Miracle-dz/UniFAR-FTUs huggingface dataset:
Translational Repression and eIF4A2 Activity Are Critical for MicroRNA-Mediated Gene Regulation

MicroRNA Mechanism MicroRNAs are small noncoding RNAs that regulate gene expression by binding complementary target messenger RNAs (mRNAs) and repressing their expression through repression of protein translation and mRNA degradation. Meijer et al. (p. 82) show that in a HeLa cell system mRNA degradation is a consequence of translational inhibition via the initiation factor eIF4A2. MicroRNAs repress target messenger RNAs with structured 5′ ends through a protein translation initiation factor. MicroRNAs (miRNAs) control gene expression through both translational repression and degradation of target messenger RNAs (mRNAs). However, the interplay between these processes and the precise molecular mechanisms involved remain unclear. Here, we show that translational inhibition is the primary event required for mRNA degradation. Translational inhibition depends on miRNAs impairing the function of the eIF4F initiation complex. We define the RNA helicase eIF4A2 as the key factor of eIF4F through which miRNAs function. We uncover a correlation between the presence of miRNA target sites in the 3′ untranslated region (3′UTR) of mRNAs and secondary structure in the 5′UTR and show that mRNAs with unstructured 5′UTRs are refractory to miRNA repression. These data support a linear model for miRNA-mediated gene regulation in which translational repression via eIF4A2 is required first, followed by mRNA destabilization.
Melanoma Cells Break Down LPA to Establish Local Gradients That Drive Chemotactic Dispersal

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient.
Chitosan–gum arabic polyelectrolyte complex films: physicochemical, mechanical and mucoadhesive properties

Abstract By blending chitosan (CS) and gum arabic (GA), a powerful biomaterial complex might be obtained due to the unique properties of CS and the low viscosity and good emulsifying properties of GA. The objectives of this study were to prepare and examine the properties of dispersions and films of CS and GA as a function of the mixing weight ratio, pH value and molecular weight of CS. The dispersions were characterized by turbidity, zeta potential and cytotoxicity and then the dispersions were cast into films. Physicochemical properties of the film were performed. CS–GA dispersions exhibited higher turbidity and a lower zeta potential with an increase in the GA ratio. Continuous films of the CS–GA could be formed at all ratios. CS and GA could molecularly interact via electrostatic forces and intermolecular hydrogen bonding. The CS–GA (1:0.5) films exhibited relatively low water uptake, erosion, water vapor permeability and puncture strength compared to the CS films. Furthermore, the CS–GA films demonstrated good mucoadhesive properties, allowing for adhesion to the mucosal membrane. Based on these results, it could be advantageous to use CS–GA films as film formers for the formulation of coatings and drug delivery systems.
Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance

ABSTRACT Purpose: The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). Materials and methods: Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods. Results: The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R2=0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R2=0.372, P=0.008). BMI-SDS was mildly associated with leptin (R2=0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R2=0.136, P=0.007). Conclusions: Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.
Differentially expressed membrane transporters in rice roots may contribute to cultivar dependent salt tolerance

Salinity tolerance in rice, like in other glycophytes, is a function of cellular ion homeostasis. The large divergence in ion homeostasis between the salt-tolerant FL478 and salt-sensitive IR29 rice varieties can be exploited to understand mechanisms of salinity tolerance. Physiological studies indicate that FL478 shows a lower Na+ influx, a reduced Na+ translocation to the shoot, and maintains a lower Na+:K+ ratio. To understand the basis of these differences, a comparative investigation of transcript regulation in roots of the two cultivars was undertaken. This analysis revealed that genes encoding aquaporins, a silicon transporter, and N transporters are induced in both cultivars. However, transcripts for cation transport proteins including OsCHX11, OsCNGC1, OsCAX, and OsTPC1 showed differential regulation between the cultivars. The encoded proteins are likely to participate in reducing Na+ influx, lowering the tissue Na+:K+ ratio and limiting the apoplastic bypass flow in roots of FL478 and are therefore important new targets to improve salt tolerance in rice.
WiWho: WiFi-Based Person Identification in Smart Spaces

There has been a growing interest in equipping the objects and environment surrounding the user with sensing capabilities. Smart indoor spaces such as smart homes and offices can implement the sensing and processing functionality, relieving users from the need of wearing or carrying smart devices. Enabling such smart spaces requires device-free effortless sensing of user's identity and activities. Device-free sensing using WiFi has shown great potential in such scenarios, however, fundamental questions such as person identification have remained unsolved. In this paper, we present WiWho, a framework that can identify a person from a small group of people in a device-free manner using WiFi. We show that Channel State Information (CSI) used in recent WiFi can identify a person's steps and walking gait. The walking gait being distinguishing characteristics for different people, WiWho uses CSI-based gait for person identification. We demonstrate how step and walk analysis can be used to identify a person's walking gait from CSI, and how this information can be used to identify a person. WiWho does not require a person to carry any device and is effortless since it only requires the person to walk for a few steps (e.g. entering a home or an office). We evaluate WiWho using experiments at multiple locations with a total of 20 volunteers, and show that it can identify a person with average accuracy of 92% to 80% from a group of 2 to 6 people. We also show that in most cases walking as few as 2-3 meters is sufficient to recognize a person's gait and identify the person. We discuss the potential and challenges of WiFi- based person identification with respect to smart space applications.
Singleton Vaginal Breech Delivery at Term: Still a Safe Option

OBJECTIVE: To examine the obstetric and perinatal outcome of pregnancies with singleton breech presentation at term when selection for vaginal delivery was based on clear prelabor and intrapartum criteria. METHODS: The outcomes of all pregnancies with a breech presentation after 37 weeks of gestation were retrospectively reviewed from January 1997 to June 2000. Criteria for prelabor cesarean or trial of vaginal breech delivery included type of breech, estimated fetal weight (more than 3,800 g), maternal preference, and gestation more than 41 weeks. An intrapartum protocol excluded induction and oxytocin augmentation of labor, combined with a low threshold for cesarean delivery for dystocic labor; an experienced obstetrician was in attendance during labor and delivery. RESULTS: Of 641 women, 343 (54%) underwent prelabor cesarean, and 298 (46%) had a trial of vaginal delivery, of whom 146 (49%) delivered vaginally. Significantly fewer nulliparas (58 of 158, 37%) than multiparas (88 of 140, 63%; P < .001) achieved vaginal delivery after trial of labor. Significantly more infants weighing more than 3,800 g were selected for prelabor (87 of 343, 25%) and intrapartum (31 of 152, 20%) cesarean than delivered vaginally (15 of 146, 10%). Two neonates (0.7%) had Apgar scores of less than 7 at 5 minutes; both were neurologically normal at 6 weeks. There were no nonanomalous perinatal deaths and no cases of significant trauma or neurological dysfunction; 3 infants delivered vaginally died due to lethal anomalies. CONCLUSION: Safe vaginal breech delivery at term can be achieved with strict selection criteria, adherence to a careful intrapartum protocol, and with an experienced obstetrician in attendance. Our protocol effectively selects larger infants for cesarean delivery. LEVEL OF EVIDENCE: II-2
Use of complementary therapy by adolescents with asthma.

BACKGROUND About 40% of adult Americans use complementary or alternative medicine (CAM) for health problems. OBJECTIVE To determine the prevalence of reported use of CAM in a population of urban adolescents with asthma. DESIGN/METHODS We used a multistaged, stratified sample approach at an inner-city high school. An asthma screening survey was administered to 3800 registered students, aged 13 to 18 years. We identified a subset of 200 respondents who answered yes to each of the following questions: (1) Does your physician think that you have asthma? (2) Do your parents think that you have asthma? (3) Do you think that you have asthma? A self-completion questionnaire was administered to a sample drawn from this cohort. Differences in proportion were tested by chi( 2) analyses. RESULTS Of the 160 participants, 63% were female, 68% were Hispanic, 26% were African American, 33% had weekly symptoms, and 14% had daily symptoms. Overall, 80% of participants reported using CAM for asthma. The most commonly reported CAM included rubs (74%), herbal teas (39%), prayer (37%), massage (36%), and Jarabe 7 syrup (24%). Subjects with daily or weekly symptoms were more likely to use CAM for each episode of asthma (72% vs 51%; P =.005). The 61% of subjects who had a family member who used CAM were more likely to use CAM again (84% vs 39%; P<.001). Of the respondents, 59% reported that CAM was effective. Subjects who perceived CAM to be effective were more likely to use it again (96% vs 22%; P<.001). CONCLUSIONS Most adolescents with asthma in this study used CAM. The prevalence of CAM use in this study population was twice the national average for adults.
Eliciting Negative Affects Using Film Clips and Real-Life Methods

Although audio-visual stimuli are among the most frequently used methods to elicit emotional reactions in experimental conditions, real-life manipulations have increasingly been used in different countries. However, the applicability of such protocols has not yet been tested in Brazilian Portuguese speakers. Thus, we conducted two experiments to investigate the effectiveness of both methods. In the first experiment, we used film clips to induce negative emotions (i.e., anger, fear, or sadness) or an emotionally neutral condition in 321 undergraduate students. After watching one of the online videos, volunteers completed an emotional assessment. As expected, there were significant differences in all groups. Our results corroborate the relatively discrete patterns in emotion elicitation using films. In the second experiment, anger was elicited in 18 male undergraduates through a hostile social interaction with a confederate and measured by the corrugator muscle activity and cortisol responses. Indeed, there was an increase in corrugator activity in the group exposed to anger induction, even after a few minutes from the end of the experimental manipulation. Implications for experiments on the negative emotions are discussed.
Mapping Traumatic Axonal Injury Using Diffusion Tensor Imaging: Correlations with Functional Outcome

Background Traumatic brain injury is a major cause of morbidity and mortality worldwide. Ameliorating the neurocognitive and physical deficits that accompany traumatic brain injury would be of substantial benefit, but the mechanisms that underlie them are poorly characterized. This study aimed to use diffusion tensor imaging to relate clinical outcome to the burden of white matter injury. Methodology/Principal Findings Sixty-eight patients, categorized by the Glasgow Outcome Score, underwent magnetic resonance imaging at a median of 11.8 months (range 6.6 months to 3.7 years) years post injury. Control data were obtained from 36 age-matched healthy volunteers. Mean fractional anisotropy, apparent diffusion coefficient (ADC), and eigenvalues were obtained for regions of interest commonly affected in traumatic brain injury. In a subset of patients where conventional magnetic resonance imaging was completely normal, diffusion tensor imaging was able to detect clear abnormalities. Significant trends of increasing ADC with worse outcome were noted in all regions of interest. In the white matter regions of interest worse clinical outcome corresponded with significant trends of decreasing fractional anisotropy. Conclusions/Significance This study found that clinical outcome was related to the burden of white matter injury, quantified by diffusivity parameters late after traumatic brain injury. These differences were seen even in patients with the best outcomes and patients in whom conventional magnetic resonance imaging was normal, suggesting that diffusion tensor imaging can detect subtle injury missed by other techniques. An improved in vivo understanding of the pathology of traumatic brain injury, including its distribution and extent, may enhance outcome evaluation and help to provide a mechanistic basis for deficits that remain unexplained by other approaches.
Training End Users: An Exploratory Study

This article presents and empirically evaluates a conceptual model of how training can impact the acceptance of information systems within the organization. Specifically, the training of end users is explored via an extensive field study of 100 middle- and upper-level managers from 20 companies. The results indicate that (1) a positive relationship exists between the computer-related training an individual receives and his/her computer-related ability, and (2) a positive relationship exists between the computer-related ability of an end user and his/her acceptance of information systems products and technologies.
Effects of colocynth alkaloids and glycosides on Wistar rats fed high-fat diet. A biochemical and morphological study.

INTRODUCTION In traditional medicine, Citrullus colocynthis is used to treat diabetes, hyperlipidemia, cardiovascular diseases, inflammation, and oxidative stress, all of which can appear when a diet rich in vegetable fats, such as palm oil, is continuously consumed. Such high-fat diets are chronic stressors of the hypothalamic-pituitary-adrenal axis. The objective of our study was to analyze and evaluate the effects of colocynth total alkaloids and glycosides on metabolic, hormonal, and structural disorders of the adrenal medulla in Wistar rats fed a high-fat diet. MATERIAL AND METHODS Twenty six Wistar rats were distributed as follows: six control animals received a standard laboratory diet; twenty experimental rats received the standard laboratory diet supplemented with palm oil - the high-fat diet (HFD). After seven months of this diet, the HFD group was subdivided into rats treated for the next 2 months with either alkaloid extract (HFD-ALk group) or ethanol extract of glycosides (HFD-GLc) or animals on HFD only. Plasma metabolites and ACTH concentrations were measured by standard methods. Sections of adrenal medulla were stained by Heidenhain-Azan method and Sudan Black. RESULTS The adrenal medulla of the HFD rats showed prominent structural changes, such as hypertrophy of chromaffin and ganglion cells, vacuolation, inflammatory foci, and fibrosis. The biochemical and hormonal parameters were significantly improved in the HFD rats treated with alkaloid and glycoside extracts of Citrullus colocynthis. Moreover, the morphological changes of the adrenal medulla were attenuated in HFD-ALk and HFD-Glc rats. CONCLUSIONS The results of the study indicate that phytotherapy using Citrullus colocynthis alkaloids may correct metabolic and hormonal perturbations as well as adrenal medulla structure of rats maintained on HFD.
Maternal separation in childhood and diurnal cortisol patterns in mid-life: findings from the Whitehall II study

Background Animal studies suggest that maternal separation is associated with alterations in the hypothalamic–pituitary–adrenal (HPA) axis through effects that occur in a critical period following birth. Evidence for an association of the diurnal cortisol rhythm with maternal separation in humans is equivocal. Method We examined whether maternal separation in childhood is associated with diurnal cortisol pattern in 3712 middle-aged men and women. Two aspects of cortisol release were examined: the cortisol awakening response (CAR) and the diurnal slope in cortisol throughout the day. Results Maternal separation in childhood was reported by 12% of participants. Those participants who reported maternal separation had a larger CAR and flatter slopes in cortisol levels compared to those who did not report maternal separation [adjusted mean CAR in those reporting no separation versus separation: 7.1, 95% confidence interval (CI) 6.7–7.5 v. 8.4, 95% CI 7.3–9.5, p = 0.02, corresponding to adjusted mean diurnal slope: −0.129 (95% CI −0.130 to −0.128) v. −0.126 (95% CI −0.128 to −0.124), p = 0.01]. In participants who reported maternal separation, the age of separation was not associated with either cortisol measure (p = 0.11). The association between maternal separation and slope in cortisol secretion was largely explained by smoking behaviour and marital status at the time of sample collection whereas that of the CAR was explained by childhood psychosocial, material factors and adult health behaviours. Conclusions Our findings suggest that maternal separation in childhood is associated with alterations in the diurnal cortisol pattern in middle age. These associations are predominantly accounted for by adult circumstances and behaviours.
Economic Evaluation of a Hospital-Based Palliative Care Program.

PURPOSE Establish costs of an inpatient palliative care unit (PCU) and conduct a threshold analysis to estimate the maximum possible costs for the PCU to be considered cost effective. METHODS We used a hospital perspective to determine costs on the basis of claims from administrative data from Johns Hopkins PCU between March 2013 and March 2014. Using existing literature, we estimated the number of quality-adjusted life years (QALYs) that the PCU could generate. We conducted a threshold analysis to assess the maximum costs for the PCU to be considered cost effective, incorporating willingness to pay ($180,000 per QALY). Three types of costs were considered, which included variable costs alone, contribution margin (ie, revenue minus variable costs), and PCU cost savings compared with usual care (from a separate publication). RESULTS The data showed that there were 153 patient encounters (PEs), variable costs of $1,050,031 ($1,343 per PE per day), a contribution margin of $318,413 ($407 per PE per day), and savings compared with usual care of $353,645 ($452 savings per PE per day). On the basis of the literature, the program could generate 3.11 QALYs from PEs (0.05 QALY) and caregivers (3.06 QALYs). The threshold analysis determined that the maximum variable cost required to be cost effective was $559,800 (an additional $716 per PE per day could be spent). CONCLUSION According to variable costs, the PCU was not cost effective; however, when considering savings of the PCU compared with usual care, the PCU was cost saving. The contribution margin showed that the PCU was cost saving. This study supports efforts to expand PCUs, which enhance care for patients and their caregivers and can generate hospital savings. Future research should prospectively explore the cost utility of PCUs.
[Necrotizing hepatitis after taking herbal remedies].

HISTORY AND CLINICAL FINDINGS Two unrelated women, aged 39 and 42 years, had been admitted (at different times) to hospital because of "recurrence of an aetiologically uncertain acute hepatitis". Both patients had a history of acute hepatitis with GPT concentration of 796 and 755 U/l, respectively. Each of them had experienced recurrences of hepatitis, each of them preceded by taking herbal remedies as alternative medication, containing kava or common (or lesser) celandine, respectively. In each patient physical examination had been unremarkable. INVESTIGATIONS Maximal values of GPT in the two patients were 422 and 350 U/l, respectively. Viral, autoimmune and metabolic causes of the hepatitis were excluded. In each of them liver biopsy revealed the picture of acute necrotizing hepatitis. DIAGNOSIS, TREATMENT AND COURSE As it was suspected that the hepatitis was medication-induced, the intake of the mentioned herbal preparations was stopped. The liver function tests quickly became normal. CONCLUSION In view of the rapid response to their withdrawal, a causal connection between intake of the herbal preparations and the recurrences of acute hepatitis is the most likely explanation in both cases.