Miracle-dz/UniFAR-FTUs huggingface dataset:
Human vitreous concentrations of citicoline following topical application of citicoline 2% ophthalmic solution

Purpose To evaluate the presence and concentration of citicoline and its metabolites (choline, cytidine and uridine) in the vitreous body in human eyes after topical application of an ophthalmic solution of citicoline 2%, in vivo. Methods Twenty-one subjects affected by epiretinal membrane with surgical indication for pars-plana vitrectomy underwent treatment with 1 drop 3 times/day of a solution of citicoline 2%, 0.2% high molecular weight hyaluronic acid and 0.01% benzalkonium chloride (OMK1, Omikron Italia s.r.l., Rome, Italy) 14 days before surgery and 2 hours prior to surgery. Five additional patients served as controls and received an OMK1 vehicle solution without citicoline. The vitreous samples were taken at the beginning of the pars-plana vitrectomy and analyzed for qualitative/quantitative determination of vitreous concentration of citicoline and its metabolites by means of high performance liquid chromatography. Results The overall mean concentration of citicoline in patients treated with citicoline 2% solution was 406.72 ± 52.99 μg/mL, while the mean concentration of choline, cytidine and uridine was 180.88 ± 41.49 μg/mL, 44.45 ± 10.19 μg/mL and 330.41 ± 75.8 μg/mL, respectively. The concentration of citicoline in phakic eyes (n = 13, 366.61 ± 129.61 μg/mL) was lower compared to that found in pseudophakic eyes (n = 8, 435.89 ± 131.42 μg/mL) and the difference was not statistically significant. The concentration of citicoline in the control eyes was 45.66 ± 26.36 μg/mL, while the concentration of choline, cytidine and uridine were 17.21 ± 9.93 μg/mL, 6.24 ± 3.6 μg/mL and 172.80 ± 99.76 μg/mL, respectively. Conclusion Citicoline can reach the human vitreous in high concentration when administered in ophthalmic solution. This evidence contributes to the build-up of the pyramid of the evidences required for determining the role of citicoline administered in ophthalmic formulation in retinal and optic nerve neurodegenerative diseases.
Innendurchmesser der Vena femoralis communis als diagnostischer und prognostischer Parameter für die CVI

Ziel: Uberprufung der Hypothese uber den Zusammenhang zwischen dem Innendurchmesser der V. femoralis communis (VFC) sowie der Magna-Krosse (M-K) und der Anwesenheit und Auspragung der chronischen Veneninsuffizienz (CVI). Methode: erstmalige phlebologische Untersuchung von 199 ambulanten Patientinnen im Alter von 20-75 Jahren mit Berucksichtigung der Duplex-sonographischen Diametervermessung der proximalen Beinvenen bei Valsalva-Presversuch. Ergebnis: Im Material von insgesamt 181 rechten Beinen erschienen 54 Extremitaten klinisch unauffallig (CVI 0), 93 mit CVI 1. , 34 mit CVI 2. oder 3. Grades. Die statistische Analyse bestatigte, das grosere Durchmesser der VFC signifikant ofter mit einer klinisch manifesten CVI einhergehen. Dagegen wurde die Hypothese uber einen Zusammenhang zwischen diesem Parameter und der CVI-Progression nicht bestatigt. In der logistischen Multivarianz-Regressionsanalyse, unter Berucksichtigung des Alters, Gewichts, der Korperlange, der Varikosis, der Wiederauffullzeit und mehrerer Refluxe, wurde die Bedeutung des Diameters der VFC fur die CVI-Manifestation bestatigt, nicht aber die vom M-K-Durchmesser (grenzwertige Signifikanz). Das Risiko einer klinisch manifesten CVI bei Frauen ohne ausgedehnte Stamm-Astvarikosis mit einem Durchmesser der VFC >14,0 mm wurde 15fach hoher eingeschatzt (95% CI 3,5-65,2) als bei Frauen mit einem Durchmesser =14,0 mm. Schlusfolgerung: Der sonographische Innendurchmesser der VFC erscheint als ein wichtiger, von anderen Faktoren unabhangiger Pradiktor der CVI.
"Worth one minute": An anonymous rewarding platform for crowd-sensing systems

Readily available and affordable consumer-grade electronics, with ever-increasing sensing, computing, and communication capabilities, have provided the ground for distributed computation and data collection systems. Crowd-sensing applications rely on volunteers providing access to their personal devices—a category encompassing smartphones, wearables, vehicles, and a wide range of ‘Internet of Things’ appliances—and using them as sensors. These systems rely on the willingness of participants to invest in a common cause, which often entails explicit efforts from users, occupation of hardware resources, and risks of sharing private data. Incentives and rewarding schemes are adopted to encourage user participation. This paper introduces the "Worth One Minute" (WOM) platform: an implementation of a generalpurpose rewarding system based on anonymous vouchers. The platform is designed to reward user efforts towards the common good, rewarding their contributions and the intrinsic social value they provide, while preserving their anonymity.
Downregulation of miR-4772-3p promotes enhanced regulatory T cell capacity in malignant pleural effusion by elevating Helios levels

Abstract Background: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. Methods: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. Results: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios+ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. Conclusion: Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.
Adding Social Comparison to Open Learner Modeling

Achieving multiplication table fluency is a major concern during all primary school years and for many pupils it is considered a challenge. ‘Rote memory’ approaches that have been deployed for years in the traditional school curriculum have contributed to the prevailing assumption of pupils that Mathematics is unpleasant and uninviting. This paper presents a game-based approach to assess and gradually improve multiplication skills by combining an adaptive mechanism for identifying and resolving pupil weaknesses, while exposing parts of the learner model to the user through easily perceivable visualizations. Moreover, the game offers social comparison information and pupils can access progress data about their peers or their entire class a feature that is expected to improve self-reflection, allow for self-regulated learning and increase user motivation. This paper also presents the feedback received by the preliminary testing of the game with a representative sample of pupils and discusses the effect of allowing access to the progress of peers and summative class scores.
Modulation of the inflammatory response by triptolide and MAP kinase phosphatase-1.

ii DEDICATION . iv ACKNOWLEGMENTS . v VITA . vi LIST OF TABLES . ix LIST OF FIGURES . x LIST OF ABBREVIATIONS . xii CHAPTER 1 .
Kinetic Energy Harvesting for Wearable Medical Sensors

The process of collecting low-level kinetic energy, which is present in all moving systems, by using energy harvesting principles, is of particular interest in wearable technology, especially in ultra-low power devices for medical applications. In fact, the replacement of batteries with innovative piezoelectric energy harvesting devices can result in mass and size reduction, favoring the miniaturization of wearable devices, as well as drastically increasing their autonomy. The aim of this work is to assess the power requirements of wearable sensors for medical applications, and address the intrinsic problem of piezoelectric kinetic energy harvesting devices that can be used to power them; namely, the narrow area of optimal operation around the eigenfrequencies of a specific device. This is achieved by using complex numerical models comprising modal, harmonic and transient analyses. In order to overcome the random nature of excitations generated by human motion, novel excitation modalities are investigated with the goal of increasing the specific power outputs. A solution embracing an optimized harvester geometry and relying on an excitation mechanism suitable for wearable medical sensors is hence proposed. The electrical circuitry required for efficient energy management is considered as well.
Proteome analysis of formalin‐fixed paraffin‐embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas

Traditional serrated adenoma (TSA) remains the least understood of all the colorectal adenomas, although these lesions have been associated with a significant cancer risk, twice that of the conventional adenoma (CAD) and of the sessile serrated adenoma (SSA/P). This study was performed to investigate the proteomic profiles of the different colorectal adenomas to better understand the pathogenesis of TSA. We performed a global quantitative proteome analysis using the label‐free quantification (LFQ) method on 44 colorectal adenoma (12 TSAs, 15 CADs, and 17 SSA/Ps) and 17 normal colonic mucosa samples, archived as formalin‐fixed paraffin‐embedded blocks. Unsupervised consensus hierarchical clustering applied to the whole proteomic profile of the 44 colorectal adenomas identified four subtypes: C1 and C2 were well‐individualized clusters composed of all the CADs (15/15) and most of the SSA/Ps (13/17), respectively. This is consistent with the fact that CADs and SSA/Ps are homogeneous and distinct colorectal adenoma entities. In contrast, TSAs were subdivided into C3 and C4 clusters, consistent with the more heterogeneous entity of TSA at the morphologic and molecular levels. Comparison of the proteome expression profile between the adenoma subtypes and normal colonic mucosa further confirmed the heterogeneous nature of TSAs, which overlapped either on CADs or SSA/Ps, whereas CADs and SSAs formed homogeneous and distinct entities. Furthermore, we identified LEFTY1 a new potential marker for TSAs that may be relevant for the pathogenesis of TSA. LEFTY1 is an inhibitor of the Nodal/TGFβ pathway, which we found to be one of the most overexpressed proteins specifically in TSAs. This finding was confirmed by immunohistochemistry. Our study confirms that CADs and SSA/Ps form homogeneous and distinct colorectal adenoma entities, whereas TSAs are a heterogeneous entity and may arise from either SSA/Ps or from normal mucosa evolving through a process related to the CAD pathway. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Central Role of Subthreshold Currents in Myotonia

It is generally thought that muscle excitability is almost exclusively controlled by currents responsible for generation of action potentials. We propose that smaller ion channel currents that contribute to setting the resting potential and to subthreshold fluctuations in membrane potential can also modulate excitability in important ways. These channels open at voltages more negative than the action potential threshold and are thus termed subthreshold currents. As subthreshold currents are orders of magnitude smaller than the currents responsible for the action potential, they are hard to identify and easily overlooked. Discovery of their importance in regulation of excitability opens new avenues for improved therapy for muscle channelopathies and diseases of the neuromuscular junction. ANN NEUROL 2020;87:175–183
Gradient-Based Joint-Variables Nonnegative Matrix Factorization for Multi-Sharpening Hyperspectral Remote Sensing Data

This paper presents a fusion method generating unobservable sharpened hyperspectral remote sensing data with high spatial and spectral resolutions. This method, related to linear spectral unmixing (LSU) techniques, and based on nonnegative matrix factorization (NMF), introduces Joint-Variables NMF (JVNMF) for fusing observable low spatial resolution hyperspectral and high spatial resolution multispectral data. It optimizes a joint-variables criterion that exploits spatial and spectral degradation models between the two considered images, and therefore considers a reduced number of unknown variables. This approach, called Grd-JVNMF, is a gradient-based method and uses iterative update rules. The proposed method is applied to realistic synthetic and semi-real data, and its effectiveness, in spatial and spectral domains, is evaluated with established performance criteria. Experimental results show that the proposed Grd-JVNMF method yields multi-sharpened hyperspectral data with good spectral and spatial fidelities. These tests also show that the proposed method outperforms tested literature ones.
The Emergence of a Stable Neuronal Ensemble from a Wider Pool of Activated Neurons in the Dorsal Medial Prefrontal Cortex during Appetitive Learning in Mice

Animals selectively respond to environmental cues associated with food reward to optimize nutrient intake. Such appetitive conditioned stimulus–unconditioned stimulus (CS-US) associations are thought to be encoded in select, stable neuronal populations or neuronal ensembles, which undergo physiological modifications during appetitive conditioning. These ensembles in the medial prefrontal cortex (mPFC) control well-established, cue-evoked food seeking, but the mechanisms involved in the genesis of these ensembles are unclear. Here, we used male Fos-GFP mice that express green fluorescent protein (GFP) in recently behaviorally activated neurons, to reveal how dorsal mPFC neurons are recruited and modified to encode CS-US memory representations using an appetitive conditioning task. In the initial conditioning session, animals did not exhibit discriminated, cue-selective food seeking, but did so in later sessions indicating that a CS-US association was established. Using microprism-based in vivo 2-Photon imaging, we revealed that only a minority of neurons activated during the initial session was consistently activated throughout subsequent conditioning sessions and during cue-evoked memory recall. Notably, using ex vivo electrophysiology, we found that neurons activated following the initial session exhibited transient hyperexcitability. Chemogenetically enhancing the excitability of these neurons throughout subsequent conditioning sessions interfered with the development of reliable cue-selective food seeking, indicated by persistent, nondiscriminated performance. We demonstrate how appetitive learning consistently activates a subset of neurons to form a stable neuronal ensemble during the formation of a CS-US association. This ensemble may arise from a pool of hyperexcitable neurons activated during the initial conditioning session. SIGNIFICANCE STATEMENT Appetitive conditioning endows cues associated with food with the ability to guide food-seeking, through the formation of a food-cue association. Neuronal ensembles in the mPFC control established cue-evoked food-seeking. However, how neurons undergo physiological modifications and become part of an ensemble during conditioning remain unclear. We found that only a minority of dorsal mPFC neurons activated on the initial conditioning session became consistently activated during conditioning and memory recall. These initially activated neurons were also transiently hyperexcitable. We demonstrate the following: (1) how stable neuronal ensemble formation in the dorsal mPFC underlies appetitive conditioning; and (2) how this ensemble may arise from hyperexcitable neurons activated before the establishment of cue-evoked food seeking.
Improvements in diabetic albuminuria and podocyte differentiation following Roux-en-Y gastric bypass surgery

Background: Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported. Methods: We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease. Results: At 12- to 18-month post-operative follow-up in patients at moderate or high risk of chronic kidney disease, significant reductions in albuminuria were observed across all tertiles of baseline albumin–creatinine ratio, with remission of albuminuria occurring in 78% of patients. Relative to sham-operated control animals, weight loss and improvements in glycaemia following Roux-en-Y gastric bypass surgery in Zucker diabetic fatty rats were paralleled by normalisation of glomerular tuft-size, reductions in podocyte expression of desmin, and preservation of podocyte foot process morphology. Conclusion: Improvements in podocyte differentiation likely underpin the reductions in albuminuria observed following Roux-en-Y gastric bypass surgery.
Development of a Gut-on-a-Chip Model for High Throughput Disease Modeling and Drug Discovery

A common bottleneck in any drug development process is finding sufficiently accurate models that capture key aspects of disease development and progression. Conventional drug screening models often rely on simple 2D culture systems that fail to recapitulate the complexity of the organ situation. In this study, we show the application of a robust high throughput 3D gut-on-a-chip model for investigating hallmarks of inflammatory bowel disease (IBD). Using the OrganoPlate platform, we subjected enterocyte-like cells to an immune-relevant inflammatory trigger in order to recapitulate key events of IBD and to further investigate the suitability of this model for compound discovery and target validation activities. The induction of inflammatory conditions caused a loss of barrier function of the intestinal epithelium and its activation by increased cytokine production, two events observed in IBD physiopathology. More importantly, anti-inflammatory compound exposure prevented the loss of barrier function and the increased cytokine release. Furthermore, knockdown of key inflammatory regulators RELA and MYD88 through on-chip adenoviral shRNA transduction alleviated IBD phenotype by decreasing cytokine production. In summary, we demonstrate the routine use of a gut-on-a-chip platform for disease-specific aspects modeling. The approach can be used for larger scale disease modeling, target validation and drug discovery purposes.
Spatial Information Inference Net: Road Extraction Using Road-Specific Contextual Information

For road extraction tasks in VHR satellite imagery, a deep neural network may perform well. But a network with certain reasoning ability as human will get a more satisfying result. To this end, we focus on how to effectively model the context information of the road and propose a well-designed spatial information inference structure (SIIS) which can add into any typical semantic segmentation network. The network with SIIS called SII-Net can not only learn the local visual characteristic of the road but also the global spatial structure information (such as the continuity and trend of the road). So, it can effectively solve the challenging occlusion problem in road detection and well preserve the continuity of the extracted road. The experimental results of two datasets show that the proposed method can improve the comprehensive performance of road extraction.
Resource Allocation Based on Interference Alignment With Clustering for Data Stream Maximization in Dense Small Cell Networks

In this paper, by allocating the limited subchannel resources based on interference alignment (IA) with clustering to mitigate the severe co-tier interference in dense small cell networks (SCNs), we aim at maximizing the number of data streams achieved by all small cell user equipments (SUEs) while guaranteeing the data stream requirement for each SUE. As the corresponding optimization problem is NP-hard, we propose a two-phases algorithm based on graph theory to obtain a suboptimal but efficient solution, which requires much lower complexity and notably reduced feedback overhead. In the first phase, all SBS-SUE pairs are grouped into disjoint clusters by the recursive partition of the constructed graph, where the edge weight is only determined by the path losses from small cell base stations (SBSs) to SUEs, so the estimation of perfect global channel state information (CSI) is avoided. Furthermore, when guaranteeing that IA is feasible within each cluster, the number of formed clusters and the size of each cluster are determined by the distributions of dense SCNs instead of being specified. In the second phase, by further treating each cluster as a new vertex, graph coloring algorithm is proposed for subchannel allocation, which only requires to estimate the perfect CSI within each cluster. The analysis of computational complexity demonstrates that the proposed two-phases algorithm has a much lower complexity compared with the optimal solution obtained by the exhaustive search. Numerical results show that the proposed solution outperforms other related schemes and exhibits a performance close to the optimal solution.
Oligodendrocytes in Development, Myelin Generation and Beyond

Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer’s disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes.