Miracle-dz/UniFAR-FTUs huggingface dataset:
Cap-Poly(A) Synergy in Mammalian Cell-free Extracts

The 5′ cap and 3′ poly(A) tail of eukaryotic mRNAs cooperate to stimulate synergistically translation initiationin vivo, a phenomenon observed to date in vitroonly in translation systems containing endogenous competitor mRNAs. Here we describe nuclease-treated rabbit reticulocyte lysates and HeLa cell cytoplasmic extracts that reproduce cap-poly(A) synergy in the absence of such competitor RNAs. Extracts were rendered poly(A)-dependent by ultracentrifugation to partially deplete them of ribosomes and associated initiation factors. Under optimal conditions, values for synergy in reticulocyte lysates approached 10-fold. By using this system, we investigated the molecular mechanism of poly(A) stimulation of translation. Maximal cap-poly(A) cooperativity required the integrity of the eukaryotic initiation factor 4G-poly(A)-binding protein (eIF4G-PABP) interaction, suggesting that synergy results from mRNA circularization. In addition, polyadenylation stimulated uncapped cellular mRNA translation and that driven by the encephalomyocarditis virus internal ribosome entry segment (IRES). These effects of poly(A) were also sensitive to disruption of the eIF4G-PABP interaction, suggesting that 5′–3′ end cross-talk is functionally conserved between classical mRNAs and an IRES-containing mRNA. Finally, we demonstrate that a rotaviral non-structural protein that evicts PABP from eIF4G is capable of provoking the shut-off of host cell translation seen during rotavirus infection.
Assessment of selected determinants of the implementation of health and physical education curriculum in public primary schools in Nandi County, Kenya

Health and Physical Education (HPE) is one of the core subjects in primary and secondary schools, as well as in teacher training colleges in Kenya. The implementation of the HPE curriculum is however not progressing as expected. The purpose of this study was therefore to assess selected determinants of implementation of HPE curriculum in public primary schools in Nandi County. The study was guided by five objectives that sought to establish the influence of teacher preparation and use of professional documents; teaching methods; teacher attitude; adequacy of equipment and facilities; and monitoring and evaluation, on implementation of the HPE curriculum. The study was grounded in the pragmatic paradigm and adopted the convergent mixed methods research design. A population of 1290 individuals (comprising of QASO, head teachers, HPE teachers, and pupils) was targeted, out of which a sample of 296 was drawn. Both stratified and simple random sampling techniques were used to ensure fair representation of study units. Data from HPE teachers were gathered using a structured questionnaire, while that from QASO and head teachers were gathered through face to face interviews. Focused group discussions involving groups of 10 pupils each were used to collect data from the pupils. Document Analysis was used to verify teachers’ preparation and use of professional documents. Data collection instruments were validated though a pilot study conducted in five primary schools in the neighbouring Uasin Gishu County. Thematic analysis was used to extract recurring themes from QASO and head teachers’ interview responses as well as from focused group discussions. Multiple regression analysis was conducted to identify determinants of implementation of HPE curriculum. Results of the multiple regression analysis revealed that professional documents (B = 0.482, p<0.05); teaching methods (B=0.332, p<0.05); teacher attitude (B=0.204, p<0.05); and teaching equipment and resources (B=0.822, p<0.05) were positive and significant determinants of HPE curriculum implementation, and explains upto 61.3% of the variance in implementation of the curriculum. Thematic analysis results indicated that implementation of HPE curriculum in public primary schools in Nandi County was being hampered by inadequate use of professional documents; lack of variety in teaching methods; negative attitude among teachers; inadequate facilities; and inadequate monitoring and evaluation of HPE instruction. The study recommended need for adherence to professional records, use of diverse teaching methods, positive attitude, adequate resources and improvement in monitoring and evaluation of HPE instruction.
Cholinergic innervation of pyramidal cells and parvalbumin‐immunoreactive interneurons in the rat basolateral amygdala

The basolateral nucleus of the amygdala receives an extremely dense cholinergic innervation from the basal forebrain that is critical for memory consolidation. Although previous electron microscopic studies determined some of the postsynaptic targets of cholinergic afferents, the majority of postsynaptic structures were dendritic shafts whose neurons of origin were not identified. To make this determination, the present study analyzed the cholinergic innervation of the anterior subdivision of the basolateral amygdalar nucleus (BLa) of the rat using electron microscopic dual‐labeling immunocytochemistry. The vesicular acetylcholine transporter (VAChT) was used as a marker for cholinergic terminals; calcium/calmodulin‐dependent protein kinase II (CaMK) was used as a marker for pyramidal cells, the principal neurons of the BLa; and parvalbumin (PV) was used as a marker for the predominant interneuronal subpopulation in this nucleus. VAChT+ terminals were visualized by using diaminobenzidine as a chromogen, whereas CAMK+ or PV+ neurons were visualized with Vector very intense purple (VIP) as a chromogen. Quantitative analyses revealed that the great majority of dendritic shafts receiving cholinergic inputs were CAMK+, indicating that they were of pyramidal cell origin. In fact, 89% of the postsynaptic targets of cholinergic terminals in the BLa were pyramidal cells, including perikarya (3%), dendritic shafts (47%), and dendritic spines (39%). PV+ structures, including perikarya and dendrites, constituted 7% of the postsynaptic targets of cholinergic axon terminals. The cholinergic innervation of both pyramidal cells and PV+ interneurons may constitute an anatomical substrate for the generation of oscillatory activity involved in memory consolidation by the BLa. J. Comp. Neurol. 519:790–805, 2011. © 2010 Wiley‐Liss, Inc.
Mixed mating system in the fern Asplenium scolopendrium: implications for colonization potential.

BACKGROUND AND AIMS Human-mediated environmental change is increasing selection pressure for the capacity in plants to colonize new areas. Habitat fragmentation combined with climate change, in general, forces species to colonize areas over longer distances. Mating systems and genetic load are important determinants of the establishment and long-term survival of new populations. Here, the mating system of Asplenium scolopendrium, a diploid homosporous fern species, is examined in relation to colonization processes. METHODS A common environment experiment was conducted with 13 pairs of sporophytes, each from a different site. Together they constitute at least nine distinct genotypes, representing an estimated approx. 95 % of the non-private intraspecific genetic variation in Europe. Sporophyte production was recorded for gametophytes derived from each parent sporophyte. Gametophytes were grown in vitro in three different ways: (I) in isolation, (II) with a gametophyte from a different sporophyte within the same site or (III) with a partner from a different site. KEY RESULTS Sporophyte production was highest in among-site crosses (III), intermediate in within-site crosses (II) and was lowest in isolated gametophytes (I), strongly indicating inbreeding depression. However, intragametophytic selfing was observed in most of the genotypes tested (eight out of nine). CONCLUSIONS The results imply a mixed mating system in A. scolopendrium, with outcrossing when possible and occasional selfing when needed. Occasional intragametophytic selfing facilitates the successful colonization of new sites from a single spore. The resulting sporophyte, which will be completely homozygous, will shed large amounts of spores over time. Each year this creates a bed of gametophytes in the vicinity of the parent. Any unrelated spore which arrives is then selectively favoured to reproduce and contribute its genes to the new population. Thus, while selfing facilitates initial colonization success, inbreeding depression promotes genetically diverse populations through outcrossing. The results provide further evidence against the overly simple dichotomous distinction of fern species as either selfing or outcrossing.
Safety of laryngeal mask airway and short‐stay practice in office‐based adenotonsillectomy

Background: It is still disputed whether laryngeal mask airway (LMA) is safe and convenient for adenotonsillectomy, and whether these procedures can be safely undertaken in an office‐based short‐stay ambulatory setting. We report the result of this practice in 1126 consecutive children <16 years of age.
Consumption Volatility Risk and the Inversion of the Yield Curve

We propose a consumption-based model that allows for an inverted term structure of real and nominal risk-free rates. In our framework the agent is subject to time-varying macroeconomic risk and interest rates at all maturities depend on her risk perception which shape saving propensities over time. In bad times, when risk is perceived to be higher in the short- than the long-term, the agent would prefer to hedge against low realizations of consumption in the near future by investing in long-term securities. This determines, in equilibrium, the inversion of the yield curve. Pricing time-varying consumption volatility risk is essential for obtaining the inversion of the real curve and allows to price the average level and slope of the nominal one. JEL Classification: G12
Linking customer satisfaction with financial performance: an empirical study of Scandinavian banks

It is generally assumed that increased satisfaction levels lead to improved financial performance. However, this assumed relationship is, by and large, still to be proven in a more general setting, especially with respect to European sectors and industries. This research aims to identify empirically relationships between customer loyalty and satisfaction and profitability measured as ROA, ROE, profit margin and operating income, as well as market indicators (market capitalisation and Tobin’s q). The research sample is made up of nine Scandinavian banks observed on an annual basis between 2004 and 2014. We can confirm that customer satisfaction and loyalty have a significant positive influence on banks’ profitability and can be considered as a predictor for future profitability as the satisfaction index of the preceding year influences the next year’s financial performance. We are also able to confirm that there is a positive link between the customer satisfaction of the preceding year and market indicators of the current year. These results are important for both decision makers in banks and investors. They mean that decision makers and investors can take the bank’s level and trend in customer satisfaction to make assumptions on its future profitability and market performance.
Relationship between motor proficiency, attention, impulse, and activity in children with ADHD

The aim of this study was to investigate the relationship between motor performance, attention deficit, impulsiveness, and hyperactivity in children with attention‐deficit–hyperactivity disorder (ADHD). Participants were 42 school‐aged children with ADHD (36 males, 6 females; mean age 8 years 2 months, SD1 year 2 months; range 6 years to 11 years), and 42 age‐ and sex‐matched children without ADHD (mean age 8 years 3 months, SD 1 year 1 month; range 6 years to 11 years). Motor abilities were assessed with the Bruininks‐Oseretsky Test of Motor Proficiency. Attention and impulse control were measured with the Gordon Diagnostic System, and assessment of activity level was based on two Activity Level Rating Scales that were completed by parents and teachers. Analysis by t‐test revealed a significant difference between children with and without ADHD in fine and gross motor skills, impulse control, and attention. Stepwise regression indicated that attention, impulse control, and parent ratings of activity level were the three best predictors of gross motor skills for children with ADHD, accounting for 55.9% of the variance. Attention and impulse control were the two best predictors of fine motor skills, accounting for 45.7% of the variance. Attention and impulse control were consistently found to be important predictors of both fine and gross motor skills in children with ADHD. However, the fact that activity level was a predictor for gross motor proficiency but not for fine motor tasks suggests that different behavioral processes are involved in fine and gross motor performance to different extents.
Clinical review: Intravenous glucocorticoids for Graves' orbitopathy: efficacy and morbidity.

CONTEXT The administration of iv glucocorticoid pulses has been advocated as a treatment approach for patients with inflammatory and moderate to severe Graves' orbitopathy (GO). This review offers an update on this controversial regimen. EVIDENCE ACQUISITION PubMed and the MeSH-Database were searched (with no temporal limit) for the following topics: management of active and severe GO; glucocorticoid therapy of GO; iv glucocorticoid administration; mechanism and pharmacokinetics of iv glucocorticoids; and adverse events, morbidity, and mortality of iv glucocorticoids. The articles were evaluated according to their setting and study design. EVIDENCE SYNTHESIS All randomized and uncontrolled trials, consensus statement, systematic reviews, and meta-analyses dealing with the efficacy and morbidity of iv glucocorticoids in GO were identified. CONCLUSIONS The current first-line treatment for active, moderate-to-severe GO is a 12-wk course of high-dose iv glucocorticoid pulses. The response rate of this regimen is approximately 80%. Intravenous glucocorticoids have a statistically significant advantage over oral treatment and cause significantly fewer adverse events. However, major side effects related to preexisting diseases, administered dose, and treatment schedule have been reported. The morbidity and mortality of iv glucocorticoid therapy are 6.5 and 0.6%, respectively. Thus, careful patient selection is warranted. Before iv glucocorticoid administration, patients should be screened for recent hepatitis, liver dysfunction, cardiovascular morbidity, severe hypertension, inadequately managed diabetes, and glaucoma. The cumulative dose should not exceed 8 g, and with the exception of sight-threatening GO the single doses preferably should not be administered on consecutive days. Monthly monitoring during subsequent treatment is warranted.
Age, CAG repeat length, and clinical progression in Huntington's disease

The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow‐up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini‐Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%. Graphical models further supported the idea that individuals with smaller triplet expansions experience a more gradual decline. CAG repeat length becomes an important determinant of clinical prognosis when accounting for age of onset. This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment. © 2011 Movement Disorder Society
Interobserver agreement on visual field progression in glaucoma: a comparison of methods

Aim: To examine the level of agreement between clinicians in assessing progressive deterioration in visual field series using two different methods of analysis. Methods: Each visual field series satisfied the following criteria: more than 19 reliable fields, patient age over 40 years, macular threshold at least 30 dB. The first three fields in each series were excluded to minimise learning effects: the following 16 were studied. Five expert clinicians assessed the progression status of each series using both standard Humphrey printouts and pointwise linear regression (progressor). The level of agreement between the clinicians was evaluated using a weighted kappa statistic. Results: A total of 432 tests comprising 27 visual field series of 16 tests each were assessed by the clinicians. The level of agreement on progression status between the clinicians was always higher when they used progressor (median kappa = 0.59) than when they used Humphrey printouts (median kappa = 0.32). This was statistically significant (p = 0.006, Wilcoxon matched pairs signed rank sum test). Conclusions: Agreement between expert clinicians about visual field progression status is poor when standard Humphrey printouts are used, even when the field series studied are long and consist solely of reliable fields. Under these ideal conditions, clinicians agree more closely about patients’ visual field progression status when using progressor than when inspecting series of Humphrey printouts.
The safety and effectiveness of robot-assisted versus laparoscopic TME in patients with rectal cancer

Background: The aim of this study was to assess the safety and effectiveness of robotic-assisted versus laparoscopic total mesorectal excision (TME) in patients with rectal cancer. Methods: We systematically searched PubMed, EMBASE, Cochrane library, Web of science, and Chinese Biomedical Literature Database up to July 2016 to identify case-controlled studies that compared robotic TME (RTME) with laparoscopic TME (LTME) for rectal cancer. GRADE was used to interpret the primary outcomes of this meta-analysis. Results: We included 17 case–control studies (3601 participants: 1726 underwent RTME and 1875 LTME for rectal cancer) that compared RTME with LTME for rectal cancer. We found no statistically significant differences between techniques for local recurrence [odds ratio (OR) = 0.68, P = . 216] and overall survival at 3 years (OR = 0.71, P = 1.140), complications (OR = 1.02, P = .883), positive circumferential resection margin (PCRM) (OR = 0.80, P = .256), the first passing flatus [weighted mean difference (WMD) = −0.11, P = . 130], reoperation (OR = 0.66, P = .080), estimated blood loss (EBL) (WMD = −12.45, P = .500), and length of stay in hospital (LOS) (WMD = −0.69, P = .089). Compared with LTME, RTME was associated with lower rate of conversion (OR = 0.35, P < .001), urinary retention (OR = 0.41, P = .025), and longer operative time (WMD = 57.43, P < .001). The overall quality of evidence was poor in all outcomes. Conclusion: RTME in patients with rectal cancer was associated with a lower rate of conversion and less incidence of urinary retention. Generally, operative time in RTME was significantly longer than in LTME. The long-term oncological and function outcomes of RTME seem to be equivalent with LTME. Therefore, analysis of current studies to date did not indicate a major benefit of RTME over LTME.
Safety of inadvertent administration of overdose of intrathecal Cytarabine in a pediatric patient

Purpose To describe a medication error of intrathecal Cytarabine overdose that was managed conservatively with no apparent toxicities. Summary An 11-year-old girl was diagnosed with bone marrow relapsed precursor B-cell acute lymphoblastic leukemia. According to her chemotherapy protocol, she was started on triple intrathecal chemotherapy consisting of Methotrexate, Cytarabine and Hydrocortisone on day 1 of the protocol. After the intrathecal therapy being administered to the patient, the pharmacist who checked the medication realized that the wrong formulation of Cytarabine was used to prepare the intrathecal therapy; this error resulted in five times overdose of Cytarabine. The patient was then managed conservatively without cerebrospinal fluid exchange. Our patient remained clinically and neurologically stable without apparent toxicities and was discharged safely from hospital. Conclusion Supportive care without the need for invasive procedures such as cerebrospinal fluid exchange may be adequate for managing intrathecal Cytarabine overdose.
The use of amino acids to enhance the aerosolisation of spray‐dried powders for pulmonary gene therapy

Pulmonary delivery of gene therapy offers the potential for the treatment of a range of lung conditions, including cystic fibrosis, asthma and lung cancer. Spray‐drying may be used to prepare dry powders for inhalation; however, aerosolisation of such powders is limited, resulting in poor lung deposition and biological functionality. In this study, we examine the use of amino acids (arginine, aspartic acid, threonine, phenylalanine) to enhance the aerosolisation of spray‐dried powders containing model non‐viral gene vectors.
Cerebral Blood Flow, Blood Volume, and Mean Transit Time Responses to Propofol and Indomethacin in Peritumor and Contralateral Brain Regions: Perioperative Perfusion-weighted Magnetic Resonance Imaging in Patients with Brain Tumors

Background:The regional cerebral blood flow (CBF) response to propofol and indomethacin may be abnormal in patients with brain tumors. First, the authors tested the hypothesis that during propofol anesthesia alone and combined with indomethacin, changes in CBF, cerebral blood volume (CBV), and plasma mean transit time (MTT) differ in the peritumoral tissue compared with the contralateral normal brain region. Second, the authors tested the hypothesis that CBF and CBV are reduced and MTT is prolonged, in both regions during propofol anesthesia and indomethacin administration compared with propofol alone. Methods:The authors studied eight patients subjected to craniotomy under propofol–fentanyl anesthesia for supratentorial brain tumors. Magnetic resonance imaging, including perfusion- and diffusion-weighted and structural sequences, was performed (1) on the day before surgery, (2) before and (3) after administration of indomethacin in the propofol–fentanyl anesthetized patient, and (4) 2 days after surgery. Maps of CBF, CBV, and MTT were calculated. The regions of interest were peritumoral gray matter and opposite contralateral gray matter. Analysis of variance was used to analyze flow data. Results:Propofol anesthesia was associated with a median 32% (range, 3–61%) and 47% (range, 17–67%) reduction in CBF in the peritumoral and contralateral regions, respectively.The interaction between intervention with propofol and indomethacin and region of interest was not significant for any flow modalities. Neither intervention nor region was significant for MTT, CBF, and CBV (P > 0.05). Conclusion:The CBF, CBV, and MTT responses to propofol and indomethacin are not different in the peritumoral region compared with contralateral brain tissue. Indomethacin did not further influence regional CBF, CBV, and MTT during propofol anesthesia.