliW-CsrA system is conserved in the deeper branches of bacterial phylogeny, and we note that the Hag-FliW-CsrA “homeostasis module” resembles a toxin-antitoxin system where, by analogy, CsrA is the “toxin,” FliW is the “antitoxin,” and Hag is the target.
Health beliefs and the valence framework in health information seeking behaviors

Purpose The purpose of this paper is to help understand consumer acceptance of online health information services by integrating the health belief model and extended valence framework. Design/methodology/approach A laboratory-based, experimental-scenarios research design is used to collect data, and the structural equation modeling technique is used to test the research model. Findings The model explains 47.6 percent of the variance in intentions to use online health information services. Trust appeared to have the strongest effect on acceptance. Perceived risk also had a significant impact on acceptance. Furthermore, health belief variables are confirmed as important factors for consumer acceptance. Self-efficacy was found to moderate the effect of perceived severity on acceptance. Research limitations/implications This study helped identify the relative salience of the health belief model and extended valence framework in consumer acceptance of online health information services. Practical implications This study can help practitioners better understand the development of trust and the profiles of consumers who may browse their sites. When online health service providers promote their information to encourage potential online health information seekers, they should use countermeasures against risk perceptions. Originality/value This study attempted to extend the valence framework to the non-commercial service context. Moreover, health beliefs and the valence framework are two fundamental aspects that health information seekers consider when making decisions about online health services.
Outcomes of hip arthroscopy for femoroacetabular impingement: The effect of morphological type and chondrolabral damage

Introduction: Hip arthroscopy for treatment of femoroacetabular impingement (FAI) has shown significant pain and functional improvement. However, the differential outcome of each of the FAI morphological types in contrast to one another remains largely unknown. This study was conducted to detect a possible difference in outcome among different FAI types treated using hip arthroscopy. Methods: In this prospective non randomized comparative study, after exclusion of non-FAI cases and cases with advanced arthritic changes, 90 hips in 85 patients that had hip arthroscopy for the treatment of FAI between 2011 and 2015 in our center were analyzed. The collected patient reported outcome measures (PROMs) included visual analog scale (VAS) of pain, the modified Harris hip score (mHHS), and the non arthritic hip score (NAHS) both preoperatively and at final follow-up. Patient satisfaction was collected at final follow-up. Postoperative PROMs were subjected to three main comparisons based on each of FAI type, labral procedure, and extent of cartilage damage. Repeat comparison based on FAI type after matching of exact chondrolabral condition was also attempted. Results: Mean follow-up was 32.8 months (five patients lost from follow-up). There was a significant improvement in the overall PROMs. This improvement was significantly higher in the cam group in contrast to the mixed group. After matching for chondrolabral condition, this difference was consistent and more evident. Discussion: The outcome of arthroscopic treatment of pure cam FAI is significantly better than that of mixed FAI. Matching of the same chondrolabral condition and repeating the comparison yields similar results.
Hybrid Techniques for Hybrid Systems

Computer controlled systems are almost omnipresent nowadays. We expect such systems to function properly at any time we need them. The malfunctioning of home electronics just irritates us, but glitches in a car, power plant or medical support system may threaten life, and faults in nuclear missile control facility may bring the end to civilisation. Such ubiquity of computer based control puts very high reliability requirements on such systems. Hybrid systems combine continuous real-time behaviour and discrete events. Research in hybrid systems aims at providing means for reliable design and production of hybrid systems. In this thesis we explore the world of hybrid systems. We acknowledge relevance and complexity of hybrid systems research, and emphasise several different research topics: modelling, analysis, testing and deployment of hybrid systems.
Comparison of chest compression quality in walking versus straddling cardiopulmonary resuscitation during stretcher transportation: A prospective randomised crossover study using manikins

The optimal strategy to ensure chest compression quality for patients being transported on a stretcher has not been established yet. We hypothesised that straddling cardiopulmonary resuscitation may improve chest compression quality in patients being transported on stretchers. We conducted a prospective randomised crossover study using manikins to investigate whether straddling cardiopulmonary resuscitation improves chest compression quality (depth, recoil, rate, correct hand position) performed on patients during stretcher transportation compared to walking cardiopulmonary resuscitation. Walking and straddling cardiopulmonary resuscitation were performed for 2 minutes each. The mean chest compression depth (mm) for 2 minutes was significantly greater in the straddling cardiopulmonary resuscitation group than in the walking cardiopulmonary resuscitation group (median, 51.3 [interquartile range, 46.7–55.5] versus 40.9 [34.6–50.1], P = 0.003). An adequate depth of chest compressions could not be achieved when walking cardiopulmonary resuscitation was performed by female participants, but the depth of chest compressions was within the acceptable range when female participants performed straddling cardiopulmonary resuscitation. On the other hand, the degree of deterioration was relatively small in male participants, even when they performed walking cardiopulmonary resuscitation. In patients with cardiac arrest being transported on a stretcher, straddling cardiopulmonary resuscitation improved the depth of chest compressions compared to walking cardiopulmonary resuscitation. Female rescuers, in particular, may consider using straddling cardiopulmonary resuscitation.
Challenges in estimating influenza vaccine effectiveness

ABSTRACT Introduction: Influenza vaccination is regarded as the most effective way to prevent influenza infection. Due to the rapid genetic changes that influenza viruses undergo, seasonal influenza vaccines must be reformulated and re-administered annually necessitating the evaluation of influenza vaccine effectiveness (VE) each year. The estimation of influenza VE presents numerous challenges. Areas Covered: This review aims to identify, discuss, and, where possible, offer suggestions for dealing with the following challenges in estimating influenza VE: different outcomes of interest against which VE is estimated, study designs used to assess VE, sources of bias and confounding, repeat vaccination, waning immunity, population level effects of vaccination, and VE in at-risk populations. Expert Opinion: The estimation of influenza VE has improved with surveillance networks, better understanding of sources of bias and confounding, and the implementation of advanced statistical methods. Future research should focus on better estimates of the indirect effects of vaccination, the biological effects of vaccination, and how vaccines interact with the immune system. Specifically, little is known about how influenza vaccination impacts an individual’s infectiousness, how vaccines wane over time, and the impact of repeated vaccination.
Association of FEF25-75% Impairment with Bronchial Hyperresponsiveness and Airway Inflammation in Subjects with Asthma-Like Symptoms

Background: Forced expiratory flow at 25 and 75% of the pulmonary volume (FEF<sub>25-75%</sub>) might be considered as a marker of early airway obstruction. FEF<sub>25-75%</sub> impairment might suggest earlier asthma recognition in symptomatic subjects even in the absence of other abnormal spirometry values. Objectives: The study was designed in order to verify whether FEF<sub>25-75%</sub> impairment in a cohort of subjects with asthma-like symptoms could be associated with the risk of bronchial hyperresponsiveness (BHR) and with airway inflammation expressed as fractional exhaled nitric oxide (Fe<smlcap>NO</smlcap>) and eosinophil counts in induced sputum. Methods: Four hundred adults with a history of asthma-like symptoms (10.5% allergic) underwent spirometry, determination of BHR to methacholine (PD<sub>20</sub>FEV<sub>1</sub>), Fe<smlcap>NO</smlcap> analysis and sputum induction. FEF<sub>25-75%</sub> <65% of predicted or <-1.64 z-score was considered abnormal. Results: All subjects had normal FVC, FEV<sub>1</sub> and FEV<sub>1</sub>/FVC, while FEF<sub>25-75%</sub> was abnormal in 27.5% of them. FEF<sub>25-75%</sub> (z-score) was associated with PD<sub>20</sub>FEV<sub>1</sub> (p < 0.001), Fe<smlcap>NO</smlcap> (p < 0.001) and sputum eosinophils (p < 0.001). Patients with abnormal FEF<sub>25-75%</sub> showed higher levels of Fe<smlcap>NO</smlcap> and eosinophils in induced sputum than did patients with normal FEF<sub>25-75%</sub> (p < 0.01 and p < 0.01, respectively). Subjects with abnormal FEF<sub>25-75%</sub> had an increased probability of being BHR positive (OR = 13.38; 95% CI: 6.7-26.7; p < 0.001). Conclusions: Our data show that abnormal FEF<sub>25-75%</sub> might be considered an early marker of airflow limitation associated with eosinophilic inflammation and BHR in subjects with asthma-like symptoms, indicating a role for FEF<sub>25-75%</sub> as a predictive marker of newly diagnosed asthma.
Embolus analogue trajectory paths under physiological flowrates through patient specific aortic arch models.

Atrial fibrillation (AF) is the most common irregular heartbeat among the world's population and is a major contributor to cardiogenic embolisms and acute ischemic stroke (AIS). A physiological simulation system designed to analyse the trajectory patterns of bovine embolus analogues (EAs) (n = 720) through four patient specific models, under three flow conditions: steady flow, normal pulsatile flow and AF pulsatile flow. Overall AF flow conditions increased trajectories through the LCCA and RCCA by 25%. There was no statistical difference in the distribution of clot trajectories when the clot was released from the right, left or anterior positions. Overall, the EA trajectory paths were proportional to the percentage flowrate split of 25 - 31% along the branching vessels. Significantly more EAs travelled through the brachiocephalic trunk experienced than through the LCCA or the left subclavian. Yet of the EAs that travelled towards the cerebral vasculature, there was a greater affiliation towards the left common carotid artery compared to the right common carotid artery (p < 0.05).
The non‐Hodgkin's lymphomas I. A retrospective clinical and pathologic analysis of 499 cases diagnosed between 1958 and 1969

A retrospective clinical and histopathological review was made of 499 previously untreated cases of non‐Hodgkin's lymphoma with adequate initial biopsy material diagnosed at Memorial Hospital between 1958 and 1969. Three hundred‐eighty‐four cases (77%) had diffuse, 104 (21%) nodular, nine (2%) nodular and diffuse, and two (< 1%) unclassifiable histologic types. Overall median survival was 16 months, and 79% of the patients died with lymphoma. For all treatments, survival of responding patients was the same as that of nonresponders, a reflection of the palliative approach. Significant differences in survival were found between patients in the various Ann Arbor stages. Median survival was 42 months for the nodular group and 11.5 months for the diffuse (P < 0.001). The ten‐year survival was 12% for the diffuse and 22% for the nodular patients. The overall difference in survival was due to early deaths in the diffuse group. Long‐term follow‐up is necessary to appreciate the usual fatal course of patients with all types of non‐Hodgkin's lymphomas treated conservatively.
Power amplifier linearization with memory effects using digital pre-distortion and genetic algorithms

This work investigates the application of genetic algorithms to linearize power amplifiers with strong memory effects using digital pre-distortion. An algorithm is presented that adapts polynomial predistortion functions to minimize adjacent channel emissions. The paper describes the implementation of this algorithm and compares its performance with those achieved by conventional wideband feedback optimization techniques. Simulation results indicate nearly optimal performance in a limited number of iterations, suggesting that this technique can be employed as a low-cost solution to meet regulatory requirements.
Elevated oxysterol levels in human and mouse livers reflect nonalcoholic steatohepatitis[S]

Nonalcoholic steatohepatitis (NASH), a primary cause of liver disease, leads to complications such as fibrosis, cirrhosis, and carcinoma, but the pathophysiology of NASH is incompletely understood. Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) and its oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-diHC) are recently discovered immune regulators. Several lines of evidence suggest a role of oxysterols in NASH pathogenesis, but rigorous testing has not been performed. We measured oxysterol levels in the livers of NASH patients by LC-MS and tested the role of the EBI2-7α,25-diHC system in a murine feeding model of NASH. Free oxysterol profiling in livers from NASH patients revealed a pronounced increase in 24- and 7-hydroxylated oxysterols in NASH compared with controls. Levels of 24- and 7-hydroxylated oxysterols correlated with histological NASH activity. Histological analysis of murine liver samples demonstrated ballooning and liver inflammation. No significant genotype-related differences were observed in Ebi2−/− mice and mice with defects in the 7α,25-diHC synthesizing enzymes CH25H and CYP7B1 compared with wild-type littermate controls, arguing against an essential role of these genes in NASH pathogenesis. Elevated 24- and 7-hydroxylated oxysterol levels were confirmed in murine NASH liver samples. Our results suggest increased bile acid synthesis in NASH samples, as judged by the enhanced level of 7α-hydroxycholest-4-en-3-one and impaired 24S-hydroxycholesterol metabolism as characteristic biochemical changes in livers affected by NASH.