Miracle-dz/UniFAR-FTUs huggingface dataset:
The Rheumatology Drugs for COVID-19 Management: Which and When?

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. ‘Repurposing’ immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patients.
Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients

To date, there is no severe acute respiratory syndrome coronavirus 2-(SARS-CoV-2)-specific prognostic biomarker available. We assessed whether SARS-CoV-2 cycle threshold (Ct) value at diagnosis could predict novel CoronaVirus Disease 2019 (COVID-19) severity, clinical manifestations, and six-month sequelae. Hospitalized and outpatient cases were randomly sampled from the diagnoses of March 2020 and data collected at 6 months by interview and from the regional database for COVID-19 emergency. Patients were stratified according to their RNA-dependent-RNA-polymerase Ct in the nasopharyngeal swab at diagnosis as follows: Group A ≤ 20.0, 20.0 < group B ≤ 28.0, and Group C > 28.0. Disease severity was classified according to a composite scale evaluating hospital admission, worst oxygen support required, and survival. Two hundred patients were included, 27.5% in Groups A and B both, 45.0% in Group C; 90% of patients were symptomatic and 63.7% were hospitalized. The median time from COVID-19 onset to swab collection was five days. Lethality, disease severity, type, and number of signs and symptoms, as well as six-month sequelae distributed inversely among the groups with respect to SARS-CoV-2 Ct. After controlling for confounding, SARS-CoV-2 Ct at diagnosis was still associated with COVID-19-related death (p = 0.023), disease severity (p = 0.023), number of signs and symptoms (p < 0.01), and presence of six-month sequelae (p < 0.01). Early quantification of SARS-CoV-2 may be a useful predictive marker to inform differential strategies of clinical management and resource allocation.
Variability of the Genes Involved in the Cellular Redox Status and Their Implication in Drug Hypersensitivity Reactions

Adverse drug reactions are a major cause of morbidity and mortality. Of the great diversity of drugs involved in hypersensitivity drug reactions, the most frequent are non-steroidal anti-inflammatory drugs followed by β-lactam antibiotics. The redox status regulates the level of reactive oxygen and nitrogen species (RONS). RONS interplay and modulate the action of diverse biomolecules, such as inflammatory mediators and drugs. In this review, we address the role of the redox status in the initiation, as well as in the resolution of inflammatory processes involved in drug hypersensitivity reactions. We summarize the association findings between drug hypersensitivity reactions and variants in the genes that encode the enzymes related to the redox system such as enzymes related to glutathione: Glutathione S-transferase (GSTM1, GSTP, GSTT1) and glutathione peroxidase (GPX1), thioredoxin reductase (TXNRD1 and TXNRD2), superoxide dismutase (SOD1, SOD2, and SOD3), catalase (CAT), aldo-keto reductase (AKR), and the peroxiredoxin system (PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, PRDX6). Based on current evidence, the most relevant candidate redox genes related to hypersensitivity drug reactions are GSTM1, TXNRD1, SOD1, and SOD2. Increasing the understanding of pharmacogenetics in drug hypersensitivity reactions will contribute to the development of early diagnostic or prognosis tools, and will help to diminish the occurrence and/or the severity of these reactions.
Influence of exercise test on platelet function in patients with coronary arterial disease

Abstract Background: Exercise test (ET) may have adverse effects on platelet function and induce acute thrombotic events in patients with coronary artery disease (CAD). The aim of this study is to investigate the platelet function and evaluate the risk of thrombotic events in CAD patients during ET. Methods: Pubmed, Embase, Cochrane Library, and Web of Science were searched for a systematic review from initiation to October 2019. The inclusion criteria were controlled clinical trails as study design; investigating platelet function in CAD patients during ET; with ET carried out by treadmill or bicycle ergometer; written in English. Included articles were screened based on title/abstract and full-text review by 2 independent reviewers. Platelet aggregation (PA), platelet surface expression of CD62p and PAC-1, plasma levels of platelet factor 4 (PF4) and beta-thromboglobulin (β-TG) were evaluated before and after ET. Results: Eighteen articles were included out of the 427 references initially identified. In most of the studies included ET was terminated because of limited symptoms. Prior to ET, no difference in platelet aggregation was observed in CAD patients compared with healthy controls in majority of the studies, with or without the treatment with Aspirin. Dual anti-platelet therapy suppressed adenosine diphosphate (ADP)-induced platelet aggregation at rest. After ET, platelet aggregation, the serum levels of β-thromboglobulin were found unchanged in majority of studies and platelet factor-4 were found unchanged in half of studies. The expression of platelet surface markers were elevated by ET in a few study. Conclusion: Symptom-limited exercise test did not affect platelet function in patients with coronary artery disease; however exercise to higher intensity may induce platelet activation.
Problematic Social Media Use and Health among Adolescents

(1) Background: The use of social media has become an integral part of adolescents’ daily lives. However, the intensive use of social media can develop into a health-threatening addiction, but unfavourable health consequences can occur even with less use. Social media user groups categorized as no-risk, moderate risk (of developing problematic behaviour), and problematic use were examined with reference to their prevalence, their associations with individual determinants and health, and the increased health risk between groups. (2) Methods: The Finnish nationally representative HBSC data (persons aged 11, 13, and 15, n = 3408) and descriptive and binary logistic regression analysis were applied. (3) Results: Problematic social media use (9.4%) was most common among older age groups, and among persons with moderate/low school achievement, low health literacy, and low parental monitoring. Belonging to a moderate risk group (33.5%) was most frequent among girls, and among adolescents with low/moderate parental monitoring and health literacy. All the negative health indicators systematically increased if the respondent belonged to a moderate risk or problematic use group. (4) Conclusions: The study confirmed the association between problematic social media use and negative health outcomes and highlighted the need to pay close attention to adolescents at moderate risk who exhibited negative health outcomes.
Allosteric and ATP-Competitive MEK-Inhibition in a Novel Spitzoid Melanoma Model with a RAF- and Phosphorylation-Independent Mutation

Simple Summary Spitzoid melanoma is a rare tumor type and so far preclinical models for translational research have also been also lacking. We established a cell line from a metastatic spitzoid melanoma that is, according to our knowledge, the first cell model from this tumor type. The cells carried a novel activating mutation in the region of the MEK1 protein that influences the sensitivity of the mutant protein to MEK inhibitors. We tested the cells’ sensitivity to clinically used and newly developed MEK inhibitors in both in vitro and in vivo models. The clinically approved MEK inhibitor strongly reduced both in vitro and in vivo tumor growth and might be an effective therapy for tumors with this kind of MEK mutation. Abstract Spitzoid melanoma is a rare malignancy with histological characteristics similar to Spitz nevus. It has a diverse genetic background and in adults, a similarly grim clinical outcome as conventional malignant melanoma. We established a spitzoid melanoma cell line (PF130) from the pleural effusion sample of a 37-year-old male patient. We found that the cell line carries a rare MEK1 mutation (pGlu102_Lys104delinsGln) that belongs to the RAF- and phosphorylation-independent subgroup of MEK1 alternations supposedly insensitive to allosteric MEK inhibitors. The in vivo tumorigenicity was tested in three different models by injecting the cells subcutaneously, intravenously or into the thoracic cavity of SCID mice. In the intrapleural model, macroscopic tumors formed in the chest cavity after two months, while subcutaneously and intravenously delivered cells showed limited growth. In vitro, trametinib—but not selumentinib—and the ATP-competitive MEK inhibitor MAP855 strongly decreased the viability of the cells and induced cell death. In vivo, trametinib but not MAP855 significantly reduced tumor growth in the intrapleural model. To the best of our knowledge, this is the first patient-derived melanoma model with RAF- and phosphorylation-independent MEK mutation and we demonstrated its sensitivity to trametinib.
Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity

Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)2 core, was encapsulated within the apoferritin (AFt) nanocage. UV-Vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy measurements confirmed metallodrug encapsulation and allowed us to determine the average amount of AP-1 trapped inside the cage. The X-ray structure of AP-1-encapsulated AFt was solved at 1.50 Å. Diffraction data revealed that an AP-1 fragment coordinates the side chain of a His residue. The biological activity of AP-1-loaded AFt was comparatively tested on a few representative cancer and non-cancer cell lines. Even though the presence of the cage reduces the overall cytotoxicity of AP-1, it improves its selectivity towards cancer cells.
The Need for Head Space: Brachycephaly and Cerebrospinal Fluid Disorders

Brachycephalic dogs remain popular, despite the knowledge that this head conformation is associated with health problems, including airway compromise, ocular disorders, neurological disease, and other co-morbidities. There is increasing evidence that brachycephaly disrupts cerebrospinal fluid movement and absorption, predisposing ventriculomegaly, hydrocephalus, quadrigeminal cistern expansion, Chiari-like malformation, and syringomyelia. In this review, we focus on cerebrospinal fluid physiology and how this is impacted by brachycephaly, airorhynchy, and associated craniosynostosis.
Effect of Kelulut Honey Nanoparticles Coating on the Changes of Respiration Rate, Ascorbic Acid, and Total Phenolic Content of Papaya (Carica papaya L.) during Cold Storage

This study evaluated the respiration rate of coated and uncoated (control) papayas (Carica papaya L.) with 15% of Kelulut honey (KH) nanoparticles (Nps) coating solution during cold storage at 12 ± 1 °C for 21 days. The respiration rate of the papayas significantly changed during storage, with an increase in CO2 and a decrease in O2 and C2H4, while the ascorbic acid and total phenolic content was maintained. The changes in respiration rate were rather slower for coated papayas when compared to control ones. A kinetic model was established from the experimental data to describe the changes of O2, CO2, and C2H4 production in papayas throughout the storage period. All O2, CO2, and C2H4 were experimentally retrieved from a closed system method and then represented by the Peleg model. The outcomes indicated the Peleg constant K1 and K2, which were gained from linear regression analysis and coefficients of determination (R2), seemed to fit well with the experimental data, whereby the R2 values exceeded 0.85 for both coated and control papayas. The model confirmed both the capability and predictability aspects of the respiration rate displayed by papayas coated with KH Nps throughout the cold storage period. This is supported by the differences in the stomatal aperture of coated and control papaya shown by microstructural images.
Influence of Systematic Gaze Patterns in Navigation and Search Tasks with Simulated Retinitis Pigmentosa

People living with a degenerative retinal disease such as retinitis pigmentosa are oftentimes faced with difficulties navigating in crowded places and avoiding obstacles due to their severely limited field of view. The study aimed to assess the potential of different patterns of eye movement (scanning patterns) to (i) increase the effective area of perception of participants with simulated retinitis pigmentosa scotoma and (ii) maintain or improve performance in visual tasks. Using a virtual reality headset with eye tracking, we simulated tunnel vision of 20° in diameter in visually healthy participants (n = 9). Employing this setup, we investigated how different scanning patterns influence the dynamic field of view—the average area over time covered by the field of view—of the participants in an obstacle avoidance task and in a search task. One of the two tested scanning patterns showed a significant improvement in both dynamic field of view (navigation 11%, search 7%) and collision avoidance (33%) when compared to trials without the suggested scanning pattern. However, participants took significantly longer (31%) to finish the navigation task when applying this scanning pattern. No significant improvements in search task performance were found when applying scanning patterns.
Anion dynamics in the first 10 milliseconds of an argon–acetylene radio-frequency plasma

The time evolution of the smallest anions (C2H− and H2CC−), just after plasma ignition, is studied by means of microwave cavity resonance spectroscopy (MCRS) in concert with laser-induced photodetachment under varying gas pressure and temperature in an argon–acetylene radio-frequency (13.56 MHz) plasma. These anions act as an initiator for spontaneous dust particle formation in these plasmas. With an intense 355 nm Nd : YAG laser pulse directed through the discharge, electrons are detached only from these anions present in the laser path. This results in a sudden increase in the electron density in the plasma, which can accurately and with sub-microsecond time resolution be measured with MCRS. By adjusting the time after plasma ignition at which the laser is fired through the discharge, the time evolution of the anion density can be studied. We have operated in the linear regime: the photodetachment signal is proportional to the laser intensity. This allowed us to study the trends of the photodetachment signal as a function of the operational parameters of the plasma. The density of the smallest anions steadily increases in the first few milliseconds after plasma ignition, after which it reaches a steady state. While keeping the gas density constant, increasing the gas temperature in the range 30–120 °C limits the number of smallest anions and saturates at a temperature of about 90 °C. A reaction pathway is proposed to explain the observed trends.
Preparation and Characterization of Nanoparticle-Doped Polymer Inclusion Membranes. Application to the Removal of Arsenate and Phosphate from Waters

Nanoparticle-doped polymer inclusion membranes (NP-PIMs) have been prepared and characterized as new materials for the removal of arsenate and phosphate from waters. PIMs are made of a polymer, cellulose triacetate (CTA), and an extractant, which interacts with the compound of interest. We have used the ionic liquid (IL) trioctylmethylammonium chloride (Aliquat 336) as the extractant and have investigated how the addition of nanoparticles can modify membrane properties. To this end, inorganic nanoparticles, such as ferrite (Fe3O4), SiO2 and TiO2, and multiwalled carbon nanotubes (MWCNTs), were blended with the polymer/extractant mixture. Scanning electron microscopy (SEM), infrared spectroscopy (FT-IR), and contact angle measurements have been used to characterize the material. Moreover, PIM stability was checked by measuring the mass loss during the experiments. Since Aliquat 336 acts as an anion exchanger, the NP-PIMs have been explored in two different applications: (i) as sorbent materials for the extraction of arsenate and phosphate anions; (ii) as an organic phase for the separation of arsenate and phosphate in a three-phase system. The presence of oleate-coated ferrite NP in the PIM formulation represents an improvement in the efficiency of NP-PIMs used as sorbents; nevertheless, a decrease in the transport efficiency for arsenate but not for phosphate was obtained. The ease with which the NP-PIMs are prepared suggests good potential for future applications in the treatment of polluted water. Future work will address three main aspects: firstly, the implementation of the Fe3O4-PIMs for the removal of As(V) in real water containing complex matrices; secondly, the study of phosphate recovery with other cell designs that allow large volumes of contaminated water to be treated; and thirdly, the investigation of the role of MWCNTs in PIM stability.
Scanning Thermal Microscopy of Ultrathin Films: Numerical Studies Regarding Cantilever Displacement, Thermal Contact Areas, Heat Fluxes, and Heat Distribution

New micro- and nanoscale devices require electrically isolating materials with specific thermal properties. One option to characterize these thermal properties is the atomic force microscopy (AFM)-based scanning thermal microscopy (SThM) technique. It enables qualitative mapping of local thermal conductivities of ultrathin films. To fully understand and correctly interpret the results of practical SThM measurements, it is essential to have detailed knowledge about the heat transfer process between the probe and the sample. However, little can be found in the literature so far. Therefore, this work focuses on theoretical SThM studies of ultrathin films with anisotropic thermal properties such as hexagonal boron nitride (h-BN) and compares the results with a bulk silicon (Si) sample. Energy fluxes from the probe to the sample between 0.6 µW and 126.8 µW are found for different cases with a tip radius of approximately 300 nm. A present thermal interface resistance (TIR) between bulk Si and ultrathin h-BN on top can fully suppress a further heat penetration. The time until heat propagation within the sample is stationary is found to be below 1 µs, which may justify higher tip velocities in practical SThM investigations of up to 20 µms−1. It is also demonstrated that there is almost no influence of convection and radiation, whereas a possible TIR between probe and sample must be considered.
Clinical Impact of Psychopathy on Bipolar Disorder

Background and Objectives. Bipolar disorder (BD) is associated with a significant burden due to affective symptoms and behavioral manifestations, but also cognitive and functional impairment. Comorbidity with other psychiatric conditions, including personality disorders, is frequent. The comorbidity with psychopathy deserves special consideration given that both disorders share some clinical characteristics, such as grandiosity, risky behavior or poor insight, among others, that can worsen the outcome of BD. Therefore, this study aimed to evaluate the prevalence of psychopathy in a sample of clinically stabilized patients with BD and its impact on the severity of BD. Materials and Methods. A sample of 111 patients with BD (38 type I and 73 type II) was studied. The Hamilton Depression Rating Scale (HAM-D) and the Young Mania Rating Scale (YMRS) served to assess the severity of BD. Psychopathy was measured by means of the Psychopathic Personality Inventory-Revised (PPI-R). Patients were divided into three groups according to the severity of psychopathy (Group 1: no psychopathy; Group 2: “psychopathic” trait; Group 3: clinical psychopathy). Other measures regarded impulsiveness (Barratt Impulsiveness Scale-11, BIS-11) and empathy (Empathy Quotient, EQ). Comparisons of mania, depression, impulsivity and empathy scores were run with MANOVA considering psychopathy and diagnosis as independent variables. Results. The prevalence of psychopathy was 5.4%. A significant association between the level of psychopathy and YMRS, attentional/cognitive impulsivity and motor impulsivity scores emerged. No interaction between psychopathy and BD diagnosis was found. Post hoc analysis demonstrated significantly higher YMRS scores in Group 3 than in Group 1; that is, patients with psychopathy have more manic symptoms. Conclusion. Psychopathy seems quite frequent among patients with BD. The association of psychopathy with BD results in higher impulsivity and manic symptoms. In light of this, psychopathy should be investigated when assessing patients with BD, regardless of the comorbidity of BD with other personality disorders.
5-Hydroxymethylfurfural Formation in Bread as a Function of Heat Treatment Intensity: Correlations with Browning Indices

5-hydroxymethylfurfural (HMF) is formed during bread baking as a Maillard reaction product (MRP); it can exert toxicity and it is regarded as a potential health risk because of its high consumption levels in western diets. The aim of this study was to evaluate HMF formation in bread as a function of heat treatment intensity (HTI) and to investigate correlations between HMF and easily detectable browning indices. White breads were baked at 200 °C and 225 °C for different baking times for a total of 24 baking trials. Browning development was evaluated by reflectance colorimetric and computer vision colour analysis; MRP were quantified spectrophotometrically at 280, 360 and 420 nm and HMF was determined by HPLC. HMF concentrations varied from 4 to 300 mg/kg dw. Colour indices (100–L*) and Intensity mean resulted significantly correlated between each other (r = −0.961) and with MRP (r ≥ 0.819). The effects of the different HTI were visualized by principal component analysis and the data were used to evaluate the best fitting regression models between HMF concentration and other browning indices, obtaining models with high correlation coefficients (r > 0.90).