Miracle-dz/UniFAR-FTUs huggingface dataset:
THE ULTRAVIOLET RADIATION ENVIRONMENT AROUND M DWARF EXOPLANET HOST STARS

The spectral and temporal behavior of exoplanet host stars is a critical input to models of the chemistry and evolution of planetary atmospheres. Ultraviolet photons influence the atmospheric temperature profiles and production of potential biomarkers on Earth-like planets around these stars. At present, little observational or theoretical basis exists for understanding the ultraviolet spectra of M dwarfs, despite their critical importance to predicting and interpreting the spectra of potentially habitable planets as they are obtained in the coming decades. Using observations from the Hubble Space Telescope, we present a study of the UV radiation fields around nearby M dwarf planet hosts that covers both far-UV (FUV) and near-UV (NUV) wavelengths. The combined FUV+NUV spectra are publicly available in machine-readable format. We find that all six exoplanet host stars in our sample (GJ 581, GJ 876, GJ 436, GJ 832, GJ 667C, and GJ 1214) exhibit some level of chromospheric and transition region UV emission. No “UV-quiet” M dwarfs are observed. The bright stellar Lyα emission lines are reconstructed, and we find that the Lyα line fluxes comprise ∼37%–75% of the total 1150–3100 Å flux from most M dwarfs; ≳103 times the solar value. We develop an empirical scaling relation between Lyα and Mg ii emission, to be used when interstellar H i attenuation precludes the direct observation of Lyα. The intrinsic unreddened flux ratio is F(Lyα)/F(Mg ii) = 10 ± 3. The F(FUV)/F(NUV) flux ratio, a driver for abiotic production of the suggested biomarkers O2 and O3, is shown to be ∼0.5–3 for all M dwarfs in our sample, >103 times the solar ratio. For the four stars with moderate signal-to-noise Cosmic Origins Spectrograph time-resolved spectra, we find UV emission line variability with amplitudes of 50%–500% on 102–103 s timescales. This effect should be taken into account in future UV transiting planet studies, including searches for O3 on Earth-like planets. Finally, we observe relatively bright H2 fluorescent emission from four of the M dwarf exoplanetary systems (GJ 581, GJ 876, GJ 436, and GJ 832). Additional modeling work is needed to differentiate between a stellar photospheric or possible exoplanetary origin for the hot (T(H2) ≈ 2000–4000 K) molecular gas observed in these objects.
COPD GWAS variant at 19q13.2 in relation with DNA methylation and gene expression

Abstract Chronic obstructive pulmonary disease (COPD) is among the major health burdens in adults. While cigarette smoking is the leading risk factor, a growing number of genetic variations have been discovered to influence disease susceptibility. Epigenetic modifications may mediate the response of the genome to smoking and regulate gene expression. Chromosome 19q13.2 region is associated with both smoking and COPD, yet its functional role is unclear. Our study aimed to determine whether rs7937 (RAB4B, EGLN2), a top genetic variant in 19q13.2 region identified in genome-wide association studies of COPD, is associated with differential DNA methylation in blood (N = 1490) and gene expression in blood (N = 721) and lungs (N = 1087). We combined genetic and epigenetic data from the Rotterdam Study (RS) to perform the epigenome-wide association analysis of rs7937. Further, we used genetic and transcriptomic data from blood (RS) and from lung tissue (Lung expression quantitative trait loci mapping study), to perform the transcriptome-wide association study of rs7937. Rs7937 was significantly (FDR < 0.05) and consistently associated with differential DNA methylation in blood at 4 CpG sites in cis, independent of smoking. One methylation site (cg11298343-EGLN2) was also associated with COPD (P = 0.001). Additionally, rs7937 was associated with gene expression levels in blood in cis (EGLN2), 42% mediated through cg11298343, and in lung tissue, in cis and trans (NUMBL, EGLN2, DNMT3A, LOC101929709 and PAK2). Our results suggest that changes of DNA methylation and gene expression may be intermediate steps between genetic variants and COPD, but further causal studies in lung tissue should confirm this hypothesis.
ICT literacy and the second digital divide: Understanding students’ experiences with technology

This work in progress paper reports on a doctoral research study investigating the ICT literacy skills of contemporary learners across primary and high school settings, in order to understand the influence of their economic, social and cultural capital to explain their relationship with and use of ICTs. Data collection will comprise a background questionnaire, an ICT proficiency test followed by semi structured interviews and series of in-class activities that will focus on exploring students’ technology use and background. This paper is structured as follows: firstly a review of the related research is presented to describe the context for the study; the research design for the study is then explained, followed by a brief discussion of the studies significance and expected outcomes.
Mechanism-Based Therapeutics for Autosomal Dominant Polycystic Kidney Disease: Recent Progress and Future Prospects

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, accounting for up to 10% of patients on renal replacement therapy. There are presently no proven treatments for ADPKD and an effective disease-modifying drug would have significant implications for patients and their families. Since the identification of PKD1 and PKD2, there has been an explosion in knowledge identifying new disease mechanisms and testing new drugs. Currently, the three major treatment strategies are to: (1) reduce cAMP levels; (2) inhibit cell proliferation, and (3) reduce fluid secretion. Several compounds shown to be effective in preclinical models have already undergone clinical trials and more are planned. In addition, a whole raft of other compounds have been developed from preclinical studies. The purpose of this paper is to evaluate the results of recent published trials, review current trials and highlight the most promising compounds in the pipeline. There appears to be no shortage of potential candidates, but several key issues need to be addressed to facilitate clinical translation.
Translation and cross-cultural adaptation of the Pediatric Confusion Assessment Method for the Intensive Care Unit into Brazilian Portuguese for the detection of delirium in pediatric intensive care units

Objective To undertake the translation and cross-cultural adaption into Brazilian Portuguese of the Pediatric Confusion Assessment Method for the Intensive Care Unit for the detection of delirium in pediatric intensive care units, including the algorithm and instructions. Methods A universalist approach for the translation and cross-cultural adaptation of health measurement instruments was used. A group of pediatric critical care specialists assessed conceptual and item equivalences. Semantic equivalence was evaluated by means of a translation from English to Portuguese by two independent translators; reconciliation into a single version; back-translation by a native English speaker; and consensus among six experts with respect to language and content understanding by means of Likert scale responses and the Content Validity Index. Finally, operational equivalence was assessed by applying a pre-test to 30 patients. Results The back-translation was approved by the original authors. The medians of the expert consensus responses varied between good and excellent, except for the feature "acute onset" of the instructions. Items with a low Content Validity Index for the features "acute onset" and "disorganized thinking" were adapted. In the pre-test, the expression "signal with your head" was modified into "nod your head" for better understanding. No further adjustments were necessary, resulting in the final version for Brazilian Portuguese. Conclusion The Brazilian version of the Pediatric Confusion Assessment Method for the Intensive Care Unit was generated in agreement with the international recommendations and can be used in Brazil for the diagnosis of delirium in critically ill children 5 years of age or above and with no developmental cognitive disabilities.
Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients

Background The lysosomal enzyme α-L-Fucosidase-1 (FUCA-1) catalyzes the hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors as its inactivation perturbs the fucosylation of proteins involved in cell adhesion, migration and metastases. Results Negativity to FUCA-1 was significantly related to the development of later recurrences in breast cancer patients with lymph node involvement at diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by FUCA-1 expression as luminal B LN+ patients with positive expression had a longer cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in breast cancer-derived cell lines confirmed an inverse relationship with tumor aggressiveness. Conclusions This study shows that, within LN+ breast cancer patients, FUCA-1 is able to identify a sub-set of non recurrent patients characterized by the positive expression of FUCA-1 and that, within luminal B LN+ patients, the expression of FUCA-1 predicts longer cancer specific survival. Methods We have analyzed FUCA-1 in 305 breast cancer patients by Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast cancer cell lines.
Influence of 18GHz microwave radiation on the enzymatic activity of Escherichia coli lactate dehydrogenase and cytochrome c oxidase

The catalytic activity of two common bacterial enzymes, lactate dehydrogenase (LDH) and cytochrome c oxidase (COX) from Escherichia coli, was examined following bacterial exposure to microwave (MW) radiation under well-defined experimental conditions. The experiments were conducted in a specialised microwave processing apparatus, with an exposure frequency of 18 GHz, and a temperature profile that was restricted to below 40oC to avoid thermal degradation of the bacteria. The absorbed power was calculated to be 1500 kW/m3 and the electric field was determined to be 300 V/m. Both values were theoretically confirmed using Computer Simulation Technology (CST) Microwave Studio 3D Electromagnetic Stimulation Software. Results showed that the activity of both enzymes was increased following MW radiation compared to negative controls and thermally treated samples subjected to similar temperature profiles. It is suggested that the increase in COX and LDH enzyme activity could not be explained by conventional heating alone, but was rather a result of micro-thermal effects that incorporated ‘undetectable’ thermal mechanisms.
Electrophysiological evidence for temporal dynamics associated with attentional processing in the zoom lens paradigm

Background Visuospatial processing requires wide distribution or narrow focusing of attention to certain regions in space. This mechanism is described by the zoom lens model and predicts an inverse correlation between the efficiency of processing and the size of the attentional scope. Little is known, however, about the exact timing of the effects of attentional scaling on visual searching and whether or not additional processing phases are involved in this process. Method Electroencephalographic recordings were made while participants performed a visual search task under different attentional scaling conditions. Two concentric circles of different sizes, presented to the participants at the center of a screen modulated the attentional scopes, and search arrays were distributed in the space areas indicated by these concentric circles. To ensure consistent eccentricity of the search arrays across different conditions, we limited our studies to the neural responses evoked by the search arrays distributed in the overlapping region of different attentional scopes. Results Consistent with the prediction of the zoom lens model, our behavioral data showed that reaction times for target discrimination of search arrays decreased and the associated error rates also significantly decreased, with narrowing the attentional scope. Results of the event-related potential analysis showed that the target-elicited amplitude of lateral occipital N1, rather than posterior P1, which reflects the earliest visuospatial attentional processing, was sensitive to changes in the scaling of visuospatial attention, indicating that the modulation of the effect of changes in the spatial scale of attention on visual processing occurred after the delay period of P1. The N1 generator exhibited higher activity as the attentional scope narrowed, reflecting more intensive processing resources within the attentional focus. In contrast to N1, the amplitude of N2pc increased with the expansion of the attentional focus, suggesting that observers might further redistribute attentional resources according to the increased task difficulty. Conclusion These findings provide electrophysiological evidence that the neural activity of the N1 generator is the earliest marker of the zoom lens effect of visual spatial attention. Furthermore, evidence from N2pc shows that there is also a redistribution of attentional resources after the action of the zoom lens mechanism, which allows for better perform of the search task in the context of low attentional resolution. On the basis of the timing of P1, N1, and N2pc, our findings provide compelling evidence that visuospatial attention processing in the zoom lens paradigm involves multi-stage dynamic processing.
Clostridium difficile – From Colonization to Infection

Clostridium difficile is the most frequent cause of nosocomial antibiotic-associated diarrhea. The incidence of C. difficile infection (CDI) has been rising worldwide with subsequent increases in morbidity, mortality, and health care costs. Asymptomatic colonization with C. difficile is common and a high prevalence has been found in specific cohorts, e.g., hospitalized patients, adults in nursing homes and in infants. However, the risk of infection with C. difficile differs significantly between these cohorts. While CDI is a clear indication for therapy, colonization with C. difficile is not believed to be a direct precursor for CDI and therefore does not require treatment. Antibiotic therapy causes alterations of the intestinal microbial composition, enabling C. difficile colonization and consecutive toxin production leading to disruption of the colonic epithelial cells. Clinical symptoms of CDI range from mild diarrhea to potentially life-threatening conditions like pseudomembranous colitis or toxic megacolon. While antibiotics are still the treatment of choice for CDI, new therapies have emerged in recent years such as antibodies against C. difficile toxin B and fecal microbial transfer (FMT). This specific therapy for CDI underscores the role of the indigenous bacterial composition in the prevention of the disease in healthy individuals and its role in the pathogenesis after alteration by antibiotic treatment. In addition to the pathogenesis of CDI, this review focuses on the colonization of C. difficile in the human gut and factors promoting CDI.
Using Individual GPS Trajectories to Explore Foodscape Exposure: A Case Study in Beijing Metropolitan Area

With the growing interest in studying the characteristics of people’s access to the food environment and its influence upon individual health, there has been a focus on assessing individual food exposure based on GPS trajectories. However, existing studies have largely focused on the overall activity space using short-period trajectories, which ignores the complexity of human movements and the heterogeneity of the spaces that are experienced by the individual over daily life schedules. In this study, we propose a novel framework to extract the exposure areas consisting of the localized activity spaces around daily life centers and non-motorized commuting routes from long-term GPS trajectories. The newly proposed framework is individual-specific and can incorporate the internal heterogeneity of individual activities (spatial extent, stay duration, and timing) in different places as well as the dynamics of the context. A pilot study of the GeoLife dataset suggests that there are significant variations in the magnitude as well as the composition of the food environment in different parts of the individual exposure area, and residential environment is not representative of the overall foodscape exposure.
Effects of a persistent binge drinking pattern of alcohol consumption in young people: a follow-up study using event-related potentials.

AIMS The objective of this study was to examine brain activity related to visual attention processes in youths who had maintained a binge drinking (BD) pattern of alcohol consumption for >2 years. METHODS The participants were 57 university students (26 binge drinkers: BDs) with no personal or family history of alcoholism or psychopathological disorders in first-degree relatives. Event-related potentials (ERPs) were recorded while participants performed a visual oddball task (twice within a 2-year interval). The latency and amplitude of the P3b component of the ERPs were analysed. RESULTS The P3b amplitude was larger in young BDs than in aged-matched controls at both evaluation times, and the difference was more pronounced after 2 years of maintenance of a BD pattern of consumption. The larger P3b amplitude was associated with an earlier onset of regular drinking and with a greater quantity and intensity of consumption. CONCLUSIONS These findings suggest that young BDs exhibit anomalies in neural activity involved in attentional/working memory processes, which increase after 2 years of maintenance of BD. This anomalous neural activity may reflect underlying dysfunctions in neurophysiological mechanisms as well as the recruitment of additional attentional/working memory resources to enable the binge drinkers to perform the task adequately.
Nitrosospira sp. Govern Nitrous Oxide Emissions in a Tropical Soil Amended With Residues of Bioenergy Crop

Organic vinasse, a residue produced during bioethanol production, increases nitrous oxide (N2O) emissions when applied with inorganic nitrogen (N) fertilizer in soil. The present study investigated the role of the ammonia-oxidizing bacteria (AOB) community on the N2O emissions in soils amended with organic vinasse (CV: concentrated and V: non-concentrated) plus inorganic N fertilizer. Soil samples and N2O emissions were evaluated at 11, 19, and 45 days after fertilizer application, and the bacterial and archaea gene (amoA) encoding the ammonia monooxygenase enzyme, bacterial denitrifier (nirK, nirS, and nosZ) genes and total bacteria were quantified by real time PCR. We also employed a deep amoA amplicon sequencing approach to evaluate the effect of treatment on the community structure and diversity of the soil AOB community. Both vinasse types applied with inorganic N application increased the total N2O emissions and the abundance of AOB. Nitrosospira sp. was the dominant AOB in the soil and was correlated with N2O emissions. However, the diversity and the community structure of AOB did not change with vinasse and inorganic N fertilizer amendment. The results highlight the importance of residues and fertilizer management in sustainable agriculture and can be used as a reference and an input tool to determine good management practices for organic fertilization.
Insulin Resistance as a Therapeutic Target in the Treatment of Alzheimer's Disease: A State-of-the-Art Review

Research in animals and humans has shown that type 2 diabetes and its prodromal state, insulin resistance, promote major pathological hallmarks of Alzheimer's disease (AD), such as the formation of amyloid plaques and neurofibrillary tangles (NFT). Worrisomely, dysregulated amyloid beta (Aβ) metabolism has also been shown to promote central nervous system insulin resistance; although the role of tau metabolism remains controversial. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted insulin signaling. They also provide strong support for the hypothesis that pharmacologically restoring brain insulin signaling could represent a promising strategy to curb the development and progression of AD. In this context, great hopes have been attached to the use of intranasal insulin. This drug delivery method increases cerebrospinal fluid concentrations of insulin in the absence of peripheral side effects, such as hypoglycemia. With this in mind, the present review will also summarize current knowledge on the efficacy of intranasal insulin to mitigate major pathological symptoms of AD, i.e., cognitive impairment and deregulation of Aβ and tau metabolism.
Supratherapeutic dose evaluation and effect of lesinurad on cardiac repolarization: a thorough QT/QTc study

Introduction Lesinurad is a selective uric acid reabsorption inhibitor approved in the United States and Europe for treatment of gout in combination with a xanthine oxidase inhibitor. A maximum tolerated dose study was conducted to determine the lesinurad supratherapeutic dose, followed by a thorough QTc study to characterize the effect of lesinurad on cardiac repolarization. Methods The maximum tolerated dose study was a randomized, double-blind, placebo-controlled, single-ascending dose study that enrolled 35 healthy men and women. Lesinurad plasma exposure (maximum observed plasma concentration and area under the plasma concentration versus time curve) was determined at doses of 800 mg, 1,200 mg, and 1,600 mg. The thorough QTc study was a double-blind, four-period, placebo-controlled crossover study with 54 healthy men and women who received single doses of lesinurad 1,600 mg (supratherapeutic dose), lesinurad 400 mg, moxifloxacin 400 mg, and placebo in randomized sequence. Digital 12-lead electrocardiograms were recorded at eleven time points over 24 hours in each treatment period. QT intervals were corrected for heart rate using an individual-specific correction factor (QTcI). Results The upper bound of the one-sided 95% confidence interval for time-matched, placebo-subtracted, baseline-adjusted QTcI intervals (ΔΔQTcI) was <10 ms for both the lesinurad 400 mg and 1,600 mg doses. ΔΔQTcI was independent of lesinurad concentrations. No QTcI thresholds >480 ms or QTcI increases >30 ms were observed. Moxifloxacin mean QTcI intervals were >5 ms, and the lower bounds of the 90% confidence interval were >5 ms at 2 hours, 3 hours, and 4 hours, confirming assay sensitivity. Conclusion Lesinurad, at supratherapeutic doses, does not have a significant effect on the QT interval in healthy male or female subjects.