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Transient abnormal myelopoiesis (TAM) is a Down syndrome-related pre-leukaemic condition characterized by somatic mutations in the haematopoietic transcription factor GATA-1 that result in exclusive production of its shorter isoform (GATA-1S). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1S, we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an in silico prediction of miRNA binding sites in the GATA-1 transcript, miR-1202 came into our sight as potential regulator of GATA-1 expression. Expression studies in K562 cells revealed that miR-1202 directly targets GATA-1, negatively regulates its expression, impairs GATA-1S production, reduces cell proliferation, and increases apoptosis sensitivity. Furthermore, data from TAM and myeloid leukaemia patients provided substantial support to our study by showing that miR-1202 down-modulation is accompanied by increased GATA-1 levels, with more marked effects on GATA-1S. These findings indicate that miR-1202 acts as an anti-oncomiR in myeloid cells and may impact leukaemogenesis at least in part by down-modulating GATA-1S levels.

Since its inception, research in the field of Artificial Intelligence (AI) has had a fundamentally logical approach; therefore, discussions have taken place to establish a way of distinguishing symbolic AI from sub-symbolic AI, basing the approach instead on the statistical approaches typical of machine learning, deep learning or Bayesian networks [...]

The Pfam protein families database is a comprehensive collection of protein domains and families used for genome annotation and protein structure and function analysis (https://www.ebi.ac.uk/interpro/). This update describes major developments in Pfam since 2020, including decommissioning the Pfam website and integration with InterPro, harmonization with the ECOD structural classification, and expanded curation of metagenomic, microprotein and repeat-containing families. We highlight how AlphaFold structure predictions are being leveraged to refine domain boundaries and identify new domains. New families discovered through large-scale sequence similarity analysis of AlphaFold models are described. We also detail the development of Pfam-N, which uses deep learning to expand family coverage, achieving an 8.8% increase in UniProtKB coverage compared to standard Pfam. We discuss plans for more frequent Pfam releases integrated with InterPro and the potential for artificial intelligence to further assist curation. Despite recent advances, many protein families remain to be classified, and Pfam continues working toward comprehensive coverage of the protein universe., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Wildfires lead to socio-economic and environmental impacts. These impacts include hydrological instability, which can cause severe damage, especially where infrastructures are present. Post-rehabilitation measures can be useful in reducing or preventing erosion or hydrogeological risks. Decision-makers are called on to prioritize post-fire intervention areas and allocate public funds for this purpose. This work focuses on the assessment of erosion and hydrological risk potential in forested slope areas affected by wildfire using a Multi-Criteria Decision Analysis (MCDA) approach integrated with a GIS environment on a regional scale. Expert perception was considered using the pairwise comparison method as part of the Analytical Hierarchy Process (AHP). This allows expert stakeholders to rank relevant criteria, providing a quantitative metric (weight) for qualitative data. Two MCDA methods are used and compared: Weighted Linear Combination (WLC) and Ordered Weighted Averaging (OWA). Fire frequency, slope (gradient and length), and proximity to infrastructures were found to be the most important factors by the stakeholders. The WLC method provides evidence classified into high and moderate suitability class areas characterized by high values for fire frequency or slope gradient. Conversely, the OWA method, ranging from low to high risks, makes it possible to adapt the method and obtain a range of suitability maps. Novelties of the MCDA-GIS combined methodology adopted in this work are its application on a regional scale and the combination of vulnerability and driving-force factors (namely presence of grey infrastructures, fire frequency). The MCDA-GIS methodology can be suitable for public administrations in that it allows for mapping a regional area more quickly and thus facilitates sector planning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Giant cell arteritis (GCA) is a chronic inflammatory vasculitis with a significant impact on vascular and patient health. It may present with non-specific symptoms and can lead to severe complications if not managed effectively. This narrative review explores the treatment of GCA with interleukin-6 (IL-6) pathway inhibitors, focusing on key studies from selected databases published between 2018 and 2024. The findings reveal that the current treatment primarily involves glucocorticoids (GCs), but their long-term use is associated with adverse effects. Targeting the IL-6 pathway offers therapeutic benefits by reducing inflammation and sparing GC use. Tocilizumab, a humanized immunoglobulin G1κ monoclonal antibody that blocks the IL-6 receptor, has demonstrated efficacy in achieving sustained remission and improving quality of life in people with GCA. However, challenges remain in understanding the optimal duration of therapy, managing relapse upon discontinuation, and addressing long-term structural vascular outcomes. Additional research is needed to further elucidate the complex pathogenesis of GCA and to optimize treatment strategies to achieve sustained remission both clinically and histologically while minimizing adverse effects. This review provides a comprehensive overview of the evidence of IL-6 inhibition in GCA management, highlighting both its therapeutic benefits and the challenges associated with its use., Competing Interests: Declaration of competing interest Maxime Samson has received remuneration from Chugai (invitation to congresses, remuneration for symposium and consulting payments), AstraZeneca (invitations to congresses, consulting payments), Novartis (research grant, consulting payments, invitation to congresses, remuneration for symposium), CSL Vifor (invitation to congresses, remuneration for symposium and consulting payments), Boehringer Ingelheim (invitation to congresses, consulting payments), Argenx (consulting payments), Fresenius Kabi (consulting payments, invitation to congresses, remuneration for symposium), and GSK (consulting payments, invitation to congresses, remuneration for symposium). Maria C. Cid has acted as a consultant for Glaxo Smith Kline, AbbVie, AstraZeneca, CSL-Vifor, Boehringer Ingelheim, Alexion, and Novartis; received a research grant from Kiniksa Pharmaceuticals Ltd.; and has received funding from Ministerio de Ciencia, Innovación y Universidades, AEI (PID2023-152265OB-I00). Christian Pagnoux reports receiving fees for serving on advisory boards from ChemoCentryx, Otsuka, GlaxoSmithKline, AstraZeneca, Sanofi, and Hoffman-LaRoche; lecture fees from Hoffman-La Roche, GlaxoSmithKline, Otsuka, and CSL Vifor; and educational grant support from Hoffman-La Roche, Otsuka, Pfizer, TEVA, Amgen, and GlaxoSmithKline. Wolfgang A. Schmidt has received consultant fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Fresenius Kabi, GlaxoSmithKline, Novartis, and Sanofi; speaker's bureau fees from AbbVie, Amgen, Bristol Myers Squibb, Chugai, GlaxoSmithKline, Lilly, Johnson & Johnson, Medac, Novartis, Pfizer, Roche, Sanofi, and UCB. He is the principal investigator in trials sponsored by AbbVie, GlaxoSmithKline, Novartis, and Sanofi. Rula A. Hajj-Ali has acted as a consultant for Amgen and GlaxoSmithKline and has received royalties from UpToDate, outside the submitted work. Bhaskar Dasgupta reports grants and personal fees from Roche, and personal fees from GSK, BMS, Sanofi, and AbbVie, outside the submitted work. Anthony Sammel and Carlo Salvarani report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Precision Oncology requires deep changes in organizational settings but little evidence has been identified about the best strategy to guarantee the delivery of this innovation to patients. In the Italian health care system, high heterogeneity could jeopardize equal access opportunity for patients. Following a consensus method, we aim to define shared solutions to address these issues in clinical practice., Method: A Delphi RAND method was chosen to record the consensus among involved health care professionals in the Italian region of Friuli Venezia Giulia. The item generation phase was conducted following a bottom-up approach., Results: Ten statements were defined on the main topics that emerged from the direct observation of the current practice, focusing on Molecular Tumor Board organization, massive parallel sequencing technology application, laboratory report content and informed consensus submission. All the statements reached a strong consensus and have been shared with the health care government authorities of our region., Conclusions: The direct observation of the current practice in different health care authorities allowed to define ten statements as solution proposals to solve the identified complexities. This methodological approach could be applied in different organizational models but aiming to achieve a homogeneous clinical outcome for patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Maria Carla Barducci reports a relationship with Roche that includes: speaking and lecture fees. Giacomo Pelizzari reports a relationship with Roche that includes: speaking and lecture fees. This work was supported by an unconditioned grant collected by the Healthcare Local Authority of Friuli Centrale (ASUFC) with a public call sponsorship. The contributions were by Roche, Bayer, and Amgen. The sponsors had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Advances in cancer detection and treatment have extended cancer survivors' (CSs) life expectancy, but their evolving health needs remain unmet. This study analyzes 14 patient-reported outcome measures (PROMs) for CSs with non-cutaneous cancers using the International Classification of Functioning, Disability and Health (ICF) framework. These 14 PROMs are derived from a recent review focusing on the implementation of the routine assessment of unmet needs in cancer survivors., Methods: Each PROM was examined for correspondence to ICF health and functioning dimensions. Two independent reviewers extracted meaningful concepts from each PROM item, linking them to ICF categories. Discrepancies were resolved through discussion with a third expert reviewer., Results: PROMs varied in ICF component correspondence, with "Activities and Participation" (37.2%) and "Environmental Factors" (31.8%) most frequently represented, highlighting their significance. "Body Structures" (1%) received minimal attention, suggesting its limited relevance to CSs' needs. The results of the linking process show the differences between the various PROMs: Candi and eHNA were primarily linked to "Body Function" (53.4% and 51.4%, respectively), NEQ and SUN to "Activities and Participation," and CaSUN and PNI to "Environmental Factors" (51.7% and 50%, respectively), while eHNA had the highest percentage of items linked to "Body Structures" (8.1%)., Conclusions: This evaluation of PROMs enhances the understanding of CSs' diverse needs so as to address them, thereby improving these individuals' quality of life., Implications for Cancer Survivors: The study underscores the importance of addressing "Activities and Participation" and "Environmental Factors" in PROMs for CSs. These insights support developing comprehensive PROMs and help healthcare providers prioritize critical areas of survivorship care, ultimately enhancing CSs' well-being., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Technological advances in high-throughput technologies improve our ability to explore the molecular mechanisms of life. Computational infrastructures for scientific applications fulfil a critical role in harnessing this potential. However, there is an ongoing need to improve accessibility and implement robust data security technologies to allow the processing of sensitive data, particularly human genetic data. Scientific clouds have emerged as a promising solution to meet these needs. We present three components of the Laniakea software stack, initially developed to support the provision of private on-demand Galaxy instances. These components can be adopted by providers of scientific cloud services built on the INDIGO PaaS layer. The Dashboard translates configuration template files into user-friendly web interfaces, enabling the easy configuration and launch of on-demand applications. The secret management and the encryption components, integrated within the Dashboard, support the secure handling of passphrases and credentials and the deployment of block-level encrypted storage volumes for managing sensitive data in the cloud environment. By adopting these software components, scientific cloud providers can develop convenient, secure and efficient on-demand services for their users., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

The main objective of this review is to examine the impact of balneotherapy on serum and salivary cortisol concentrations. A systematic search was conducted in PubMed, Scopus, Web of Science, PEDro, and Google Scholar. The databases were screened from inception up until April 2024. After screening the scientific literature, 845 articles were retrieved and 17 studies, involving a total of 765 participants, were eventually included in the review. Among them, four were randomized controlled trials, five were non-randomized studies, and eight were pre-post studies with no control group. The evidence gathered in this review indicates a significant short-term reduction in cortisol levels in healthy individuals undergoing balneotherapy, particularly those experiencing high levels of stress. Conversely, in patients with rheumatic conditions (especially if elderly), increases in cortisol levels induced by balneotherapy can act as beneficial hormetic stress, reducing inflammatory mediators and improving pain and functional quality of life. The meta-analysis shows an overall trend of reduction in stress hormone levels, more pronounced in the intervention group undergoing mud-balneotherapy compared to the control group, a finding that, however, does not reach statistical significance (g=-0.11 [95% CI: -0.30; 0.08]; p > 0.05). Current scientific evidence demonstrates that balneotherapy has a positive impact on the regulation of cortisol levels. The regulation of the hypothalamic-pituitary-adrenal axis and the beneficial effects observed on health parameters and quality of life allow mud-balneotherapy to be classified as eustressful stimuli useful in preventing stress-related pathologies in healthy individuals and in alleviating symptoms in patients with chronic conditions. Future research on the topic is advised., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

The dissolution of CO 2 in seawater in the form of bicarbonate ions is an attractive alternative to storage in geological formations, on the condition that the storage is stable over long periods and does not harm the marine environment. In this work, we focus on the long-term chemical stability of CO 2 absorbed in seawater as bicarbonate by monitoring the physico-chemical properties of the solutions (pH, dissolved inorganic carbon and alkalinity) in six different sets of experiments on both natural and artificial seawater lasting up to three months. The bicarbonate treatment of natural seawater consists of mixing it with pre-equilibrated solutions obtained from the reaction of CO 2 and Ca(OH) 2 , with the same pH as natural seawater. This was achieved with a pilot plant working with tons of seawater, while small-scale laboratory experiments were carried out by adding sodium bicarbonate to artificial seawater solutions. If the increase in the overall carbon concentration in the final mixture does not exceed a critical threshold (about 1000-1500 μmol/L), the resulting bicarbonate-rich solutions are found to be stable for over three months.

The greater amberjack Seriola dumerili is a promising candidate for aquaculture production. This study compares the ovary transcriptome of greater amberjack sampled in the wild (WILD) with hatchery-produced breeders reared in aquaculture sea cages in the Mediterranean Sea. Among the seven sampled cultured fish, three were classified as reproductively dysfunctional (DysF group), while four showed no signs of reproductive alteration (NormalF group). The DysF fish showed 1,166 differentially expressed genes (DEGs) compared to WILD females, and 755 DEGs compared to the NormalF. According to gene ontology (GO) analysis, DysF females exhibited enrichment of genes belonging to the biological categories classified as Secreted, ECM-receptor interaction, and Focal adhesion. Protein-protein interaction analysis revealed proteins involved in the biological categories of ECM-receptor interaction, Enzyme-linked receptor protein signaling, Wnt signal transduction pathways, and Ovulation cycle. KEGG pathway analysis showed DEGs involved in 111 pathways, including Neuroactive ligand-receptor interaction, Steroid hormone biosynthesis, Cell cycle, Oocyte meiosis, Necroptosis, Ferroptosis, Apoptosis, Autophagy, Progesterone-mediated oocyte maturation, Endocytosis and Phagosome, as well as Hedgehog, Apelin, PPAR, Notch, and GnRH signalling pathways. Additionally, DysF females exhibited factors encoded by upregulated genes associated with hypogonadism and polycystic ovary syndrome in mammals. This study -which is part of a broader research effort examining the transcriptome of the entire reproductive axis in greater amberjack of both sexes-, enhances our comprehension of the mechanisms underlying the appearance of reproductive dysfunctions when fish are reared under aquaculture conditions., (© 2024. The Author(s).)

Purpose: This systematic review aimed to investigate the therapeutic relationship (TR) between mental health professionals (MHPs) and their patients in community mental health services (CMHS)., Methods: PubMed (Medline), PsycINFO, CINAHL, CENTRAL, and Web of Science were searched for studies that assessed TR in CMHS using quantitative measures developed specifically for this setting (i.e., Helping Alliance Scale [HAS] and the Scale to Assess the Therapeutic Relationship [STAR]). Studies were included if they considered adult patients with a psychiatric disorder and/or any MHP working in CMHS. Meta-analysis and narrative synthesis assessed the association between patients' and MHPs' ratings and identified predictors of TR., Results: Of 1934 studies, 15 were included in the review, including 3004 patients. A total of 1127 patients and 963 MHPs were considered in the meta-analysis. The heterogeneity of the studies was high, and there was no significant difference between the patients' and MHPs' TR ratings in the random-effects model (standardized mean difference [SMD]: - 0.39 [95% CI: - 1.03; 0.24]). In the multivariable meta-regression, only duration of illness was significantly associated with TR ratings (unstandardized regression coefficient [B]: 0.388 [95% CI: 0.217; 0.558]). A recovery-oriented service, shared decision-making, and the recognition of patient needs contributed to more positive TR ratings., Conclusion: Patients and MHPs converged in their TR ratings, although patients gave lower ratings. Routine assessment of TR in CMHS can inform reflective practice and service development, as TR can be assessed easily and early in the treatment process. Future research should focus on developing and testing interventions to improve TR in CMHS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The DisProt database is a resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect structural and functional information into proteins that lack a fixed three-dimensional structure. Today, DisProt has evolved into a major repository that not only collects experimental data but also contributes to our understanding of the IDPs/IDRs roles in various biological processes, such as autophagy or the life cycle mechanisms in viruses or their involvement in diseases (such as cancer and neurodevelopmental disorders). DisProt offers detailed information on the structural states of IDPs/IDRs, including state transitions, interactions and their functions, all provided as curated annotations. One of the central activities of DisProt is the meticulous curation of experimental data from the literature. For this reason, to ensure that every expert and volunteer curator possesses the requisite knowledge for data evaluation, collection and integration, training courses and curation materials are available. However, biocuration guidelines concur on the importance of developing robust guidelines that not only provide critical information about data consistency but also ensure data acquisition.This guideline aims to provide both biocurators and external users with best practices for manually curating IDPs and IDRs in DisProt. It describes every step of the literature curation process and provides use cases of IDP curation within DisProt. Database URL: https://disprot.org/., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Macroalgae, especially reds (Rhodophyta Division) and browns (Phaeophyta Division), are known for producing various halogenated compounds. Yet, the reasons underlying their production and the fate of these metabolites remain largely unknown. Some theories suggest their potential antimicrobial activity and involvement in interactions between macroalgae and prokaryotes. However, detailed investigations are currently missing on how the genetic information of prokaryotic communities associated with macroalgae may influence the fate of organohalogenated molecules., Results: To address this challenge, we created a specialized dataset containing 161 enzymes, each with a complete enzyme commission number, known to be involved in halogen metabolism. This dataset served as a reference to annotate the corresponding genes encoded in both the metagenomic contigs and 98 metagenome-assembled genomes (MAGs) obtained from the microbiome of 2 red (Sphaerococcus coronopifolius and Asparagopsis taxiformis) and 1 brown (Halopteris scoparia) macroalgae. We detected many dehalogenation-related genes, particularly those with hydrolytic functions, suggesting their potential involvement in the degradation of a wide spectrum of halocarbons and haloaromatic molecules, including anthropogenic compounds. We uncovered an array of degradative gene functions within MAGs, spanning various bacterial orders such as Rhodobacterales, Rhizobiales, Caulobacterales, Geminicoccales, Sphingomonadales, Granulosicoccales, Microtrichales, and Pseudomonadales. Less abundant than degradative functions, we also uncovered genes associated with the biosynthesis of halogenated antimicrobial compounds and metabolites., Conclusion: The functional data provided here contribute to understanding the still largely unexplored role of unknown prokaryotes. These findings support the hypothesis that macroalgae function as holobionts, where the metabolism of halogenated compounds might play a role in symbiogenesis and act as a possible defense mechanism against environmental chemical stressors. Furthermore, bacterial groups, previously never connected with organohalogen metabolism, e.g., Caulobacterales, Geminicoccales, Granulosicoccales, and Microtrichales, functionally characterized through MAGs reconstruction, revealed a biotechnologically relevant gene content, useful in synthetic biology, and bioprospecting applications. Video Abstract., (© 2024. The Author(s).)

Intravascular large B-cell lymphoma (IVLBCL) is a rare aggressive extranodal non-Hodgkin lymphoma. The predominant, if not exclusive, growth of neoplastic cells within the lumina of small-sized vessels represents the hallmark of the disease. Diagnosis is challenging due to the absence of marked lymphadenopathy, the highly heterogeneous clinical presentation, and the rarity of the condition. Clinical presentation is characterized by variable combinations of nonspecific signs and symptoms (such as fever and weight loss), organ-specific focal manifestations due to altered perfusion, and hemophagocytic syndrome. The rarity of this entity and the paucity of neoplastic cells in biopsy samples hamper the study of recurrent molecular abnormalities. The purpose of this study was to explore the feasibility of a different approach to recover a sufficient amount of DNA of acceptable quality to perform next-generation sequencing studies. Here, we report the findings of whole-exome next-generation sequencing performed on a fresh-frozen cutaneous sample of IVLBCL, paired with the patient saliva used as germline DNA. To increase the cancer cell fraction, only the subcutaneous tissue was selected. With this approach, we obtained high-quality DNA and were able to identify oncogenic mutations specific for this entity and recapitulating its post-germinal center origin, even if the tumor fraction was low. Molecular studies performed on fresh-frozen cutaneous sample are feasible in IVLBCL, especially when analysis is restricted to the subcutaneous tissue. Wide adoption of this reproducible and cost-effective approach may foster further studies, which may be of help in supporting diagnosis, providing pathogenetic insights, and guiding treatment decisions., (© 2024. The Author(s).)

The MiniMed™ 780G is a second-generation automated insulin delivery system that implements a modified proportional-integral-derivative algorithm with some features of an MD-Logic artificial pancreas algorithm. The system may deliver automatic correction boluses up to every 5 min, and it allows the user to choose between three glucose target setpoints (100, 110 and 120 mg/dL). We aimed to review the current evidence on this device in children, adolescents, and young adults living with type 1 diabetes. We screened 783 papers, but only 31 manuscripts were included in this review. Data on metabolic outcomes show that this system is safe as regards severe hypoglycaemia and diabetic ketoacidosis. The glycated haemoglobin may drop to levels about 7%, with CGM reports showing a time in range of 75-80%. The time above range and the time below range are within the recommended target in most of the subjects. Few studies evaluated the psychological outcomes. This system seems to be more effective than the first-generation automated insulin delivery systems. The MiniMed™ 780G has been associated with an improvement in sleep quality in subjects living with diabetes and their caregivers, along with an improvement in treatment satisfaction. Psychological distress is as reduced as the glucose control is improved. We also discuss some case reports describing particular situations in clinical practice. Finally, we think that data show that this system is a further step towards the improvement of the treatment of diabetes as concerns both metabolic and psychological outcomes., (© 2023. The Author(s).)

Chronic diseases are a growing problem for global health due to the large number of people they involve, the repercussions they have on the mental and physical well-being of those affected, and the costs to society. Particularly, chronic illnesses of childhood have important psychological implications, not only for affected children but also for their parents. Among these pathologies, neurodevelopmental disorders (NDDs) and uveitis associated with juvenile idiopathic arthritis (JIA-U) may affect mental and physical health, emotions, memory, learning, and socializing. This study evaluates the psychological and behavioral/emotional impact of NDDs and JIA-U on children and parents. Specifically, 30 children with active JIA-U and 30 children with NDDs and their parents completed the Child Behavior Checklist (CBCL) and Parent Stress Index-Short Form (PSI) questionnaires. Children with NDDs have statistically significant differences in all the emotional and behavioral variables compared to JIA-U children, and parents of children with NDDs experience an increased stress load compared to parents of children with JIA-U. This study emphasizes the wide range of emotional and behavioral challenges that parents face with NDDs. This study emphasizes that parents of children with NDDs not only experience higher levels of stress compared to parents of normally developing children but also experience higher levels of stress compared to parents of children with potentially debilitating chronic diseases such as JIA-U.

The combination of neuroendocrine/non neuroendocrine lung tumors (CNNELT) mentioned in the last edition of the World Health Organization (WHO) of Thoracic Tumors refers to small cell carcinoma (SCLC) or large cell neuroendocrine carcinoma (LCNEC) mixed with any other non-small cell lung carcinoma (NSCLC). Typical Carcinoid (TC)/Atypical Carcinoid (AC) combined with NSCLC is not included among this category. However, case reports of TC/AC combined with NSCLC have been described. We previously reported 2 cases of lung adenocarcinoma (LUA) mixed with carcinoid sharing mutations in both components supporting the hypothesis of a clonal origin. We extended our analysis to other four cases of mixed NSCLC-carcinoid by performing targeted-DNA and RNA-based NGS analysis in both primary and their paired lymph nodes metastasis. In all cases, LUA and AC components shared at least 1 common mutation (KRAS driver mutation p.Gly12Val in cases 1 and 3, AKAP13-RET fusion in case 2, and missense KRAS driver mutation p.Gly12Ala in case 4, reinforcing the hypothesis of a clonal origin. Moreover, the same mutation was detected in the metastasis constituted only by AC (cases 2 and 4). Although it is a rare malignancy in the lung, mixed LUA and TC/AC could be included among the histotypes for which a deep molecular characterization of both components is needed to identify the presence of potential druggable genetic alterations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mass spectrometry has been widely accepted as a confirmatory tool for the sensitive detection of undeclared presence of allergenic ingredients. Multiple methods have been developed so far, achieving different levels of sensitivity and robustness, still lacking harmonization of the analytical validation and impairing comparability of results. In this investigation, a quantitative method has been validated in-house for the determination of six allergenic ingredients (cow's milk, hen's egg, peanut, soybean, hazelnut, and almond) in a chocolate-based matrix. The latter has been produced in a food pilot plant to provide a real and well-characterized matrix for proper assessment of method performance characteristics according to official guidelines. In particular, recent considerations issued by the European Committee for Standardization have been followed to guide a rigorous single-laboratory validation and to feature the main method performance, such as selectivity, linearity, and sensitivity. Synthetic surrogates of the peptide markers have been used both in native and labelled forms in matrix-matched calibration curves as external calibrants and internal standards, respectively. A two-order of magnitude range was investigated, focusing on the low concentration range for proper assessment of the detection and quantification limits (LOD and LOQ) by rigorous calibration approach. Conversion factors for all six allergenic ingredients have been determined for the first time to report the final quantitative information as fraction of total allergenic food protein (TAFP) per mass of food (µg TAFP /g food ), since such a reporting unit is exploitable in allergenic risk assessment plans. The method achieved good sensitivity with LOD values ranging between 0.08 and 0.2 µg TAFP /g food , for all ingredients besides egg and soybean, whose quantitative markers reported a slightly higher limit (1.1 and 1.2 µg TAFP /g food , respectively). Different samples of chocolate bar incurred at four defined concentration levels close to the currently available threshold doses have been analyzed to test the quantitative performance of the analytical method, with a proper estimate of the measurement uncertainty from different sources of variability. The sensitivity achieved resulted in compliance with the various threshold doses issued or recommended worldwide., (© 2023. The Author(s).)

In recent years, nucleic acids have emerged as powerful biomaterials, revolutionizing the field of biomedicine. This review explores the multifaceted applications of nucleic acids, focusing on their pivotal role in various biomedical applications. Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), possess unique properties such as molecular recognition ability, programmability, and ease of synthesis, making them versatile tools in biosensing and for gene regulation, drug delivery, and targeted therapy. Their compatibility with chemical modifications enhances their binding affinity and resistance to degradation, elevating their effectiveness in targeted applications. Additionally, nucleic acids have found utility as self-assembling building blocks, leading to the creation of nanostructures whose high order underpins their enhanced biological stability and affects the cellular uptake efficiency. Furthermore, this review delves into the significant role of oligonucleotides (ODNs) as indispensable tools for biological studies and biomarker discovery. ODNs, short sequences of nucleic acids, have been instrumental in unraveling complex biological mechanisms. They serve as probes for studying gene expression, protein interactions, and cellular pathways, providing invaluable insights into fundamental biological processes. By examining the synergistic interplay between nucleic acids as powerful biomaterials and ODNs as indispensable tools for biological studies and biomarkers, this review highlights the transformative impact of these molecules on biomedical research. Their versatile applications not only deepen our understanding of biological systems but also are the driving force for innovation in diagnostics and therapeutics, ultimately advancing the field of biomedicine.

Chemical space modelling has great importance in unveiling and visualising latent information, which is critical in predictive toxicology related to drug discovery process. While the use of traditional molecular descriptors and fingerprints may suffer from the so-called curse of dimensionality, complex networks are devoid of the typical drawbacks of coordinate-based representations. Herein, we use chemical space networks (CSNs) to analyse the case of the developmental toxicity (Dev Tox), which remains a challenging endpoint for the difficulty of gathering enough reliable data despite very important for the protection of the maternal and child health. Our study proved that the Dev Tox CSN has a complex non-random organisation and can thus provide a wealth of meaningful information also for predictive purposes. At a phase transition, chemical similarities highlight well-established toxicophores, such as aryl derivatives, mostly neurotoxic hydantoins, barbiturates and amino alcohols, steroids, and volatile organic compounds ether-like chemicals, which are strongly suspected of the Dev Tox onset and can thus be employed as effective alerts for prioritising chemicals before testing., (© 2023. The Author(s).)

The accurate characterisation of metabolic profiles is an important prerequisite to determine the rate and the efficiency of the metabolic pathways taking place in the cells. Changes in the balance of metabolites involved in vital processes such as glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), as well as in the biochemical pathways related to amino acids, lipids, nucleotides, and their precursors reflect the physiological condition of the cells and may contribute to the development of various human diseases. The feasible and reliable measurement of a wide array of metabolites and biomarkers possesses great potential to elucidate physiological and pathological mechanisms, aid preclinical drug development and highlight potential therapeutic targets. An effective, straightforward, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was developed for the simultaneous quali-quantitative analysis of 41 compounds in both cell pellet and cell growth medium obtained from brain-derived cell cultures. Sample pretreatment miniaturisation was achieved thanks to the development and optimisation of an original extraction/purification approach based on digitally programmed microextraction by packed sorbent (eVol®-MEPS). MEPS allows satisfactory and reproducible clean-up and preconcentration of both low-volume homogenate cell pellet lysate and cell growth medium with advantages including, but not limited to, minimal sample handling and method sustainability in terms of sample, solvents, and energy consumption. The MEPS-LC-MS/MS method showed good sensitivity, selectivity, linearity, and precision. As a proof of concept, the developed method was successfully applied to the analysis of both cell pellet and cell growth medium obtained from a line of mouse immortalised oligodendrocyte precursor cells (OPCs; Oli-neu cell line), leading to the unambiguous determination of all the considered target analytes. This method is thus expected to be suitable for targeted, quantitative metabolic profiling in most brain cell models, thus allowing accurate investigations on the biochemical pathways that can be altered in central nervous system (CNS) neuropathologies, including e.g., mitochondrial respiration and glycolysis, or use of specific nutrients for growth and proliferation, or lipid, amino acid and nucleotide metabolism., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Congenital clubfoot is a fairly common and severe congenital malformation, most often of idiopathic origin. A smaller percentage of cases is related to chromosomal abnormalities and genetic syndromes. It is estimated that 0.5/1000 newborns are affected worldwide, with a male to female ratio of 2:1 and greater distribution in developing countries (80%). The "European Surveillance of Congenital Anomalies (EUROCAT)" reported clubfoot prevalence in European newborns, but data regarding Italy are missing or poor. We aim to provide detailed data on clubfoot incidence according to the Apulian Regional Registry on Congenital Malformations and to report current knowledge on clubfoot genetic factors., Methods: We extrapolated data from the Regional Registry of Congenital Malformations to evaluate incidence and prevalence of congenital clubfoot in Apulia, Italy over a period of four years (2015-2018). We also performed a narrative review focusing on genetic mutations leading to congenital clubfoot., Results: Over the period from 2015 to 2018 in Apulia, Italy, 124,017 births were recorded and 209 cases of clubfoot were found, accounting for an incidence rate of 1.7/1,000 and a prevalence rate of 1.6/1,000. Six families of genes have been reported to have an etiopathogenetic role on congenital clubfoot., Conclusions: Incidence and prevalence of congenital clubfoot in Apulia, Italy, are comparable with those reported in the other Italian regions but higher than those reported in previous studies from Europe. Genetic studies to better classify congenital clubfoot in either syndromic or isolated forms are desirable., (© 2023. The Author(s).)

Executive Functions (EFs) are high-order cognitive processes relevant to learning and adaptation and frequently impaired in children with specific learning disorders (SLDs). This study aimed to investigate EFs in children with SLD and explore the role of specific EF-related subprocesses, such as stimuli processing and processing speed. Fifty-seven SLD and 114 typically developing (TD) children, matched for gender and age, completed four tasks measuring response inhibition, interference control, shifting, and updating on a web-based teleassessment platform. The results show that SLD children performed lower in all EF tasks than TD children, regardless of stimulus type and condition. Mediation analyses suggested that differences between the SLD and TD groups are mediated by EF-related subprocesses, offering an interpretative model of EF deficits in children with SLD., Competing Interests: Declaration of interest statement MIUR Project RiDi Fisr2020 – TD MEPA 1760961 and Regione Toscana PROTENEUCO project CUP: C89C20000290002., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

As the number of cancer survivors (CSs) is increasing worldwide, providing services relevant to the specific, unmet needs of these individuals is crucial. There are currently various patient-reported outcome measures (PROMs) whose aim is to identify the unmet needs of CSs. Still, limited guidance supports healthcare providers in choosing the most valid and reliable PROMs for this purpose. We conducted this overview of systematic reviews (SRs) on the psychometric properties of PROMs addressing the unmet needs of adult CSs suffering from non-cutaneous cancers. We searched databases for SRs published between 2012 and January 2023. Two SRs were included, covering 14 PROMs tested on 19,151 CSs. These were assessed according to the COSMIN methodology for SRs of PROMs for the quality of their measurement properties and risk of bias, thus providing guidance in selecting PROMs that appropriately reflect the unmet needs of CSs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite being at higher risk of severe disease and pregnancy complications, evidence on susceptibility to SARS-CoV-2 infection in pregnancy is still limited. The aim of the study is to compare the likelihood of undergoing a SARS-CoV-2 test and testing positive for COVID-19 in pregnancy and puerperium with that of the general female population of reproductive age., Methods: This is a retrospective population-based cohort study including 117,606 women of reproductive age (March 2020-September 2021) with 6608 (5.6%) women having ≥ 1 pregnancy. Women were linked to the pregnancy registry to be classified as "non-pregnant", "pregnant", and "puerperium"; then, according to the national case-based integrated COVID-19 surveillance system, all women undergoing a SARS-CoV-2 test during the study period were identified. The Incidence Rate Ratio was calculated to compare the likelihood of being tested for SARS-CoV-2 in pregnant, puerperium and non-pregnant women among all women included. The likelihood of having a COVID-19 diagnosis was calculated using two comparators (not-pregnant women and the person-time before/after pregnancy) by means of Cox proportional hazards models, adjusting for age and with the cluster option to control standard error calculation in repeated pregnancies. Only first infection and swabs before the first one positive were included., Results: The probability of being tested for SARS-CoV-2 was 4.9 (95% CI: 4.8-5.1) and 3.6 times higher (95%CI: 3.4-3.9) in pregnancy (including spontaneous miscarriages) and in the puerperium, respectively. The Hazard Ratio (HR) of covid-19 diagnosis during pregnancy vs. non-pregnancy was 1.17 (95% CI 1.03-1.33) with similar results when comparing the risk during pregnancy with that of the same women outside pregnancy (puerperium excluded), with an HR of 1.13 (95% CI 0.96-1.33); the excess decreased when excluding the test performed at admission for delivery (HR 1.08 (95%CI 0.90-1.30). In the puerperium, the HR was 0.62 (95% CI 0.41-0.92) comparing women with ≥ 1childbirth with all other women and excluding the first two weeks of puerperium., Conclusions: Women during pregnancy showed a small increase in the risk of infection, compatible with a higher likelihood of being tested. A lower probability of infection during the puerperium was observed during the entire pandemic period, suggesting likely protective behaviors which were effective in reducing their probability of infection., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The occurrence of methyl carbamates of phosphatidylethanolamines and phosphatidylserines in the lipid extract of mitochondria obtained from mouse embryonic fibroblasts was ascertained by hydrophilic interaction liquid chromatography with electrospray ionization single and multi-stage mass spectrometry, performed using sinergically a high resolution (quadrupole-Orbitrap) and a low resolution (linear ion trap) spectrometer. Two possible routes to the synthesis of methyl carbamates of phospholipids were postulated and evaluated: (i) a chemical transformation involving phosgene, occurring as a photooxidation by-product in the chloroform used for lipid extraction, and methanol, also used for the latter; (ii) an enzymatic methoxycarbonylation reaction due to an accidental bacterial contamination, that was unveiled subsequently on the murine mitochondrial sample. A specific lipid extraction performed on a couple of standard phosphatidyl-ethanolamines/-serines, based on purposely photo-oxidized chloroform and deuterated methanol, indicated route (i) as negligible in the specific case, thus highlighting the enzymatic route related to bacterial contamination as the most likely source of methyl carbamates. The unambiguous recognition of the latter might represent the starting point toward a better understanding of their generation in biological systems and a minimization of their occurrence when an artefactual formation is ascertained., (© 2023. Springer Nature Limited.)

Reproductive dysfunctions have been recently documented in male greater amberjack Seriola dumerili caught from the wild and reared in captivity. In the present study, we compared testis transcriptome in wild fish (WILD), hatchery-produced fish with apparently normal spermatogenesis (Normal Farmed; NormalF) and hatchery-produced fish with evident reproductive dysfunction (Dysfunctional Farmed; DysF). Gene expression analysis identified 2157, 1985 and 74 differentially expressed genes (DEGs) in DysF vs WILD, NormalF vs DysF and NormalF vs WILD comparisons, respectively. In DysF, a dysregulation of several interconnected biological processes, including cell assembly, steroidogenesis and apoptosis was found. Gene enrichment of progesterone-mediated oocyte maturation, oocyte meiosis and cell cycle pathways were identified in the DysF vs NormalF comparison. Most of the DEGs involved in the enriched pathways were downregulated in DysF. The comparison of NormalF vs WILD showed that most of the DEGs were downregulated in NormalF, including a gene that encodes for a regulatory protein with a protective role in apoptosis regulation (ptpn6), indicating that spermatogenesis was dysfunctional also in the apparently "normal" hatchery-produced fish. Hence, rearing of male greater amberjack in captivity, from eggs produced by captive breeders, did not prevent the appearance of reproductive dysfunctions, and these dysfunctions involved several biological processes and metabolic pathways., (© 2023. Springer Nature Limited.)

Gene and genome comparison represent an invaluable tool to identify evolutionarily conserved sequences with possible functional significance. In this work, we have analyzed orthologous genes encoding subunits and assembly factors of the V-ATPase complex, an important enzymatic complex of the vacuolar and lysosomal compartments of the eukaryotic cell with storage and recycling functions, respectively, as well as the main pump in the plasma membrane that energizes the epithelial transport in insects. This study involves 70 insect species belonging to eight insect orders. We highlighted the conservation of a short sequence in the genes encoding subunits of the V-ATPase complex and their assembly factors analyzed with respect to their exon-intron organization of those genes. This study offers the possibility to study ultra-conserved regulatory elements under an evolutionary perspective, with the aim of expanding our knowledge on the regulation of complex gene networks at the basis of organellar biogenesis and cellular organization.

Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome and myocardial infarction, more frequent among young women. Invasive coronary angiography (ICA) is the gold standard for the diagnosis of SCAD, although the risk of propagating dissection flap is considerable. Therefore, coronary computed tomography angiography (CCTA) is an emerging alternative modality to diagnose SCAD with the advantage of being a non-invasive technique. Clinicians should be aware of the predisposing conditions and pathophysiology to raise the pre-test probability of SCAD and select the most appropriate diagnostic tools. In recent times, improvements in spatial and temporal resolution and the use of semi-automated software providing quantitative assessment make CCTA a valid alternative to ICA also for the follow-up. Moreover, CCTA may be helpful to screen and evaluate extra-coronary arteriopathies closely related to SCAD. In this review, we illustrate the current and the potential role of CCTA in the diagnosis of SCAD, highlighting advantages and disadvantages of this imaging modality compared to ICA., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The increasing size of the human population and the shortage of highly valuable proteinaceous ingredients has prompted the international community to scout for new, sustainable, and natural protein resources from invertebrates (e.g., insects) and underutilized legume crops, unexploited terrestrial and aquatic weeds, and fungi. Insect proteins are known for their nutritional value, being rich in proteins with a good balance of essential amino acids and being a valuable source of essential fatty acids and trace elements. Unconventional legume crops were found rich in nutritional, phytochemical, and therapeutic properties, showing excellent abilities to survive extreme environmental conditions. This review evaluates the recent state of underutilized legume crops, aquatic weeds, fungi, and insects intended as alternative protein sources, from ingredient production to their incorporation in food products, including their food formulations and the functional characteristics of alternative plant-based proteins and edible insect proteins as novel foods. Emphasis is also placed on safety issues due to the presence of anti-nutritional factors and allergenic proteins in insects and/or underutilized legumes. The functional and biological activities of protein hydrolysates from different protein sources are reviewed, along with bioactive peptides displaying antihypertensive, antioxidant, antidiabetic, and/or antimicrobial activity. Due to the healthy properties of these foods for the high abundance of bioactive peptides and phytochemicals, more consumers are expected to turn to vegetarianism or veganism in the future, and the increasing demand for such products will be a challenge for the future.

Earthworms and soil microorganisms contribute to soil health, quality, and fertility, but their importance in agricultural soils is often underestimated. This study aims at examining whether and to what extent the presence of earthworms ( Eisenia sp.) affected the (a) soil bacterial community composition, (b) litter decomposition, and (c) plant growth ( Brassica oleracea L., broccoli; Vicia faba L., faba bean). We performed a mesocosm experiment in which plants were grown outdoors for four months with or without earthworms. Soil bacterial community structure was evaluated by a 16S rRNA-based metabarcoding approach. Litter decomposition rates were determined by using the tea bag index (TBI) and litter bags (olive residues). Earthworm numbers almost doubled throughout the experimental period. Independently of the plant species, earthworm presence had a significant impact on the structure of soil bacterial community, in terms of enhanced α - and β -diversity (especially that of Proteobacteria, Bacteroidota, Myxococcota, and Verrucomicrobia) and increased 16S rRNA gene abundance (+89% in broccoli and +223% in faba bean). Microbial decomposition (TBI) was enhanced in the treatments with earthworms, and showed a significantly higher decomposition rate constant ( k TBI ) and a lower stabilization factor ( S TBI ), whereas decomposition in the litter bags ( d litter ) increased by about 6% in broccoli and 5% in faba bean. Earthworms significantly enhanced root growth (in terms of total length and fresh weight) of both plant species. Our results show the strong influence of earthworms and crop identity in shaping soil chemico-physical properties, soil bacterial community, litter decomposition and plant growth. These findings could be used for developing nature-based solutions that ensure the long-term biological sustainability of soil agro- and natural ecosystems.

Microalgae are aquatic unicellular microorganisms and, although various species are approved for human consumption, Arthrospira and Chlorella are the most widespread. Several nutritional and functional properties have been bestowed to microalgae principal micro- and macro-nutrients, with antioxidant, immunomodulatory and anticancer being the most common. The many references to their potential as a food of the future is mainly ascribed to the high protein and essential amino acid content, but they are also a source of pigments, lipids, sterols, polysaccharides, vitamins, and phenolic compounds with positive effects on human health. Nevertheless, microalgae use is often hindered by unpleasant color and flavor and several strategies have been sought to minimize such challenges. This review provides an overview of the strategies so far proposed and the main nutritional and functional characteristic of microalgae and the foods made thereof. Processing treatments have been used to enrich microalgae-derived substrates in compounds with antioxidant, antimicrobial, and anti-hypertensive properties. Extraction, microencapsulation, enzymatic treatments, and fermentation are the most common, each with their own pros and cons. Yet, for microalgae to be the food of the future, more effort should be put into finding the right pre-treatments that can allow the use of the whole biomass and be cost-effective while bringing about features that go beyond the mere increase of proteins.

Cannabinoid type 2 receptor (CB2R) is a G-protein-coupled receptor that, together with Cannabinoid type 1 receptor (CB1R), endogenous cannabinoids and enzymes responsible for their synthesis and degradation, forms the EndoCannabinoid System (ECS). In the last decade, several studies have shown that CB2R is overexpressed in activated central nervous system (CNS) microglia cells, in disorders based on an inflammatory state, such as neurodegenerative diseases, neuropathic pain, and cancer. For this reason, the anti-inflammatory and immune-modulatory potentials of CB2R ligands are emerging as a novel therapeutic approach. The design of selective ligands is however hampered by the high sequence homology of transmembrane domains of CB1R and CB2R. Based on a recent three-arm pharmacophore hypothesis and latest CB2R crystal structures, we designed, synthesized, and evaluated a series of new N-adamantyl-anthranil amide derivatives as CB2R selective ligands. Interestingly, this new class of compounds displayed a high affinity for human CB2R along with an excellent selectivity respect to CB1R. In this respect, compounds exhibiting the best pharmacodynamic profile in terms of CB2R affinity were also evaluated for the functional behavior and molecular docking simulations provided a sound rationale by highlighting the relevance of the arm 1 substitution to prompt CB2R action. Moreover, the modulation of the pro- and anti-inflammatory cytokines production was also investigated to exert the ability of the best compounds to modulate the inflammatory cascade., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mabel Loza and Pepo Brea reports financial support was provided by Agencia Estatal de Investigación. Mabel Loza and Pepo Brea reports financial support was provided by Xunta de Galicia Consellería de Sanidade. Eddy Sotelo reports financial support was provided by Galician Government., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The optimal adjuvant endocrine therapy for HR-positive/HER2-positive breast cancer patients is unknown. We included in this analysis 784 patients with HR-positive/HER2-positive BC from the randomized ShortHER trial of adjuvant trastuzumab (1 year vs 9 weeks) + chemotherapy. At a median follow-up of 8.7 years, patients who received AI had a significantly better DFS vs patients who received TAM or TAM-AI: 8-yr DFS 86.4 vs 79.7%, log-rank P = 0.013 (HR 1.52, 95% CI 1.09-2.11). In multivariate analysis, the type of endocrine therapy maintained a significant association with DFS (HR 1.64, 95% CI 1.07-2.52, p = 0.025 for TAM/TAM-AI vs AI). Among premenopausal patients aged ≤45 years, the use of GnRHa was associated with longer DFS: 8-yr DFS rate 85.2 vs 62.6% (log-rank p = 0.019, HR 0.41, 95% CI 0.19-0.88). In this post-hoc analysis of the ShortHER trial adjuvant treatment with AI was independently associated with improved DFS. Subgroup analysis in premenopausal patients suggests benefits with ovarian suppression.Trial registration: NCI ClinicalTrials.gov number: NCT00629278., (© 2023. The Author(s).)

The realization of electron microscopy facilities all over the world has experienced a paramount increase in the last decades. This means huge investments of public and private money due to the high costs of equipment, but also for maintenance and running costs. The proper design of a transmission electron microscopy facility is mandatory to fully use the advanced performances of modern equipment, capable of atomic resolution imaging and spectroscopies, and it is a prerequisite to conceive new methodologies for future advances of the knowledge. Nonetheless, even today, in too many cases around the world, the realization of the environment hosting the equipment is not appropriate and negatively influences the scientific quality of the results during the life of the infrastructure, practically vanishing the investment made. In this study, the key issues related to the realization of an advanced electron microscopy infrastructure are analyzed based on personal experience of more than thirty years, and on the literature.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease common in children and young adults. Uveitis is the most frequent serious extra-articular JIA manifestation and can lead to severe ocular complications, vision loss, and permanent blindness. This study aims to evaluate the psychological condition and the quality of life of children affected by JIA associated with uveitis (JIA-U) and the repercussion of this condition on parents. Thirty children and adolescents with active uveitis (Uveitis group) and comorbid joint symptoms of JIA were referred to the Unit of Ophthalmology, Giovanni XXIII Hospital of Bari, and 30 age-matched healthy controls (Healthy group) were enrolled with their parents. Four questionnaires were administered: Child Behaviour Checklist (CBCL), Parent Stress Index in Short Form (PSI), Pediatric Quality of Life Inventory (PedsQL), and Coping Inventory for Stressful Situations (CISS). The data were collected from February 2021 to December 2021. No significant differences between the two groups in CBCL, PSI, or CISS tests were shown (p > 0.05). Conversely, significant differences between the two groups were observed in the PedsQL (p < 0.05). This study shows how several ocular complications, recurrent eye examinations, and the rigor of long-term treatment may negatively influence health-related quality of life in children with JIA-U.

Purpose: The aim of this study was to explore prematurity as a psycho-social process from the point of view of both parents and healthcare professionals., Design and Methods: We conducted a Grounded Theory study through semi-structured interviews. Participants were from an Italian Neonatal Intensive Care Unit, including parents of premature children, and health professionals. Interviews were analyzed according to Grounded Theory coding strategies, to hypothesize a theoretical model., Results: On one side, behaviors, emotions, and feelings of parental couples; on the other one, the activities and reactions of professionals have been interpreted in a four-phase negotiated process: 1) the initial breakup; 2) the floating family; 3) the event processing; 4) the reconstruction of a new family., Conclusions: Managing prematurity is a negotiated process which could be better managed through a family-centered approach as fundamental in neonatal and pediatric services. Being open in listening, coherent in the given answers, and knowing the entire process and story of being suddenly parents of a premature child can make the difference in the future definition of a new family., Practice Implications: Perinatal care would benefit from the following suggested practical implications: i) reducing feelings of separation and solitude by integrating diverse professionals around the family systems; ii) expediting prematurity-related changes through peer-support during hospitalization and attention to rooms' organization; iii) enhancing information exchange between all professionals involved in the care of dyads/parents and new-borns, starting since the pregnancy and continuing after the child's birth by implementing multidisciplinary meetings or appropriate care pathways., (Copyright © 2022. Published by Elsevier Inc.)

Background: Fermented foods are attracting increasing interest due to their nutritional and health benefits, including a positive impact on gut microbiota exerted by their associated microbes. However, information relative to traditional fermented dairy products, along with their autochthonous microbiota, is still fragmented and poorly standardized. Therefore, our aim was to collect and aggregate data useful for obtaining a comprehensive overview translated in a classical database interface that can be easily handled by users., Methods: a preliminary inventory was built up by systematically collecting data from publicly available resources for the creation of a list of traditional dairy foods produced worldwide, including additional metadata useful for stratifying, and collapsing subgroups., Results: we developed the Fermented Dairy Food Database (FDF-DB), a feasible resource comprising 1852 traditional dairy foods (cheeses, fermented milks, and yogurt) for which microbial content and other associated metadata such as geographical indication label, country/region of origin, technological aspects were gathered., Conclusions: FDF-DB is a useful and user-friendly resource where taxonomic information and processing production details converge. This resource will be of great aid for researchers, food industries, stakeholders and any user interested in the identification of technological and microbiological features characterizing traditional fermented dairy products.

Congenital clubfoot is a common pediatric malformation that affects approximately 0.1% of all births. 80% of the cases appear isolated, while 20% can be secondary or associated with complex syndromes. To date, two genes that appear to play an important role are PTIX1 and TBX4 , but their actual impact is still unclear. Our study aimed to evaluate the prevalence of pathogenic variants in PITX1 and TBX4 in Italian patients with idiopathic clubfoot. PITX1 and TBX4 genes were analyzed by sequence and SNP array in 162 patients. We detected only four nucleotide variants in TBX4 , predicted to be benign or likely benign. CNV analysis did not reveal duplications or deletions involving both genes and intragenic structural variants. Our data proved that the idiopathic form of congenital clubfoot was rarely associated with mutations and CNVs on PITX1 and TBX4 . Although in some patients, the disease was caused by mutations in both genes; they were responsible for only a tiny minority of cases, at least in the Italian population. It was not excluded that other genes belonging to the same TBX4-PITX1 axis were involved, even if genetic complexity at the origin of clubfoot required the involvement of other factors.