Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuovi aspetti immunologici del trapianto di rene in eta' pediatrica = Novel immunological aspects of pediatric kidney transplantation

Pediatric kidney transplantation has been a serious challenge from the outset. The main reason lies in the immune system of children, which presents significant differences in terms of lymphocyte subpopulation distribution and alloimmune response activation from the adult immune system. These differences are greatest between neonates and adults, while they decrease in a linear and age-dependent fashion. In the past, kidney transplantation in children was a courageous initiative, given the poorer outcomes compared with adult recipients. Today, thanks to advances in therapy protocols and a better knowledge of the pediatric immune system, graft survival in pediatric patients has significantly improved and transplantation is the standard of care for the treatment of chronic organ failure in children. Moreover, there is growing interest in the field of pediatric transplantation because of the recipients’ peculiar infective risk profile, the underestimated cardiovascular risk, and the necessity to identify both new non-invasive diagnostic techniques and the characteristics that make the pediatric immune system so peculiar. Acquiring new knowledge in those fields may slow down the adoption of new therapies but, on the other hand, it may represent a starting point to provide pediatric allograft recipients with diagnostic and therapeutic advantages and ultimately achieve allograft tolerance.
Access to Highly Purified Chondroitin Sulfate for Appropriate Treatment of Osteoarthritis: A Review

Current pharmacological therapies for osteoarthritis are symptom-focused and aimed at controlling pain. However, currently approved symptom-modifying agents do not restore the structure and function of damaged joints. Symptomatic slow-acting drugs in osteoarthritis (SySADOAs), including the sulfated glycosaminoglycan, chondroitin sulfate, have shown promising beneficial effects on the pain and other symptoms of osteoarthritis, and some may also have a positive effect on cartilage, slowing the progression of joint deterioration in osteoarthritis. A highly-purified, standardized, pharmaceutical-grade preparation of chondroitin sulfate has shown activity in osteoarthritis and has become one of the most prescribed SySADOAs. However, in many countries, formulations of chondroitin sulfate of various sources and purity are available as food supplements or nutraceuticals. As the effects of chondroitin sulfate could vary according to the characteristics of the chondroitin sulfate employed, including source, purity, or structural organization, clinical data from well-designed studies of pharmaceutical-grade chondroitin sulfate should not be extrapolated to support clinical efficacy claims of food supplements; nor should results from trials of chondroitin sulfate-containing food supplements be used to draw conclusions about the efficacy of pharmaceutical-grade chondroitin sulfate. This article reviews the evidence for the role of highly-purified pharmaceutical-grade chondroitin sulfate in the treatment of osteoarthritis and examines the efficacy and safety concerns of other formulations of chondroitin sulfate. Highly-purified pharmaceutical-grade chondroitin sulfate has mild-to-moderate efficacy in the treatment of symptomatic osteoarthritis, with clinically meaningful efficacy.
Parental identification and response to adolescent substance use and substance use disorders

Abstract Previous research showing that parents tend to underestimate adolescent substance use is consistent with concerns that adolescent substance use may develop because parents delay in reacting to it. However, little research has examined parental decisions regarding how and when to intervene on adolescent substance use. This study examines the actions that parents report they would take after (a) discovering substance use to intoxication and (b) when they believe their child has a substance use problem. Internet surveys were conducted asking parents (N = 975) how they would respond to (a) evidence of their child’s use to intoxication and (b) their child’s significant problem with either alcohol, cannabis, prescription opioids, or illicit drugs. While parental response to alcohol and cannabis intoxication focused on talking with their children (34% and 45%, respectively) and punishment (30% and 18%, respectively), parents were significantly more likely to report help-seeking behaviors when responding to prescription opioid or illicit drug use intoxication (37% and 30%, respectively). More effective public health initiatives are needed to provide parents with practical strategies to address adolescent substance use and to increase parental engagement in the services offered by addiction specialists.
Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study

PURPOSE Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors (GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT. PATIENTS AND METHODS In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of β-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase. RESULTS For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p. CONCLUSION The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.
Long Noncoding RNA and Protein Interactions: From Experimental Results to Computational Models Based on Network Methods

Non-coding RNAs with a length of more than 200 nucleotides are long non-coding RNAs (lncRNAs), which have gained tremendous attention in recent decades. Many studies have confirmed that lncRNAs have important influence in post-transcriptional gene regulation; for example, lncRNAs affect the stability and translation of splicing factor proteins. The mutations and malfunctions of lncRNAs are closely related to human disorders. As lncRNAs interact with a variety of proteins, predicting the interaction between lncRNAs and proteins is a significant way to depth exploration functions and enrich annotations of lncRNAs. Experimental approaches for lncRNA–protein interactions are expensive and time-consuming. Computational approaches to predict lncRNA–protein interactions can be grouped into two broad categories. The first category is based on sequence, structural information and physicochemical property. The second category is based on network method through fusing heterogeneous data to construct lncRNA related heterogeneous network. The network-based methods can capture the implicit feature information in the topological structure of related biological heterogeneous networks containing lncRNAs, which is often ignored by sequence-based methods. In this paper, we summarize and discuss the materials, interaction score calculation algorithms, advantages and disadvantages of state-of-the-art algorithms of lncRNA–protein interaction prediction based on network methods to assist researchers in selecting a suitable method for acquiring more dependable results. All the related different network data are also collected and processed in convenience of users, and are available at https://github.com/HAN-Siyu/APINet/.
Positive Short-Term Effect of Low-Dose Rosuvastatin in a Patient with SYNGAP1-Associated Epilepsy

1Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Vogtareuth, Germany 2Research Institute for Rehabilitation, Transition and Palliation, PMU Salzburg, Austria 3Comprehensive Epilepsy Program for Children, Division of Pediatric Neurology, DevelopmentalMedicine and Social Pediatrics, Department of Pediatrics, University Hospital Munich, Munich, Germany 4Epilepsy Unit for Adult Patients, Schön Klinik Vogtareuth, Vogtareuth, Germany
A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model

The zebrafish is being increasingly used in biomedical research and drug discovery to conduct large-scale compound screening. However, there is a lack of accessible methodologies to enable automated imaging and scoring of tissue-specific phenotypes at enhanced resolution. Here, we present the development of an automated imaging pipeline to identify chemical modifiers of glomerular cyst formation in a zebrafish model for human cystic kidney disease. Morpholino-mediated knockdown of intraflagellar transport protein Ift172 in Tg(wt1b:EGFP) embryos was used to induce large glomerular cysts representing a robustly scorable phenotypic readout. Compound-treated embryos were consistently aligned within the cavities of agarose-filled microplates. By interfacing feature detection algorithms with automated microscopy, a smart imaging workflow for detection, centring and zooming in on regions of interests was established, which enabled the automated capturing of standardised higher resolution datasets of pronephric areas. High-content screening datasets were processed and analysed using custom-developed heuristic algorithms implemented in common open-source image analysis software. The workflow enables highly efficient profiling of entire compound libraries and scoring of kidney-specific morphological phenotypes in thousands of zebrafish embryos. The demonstrated toolset covers all the aspects of a complex whole organism screening assay and can be adapted to other organs, specimens or applications.
Characterization of Vertically Aligned Carbon Nanotube Forests Grown on Stainless Steel Surfaces

Vertically aligned carbon nanotube (CNT) forests are a particularly interesting class of nanomaterials, because they combine multifunctional properties, such as high energy absorption, compressive strength, recoverability, and super-hydrophobicity with light weight. These characteristics make them suitable for application as coating, protective layers, and antifouling substrates for metallic pipelines and blades. Direct growth of CNT forests on metals offers the possibility of transferring the tunable CNT functionalities directly onto the desired substrates. Here, we focus on characterizing the structure and mechanical properties, as well as wettability and adhesion, of CNT forests grown on different types of stainless steel. We investigate the correlations between composition and morphology of the steel substrates with the micro-structure of the CNTs and reveal how the latter ultimately controls the mechanical and wetting properties of the CNT forest. Additionally, we study the influence of substrate morphology on the adhesion of CNTs to their substrate. We highlight that the same structure-property relationships govern the mechanical performance of CNT forests grown on steels and on Si.
Transposable elements drive rapid phenotypic variation in Capsella rubella

Significance The mechanisms underlying rapid adaptation to changing environments in species with reduced genetic variation, referred to as the “genetic paradox of invasion,” are unknown. We report that transposable elements (TEs) are highly enriched in the gene promoter regions of Capsella rubella compared with its outcrossing sister species Capsella grandiflora. We also show that a number of polymorphic TEs in C. rubella are associated with changes in gene expression. Frequent TE insertions at FLOWERING LOCUS C of C. rubella affect flowering-time variation, an important life history trait correlated with fitness. These results indicate that TE insertions drive rapid phenotypic variation, which could potentially help adapting to novel environments in species with limited genetic variation. Rapid phenotypic changes in traits of adaptive significance are crucial for organisms to thrive in changing environments. How such phenotypic variation is achieved rapidly, despite limited genetic variation in species that experience a genetic bottleneck is unknown. Capsella rubella, an annual and inbreeding forb (Brassicaceae), is a great system for studying this basic question. Its distribution is wider than those of its congeneric species, despite an extreme genetic bottleneck event that severely diminished its genetic variation. Here, we demonstrate that transposable elements (TEs) are an important source of genetic variation that could account for its high phenotypic diversity. TEs are (i) highly enriched in C. rubella compared with its outcrossing sister species Capsella grandiflora, and (ii) 4.2% of polymorphic TEs in C. rubella are associated with variation in the expression levels of their adjacent genes. Furthermore, we show that frequent TE insertions at FLOWERING LOCUS C (FLC) in natural populations of C. rubella could explain 12.5% of the natural variation in flowering time, a key life history trait correlated with fitness and adaptation. In particular, we show that a recent TE insertion at the 3′ UTR of FLC affects mRNA stability, which results in reducing its steady-state expression levels, to promote the onset of flowering. Our results highlight that TE insertions can drive rapid phenotypic variation, which could potentially help with adaptation to changing environments in a species with limited standing genetic variation.
Chemical and Biological Components of Urban Aerosols in Africa: Current Status and Knowledge Gaps

Aerosolized particulate matter (PM) is a complex mixture that has been recognized as the greatest cause of premature human mortality in low- and middle-income countries. Its toxicity arises largely from its chemical and biological components. These include polycyclic aromatic hydrocarbons (PAHs) and their nitro-derivatives (NPAHs) as well as microorganisms. In Africa, fossil fuel combustion and biomass burning in urban settings are the major sources of human exposure to PM, yet data on the role of aerosols in disease association in Africa remains scarce. This review is the first to examine studies conducted in Africa on both PAHs/NPAHs and airborne microorganisms associated with PM. These studies demonstrate that PM exposure in Africa exceeds World Health Organization (WHO) safety limits and carcinogenic PAHs/NPAHs and pathogenic microorganisms are the major components of PM aerosols. The health impacts of PAHs/NPAHs and airborne microbial loadings in PM are reviewed. This will be important for future epidemiological evaluations and may contribute to the development of effective management strategies to improve ambient air quality in the African continent.
A comparison of cognitive emotion regulation, lifestyle, and dimensions of adjustment in 3 groups of patients with multiple sclerosis, patients with cancer under chemotherapy and patients relieved from brain tumor

The purpose of the present study WAS to compare cognitive emotion regulation, lifestyle, and dimensions of adjustment in 3 groups of patients with multiple sclerosis (MS), patients with cancer under chemotherapy and patients relieved from brain tumor. The statistical sample included 72 patients that were all selected by convenience sampling method. They filled out the questionnaires of cognitive emotion regulation questionnaire, multidimensional adjustment scales, and lifestyle questionnaire. The results showed that in the score of positive and negative cognitive emotion regulation, the mean score of the MS group was significantly more than the cancer group. In lifestyle, the mean score of the brain tumor group was significantly more than the other two groups. In adjustment and personal, social, job, and family dimensions, the scores of the cancer group were significantly more than the other two groups.
Re‐evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a) as food additives

Abstract The present opinion deals with the re‐evaluation of the safety of food‐grade carrageenan (E 407) and processes Eucheuma seaweed (E 407a) used as food additives. Because of the structural similarities, the Panel concluded that processed Eucheuma seaweed can be included in the evaluation of food‐grade carrageenan. Poligeenan (average molecular weight 10–20 kDa) has not been authorised as a food additive and is not used in any food applications. In its evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a), the Panel noted that the ADME database was sufficient to conclude that carrageenan was not absorbed intact; in a subchronic toxicity study performed with carrageenan almost complying with the EU specification for E 407 in rats, the no‐observed‐adverse‐effect level (NOAEL) was 3,400–3,900 mg/kg body weight (bw) per day, the highest dose tested; no adverse effects have been detected in chronic toxicity studies with carrageenan in rats up to 7,500 mg/kg bw per day, the highest dose tested; there was no concern with respect to the carcinogenicity of carrageenan; carrageenan and processed Eucheuma seaweed did not raise a concern with respect to genotoxicity; the NOAEL of sodium and calcium carrageenan for prenatal developmental dietary toxicity studies were the highest dose tested; the safety of processed Eucheuma seaweed was sufficiently covered by the toxicological evaluation of carrageenan; data were adequate for a refined exposure assessment for 41 out of 79 food categories. However, the Panel noted uncertainties as regards the chemistry, the exposure assessment and biological and toxicological data. Overall, taking into account the lack of adequate data to address these uncertainties, the Panel concluded that the existing group acceptable daily intake (ADI) for carrageenan (E 407) and processed Eucheuma seaweed (E 407a) of 75 mg/kg bw per day should be considered temporary, while the database should be improved within 5 years after publication of this opinion.
Sustainability of Eribulin Treatment for Patients with Metastatic Breast Cancer: is the Cost of the Drug Related to the Benefit Produced (Effectiveness and Safety)? a Single Center Experience

Objective:To report the clinical outcomes and health care costs of Metastatic Breast Cancer patients treated with Eribulin, in the Medical Oncology Unit of the Messina University. Method:We retrospectively analyzed the costs associated with eribulin treatment in 15 MBC patients from January 2014 to December 2016 at Messina University Hospital. The PFS , ORR , DCR and the average cost of patient therapy were calculated. Result:15 patients were included in this analysis. They had received a median of 4 lines of therapy previously (including adjuvant treatment) and had significant visceral involvement (median 3 organs). A median of 4 cycles of eribulin was delivered. There were partial responses in 20% patients , stable disease status in 14% , and progressive disease in 66% . The median progression-free survival was 15 weeks (3.5 months), ORR was 20%, DCR was 33% . The most frequent treatment-related adverse events were neutropenia (26%), and febrile neutropenia (20%). Therapy for these patients resulted in a cost of euros 158.244,76. Assessing the repayment by the pharmaceutical company equals to euros 20.238,37 for non â€“responders patients , there is a net cost of euros 138.006,39. Conclusion: Our results have shown that treatment with eribulin applied to patients pretreated in III / IV metastatic line and beyond, so the high percentage of non-responders is determined because of the already expired general conditions at the beginning of treatment. Despite this ,eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with MBC. The costs associated with eribulin therapy have shown that payment by result contributes to making the cost of therapy more sustainable by the National Health Service
Niclosamide Triggers Non-Canonical LC3 Lipidation

Autophagy is a highly- evolutionarily-conserved catabolic pathway activated by various cellular stresses. Recently, non-canonical autophagy (NCA), which does not require all of the ATG proteins to form autophagosome or autophagosome-like structures, has been found in various conditions. Moreover, mounting evidence has indicated that non-canonical LC3 lipidation (NCLL) may reflect NCA. We and others have reported that niclosamide (Nic), an anti-helminthic drug approved by the Food and Drug Administration, could induce canonical autophagy via a feedback downregulation of mTOR complex 1. In this study, we found that Nic could also induce NCLL, which is independent of the ULK1 complex and Beclin 1 complex, but dependent on ubiquitin-like conjugation systems. Although bafilomycin A1 and concanamycin A, two known V-ATPase inhibitors, significantly inhibited Nic-induced NCLL, Nic-induced NCLL was demonstrated to be independent of V-ATPase. In addition, the Golgi complex and vimentin were involved in Nic-induced NCLL, which might be a platform or membrane source for Nic-induced LC3-positive structures. These results would be helpful to broaden our understanding of the working mechanisms of Nic and evaluate its pharmacological activities in diseases.
Molecular Mechanisms of Hypothalamic Insulin Resistance

Insulin exists in the central nervous system, where it executes two important functions in the hypothalamus: the suppression of food intake and the improvement of glucose metabolism. Recent studies have shown that both are exerted robustly in rodents and humans. If intact, these functions exert beneficial effects on obesity and diabetes, respectively. Disruption of both occurs due to a condition known as hypothalamic insulin resistance, which is caused by obesity and the overconsumption of saturated fat. An enormous volume of literature addresses the molecular mechanisms of hypothalamic insulin resistance. IKKβ and JNK are major players in the inflammation pathway, which is activated by saturated fatty acids that induce hypothalamic insulin resistance. Two major tyrosine phosphatases, PTP-1B and TCPTP, are upregulated in chronic overeating. They dephosphorylate the insulin receptor and insulin receptor substrate proteins, resulting in hypothalamic insulin resistance. Prolonged hyperinsulinemia with excessive nutrition activates the mTOR/S6 kinase pathway, thereby enhancing IRS-1 serine phosphorylation to induce hypothalamic insulin resistance. Other mechanisms associated with this condition include hypothalamic gliosis and disturbed insulin transport into the central nervous system. Unveiling the precise molecular mechanisms involved in hypothalamic insulin resistance is important for developing new ways of treating obesity and type 2 diabetes.