Miracle-dz/UniFAR-FTUs huggingface dataset:
25(OH)D Levels in Relation to Gender, Overweight, Insulin Resistance, and Inflammation in a Cross-Sectional Cohort of Northern Italian Workers: Evidence in Support of Preventive Health Care Programs

ABSTRACT Objective: In recent years, the welfare of workers and the prevention of chronic disabling diseases has become a topic of great interest. This study investigates serum levels of total 25-hydroxyvitamin D (25(OH)D) in a cohort of overweight–obese and insulin-resistant northern Italian indoor workers in apparent good health followed a nutritional education program. Methods: An observational cross-sectional study on 385 patients (females = 291, males = 94), age range 18–69 years and body mass index (BMI) > 25 kg/m2, was performed at the Department of Occupational Medicine Milan, Italy, latitude 45.465454 N. We evaluated nutritional intakes, occupational and leisure physical activity, anthropometric measurements, impedance evaluation, blood pressure, the presence of metabolic syndrome (MetS) and nonalcoholic fatty liver diseases (NAFLD) by fatty liver index (FLI). Hematologic and biochemical parameters and (25(OH)D) levels were evaluated from fasting blood samples. Results: Only 10.91% of subjects had optimal values of 25(OH)D; 17.40% of the remaining 89.09% subjects were severely deficient, with no gender difference and insufficient intake of vitamin D. Only 28% declared leisure physical activity; 39.48% had metabolic syndrome and 62.60% had an FLI > 30. An inverse relationship between 25(OH)D levels and BMI was found, with a significant reduction of total 25(OH)D serum concentrations in winter. The homeostasis model assessment–insulin resistance (HOMA-IR) is positively related to BMI and inversely related to 25(OH)D concentrations. A positive correlation between vitamin D and leisure physical activity was found. At univariate analysis adjusted for age, gender and BMI, an inverse relationship between vitamin D and FLI was observed in both genders. The correlation between 25(OH)D levels, inflammation markers, BMI, and FLI showed an increased risk of cardiovascular disease in this cohort of workers. Conclusion: Our results suggest the rationale for a large-scale screening program for vitamin D by means of easily implementable low-cost preventive supplementation.
Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction

Ketamine is a potent dissociative anesthetic and the most commonly used illicit drug. Many addicts are women at childbearing age. Although ketamine has been extensively studied as a clinical anesthetic, its effects on embryonic development are poorly understood. Here, we applied the Xenopus model to study the effects of ketamine on development. We found that exposure to ketamine from pre-gastrulation (stage 7) to early neural plate (stage 13.5) resulted in disruption of neural crest (NC) derivatives. Ketamine exposure did not affect mesoderm development as indicated by the normal expression of Chordin, Xbra, Wnt8, and Fgf8. However, ketamine treatment significantly inhibited Zic5 and Slug expression at early neural plate stage. Overexpression of Zic5 rescued ketamine-induced Slug inhibition, suggesting the blockage of NC induction was mediated by Zic5. Furthermore, we found Notch signaling was altered by ketamine. Ketamine inhibited the expression of Notch targeted genes including Hes5.2a, Hes5.2b, and ESR1 and ketamine-treated embryos exhibited Notch-deficient somite phenotypes. A 15 bp core binding element upstream of Zic5 was induced by Notch signaling and caused transcriptional activation. These results demonstrated that Zic5 works as a downstream target gene of Notch signaling in Xenopus NC induction. Our study provides a novel teratogenic mechanism whereby ketamine disrupts NC induction via targeting a Notch-Zic5 signaling pathway.
From Mirroring to Guiding: A Review of State of the Art Technology for Supporting Collaborative Learning

We review a representative selection of systems that support the management of collaborative learning interaction, and characterize them within a simple classification framework. The framework distinguishes between mirroring systems, which display basic actions to collaborators, metacognitive tools, which represent the state of interaction via a set of key indicators, and coaching systems, which offer advice based on an interpretation of those indicators. The reviewed systems are further characterized by the type of interaction data they assimilate, the processes they use for deriving higher-level data representations, the variables or indicators that characterize these representations, and the type of feedback they provide to students and teachers. This overview of technological capabilities is designed to lay the groundwork for further research into which technological solutions are appropriate for which learning situations.
Cardiovascular magnetic resonance imaging in heart failure

ABSTRACT Introduction: Heart failure is a complex clinical syndrome resulting from heart structural remodeling and impaired function in ejecting blood; its incidence is increasing markedly worldwide. The observed variations in the structure and function of the heart are attributable to differences in etiology of heart failure. Cardiac magnetic resonance imaging (CMR) can characterize myocardial tissue, assess myocardial viability, and help diagnose specific cardiomyopathies. The emergence of T1 mapping techniques further improves our knowledge and the clinical assessment of myocardial diffuse fibrosis. Physicians, therefore, must identify the variations using CMR to improve patient’s symptoms, survival, and quality of life. Area covered: Current reports regarding CMR and the evidence for heart failure diagnosis and therapy as a potential marker of therapeutic response, including low- and high-risk patients, were reviewed. Literature search was performed using PubMed and Google Scholar for literature relevant to CMR, late gadolinium enhancement, T1 mapping, assessment of fibrosis and remodeling, coronary artery, myocardial infarction, heart failure, and its outcomes. Expert commentary: The authors review current evidence and discuss the potential ability of CMR to guide, diagnose, plan risk strategies, and treat patients with heart failure.
Hypoxia and sterile inflammation in cystic fibrosis airways: mechanisms and potential therapies

Cystic fibrosis is one of the most common autosomal recessive genetic diseases in Caucasian populations. Diagnosis via newborn screening and targeted nutritional and antibiotic therapy have improved outcomes, however respiratory failure remains the key cause of morbidity and mortality. Progressive respiratory disease in cystic fibrosis is characterised by chronic neutrophilic airway inflammation associated with structural airway damage leading to bronchiectasis and decreased lung function. Mucus obstruction is a characteristic early abnormality in the cystic fibrosis airway, associated with neutrophilic inflammation often in the absence of detectable infection. Recent studies have suggested a link between hypoxic cell death and sterile neutrophilic inflammation in cystic fibrosis and other diseases via the IL-1 signalling pathway. In this review, we consider recent evidence regarding the cellular responses to respiratory hypoxia as a potential driver of sterile neutrophilic inflammation in the lung, current knowledge on hypoxia as a pathogenic mechanism in cystic fibrosis and the potential for current and future therapies to alleviate hypoxia-driven sterile inflammation. Hypoxia and sterile inflammation is characteristic in cystic fibrosis airways leading to lung damage in early life http://ow.ly/NnHf304acAZ
Representation of texts as complex networks: a mesoscopic approach

Statistical techniques that analyze texts, referred to as text analytics, have departed from the use of simple word count statistics towards a new paradigm. Text mining now hinges on a more sophisticated set of methods, including the representations in terms of complex networks. While well-established word-adjacency (co-occurrence) methods successfully grasp syntactical features of written texts, they are unable to represent important aspects of textual data, such as its topical structure, i.e. the sequence of subjects developing at a mesoscopic level along the text. Such aspects are often overlooked by current methodologies. In order to grasp the mesoscopic characteristics of semantical content in written texts, we devised a network model which is able to analyze documents in a multi-scale fashion. In the proposed model, a limited amount of adjacent paragraphs are represented as nodes, which are connected whenever they share a minimum semantical content. To illustrate the capabilities of our model, we present, as a case example, a qualitative analysis of "Alice's Adventures in Wonderland". We show that the mesoscopic structure of a document, modeled as a network, reveals many semantic traits of texts. Such an approach paves the way to a myriad of semantic-based applications. In addition, our approach is illustrated in a machine learning context, in which texts are classified among real texts and randomized instances.
A case of “ second generation ” disadvantage in internal migration : a challenge to theory ?

The paper uses data from the Turin Longitudinal Study (Studio longitudinale torinese, henceforth SLT) of linked census data from the 1971, 1981, 1991 and 2001 censuses to show the existence of educational inequalities among the children of regional migrants to Turin. As we will show, using the relatively sparse data on international migrants in the current SLT database and references to the literature, the patterns are surprisingly similar to those documented for children of international migrants. In other words, in this case, regional labour migration is associated with occupational and educational disadvantage among a "second generation", not dissimilar to that documented for many groups in the wake of international migration. We believe these results are not only of local interest, because they have implications for the way disadvantage is generated (or not generated) among children of migrants generally. This kind of situation of regional migration is in fact an interesting test case, because several important factors often associated with disadvantage in international migration are missing. Regional migrants were, of course, citizens, and did not have the disadvantages of being undocumented which many international migrants do, at least in the first generation. In addition, we argue that "cultural differences" between migrants and locals – often evoked to explain second generation disadvantage – were probably quite small in the Turin case so we believe other explanations are needed.
Digenic inheritance and genetic modifiers

Digenic inheritance (DI) concerns pathologies with the simplest form of multigenic etiology, implicating more than 1 gene (and perhaps the environment). True DI is when biallelic or even triallelic mutations in 2 distinct genes, in cis or in trans, are necessary and sufficient to cause pathology with a defined diagnosis. In true DI, a heterozygous mutation in each of 2 genes alone is not associated with a recognizable phenotype. Well‐documented diseases with true DI are so far rare and follow non‐Mendelian inheritance. DI is also encountered when by serendipity, pathogenic mutations responsible for 2 distinct disease entities are co‐inherited, leading to a mixed phenotype. Also, we can consider many true monogenic Mendelian conditions, which show impressively broad spectrum of phenotypes due to pseudo‐DI, as a result of co‐inheriting genetic modifiers (GMs). I am herewith reviewing examples of GM and embark on presenting some recent notable examples of true DI, with wider discussion of the literature. Undeniably, the advent of high throughput sequencing is bound to unravel more patients suffering with true DI conditions and elucidate many important GM, thus impacting precision medicine.
Low Activity Microstates During Sleep

A better understanding of sleep requires evaluating the distinct activity patterns of the brain during sleep. We performed extracellular recordings of large populations of hippocampal region CA1 neurons in freely moving rats across sleep and waking states. Throughout non-REM (non-rapid eye movement) sleep, we observed periods of diminished oscillatory and population spiking activity lasting on the order of seconds, which we refer to as “LOW” activity sleep states. LOW states featured enhanced firing in a subset of “LOW-active” cells, and greater firing in putative interneurons compared to DOWN/OFF states. LOW activity sleep was preceded and followed by increased sharp-wave ripple (SWR) activity. We also observed decreased slow-wave activity (SWA) and sleep spindles in the hippocampus local-field potential (LFP) and neocortical electroencephalogram (EEG) upon LOW onset, but only a partial rebound immediately after LOW. LOW states demonstrated LFP, EEG, and EMG patterns consistent with sleep, but frequently transitioned into microarousals (MAs) and showed EMG and LFP spectral differences from previously described small-amplitude irregular activity (SIA) during quiet waking. Their likelihood increased over the course of sleep, particularly following REM sleep. To confirm that LOW is a brain-wide phenomenon, we analyzed data from the entorhinal cortex of rats, medial prefrontal cortex, and anterior thalamus of mice, obtained from crcns.org and found that LOW states corresponded to markedly diminished activity simultaneously in all of these regions. We propose that LOW states are an important microstate within non-REM sleep that provide respite from high-activity sleep, and may serve a restorative function.
Interference Management in Full-Duplex Wireless Cellular Networks via Fractional Programming - Invited Paper

Mutual interference is a key obstacle in the realistic adoption of full-duplex (FD) technique in future wireless cellular networks. Interference is a much more pressing problem for FD system than for the conventional half-duplex (HD) system, because FD allows the same time-frequency resource to be used for both uplink and downlink, thus possibly creating myriad interference between multiple transmissions throughout the network. Without proper interference control, FD may not even outperform HD in a multicell setup. The main objective of this paper is to show that coordinated scheduling and power control enables wireless cellular networks to reap significant system-level performance improvement due to FD. Toward this end, this paper utilizes fractional programming to derive a sequence of convex reformulations that allow distributed and efficient iterative optimization. Numerical results suggest that the proposed system-level interference management can provide 30-40% rate gain for an optimized FD multicell network as compared to optimized HD.
The dual‐gate model for pentameric ligand‐gated ion channels activation and desensitization

Pentameric ligand‐gated ion channels (pLGICs) mediate fast neurotransmission in the nervous system. Their dysfunction is associated with psychiatric, neurological and neurodegenerative disorders such as schizophrenia, epilepsy and Alzheimer's disease. Understanding their biophysical and pharmacological properties, at both the functional and the structural level, thus holds many therapeutic promises. In addition to their agonist‐elicited activation, most pLGICs display another key allosteric property, namely desensitization, in which they enter a shut state refractory to activation upon sustained agonist binding. While the activation mechanisms of several pLGICs have been revealed at near‐atomic resolution, the structural foundation of desensitization has long remained elusive. Recent structural and functional data now suggest that the activation and desensitization gates are distinct, and are located at both sides of the ion channel. Such a ‘dual gate mechanism’ accounts for the marked allosteric effects of channel blockers, a feature illustrated herein by theoretical kinetics simulations. Comparison with other classes of ligand‐ and voltage‐gated ion channels shows that this dual gate mechanism emerges as a common theme for the desensitization and inactivation properties of structurally unrelated ion channels.
Noninvasive skin tightening: focus on new ultrasound techniques

Microfocused ultrasound (MFU) has been recently developed to meet the ever-growing public demand for achieving significant, noninvasive skin lifting and tightening. MFU can be focused on subcutaneous tissue where the temperature briefly reaches greater than 60°C, producing small (<1 mm3) thermal coagulation points to a depth of up to 5 mm within the mid-to-deep reticular layer of the dermis and subdermis. The intervening papillary dermal and epidermal layers of skin remain unaffected. The application of heat at these discrete thermal coagulation points causes collagen fibers in the facial planes such as the superficial musculoaponeurotic system and platysma, as well as the deep reticular dermis, to become denatured, contracting and stimulating de novo collagen. A commercially available device combines MFU with high-resolution ultrasound imaging (MFU-V), which enables visualization of tissue planes to a depth of 8 mm and allows the user to see where the MFU energy will be applied (Ultherapy®; Ulthera Inc., Mesa, AZ, USA). Using different transducers, MFU-V treatment can be customized to meet the unique physical characteristics of each patient by adjusting energy and focal depth of the emitted ultrasound. By targeting the facial superficial musculoaponeurotic system, noninvasive tightening and lifting of sagging facial and neck skin and improvements in the appearance of wrinkles can be achieved. MFU-V can also improve lines and wrinkles of the décolleté. Treatment protocols for the use of MFU-V continue to be refined, and its use in combination with other rejuvenation techniques has been demonstrated. Brief discomfort that often occurs during treatment can be minimized with oral nonsteroidal anti-inflammatory drugs. Other treatment-related adverse events include transient erythema, edema, and occasional bruising. MFU-V is best suited for patients with mild-to-moderate skin and soft tissue laxity. For older patients with severe skin laxity and marked platysmal banding, surgical treatment should be considered.
Informative Gene Selection for Cancer Classification with Microarray Data Using a Metaheuristic Framework

Objective: Cancer diagnosis is one of the most vital emerging clinical applications of microarray data. Due to the high dimensionality, gene selection is an important step for improving expression data classification performance. There is therefore a need for effective methods to select informative genes for prediction and diagnosis of cancer. The main objective of this research was to derive a heuristic approach to select highly informative genes. Methods: A metaheuristic approach with a Genetic Algorithm with Levy Flight (GA-LV) was applied for classification of cancer genes in microarrays. The experimental results were analyzed with five major cancer gene expression benchmark datasets. Result: GA-LV proved superior to GA and statistical approaches, with 100% accuracy for the dataset for Leukemia, Lung and Lymphoma. For Prostate and Colon datasets the GA-LV was 99.5% and 99.2% accurate, respectively. Conclusion: The experimental results show that the proposed approach is suitable for effective gene selection with all benchmark datasets, removing irrelevant and redundant genes to improve classification accuracy.
Sustainable blockchain-enabled services: Smart contracts

This paper introduces some of the interdependent components within the multifaceted solution our team is developing towards accelerating the functionality, complexity and versatility of blockchain-enabled services. The focus here is particularly on introducing and bringing together selected individual components of the solution to achieve a synergistic effect in expanding the functionality of blockchain-enforced smart contracts. The contributions of this paper include: (i) proposing a method for automated management of contracts with hierarchical conditionality structures through an hierarchy of intelligent agents and the use of hierarchical cryptographic key-pairs; (ii) proposing a method for efficient and secure matching and transfer of smart-contract underlyings (entities) among disparate smart contracts/subcontracts; (iii) proposing a method for producing an hierarchy of common secrets to facilitate hierarchical communication channels of increased security, and applying this method both in the context of method (i) and method (ii); and (iv) proposing the use of distributed hash tables DHT in building secure and optimized repositories in the context of method (i) and in the context method (ii), where the former involves a DHT repository of smart contracts and the latter involves a DHT repository of entities underlying smart contracts that are being exchanged among different smart contracts and subcontracts. The smart-contract focused methods introduced in this paper contribute to the overall goal towards a sustainable adaptive mechanism for processing evolving volumes, versatility, and complexity of blockchain transactions, traffic, and services. Blockchain-enabled services are efficient, secure, automated, and allowing worldwide distribution of resources. They present a more efficient and sustainable alternative to current service infrastructures within a range of domains, particularly the legal and financial domains. They also set a sustainable infrastructure for emerging Internet-of-things services.
Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery

Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs. We analyzed the melatonergic agonist drugs, agomelatine, prolonged-release melatonin, ramelteon, and tasimelteon; the dual orexin receptor antagonist suvorexant; the modulators of the α2δ subunit of voltage-sensitive calcium channels, gabapentin and pregabalin; the H1 antagonist, low-dose doxepin; and the histamine and serotonin receptor antagonists, amitriptyline, mirtazapine, trazodone, olanzapine, and quetiapine. The pharmacology and mechanism of action of these treatments and the evidence-base for the use of these drugs in clinical practice is outlined along with novel pipelines. There is evidence to recommend suvorexant and low-dose doxepin for sleep maintenance insomnia; there is also sufficient evidence to recommend ramelteon for sleep onset insomnia. Although there is limited evidence for the use of the quetiapine, trazodone, mirtazapine, amitriptyline, pregabalin, gabapentin, agomelatine, and olanzapine as treatments for insomnia disorder, these drugs may improve sleep while successfully treating comorbid disorders, with a different side effect profile than the BZDs and Z-drugs. The unique mechanism of action of each drug allows for a more personalized and targeted medical management of insomnia.