Miracle-dz/UniFAR-FTUs huggingface dataset:
Synovial Immunohistological Biomarkers of the Classification of Undifferentiated Arthritis Evolving to Rheumatoid or Psoriatic Arthritis

Background: Undifferentiated arthritis (UA) is defined as an inflammatory arthritis that does not fulfill criteria for a definite diagnosis. Delay in reaching a specific diagnostic and therapy may lead to impaired functional outcomes. Our aim was to identify synovial biomarkers associated with definitive diagnostic classification in patients with UA. Methods: DMARD-naïve UA patients with available initial synovial tissue (ST) and a final diagnosis of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) during follow-up were included and compared with patients with well-defined disease (RA or PsA). Clinical, arthroscopic, and pathological data were compared between groups. Pathology included quantitative immunohistochemical (IHC) analysis of cell types and human interferon-regulated MxA. Principal component analysis (PCA) was performed to extract disease patterns. Results: One hundred and five patients were included: 31 patients with DMARD-naïve UA (19 evolving to RA and 12 to PsA during a median follow up of 7 years), 39 with established RA, and 35 with established PsA. ST from the UA group showed higher macrophage density compared with the established RA and PsA groups. Patients with UA evolving to RA (UA-RA) showed higher MxA expression and CD3+ T-cell density compared with established RA. UA patients evolving to PsA (UA-PsA) showed increased vascularity and lining synovial fibroblast density compared with established PsA. Synovitis of UA-PsA patients showed more mast cells and lining fibroblasts compared with UA-RA. No between-group differences in local or systemic inflammation markers were found. Conclusions: Our results show differences in the cellular composition of UA synovium compared with RA and PsA, with higher density of the cellular infiltrate in the UA groups. Initial expression of the interferon inducible gene MxA could be a biomarker of progression to RA, while higher mast cell and fibroblastic density may be associated with PsA progression.
Premature Mortality, Risk Factors, and Causes of Death Following Childhood-Onset Neurological Impairments: A Systematic Review

Background: Neurological impairment (NI) and disability are associated with reduced life expectancy, but the risk and magnitude of premature mortality in children vary considerably across study settings. We conducted a systematic review to estimate the magnitude of premature mortality following childhood-onset NI worldwide and to summarize known risk factors and causes of death. Methods: We searched various databases for published studies from their inception up to 31st October 2020. We included all cohort studies that assessed the overall risk of mortality in individuals with childhood-onset epilepsy, intellectual disability (ID), and deficits in hearing, vision and motor functions. Comparative measures of mortality such as the standardized mortality ratio (SMR), risk factors and causes were synthesized quantitatively under each domain of impairment. This review is registered on the PROSPERO database (registration number CRD42019119239). Results: The search identified 2,159 studies, of which 24 studies were included in the final synthesis. Twenty-two (91.7%) studies originated from high-income countries (HICs). The median SMR was higher for epilepsy compared with ID (7.1 [range 3.1–22.4] vs. 2.9 [range 2.0–11.6]). In epilepsy, mortality was highest among younger age groups, comorbid neurological disorders, generalized seizures (at univariable levels), untreatable epilepsy, soon after diagnosis and among cases with structural/metabolic types, but there were no differences by sex. Most deaths (87.5%) were caused by non-epilepsy-related causes. For ID, mortality was highest in younger age groups and girls had a higher risk compared to the general population. Important risk factors for premature mortality were severe-to-profound severity, congenital disorders e.g., Down Syndrome, comorbid neurological disorders and adverse pregnancy and perinatal events. Respiratory infections and comorbid neurological disorders were the leading causes of death in ID. Mortality is infrequently examined in impairments of vision, hearing and motor functions. Summary: The risk of premature mortality is elevated in individuals with childhood-onset NI, particularly in epilepsy and lower in ID, with a need for more studies for vision, hearing, and motor impairments. Survival in NI could be improved through interventions targeting modifiable risk factors and underlying causes.
On the Factors Influencing Green Purchase Intention: A Meta-Analysis Approach

This study systematically analyzes the factors that affect consumers’ green purchase intention. Through a comprehensive literature review, the influencing factors of consumers’ green purchase intention are organized into three categories: cognitive factors, consumer individual characteristics, and social factors. Next, a meta-analysis of 54 empirical papers was conducted using Comprehensive Meta-Analysis 3.0 software to quantitatively assess these relationships. The results revealed that green perceived value, attitude, and green trust have a significant positive influence on green purchase intention. Perceived behavior control, perceived consumer effectiveness, and subjective norm also has a strong positive impact on green purchase intention. Collectivism has a positive effect on green purchase intention. Green perceived risk has a significant negative impact on green purchase intention. The study’s findings provide references for enterprises engaged in green product diffusion and organizations responsible for environmental protection.
Kynurenic Acid Analog Attenuates the Production of Tumor Necrosis Factor-α, Calgranulins (S100A 8/9 and S100A 12), and the Secretion of HNP1–3 and Stimulates the Production of Tumor Necrosis Factor-Stimulated Gene-6 in Whole Blood Cultures of Patients With Rheumatoid Arthritis

Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease with complex pathogenesis involving a variety of immunological events. Recently, it has been suggested that kynurenic acid (KYNA) might be a potential regulator of inflammatory processes in arthritis. KYNA has a definitive anti-inflammatory and immunosuppressive function. The aim of the present study is to investigate the complex effects of a newly synthesized KYNA analog—SZR72 on the in vitro production of tumor necrosis factor-α (TNF-α), tumor necrosis factor-stimulated gene-6 (TSG-6), calprotectin (SA1008/9), SA100 12 (EN-RAGE), and HNP1–3 (defensin-α) in the peripheral blood of patients with RA and the various effects of the disease. Methods: Patients with RA (n = 93) were selected based on the DAS28 score, medication, and their rheumatoid factor (RF) status, respectively. Peripheral blood samples from 93 patients with RA and 50 controls were obtained, and activated by heat-inactivated S. aureus. Parallel samples were pretreated before the activation with the KYNA analog N-(2-N, N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride. Following the incubation period (18 h), the supernatants were tested for TNF-α, TSG-6, calprotectin, S100A12, and HNP1–3 content by ELISA. Results: SZR72 inhibited the production of the following inflammatory mediators: TNF-α, calprotectin, S100A12, and HNP1–3 in whole blood cultures. This effect was observed in each group of patients in various phases of the disease. The basic (control) levels of these mediators were higher in the blood of patients than in healthy donors. In contrast, lower TSG-6 levels were detected in patients with RA compared to healthy controls. In addition, the KYNA analog exerted a stimulatory effect on the TSG-6 production ex vivo in human whole blood cultures of patients with RA in various phases of the disease. Conclusion: These data further support the immunomodulatory role of KYNA in RA resulting in anti-inflammatory effects and draw the attention to the importance of the synthesis of the KYNA analog, which might have a future therapeutic potential.
Training in Rhythmic Gymnastics During the Pandemic

The pandemic caused by the COVID 19 Virus creates an unprecedented situation of global confinement altering the development of competition and sports training at all levels of participation and in all sports, including rhythmic gymnastics (RG). To avoid possible effects of physical, technical and psychological detraining, coaches looked for home training alternatives. The objectives of the study were to know how rhythmic gymnastics training developed during the lockdown period (the conditions, type of training, performance monitoring means, and determinants of gymnasts’ participation) and to provide recommendations for a possible future lockdown. Three hundred and two RG coaches from twenty-six different countries throughout the five continents and four professional levels took part in the study: national team (28), international (26), national (172) and regional (75). The data collection tool was a questionnaire consisting of 39 closed questions structured in three dimensions: identification data of the coaches, training data during confinement and gymnast participation data. The independent variable was the gymnasts’ performance levels and the dependent variables organized in four categories: the technical media used to conduct and monitor the training sessions, the type of training done, the mechanisms for monitoring training performance and the aspects that determined participation. Most coaches kept their gymnasts training during confinement, although 76.5% confirm abandonment of any of their gymnasts. The main means used were real-time video conferencing, although at the lower practice levels the media stand out in deferred time. The contents of the training were mainly body technique, physical preparation and body difficulties. For performance monitoring, challenges, physical, and technical tests were predominant. The determinants for the development of training in the confinement vary depending on the level of the gymnasts, connectivity and electronic resources at the highest level, and the availability of spaces and social distancing at lower levels. For future lockdowns, it is necessary to review the content of the trainings, as well as the performance evaluation and the means necessary for it.
Antimicrobial-Loaded Polymeric Micelles Inhibit Enteric Bacterial Pathogens on Spinach Leaf Surfaces During Multiple Simulated Pathogen Contamination Events

Protecting fresh-packed produce microbiological safety against pre- and post-harvest microbial pathogen contamination requires innovative antimicrobial strategies. Although largely ignored in the scientific literature, there exists the potential for gross failure in food safety protection of fresh fruits and vegetables leading to opportunity for multiple produce contamination events to occur during production and post-harvest handling of food crops. The primary objective of this research was to determine the efficacy of plant-derived antimicrobial-loaded nanoparticles to reduce Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium on spinach leaf surfaces whilst simulating multiple pathogen contamination events (pre-harvest and post-harvest). Spinach samples were inoculated with a blend of E. coli O157:H7 and S. Typhimurium, each diluted to ~8.0 log10 CFU/mL. The inoculated samples were then submerged in solutions containing nanoparticles loaded with geraniol (GPN; 0.5 wt.% geraniol), unencapsulated geraniol (UG; 0.5 wt.%), or 200 ppm chlorine (HOCl; pH 7.0), with untreated samples serving for controls. Following antimicrobial treatment application, samples were collected for surviving pathogen enumeration or were placed under refrigeration (5°C) for up to 10 days, with periodic enumeration of pathogen loads. After 3 days of refrigerated storage, all samples were removed, aseptically opened and subjected to a second inoculation with both pathogens. Treatment of spinach surfaces with encapsulated geraniol reduced both pathogens to non-detectable numbers within 7 days of refrigerated storage, even with a second contamination event occurring 3 days after experiment initiation. Similar results were observed with the UG treatment, except that upon recontamination at day 3, a higher pathogen load was detected on UG-treated spinach vs. GPN-treated spinach. These data fill a research gap by providing a novel tool to reduce enteric bacterial pathogens on spinach surfaces despite multiple contamination events, a potential food safety risk for minimally processed edible produce.
Liquid PRF Reduces the Inflammatory Response and Osteoclastogenesis in Murine Macrophages

Macrophage activation and osteoclastogenesis are hallmarks of inflammatory osteolysis and may be targeted by the local application of liquid platelet-rich fibrin (PRF). Liquid PRF is produced by a hard spin of blood in the absence of clot activators and anticoagulants, thereby generating an upper platelet-poor plasma (PPP) layer, a cell-rich buffy coat layer (BC; termed concentrated-PRF or C-PRF), and the remaining red clot (RC) layer. Heating PPP has been shown to generate an albumin gel (Alb-gel) that when mixed back with C-PRF generates Alb-PRF having extended working properties when implanted in vivo. Evidence has demonstrated that traditional solid PRF holds a potent anti-inflammatory capacity and reduces osteoclastogenesis. Whether liquid PRF is capable of also suppressing an inflammatory response and the formation of osteoclasts remains open. In the present study, RAW 264.7 and primary macrophages were exposed to lipopolysaccharides (LPS), lactoferrin, and agonists of Toll-like receptors (TLR3 and TLR7) in the presence or absence of lysates prepared by freeze-thawing of liquid PPP, BC, Alb-gel, and RC. For osteoclastogenesis, primary macrophages were exposed to receptor activator of nuclear factor kappa B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and human transforming growth factor-β1 (TGF-β1) in the presence or absence of PPP, BC, Alb-gel, RC lysates and hemoglobin. We show here that it is mainly the lysates prepared from PPP and BC that consistently reduced the agonist-induced expression of interleukin 6 (IL6) and cyclooxygenase-2 (COX2) in macrophages, as determined by RT-PCR and immunoassay. With respect to osteoclastogenesis, lysates from PPP and BC but also from RC, similar to hemoglobin, reduced the expression of osteoclast marker genes tartrate-resistant acid phosphatase (TRAP) and cathepsin K, as well as TRAP histochemical staining. These findings suggest that liquid PRF holds a potent in vitro heat-sensitive anti-inflammatory activity in macrophages that goes along with an inhibition of osteoclastogenesis.
Genetic Variability of Human Cytomegalovirus Clinical Isolates Correlates With Altered Expression of Natural Killer Cell-Activating Ligands and IFN-γ

Human cytomegalovirus (HCMV) infection often leads to systemic disease in immunodeficient patients and congenitally infected children. Despite its clinical significance, the exact mechanisms contributing to HCMV pathogenesis and clinical outcomes have yet to be determined. One of such mechanisms involves HCMV-mediated NK cell immune response, which favors viral immune evasion by hindering NK cell-mediated cytolysis. This process appears to be dependent on the extent of HCMV genetic variation as high levels of variability in viral genes involved in immune escape have an impact on viral pathogenesis. However, the link between viral genome variations and their functional effects has so far remained elusive. Thus, here we sought to determine whether inter-host genetic variability of HCMV influences its ability to modulate NK cell responses to infection. For this purpose, five HCMV clinical isolates from a previously characterized cohort of pediatric patients with confirmed HCMV congenital infection were evaluated by next-generation sequencing (NGS) for genetic polymorphisms, phylogenetic relationships, and multiple-strain infection. We report variable levels of genetic characteristics among the selected clinical strains, with moderate variations in genome regions associated with modulation of NK cell functions. Remarkably, we show that different HCMV clinical strains differentially modulate the expression of several ligands for the NK cell-activating receptors NKG2D, DNAM-1/CD226, and NKp30. Specifically, the DNAM-1/CD226 ligand PVR/CD155 appears to be predominantly upregulated by fast-replicating (“aggressive”) HCMV isolates. On the other hand, the NGK2D ligands ULBP2/5/6 are downregulated regardless of the strain used, while other NK cell ligands (i.e., MICA, MICB, ULBP3, Nectin-2/CD112, and B7-H6) are not significantly modulated. Furthermore, we show that IFN-γ; production by NK cells co-cultured with HCMV-infected fibroblasts is directly proportional to the aggressiveness of the HCMV clinical isolates employed. Interestingly, loss of NK cell-modulating genes directed against NK cell ligands appears to be a common feature among the “aggressive” HCMV strains, which also share several gene variants across their genomes. Overall, even though further studies based on a higher number of patients would offer a more definitive scenario, our findings provide novel mechanistic insights into the impact of HCMV genetic variability on NK cell-mediated immune responses.
Neurotropic Viruses, Astrocytes, and COVID-19

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered in China, causing a new coronavirus disease, termed COVID-19 by the WHO on February 11, 2020. At the time of this paper (January 31, 2021), more than 100 million cases have been recorded, which have claimed over 2 million lives worldwide. The most important clinical presentation of COVID-19 is severe pneumonia; however, many patients present various neurological symptoms, ranging from loss of olfaction, nausea, dizziness, and headache to encephalopathy and stroke, with a high prevalence of inflammatory central nervous system (CNS) syndromes. SARS-CoV-2 may also target the respiratory center in the brainstem and cause silent hypoxemia. However, the neurotropic mechanism(s) by which SARS-CoV-2 affects the CNS remain(s) unclear. In this paper, we first address the involvement of astrocytes in COVID-19 and then elucidate the present knowledge on SARS-CoV-2 as a neurotropic virus as well as several other neurotropic flaviviruses (with a particular emphasis on the West Nile virus, tick-borne encephalitis virus, and Zika virus) to highlight the neurotropic mechanisms that target astroglial cells in the CNS. These key homeostasis-providing cells in the CNS exhibit many functions that act as a favorable milieu for virus replication and possibly a favorable environment for SARS-CoV-2 as well. The role of astrocytes in COVID-19 pathology, related to aging and neurodegenerative disorders, and environmental factors, is discussed. Understanding these mechanisms is key to better understanding the pathophysiology of COVID-19 and for developing new strategies to mitigate the neurotropic manifestations of COVID-19.
Machine Learning for Predicting Mycotoxin Occurrence in Maize

Meteorological conditions are the main driving variables for mycotoxin-producing fungi and the resulting contamination in maize grain, but the cropping system used can mitigate this weather impact considerably. Several researchers have investigated cropping operations’ role in mycotoxin contamination, but these findings were inconclusive, precluding their use in predictive modeling. In this study a machine learning (ML) approach was considered, which included weather-based mechanistic model predictions for AFLA-maize and FER-maize [predicting aflatoxin B1 (AFB1) and fumonisins (FBs), respectively], and cropping system factors as the input variables. The occurrence of AFB1 and FBs in maize fields was recorded, and their corresponding cropping system data collected, over the years 2005–2018 in northern Italy. Two deep neural network (DNN) models were trained to predict, at harvest, which maize fields were contaminated beyond the legal limit with AFB1 and FBs. Both models reached an accuracy >75% demonstrating the ML approach added value with respect to classical statistical approaches (i.e., simple or multiple linear regression models). The improved predictive performance compared with that obtained for AFLA-maize and FER-maize was clearly demonstrated. This coupled to the large data set used, comprising a 13-year time series, and the good results for the statistical scores applied, together confirmed the robustness of the models developed here.
Neuropsychiatric Symptoms in Pediatric Chronic Pain and Outcome of Acceptance and Commitment Therapy

Considerable heterogeneity among pediatric chronic pain patients may at least partially explain the variability seen in the response to behavioral therapies. The current study tested whether autistic traits and attention-deficit/hyperactivity disorder (ADHD) symptoms in a clinical sample of children and adolescents with chronic pain are associated with socioemotional and functional impairments and response to acceptance and commitment therapy (ACT) treatment, which has increased psychological flexibility as its core target for coping with pain and pain-related distress. Children and adolescents aged 8–18 years (N = 47) were recruited. Patients and their parents completed questionnaires pre- and post-ACT of 17 sessions. Correlational analyses and mixed-effects models were used to assess the role of autistic traits and ADHD symptoms in pretreatment functioning and ACT-treatment response. Outcome variables were degree to which pain interfered with daily activities (i.e., pain interference, sleep, and physical and school functioning), socioemotional functioning (i.e., depressive symptoms, emotional, and social functioning), psychological inflexibility, and pain intensity. Autistic traits and ADHD symptoms, pain frequency, and pain duration were measured at pretreatment only. Higher autistic traits were associated with greater pain interference, higher depression, and greater psychological inflexibility. Higher ADHD symptomatology was associated with greater pretreatment pain interference, lower emotional functioning, greater depression, and longer duration of pain. Across patients, all outcome variables, except for sleep disturbances and school functioning, significantly improved from pre- to post-ACT. Higher autistic traits were associated with greater pre- to post-ACT improvements in emotional functioning and sleep disturbance and non-significant improvements in pain interference. ADHD symptomatology was not associated with treatment outcome. The current results showed that neuropsychiatric symptoms in pediatric chronic pain patients are associated with lower functioning, particularly pain interfering with daily life and lower socioemotional functioning. The results suggest that not only pediatric chronic pain patients low in neuropsychiatric symptoms may benefit from ACT, but also those high in autism traits and ADHD symptoms. With the present results in mind, pediatric chronic pain patients higher in autistic traits may actually derive extra benefit from ACT. Future research could assess whether increased psychological flexibility, the core focus of ACT, enabled those higher in autism traits to cope relatively better with pain-related distress and thus to gain more from the treatment, as compared to those lower in autism traits. Moreover, to address specific effects of ACT, inclusion of an appropriate control group is key.