Miracle-dz/UniFAR-FTUs huggingface dataset:
Rupatadine oral solution for 2–5-year-old children with allergic rhinitis: a safety, open-label, prospective study

Background There are few clinical trials that assess the efficacy of antihistamines in very young children. Rupatadine is a second-generation antihistamine indicated for the treatment of allergic rhinitis (AR) and urticaria. In this study, AR symptoms were evaluated before and after daily 1 mg/mL rupatadine oral solution administration in 2–5-year-old children. Methods A multicenter open-label study was carried out in 2–5-year-old children with AR. Safety assessments were collected during the study including spontaneous adverse events, vital signs, and electrocardiogram (QTc interval). Additionally, evaluations of Total Five Symptoms Score (T5SS, including: nasal congestion; sneezing; rhinorrhoea; itchy nose, mouth, throat, and/or ears; and itchy, watery, and red eyes) were analyzed. Symptoms were evaluated by parents/legal guardian before and after 4 weeks of rupatadine administration, dosed according to body weight. Results A total of 44 children received the study treatment. Only 15 adverse events were reported. All of them were of mild intensity and considered not related to the study treatment. No patient exceeded the standard parameter of >450 ms in the last visit, for the QTc interval on their electrocardiograms. From a maximum score value of 15, T5SS values at Day 14 (6.35) and Day 28 (5.42) were both statistically significant different (p<0.001) from the baseline T5SS value (mean 8.65), with a reduction of 26.6% and 37.4%, respectively. All individual symptoms, including nasal congestion, showed also a decrease from baseline at both 14 and 28 days. Conclusion Rupatadine 1 mg/mL oral solution was found to be safe in 2–5-year-old children, correlating with an improvement of AR symptoms, overall and each individually, after a daily dose administration. With this study, we enlarge the available information in this very young pediatric patients’ group, in which there is a general lack of clinical evidence.
Spongispora temasekensis, a new boletoid genus and species from Singapore

ABSTRACT Dipterocarp forests are a typical and widespread type of vegetation in tropical lowlands of southeast Asia that harbor a high diversity of ectomycorrhizal fungi, including boletes. Based on molecular and morphological characters, a unique bolete found in Singapore associated with the dipterocarp Hopea odorata was proven to represent a new species in the proposed new genus Spongispora. Phylogenetic analyses of five loci indicate that Spongispora is nested in the subfamily Leccinoideae of the Boletaceae, most closely related to an inclusive clade of Leccinum, Leccinellum, Octaviania, Rossbeevera, and Turmalinea. However, genetic distances between Spongispora and genera in Leccinoideae are mostly higher than that between any two known genera in this subfamily, which supports the proposal of a new genus. Spongispora temasekensis is characterized by a whitish to pale yellow hymenophore that stains brown where injured, coarsely reticulate stipe, interwoven trichodermial pileipellis, and broadly elliptical to ovoid basidiospores with sponge-like ornamentation perforated by irregular clefts, cracks, and warts under scanning electron microscopy. Morphological descriptions, illustrations, and comparisons with allied taxa are made, and a key to the genera of the subfamily Leccinoideae is provided.
The Impact of Consumer Search Cost on Assortment Planning and Pricing

Consumers search for product information to resolve valuation uncertainties before purchase. We incorporate search cost into consumer choice models and study the two-stage consider-then-choose policy. In the first stage, a consumer forms her consideration set by balancing utility uncertainty and search cost. In the second stage, she evaluates all products in her consideration set and chooses the one with the highest net utility. We show that the revenue-ordered assortment (i.e., the offer set that includes products in the revenue-decreasing order) fails to be optimal, although it can obtain at least half the optimal revenue. We propose a k-quasi-attractiveness-ordered assortment and show that it can be arbitrarily near optimal for the market share maximization problem. The assortment problems with search cost are generally NP-hard, so we develop efficient approximation or relatively fast exact algorithms for a variety of assortment problems under the consider-then-choose models with search cost. For the j.
Neuronal Migration and Axonal Pathways Linked to Human Fetal Insular Development Revealed by Diffusion MR Tractography

Abstract The insula is a multimodal sensory integration structure that, in addition to serving as a gateway between somatosensory areas and limbic structures, plays a crucial role in autonomic nervous system function. While anatomical studies following the development of the insula have been conducted, currently, no studies have been published in human fetuses tracking the development of neuronal migration or of white matter tracts in the cortex. In this study, we aimed to follow the neuronal migration and subsequent maturation of axons in and around the insula in human fetal ages. Using high‐angular resolution diffusion magnetic resonance imaging tractography, major white matter pathways to/from the insula and its surrounding operculum were identified at a number of time points during human gestation. Pathways likely linked to neuronal migration from the ventricular zone to the inferior frontal gyrus, superior temporal region, and the insular cortex were detected in the earliest gestational age studied (15 GW). Tractography reveals neuronal migration to areas surrounding the insula occurred at different time points. These results, in addition to demonstrating key time points for neuronal migration, suggest that neurons and axonal fiber pathways underlying the insula and its surrounding gyri mature differentially despite their relationship during cortical folding.
Protective effects of extracellular polymeric substances from Aphanizomenon flos-aquae on neurotoxicity induced by local anesthetics

The neurotoxicity of local anesthetics has received an increasing amount of attention and more effective therapeutic agents are required. Extracellular polymeric substances from Aphanizomenon flos-aquae (EPS-A) are high molecular weight polysaccharides. The present study aimed to elucidate the protective effects of EPS-A on neurotoxicity induced by local anesthetics in an intraperitoneal injection bupivacaine rat model. The results of immunohistochemical staining inicated that following intraperitoneal injection of EPS-A the levels of apoptosis and caspase-3 decreased, and the expression levels of microtubule-associated protein 1A light chain 3 (LC3) and beclin1 increased. In order to further clarify the mechanism of the EPS-A-mediated protection, the expression of key proteins associated with autophagy was investigated by western blotting. The results suggested that the ratio of LC3-II/LC3-I and the expression level of beclin1 increased. Taken together, the results indicated that EPS-A induced neuroprotective effects on bupivacaine-induced neurotoxicity. The underlying mechanism may be associated with the inhibition of apoptosis, upregulation of autophagy and improvement of cell survival. The results suggested that EPS-A may be a candidate neuroprotective agent against neurotoxicity caused by local anesthetics.
Distinctive structural basis for DNA recognition by the fission yeast Zn2Cys6 transcription factor Pho7 and its role in phosphate homeostasis

Abstract Pho7, a member of the Zn2Cys6 family of fungal transcription factors, is the key transcriptional activator underlying fission yeast phosphate homeostasis, a physiological response to phosphate starvation in which the pho1, pho84 and tgp1 genes are upregulated. Here, we delineated a minimized 61-amino-acid Pho7 DNA-binding domain (DBD) and determined the 1.7 Å crystal structure of the DBD at its target site in the tgp1 promoter. Two distinctive features of the Pho7 DBD are: it binds DNA as a monomer, unlike most other fungal zinc-cluster factors that bind as homodimers; and it makes extensive interactions with its asymmetric target sequence over a 14-bp footprint that entails hydrogen bonding to 13 individual bases within, and remote from, the CGG triplet typically recognized by other Zn2Cys6 DBDs. Base pair substitutions at Pho7 sites in the tgp1 and pho1 promoters highlight the importance of the 5′-CGG triplet for Pho7 binding in vitro and Pho7-dependent gene expression in vivo. We identify several DBD amino acids at which alanine substitution effaced or attenuated the pho1 phosphate starvation response and concordantly reduced Pho7 binding to a pho1 promoter site.
PHARMACOKINETICS OF ORAL GABAPENTIN IN CARIBBEAN FLAMINGOS (PHOENICOPTERUS RUBER RUBER)

Abstract Gabapentin is a first-line treatment for neuropathic pain and adjunct anticonvulsant medication in humans and other species. Gabapentin may have advantages over other analgesics because of its broad therapeutic range with limited adverse effects and wide availability as an oral formulation. This study determined the pharmacokinetics of gabapentin in Caribbean flamingos (Phoenicopterus ruber ruber) after a single-dose oral administration of either 15 mg/kg (n = 6) or 25 mg/kg (n = 6). Plasma gabapentin concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using noncompartmental methods. Respectively for the 15 mg/kg and 25 mg/kg dose, mean peak plasma concentration (Cmax) was (mean ± pseudo SD) 13.23 ± 1.47 and 24.48 ± 5.81 μg/ml; mean time to peak plasma concentration (Tmax) was 0.50 ± 0.24 and 0.56 ± 0.28 hr; mean area under the curve (AUC) was 76.0 ± 26.3 and 114.7 ± 27.5 hr·μg/ml; and mean terminal half-life (T1/2) was 3.39 ± 0.90 and 4.46 ± 1.12 hr. Based on the results of this study, gabapentin dosed at 25 mg/kg orally in most Caribbean flamingos is likely to maintain plasma concentrations above the therapeutic range established for humans for approximately 12 hr.
Structure and function of archaeal histones

The genomes of all organisms throughout the tree of life are compacted and organized in chromatin by association of chromatin proteins. Eukaryotic genomes encode histones, which are assembled on the genome into octamers, yielding nucleosomes. Post-translational modifications of the histones, which occur mostly on their N-terminal tails, define the functional state of chromatin. Like eukaryotes, most archaeal genomes encode histones, which are believed to be involved in the compaction and organization of their genomes. Instead of discrete multimers, in vivo data suggest assembly of “nucleosomes” of variable size, consisting of multiples of dimers, which are able to induce repression of transcription. Based on these data and a model derived from X-ray crystallography, it was recently proposed that archaeal histones assemble on DNA into “endless” hypernucleosomes. In this review, we discuss the amino acid determinants of hypernucleosome formation and highlight differences with the canonical eukaryotic octamer. We identify archaeal histones differing from the consensus, which are expected to be unable to assemble into hypernucleosomes. Finally, we identify atypical archaeal histones with short N- or C-terminal extensions and C-terminal tails similar to the tails of eukaryotic histones, which are subject to post-translational modification. Based on the expected characteristics of these archaeal histones, we discuss possibilities of involvement of histones in archaeal transcription regulation.
Gumpy: a Python toolbox suitable for hybrid brain–computer interfaces

Objective. The objective of this work is to present gumpy, a new free and open source Python toolbox designed for hybrid brain–computer interface (BCI). Approach. Gumpy provides state-of-the-art algorithms and includes a rich selection of signal processing methods that have been employed by the BCI community over the last 20 years. In addition, a wide range of classification methods that span from classical machine learning algorithms to deep neural network models are provided. Gumpy can be used for both EEG and EMG biosignal analysis, visualization, real-time streaming and decoding. Results. The usage of the toolbox was demonstrated through two different offline example studies, namely movement prediction from EEG motor imagery, and the decoding of natural grasp movements with the applied finger forces from surface EMG (sEMG) signals. Additionally, gumpy was used for real-time control of a robot arm using steady-state visually evoked potentials (SSVEP) as well as for real-time prosthetic hand control using sEMG. Overall, obtained results with the gumpy toolbox are comparable or better than previously reported results on the same datasets. Significance. Gumpy is a free and open source software, which allows end-users to perform online hybrid BCIs and provides different techniques for processing and decoding of EEG and EMG signals. More importantly, the achieved results reveal that gumpy’s deep learning toolbox can match or outperform the state-of-the-art in terms of accuracy. This can therefore enable BCI researchers to develop more robust decoding algorithms using novel techniques and hence chart a route ahead for new BCI improvements.
General Deep Image Completion with Lightweight Conditional Generative Adversarial Networks

Recent image completion researches using deep neural networks approaches have shown remarkable progress by using generative adversarial networks (GANs). However, these approaches still have the problems of large model sizes and lack of generality for various types of corruptions. In addition, the conditional GANs often suffer from the mode collapse and unstable training problems. In this paper, we overcome these shortcomings in the previous models by proposing a lightweight model of conditional GANs with integrating a stable way in adversarial training. Moreover, we present a new training strategy to trigger the model to learn how to complete different types of corruptions or missing regions in images. Experimental results demonstrate qualitatively and quantitatively that the proposed model provides significant improvement over a number of representative image completion methods on public datasets. In addition, we show that our model requires much less model parameters to achieve superior results for different types of unseen corruption masks.
PAX5A and PAX5B isoforms are both efficient to drive B cell differentiation

Pax5 is the guardian of the B cell identity since it primes or enhances the expression of B cell specific genes and concomitantly represses the expression of B cell inappropriate genes. The tight regulation of Pax5 is therefore required for an efficient B cell differentiation. A defect in its dosage can translate into immunodeficiency or malignant disorders such as leukemia or lymphoma. Pax5 is expressed from two different promoters encoding two isoforms that only differ in the sequence of their first alternative exon. Very little is known regarding the role of the two isoforms during B cell differentiation and the regulation of their expression. Our work aims to characterize the mechanisms of regulation of the expression balance of these two isoforms and their implication in the B cell differentiation process using murine ex vivo analyses. We show that these two isoforms are differentially regulated but have equivalent function during early B cell differentiation and may have functional differences after B cell activation. The tight control of their expression may thus reflect a way to finely tune Pax5 dosage during B cell differentiation process.
FIGO Versus Silverberg Grading Systems in Ovarian Endometrioid Carcinoma: A Comparative Prognostic Analysis

The International Federation of Obstetrics and Gynecology (FIGO) grading system for endometrial carcinoma is currently applied to ovarian endometrioid carcinoma (OEC) in many practices. However, previous reports claim superior prognostication by using the Silverberg grading system for ovarian carcinoma. Thus, a thorough comparison between FIGO and Silverberg in OEC is still warranted. A total of 72 OECs diagnosed at our institution were independently graded using both systems. Grade (G) following Silverberg was based on combined scores for architecture, nuclear atypia, and mitotic activity. FIGO grading was based on the % of nonsquamous solid component; severe atypia warranted upgrade to the architectural FIGO grade (G1 to G2 or G2 to G3). Case grouping by grade was correlated with disease-free (DFS), disease-specific (DSS), and overall (OS) survival. Eleven (15.3%) OECs were bilateral, 26 (36.1%) had ovarian surface involvement, and 12 (16.7%) had lymphovascular space invasion. Forty-seven OECs were stage I (65%), 16 (22%) stage II, and 9 (13%) stage III. Median follow-up period was 62 months (range: 1 to 179 mo). Median DFS was 60.5 months (1 to 179 mo); median OS was 61 months (1 to 179 mo). Sixteen (22%) OECs recurred and 9 (13%) patiets died of disease. In univariate analysis, both FIGO and Silverberg correlated significantly with DFS, DSS, and OS (all with P<0.05). However, when compared in multivariate analysis, only Silverberg retained statistical correlation with survival (P<0.05). G1+G2 OEC by Silverberg had significantly better DFS, DSS, and OS compared with G3; such separation was not seen with FIGO. Survival was similar in Silverberg G1 and G2 tumors even 5 years after diagnosis, whereas FIGO G2 tumors had survival approaching G1 in the first 5 years, but declined after the 5-year mark approaching G3 tumors. Tumor laterality, lymphovascular space invasion, and stage also correlated with outcome. Stage showed prognostication superior to all other variables in multivariate analysis. As currently defined, the Silverberg grading system is a better predictor of survival than FIGO. Such differences may be explained by the G2 OEC groups, with G2 Silverberg clustering with G1 tumors, and having a more favorable behavior compared with G2 FIGO. Thus, Silverberg may be preferable in order to stratify patients in low and high-risk categories for prognosis and disease management.
Performance of uplink WFRFT-based hybrid carrier systems with non-orthogonal multiple access

In this paper, the performance of hybrid carrier (HC) systems based on weighted fractional Fourier transform (WFRFT) is investigated in an uplink non-orthogonal multiple access (NOMA) scenario. NOMA is a promising technology to improve the system capacity, in which two users (far-user and near-user relative to a base station) are allocated to use the same time-frequency resources, and the successive interference cancellation (SIC) technique is implemented to decode signals at the receiver. Considering the actual error decoding in the SIC process (i.e. imperfect SIC), NOMA cannot avoid the inter-user interference (IUI) and residual interference (or error propagation). Therefore, firstly IUI and residual interference are analysed, and signal to interference plus noise ratio (SINR) of the far-user is expressed mathematically considering the residual interference. Then, based on the analysis of IUI, considering different WFRFT orders, a near-user BER expression over additive white Gaussian noise (AWGN) channels is derived. Furthermore, the optimal WFRFT order selection to minimise the interference influence in the uplink is formulated and solved efficiently. Simulation results have verified the mathematical expression of SINR, the near-user theoretical BER expression, and the proposed optimal WFRFT order selection to obtain the maximum sum spectral efficiency.
Aspirin cooperates with p300 to activate the acetylation of H3K9 and promote FasL-mediated apoptosis of cancer stem-like cells in colorectal cancer

Cancer stem-like cells (CSCs) have been proposed as a key driving force of tumor growth and relapse in colorectal cancer (CRC), and therefore, they are promising targets for cancer therapy. Epidemiological evidence has suggested that the daily use of aspirin reduces overall mortality of CRC and the risk of distant metastasis. We investigated the effect and mechanism of aspirin on CSCs in CRC. Methods: The ratio of CSCs was analyzed after aspirin treatment both in a cell model and patient samples. Chemically modified aspirin and immunoprecipitation were adopted to detect the target proteins of aspirin. A locus-specific light-inducible epigenetic modification system based on CRISPR technology was constructed to verify the causal relationship in these molecular events. In vivo characterization was performed in a xenograft model. Results: We found that aspirin induces apoptosis in enriched colorectal CSCs, inhibits tumor progression, and enhances the anti-neoplastic effects of chemotherapeutic agents. Furthermore, aspirin directly interacts with p300 in the nucleus, promotes H3K9 acetylation, activates FasL expression, and induces apoptosis in colorectal CSCs. Notably, these effects of aspirin are absent in non-CSCs since H3K9 is hypermethylated in non-CSCs and the effects are not induced by other NSAIDs. In addition, aspirin can suppress oxaliplatin-enriched CSCs and serve as an adjuvant therapy. Conclusions: Taken together, we revealed a unique epigenetic and cox-independent pathway (p300-AcH3K9-FasL axis) by which aspirin eliminates colorectal CSCs. These findings establish an innovative framework of the therapeutic significance of aspirin.
Investigating the impact of cigarette smoking behaviours on DNA methylation patterns in adolescence

Abstract Smoking usually begins in adolescence, and early onset of smoking has been linked to increased risk of later life disease. There is a need to better understand the biological impact of cigarette smoking behaviours in adolescence. DNA methylation profiles related to smoking behaviours and cessation in adulthood have been previously identified, but alterations arising from smoking initiation have not been thoroughly investigated. We aimed to investigate DNA methylation in the Avon Longitudinal Study of Parents and Children in relation to (1) different smoking measures, (2) time since smoking initiation and frequency of smoke exposure and (3) latent classes of smoking behaviour. Using 2620 CpG sites previously associated with cigarette smoking, we investigated DNA methylation change in relation to own smoking measures, smoke exposure duration and frequency, and using longitudinal latent class analysis of different smoking behaviour patterns in 968 adolescents. Eleven CpG sites located in seven gene regions were differentially methylated in relation to smoking in adolescence. While only AHRR (cg05575921) showed a robust pattern of methylation in relation to weekly smoking, several CpGs showed differences in methylation among individuals who had tried smoking compared with non‐smokers. In relation to smoke exposure duration and frequency, cg05575921 showed a strong dose‐response relationship, while there was evidence for more immediate methylation change at other sites. Our findings illustrate the impact of cigarette smoking behaviours on DNA methylation at some smoking‐responsive CpG sites, even among individuals with a short smoking history.