Miracle-dz/UniFAR-FTUs huggingface dataset:
Linking nuclear mRNP assembly and cytoplasmic destiny

From the very beginning, mRNAs have a complex existence. They are transcribed, capped, spliced, modified at the 3′end, exported from the nucleus, translated, and eventually degraded. These many events not only affect the overall survival and properties of an mRNA, but are also carefully co‐ordinated and integrated with quality control mechanisms that function to ensure that only ‘proper’ mRNAs are translated at the correct developmental time and place. This does not mean that all mRNAs follow a single or uniform path from synthesis to death. Instead, there are diverse means by which the activities of specific mRNAs are regulated, and these controls often depend upon multiple events in the mRNA's life. mRNAs are not found naked in the cell, instead they are part of complex RNPs (ribonucleoproteins) that consist of many factors. These RNPs are highly dynamic structures that change during the lifetime of a given RNA; linking events such as synthesis and processing to the final fate of the mRNA. Here, we will discuss what is known of the assembly of RNPs in general, with specific reference to the myriad of connections between different nuclear events and the cytoplasmic activity of an mRNA. Due to space limitations this review is not comprehensive, instead we focus on specific examples to illustrate these emerging themes in gene expression.
Target tracking through a coordinated turn

Allowing for perturbations in speed and turn rate, the state of a target moving in a coordinated turn obeys a nonlinear stochastic differential equation which cannot be discretised exactly. Existing algorithms for coordinated turn tracking avoid this problem by ignoring perturbations in the continuous-time model and adding process noise only after discretisation. We retain this modelling by discretising using first and second order Taylor approximations to the continuous-time coordinated turn dynamic model. The discrete-time models are used as the basis for a particle filter for tracking a target moving in a coordinated turn. The performances of the discretisation techniques and the effect of different coordinate systems on tracking performance are examined.
A complexity measure for selective matching of signals by the brain.

We have previously derived a theoretical measure of neural complexity (CN) in an attempt to characterize functional connectivity in the brain. CN measures the amount and heterogeneity of statistical correlations within a neural system in terms of the mutual information between subsets of its units. CN was initially used to characterize the functional connectivity of a neural system isolated from the environment. In the present paper, we introduce a related statistical measure, matching complexity (CM), which reflects the change in CN that occurs after a neural system receives signals from the environment. CM measures how well the ensemble of intrinsic correlations within a neural system fits the statistical structure of the sensory input. We show that CM is low when the intrinsic connectivity of a simulated cortical area is randomly organized. Conversely, CM is high when the intrinsic connectivity is modified so as to differentially amplify those intrinsic correlations that happen to be enhanced by sensory input. When the input is represented by an individual stimulus, a positive value of CM indicates that the limited mutual information between sensory sheets sampling the stimulus and the rest of the brain triggers a large increase in the mutual information between many functionally specialized subsets within the brain. In this way, a complex brain can deal with context and go "beyond the information given. "
Inhibition by fatty acids of cyclic AMP‐dependent protein kinase activity in brush border membranes isolated from human placental vesicles

1 The inhibitory effects of arachidonic acid (AA) and a number of structurally related fatty acids on cyclic AMP‐dependent protein kinase activity have been investigated in brush border membranes (BBM) prepared from human placental vesicles. 2 BBM vesicles were characterized by electron microscopy and displayed enrichment of the appropriate marker enzymes, alkaline phosphatase and γ‐glutamyltranspeptidase; BBM were prepared by vesicle lysis in hypotonic medium. 3 Cyclic AMP‐dependent protein kinase (PKA) activity was measured in BBM. At 1 μm, cyclic AMP stimulated a 4.2 ± 0.06 fold increase over basal levels of [32P]‐phosphate incorporation into the synthetic substrate kemptide and this effect was abolished by a selective PKA inhibitor. By use of synergistic pairs of site‐selective cyclic AMP analogues, the kinase was identified as the type II enzyme. 4 Cyclic AMP‐stimulated PKA activity was inhibited by 10 μm AA and this effect was significantly enhanced by nordihydroguaiaretic acid (NDGA) + indomethacin (Indo), inhibitors of the lipoxygenase and cyclo‐oxygenase pathways of AA metabolism respectively. 5 Oleic acid, elaidic acid, but not caprylic or palmitic acids, also significantly inhibited PKA activity and this effect was again enhanced by NDGA + Indo. While arachidonyl alcohol alone was not inhibitory, in the presence of the metabolic inhibitors a significant reduction in stimulated activity was observed. 6 The commercially available PKA type II holoenzyme (activated by cyclic AMP), but not the free catalytic subunit, was inhibitable by AA, oleic or elaidic acids. 7 These results suggest that PKA localized to the brush border membrane of human placental vesicles is inhibited by fatty acids which may compete with cyclic AMP for binding to the kinase regulatory subunit. The reported inhibition by fatty acids of cyclic AMP‐dependent Cl− secretion in epithelial cells may therefore be due in part to negative regulation of a Cl− channel‐associated PKA.
On exosome functional role in cancer: miR-494 complex regulation in melanoma cells and corresponding exosomes

Cutaneous melanoma represents a major worldwide health issue, nearly accounting for 75% of skin cancer deaths (1). Although in the last decade novel promising therapies have been developed, surgical treatment in melanoma early stages still provides the best opportunity for cure. Indeed, despite important successes obtained with targeted therapy and immune checkpoint inhibitors, most patients undergo resistance and responses are not durable (2). In addition, a number of meta-analyses reported significant gender-specific differences in the efficacy of therapeutic approaches, unexpectedly indicating a higher increment of overall survival in men than in women, particularly when treated with immune checkpoint inhibitors (3). Taking in mind all these points, the identification of informative biomarkers, useful either to choose first line therapies, or to predict relapses and clinical outcomes, represent a fundamental point providing a rationale for making the best therapeutic choice for each single patient.
Edge computing in the ePC: a reality check

Mobile Edge Computing (MEC) has received much attention from the research community in recent years. A significant part of the published work has studied the telecom-centric MEC architecture, which assumes that the computing resource is located at the edge of the mobile access network (e.g., the Evolved Packet Core), typically at the first aggregation level. Many authors make a silent assumption in their analyses that the latency at this stage of the network is negligible. In this paper we show not only that this assumption false, but that in some common cases the latency of the first-aggregation stage dominates the end-to-end latency. We challenge the latency argument in the context of present-day access networks and discuss what must be done to pave the way for practical deployments of MEC.
Dronedarone: is it time to turn it down?

Despite the widespread adoption of catheter ablation for the treatment of atrial fibrillation (AF) over the past decade, drug therapy remains a mainstay for the management of this common arrhythmia. Dronedarone is the latest drug to be developed for treating AF and is the first antiarrhythmic agent approved by the U.S. Food and Drug Administration (FDA) since 1999. Produced by the same manufacturer as Amiodarone, Dronedarone was designed to resemble Amiodarone, except the iodine moieties of Amiodarone were replaced by a hydrophilic methanesulfonamyl group. The pharmaceutical company has had imagined their ‘holy grail’: Dronedarone would be as effective as Amiodarone but with fewer side effects. Early clinical trials with Dronedarone showed that it was moderately effective in maintaining sinus rhythm in patients with paroxysmal or persistent AF. Additionally, the Prevention of Cardiovascular Hospitalization or Death from any Cause in Patients with Atrial Fibrillation/Atrial Flutter (ATHENA) study demonstrated a reduction in the risk of all-causemortality or cardiovascular hospitalization and a reduction in stroke associated with Dronedarone use. Dronedarone is currently the only antiarrhythmic drug (AAD) that has been associated with a reduction in stroke risk in AF patients [1]. Based on these facts, the FDA approved Dronedarone in 2009 to reduce the risk of cardiovascular hospitalization in the treatment of AF and atrial flutter. This medication was then recommended by the Guideline [2] as the first-line therapy to maintain sinus rhythm in paroxysmal or persistent AF patients, except for those with NYHA Class III -IV heart failure. However, the post-market safety data raised multiple concerns about Dronedarone. Adverse events including renal failure, severe liver injury, worsened heart failure and drug-interaction with Warfarin and Digoxin have been reported with Dronedarone use. These adverse events ultimately led to a FDA Safety Communication [3] and a modification of the drug label [4]. Last year, the Permanent Atrial fibriLLAtion Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS) study was prematurely halted after the data monitoring committee found a twofold increase in death, as well as twofold increase in stroke and hospitalization for heart failure in permanent AF patients receiving Dronedarone, compared to patients taking a placebo [5]. Influenced by the disappointing results of the PALLAS study, the EuropeanMedicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended restricting the use of Dronedarone [6]. The hope that Dronedarone could be an effective, safe, and ease-of-use drug in daily clinical practice for the management of AF has evaporated. It seems that many clinicians believe Dronedarone has become ‘tasteless but wasteful to discard’. What in the world has happened to Dronedarone after only 3 years since its approval?
Direct current stimulation of prefrontal cortex modulates error‐induced behavioral adjustments

Commission of errors and conflict between choices might induce behavioral modulations through adjustments in the executive control of behavior and altered patterns of these modulations are detected in neuropsychiatric disorders. We examined the effects of transcranial Direct Current Stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) on error‐ and conflict‐induced behavioral modulations. Two separate cohorts of participants performed two clinically relevant tests of executive control, respectively. In the Wisconsin Card Sorting Test (WCST), the relevant rule for matching items frequently changed and therefore participants had to detect these unannounced changes by trial and error and alter their rule‐based behavior. In the Stop task, participants had to rapidly respond to a directional go‐signal but inhibit their responses when a stop signal appeared after the go‐signal. Each participant received tDCS (sham, cathodal or anodal) in three separate sessions. Errors led to a slower response in the next trial (post‐error slowing) in both tasks. The tDCS significantly modulated the post‐error slowing in both tasks but did not affect the behavioral adjustments induced by the conflict. The modulation of post‐error slowing by tDCS were polarity‐dependent and also trial specific appearing immediately after errors. In the WCST and Stop task, the post‐error slowing may reflect different processes involved in shifting the behavior‐guiding rule and adjustments in inhibitory control of responses, respectively, and we found that the effective tDCS polarity differed between the two tasks. Here, we show that in two separate cognitive tasks direct current stimulation of DLPFC significantly modulated error‐induced behavioral modulations.
Improved Nutrition Knowledge and Practice through Intensive Nutrition Education: A Study among Caregivers of Mildly Wasted Children on Nias Island, Indonesia

Background Inappropriate nutrition knowledge and feeding practices of caregivers are among several important causes of persistent malnutrition problems in young children. Thus, it is essential to provide caregivers with the necessary knowledge to help them modify their feeding practices. Objective To examine the effectiveness of two different nutrition education methods, weekly intensive nutrition education (INE) and monthly nonintensive nutrition education (NNE), designed for caregivers of mildly wasted children (weight-for-height z-score ≥ −1.5 to < −1) aged ≥ 6 to < 60 months on Nias Island, Indonesia. Methods To assess the impact of the two different nutrition education approaches on nutrition knowledge and practice of caregivers with their children, respondents were assigned to receive either weekly INE (n = 114) or monthly NNE (n = 96). The knowledge and practice levels of the mothers in each group were assessed and compared using a pretested validated questionnaire at admission and after the intervention period. Results At admission, the knowledge and practice levels of caregivers in both groups were not statistically significantly different. After participating in the nutrition education program, the percentage of correct answers on nutrition knowledge and practice in the INE group was significantly higher than that in the NNE group. Significant improvement in knowledge and practice scores was observed in the INE group after the intervention (p < 0.001), whereas only a significant improvement in knowledge was found in the NNE group (p < .05). Conclusions In comparison with NNE, the INE approach was significantly better in bringing about a positive change in knowledge and practice of caregivers of mildly wasted children in the study area.
Dormance vybraných odrůd sladovnického ječmene v letech 2001 až 2003.

Dormance již dnes patři k parametrům hodnoceni jakosti sladovnickeho jecmene. Intenzita dormance jecmene byla ověřena pomoci stanoveni klicive energie na Petriho miskach se 4 ml vody za 72 h v termostatu při 20 °C. Urceni rychlosti kliceni bylo provedeno výpoctem z udajů klicive energie podle dřive publikovaneho vzorce. Stanoveni klicive energie sladovnickeho jecmene proběhlo v letech 2001 až 2003 vždy 6 týdnů po sklizni. Byly hodnoceny odrůdy sladovnickeho jecmene Jersey, Kompakt, Prestige, Scarlett a Tolar, ktere jsou nosnými sladařskými odrůdami. Vzorky byly vybrany na zakladě nasledujicich parametrů jakosti: obsah bilkovin v jecmeni v rozmezi 10-12 % v susině a klicivost jecmene vyssi než 96 %. Ukazalo se, že se výrazně zvýsil pocet předplodin, po kterých je jecmen pěstovan. Potvrdilo se, že dormanci jecmene nejvice ovlivňuje rocnik, rozdily mezi odrůdami jsou male. Nejlepsi předplodinou (vliv na klicivou energii) byla okopanina, mezi obilninou a olejninou neni statisticky významný rozdil. Prokazalo se, že použiti výpoctu rychlosti kliceni z udajů klicive energie umožni zřetelnějsi rozliseni vlivu jednotlivých faktorů. Předložene výsledky byly ziskany v ramci řeseni výzkumneho projektu NAZV, ev. c. QC 1096 "Výzkum faktorů optimalizace kvality produkce obilovin v CR", který je řesen v letech 2001-2004.
Predictive Validity of the Strain Index in Turkey Processing

The Strain Index is a job analysis method for determining if workers are exposed to increased risk of developing distal upper extremity disorders. Its predictive and external validity was initially demonstrated in a pork processing plant. The purpose of this study was to evaluate the predictive validity of the Strain Index in one turkey processing plant. While blinded to health outcomes, investigators analyzed the right and left sides of workers in 28 jobs using the Strain Index and classified them as “hazardous” or “safe” based on the Strain Index score. Subsequently, OSHA 200 logs were used to ascertain the occurrence of distal upper extremity disorders retrospectively. If at least one such disorder had occurred on the right or left side during the previous 3 years, that side was classified as “positive. ” If no such disorder was reported during the previous 3 years, that side was classified as “negative. ” When comparing sides, symmetry between morbidity and hazard classification was required. When comparing jobs, such symmetry was not required. Evidence of association between the hazard classifications and the morbidity classifications for the 56 sides and the 28 jobs was evaluated using 2 × 2 contingency tables. For the sides, the association between hazard classification and morbidity classification was statistically significant, with an odds ratio of 22.0. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.86, 0.79, 0.92, and 0.65, respectively. Similar results were noted for the jobs—the odds ratio was 50.0, and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.91, 0.83, 0.95, and 0.71. These results provide additional evidence of the external validity and predictive validity of the Strain Index.
A Secreted Serine-Threonine Kinase Determines Virulence in the Eukaryotic Pathogen Toxoplasma gondii

Toxoplasma gondii strains differ dramatically in virulence despite being genetically very similar. Genetic mapping revealed two closely adjacent quantitative trait loci on parasite chromosome VIIa that control the extreme virulence of the type I lineage. Positional cloning identified the candidate virulence gene ROP18, a highly polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion. Transfection of the virulent ROP18 allele into a nonpathogenic type III strain increased growth and enhanced mortality by 4 to 5 logs. These attributes of ROP18 required kinase activity, which revealed that secretion of effectors is a major component of parasite virulence.
Cognitive impairment and mental disorders in HIV-infected patients with early stages of syphilis

The objective of the study was to determine the correlations between cognitive impairment in HIVinfected patients with early syphilis and mental disorders. 65 HIV-infected patients with early syphilis were examined by a clinical method and BNCE test. We revealed a high incidence of addictions (46.2 %). Cognitive impairment was found in 43.1 % of patients and was characterized by mild cognitive disorders. The severity of cognitive impairment was linked to hepatitis C co-infection (R = –0.38, p = 0.003), substance abuse (R = –0.39, p = 0.002) and intravenous drug use (R = –0.51, p < 0.0001). Cognitive impairment was associated with mental disorders due to brain damage (R = –0.93; p < 0.0001), dependence on stimulants (R = –0.69; p = 0.014), opiate dependence (R = –0.48; p < 0.001), and dependence on alcohol (R = –0.28; p = 0.037). Refs 15. Tables 2.
Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites

Proton pump inhibitors (PPIs) may be a risk factor for hepatic encephalopathy (HE) in patients with cirrhosis, possibly through translocation of gut bacteria, which can also lead to spontaneous bacterial peritonitis (SBP). We examined the associations between PPIs and development of HE or SBP in patients with cirrhosis with ascites. We used data from three 1‐year trials of satavaptan for ascites control. We used Cox regression to compare HE and SBP rates between users and nonusers of PPIs. At inclusion, 39% of the 865 patients with cirrhosis with ascites used PPIs, 52% used them at some point during the follow‐up, and the proportion of current users was always in the 30%‐39% range. There were 189 first‐time HE episodes during the follow‐up, and the cumulative 1‐year risk was 31% for those who used PPIs at baseline versus 25% for those who did not. The confounder‐adjusted hazard ratio (HR) of HE for current PPI use versus current nonuse was 1.36 (95% confidence interval [CI], 1.01‐1.84). The HR for overt HE was higher (adjusted HR = 1.88; 95% CI, 1.21‐1.91). During the follow‐up, 86 patients developed SBP. The adjusted HR of SBP for current PPI users versus nonusers was 1.72 (95% CI, 1.10‐2.69). Conclusion: PPIs were used by 52% of this international cirrhosis cohort during a 1‐year period and was a risk factor for developing HE and SBP. These findings are consistent with the hypothesis that PPIs may increase translocation of gut bacteria. (Hepatology 2016;64:1265‐1272)
Topical Corticosteroid Abuse in Dermatology

Topical corticosteroids are the most widely used therapeutic agents in modern dermatologic therapy. The increasing frequency of use of topical steroids has led to the detection of a number of adverse effects and is dependent upon chemical nature of the drug, the vehicle, and the location of its application. The common adverse effects on face are erythema, telangiectasia, xerosis, photosensitivity and rebound phenomenon. The improper advertisement by manufacturers, availability of steroids without prescription, improper prescribing by doctors, has resulted in the rapid emergence of topical steroid abuse. Aims and Objectives: To analyse the magnitude and adverse effects of topical steroids abuse in dermatology. Materials & Methods: This is a prospective questionnaire type study conducted in outpatient clinic of the Department of Dermatology in a tertiary hospital. A total of 200 patients of any age and of both sexes are recruited consecutively. A questionnaire eliciting demographic variables, characteristics of topical steroid use, prescription source, duration of application and adverse effects is administered to all eligible patient. Patients not consenting to answer the questionnaire or patients with co-morbidities that could cause similar changes to topical steroid side effects like Cushing‘s syndrome, thyroid disorders, polycystic ovaries were excluded. Statistical analysis was done using SPSS ver. 21. Results: The most common age group in which these side effects were observed is 21-30 years. Clobetasol propionate, betamethasone valerate and mometasonefuroate were the commonly used steroid by patients. It was found that 29% of patients using topical steroid were recommended by friend or pharmacist and 71% by a medical practitioner. Topical steroid abuse was seen in all 58 patients (100%) prescribed by friend or pharmacist and 58 out of 142 patients (40.84%) prescribed by medical practitioner. Tinea incognito and striae were the common side effects and were seen more commonly in non-dermatologists group. Conclusion: This study reveals that problem of topical steroid misuse is common in our country. The prevalence of side effects is significantly higher among the potent steroid users. The prevalence of side effects is significantly higher among patients of non-dermatologists (p<.05) indicating that the schedule and explanation of guidelines for correct application of steroids is a drawback among non-dermatologists. Recommendation: Education of the general public through special media programmes and the continuing medical education programme for medical and paramedical personnel are probably the most important steps that could be undertaken to reduce this problem.