Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth-Promoting Properties of Epstein-Barr Virus EBER-1 RNA Correlate with Ribosomal Protein L22 Binding

ABSTRACT The Epstein-Barr virus (EBV)-encoded RNAs, EBER-1 and EBER-2, are highly abundant noncoding nuclear RNAs expressed during all forms of EBV latency. The EBERs have been shown to impart significant tumorigenic potential upon EBV-negative Burkitt lymphoma (BL) cells and to contribute to the growth potential of other B-cell lymphoma-, gastric carcinoma-, and nasopharyngeal carcinoma-derived cell lines. However, the mechanisms underlying this EBER-dependent enhancement of cell growth potential remain to be elucidated. Here we focused on the known interaction between EBER-1 and the cellular ribosomal protein L22 and the consequences of this interaction with respect to the growth-promoting properties of the EBERs. L22, a component of 60S ribosomal subunits, binds three sites on EBER-1, and a substantial fraction of available L22 is relocalized from nucleoli to the nucleoplasm in EBV-infected cells. To investigate the hypothesis that EBER-1-mediated relocalization of L22 in EBV-infected cells is critical for EBER-dependent functions, we investigated whether EBER-1 expression is necessary and sufficient for nucleoplasmic retention of L22. Following demonstration of this, we utilized RNA-protein binding assays and fluorescence localization studies to demonstrate that mutation of the L22 binding sites on EBER-1 prevents L22 binding and inhibits EBER-1-dependent L22 relocalization. Finally, the in vivo consequence of preventing L22 relocalization in EBER-expressing cells was examined in soft agar colony formation assays. We demonstrate that BL cells expressing mutated EBER-1 RNAs rendered incapable of binding L22 have significantly reduced capacity to enhance cell growth potential relative to BL cells expressing wild-type EBERs.
Smurf1 ubiquitin ligase causes downregulation of BMP receptors and is induced in monocrotaline and hypoxia models of pulmonary arterial hypertension

Reduced bone morphogenetic protein (BMP) receptor (BMPR) expression and BMP signaling have been implicated in vascular cell proliferation and remodeling associated with pulmonary arterial hypertension (PAH). The low penetrance of the BMPR II disease gene in familial PAH suggests that additional genetic or environmental factors are involved in clinical manifestation of PAH. Smurf1 ubiquitin ligase, together with inhibitory SMAD 6/7, forms a negative feedback loop for the attenuation of BMP signals by downregulating BMPR and signaling molecules and, in addition, functions in the integration of MAPK/Ras mitogenic pathways. The present study found that Smurf1 was significantly elevated in pulmonary arteries of monocrotaline and hypoxia-induced PAH rats. In the pulmonary artery of hypoxia-exposed mice, elevation of Smurf1 and SMAD7 was correlated with reduced expression of BMPR II protein. Over-expression of Smurf1 in cultured cells induced ubiquitination and degradation of BMPR I and II whereas ligase-inactive Smurf1 reduced ubiquitination and elevated their protein levels, thus serving a dominant-negative function. Smurf1-induced receptor degradation was inhibited by both proteasomal and lysosomal inhibitors. Thus, Smurf1 reduces steady-state levels of BMPRs by ubiquitination and subsequent degradation involving proteasomes and lysosomes. Therefore, these results show that Smurf1 induction could be a key event for triggering downregulation of BMP signaling and causing vascular cell proliferation and remodeling in PAH and that abrogating Smurf1 function could be a strategy for PAH therapeutics.
Organisation-based self-esteem mediates the effects of social support and job satisfaction on intention to stay in nurses.

AIM This study examined the effect of underlying contextual factors on the intention to stay in nurses. BACKGROUND Workplace promotion, social support, work stress, job satisfaction and organisation-based self-esteem (OBSE) are psychosocial factors influencing the intention to stay in nurses. However, few studies have analysed the relationships among these factors. METHOD A cross-sectional survey was conducted and a sample was recruited in convenience sampling method from a medical centre in Taiwan. A total of 791 nurses completed a self-report questionnaire over a 3-month period in 2013. RESULTS Social support, work stress, job satisfaction and OBSE significantly affected the intention to stay in nurses. Furthermore, social support and job satisfaction showed a positive direct effect on the intention to stay and an indirect effect on the intention to stay; the indirect effect was mediated by OBSE. CONCLUSION Organisation-based self-esteem mediates the effects of social support and job satisfaction on the intention to stay in nurses. IMPLICATIONS FOR NURSING MANAGEMENT The results showing the influence of OBSE on the intention to stay in nurses can serve as insight for hospital managers to make decisions when encouraging and managing employees.
Edge-Facilitated Wireless Distributed Computing

We propose a framework for edge-facilitated wireless distributed computing, in which several mobile users connected to an access point collaborate for a distributed computing task. We characterize the minimum communication load, both in uplink (from users to the access point) and downlink (from access point to the users), required for distributed computing. In particular, we develop a communication scheme and a dataset placement strategy that induces a particular overlap of computations at the users, which can then be exploited for coding at both users and the access point to significantly reduce the communication load. We demonstrate that the reduction in communication load (compared to uncoded solutions) can scale linearly with the size of the network (i.e., the number of users), hence our proposed scheme can result in a "scalable" design for edge- facilitated wireless distributed computing (i.e., accommodating any number of users without incurring extra communication load). Furthermore, we establish the optimality of the proposed scheme by developing a tight information theoretic outer- bound, and demonstrate that the proposed scheme achieves the minimum uplink and downlink communication load simultaneously. We also generalize the results to a decentralized setting, in which a random and a priori unknown subset of users may participate in distributed computing at each time, and characterize the minimum communication load for uniformly random dataset placement at users.
Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study.

BACKGROUND Cetuximab in combination with platinum and 5-fluorouracil is the standard of care in the first-line treatment of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Cetuximab and taxane combinations have shown promising activity. This study evaluated the efficacy and safety of four cycles of docetaxel associated with cisplatin and cetuximab (TPEx), followed by maintenance with cetuximab every 2 weeks. PATIENTS AND METHODS Patients with a histologically confirmed HNSCC with metastasis or recurrence unsuitable for locoregional curative treatment received docetaxel and cisplatin (75 mg/m(2) both) at day 1 and weekly cetuximab 250 mg/m(2) (loading dose of 400 mg/m(2)), repeated every 21 days for four cycles, followed by maintenance cetuximab 500 mg/m(2) every 2 weeks until progression or unacceptable toxicity. Prophylactic administration of granulocyte colony-stimulating factor was done systematically after each chemotherapy cycle. Patients had a good general status (performance status ≤1) and were under 71 years. Prior total doses of cisplatin exceeding 300 mg/m(2) were not allowed. The primary end point was objective response rate (ORR) after four cycles. RESULTS Fifty-four patients were enrolled. The primary end point was met with an ORR of 44.4% (95% CI 30.9-58.6). Median overall and progression-free survivals were, respectively, 14 months (95% CI 11.3-17.3) and 6.2 months (95% CI 5.4-7.2). The most common grade 3/4 adverse events were skin rash (16.6%) and non-febrile neutropenia (20.4%). There were one pulmonary embolism and two infectious events leading to death. CONCLUSIONS The TPEx regimen showed promising activity as first-line treatment in fit patients with recurrent/metastatic HNSCC. Further studies are needed to compare the TPEx versus EXTREME regimen in this population. CLINICALTRIALGOV NCT01289522.
In vivo cleavage specificity of Trypanosoma brucei editosome endonucleases

Abstract RNA editing is an essential post-transcriptional process that creates functional mitochondrial mRNAs in Kinetoplastids. Multiprotein editosomes catalyze pre-mRNA cleavage, uridine (U) insertion or deletion, and ligation as specified by guide RNAs. Three functionally and compositionally distinct editosomes differ by the mutually exclusive presence of the KREN1, KREN2 or KREN3 endonuclease and their associated partner proteins. Because endonuclease cleavage is a likely point of regulation for RNA editing, we elucidated endonuclease specificity in vivo. We used a mutant gamma ATP synthase allele (MGA) to circumvent the normal essentiality of the editing endonucleases, and created cell lines in which both alleles of one, two or all three of the endonucleases were deleted. Cells lacking multiple endonucleases had altered editosome sedimentation on glycerol gradients and substantial defects in overall editing. Deep sequencing analysis of RNAs from such cells revealed clear discrimination by editosomes between sites of deletion versus insertion editing and preferential but overlapping specificity for sites of insertion editing. Thus, endonuclease specificities in vivo are distinct but with some functional overlap. The overlapping specificities likely accommodate the more numerous sites of insertion versus deletion editing as editosomes collaborate to accurately edit thousands of distinct editing sites in vivo.
Quantitative Comparison of the Effect of 10% Phenylephrine Instillation and Manual Elevation in Patients with Involutional Blepharoptosis

Abstract Objective: To compare the effect of 10% phenylephrine (PE) instillation and manual elevation (ME) on the upper eyelid position of the tested eye and the contralateral eye in patients with involutional blepharoptosis (IB). Methods: IB patients were submitted to two tests followed by observation of the effect on the contralateral eyelid: (1) ME of the more ptotic eyelid; and (2) instillation of two drops of 10% PE (phenylephrine test) in the more ptotic eye. The patients were filmed before and 5, 10, and 15 minutes after instillation. The upper eyelid margin reflex distance (MRD1) was measured using the software Image J, and the results were analyzed with the linear mixed-effects model. Results: The study included 70 patients aged 44–86 years, 64 of whom were female (91.43%), divided into three groups: subjects with unilateral IB, subjects with bilateral IB, and controls. The eye submitted to instillation with 10% PE displayed significant elevation during the first 10 min: from 1.33 ± 0.66 mm to 2.06 ± 0.89 mm (unilateral group), from 1.26 ± 0.63 mm to 2.29 ± 0.86 mm (bilateral group), and from 3.12 ± 0.68 mm to 4.06 ± 0.92 mm (control group). MRD1 decreased in the contralateral eye in IB patients, significantly more so after the phenylephrine test: PE vs. ME = 18.9% versus 17.2% reduction in the unilateral group, and 13.6% versus 10.7% reduction in the bilateral group. The outcome was not influenced by IB severity and the concurrence of IB and eye dominance. Conclusion: Both ME and 10% PE affected the contralateral upper eyelid, but the response was significantly better with the latter.
The three-dimensional hydrogen-bonded structures in the ammonium and sodium salt hydrates of 4-aminophenylarsonic acid.

The structures of two hydrated salts of 4-aminophenylarsonic acid (p-arsanilic acid), namely ammonium 4-aminophenylarsonate monohydrate, NH4(+)·C6H7AsNO3(-)·H2O, (I), and the one-dimensional coordination polymer catena-poly[[(4-aminophenylarsonato-κO)diaquasodium]-μ-aqua], [Na(C6H7AsNO3)(H2O)3]n, (II), have been determined. In the structure of the ammonium salt, (I), the ammonium cations, arsonate anions and water molecules interact through inter-species N-H.O and arsonate and water O-H.O hydrogen bonds, giving the common two-dimensional layers lying parallel to (010). These layers are extended into three dimensions through bridging hydrogen-bonding interactions involving the para-amine group acting both as a donor and an acceptor. In the structure of the sodium salt, (II), the Na(+) cation is coordinated by five O-atom donors, one from a single monodentate arsonate ligand, two from monodentate water molecules and two from bridging water molecules, giving a very distorted square-pyramidal coordination environment. The water bridges generate one-dimensional chains extending along c and extensive interchain O-H.O and N-H.O hydrogen-bonding interactions link these chains, giving an overall three-dimensional structure. The two structures reported here are the first reported examples of salts of p-arsanilic acid.
Observational study on the occurrence of surgical glove perforation and associated risk factors in large animal surgery

OBJECTIVE To determine the incidence of and associated risk factors for glove perforation in large animal surgery. STUDY DESIGN Prospective observational cohort study. SAMPLE POPULATION Surgical gloves (n = 917) worn during 103 large animal surgical procedures. METHODS Gloves worn by personnel involved in sterile preparation and surgical procedures were tested for perforation by 2 previously validated methods, water leak test (WLT) and electroconductivity testing (ECT). The association between surgical and glove-related variables and glove perforation was assessed by using a multivariable mixed-effect logistic regression model. RESULTS At least 1 glove perforation was detected in 66% of surgical procedures, and 17.9% (164/917) of gloves tested were identified as perforated. All perforations were detected by ECT, whereas only 110/178 (61.8%) were detected by WLT. All perforations detected by WLT were also detected by ECT. The risk of glove perforation increased with duration of wear (>60 minutes odds ratio [OR] 2.3, 95% CI 1.4-3.7; P < .001) and with invasiveness of procedures (OR 7.9, 95% CI 3.2-19.5; P < .001). Primary surgeons were at higher risk for glove perforation than first (OR 1.7, 95% CI 1.1-2.5; P = .008) and second (OR 3.4, 95% CI 2-6.7; P < .001) assistants. Only 25% of glove perforations were detected intraoperatively by the wearer. CONCLUSION Incidence of glove perforation is similar in large animal, human, and small animal surgery and is influenced by duration of wear, invasiveness of the surgery, and role of the wearer. ECT is more sensitive than WLT for detection of glove perforation.
Sensitivity shaping with degree constraint via convex optimization

We present an approach for shaping closed-loop operators while keeping their Mcmillan degree bounded by the sum of unstable plant-poles and non-minimum phase plant-zeros. We make use of recent developments in analytic interpolation with degree constraint and we focus on the paradigm of sensitivity minimization. The sensitivity function can be obtained as the minimizer of a convex weighted-entropy functional. It is the choice of this weight that we formulate as a convex optimization problem in this paper
Corticosteroids Versus NSAIDs on Intraocular Pressure and the Hypertensive Phase After Ahmed Glaucoma Valve Surgery

PurposeTo compare the effect of topical steroids versus nonsteroidal anti-inflammatory drugs on intraocular pressure (IOP) and the hypertensive phase (HP) after Ahmed glaucoma valve surgery. Patients and MethodsProspective, randomized, double-masked controlled trial. Twenty-eight consecutive consenting patients scheduled for Ahmed glaucoma valve surgery were randomized to receive either postoperative topical dexamethasone or ketorolac. The main outcome measure was IOP. Secondary outcomes included incidence of HP, visual acuity, number of glaucoma medications, postoperative complications, and subsequent procedures. ResultsThe mean postoperative IOP (in mm Hg) in the ketorolac versus dexamethasone arms respectively was as follows: 8.8±4.7 versus 10.0±4.5 at week 1 (P=0.500); 10.7±6.7 versus 17.5±10.4 at week 2 (P=0.053); 11.0±6.5 versus 18.0±7.3 at week 4 (P=0.013); 14.8±8.6 versus 17.5±5.2 at week 6 to 8 (P=0.323); and 14.8±9.6 versus 17.8±7.5 at week 10 to 12 (P=0.374). Four patients (31%) in the ketorolac arm versus 8 patients (53%) in the dexamethasone arm exhibited the HP (P=0.276). Wound leak was the most severe complication and there were 3 cases (23%) in the ketorolac group versus nil in the steroid group (P=0.087). Conjunctival retraction was observed in 8 patients (62%) in the ketorolac arm versus 2 patients (13%) in the dexamethasone arm (P=0.016). ConclusionsMean IOP was greater at all time points postoperatively in the steroid group with the difference between groups statistically significant at week 4. The nonsteroidal anti-inflammatory drug group showed greater wound-healing problems.
Subretinal perfluorodecalin toxicity.

BACKGROUND Subretinal injection of perfluorocarbon liquids (PFCL) can occur during vitreoretinal surgery. The long-term effects of this complication are not well established. METHODS A case report is presented of a patient with retained subretinal perfluorodecalin following retinal detachment repair for a giant retinal tear. RESULTS In the early postoperative period, the macular retinal pigment epithelium (RPE) became opalescent in appearance and by 2 months postoperatively the patient developed macular RPE atrophy with resulting poor central vision. CONCLUSIONS Toxicity of subretinal perfluorodecalin causing RPE atrophy is proposed. We recommend all traces of PFCL should be removed if possible.
The Benefits of Sunflower Oleodistillate (SOD) in Pediatric Dermatology

Abstract: For millennia, sunflower seed oil has been used in folk medicine for both skin care and the treatment of skin disorders. In its natural state, the oil contains high levels of essential fatty acids, particularly linoleic acid, which has skin barrier‐enhancing properties. A sunflower oleodistillate (SOD), which is produced through a molecular distillation process without the use of solvents, has been shown to increase the epidermal key lipid synthesis and to reduce inflammation in vitro and in animal models. It has also been shown to activate peroxisome proliferative‐activated receptor‐α (PPAR‐α) in vitro. As PPAR‐α agonists have been shown to stimulate keratinocyte differentiation, improve barrier function, and enhance lipid metabolism in the skin, it has been suggested that SOD might also be efficacious in atopic dermatitis (AD). An initial clinical evaluation of the care effect of a 2% SOD emulsion in 20 adult volunteers with atopic skin revealed the moisturizing properties of SOD. Finally, a strong steroid‐sparing effect and a positive effect on quality‐of‐life parameters were clearly demonstrated for the 2% SOD cream in studies in infants and babies with AD.
Inducible overexpression of cingulin in stably transfected MDCK cells does not affect tight junction organization and gene expression

Cingulin is a component of the cytoplasmic domain of vertebrate tight junctions (TJ). Mutation or down-regulation of cingulin in cultured cells results in changes in gene expression. Some of these changes are dependent on RhoA, whose activity is regulated by GEF-H1, which is inactivated by binding to cingulin at junctions. To gain further insights on the function of cingulin through dominant-negative effects, we cloned and sequenced canine cingulin, and developed stable MDCK cell lines where either full-length cingulin, or head or rod+tail domains were inducibly overexpressed. Surprisingly, analysis of these clones by immunoblotting, microarray, immunofluorescence, measurement of transepithelial resistance, and cell density showed that the overexpression of either full-length cingulin or its domains does not significantly affect TJ protein levels, gene expression, RhoA activity, cell density, doubling time, and the organization and function of TJ. These results suggest that compensatory mechanisms prevent dominant-negative effects in this model system, and that modulation of cellular functions by cingulin occurs within physiological protein levels.
Bias in meta-analysis detected by a simple, graphical test

Abstract Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure