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Background: Although mood disorders have been well characterized by immune-mediated inflammatory diseases, physical function and satisfaction with social roles have not yet been defined as independent domains. Objective: The study aims to assess satisfaction with social roles and physical function alterations in a population with immune-mediated inflammatory diseases and identify associated characteris-tics. Methods: Physical function and social role satisfaction were evaluated through the Patient-reported Outcomes Measurement System. Besides comparison between groups, univariate and multivariable logistic regression analyses were performed to identify independent predictors. Results: Two hundred sixty-five patients with immune-mediated inflammatory diseases and 206 controls were recruited. Compared to controls, patients with inflammatory bowel diseases had impaired physical function (p Conclusion: Immune-mediated inflammatory diseases determine alterations in physical function and social life satisfaction. Gender and treatment are independently associated factors. Patient-reported outcomes should be considered in clinical management to define patients’ real needs.

O presente trabalho tem como objetivo analisar o contrato de engineering, apontando seu aspecto evolutivo. Neste contexto, são apresentados os elementos essenciais desta modalidade contratual, sua interface com a legislação pátria e os motivos pelos quais trata-se de contrato de natureza empresarial o qual não pode ser compreendido como uma espécie do tipo empreitada, regulada nos artigos 610 a 626 do Código Civil Brasileiro. Outrossim, também são enumeradas algumas cláusulas específicas as quais possuem grande relevo para que haja um sucesso na estruturação e na consequente regulação de um contrato de engineering.

Background Blood transfusions represent common medical procedures, which provide essential supportive therapy. However, these procedures are notoriously expensive for healthcare services and not without risk. The potential threat of transfusion-related complications, such as the development of pathogenic infections and the occurring of alloimmunization events, alongside the donor’s dependence, strongly limits the availability of transfusion units and represents significant concerns in transfusion medicine. Moreover, a further increase in the demand for donated blood and blood transfusion, combined with a reduction in blood donors, is expected as a consequence of the decrease in birth rates and increase in life expectancy in industrialized countries. Main body An emerging and alternative strategy preferred over blood transfusion is the in vitro production of blood cells from immortalized erythroid cells. The high survival capacity alongside the stable and longest proliferation time of immortalized erythroid cells could allow the generation of a large number of cells over time, which are able to differentiate into blood cells. However, a large-scale, cost-effective production of blood cells is not yet a routine clinical procedure, as being dependent on the optimization of culture conditions of immortalized erythroid cells. Conclusion In our review, we provide an overview of the most recent erythroid cell immortalization approaches, while also describing and discussing related advancements of establishing immortalized erythroid cell lines.

Research projects heavily rely on the exchange and processing of data and in this context Pangeo (https://pangeo.io/), a world-wide community of scientists and developers, thrives to facilitate the deployment of ready to use and community-driven platforms for big data geoscience. The European Open Science Cloud (EOSC) is the main initiative in Europe for providing a federated and open multi-disciplinary environment where European researchers, innovators, companies and citizens can share, publish, find and re-use data, tools and services for research, innovation and educational purposes. While a number of services based on Jupyter Notebooks were already available, no public Pangeo deployments providing fast access to large amounts of data and compute resources were accessible on EOSC. Most existing cloud-based Pangeo deployments are USA-based, and members of the Pangeo community in Europe did not have a shared platform where scientists or technologists could exchange know-how. Pangeo teamed up with two EOSC projects, namely EGI-ACE (https://www.egi.eu/project/egi-ace/) and C-SCALE (https://c-scale.eu/) to demonstrate how to deploy and use Pangeo on EOSC and emphasise the benefits for the European community. The Pangeo Europe Community together with EGI deployed a DaskHub, composed of Dask Gateway (https://gateway.dask.org/) and JupyterHub (https://jupyter.org/hub), with Kubernetes cluster backend on EOSC using the infrastructure of the EGI Federation (https://www.egi.eu/egi-federation/). The Pangeo EOSC JupyterHub deployment makes use of 1) the EGI Check-In to enable user registration and thereby authenticated and authorised access to the Pangeo JupyterHub portal and to the underlying distributed compute infrastructure; and 2) the EGI Cloud Compute and the cloud-based EGI Online Storage to distribute the computational tasks to a scalable compute platform and to store intermediate results produced by the user jobs. To facilitate future Pangeo deployments on top of a wide range of cloud providers (AWS, Google Cloud, Microsoft Azure, EGI Cloud Computing, OpenNebula, OpenStack, and more), the Pangeo EOSC JupyterHub deployment is now possible through the Infrastructure Manager (IM) Dashboard (https://im.egi.eu/im-dashboard/login). All the computing and storage resources are currently supplied by CESNET (https://www.cesnet.cz/?lang=en) in the frame of EGI-ACE project (https://im.egi.eu/). Several deployments have been made to serve the geoscience community, both for teaching and for research work. To date, more than 100 researchers have been trained on Pangeo@EOSC deployments and more are expected to join, in particular with easy access to large amounts of Copernicus data through a recent collaboration established with the C-SCALE project. In this presentation, we will provide details on the different deployments, how to get access to JupyterHub deployments and more generally how to contribute to Pangeo@EOSC.

In most places on the planet vegetation thrives: it is known as “greening Earth”. However in certain regions, especially in the Arctic, there are areas exhibiting a browning trend. This phenomenon is well known but not fully understood yet, and grasping its impact on local ecosystems requires involvement of scientists from different disciplines, including social sciences and humanities, as well as local populations. Here we focus on the Troms and Finnmark counties in northern Norway to assess the extent of the problem and any link with local environmental conditions as well as potential impacts. We have chosen to adopt an open and collaborative process and take advantage of the services offered by RELIANCE on the European Open Science Cloud (EOSC). RELIANCE delivers a suite of innovative and interconnected services that extend the capabilities of the European Open Science Cloud (EOSC) to support the management of the research lifecycle within Earth Science Communities and Copernicus Users. The RELIANCE project has delivered 3 complementary technologies: Research Objects (ROs), Data Cubes and AI-based Text Mining. RoHub is a Research Object management platform that implements these 3 technologies and enables researchers to collaboratively manage, share and preserve their research work. We will show how we are using these technologies along with EGI notebooks to work open and share an executable Jupyter Notebook that is fully reproducible and reusable. We use a number of Python libraries from the Pangeo software stack such as Xarray, Dask and Zarr. Our Jupyter Notebook is bundled with its computational environment, datacubes and related bibliographic resources in an executable Research Object. We believe that this approach can significantly speed up the research process and can drive it to more exploitable results. Up to now, we have used indices derived from satellite data (in particular Sentinel-2) to assess how the vegetation cover in Troms and Finnmark counties has changed. To go a bit further we are investigating how to relate such information to relevant local parameters obtained from meteorological reanalysis data (ERA5 and ERA5-land from ECMWF). That should give a good basis for training an Artificial Intelligence algorithm and testing it, with the objective of getting an idea about the possibility of “predicting” what is likely to happen in the near future with certain types of vegetation like mosses and lichens which are essential for local populations and animals.

The ever increasing number of scientific datasets made available by authoritative data providers (NASA, Copernicus, etc.) and provided by the scientific community opens new possibilities for advancing the state of the art in many areas of the natural sciences. As a result, researchers, innovators, companies and citizens need to acquire computational and data analysis skills to optimally exploit these datasets. Several educational programs dispense basic courses to students, and initiatives such as “The Carpentries” (https://carpentries.org/) complement this offering but also reach out to established researchers to fill the skill gap thereby empowering them to perform their own data analysis. However, most researchers find it challenging to go beyond these training sessions and face difficulties when trying to apply their newly acquired knowledge to their own research projects. To this regard, hackathons have proven to be an efficient way to support researchers in becoming competent practitioners but organising good hackathons is difficult and time consuming. In addition, the need for large amounts of computational and storage resources during the training and hackathons requires a flexible solution. Here, we propose an approach where researchers work on realistic, large and complex data analysis problems similar to or directly part of their research work. Researchers access an infrastructure deployed on the European Ocean Science Cloud (EOSC) that supports intensive data analysis (large compute and storage resources). EOSC is a European Commission initiative for providing a federated and open multi-disciplinary environment where data, tools and services can be shared, published, found and re-used. We used jupyter book for delivering a collection of FAIR training materials for data analysis relying on Pangeo EOSC deployments as its primary computing platform. The training material (https://pangeo-data.github.io/foss4g-2022/intro.html, https://pangeo-data.github.io/clivar-2022/intro.html, https://pangeo-data.github.io/escience-2022/intro.html) is customised (different datasets with similar analysis) for different target communities and participants are taught the usage of Xarray, Dask and more generally how to efficiently access and analyse large online datasets. The training can be completed by group work where attendees can work on larger scale scientific datasets: the classroom is split into several groups. Each group works on different scientific questions and may use different datasets. Using the Pangeo (http://pangeo.io) ecosystem is not always new for all attendees but applying Xarray (http://xarray.pydata.org) and Dask (https://www.dask.org/) on actual scientific “mini-projects” is often a showstopper for many researchers. With this approach, attendees have the opportunity to ask questions, collaborate with other researchers as well as Research Software Engineers, and apply Open Science practices without the burden of trying and failing alone. We find the involvement of scientific computing research engineers directly in the training is crucial for success of the hackathon approach. Feedback from attendees shows that it provides a solid foundation for big data geoscience and helps attendees to quickly become competent practitioners. It also gives infrastructure providers and EOSC useful feedback on the current and future needs of researchers for making their research FAIR and open. In this presentation, we will provide examples of achievements from attendees and present the feedback EOSC providers have received.

Multiple sclerosis (MS) is a neurological disease characterized by immune dysregulations. Different viruses may act as MS triggering agents. MS patients respond differently to distinct viruses. The aim of our study is to verify the association between the polyomavirus BKPyV and MS, together with other neurological diseases, through the investigation of serum IgG antibodies against the virus. Sera were from patients affected by MS and other neurologic diseases, both inflammatory (OIND) and noninflammatory (NIND). Control sera were from healthy subjects (HS). Samples were analyzed for IgG antibodies against BKPyV with an indirect ELISA with synthetic peptides mimicking the viral capsid protein 1 (VP1) antigens. As control, ELISAs were carried out to verify the immune response against the Epstein-Barr virus (EBV) of patients and controls. In addition, we assessed values for total IgG in each experimental groups. A significant lower prevalence of IgG antibodies against BKPyV VP 1 epitopes, together with a low titer, was detected in sera from MS patients and other inflammatory neurologic diseases than HS. In MS patients and OIND and NIND groups, the EBV-antibody values and total IgG did not differ from HS. Experimental data indicate that patients affected by neurological diseases, including MS, are poor responders to BKPyV VP 1 antigens, thus suggesting specific immunologic dysfunctions for this polyomavirus. Our findings are relevant in understanding the immune reactions implicated in neurological disorders.

The pathways of gametogenesis encompass elaborate cellular specialization accompanied by precise partitioning of the genome content in order to produce fully matured spermatozoa and oocytes. Transcription factors are an important class of molecules that function in gametogenesis to regulate intrinsic gene expression programs, play essential roles in specifying (or determining) germ cell fate and assist in guiding full maturation of germ cells and maintenance of their populations. Moreover, in order to reinforce or redirect cell fate in vitro, it is transcription factors that are most frequently induced, over-expressed or activated. Many reviews have focused on the molecular development and genetics of gametogenesis, in vivo and in vitro, in model organisms and in humans, including several recent comprehensive reviews: here, we focus specifically on the role of transcription factors. Recent advances in stem cell biology and multi-omic studies have enabled deeper investigation into the unique transcriptional mechanisms of human reproductive development. Moreover, as methods continually improve, in vitro differentiation of germ cells can provide the platform for robust gain- and loss-of-function genetic analyses. These analyses are delineating unique and shared human germ cell transcriptional network components that, together with somatic lineage specifiers and pluripotency transcription factors, function in transitions from pluripotent stem cells to gametes. This grand theme review offers additional insight into human infertility and reproductive disorders that are linked predominantly to defects in the transcription factor networks and thus may potentially contribute to the development of novel treatments for infertility.

The epigenetic role of microRNAs is established at both physiological and pathological levels. Dysregulated miRNAs and their targets appear to be a promising approach for innovative anticancer therapies. In our previous study, circulating miR-197-3p tested dysregulated in workers ex-exposed to asbestos (WEA). Herein, an epigenetic investigation on this circulating miRNA was carried out in sera from malignant pleural mesothelioma (MPM) patients. MiR-197-3p was quantified in MPM (n = 75) sera and comparatively analyzed to WEA (n = 75) and healthy subject (n = 75) sera, using ddPCR and RT-qPCR techniques. Clinicopathological characteristics, occupational, non-occupational information and overall survival (OS) were evaluated in correlation studies. MiR-197-3p levels, analyzed by ddPCR, were significantly higher in MPM than in WEA cohort, with a mean copies/µl of 981.7 and 525.01, respectively. Consistently, RT-qPCR showed higher miR-197-3p levels in sera from MPM with a mean copies/µl of 603.7, compared to WEA with 336.1 copies/µl. OS data were significantly associated with histologic subtype and pleurectomy. Circulating miR-197-3p is proposed as a new potential biomarker for an early diagnosis of the MPM onset. Indeed, miR-197-3p epigenetic investigations along with chest X-ray, computed tomography scan and spirometry could provide relevant information useful to reach an early and effective diagnosis for MPM.

Supplementary Figure S1 - PDF file 1194K, Gamma-H2AX foci and Comet assay normalized of LNCaP plus or minus androgen normalized to time 0

Supplementary Table S2 - PDF file 250K, Defining AR-regulated DNA repair genes in LNCaP

Supplementary Figure S2 - PDF file 1705K, LNCaP cell cycle distribution by PI and BrdU analyses plus or minus androgen

Supplementary Figure S4 - PDF file 793K, Immunoblot of LNCaP demonstrating LIG4 knockdown

Supplementary Figure S3 - PDF file 1337K, LNCaP cell cycle distribution by PI and BrdU analyses plus or minus ARN-509

Supplementary Table S1 - PDF file 170K, Gene set enrichment analysis of ARN-509-treated LNCaP-AR xenografts

Este trabalho tem como objetivo apresentar um estudo sobre a relação entre Estado e Família na garantia da saúde das crianças e dos adolescentes, analisando os limites da autonomia privada em face das imposições estatais. A temática central do texto versará sobre vacinação, que merece especial atuação em razão a pandemia da Covid-19, a qual reacendeu debates nessa esfera. Para tanto, entre outros pontos, será examinada a tese fixada e o julgamento do Tema 1103 do Supremo Tribunal Federal, o qual enfrentou a problemática relacionada à obrigatoriedade de vacinação imposta pelo estado e a liberdade das convicções pessoais dos pais e responsáveis. Por fim, na conclusão, serão apontadas algumas sugestões sobre a aplicabilidade da tese e o cuidado que se deve ter com a imposição de medidas indiretas e punições para que não afetem as próprias crianças e adolescentes.

Overview of the NICEST2 project and reflection on the successes, failures and possible improvements for follow-up projects.

In this study, we focusing on understanding changes in air and water quality during the Covid-19 lockdown in the Venice Lagoon. We are re-using existing Research Objects, and in particular Jupyter Notebooks that were created in previous studies.

Fatigue is a main symptom of chronic diseases, including immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD) and inflammatory arthritis (IA); however, the pathophysiological mechanisms are not completely understood. The aim of this study was to assess the prevalence of fatigue and the associated factors in an IMIDs population. A control group, IBD, and IA patients, were enrolled. The PROMIS® fatigue questionnaire was used to evaluate the symptoms. Information on demographics, anthropometrics, disease characteristics, and medications was collected for each participant. A total of 471 subjects (137 with IBD, 103 with IA, and 206 controls) were enrolled. IBD and IA patients reported greater fatigue than controls (p < 0.001, each). In univariate regression, patients with anxiety and depression were more likely to report fatigue (p = 1.40 × 10−9 and p = 3.80 × 10−11, respectively). Males, holding a high school diploma, and being employed were inversely correlated to the domain (p = 1.3 × 10−5; p = 0.003 and p = 0.005, respectively). The use of steroids and disease activity determined increased fatigue (p = 0.014 and p = 0.019; respectively). In the multivariate analysis, anxiety and depression remained associated (p = 0.002 and p = 1.3 × 10−5, respectively). IMIDs patients present increased fatigue compared with healthy subjects. Anxiety and depression are the main associated factors, suggesting a psychological component of the symptom; thus, a holistic management should be established.

Four methods for the efficient extraction of copper from bovine and ovine liver were optimized. Sample preparation consisted of extractions with dilute nitric acid or dilute tetramethyl ammonium hydroxide, assisted by an ultrasonic bath or an ultrasonic probe. Copper was determined by flame atomic absorption spectrometry. The experimental conditions were optimized using multivariate experiments. All methods were considered adequate for copper extraction, however, the two methods involving the probe turned out to be more efficient and faster, so they were selected for subsequent validation. Trueness was verified after the analysis of a certified reference material and the performance of a microwave-assisted extraction. Results were statistically equivalent, at the 95% significance level, to the values declared on the certificate. Precision (expressed as relative standard deviation) was better than 5% for all methods. Samples obtained from Uruguayan animals were analyzed. Obtained results agreed with previous results from sheep and cattle abroad. The proposed methods are simple alternatives for food surveillance and animal status monitoring, being straightforward and aligned with Green Chemistry principles, as it was demonstrated by performing the analytical Eco-Scale comprehensive approach. A discussion related to the particle size distribution obtained during the multivariate experiments was also included, to give some deeper insight into ultrasound effect on the biological tissue in different media. In addition, ultrasound-assisted extraction was compared to magnetic stirring to prove the effect of ultrasound.

An analytical method for sample preparation and subsequent determination of Cd, Pb and Se in beef using aerosol dilution by inductively coupled plasma-mass spectrometry was developed. The use of high matrix introduction technology allowed the introduction of a complex sample into the plasma with higher content of total dissolved solids a residual acidity of 4% and better tolerance to matrix effects. Trueness was verified by the analysis of two reference materials. At the 95% significance level, results were statistically equivalent to the certified or informed values. Analytical precision expressed as relative standard deviation was less than 9% in all cases. After validation, a total of 12 beef samples from Uruguay were analyzed. Obtained levels for Cd and Pb were far below the maximum limits established by international regulations in all samples. Also, results showed that beef from this region is a good source of Se in the range 0.120–0.870 mg kg−1 with an interesting contribution to the daily intake of this essential element.

IntroductionHigh-flow nasal cannula (HFNC) provides benefits to patients undergoing flexible bronchoscopy (FOB). We compared the effects of HFNC versus standard therapy (ST) on gas exchange, lung volume and diaphragm function in patients undergoing FOB for bronchoalveolar lavage (BAL).Methods36 outpatients were randomised to ST or HFNC. Arterial blood gases, episodes of severe desaturation, changes of end-expiratory lung impedance (ΔEELI), diaphragm ultrasound were recorded. Measurements were done at baseline (T0), after bronchoscope insertion (T1), at the end of the procedure (T2) and 10 min afterwards (T3).ResultsArterial partial oxygen pressure (PaO2) was not different between T0 (10.8 (95% CI 8.7 to 12.0) kPa and T2 (11.1 (95% CI 10.4 to 12.0) kPa) with HFNC, while decreased from 11.1 (95% CI 10.5 to 12.1) to 9.1 (95% CI 8.4 to 9.8) kPa with ST. At T2, PaO2 was significantly higher with HFNC than with ST (pConclusionsDuring FOB for BAL, HFNC improves gas exchange, avoiding loss of end-expiratory lung volume and preventing increase of diaphragm activation.Trial registration numberNCT04016480.

Bone defects in maxillofacial regions lead to noticeable deformity and dysfunctions. Therefore, the use of biomaterials/scaffolds for maxillofacial bone regrowth has been attracting great interest from many surgical specialties and experts. Many approaches have been devised in order to create an optimal bone scaffold capable of achieving desirable degrees of bone integration and osteogenesis. Osteogenesis represents a complex physiological process involving multiple cooperating systems. A tight relationship between the immune and skeletal systems has lately been established using the concept of “osteoimmunology,” since various molecules, particularly those regulating immunological and inflammatory processes, are shared. Inflammatory mediators are now being implicated in bone remodeling, according to new scientific data. In this study, a profiler PCR array was employed to evaluate the expression of cytokines and chemokines in human adipose derived-mesenchymal stem cells (hASCs) cultured on porous hydroxylapatite (HA)/Collagen derived Bio-Oss®/Avitene scaffolds, up to day 21. In hASCs grown on the Bio-Oss®/Avitene biomaterial, 12 differentially expressed genes (DEGs) were found to be up-regulated, together with 12 DEG down-regulated. Chemokine CCL2, which affects bone metabolism, tested down-regulated. Interestingly, the Bio-Oss®/Avitene induced the down-regulation of pro-inflammatory inter-leukin IL-6. In conclusion, our investigation carried out on the Bio-Oss®/Avitene scaffold indicates that it could be successfully employed in maxillofacial surgery. Indeed, this composite material has the advantage of being customized on the basis of the individual patients favoring a novel personalized medicine approach.

Introduction Parastomal hernia is a type of incisional hernia occurring in abdominal integuments in the vicinity of a stoma. The best surgical approach for PSH remains controversial. Most studies report short follow-up time after surgery and a low number of cases to allow conclusions. Actually, we don't have a relevant recommendation about an optimal surgical technique or the most effective mesh for PSH repair. Presentation of the case Once packaged the latero-lateral mechanical anastomosis to restore the continuity of the intestinal tract of the patient, an adequate disinfection of trough of the stoma was done. The lateral and medial margins of the defect are then transposed towards each other and kept side by side with a gripper; a 60 mm tristaple linear stapler was placed, incorporating both edges and the charge is fired to obtain a perfect synthesis of the retromuscular plane. Discussion In the literature has been described several surgical techniques for its repair: suture repair, relocation, mesh-based technique with open or laparoscopic approach. Both, the simple corrective surgery of Thorlakson in 1965 and the use of the peritoneomuscular flap for closing the defect, suggested by Bewes, led to high incidence of recurrence. An important reduction in the rate of parastomal hernia derives also from the mesh reinforcement of the stoma trephine. Conclusion The authors suggest that this technique should be help the surgeons to repair parastomal hernia in patients with multiple risk factors to develop a recurrence of parastomal hernia., Highlights • The best surgical approach for Parastomal Hernia repair (PSH) remains controversial. • Causes that predispose to the development of incisional hernia are multiple, such as obesity and diabetes. • This technique may help the surgeons to repair the PSH in patients with risk factors to develop a recurrence after surgery.

Summary Objectives Polyomavirus (PyV) infections have been associated with different diseases. BK (BKPyV), JC (JCPyV) and simian virus 40 (SV40) are the three main PyVs whose primary infection occurs early in life. Their vertical transmission was investigated in this study. Methods PyV sequences were analyzed by the digital droplet PCR in blood, serum, placenta, amniotic fluid, vaginal smear from two independent cohorts of pregnant females and umbilical cord blood (UCB) samples. IgG antibodies against the three PyVs were investigated by indirect E.L.I.S.As with viral mimotopes. Results DNAs from blood, vaginal smear and placenta tested BKPyV-, JCPyV- and SV40-positive with a distinct prevalence, while amniotic fluids were all PyVs-negative. A prevalence of 3%, 7%, and 3% for BKPyV, JCPyV and SV40 DNA sequences, respectively, was obtained in UCBs. Serum IgG antibodies from pregnant females reached an overall prevalence of 62%, 42% and 17% for BKPyV, JCPyV and SV40, respectively. Sera from newborns (UCB) tested IgG-positive with a prevalence of 10% for BKPyV/JCPyV and 3% for SV40. Conclusions In this investigation, PyV vertical transmission was revealed by detecting PyV DNA sequences and IgG antibodies in samples from females and their offspring suggesting a potential risk of diseases in newborns.

Background: Anxiety and depression are the most common psychological disorders found in Inflammatory Bowel Disease (IBD) patients. Accurate measuring of these disorders should be proposed for prompt management. Patient-reported outcome measurements (PROMs) allow patients to self-report their psychological symptoms. Objective: The objective of this study is to highlight the presence of PROMs measuring anxiety and depression in IBD setting, evaluating the most used psychometric tools. Methods: We reviewed the literature from 2010 up to September 2021. Articles on adult IBD patients assessing depression and anxiety by PROMs in English language were included. Results: Thirty-six studies, including 11 psychometric tools were found. Hospital Anxiety and Depression Scale (21 studies), Beck Depression Inventory II (5 studies), Spielberg State-Trait Anxiety Inventory (3 studies), Patient-Reported Outcomes Measurement Information System (3 studies), Symptom Checklist-90 (2 studies), Euro Quality of Life (2 studies) mostly used psychometric tools for anxiety and depression in IBD settings. Conclusion: Our review analyzed psychometric tools used for PROMs evaluating anxiety and depression in IBD setting. No chronological differences have emerged, all have been used in the last ten years, highlighting lack of specificity. The strong association between IBD and mood disorders suggests that clinicians should consider the evaluation of depression and anxiety as integral parts of IBD clinical care. It is essential to identify tools enabling these items to be detected better. A global view of IBD patients, accounting not only for physical but also for psychical symptoms with an early and feasible assessment of unrecognized psychiatric disorders, can have a strong impact on their management strategy.

The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant gender-related differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown.We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 ± 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3'Regulatory Region (3'RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region.In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ERα) in the polymorphic enhancer hs1.2 of 3'RR-1, was significantly enriched in women with a less severe disease.These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans.

Nanoparticles (NPs) are used for drug delivery with enhanced selectivity and reduced side-effect toxicity in cancer treatments. Based on the literature, the influence of the NPs mechanical and geometrical properties on their cellular uptake has been studied through experimental investigations. However, due to the difficulty to vary the parameters independently in such a complex system, it remains hard to efficiently conclude on the influence of each one of them on the cellular internalization of a NP. In this context, different mechanical / mathematical models for the cellular uptake of NPs have been developed. In this paper, we numerically investigate the influence of the NP's aspect ratio, the membrane tension and the cell-NP adhesion on the uptake of the NP using the model introduced in

Bone defects in maxillofacial regions lead to noticeable deformity and dysfunctions. Therefore, the use of biomaterials/scaffolds for maxillofacial bone regrowth has been attracting great interest from many surgical specialties and experts. Many approaches have been devised in order to create an optimal bone scaffold capable of achieving desirable degrees of bone integration and osteogenesis. Osteogenesis represents a complex physiological process involving multiple cooperating systems. A tight relationship between the immune and skeletal systems has lately been established using the concept of "osteoimmunology," since various molecules, particularly those regulating immunological and inflammatory processes, are shared. Inflammatory mediators are now being implicated in bone remodeling, according to new scientific data. In this study, a profiler PCR array was employed to evaluate the expression of cytokines and chemokines in human adipose derived-mesenchymal stem cells (hASCs) cultured on porous hydroxylapatite (HA)/Collagen derived Bio-Oss

Presentation (slides) and demo (video) by Anne Fouilloux for the RELIANCE use case on Climate Change. The presentation and demo were given during the pan-europeans digital assets supporting research communities. Agenda of the event: On 5-6 December 2022, EOSC Future and the INFRAEOSC-07 projects (C-SCALE, DICE, EGI-ACE, OpenAIRE Nexus, Reliance) are hosting an online use case showcase. Check out the agenda and register for this online interactive event by 4 December, 23.59 CET. Over 2 half-day webinars, actual EOSC users will present how their research communities are using EOSC digital assets to address scientific and societal challenges related to 3 UN Sustainable Development Goals (SDGs): • Climate action (SDG 13) • Industry, Innovation & infrastructure (SDG 9) • Good health & well-being (SDG 3) There will also be a session with use cases related to Open Science more broadly. Why ‘use cases’? The demonstrative, first-hand format of the event will enable real research communities to show how their work can be leveraged by EOSC. Researchers, disciplinary groups and anyone interested to learn about both EOSC-related tools and services for data sharing and discoverability as well as discipline-related solutions are invited to the webinar. Attendees will also hear first-hand accounts from early-adopter communities that have integrated some of these core EOSC services. 1 programme, 2 days Check out the agenda to get a glimpse of the cases in the programme, in addition to a at the users, EU and UN officials who will be weighing in on discussions. Day 1 – 5 December • 09.30-11.00: Digital assets supporting SDG 13: Climate action • 11.15-12.00: Digital assets supporting SDG 3: Good health and well-being • 12:15-13:00: Discovering services for open science Day 2 – 6 December • 09.00-09.45: Digital assets supporting SDG 9 Industry, innovation and infrastructure • 10.00-10.45: Experiences from Early Adopters approaching EOSC: the RELIANCE Open challenge • 11.00-12.00: Lessons Learnt from use cases and Looking forward

This Research Object demonstrates how to use CAMS European air quality analysis from Copernicus Atmosphere Monitoring with RELIANCE services and compute monthly map of NO2 over a given geographical area, here Spain

This Research Object aggregates all the different Research Objects and resources used for presenting the Environmental Data Science Book at AGU 2022. The Environmental Data Science book is a living, open and community-driven online resource to showcase and support the publication of data, research and open-source tools for collaborative, reproducible and transparent Environmental Data Science. The Environmental Data Science is: a book a community a global collaboration We target to make sense of: environmental systems environmental data and sensors innovative research in Environmental Data Science open-source tools for Environmental Data Science We hope you find the content in the resource helpful. The resource and executable notebooks are free under a CC-BY licence and OSI-approved MIT license, respectively.

Systemic Sclerosis (SSc) is an autoimmune disorder characterized by organ and tissue fibrosis in which the incidence of atherosclerosis and cardiovascular events is increased, although the exact underlying mechanism remains unclear. Arterial stiffness is a marker of vascular damage that can predict cardiovascular events; therefore, this study aimed to assess the augmentation index (AIx) and pulse wave velocity (PWV), markers of stiffness, in a Systemic Sclerosis population and to detect potentially associated variables. Fourteen female Systemic Sclerosis patients and 14 age- and sex-matched controls were enrolled. Demographic, anthropometric, sero-hematological parameters and disease characteristics were collected for each participant. Arterial stiffness was evaluated using an applanation tonometry system. No differences were found between groups, except for BMI, fasting blood glucose, red blood cells count, hemoglobin, and treatment. Patients had increased augmentation index than the controls (p = 0.008). PWV was significantly decreased in SSc patients compared with the controls (p = 0.007). PWV was correlated with age (r = 0.462; p = 0.048) and BMI (r = 0.458; p = 0.050). Finally, patients with no specific auto-antibody pattern had greater AIx than those expressing anticentromere antibodies. Our study demonstrated that SSc patients had greater AIx, but lower PWV than the controls. In addition, few variables were correlated to arterial stiffness. Further studies are necessary to validate these findings and to establish medication’s role in modifying cardiovascular risk.

Background: The introduction of biological agents into the clinical armamentarium has modified the management of moderate-severe inflammatory arthritis (IA). However, these drugs can lead to serious adverse events (SAEs) and unpredictable adverse events (AEs) that are difficult to detect in pre-marketing clinical trials. This pharmacovigilance project aimed to study the AEs associated with biologics use in rheumatology. Methods: The current investigation is a multicenter, prospective, observational cohort study based on the Calabria Biologics Pharmacovigilance Program. Patients treated with one biologic agent from January 2016 to January 2022 were enrolled. Results: Overall, 729 (86.3%) of a total of 872 patients did not develop AEs or SAEs, whereas 143 (16.4%) patients experienced at least one AE, of which 16 (1.8%) had at least one SAE. The most common AEs were administration site conditions followed by gastrointestinal, nervous system and skin disorders. We reported a total of 173 switches and 156 swaps. Switches mainly occurred for inefficacy (136; 77.7%), whereas only 39 (22.3%) were due to the onset of an AE. Primary/secondary failure was the most frequent reason for swaps (124, 79%), while AEs onset led to 33 (21%) swaps. Conclusions: This study supports the validity of our program in monitoring and detecting AEs in the rheumatological area, confirming the positive beneficial/risk ratio of biologics.

International audience; Merkel cell polyomavirus (MCPyV), a small DNA tumor virus, has been detected in Merkel cell carcinoma (MCC) and in normal tissues. Since MCPyV infection occurs in both MCC-affected patients and healthy subjects (HS), innovative immunoassays for detecting antibodies (abs) against MCPyV are required. Herein, sera from HS were analyzed with a novel indirect ELISA using two synthetic peptides mimicking MCPyV capsid protein epitopes of VP1 and VP2. Synthetic peptides were designed to recognize IgGs against MCPyV VP mimotopes using a computer-assisted approach. The assay was set up evaluating its performance in detecting IgGs anti-MCPyV on MCPyV-positive (n=65) and -negative (n=67) control sera. Then, the ELISA was extended to sera (n=548) from HS aged 18-65 yrs old. Age-specific MCPyV-seroprevalence was investigated. Performance evaluation indicated that the assay showed 80% sensitivity, 91% specificity and 83.9% accuracy, with positive and negative predictive values of 94.3% and 71%, respectively. The ratio expected/obtained data agreement was 86%, with a Cohen’s kappa of 0.72. Receiver-operating characteristic (ROC) curves analysis indicated that the areas under the curves (AUCs) for the two peptides were 0.82 and 0.74, respectively. Intra-/inter-run variations were below 9%. The overall prevalence of serum IgGs anti-MCPyV in HS was 62.9% (345/548). Age-specific MCPyV-seroprevalence was 63.1% (82/130), 56.7% (68/120), 64.5% (91/141), and 66.2% (104/157) in HS aged 18-30, 31-40, 41-50 and 51-65 yrs old, respectively (p>0.05). Performance evaluation suggests that our indirect ELISA is reliable in detecting IgGs anti-MCPyV. Our immunological data indicate that MCPyV infection occurs asymptomatically, at a relatively high prevalence, in humans.

Over the past decades, age-related pathologies have increased abreast the aging population worldwide. The increased age of the population indicates that new tools, such as biomaterials/scaffolds for damaged tissues, which display high efficiency, effectively and in a limited period of time, for the regeneration of the body's tissue are needed. Indeed, scaffolds can be used as templates for three-dimensional tissue growth in order to promote the tissue healing stimulating the body's own regenerative mechanisms. In tissue engineering, several types of biomaterials are employed, such as bioceramics including calcium phosphates, bioactive glasses, and glass–ceramics. These scaffolds seem to have a high potential as biomaterials in regenerative medicine. In addition, in conjunction with other materials, such as polymers, ceramic scaffolds may be used to manufacture composite scaffolds characterized by high biocompatibility, mechanical efficiency and load-bearing capabilities that render these biomaterials suitable for regenerative medicine applications. Usually, bioceramics have been used to repair hard tissues, such as bone and dental defects. More recently, in the field of soft tissue engineering, this form of scaffold has also shown promising applications. Indeed, soft tissues are continuously exposed to damages, such as burns or mechanical traumas, tumors and degenerative pathology, and, thereby, thousands of people need remedial interventions such as biomaterials-based therapies. It is known that scaffolds can affect the ability to bind, proliferate and differentiate cells similar to those of autologous tissues. Therefore, it is important to investigate the interaction between bioceramics and somatic/stem cells derived from soft tissues in order to promote tissue healing. Biomimetic scaffolds are frequently employed as drug-delivery system using several therapeutic molecules to increase their biological performance, leading to ultimate products with innovative functionalities. This review provides an overview of essential requirements for soft tissue engineering biomaterials. Data on recent progresses of porous bioceramics and composites for tissue repair are also presented.

The electrical signal emitted by the eyes movement produces a very strong artifact on EEG signal due to its close proximity to the sensors and abundance of occurrence. In the context of detecting eye blink artifacts in EEG waveforms for further removal and signal purification, multiple strategies where proposed in the literature. Most commonly applied methods require the use of a large number of electrodes, complex equipment for sampling and processing data. The goal of this work is to create a reliable and user independent algorithm for detecting and removing eye blink in EEG signals using CNN (convolutional neural network). For training and validation, three sets of public EEG data were used. All three sets contain samples obtained while the recruited subjects performed assigned tasks that included blink voluntarily in specific moments, watch a video and read an article. The model used in this study was able to have an embracing understanding of all the features that distinguish a trivial EEG signal from a signal contaminated with eye blink artifacts without being overfitted by specific features that only occurred in the situations when the signals were registered. Los potenciales eléctricos generados por parpadeos oculares producen ruidos muy significativos en las señales de electroencefalografía (EEG). La presencia numerosa de este tipo de artefacto se debe a la proximidad de los ojos a los sensores utilizados para capturar las señales. En la literatura se proponen muchas estrategias para detectar tales artefactos, con el objetivo de eliminarlos para purificar la señal de EEG. Los métodos mas comúnmente utilizados requieren el uso de una gran cantidad de electrodos y equipos complejos para el procesamiento de señales. El objetivo de éste proyecto es utilizar un modelo de red neuronal convolucional (CNN) para crear un algoritmo independiente y confiable capaz de detectar artefactos de parpadeos para que puedan ser eliminados. Para el proceso de entrenamiento y validación del modelo creado, se utilizaron tres conjuntos de datos de dominio público recolectados a través de experimentos llevados a cabo por expertos en la materia. Los tres conjuntos utilizados contienen señales recolectadas, mientras los participantes del experimento realizaron tareas tales como parpadear voluntariamente, ver un video y leer un artículo. El modelo desarrollado en este proyecto logró aprender ampliamente las características que diferencian una señal EEG normal de una señal contaminada por ruido de parpadeo ocular, sin necesidad de utilizar registros de eventos particulares que ocurren durante la recolección de las señales. Os potenciais elétricos emitidos pelas piscadas dos olhos produzem ruídos muito fortes em sinais de eletroencefalografia (EEG). A numerosa presença desse artefato é causada pela grande proximidade entre os olhos e os sensores usados para captação dos sinais. Muitas estratégias para detectar tais artefatos são propostas na literatura, visando sua remoção para purificação do sinal de EEG. Os métodos comumente aplicados requerem a utilização de um grande número de eletrodos e equipamentos complexos para tratamento e processamento dos sinais. O objetivo desse projeto é utilizar um modelo de rede neural convolucional (CNN) para criar um algoritmo independente e confiável, capaz de detectar artefatos provenientes de piscadas para que possam ser removidos. Para o processo de treino e validação do modelo criado, foram usados três conjuntos de dados de domínio público disponibilizados por experimentos realizados por estudiosos da área. Os três conjuntos usados contêm amostras coletadas, enquanto os participantes do experimento realizavam diferentes tarefas, tais como piscar voluntariamente, assistir a um vídeo e ler um artigo. O modelo desenvolvido nesse projeto foi capaz de ter um amplo aprendizado sobre as características que diferenciam um sinal normal de EEG de um sinal contaminado por ruídos de piscadas sem ficar preso a características particulares ocorridas somente durante a realização de cada tarefa.

The term altruism in Italian contains semantic root “other” that means the one who is distinct from itself. Its meaning indicates love towards one's neighbor, more particularly, the attitude of one who directs his work towards the goal of achieving the good of others (or if you prefer, to find the own good in the good of others). Educating the students requires a particular educational-training plan. The school is responsible of this type of education, which is not only necessary within the class, but it is the necessary attitude to face the increasingly complex social problems of our time. The self-centered culture is infusing in everyone the convinction that people do not need a community anymore, promoting the abandonment of feelings, and of the sharing of relationships with the neighbor. The path to take is based on the education to the developmet of pro-socal competences, bringing into play the community as a relationship founded on the research of the common welfare.

The Community Earth System Model (CESM) from the National Center for Atmospheric Research is a fully-coupled, community, global climate model allowing state-of-the-art computer simulations of the Earth’s past, present and future climates. The Norwegian Earth System Model (NorESM) builds on it, with major changes in the aerosol-cloud chemistry (developed at the Meteorological Institute and University of Oslo), the ocean and its biogeochemistry (originally Miami Isopycnic Coordinate Ocean Model and Hamburg Model of Ocean Carbon Cycle, respectively, modified at the University of Bergen, Nansen Environmental and Remote Sensing Center, and Norwegian Research Center AS). In addition schemes are implemented to compute turbulent atmosphere-ocean fluxes, for atmospheric energy and momentum conservation, etc. Basically CESM/NorESM are composed of separate components to simulate the Earth’s atmosphere, ocean, land, river run-off, land-ice, and sea-ice, plus one central coupler/moderator synchronizing exchanges between them. CESM/NorESM make it possible to conduct fundamental research into the biological, geophysical and chemical processes governing the system and to explore socioeconomic scenarios for instance in Coupled Model Intercomparison Projects (CMIPs). Users of CESM/NorESM (or similar models) do not have the same computational resource needs. On the one side production (to simulate hundreds or thousands of years) demand maximum power (in Petaflops range) which only large national and European High-Performance Computers (HPCs) can deliver. On the other side, for model developments, debugging, testing and validation as well as for teaching purposes what matters most is a flexible framework. For post-processing, analysis and visualization of model data, co-location of the tools (Jupyter notebooks, as an example) and data is paramount to avoid transfers. When it comes to collaborations and reproducible research, sine qua non conditions are the possibility of sharing files and using the same run-time environment. Far from competing against HPCs in terms of sheer computing power, Galaxy is nonetheless capable of satisfying the everyday needs of the vast majority of CESM/NorESM users described hereinabove, thereby becoming an asset in environmental research communities. Galaxy/Live with its Interactive Climate JupyterLab offers: a Virtual Laboratory for developing, testing and deploying climate model workflows before they are ready to go in production on larger systems, as well as for training, to instill the fundamentals of the Earth System; a Data analysis platform for analyzing and visualizing Climate data produced by researchers as well as from national and international projects such as CMIP, the Coordinated Regional Downscaling Experiment (CORDEX) and/or Copernicus Climate Change Service (C3S)., EOSC-Nordic project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 857652

Bone metabolism consists of a balance between bone formation and bone resorption, which is mediated by osteoblast and osteoclast activity, respectively. In order to ensure bone plasticity, the bone remodeling process needs to function properly. Mesenchymal stem cells differentiate into the osteoblast lineage by activating different signaling pathways, including transforming growth factor β (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1 (Wnt)/β-catenin pathways. Recent data indicate that bone remodeling processes are also epigenetically regulated by DNA methylation, histone post-translational modifications, and non-coding RNA expressions, such as micro-RNAs, long non-coding RNAs, and circular RNAs. Mutations and dysfunctions in pathways regulating the osteoblast differentiation might influence the bone remodeling process, ultimately leading to a large variety of metabolic bone diseases. In this review, we aim to summarize and describe the genetics and epigenetics of the bone remodeling process. Moreover, the current findings behind the genetics of metabolic bone diseases are also reported.

Cu and Zn bioaccessibility was studied in two different beef cuts (rib plate and top sirloin), through the development of an in vitro assay. Samples were cooked at two degrees of doneness (medium and well-done) as usually consumed locally, to establish the contribution to the recommended daily allowance (RDA). Simulated gastrointestinal conditions were optimized and trueness of the method was evaluated by performing mass balances. Analytical determinations were performed by atomic absorption spectrometry and microwave-induced plasma optical emission spectrometry. No significant differences were found between the studied cuts nor between the degrees of doneness evaluated. Mean bioaccessible fraction (BF) of Zn was 83%, for both cuts and both degrees of doneness. In the case of Cu, rib plate presented a mean BF of 20%, while for top sirloin was of 38%. However, these differences found between cuts and degrees of doneness were not statistically significant. The contribution of Cu and Zn to the RDA for adults over 19 years was estimated, as an example, considering a 200 g portion. Results showed that the RDA of Zn would be completely covered, while the contribution to the RDA of Cu would be up to 33%.

Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens to drive expression of the normally silent E26 transformation-specific (ETS) transcription factor ERG in prostate cells. Recent genomic landscape studies of such cancers have reported recurrent point mutations and focal deletions of another ETS member, the ETS2 repressor factor ERF. Here we show these ERF mutations cause decreased protein stability and mostly occur in tumours without ERG upregulation. ERF loss recapitulates the morphological and phenotypic features of ERG gain in normal mouse prostate cells, including expansion of the androgen receptor transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of Pten loss that yields oncogenic activity by ERG. In the more common scenario of ERG upregulation, chromatin immunoprecipitation followed by sequencing indicates that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites both in normal and in cancerous prostate cells. Consistent with a competition model, ERF overexpression blocks ERG-dependent tumour growth, and ERF loss rescues TMPRSS2-ERG-positive prostate cancer cells from ERG dependency. Collectively, these data provide evidence that the oncogenicity of ERG is mediated, in part, by competition with ERF and they raise the larger question of whether other gain-of-function oncogenic transcription factors might also inactivate endogenous tumour suppressors.