Miracle-dz/UniFAR-FTUs huggingface dataset:
Progress of Induced Pluripotent Stem Cell Technologies to Understand Genetic Epilepsy

The study of the pathomechanisms by which gene mutations lead to neurological diseases has benefit from several cellular and animal models. Recently, induced Pluripotent Stem Cell (iPSC) technologies have made possible the access to human neurons to study nervous system disease-related mechanisms, and are at the forefront of the research into neurological diseases. In this review, we will focalize upon genetic epilepsy, and summarize the most recent studies in which iPSC-based technologies were used to gain insight on the molecular bases of epilepsies. Moreover, we discuss the latest advancements in epilepsy cell modeling. At the two dimensional (2D) level, single-cell models of iPSC-derived neurons lead to a mature neuronal phenotype, and now allow a reliable investigation of synaptic transmission and plasticity. In addition, functional characterization of cerebral organoids enlightens neuronal network dynamics in a three-dimensional (3D) structure. Finally, we discuss the use of iPSCs as the cutting-edge technology for cell therapy in epilepsy.
A Fail-Operational Control Architecture Approach and Dead-Reckoning Strategy in Case of Positioning Failures

Presently, in the event of a failure in Automated Driving Systems, control architectures rely on hardware redundancies over software solutions to assure reliability or wait for human interaction in takeover requests to achieve a minimal risk condition. As user confidence and final acceptance of this novel technology are strongly related to enabling safe states, automated fall-back strategies must be assured as a response to failures while the system is performing a dynamic driving task. In this work, a fail-operational control architecture approach and dead-reckoning strategy in case of positioning failures are developed and presented. A fail-operational system is capable of detecting failures in the last available positioning source, warning the decision stage to set up a fall-back strategy and planning a new trajectory in real time. The surrounding objects and road borders are considered during the vehicle motion control after failure, to avoid collisions and lane-keeping purposes. A case study based on a realistic urban scenario is simulated for testing and system verification. It shows that the proposed approach always bears in mind both the passenger’s safety and comfort during the fall-back maneuvering execution.
Burden of comorbidities is higher among elderly survivors of oropharyngeal cancer compared with controls

The prevalence of survivors of oropharyngeal cancer (OPC) is increasing due to improved survival for individuals with human papillomavirus (HPV)–related disease. Although elderly survivors of OPC are known to have a high burden of comorbidities, to the authors' knowledge it is unknown how this compares with a similar cohort without a history of cancer.
Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles Using Intrinsic Fluorescence

Reconstituted high-density lipoprotein (HDL) containing apolipoprotein A-I (Apo A-I) mimics the structure and function of endogenous (human plasma) HDL due to its function and potential therapeutic utility in atherosclerosis, cancer, neurodegenerative diseases, and inflammatory diseases. Recently, a new class of HDL mimetics has emerged, involving peptides with amino acid sequences that simulate the the primary structure of the amphipathic alpha helices within the Apo A-I protein. The findings reported in this communication were obtained using a similar amphiphilic peptide (modified via conjugation of a myristic acid residue at the amino terminal aspartic acid) that self-assembles (by itself) into nanoparticles while retaining the key features of endogenous HDL. The studies presented here involve the macromolecular assembly of the myristic acid conjugated peptide (MYR-5A) into nanomicellar structures and its characterization via steady-state and time-resolved fluorescence spectroscopy. The structural differences between the free peptide (5A) and MYR-5A conjugate were also probed, using tryptophan fluorescence, Fӧrster resonance energy transfer (FRET), dynamic light scattering, and gel exclusion chromatography. To our knowledge, this is the first report of a lipoprotein assembly generated from a single ingredient and without a separate lipid component. The therapeutic utility of these nanoparticles (due to their capablity to incorporate a wide range of drugs into their core region for targeted delivery) was also investigated by probing the role of the scavenger receptor type B1 in this process. SIGNIFICANCE STATEMENT Although lipoproteins have been considered as effective drug delivery agents, none of these nanoformulations has entered clinical trials to date. A major challenge to advancing lipoprotein-based formulations to the clinic has been the availability of a cost-effective protein or peptide constituent, needed for the assembly of the drug/lipoprotein nanocomplexes. This report of a robust, spontaneously assembling drug transport system from a single component could provide the template for a superior, targeted drug delivery strategy for therapeutics of cancer and other diseases (Counsell and Pohland, 1982).
Locally Adaptive Total p-Variation Regularization for Non-Rigid Image Registration With Sliding Motion

Due to the complicated thoracic movements which contain both sliding motion occurring at lung surfaces and smooth motion within individual organs, respiratory estimation is still an intrinsically challenging task. In this paper, we propose a novel regularization term called locally adaptive total p-variation (LaTpV) and embed it into a parametric registration framework to accurately recover lung motion. LaTpV originates from a modified Lp-norm constraint (1 < p < 2), where a prior distribution of p modeled by the Dirac-shaped function is constructed to specifically assign different values to voxels. LaTpV adaptively balances the smoothness and discontinuity of the displacement field to encourage an expected sliding interface. Additionally, we also analytically deduce the gradient of the cost function with respect to transformation parameters. To validate the performance of LaTpV, we not only test it on two mono-modal databases including synthetic images and pulmonary computed tomography (CT) images, but also on a more difficult thoracic CT and positron emission tomography (PET) dataset for the first time. For all experiments, both the quantitative and qualitative results indicate that LaTpV significantly surpasses some existing regularizers such as bending energy and parametric total variation. The proposed LaTpV based registration scheme might be more superior for sliding motion correction and more potential for clinical applications such as the diagnosis of pleural mesothelioma and the adjustment of radiotherapy plans.
Charge Displacement Analysis—A Tool to Theoretically Characterize the Charge Transfer Contribution of Halogen Bonds

Theoretical bonding analysis is of prime importance for the deep understanding of the various chemical interactions, covalent or not. Among the various methods that have been developed in the last decades, the analysis of the Charge Displacement function (CD) demonstrated to be useful to reveal the charge transfer effects in many contexts, from weak hydrogen bonds, to the characterization of σ hole interactions, as halogen, chalcogen and pnictogen bonding or even in the decomposition of the metal-ligand bond. Quite often, the CD analysis has also been coupled with experimental techniques, in order to give a complete description of the system under study. In this review, we focus on the use of CD analysis on halogen bonded systems, describing the most relevant literature examples about gas phase and condensed phase systems. Chemical insights will be drawn about the nature of halogen bond, its cooperativity and its influence on metal-ligand bond components.
The efficacy of sour tea (Hibiscus sabdariffa L.) on selected cardiovascular disease risk factors: A systematic review and meta‐analysis of randomized clinical trials

This study sought to summarize clinical evidence of sour tea (Hibiscus sabdariffa L.) administration on cardiovascular disease risk factors. PubMed, Scopus, Institute for Scientific Information Web of Science, and Google Scholar were systematically searched from inception to June 2019 to identify randomized clinical trials, which assessed the effect of sour tea consumption on lipid profiles, fasting plasma glucose, and blood pressure in adult populations. Mean and standard deviation for each parameter were extracted to calculate effect size. Cochrane Collaboration tools were used to evaluate risk of bias assessment. A total of seven randomized clinical trials consisting 362 participants were included in the meta‐analysis. Pooled effect size demonstrated that sour tea consumption significantly reduces fasting plasma glucose (−3.67 mg/dl, 95% confidence interval, CI [−7.07, −0.27]; I2 = 37%), systolic blood pressure (−4.71 mmHg, 95% CI [−7.87, −1.55]; I2 = 53%), and diastolic blood pressure (−4.08 mmHg, 95% CI [−6.48, −1.67]; I2 = 14%). Although no significant effect was observed on triacylglycerol, total cholesterol, and high‐density lipoprotein cholesterol following sour tea consumption, a trend toward a significant reduction was found in low‐density lipoprotein cholesterol serum concentrations (p = 0.08). This systematic review and meta‐analysis suggests that sour tea consumption could have beneficial effect in controlling glycemic status and blood pressure among adult population.
The Nucleolin Antagonist N6L Inhibits LINE1 Retrotransposon Activity in Non-Small Cell Lung Carcinoma Cells

Lung cancer is the most common cause of cancer death in the United States. The genome of non-small cell lung cancer (NSCLC), the most frequent lung cancer type, is strongly affected by Long Interspersed Nuclear Element (LINE1) insertions. Active LINE1s are repetitive DNA sequences that can amplify themselves in the genome utilizing a retrotransposition mechanism whereby LINE1 is copied via reverse transcription and inserted at target sites. ORF1p and ORF2p are LINE1 encoded proteins essential for LINE1 retrotransposition. LINE1s are silenced epigenetically in somatic tissues, and their reactivation has been associated with cancer pathogenesis. Here, we present evidence that nucleolin (NCL) regulates expression of LINE1-ORF1p (L1-ORF1p) in NSCLC cells. Genetic knockdown of NCL significantly inhibited expression of L1-ORF1p in various NSCLC cell lines. Treatment with the investigational NCL antagonist N6L ablated L1-ORF1p expression in all cell lines constitutively expressing L1-ORFp. N6L displayed a stronger antiproliferative activity in NSCLC tumor cell lines expressing the highest L1-ORF1p protein levels. Moreover, N6L treatment of nude mice bearing NSCLC tumor xenografts blocked L1-ORF1p expression and effectively inhibited tumor growth. These data indicate that L1-ORF1p expression is regulated by NCL and identify NCL as a novel promising target for pharmacological inhibition of LINE1.
Adsorption of Organic Friction Modifier Additives.

Organic friction modifier additives (OFMs) are surfactant molecules added to engine oils to reduce friction in the boundary lubrication regime. They are thought to work by forming an absorbed layer which provides low friction. This paper studied the relationship between the adsorption of OFMs and their friction and wear reducing properties in a rubbing contact formed by a stationary glass ball and a rotating silicon disk under the boundary lubrication regime. The effect of molecular structure was investigated by using OFMs of various tail saturation and head group chemistry. OFM tested were oleic acid, octadecylamine, oleylamine and glycerol monooleate. The thickness of an OFM adsorbed layer in hexadecane, examined in-situ by spectroscopic ellipsometry and quartz crystal microbalance (QCM), depends on the molecular structure and the concentration of the OFM. As expected, saturated, linear chain gives the thickest film. A critical OFM layer thickness of about 0.6 nm is necessary to achieve low initial and maximum friction. The thicker OFM layers are accompanied by narrower wear tracks, which are rougher than the wider, smoother wear tracks formed with thinner OFM layers. The interplay between the thickness of the OFM layer and wear track surface roughness results in all OFM layers having similar steady friction. This shows that the apparent effect of OFM depends on the stage of rubbing test: initially on friction; and then subsequently on surface damage. Despite OFMs and the base oil having similar refractive indices, ellipsometry was found to be a suitable technique for examining the adsorption of OFM additives from an oil based solution, and showed reasonable correlation with QCM results.
Bipartite Tracking Consensus of Generic Linear Agents With Discrete-Time Dynamics Over Cooperation–Competition Networks

This article addresses the bipartite tracking consensus for a set of mobile autonomous agents over directed cooperation–competition networks. Here, cooperative and competitive interactions among the agents are described by positive and negative edges of the directed network topology, respectively. Both fixed and switching network topologies are considered. For the case with fixed network topology, the matrix product technique is utilized to derive the convergence result. For the case with switching network topologies, some key results related to the composition of binary relations are the main technical tools of analyzing the error system. In addition, the upper bound for the spectral radius of the system matrix is given to ensure the convergence of the system even if the single uncoupled system is strictly unstable. The applicability of the derived results is verified through two simulation experiments.
Evaluation of the Stability of Fatty Acids in Erythrocytes from Human Umbilical Cord.

The interest in the amount of polyunsaturated fatty acids (PUFA) in the umbilical cord blood (UCB) is increasing, but the stability of erythrocyte PUFA in these samples during storage and washing of the erythrocytes has not been directly evaluated. The purpose of this study was to analyze the effect of the lapse of time on the fatty acid (FA) content from UCB sample collection and maintained at 4 °C (0-12 h) until erythrocyte separation and washing. Palmitic acid (16:0), stearic acid (18:0), 18:1n-7/n-9, linoleic acid (18:2n-6), arachidonic acid (20:4n-6), 22:4n-6, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and docosahexaenoic acid (22:6n-3) together accounted for 87% of the FA profile in the umbilical vein erythrocytes. No difference was observed in the concentration of any of the FA studied, nor in the sum of saturated fatty acids (SFA), PUFA, or LC-PUFA in umbilical erythrocytes obtained at delivery and stored up to 12 h before the separation of erythrocytes. However, if a washing step was included in the processing of the erythrocytes, a decrease in the concentration of 16:0, 18:0, 18:3n-3, 20:4n-6, 22:4n-6, total SFA, PUFA, LC-PUFA, and n-6 LC-PUFA was evidenced, compared to unwashed erythrocytes. The FA concentration in umbilical cord erythrocytes did not change between samples stored from 0 to 12 h until erythrocyte separation. Erythrocyte washing before storage decreased the concentration of significant individual and total SFA, PUFA, and LC-PUFA. These results should be considered when planning the collection of UCB samples for the study of fatty acid concentration due to the nonscheduled timing of deliveries.
Distinct genomic traits of acral and mucosal melanomas revealed by targeted mutational profiling

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non‐cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture‐based next‐generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm‐level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non‐cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.
Neuroprotective and Neurestorative Effects of Epo and VEGF: Perspectives for New Therapeutic Approaches to Neurological Diseases.

BACKGROUND Erythropoietin (Epo) and vascular endothelial growth factor (VEGF) are two vasoactive molecules with essential trophic effects for brain development. The expression and secretion of both molecules increase in response to neuronal damage and they exert protective and restorative effects, which may also be accompanied by adverse side effects. OBJECTIVE We review the most relevant evidence on the neuroprotective and neurorestorative effects of Epo and VEGF in three of the most frequent neurological disorders, namely, stroke, epilepsy and Alzheimer's disease, to develop new therapeutic approaches. METHOD Several original scientific manuscripts and reviews that have discussed the evidence in critical way, considering both the beneficial and adverse effects of Epo and VEGF in the selected neurological disorders, were analysed. In addition, throughout this review, we propose several considerations to take into account in the design of therapeutic approaches based on Epo and VEGF signalling. RESULTS Although the three selected disorders are triggered by different mechanisms, they evolve through similar processes: excitotoxicity, oxidative stress, neuroinflammation, neuronal death, glial reactivity and vascular remodelling. Epo and VEGF exert neuroprotective and neurorestorative effects by acting on these processes due to their pleiotropism. In general, the evidence shows that both Epo and VEGF reduce neuronal death but that at the vascular level, their effects are contradictory. CONCLUSION Because the Epo and VEGF signalling pathways are connected in several ways, we conclude that more experimental studies, primarily studies designed to thoroughly assess the functional interactions between Epo and VEGF in the brain under both physiological and pathophysiological conditions, are needed.
Development and validation of the audio processor satisfaction questionnaire (APSQ) for hearing implant users

Abstract Objective: The satisfaction experienced with using an audio processor is very important to hearing implant system users. Currently there are no measures that can be used to assess user satisfaction with an audio processor. This study aims to develop and validate a specific and standardised questionnaire that focuses on user satisfaction with their audio processor. Design: A preliminary version of the questionnaire was initially developed by experts in the field. Following validation of these results, the final version of the Audio Processor Satisfaction Questionnaire (APSQ) was developed consisting of 15 items. Item analyses and questionnaire validation measurements were assessed. Study sample: Sixty-nine subjects were recruited and asked to complete the APSQ twice within 2–4 weeks. Results: Subjects reported a high user satisfaction with the questionnaire and with their audio processor. The questionnaire had good reliability and results for test-retest reliability were high and significant across all items and across subscale analyses. Conclusion: Item analyses and reliability analyses show that the questionnaire is a valid and reliable tool to assess user satisfaction across different audio processors and hearing implant systems. The APSQ is a quick and easy tool to measure user satisfaction with their audio processor.
Importance of Outcome Domain for Patients With Musculoskeletal Pain: Characterizing Subgroups and Their Response to Treatment

Abstract Background Patient-centered care models allow for the ability to tailor treatment to outcomes of importance to patients. Objective The purposes of this study were to (1) define patient subgroups based on outcomes of importance; (2) determine whether patient subgroups based on outcomes of importance differed in demographic, clinical, and psychological measures; and (3) determine whether outcome domain subgroups differed in treatment responses. Design This was a prospective, longitudinal observational study. Methods This was a secondary analysis of the Optimal Screening for Prediction of Referral and Outcome study. Patients in the development phase completed the Patient Centered Outcome Questionnaire (PCOQ) and questionnaires related to negative mood, fear avoidance, and positive coping, as well as region-specific questionnaires. Patients in the validation cohort completed the PCOQ, measures of treatment satisfaction and region-specific questionnaires at 4 weeks, 6 months, and 1 year. A hierarchical agglomerative cluster analysis identified profiles based on importance outcomes as determined by the PCOQ. Analysis of variance and chi-squared assessed baseline subgroup differences in demographics, psychological factors, and clinical outcomes. Repeated-measure analysis of variance considered subgroup differences in outcomes longitudinally. Results Cluster analysis identified 3 subgroups: (1) “Multiple Outcome Domains Important” subgroup characterized by high importance attached to improvement in all domains, (2) “Pain and Function Outcomes Important” subgroup characterized by high importance attached to improvement in pain and interference, and (3) “Pain Important” subgroup characterized by greatest importance attached to improvement in pain. Limitations Our sample included patients from outpatient physical therapy and may not be representative of patients in other settings. Conclusion Patients can be characterized by the importance attached to improvement in outcome domains. The identified subgroups differed in baseline measures as well as response to treatment.