Miracle-dz/UniFAR-FTUs huggingface dataset:
Global analysis of LARP1 translation targets reveals tunable and dynamic features of 5′ TOP motifs

Significance The mTORC1 signaling pathway senses nutrient signals and controls cell growth partly by regulating mRNA translation. 5′ TOP motifs are defining features of mTORC1-regulated mRNAs, but their prevalence throughout the transcriptome and the mechanism that controls them are not fully understood. Here we show that the mTORC1 effector LARP1 is the master regulator of TOP mRNAs genome-wide. We discover features of TOP sequences that tune their regulatory potential across a continuous spectrum and define a metric called a TOPscore that quantifies them. Analysis of TOPscores across the transcriptomes of 16 mammalian tissues defines both constitutive TOP mRNAs and tissue-specific variants resulting from alternative transcription initiation. These results establish global principles of a dynamic and tunable program of nutrient-regulated gene expression. Terminal oligopyrimidine (TOP) motifs are sequences at the 5′ ends of mRNAs that link their translation to the mTOR Complex 1 (mTORC1) nutrient-sensing signaling pathway. They are commonly regarded as discrete elements that reside on ∼100 mRNAs that mostly encode translation factors. However, the full spectrum of TOP sequences and their prevalence throughout the transcriptome remain unclear, primarily because of uncertainty over the mechanism that detects them. Here, we globally analyzed translation targets of La-related protein 1 (LARP1), an RNA-binding protein and mTORC1 effector that has been shown to repress TOP mRNA translation in a few specific cases. We establish that LARP1 is the primary translation regulator of mRNAs with classical TOP motifs genome-wide, and also that these motifs are extreme instances of a broader continuum of regulatory sequences. We identify the features of TOP sequences that determine their potency and quantify these as a metric that accurately predicts mTORC1/LARP1 regulation called a TOPscore. Analysis of TOPscores across the transcriptomes of 16 mammalian tissues defines a constitutive “core” set of TOP mRNAs, but also identifies tissue-specific TOP mRNAs produced via alternative transcription initiation sites. These results establish the central role of LARP1 in TOP mRNA regulation on a transcriptome scale and show how it connects mTORC1 to a tunable and dynamic program of gene expression that is tailored to specific biological contexts.
An Exploratory Study of Adult Baby-Diaper Lovers’ Characteristics in an Italian Online Sample

Background: Knowledge of the Adult Baby-Diaper Lovers (ABDL) phenomena is quite recent and there are, of yet, few studies on this phenomenon. Aim: This study was conceived to investigate the functions of ABDL behaviours and the characteristics of ABDL in an online Italian community sample. We hypothesized that ABDL phenomena were associated with general psychological maladjustment and with an experience of parental rejection during childhood. It was also assumed that there would be differences in ABDL profiles based on the age of appearance of their first Adult Baby-Diaper Lover (ABDL) fantasies. Method: An internet-based study was conducted and it involved 38 adults aged between 18 and 74 years (M = 34.95; SD = 12.25). Participants were first given an ad hoc questionnaire, which was devised to obtain information about the anamnestic variables related to ABDL. Then, the participants filled out the Cognitive Behaviour Assessment 2.0 battery to obtain anamnestic information regarding their psychological, medical, and personal history and to evaluate primary psychological dimensions in clinical practice. Finally, they filled out the Adult Parental Acceptance–Rejection Questionnaire, to evaluate their recollections of parental perceived rejection, and the Personality Assessment Questionnaire, to evaluate the primary psychological aspects related to parental rejection. Results: The data indicated that adults with ABDL showed the presence of anxious traits and recollections of parental rejection during childhood. Moreover, associations were observed between current or previous ABDL phenomena enuresis and negative mood states. Conclusion: Specific kinds of parental modes, anxiety traits, and enuresis seem to be the source of ABDL interests. Moreover, ADBL behaviours seem to assume different functions and meanings.
Gradient HPLC Method for Simultaneous Determination of Eight Sartan and Statin Drugs in Their Pure and Dosage Forms

A gradient HPLC method was developed and validated for rapid simultaneous separation and determination of the following eight drugs of sartan and statin classes in their pure and dosage forms within 15 minutes: irbesartan (IRB), losartan (LOS), valsartan (VAL), olmesartan (OLM), rosuvastatin (ROS), atorvastatin (ATR), lovastatin (LOV), and simvastatin (SIM). Separation was carried out on a Kinetex C18 100A column (2.60 μm, 4.60 mm × 100 mm) using a gradiant binary mobile phase of 0.05M potassium dihydrogen phosphate buffer (pH 3.50 adjusted by ortho-phosphoric acid) and acetonitrile at room temperature. The flow rate was 1.00 mL/min and maximum absorption was measured using a DAD detector at 280 nm. The retention times of IRB, LOS, ROS, VAL, ATR, LOV, OLM, and SIM were recorded to be 4.72, 5.32, 6.06, 7.19, 7.96, 9.30, 11.91, and 14.66 minutes, respectively. Limits of detection were reported to be 2.01, 1.32, 1.10, 0.76, 0.21, 1.50, 0.38, and 0.55 mM for the same sequence of drugs, respectively, showing a high degree of method sensitivity. The method was then validated according to the international conference of harmonization (ICH) guidelines for the determination of the drugs in their dosage forms with highly precise recoveries. Also, a statistical comparison with reference methods was performed showing no significant differences between the proposed method and reported ones in terms of precision and accuracy.
Extraction and Modification of Macroalgal Polysaccharides for Current and Next-Generation Applications

Marine macroalgal (seaweed) polysaccharides are highly promising for next-generation applications in several industries. However, despite the reported comprehensive potential of these polysaccharides, commercial products are scarce on the market. Seaweed cultivations are increasing in number and production quantity, owing to an elevated global trend of utilization interest in seaweed. The extraction of polysaccharides from seaweed generally generates low yields, but novel methods are being developed to facilitate and improve the extraction processes. Current areas of applications for seaweed polysaccharides mainly take advantage of the physicochemical properties of certain polysaccharides, such as gelling, thickening and emulsifying. However, many of the numerous bioactivities reported are still only at research level and lack clinical evidence for commercialization. It has been suggested the construction of smaller units may generate better defined molecules that are more suitable for biomedical applications. Enzymatic modification is a promising tool for the generation of more defined, targeted biomolecules. This review covers; structural differences between the most predominant marine algal polysaccharides, extraction processes, modification alternatives, as well as a summary of current and potential next-generation application areas.
Compressive Radar Imaging of Stationary Indoor Targets With Low-Rank Plus Jointly Sparse and Total Variation Regularizations

This paper addresses the problem of wall clutter mitigation and image reconstruction for through-wall radar imaging (TWRI) of stationary targets by seeking a model that incorporates low-rank (LR), joint sparsity (JS), and total variation (TV) regularizers. The motivation of the proposed model is that LR regularizer captures the low-dimensional structure of wall clutter; JS guarantees a small fraction of target occupancy and the similarity of sparsity profile among channel images; TV regularizer promotes the spatial continuity of target regions and mitigates background noise. The task of wall clutter mitigation and target image reconstruction is formulated as an optimization problem comprising LR, JS, and TV regularization terms. To handle this problem efficiently, an iterative algorithm based on the forward-backward proximal gradient splitting technique is introduced, which captures wall clutter and yields target images simultaneously. Extensive experiments are conducted on real radar data under compressive sensing scenarios. The results show that the proposed model enhances target localization and clutter mitigation even when radar measurements are significantly reduced.
A bootstrap semiparametric homogeneity test for the distributions of multigroup proportional data, with applications to analysis of quality of life outcomes in clinical trials

This article is concerned about the test for the difference in the distributions of multigroup proportional data, which is motivated by the problem of comparing the distributions of quality of life (QoL) outcomes among different treatment groups in clinical trials. The proportional data, such as QoL outcomes assessed by answers to questions on a questionnaire, are bounded in a closed interval such as [0,1] with continuous observations in (0,1) and, in addition, excess observations taking the boundary values 0 and/or 1. Common statistical procedures used in practice, such as t‐ and rank‐based tests, may not be very powerful since they ignore the specific feature of the proportional data. In this article, we propose a three‐component mixture model for the proportional data and a density ratio model for the distributions of continuous observations in (0,1). A semiparametric test statistic for the homogeneity of distributions of multigroup proportional data is derived based on the empirical likelihood ratio principle and shown to be asymptotically distributed as a chi‐squared random variable under null hypothesis. A nonparametric bootstrap procedure is proposed to further improve the performance of the semiparametric test. Simulation studies are performed to evaluate the empirical type I error and power of the proposed test procedure and compare it with likelihood ratio tests (LRTs) under parametric distribution assumptions, rank‐based Kruskal‐Wallis test, and Wald‐type test. The proposed test procedure is also applied to the analysis of QoL outcomes from a clinical trial on colorectal cancer that motivated our study.
A survey of gene expression meta-analysis: methods and applications

The increasing use of high-throughput gene expression quantification technologies over the last two decades and the fact that most of the published studies are stored in public databases has triggered an explosion of studies available through public repositories. All this information offers an invaluable resource for reuse to generate new knowledge and scientific findings. In this context, great interest has been focused on meta-analysis methods to integrate and jointly analyze different gene expression datasets. In this work, we describe the main steps in the gene expression meta-analysis, from data preparation to the state-of-the art statistical methods. We also analyze the main types of applications and problems that can be approached in gene expression meta-analysis studies and provide a comparative overview of the available software and bioinformatics tools. Moreover, a practical guide for choosing the most appropriate method in each case is also provided.
Survey of Procedural Methods for Two-Dimensional Texture Generation

Textures are the most important element for simulating real-world scenes and providing realistic and immersive sensations in many applications. Procedural textures can simulate a broad variety of surface textures, which is helpful for the design and development of new sensors. Procedural texture generation is the process of creating textures using mathematical models. The input to these models can be a set of parameters, random values generated by noise functions, or existing texture images, which may be further processed or combined to generate new textures. Many methods for procedural texture generation have been proposed, but there has been no comprehensive survey or comparison of them yet. In this paper, we present a review of different procedural texture generation methods, according to the characteristics of the generated textures. We divide the different generation methods into two categories: structured texture and unstructured texture generation methods. Example textures are generated using these methods with varying parameter values. Furthermore, we survey post-processing methods based on the filtering and combination of different generation models. We also present a taxonomy of different models, according to the mathematical functions and texture samples they can produce. Finally, a psychophysical experiment is designed to identify the perceptual features of the example textures. Finally, an analysis of the results illustrates the strengths and weaknesses of these methods.
Pain thresholds and intensities of CRPS type I and neuropathic pain in respect to sex

Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers.
Decline in Dental Fluorosis Severity during Adolescence: A Cohort Study

Dental fluorosis occurs from overingestion of fluoride during tooth formation. However, there is little evidence in the literature on whether or how fluorosis prevalence and severity change over time after tooth eruption. Permanent dentition dental examinations were conducted at ages 9, 13, 17, and 23 as part of the Iowa Fluoride Study, which has followed a cohort from birth. Fluorosis was assessed using the Fluorosis Risk Index (FRI) and Russell’s criteria for differential diagnosis. Measures of fluorosis severity at the person and tooth level were calculated: second highest FRI score at the person level (the maximum FRI score for each tooth was determined and the tooth with the second highest maximum FRI score was used) and highest FRI score at the tooth level. At both the person and tooth levels, a decline in mild to moderate fluorosis severity was observed across adolescence and young adulthood. Across each pair of adjacent examinations at the person level, for participants with a baseline second highest FRI of 0, most participants stayed at 0 (82% to 91%). Many participants with a baseline second highest FRI of 1 had a follow-up score of 0 (47% to 54%), while about a third had a follow-up score of 1 (34% to 38%), and a lower percentage had an increase to a score of 2 (9% to 15%). For participants with baseline second highest FRI score of 2, between 25% and 44% of participants had follow-up FRI scores each of 0, 1, and 2. Similar patterns were observed at the tooth level. These results were consistent with most of the existing, limited literature. Overall, fluorosis severity, which was initially mild to moderate, tended to decline during adolescence and young adulthood. Additional study of how this trend affects esthetic perceptions of fluorosis is warranted.
A Computational Pipeline to Predict Cardiotoxicity

Supplemental Digital Content is available in the text. Rationale: Drug-induced proarrhythmia is so tightly associated with prolongation of the QT interval that QT prolongation is an accepted surrogate marker for arrhythmia. But QT interval is too sensitive a marker and not selective, resulting in many useful drugs eliminated in drug discovery. Objective: To predict the impact of a drug from the drug chemistry on the cardiac rhythm. Methods and Results: In a new linkage, we connected atomistic scale information to protein, cell, and tissue scales by predicting drug-binding affinities and rates from simulation of ion channel and drug structure interactions and then used these values to model drug effects on the hERG channel. Model components were integrated into predictive models at the cell and tissue scales to expose fundamental arrhythmia vulnerability mechanisms and complex interactions underlying emergent behaviors. Human clinical data were used for model framework validation and showed excellent agreement, demonstrating feasibility of a new approach for cardiotoxicity prediction. Conclusions: We present a multiscale model framework to predict electrotoxicity in the heart from the atom to the rhythm. Novel mechanistic insights emerged at all scales of the system, from the specific nature of proarrhythmic drug interaction with the hERG channel, to the fundamental cellular and tissue-level arrhythmia mechanisms. Applications of machine learning indicate necessary and sufficient parameters that predict arrhythmia vulnerability. We expect that the model framework may be expanded to make an impact in drug discovery, drug safety screening for a variety of compounds and targets, and in a variety of regulatory processes.
Integrated Metabolomic and Transcriptomic Analysis to Characterize Cutin Biosynthesis between Low- and High-Cutin Genotypes of Capsicum chinense Jacq

Habanero peppers constantly face biotic and abiotic stresses such as pathogen/pest infections, extreme temperature, drought and UV radiation. In addition, the fruit cutin lipid composition plays an important role in post-harvest water loss rates, which in turn causes shriveling and reduced fruit quality and storage. In this study, we integrated metabolome and transcriptome profiling pertaining to cutin in two habanero genotypes: PI 224448 and PI 257145. The fruits were selected by the waxy or glossy phenotype on their surfaces. Metabolomics analysis showed a significant variation in cutin composition, with about 6-fold higher cutin in PI 257145 than PI 224448. It also revealed that 10,16-dihydroxy hexadecanoic acid is the most abundant monomer in PI 257145. Transcriptomic analysis of high-cutin PI 257145 and low-cutin PI 224448 resulted in the identification of 2703 statistically significant differentially expressed genes, including 1693 genes upregulated and 1010 downregulated in high-cutin PI 257145. Genes and transcription factors such as GDSL lipase, glycerol-3 phosphate acyltransferase 6, long-chain acyltransferase 2, cytochrome P450 86A/77A, SHN1, ANL2 and HDG1 highly contributed to the high cutin content in PI 257145. We predicted a putative cutin biosynthetic pathway for habanero peppers based on deep transcriptome analysis. This is the first study of the transcriptome and metabolome pertaining to cutin in habanero peppers. These analyses improve our knowledge of the molecular mechanisms regulating the accumulation of cutin in habanero pepper fruits. These resources can be built on for developing cultivars with high cutin content that show resistance to biotic and abiotic stresses with superior postharvest appearance.
Pairwise Constraint Propagation With Dual Adversarial Manifold Regularization

Pairwise constraints (PCs) composed of must-links (MLs) and cannot-links (CLs) are widely used in many semisupervised tasks. Due to the limited number of PCs, pairwise constraint propagation (PCP) has been proposed to augment them. However, the existing PCP algorithms only adopt a single matrix to contain all the information, which overlooks the differences between the two types of links such that the discriminability of the propagated PCs is compromised. To this end, this article proposes a novel PCP model via dual adversarial manifold regularization to fully explore the potential of the limited initial PCs. Specifically, we propagate MLs and CLs with two separated variables, called similarity and dissimilarity matrices, under the guidance of the graph structure constructed from data samples. At the same time, the adversarial relationship between the two matrices is taken into consideration. The proposed model is formulated as a nonnegative constrained minimization problem, which can be efficiently solved with convergence theoretically guaranteed. We conduct extensive experiments to evaluate the proposed model, including propagation effectiveness and applications on constrained clustering and metric learning, all of which validate the superior performance of our model to state-of-the-art PCP models.
Relationship between fibrinogen level and its regulatory gene with Alzheimer’s disease and vascular dementia

Objective Several investigations have shown that the level of fibrinogen (Fg) is associated with the susceptibility to dementia and is usually affected by polymorphisms in its gene. Our study aimed to investigate the relationship between Fg level and the fibrinogen β (FGB) −148C/T gene polymorphism in patients with Alzheimer’s disease (AD) and vascular dementia (VaD). Methods The study included 64 AD patients, 72 VaD patients, and 56 healthy controls (HC). Plasma Fg level was detected by turbidimetry. Among the participants, 64 AD patients, 52 VaD patients, and 56 HC underwent FGB −148C/T polymorphism analysis using restriction fragment length polymorphism-PCR. Results Plasma Fg was significantly higher in AD and VaD groups than in HC. The AD and VaD patients with FGB −148 TT genotype had significantly higher plasma Fg than those with CC or CT genotypes. The distribution of CC and CT+TT genotypes differed in the three groups, with the frequency of CT+TT genotypes being higher in AD patients than in the HC group. Conclusions Plasma Fg level was significantly correlated with AD and VaD and related to the −148C/T polymorphism of FGB. The TT+CT genotypes and the distribution frequency of the T allele may be related to AD.
The similarity of the effect of carbohydrase or prebiotic supplementation in broilers aged 21 days, fed mixed cereal diets and challenged with coccidiosis infection

The aim of this study was to investigate the effect on growth performance and nutrient utilisation when supplementing diets deficient in energy and protein with carbohydrase enzymes or xylo-oligosaccharide in broilers challenged with coccidia. 960 Ross 308 broilers were used in this 21-day study. The treatments were arranged into a 2×4 factorial with 2 challenge states (challenged and non-challenged) and 4 different additive types (control, xylanase alone, xylanase and β-glucanase mixture and xylo-oligosaccharide). On day 14, the challenged group received 12× the recommended dose of coccidiosis vaccine while the non-challenged group received a sham treatment of water only. The birds and feed were weighed on days 0, 14 and 21. On day 21, two birds per pen were euthanized, the caeca were removed and the contents collected for short chain fatty acid analysis. Six more birds per pen were euthanized and ileal digesta were collected and pooled per pen for nutrient digestibility analysis. Feed intake was greater (P < 0.05) on days 14 and 21 when xylo-oligosaccharide was included in the diet compared to the xylanase and β-glucanase mixture in birds challenged with coccidiosis. Including xylo-oligosaccharide in the diet improved (P < 0.05) the digestibility of nitrogen and supplementing diets with the xylanase and β-glucanase mixture improved (P < 0.05) the digestibility of several amino acids. The concentration of arabinose and xylose was (P < 0.001) greater when broiler diets were supplemented with carbohydrase enzymes or xylo-oligosaccharide compared to the control. Although there was an increase in short chain fatty acid production due to the addition of carbohydrase enzymes or xylo-oligosaccharide, there was no additive effect on the %G+C profile of caecal bacteria however there was a negative effect of coccidiosis. In conclusion, the similarity in the response to carbohydrase enzymes or xylo-oligosaccharide supplementation illustrates that the hydrolysis products from carbohydrase activity may have prebiotic like effects.