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Fungi of the genus Aspergillus are widespread in the environment, where they produce large quantities of airborne conidia. Inhalation of Aspergillus spp. conidia in immunocompromised individuals can cause a wide spectrum of diseases, ranging from hypersensitivity responses to lethal invasive infections. Upon deposition in the lung epithelial surface, conidia encounter and interact with complex microbial communities that constitute the lung microbiota. The lung microbiota has been suggested to influence the establishment and growth of Aspergillus spp. in the human airways. However, the mechanisms underlying this interaction have not yet been sufficiently investigated. In this study, we aimed to enrich and isolate bacterial strains capable of inhibiting the germination and growth of A. fumigatus conidia from bronchoalveolar lavage fluid (BALF) samples of lung transplant recipients using a novel enrichment method. This method is based on a soft agar overlay plate assay in which bacteria are directly in contact with conidia, allowing inhibition to be readily observed during enrichment. We isolated a total of five clonal bacterial strains with identical genotypic fingerprints, as shown by random amplified polymorphic DNA PCR (RAPD–PCR). All strains were identified as Pseudomonas aeruginosa (strains b1–b5). The strains were able to inhibit the germination and growth of Aspergillus fumigatus in a soft agar confrontation assay, as well as in a germination multiplate assay. Moreover, when compared with ten P. aeruginosa strains isolated from expectoration through standard methods, no significant differences in inhibitory potential were observed. Additionally, we showed inhibition of A. fumigatus growth on Calu-3 cell culture monolayers. However, the isolated P. aeruginosa strains were shown to cause significant damage to the cell monolayers. Overall, although P. aeruginosa is a known opportunistic lung pathogen and antagonist of A. fumigatus, we validated this novel one-step enrichment approach for the isolation of bacterial strains antagonistic to A. fumigatus from BALF samples as a proof-of-concept. This opens up a new venue for the targeted enrichment of antagonistic bacterial strains against specific fungal pathogens.

Background: In Italy, Diagnosis-Related Groups (DRGs) have been adopted for hospital services reimbursement. In some Italian regions, nurse staffing allocation is purely volume-based, with different minutes/patient/day categories determined by the type of hospital ward. The Information System of Nursing Performance (SIPI) is a valid and reliable tool assessing nursing care complexity as an indicator of the actual nursing care demand. Evidence is lacking about the ability of current resource allocation methods to account for the nursing care demand. Objective: To evaluate the association between (1) DRG rates and nursing care complexity and (2) hospital ward categories of nurse staffing and nursing care complexity. Methods: All patients discharged from the medical department of an Italian hospital over a data collection period were eligible. To assess the association between nursing care complexity (SIPI) and DRGs, the distribution of the DRG rate (median and first–third quartile) was compared for cases with high or low complexity. To evaluate the association between nursing care complexity (SIPI) and nurse staffing, the frequency of high complexity within nurse staffing categories (120/180/240 min/patient/day) was compared. Because the sample was very large, methods of statistical inference were not applied, and only descriptive measures were reported. Results: 6872 hospitalizations were included. The median DRG rate for high and low complexity admissions were very similar (EUR 3536 and EUR 3285, respectively). The proportion of admissions with high complexity decreased for wards with higher staffing allocation rates. Conclusion: DRG reimbursement and the nurse staffing allocation systems were ineffective in accounting for nursing care complexity. The SIPI could help identify areas requiring more financial and staffing resources for nursing care.

Ontologies are essential for the management and integration of heterogeneous datasets. This paper presents OntoBuilder, an advanced tool that leverages the structural capabilities of semantic labeled property graphs (SLPGs) in strict alignment with semantic web standards to create a sophisticated framework for data management. We detail OntoBuilder’s architecture, core functionalities, and application scenarios, demonstrating its proficiency and adaptability in addressing complex ontological challenges. Our empirical assessment highlights OntoBuilder’s strengths in enabling seamless visualization, automated ontology generation, and robust semantic integration, thereby significantly enhancing user workflows and data management capabilities. The performance of the linked data tools across multiple metrics further underscores the effectiveness of OntoBuilder.

Supersaturated alloys can exhibit superior properties and electrodeposition is a cost-effective and versatile technique to produce them. In this review, the chemical, mechanical and structural properties of supersaturated alloys are discussed, and connections with metallic glasses and high entropy alloys are also exposed. After discussing mechanisms causing supersaturation in electrodeposited alloys, an overview of the most important electrodeposited metastable alloys is provided, showing that they are mainly used as protective coatings able to improve corrosion resistance and tribological performance of a large variety of industrial components. Composition of the electrolytic baths and deposition parameters are also considered and discussed.

Lysine, methionine, and threonine are essential amino acids with vital functions for muscle and connective tissue health, metabolic balance, and the immune system. During illness, the demand for these amino acids typically increases, which puts patients at risk for deficiencies with harmful clinical consequences. In a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), which compared individualized nutritional support to usual care nutrition in patients at nutritional risk, we investigated the prognostic impact of the lysine, methionine, and threonine metabolism. We had complete clinical and amino acid data in 237 patients, 58 of whom reached the primary endpoint of death at 30 days. In a model adjusted for comorbidities, sex, nutritional risk, and trial intervention, low plasma methionine levels were associated with 30-day mortality (adjusted HR 1.98 [95% CI 1.16 to 3.36], p = 0.01) and with a decline in functional status (adjusted OR 2.06 [95% CI 1.06 to 4.01], p = 0.03). The results for lysine and threonine did not show statistically significant differences regarding clinical outcomes. These findings suggest that low levels of methionine may be critical during hospitalization among patients at nutritional risk. Further studies should investigate the effect of supplementation of methionine in this patient group to improve outcomes.

The decade from 2010–2020 has seen the development of cone beam weight-bearing CT (WBCT) as a major innovation in the foot and ankle realm, becoming an important modality for bone and joint imaging. The ability to provide three-dimensional images of the naturally loaded skeleton has enabled several subsequent innovations to arise with aims to hasten image processing and to extend the clinical applications of WBCT. The objective of this work was to identify, categorize and explain those emerging techniques. We performed a structured review of the literature according to PRISMA standards, finally including 50 studies. We subsequently proposed a classification of these techniques. Segmentation and distance mapping were identified as key features. We conclude that although WBCT has already been adopted in a number of clinical communities with an immediate improvement in patient workflows, adoption of advanced techniques is yet to come. However, that relies mostly not on the technology itself, but on improvements in AI software allowing practitioners to quickly process images in daily practice and enabling the clinicians to obtain an accurate three-dimensional evaluation of the segment considered. Standardization will be paramount to amass large amounts of comparable data, which will fuel further innovations in a potentially virtuous circle.

The knowledge of the mechanical behavior of a 3D-printed material is fundamental for the 3D printing outbreaking technology to be considered for a range of applications. In this framework, the significance, reliability, and accuracy of the information obtained by testing material coupons assumes a pivotal role. The present work focuses on an evaluation of the static mechanical properties and failure modes of a 3D-printed short carbon fiber-reinforced polyamide in relation to the specimen’s unique meso-structural morphology and water content. Within the manufacturing limitations of a commercially available printer, specimens of dedicated combinations of geometry and printing patterns were specifically conceived and tested. The specimens’ meso-structure morphologies were investigated by micro-computed tomography. The material failure mechanisms were inferred from an analysis of the specimens’ fracture surfaces and failure morphologies. The outcomes of the present analysis indicate that each test specimen retained proper mechanical properties, thereby suggesting that they should be accurately designed to deliver representative information of the underlying material beads or of their deposition layout. Suggestions on the adoption of preferred test specimens for evaluating specific material properties were proposed.

The measurement of partial pressures of oxygen (O2) and carbon dioxide (CO2) is fundamental for evaluating a patient’s conditions in clinical practice. There are many ways to retrieve O2/CO2 partial pressures and concentrations. Arterial blood gas (ABG) analysis is the gold standard technique for such a purpose, but it is invasive, intermittent, and potentially painful. Among all the alternative methods for gas monitoring, non-invasive transcutaneous O2 and CO2 monitoring has been emerging since the 1970s, being able to overcome the main drawbacks of ABG analysis. Clark and Severinghaus electrodes enabled the breakthrough for transcutaneous O2 and CO2 monitoring, respectively, and in the last twenty years, many innovations have been introduced as alternatives to overcome their limitations. This review reports the most recent solutions for transcutaneous O2 and CO2 monitoring, with a particular consideration for wearable measurement systems. Luminescence-based electronic paramagnetic resonance and photoacoustic sensors are investigated. Optical sensors appear to be the most promising, giving fast and accurate measurements without the need for frequent calibrations and being suitable for integration into wearable measurement systems.

This study compared SARS-CoV-2 RNA loads at different anatomical sites, and the impact of self-swabbing and food intake. Adult symptomatic patients with SARS-CoV-2 or non-SARS-CoV-2 respiratory tract infection were included between 2021 and 2022. Patients performed a nasal and buccal swab before a professionally collected nasopharyngeal/oropharyngeal swab (NOPS). Buccal swabs were collected fasting and after breakfast in a subgroup of patients. SARS-CoV-2 RNA loads were determined by nucleic acid testing. Swabbing convenience was evaluated using a survey. The median age of 199 patients was 54 years (interquartile range 38–68); 42% were female and 52% tested positive for SARS-CoV-2. The majority of patients (70%) were hospitalized. The mean SARS-CoV-2 RNA load was 6.6 log10 copies/mL (standard deviation (SD), ±1.5), 5.6 log10 copies/mL (SD ± 1.9), and 3.4 log10 copies/mL (SD ± 1.9) in the professionally collected NOPS, and self-collected nasal and buccal swabs, respectively (p < 0.0001). Sensitivity was 96.1% (95% CI 90.4–98.9) and 75.3% (95% CI 63.9–81.8) for the nasal and buccal swabs, respectively. After food intake, SARS-CoV-2 RNA load decreased (p = 0.0006). Buccal swabbing was the preferred sampling procedure for the patients. In conclusion, NOPS yielded the highest SARS-CoV-2 RNA loads. Nasal self-swabbing emerged as a reliable alternative in contrast to buccal swabs. If buccal swabs are used, they should be performed before food intake.

Listeria monocytogenes is a Gram-positive pathogenic bacterium which can be found in soil or water. Infection with the microorganism can occur after ingestion of contaminated food products. Small and large outbreaks of listeriosis have been described in the past. L. monocytogenes can cause a number of different clinical syndromes, most frequently sepsis, meningitis, and rhombencephalitis, particularly in immunocompromised hosts. L. monocytogenes systemic infections can develop following tissue penetration across the gastrointestinal tract or to hematogenous spread to sterile sites, possibly evolving towards bacteremia. L. monocytogenes only rarely causes bone or joint infections, usually in the context of prosthetic material that can provide a site for bacterial seeding. We describe here the clinical findings of invasive listeriosis, mainly focusing on the diagnosis, clinical management, and treatment of bone and vertebral infections occurring in the context of invasive listeriosis.

Glutamine and its metabolite glutamate serve as the main energy substrates for immune cells, and their plasma levels drop during severe illness. Therefore, glutamine supplementation in the critical care setting has been advocated. However, little is known about glutamine metabolism in severely but not critically ill medical patients. We investigated the prognostic impact of glutamine metabolism in a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial comparing individualized nutritional support to usual care in patients at nutritional risk. Among 234 patients with available measurements, low plasma levels of glutamate were independently associated with 30-day mortality (adjusted HR 2.35 [95% CI 1.18–4.67, p = 0.015]). The impact on mortality remained consistent long-term for up to 5 years. No significant association was found for circulating glutamine levels and short- or long-term mortality. There was no association of glutamate nor glutamine with malnutrition parameters or with the effectiveness of nutritional support. This secondary analysis found glutamate to be independently prognostic among medical inpatients at nutritional risk but poorly associated with the effectiveness of nutritional support. In contrast to ICU studies, we found no association between glutamine and clinical outcome.

In the last few years, the manufacturing of microelectromechanical systems (MEMS) by means of innovative tridimensional and bidimensional printing technologies has significantly catalyzed the attention of researchers. Inkjet material deposition, in particular, can become a key enabling technology for the production of polymer-based inertial sensors characterized by low cost, high manufacturing scalability and superior sensitivity. In this paper, a fully inkjet-printed polymeric accelerometer is proposed, and its manufacturing steps are described. The manufacturing challenges connected with the inkjet deposition of SU-8 as a structural material are identified and addressed, resulting in the production of a functional spring-mass sensor. A step-crosslinking process allows optimization of the final shape of the device and limits defects typical of inkjet printing. The resulting device is characterized from a morphological point of view, and its functionality is assessed in performing optical readout. The acceleration range of the optimized device is 0–0.7 g, its resolution is 2 × 10−3 g and its sensitivity is 6745 nm/g. In general, the work demonstrates the feasibility of polymeric accelerometer production via inkjet printing, and these characteristic parameters demonstrate their potential applicability in a broad range of uses requiring highly accurate acceleration measurements over small displacements.

This paper introduces Semantic Knowledge Advanced Tool for Extraction Browsing Organisation Annotation Retrieval and Discovery (SKATEBOARD), a tool designed to facilitate knowledge exploration through the application of semantic technologies. The demand for advanced solutions that streamline Knowledge Extraction, management, and visualisation, characterised by abundant information, has grown substantially in the current era. Graph-based representations have emerged as a robust approach for uncovering intricate data relationships, complementing the capabilities offered by AI models. Acknowledging the transparency and user control challenges faced by AI-driven solutions, SKATEBOARD offers a comprehensive framework encompassing Knowledge Extraction, ontology development, management, and interactive exploration. By adhering to Linked Data principles and adopting graph-based exploration, SKATEBOARD provides users with a clear view of data relationships and dependencies. Furthermore, it integrates recommendation systems and reasoning capabilities to augment the knowledge discovery process, thus introducing a serendipity effect generated by the SKATEBOARD interface exploration. This paper elucidates SKATEBOARD’s functionalities while emphasising its user-centric design. After reviewing related research, we provide an overview of the SKATEBOARD pipeline, demonstrating its capacity to bridge RDF and LPG representations. Subsequent sections delve into Knowledge Extraction and exploration, culminating in the evaluation of the tool. SKATEBOARD empowers users to make informed decisions and uncover valuable insights within their data domains, with the added dimension of serendipitous discoveries facilitated by its interface exploration capabilities.

With the progressive improvements in the power, effectiveness, and reliability of AI solutions, more and more critical human problems are being handled by automated AI-based tools and systems. For more complex or particularly critical applications, the level of knowledge, not just information, must be handled by systems where explicit relationships among objects are represented and processed. For this purpose, the knowledge representation branch of AI proposes Knowledge Graphs, widely used in the Semantic Web, where different online applications may interact by understanding the meaning of the data they process and exchange. This paper describes a framework and online platform for the Internet-based knowledge graph definition, population, and exploitation based on the LPG graph model. Its main advantages are its efficiency and representational power and the wide range of functions that it provides to its users beyond traditional Semantic Web reasoning: network analysis, data mining, multistrategy reasoning, and knowledge browsing. Still, it can also be mapped onto the SW.

(1) Background: Despite the advantages of COVID-19 vaccination, rare cases of acute hepatitis developing after the administration of the COVID-19 vaccine or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. The aim of the study is to describe a case series of patients who experienced the onset of acute hepatitis, with or without autoimmune features, following SARS-CoV-2 vaccination or infection and to hypothesize a genetic susceptibility in the pathogenesis. (2) Methods: A group of patients with acute onset hepatitis following SARS-CoV-2 vaccination or infection were evaluated in our hepatology outpatient clinic, where they underwent biochemical and autoimmune tests. Hepatitis A (HAV), B (HBV), and C virus (HCV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human immunodeficiency virus (HIV) infections were excluded. Patients with a diagnosis of autoimmune hepatitis (AIH) or drug-induced liver injury (DILI) underwent HLA typing and histological testing. (3) Results: Five patients experienced new-onset AIH after COVID-19 vaccination, one of which developed mild symptoms after vaccination that strongly worsened during subsequent SARS-CoV-2 infection. One patient had AIH relapse after COVID-19 vaccination while on maintenance immunosuppressive treatment. All of them had HLA DRB1 alleles known to confer susceptibility to AIH (HLA DRB1*03,*07,*13,*14), and in three of them, HLA DRB1*11 was also detected. Two patients developed acute hepatitis without autoimmune hallmarks which resolved spontaneously, both positive for HLA DRB1*11. (4) Conclusions: An association between AIH and COVID-19 vaccine or infection can be hypothesized in individuals with a genetic predisposition. In patients without autoimmune features and spontaneous improvement of hypertransaminasemia, the diagnosis of drug-induced liver injury (DILI) is probable. Further studies are needed to determine the presence of an actual association and identify a possible role of HLA DRB1*11 in the pathogenesis of acute liver injury after SARS-CoV2 vaccination or infection.

(1) Background: Anaemia is a common finding in patients with colon cancer and is commonly corrected by blood transfusion prior to surgery. However, the prognostic role of perioperative transfusions is still debated. The aim of the present study was to investigate the role of preoperative anaemia and preoperative blood transfusion in influencing the prognosis in colon cancer. (2) Patients and Methods: Patients undergoing elective surgery for colon cancer at a tertiary referral university hospital between January 2010 and December 2018 were included in a retrospective review of a prospectively collected database. Univariate and regression analyses were performed to identify the prognostic role of preoperative anaemia and preoperative transfusions in this homogeneous cohort of patients. (3) Results: A total of 780 patients were included in the final analysis. The estimated five-year overall survival rate was significantly worse in the anaemic group (83.8% in non-anaemic patients, 60.6% in mild anaemic patients, 61.3% in moderate anaemic patients and 58.4% in severe anaemic patients; log-rank < 0.001 vs. non-anaemic patients). Anaemic status was found to be an independent adverse prognostic factor (hazard ratio (HR): 1.46; 95% confidence interval (CI): 1.02–2.07) during multivariate analysis. Among moderate to severe anaemic patients, no significant association was found between preoperative transfusions and the risk of mortality or recurrence. (4) Conclusions: Preoperative anaemia, regardless of its severity, and not preoperative blood transfusion, was independently associated with a worse prognosis after surgery in patients with colonic cancer.

In the era of big data, linked data interfaces play a critical role in enabling access to and management of large-scale, heterogeneous datasets. This survey investigates forty-seven interfaces developed by the semantic web community in the context of the Web of Linked Data, displaying information about general topics and digital library contents. The interfaces are classified based on their interaction paradigm, the type of information they display, and the complexity reduction strategies they employ. The main purpose to be addressed is the possibility of categorizing a great number of available tools so that comparison among them becomes feasible and valuable. The analysis reveals that most interfaces use a hybrid interaction paradigm combining browsing, searching, and displaying information in lists or tables. Complexity reduction strategies, such as faceted search and summary visualization, are also identified. Emerging trends in linked data interface focus on user-centric design and advancements in semantic annotation methods, leveraging machine learning techniques for data enrichment and retrieval. Additionally, an interactive platform is provided to explore and compare data on the analyzed tools. Overall, there is no one-size-fits-all solution for developing linked data interfaces and tailoring the interaction paradigm and complexity reduction strategies to specific user needs is essential.

Hands represent an important aspect of pictorial narration but have rarely been addressed as an object of study in art history and digital humanities. Although hand gestures play a significant role in conveying emotions, narratives, and cultural symbolism in the context of visual art, a comprehensive terminology for the classification of depicted hand poses is still lacking. In this article, we present the process of creating a new annotated dataset of pictorial hand poses. The dataset is based on a collection of European early modern paintings, from which hands are extracted using human pose estimation (HPE) methods. The hand images are then manually annotated based on art historical categorization schemes. From this categorization, we introduce a new classification task and perform a series of experiments using different types of features, including our newly introduced 2D hand keypoint features, as well as existing neural network-based features. This classification task represents a new and complex challenge due to the subtle and contextually dependent differences between depicted hands. The presented computational approach to hand pose recognition in paintings represents an initial attempt to tackle this challenge, which could potentially advance the use of HPE methods on paintings, as well as foster new research on the understanding of hand gestures in art.

Having access to accurate electron densities in chemical systems, especially for dynamical systems involving chemical reactions, ion transport, and other charge transfer processes, is crucial for numerous applications in materials chemistry. Traditional methods for computationally predicting electron density data for such systems include quantum mechanical (QM) techniques, such as density functional theory. However, poor scaling of these QM methods restricts their use to relatively small system sizes and short dynamic time scales. To overcome this limitation, we have developed a deep neural network machine learning formalism, which we call deep charge density prediction (DeepCDP), for predicting charge densities by only using atomic positions for molecules and condensed phase (periodic) systems. Our method uses the weighted smooth overlap of atomic positions to fingerprint environments on a grid-point basis and map it to electron density data generated from QM simulations. We trained models for bulk systems of copper, LiF, and silicon; for a molecular system, water; and for two-dimensional charged and uncharged systems, hydroxyl-functionalized graphane, with and without an added proton. We showed that DeepCDP achieves prediction R2 values greater than 0.99 and mean squared error values on the order of 10−5e2 Å−6 for most systems. DeepCDP scales linearly with system size, is highly parallelizable, and is capable of accurately predicting the excess charge in protonated hydroxyl-functionalized graphane. We demonstrate how DeepCDP can be used to accurately track the location of charges (protons) by computing electron densities at a few selected grid points in the materials, thus significantly reducing the computational cost. We also show that our models can be transferable, allowing prediction of electron densities for systems on which it has not been trained but that contain a subset of atomic species on which it has been trained. Our approach can be used to develop models that span different chemical systems and train them for the study of large-scale charge transport and chemical reactions.

Understanding which factors predict the outcome of internet-based cognitive behavioral therapy for insomnia (iCBT-I) may help to tailor this intervention to the patient’s needs. We have conducted a secondary analysis of a randomized, controlled trial comparing a multicomponent iCBT-I (MCT) and an online sleep restriction therapy (SRT) for 83 chronic insomnia patients. The difference in the Insomnia Severity Index from pre- to post-treatment and from pre-treatment to follow-up at 6 months after treatment was the dependent variable. Prognostic and treatment-predictive factors assessed at baseline were analyzed with multiple linear regression. The shorter duration of insomnia, female gender, high health-related quality of life, and the higher total number of clicks had prognostic value for a better outcome. Other factors were found to be prognostic for outcome at the follow-up assessment: treatment with benzodiazepines, sleep quality, and personal significance of sleep problems. A high level of dysfunctional beliefs and attitudes about sleep (DBAS) was a moderator for better effects in the MCT at post-treatment assessment. Various prognostic factors (e.g., duration of insomnia, gender, or quality of life) may influence the success of treatment. The DBAS scale may be recommended to select patients for MCT rather than SRT.

Chemotherapy-induced neurotoxicity is a well-known complication of several very effective systemic anticancer treatments, mainly presenting as cognitive impairment (“chemo-brain”) and peripheral neuropathy. The social and economic effects of long-lasting chemotherapy-induced neurotoxicity on patients’ lifestyles and their relationships are under-investigated, and their impact is, therefore, largely unknown. In this study, we used a web-based questionnaire to record the self-reported perception of chemotherapy-induced neurotoxicity on cancer patients’ health status, but also on several different aspects of their daily life. From the study results, it emerged that the impact of chemotherapy-induced neurotoxicity on personal, social, and working activities is very high. A similar effect was also observed when the psychological impact is assessed. Moreover, there is evidence suggesting that the management of CIPN is suboptimal; this is partially due to a lack of effective drugs, but also of appropriate advice from healthcare providers. In conclusion, this study provides evidence for the relevance of the impact on the explored aspects of the daily life of cancer patients and spotlights the need for a larger and more structured investigation on these long-term side effects of anticancer chemotherapy.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The prognosis for patients with high-grade and metastatic disease is still very poor, and survivors are burdened with long-lasting side effects. Therefore, more effective and less toxic therapies are needed. Surface proteins are ideal targets for antibody-based therapies, like bispecific antibodies, antibody-drug conjugates, or chimeric antigen receptor (CAR) T-cells. Specific surface targets for RMS are scarce. Here, we performed a surfaceome profiling based on differential centrifugation enrichment of surface/membrane proteins and detection by LC-MS on six fusion-positive (FP) RMS cell lines, five fusion-negative (FN) RMS cell lines, and three RMS patient-derived xenografts (PDXs). A total of 699 proteins were detected in the three RMS groups. Ranking based on expression levels and comparison to expression in normal MRC-5 fibroblasts and myoblasts, followed by statistical analysis, highlighted known RMS targets such as FGFR4, NCAM1, and CD276/B7-H3, and revealed AGRL2, JAM3, MEGF10, GPC4, CADM2, as potential targets for immunotherapies of RMS. L1CAM expression was investigated in RMS tissues, and strong L1CAM expression was observed in more than 80% of alveolar RMS tumors, making it a practicable target for antibody-based therapies of alveolar RMS.

Three-dimensional printed polymers offer unprecedented advantages for prosthetic applications, namely in terms of affordability and customisation. This work thus investigates the possibility of designing an additively manufactured prosthetic foot using continuous fibre-reinforced polymers as an alternative to composite laminate ones. A numerical approach was thus proposed and validated as a possible design tool for additively manufactured composite feet. This approach was based on explicit separate simulations of the infill, aiming to capture its homogenised engineering constants. The approach was validated on simple sandwich specimens with a different infill geometry: stiffness predictions were within the experimental standard deviation for 3D simulations. Such an approach was thus applied to redesign a laminated component of a foot prosthesis inspired by a commercial one with new additive technology. The new component was about 83% thicker than the reference one, with 1.6 mm of glass fibre skins out of about 22 mm of the total thickness. Its stiffness was within 5% of the reference laminated one. Overall, this work showed how additive manufacturing could be used as a low-cost alternative to manufacturing affordable prosthetic feet.

Shaping two-dimensional (2D) materials in arbitrarily complex geometries is a key to designing their unique physical properties in a controlled fashion. This is an elegant solution, taking benefit from the extreme flexibility of the 2D layers but requiring the ability to force their spatial arrangement from flat to curved geometries in a delicate balance among free-energy contributions from strain, slip-and-shear mechanisms, and adhesion to the substrate. Here, we report on a chemical vapor deposition approach, which takes advantage of the surfactant effects of organic molecules, namely the tetrapotassium salt of perylene-3,4,9,10-tetracarboxylic acid (PTAS), to conformally grow atomically thin layers of molybdenum disulphide (MoS2) on arbitrarily nanopatterned substrates. Using atomically resolved transmission electron microscope images and density functional theory calculations, we show that the most energetically favorable condition for the MoS2 layers consists of its adaptation to the local curvature of the patterned substrate through a shear-and-slip mechanism rather than strain accumulation. This conclusion also reveals that the perylene-based molecules have a role in promoting the adhesion of the layers onto the substrate, no matter the local-scale geometry.

Thousands of natural or manufactured chemicals were defined as endocrine-disrupting chemicals (EDCs) because they can interfere with hormone activity and the endocrine system. We summarize and discuss what we know and what we still need to learn about EDCs’ pathogenic mechanisms of action, as well as the effects of the most common EDCs on endocrine system health in childhood. The MEDLINE database (PubMed) was searched on 13 May 2022, filtering for EDCs, endocrine diseases, and children. EDCs are a group of compounds with high heterogeneity, but usually disrupt the endocrine system by mimicking or interfering with natural hormones or interfering with the body’s hormonal balance through other mechanisms. Individual EDCs were studied in detail, while humans’ “cocktail effect” is still unclear. In utero, early postnatal life, and/or pubertal development are highly susceptible periods to exposure. Human epidemiological studies suggest that EDCs affect prenatal growth, thyroid function, glucose metabolism, obesity, puberty, and fertility through several mechanisms. Further studies are needed to clarify which EDCs can mainly act on epigenetic processes. A better understanding of EDCs’ effects on human health is crucial to developing future regulatory strategies to prevent exposure and ensure the health of children today, in future generations, and in the environment.

The current literature on the diagnosis of periprosthetic joint infection provides controversial evidence on the diagnostic accuracy of MLR, NLR, PVR, and PLR. Therefore, this critical literature search and meta-analysis was aimed to summarize the diagnostic accuracy of these biomarkers for the diagnosis of hip and knee prosthetic infection. According to the PRISMA flowchart, we searched MEDLINE, Scopus, and Web of Science, for studies on these ratios for diagnosing PJI. Sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and AUC were analyzed. We included 11 articles in our meta-analysis, including 7537 patients who underwent total hip and knee arthroplasties; among these, 1974 (26%) patients reported a joint infection. The pooled sensitivity and specificity were 0.72 and 0.74, respectively, for NLR, 0.72 and 0.77 for PVR, and 0.77 and 0.75 for PLR. The sensitivity of MLR ranges from 0.54 to 0.81, while the specificity ranges from 0.78 to 0.81. Regarding the evaluation of AUCs, the best diagnostic performance was achieved by MLR (AUC = 0.77) followed by PLR (AUC = 0.75), NLR (AUC = 0.73), and PVR (AUC = 0.70). This meta-analysis demonstrates a fair diagnostic accuracy of these ratios, thus not being useful as a screening tool.

Municipal solid waste incineration fly ash (FA) can represent a sustainable supply of supplementary material to the construction industries if it is pre-treated to remove hazardous substances such as chloride, sulfate, and heavy metals. In this paper, the phenomenology associated with a water washing multi-cycle treatment of FA is investigated, focusing attention upon the mineral dissolution process. The efficacy of the treatment is assessed by leaching tests, according to the European Standard, and discussed in light of the occurring mineral phases. The water-to-solid (L/S) ratio is a crucial parameter, along with the number of washing cycles, for removing halite and sylvite, whereas quartz, calcite, anhydrite, and an amorphous phase remain in the solid residue. The sequential extraction method and dissolution kinetics modelling provide further elements to interpret leaching processes, and suggest that dissolution takes place through a two-step mechanism. Altogether, multi-step washing with L/S = 5 is effective in reducing contaminants under the legal limits for non-hazardous waste disposal, while the legal limits for non-reactive or reusable material cannot be completely reached, owing to sulfate and some heavy metals which still leached out from the residue.

The complement system plays a key role in myasthenia gravis (MG). Anti-complement drugs are emerging as effective therapies to treat anti-acetylcholine receptor (AChR) antibody-positive MG patients, though their usage is still limited by the high costs. Here, we searched for plasma complement proteins as indicators of complement activation status in AChR-MG patients, and potential biomarkers for tailoring anti-complement therapy in MG. Plasma was collected from AChR-MG and MuSK-MG patients, and healthy controls. Multiplex immunoassays and ELISA were used to quantify a panel of complement components (C1Q, C2, C3, C4, C5, Factor B, Factor H, MBL, and properdin) and activation products (C4b, C3b, C5a, and C5b-9), of classical, alternative and lectin pathways. C2 and C5 levels were significantly reduced, and C3, C3b, and C5a increased, in plasma of AChR-MG, but not MuSK-MG, patients compared to controls. This protein profile was indicative of complement activation. We obtained sensitivity and specificity performance results suggesting plasma C2, C3, C3b, and C5 as biomarkers for AChR-MG. Our findings reveal a plasma complement “C2, C3, C5, C3b, and C5a” profile associated with AChR-MG to be further investigated as a biomarker of complement activation status in AChR-MG patients, opening new perspectives for tailoring of anti-complement therapies to improve the disease treatment.

Helicobacter pylori protects itself from stressful environments by forming biofilms, changing its morphology, or invading eukaryotic cells, including yeast cells. There is little knowledge about the environmental factors that influence the endosymbiotic relationship between bacterium and yeasts. Here, we studied if oxygen availability stimulated the growth of H. pylori within Candida and if this was a bacterial- or yeast strain-dependent relationship. Four H. pylori strains and four Candida strains were co-cultured in Brucella broth plus 5% fetal bovine serum, and incubated under microaerobic, anaerobic, or aerobic conditions. Bacteria-like bodies (BLBs) within yeast cells (Y-BLBs) were detected by microscopy. H. pylori was identified by FISH and by PCR amplification of the 16S rRNA gene of H. pylori from total DNA extracted from Y-BLBs from H. pylori and Candida co-cultures. BLBs viability was confirmed by SYTO-9 fluorescence. Higher Y-BLB percentages were obtained under anaerobic conditions and using H. pylori J99 and C. glabrata combinations. Thus, the H. pylori–Candida endosymbiotic relationship is strain dependent. The FISH and PCR results identified BLBs as intracellular H. pylori. Conclusion: Stressful conditions such as an anaerobic environment significantly increased H. pylori growth within yeast cells, where it remained viable, and the bacterium–yeast endosymbiotic relationship was bacterial strain dependent with a preference for C. glabrata.

Integration of the prototypical GeSbTe (GST) ternary alloys, especially on the GeTe-Sb2Te3 tie-line, into non-volatile memory and nanophotonic devices is a relatively mature field of study. Nevertheless, the search for the next best active material with outstanding properties is still ongoing. This search is relatively crucial for embedded memory applications where the crystallization temperature of the active material has to be higher to surpass the soldering threshold. Increasing the Ge content in the GST alloys seems promising due to the associated higher crystallization temperatures. However, homogeneous Ge-rich GST in the as-deposited condition is thermodynamically unstable, and phase separation upon annealing is unavoidable. This phase separation reduces endurance and is detrimental in fully integrating the alloys into active memory devices. This work investigated the phase separation of Ge-rich GST alloys, specifically Ge5Sb2Te3 or GST523, into multiple (meta)stable phases at different length scales in melt-quenched bulk and annealed thin film. Electron microscopy-based techniques were used in our work for chemical mapping and elemental composition analysis to show the formation of multiple phases. Our results show the formation of alloys such as GST213 and GST324 in all length scales. Furthermore, the alloy compositions and the observed phase separation pathways agree to a large extent with theoretical results from density functional theory calculations.

We hypothesize that patterns of sexual behavior play a role in the conformation of transmission networks, i.e., the way you behave might influence whom you have sex with. If that was the case, behavioral grouping might in turn correlate with, and potentially predict transmission networking, e.g., proximity in a viral phylogeny. We rigorously present an intuitive approach to address this hypothesis by quantifying mapped interactions between groups defined by similarities in sexual behavior along a virus phylogeny while discussing power and sample size considerations. Data from the Swiss HIV Cohort Study on condom use and hepatitis C virus (HCV) sequences served as proof-of-concept. In this case, a strict inclusion criteria contrasting with low HCV prevalence hindered our possibilities to identify significant relationships. This manuscript serves as guide for studies aimed at characterizing interactions between behavioral patterns and transmission networks. Large transmission networks such as those of HIV or COVID-19 are prime candidates for applying this methodological approach.

Background: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. Methods: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. Results: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05–0.69, p = 0.01), zinc (0.73, 95% CI 0.55–0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78–0.98, p = 0.02). Conclusions: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.

In this study, we present a full characterization of the electronic properties of phase change material (PCM) double-layered heterostructures deposited on silicon substrates. Thin films of amorphous Ge-rich Ge-Sb-Te (GGST) alloys were grown by physical vapor deposition on Sb2Te3 and on Ge2Sb2Te5 layers. The two heterostructures were characterized in situ by X-ray and ultraviolet photoemission spectroscopies (XPS and UPS) during the formation of the interface between the first and the second layer (top GGST film). The evolution of the composition across the heterostructure interface and information on interdiffusion were obtained. We found that, for both cases, the final composition of the GGST layer was close to Ge2SbTe2 (GST212), which is a thermodynamically favorable off-stoichiometry GeSbTe alloy in the Sb-GeTe pseudobinary of the ternary phase diagram. Density functional theory calculations allowed us to calculate the density of states for the valence band of the amorphous phase of GST212, which was in good agreement with the experimental valence bands measured in situ by UPS. The same heterostructures were characterized by X-ray diffraction as a function of the annealing temperature. Differences in the crystallization process are discussed on the basis of the photoemission results.

Enrichment of GeSbTe alloys with germanium has been proposed as a valid approach to increase the crystallization temperature and therefore to address high-temperature applications of non-volatile phase change memories, such as embedded or automotive applications. However, the tendency of Ge-rich GeSbTe alloys to decompose with the segregation of pure Ge still calls for investigations on the basic mechanisms leading to element diffusion and compositional variations. With the purpose of identifying some possible routes to limit the Ge segregation, in this study, we investigate Ge-rich Sb2Te3 and Ge-rich Ge2Sb2Te5 with low (40 at %) amounts of Ge. The formation of the crystalline phases has been followed as a function of annealing temperature by X-ray diffraction. The temperature dependence of electrical properties has been evaluated by in situ resistance measurements upon annealing up to 300 °C. The segregation and decomposition processes have been studied by scanning transmission electron microscopy (STEM) and discussed on the basis of density functional theory calculations. Among the studied compositions, Ge-rich Ge2Sb2Te5 is found to be less prone to decompose with Ge segregation.

Background and Objectives: Complementary and alternative medicines (CAMs) are generally considered non-scientific and poor effective therapies. Nevertheless, CAMs are extensively used in common clinical practice in Western countries. We decided to promote a Delphi consensus to intercept the opinion of Italian physicians on CAM use in clinical practice. Materials and Methods: We run a Delphi-based consensus, interviewing anonymously 97 physicians. Of these, only 78 participate to the questionnaire. Results: Consensus about agreement and disagreement have been reached in several topics, including indication, as well as safety issues concerning CAMs. Conclusions: The use of CAMs in clinical practice still lacks evidence. Experts agree about the possibility to safely use CAMs in combination with conventional medicines to treat non-critical medical conditions.

Calcium oxalates are naturally occurring biominerals and can be found as a byproduct of some industrial processes. Recently, a new and green method for carbon capture and sequestration in stable calcium oxalate from oxalic acid produced by carbon dioxide reduction was proposed. The reaction resulted in high-quality weddellite crystals. Assessing the stability of these weddellite crystals is crucial to forecast their reuse as solid-state reservoir of pure CO2 and CaO in a circular economy perspective or, eventually, their disposal. The thermal decomposition of weddellite obtained from the new method of carbon capture and storage was studied by coupling in-situ high-temperature X-ray powder diffraction and thermogravimetric analysis, in order to evaluate the dehydration, decarbonation, and the possible production of unwanted volatile species during heating. At low temperature (119–255 °C), structural water release was superimposed to an early CO2 feeble evolution, resulting in a water-carbon dioxide mixture that should be separated for reuse. Furthermore, the storage temperature limit must be considered bearing in mind this CO2 release low-temperature event. In the range 390–550 °C, a two-component mixture of carbon monoxide and dioxide is evolved, requiring oxidation of the former or gas separation to reuse pure gases. Finally, the last decarbonation reaction produced pure CO2 starting from 550 °C.

Since the beginning of 2020, the COVID-19 pandemic has posed unprecedented challenges to viral data analysis and connected host disease diagnostic methods. We propose VirusLab, a flexible system for analysing SARS-CoV-2 viral sequences and relating them to metadata or clinical information about the host. VirusLab capitalizes on two existing resources: ViruSurf, a database of public SARS-CoV-2 sequences supporting metadata-driven search, and VirusViz, a tool for visual analysis of search results. VirusLab is designed for taking advantage of these resources within a server-side architecture that: (i) covers pipelines based on approaches already in use (ARTIC, Galaxy) but entirely cutomizable upon user request; (ii) predigests analysis of raw sequencing data from different platforms (Oxford Nanopore and Illumina); (iii) gives access to public archives datasets; (iv) supplies user-friendly reporting – making it a tool that can also be integrated into a business environment. VirusLab can be installed and hosted within the premises of any organization where information about SARS-CoV-2 sequences can be safely integrated with information about hosts (e.g., clinical metadata). A system such as VirusLab is not currently available in the landscape of similar providers: our results show that VirusLab is a powerful tool to generate tabular/graphical and machine readable reports that can be integrated in more complex pipelines. We foresee that the proposed system can support many research-oriented and therapeutic scenarios within hospitals or the tracing of viral sequences and their mutational processes within organizations for viral surveillance.

Helicobacter pylori is capable of entering into yeast, but the factors driving this endosymbiosis remain unknown. This work aimed to determine if temperatures outside the optimal range for H. pylori increase its harboring within Candida. H. pylori strains were co-cultured with Candida strains in Brucella broth supplemented with 5% fetal bovine serum and incubated at 4, 25, 37 or 40 °C. After co-culturing, yeasts containing bacteria-like bodies (Y-BLBs) were observed by optical microscopy, and the bacterium were identified as H. pylori by FISH. The H. pylori 16S rRNA gene was amplified from the total DNA of Y-BLBs. The viability of intra-yeast H. pylori cells was confirmed using a viability assay. All H. pylori strains were capable of entering into all Candida strains assayed. The higher percentages of Y-BLBs are obtained at 40 °C with any of the Candida strains. H pylori also increased its harboring within yeast in co-cultures incubated at 25 °C when compared to those incubated at 37 °C. In conclusion, although H. pylori grew significantly at 40 °C, this temperature increased its harboring within Candida. The endosymbiosis between both microorganisms is strain-dependent and permits bacterial cells to remain viable under the stressing environmental conditions assayed.

Chalcogenide GeSbTe (GST) alloys are exploited as phase change materials in a variety of applications ranging from electronic non-volatile memories to neuromorphic and photonic devices. In most applications, the prototypical Ge2Sb2Te5 compound along the GeTe-Sb2Te3 pseudobinary line is used. Ge-rich GST alloys, off the pseudobinary tie-line with a crystallization temperature higher than that of Ge2Sb2Te5, are currently explored for embedded phase-change memories of interest for automotive applications. During crystallization, Ge-rich GST alloys undergo a phase separation into pure Ge and less Ge-rich alloys. The detailed mechanisms underlying this transformation are, however, largely unknown. In this work, we performed high-throughput calculations based on Density Functional Theory (DFT) to uncover the most favorable decomposition pathways of Ge-rich GST alloys. The knowledge of the DFT formation energy of all GST alloys in the central part of the Ge-Sb-Te ternary phase diagram allowed us to identify the cubic crystalline phases that are more likely to form during the crystallization of a generic GST alloy. This scheme is exemplified by drawing a decomposition map for alloys on the Ge-Ge1Sb2Te4 tie-line. A map of decomposition propensity is also constructed, which suggests a possible strategy to minimize phase separation by still keeping a high crystallization temperature.

Epilepsy affects about 1% of the world’s population, and up to 30% of all patients will ultimately not achieve freedom from seizures with anticonvulsive medication alone. While surgical resection of a magnetic resonance imaging (MRI) -identifiable lesion remains the first-line treatment option for drug-refractory epilepsy, surgery cannot be offered to all. Neuromodulatory therapy targeting “seizures” instead of “epilepsy” has emerged as a valuable treatment option for these patients, including invasive procedures such as deep brain stimulation (DBS), responsive neurostimulation (RNS) and peripheral approaches such as vagus nerve stimulation (VNS). The purpose of this review is to provide in-depth information on current concepts and evidence on network-level aspects of drug-refractory epilepsy. We reviewed the current evidence gained from studies utilizing advanced imaging methodology, with a specific focus on their contributions to neuromodulatory therapy.

Cancer patients are identified as fragile patients who are often immunodepressed and subject to secondary diseases. The Ada cohort comprises cancer survivors aged 15–39 years at diagnosis included in 34 Italian cancer registries. This study aimed to analyze the possible excess of non-cancer medicines use on the basis of the medicine database of the Ada cohort. Records of medicines present in the pharmaceutical flows collected by eight Lombardy cancer registries and used by patients with any type of cancer were extracted for the year 2012. Medicine consumption data were processed to assign a defined daily dose value and to evaluate the consumption of medicines belonging to different groups of the ATC (Anatomical Therapeutic Chemical) classification. The values were compared with values in the Lombardy population. Medicine consumption related to 8150 patients was analyzed, for a total of 632,675 records. ATC groups A and C for females and group N for both sexes showed significant increases. Group J for males and group M for females showed intermediate increases, and group H for both sexes showed smaller increases. This method allowed the identification of excess medicine use to reduce cancer therapy side effects and primary disease sequelae in this group of patients.

In the last few decades, the introduction of microrobotics has drastically changed the way medicine will be approached in the future. The development of untethered steerable microdevices able to operate in vivo inside the human body allows a high localization of the therapeutical action, thus limiting invasiveness and possible medical complications. This approach results are particularly useful in drug delivery, where it is highly beneficial to administer the drug of choice exclusively to the target organ to avoid overdosage and side effects. In this context, drug releasing layers can be loaded on magnetically moveable platforms that can be guided toward the target organ to perform highly targeted release. In the present paper, we evaluate the possible application of alginate hydrogel layers on moveable platforms manufactured by coupling additive manufacturing with wet metallization. Such alginate layers are reticulated using three different physical crosslinkers: Ca, Zn or Mn. Their effect on drug release kinetics and on device functionality is evaluated. In the case of alginate reticulated using Mn, the strongly pH dependent behavior of the resulting hydrogel is evaluated as a possible way to introduce a triggered release functionality on the devices.

Following school closures due to the SARS-CoV-2 pandemic, for some months, children received only distance learning. The effects of this approach, however, are not clear for children with dyslexia. We conducted a cross-sectional comparison between children with and without dyslexia after the so-called “lockdown” and a comparison between pre- and post-lockdown parameters in children with dyslexia. We recruited sixty-five children with dyslexia (dyslexia group, DG) from an outpatient facility in Pavia (Lombardy, Italy) and fifty-two children without specific learning disabilities as the control group (CG) from summer camps in the same province. We performed neuropsychological tests to explore reading skills and an ad hoc questionnaire to explore how parents and children had experienced the measures taken to reduce spreading of SARS-CoV-2 infection. Between 59 to 63% of children with dyslexia did not reach the average expected increase of reading skills. According to their parents, they also showed greater social isolation and fewer worries about the pandemic and the school’s closure. Our data indicate that children with dyslexia are at increased risk of consequences on their learning potential in case of school closure. They also seem to have a peculiar psychological experience of school closure. Specific interventions should therefore be provided to minimize the risk of negative effects on global development.

Helicobacter pylori, a Gram-negative bacterium, has as a natural niche the human gastric epithelium. This pathogen has been reported to enter into Candida yeast cells; however, factors triggering this endosymbiotic relationship remain unknown. The aim of this work was to evaluate in vitro if variations in nutrient concentration in the cultured medium trigger the internalization of H. pylori within Candida cells. We used H. pylori–Candida co-cultures in Brucella broth supplemented with 1%, 5% or 20% fetal bovine serum or in saline solution. Intra-yeast bacteria-like bodies (BLBs) were observed using optical microscopy, while intra-yeast BLBs were identified as H. pylori using FISH and PCR techniques. Intra-yeast H. pylori (BLBs) viability was confirmed using the LIVE/DEAD BacLight Bacterial Viability kit. Intra-yeast H. pylori was present in all combinations of bacteria–yeast strains co-cultured. However, the percentages of yeast cells harboring bacteria (Y-BLBs) varied according to nutrient concentrations and also were strain-dependent. In conclusion, reduced nutrients stresses H. pylori, promoting its entry into Candida cells. The starvation of both H. pylori and Candida strains reduced the percentages of Y-BLBs, suggesting that starving yeast cells may be less capable of harboring stressed H. pylori cells. Moreover, the endosymbiotic relationship between H. pylori and Candida is dependent on the strains co-cultured.

Motor neuron diseases (MNDs) are neurodegenerative disorders characterized by upper and/or lower MN loss. MNDs include amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). Despite variability in onset, progression, and genetics, they share a common skeletal muscle involvement, suggesting that it could be a primary site for MND pathogenesis. Due to the key role of muscle-specific microRNAs (myomiRs) in skeletal muscle development, by real-time PCR we investigated the expression of miR-206, miR-133a, miR-133b, and miR-1, and their target genes, in G93A-SOD1 ALS, Δ7SMA, and KI-SBMA mouse muscle during disease progression. Further, we analyzed their expression in serum of SOD1-mutated ALS, SMA, and SBMA patients, to demonstrate myomiR role as noninvasive biomarkers. Our data showed a dysregulation of myomiRs and their targets, in ALS, SMA, and SBMA mice, revealing a common pathogenic feature associated with muscle impairment. A similar myomiR signature was observed in patients’ sera. In particular, an up-regulation of miR-206 was identified in both mouse muscle and serum of human patients. Our overall findings highlight the role of myomiRs as promising biomarkers in ALS, SMA, and SBMA. Further investigations are needed to explore the potential of myomiRs as therapeutic targets for MND treatment.

Responding to the recent COVID-19 outbreak, several organizations and private citizens considered the opportunity to design and publish online explanatory data visualization tools for the communication of disease data supported by a spatial dimension. They responded to the need of receiving instant information arising from the broad research community, the public health authorities, and the general public. In addition, the growing maturity of information and mapping technologies, as well as of social networks, has greatly supported the diffusion of web-based dashboards and infographics, blending geographical, graphical, and statistical representation approaches. We propose a broad conceptualization of Web visualization tools for geo-spatial information, exceptionally employed to communicate the current pandemic; to this end, we study a significant number of publicly available platforms that track, visualize, and communicate indicators related to COVID-19. Our methodology is based on (i) a preliminary systematization of actors, data types, providers, and visualization tools, and on (ii) the creation of a rich collection of relevant sites clustered according to significant parameters. Ultimately, the contribution of this work includes a critical analysis of collected evidence and an extensive modeling effort of Geo-Online Exploratory Data Visualization (Geo-OEDV) tools, synthesized in terms of an Entity-Relationship schema. The COVID-19 pandemic outbreak has offered a significant case to study how and how much modern public communication needs spatially related data and effective implementation of tools whose inspection can impact decision-making at different levels. Our resulting model will allow several stakeholders (general users, policy-makers, and researchers/analysts) to gain awareness on the assets of structured online communication and resource owners to direct future development of these important tools.

Background: Helicobacter pylori transmission routes are not entirely elucidated. Since yeasts are postulated to transmit this pathogen, this study aimed to detect and genotype intracellular H. pylori harbored within vaginal yeast cells. Methods: A questionnaire was used to determine risk factors of H. pylori infection. Samples were seeded on Sabouraud Dextrose Agar and horse blood-supplemented Columbia agar. Isolated yeasts were identified using and observed by optical microscopy searching for intra-yeast H. pylori. Total yeast DNA, from one random sample, was extracted to search for H. pylori virulence genes by PCR and bacterial identification by sequencing. Results: 43% of samples contained yeasts, mainly Candida albicans (91%). Microscopy detected bacteria such as bodies and anti-H. pylori antibodies binding particles in 50% of the isolated yeasts. Total DNA extracted showed that 50% of the isolated yeasts were positive for H. pylori 16S rDNA and the sequence showed 99.8% similarity with H. pylori. In total, 32% of H. pylori DNA positive samples were cagA+ vacAs1a vacAm1 dupA−. No relationship was observed between possible H. pylori infection risk factors and vaginal yeasts harboring this bacterium. Conclusion: H. pylori having virulent genotypes were detected within vaginal yeasts constituting a risk for vertical transmission of this pathogen.

The mechanism upon which human kidneys undergo regeneration is debated, though different lineage-tracing mouse models have tried to explain the cellular types and the mechanisms involved. Different sources of human renal progenitors have been proposed, but it is difficult to argue whether these populations have the same capacities that have been described in mice. Using the nephrosphere (NS) model, we isolated the quiescent population of adult human renal stem-like PKHhigh/CD133+/CD24− cells (RSC). The aim of this study was to deepen the RSC in vitro multipotency capacity. RSC, not expressing endothelial markers, generated secondary nephrospheres containing CD31+/vWf+ cells and cytokeratin positive cells, indicating the coexistence of endothelial and epithelial commitment. RSC cultured on decellularized human renal scaffolds generated endothelial structures together with the proximal and distal tubular structures. CD31+ endothelial committed progenitors sorted from nephrospheres generated spheroids with endothelial-like sprouts in Matrigel. We also demonstrated the double commitment toward endothelial and epithelial lineages of single RSC. The ability of the plastic RSC population to recapitulate the development of tubular epithelial and endothelial renal lineages makes these cells a good tool for the creation of organoids with translational relevance for studying the parenchymal and endothelial cell interactions and developing new therapeutic strategies.

Spinel gahnite (ZnAl2O4) has been obtained through a hydrothermal synthesis method with a grain size of about 2 nm. The sample was calcined for a few hours at two different temperatures (800 and 900 °C) in order to obtain larger grain sizes to be analyzed by means of powder diffraction with the Rietveld method, and by means of total scattering with the Pair Distribution Function (PDF) method. The idea is to compare the average to the local structure, as a function of increasing grain size. The total scattering data were collected at the European Synchrotron Radiation Facility (ESRF), Grenoble. The samples have been also characterised by means of high resolution Transmission Electron Microscopy (TEM), showing an increasing grain size up to about 9 nm. The average structure presented variations in the inversion degree and an increase in grain size. TEM observations demonstrated that the small crystals are well crystallised: the high resolution images neatly showed the atomic planes, even in the smallest particles. However, the average structure did not properly fit the PDF data in the local region, owing to a slightly different coordination among the octahedra. A new structural model is proposed for the local region of the PDF, that helped our understanding of the differences between a real nanostructured sample and that of a microcrystalline one. The oxygen disorder, due to the inversion grade of the spinel, is demonstrates to be at the basis of the local deviation. No signals of interstitial Zn atoms were detected.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by mutations in survival motor neuron (SMN) 1 gene, resulting in a truncated SMN protein responsible for degeneration of brain stem and spinal motor neurons. The paralogous SMN2 gene partially compensates full-length SMN protein production, mitigating the phenotype. Antisense oligonucleotide nusinersen (Spinraza®) enhances SMN2 gene expression. SMN is involved in RNA metabolism and biogenesis of microRNA (miRNA), key gene expression modulators, whose dysregulation contributes to neuromuscular diseases. They are stable in body fluids and may reflect distinct pathophysiological states, thus acting as promising biomarkers. Muscle-specific miRNAs (myomiRs) as biomarkers for clinical use in SMA have not been investigated yet. Here, we analyzed the expression of miR-133a, -133b, -206 and -1, in serum of 21 infantile SMA patients at baseline and after 6 months of nusinersen treatment, and correlated molecular data with response to therapy evaluated by the Hammersmith Functional Motor Scale Expanded (HFMSE). Our results demonstrate that myomiR serological levels decrease over disease course upon nusinersen treatment. Notably, miR-133a reduction predicted patients’ response to therapy. Our findings identify myomiRs as potential biomarkers to monitor disease progression and therapeutic response in SMA patients.