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Background: Liquid biopsy (LB) is a laboratory test performed on a fluid sample aiming at analyzing molecular data derived from circulating cells and related entities, or from nucleic acids. This umbrella review aims to map and evaluate the evidence supporting the use of LB in medicine across different medical specialities and conditions. Methods: We searched three repositories from database inception up to October 1, 2023 and we included meta-analyses of observational studies reporting data on the use of LB, compared to gold standard, and its accuracy (area under the curve, AUC). Results: Among 726 articles initially screened, 42 systematic reviews were included. Most of the outcomes explored (202/211) were related to cancer. We found that 75/211 had an excellent accuracy (AUC >0.90), with one comparison with an AUC equal to 1, i.e., Cell-Free Human Papillomavirus DNA (cfHPV-DNA) for HPV-positive oropharyngeal squamous cell carcinoma. However, considering published meta-analyses, all the outcomes were graded as very low on the GRADE criteria, and the heterogeneity was never reported. Discussion: The literature about LB is rapidly increasing and some promising data about precision oncology are now available. However, this umbrella review on existing meta-analyses highlighted some critical issues for providing quantitative estimations on the different roles of LB.

Background: HIV infection has been associated with an increased risk of cancer development and Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancers have been a manifestation of AIDS. With the advent of antiretroviral therapy, a collateral appearance of non-AIDS defining cancers (NADC) has been observed in HIV positive patients. Methods: From January 1997 to December 2022, we performed an observational cross-sectional study, involving HIV-infected outpatients with both AIDS-defining cancers (ADC) and NADC, followed up in a tertiary hospital in Italy. Results: Overall, 153 cases of malignancy were observed, with a higher percentage of NADC (60.8 %) rather than ADC (39.2 %). Mean age at tumour diagnosis was significantly lower for ADC than for NADC in HIV positive individuals (p-value= 0.001). No statistical difference was found between the mean values of zenith HIV-RNA and CD4 count in HIV outpatients with cancer and in those without cancer, while a statistically significant difference was found between the HIV-RNA zenith in HIV outpatients with ADC as compared with NADC (10.2 copies/mL versus 8.1 copies/mL; p-value= 0.007). Conclusions: Our study revealed a considerably high proportion of non-AIDS defining malignancies in HIV individuals, emphasizing the need to improve the management of these cancer patients at follow up according to the risk profiles and the changing epidemiology.

Background: Multiple factors can fuel nurses’ intention to leave their employing hospital or their profession. Job dissatisfaction and burnout are contributors to this decision. Sociodemographic and work context factors can also play a role in explaining nurses’ intention to leave. Objective: To investigate the role of sociodemographic and work context factors, including job resources, job demands, job dissatisfaction, depersonalization, and emotional exhaustion, on nurses’ intention to leave their hospital or their profession. Design: Multicentre cross-sectional study. Setting(s): Eight European hospitals, two per each country, including Belgium, the Netherlands, Italy, and Poland. Participants: From May 16 to September 30, 2022, we collected 1,350 complete responses from nurses working at the selected hospitals (13 % response rate). Methods: The intention to leave was assessed through two 5-Likert scale outcomes, agreeing with the intention to leave the profession and the intention to leave the hospital. Logistic regression models were used for statistical analysis. Results: At the multivariable analysis, a higher intention to leave the hospital was observed for: younger age, having served on the frontline against COVID-19, lack of quipment, living in the Netherlands, emotional exhaustion, dissatisfaction with work prospects, and dissatisfaction with the use of professional abilities. There was a higher intention to leave the profession for: younger age, living in the Netherlands, having work-related health problems, depersonalization, emotional exhaustion, low possibilities of professional development, dissatisfaction with work prospects, lack of use of professional abilities, overall ob issatisfaction, and dissatisfaction with salary. Nurses living in Italy expressed the lowest intention to leave. Conclusion: While confirming the role of job dissatisfaction and burnout, we found higher intention to leave for young nurses, nurses with work-related health problems, and caregivers during the COVID-19 pandemic. Dissatisfaction with work prospects, professional development, and salary also increased the intention to leave. We call for educators, managers, and policymakers to address these factors to retain at-risk nursing categories, implementing strategies to mitigate intentions to leave.

BackgroundCardiovascular diseases (CVDs) pose a significant global health challenge, necessitating innovative approaches for primary prevention. Personalized prevention, based on genetic risk scores (PRS) and digital technologies, holds promise in revolutionizing CVD preventive strategies. However, the clinical efficacy of these interventions requires further investigation. This study presents the protocol of the INNOPREV randomized controlled trial, aiming to evaluate the clinical efficacy of PRS and digital technologies in personalized cardiovascular disease prevention.MethodsThe INNOPREV trial is a four-arm RCT conducted in Italy. A total of 1,020 participants, aged 40–69 with high 10-year CVD risk based on SCORE 2 charts, will be randomly assigned to traditional CVD risk assessment, genetic testing (CVD PRS), digital intervention (app and smart band), or a combination of genetic testing and digital intervention. The primary objective is to evaluate the efficacy of providing CVD PRS information, measured at baseline, either alone or in combination with the use of an app and a smart band, on two endpoints: changes in lifestyle patterns, and modification in CVD risk profiles. Participants will undergo a comprehensive assessment and cardiovascular evaluation at baseline, with follow-up visits at one, five, and 12 months. Lifestyle changes and CVD risk profiles will be assessed at different time points beyond the initial assessment, using the Life's Essential 8 and SCORE 2, respectively. Blood samples will be collected at baseline and at study completion to evaluate changes in lipid profiles. The analysis will employ adjusted mixed-effect models for repeated measures to assess significant differences in the data collected over time. Additionally, potential moderators and mediators will be examined to understand the underlying mechanisms of behavior change.DiscussionAs the largest trial in this context, the INNOPREV trial will contribute to the advancement of personalized cardiovascular disease prevention, with the potential to positively impact public health and reduce the burden of CVDs on healthcare systems. By systematically examining the clinical efficacy of PRS and digital interventions, this trial aims to provide valuable evidence to guide future preventive strategies and enhance population health outcomes.

Dietary changes expose consumers to risks from Anisakis larvae in seafood, leading to parasitic diseases and allergies. Anisakis is recognized by EFSA as a significant hazard, with potential oncogenic implications. Diagnostic advancements, like the Basophil Activation Test (BAT), enhance sensitivity and accuracy in identifying Anisakis sensitization, complementing traditional IgE tests. We conducted a cross-sectional study on patients with allergic symptoms from April 2021 to April 2023 at two outpatient clinics in western Sicily. Our goal was to assess the prevalence of Anisakis-related allergies and to identify risk profiles using specific Anisakis IgE and the BAT, especially in regions with high raw fish consumption. The study evaluated specific Anisakis IgE as a screening tool for Anisakis sensitization, using questionnaires, blood samples, and immuno-allergology analyses. Anisakis-specific IgE values were compared with the BAT results, with statistical analyses including Fisher’s exact test and logistic regression. The results showed an 18.5% seroprevalence of Anisakis IgE, while the BAT as a second-level test showed 4.63%, indicating the BAT’s superior specificity and accuracy. The study highlighted the importance of the BAT in diagnosing Anisakis sensitization, especially in cases of cross-reactivity with Ascaris and tropomyosin. The findings confirm the BAT’s exceptional specificity in identifying Anisakis sensitization and support using Anisakis-specific IgE for population-based risk profiling. The BAT can effectively serve as a confirmatory test.

IntroductionWork-related stress is an occupational risk that has been linked to the development of cardiovascular disease (CVD). While previous studies have explored this association in various work contexts, none have focused specifically on logistics and distribution personnel. These workers may be exposed to significant job stress, which potentially increases the risk of CVD.MethodsIn this study, we aimed to examine the relationship between work-related stress and cardiovascular risk in a sample of 413 healthy workers of a logistics and distribution company. To assess work-related stress and cardiovascular risk, we used the organisational well-being questionnaire proposed by the Italian National Anti-Corruption Authority, the Framingham Heart Study General Cardiovascular Disease (CVD) Risk Prediction Score and the WHO General Wellbeing Index (WHO-5).ResultsOur results revealed that individuals with low job support had a significantly higher CVD risk score and lower well-being index than those reporting high job support. Furthermore, workers with high-stress tasks showed higher well-being index scores than those with passive tasks. Approximately 58% of the subjects were classified as low CVD risk (CVD risk 20%). The overall median CVD risk for the population was moderate (6.9%), with individual scores ranging from 1 to 58%.DiscussionFurther analyses confirmed the protective effect of work support, also identifying physical inactivity, regular alcohol consumption and low educational level as factors contributing to an increased risk of CVD. Interestingly, factors such as job control and work support demonstrated a positive impact on psychological well-being. These results emphasise the importance of intervention strategies aimed at promoting health in the workplace. By addressing these combined factors, organisations can effectively reduce the risk of CVD and improve the general well-being of their workforce.

IntroductionBreast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T-cell lymphoma associated with breast reconstruction post-mastectomy or cosmetic-additive mammoplasty. The increasing use of implants for cosmetic purposes is expected to lead to an increase in BIA-ALCL cases. This study investigated the main characteristics of the disease and the factors predicting BIA-ALCL onset in patients with and without an implant replacement.MethodsA quantitative analysis was performed by two independent researchers on cases extracted from 52 primary studies (case report, case series, and systematic review) published until April 2022 and searched in PubMed, Scopus, and Google-Scholar databases using “Breast-Implant” AND/OR “Associated” AND/OR “Anaplastic-Large-Cell-Lymphoma”. The statistical significance was verified by Student’s t-test for continuous variables, while Fisher’s exact test was applied for qualitative variables. Cox model with time-dependent covariates was used to estimate BIA-ALCL’s onset time. The Kaplan–Meier model allowed the estimation of the probability of survival after therapy according to breast implant exposure time.ResultsOverall, 232 patients with BIA-ALCL were extracted. The mean age at diagnosis was 55 years old, with a mean time to disease onset from the first implant of 10.3 years. The hazard of developing BIA-ALCL in a shorter time resulted significantly higher for patients not having an implant replacement (hazard ratio = 0.03; 95%CI: 0.005–0.19; p-value < 0.01). Patients with implant replacement were significantly older than patients without previous replacement at diagnosis, having a median time to diagnosis since the first implant of 13 years (7 years in patients without replacement); anyway, the median time to BIA-ALCL occurrence since the last implantation was equal to 5 years.DiscussionOur findings suggest that, in BIA-ALCL patients, the implant substitution and/or capsulectomy may delay the disease’s onset. However, the risk of reoccurrence in an earlier time should be considered in these patients. Moreover, the time to BIA-ALCL onset slightly increased with age. Selection bias, lack of awareness, misdiagnosis, and limited data availability could be identified as limits of our study. An implant replacement should be considered according to a risk stratification approach to delay the BIA-ALCL occurrence in asymptomatic patients, although a stricter follow-up after the implant substitution should be recommended.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023446726.

IntroductionExtracellular vesicles (EVs) are nanometric-membrane-bound sub-cellular structures, which can be recovered from milk. Milk EVs have drawn increasing interest due to their potential biomedical applications, therefore it is important to investigate their impact on key immune cells, such as macrophages.MethodsIn this work, the immunomodulatory effects of goat milk EVs on untreated (moMФ) and classically activated (moM1) porcine monocyte-derived macrophages were investigated using flow cytometry, ELISA, and gene expression assays.ResultsThese particles were efficiently internalized by macrophages and high doses (60 mg protein weight) triggered the upregulation of MHC I and MHC II DR on moMФ, but not on moM1. In moMФ, exposure to low doses (0.6 mg) of mEVs enhanced the gene expression of IL10, EBI3, and IFNB, whereas high doses up-regulated several pro-inflammatory cytokines. These nanosized structures slightly modulated cytokine gene expression on moM1. Accordingly, the cytokine (protein) contents in culture supernatants of moMФ were mildly affected by exposure to low doses of mEVs, whereas high doses promoted the increased release of TNF, IL-8, IL-1a, IL-1b, IL-1Ra, IL-6, IL-10, and IL-12. The cytokines content in moM1 supernatants was not critically affected.DiscussionOverall, our data support a clinical application of these molecules: they polarized macrophages toward an M1-like phenotype, but this activation seemed to be controlled, to prevent potentially pathological over-reaction to stressors.

Simple Summary: Prostheses are highly beneficial as they reduce the need for formal healthcare and support services, but they are not without side effects. Despite advancements, issues such as implant rejection and perioperative complications persist, and new concerns have arisen, including the potential link between long-term prosthetic use and cancer, specifically lymphoma. While the overall risk of developing lymphoma from prosthetic implants remains low, it is essential to explore the factors contributing to this risk. This highlights the need for ongoing research into the safety and long-term effects of prosthetic devices. Based on this evidence, we conducted a descriptive analysis using individual patient data from primary studies to investigate the relationship between lymphomas and different types of prosthetic devices, excluding breast implants. Background: Medical devices used for functional or esthetic purposes improve health and quality of life; however, they are not risk-free. Anaplastic large-cell lymphoma (ALCL), associated with breast implants, is a well-known and recognized distinct lymphoma entity. More recently, additional lymphomas have been reported in relation to prosthesis other than breast implants, as these allow the pericyte to develop into a clone that undergoes a maturation process, progressing toward full malignancy. Methods: We performed a systematic review with a descriptive analysis of data extracted from primary studies following PRISMA guidelines, including the search string "(IMPLANT* OR PROSTHES*) AND LYMPHOM*" in the PubMed, Scopus, Embase, and Google-Scholar databases. Data such as patient sex, age, implant site, prosthesis material, and lymphoma type were analyzed. Statistical methods, including Student's t-test and Fisher's exact test, were employed to compare lymphoma characteristics, with significance set at a p-value < 0.05. Results: From a total of 5992 studies, we obtained 43 case reports and series on a total of 52 patients diagnosed with prosthesis-associated lymphomas. The majority of implant-related lymphoma cases (85%) were of the B-cell type, mostly fibrin-associated large B-cell lymphoma (LBCL). This lymphoma type was more associated with biological (non-human-derived biological tissue), metallic, and synthetic implants (synthesized from non-organic components) (p-value = 0.007). Patients with ALCL had equal frequencies of metal and silicone prostheses (37.5%, 3 cases each), followed by synthetic prostheses (25%, 2 cases). ALCL cases were most common at skeletal (50%) and muscular-cutaneous sites (25%), whereas B-cell lymphomas were predominantly found in cardiovascular implants (50%), followed by skeletal (27%) and muscular-cutaneous (21%) sites. Death attributed to lymphoma took place in 67% of the cases, mostly LBCL occurring in cardiovascular sites. Conclusions: Because the included studies were limited to case reports and series, a potential non-causal link might have been documented between different implant materials, implant sites and lymphoma types. This underscores the importance of further comprehensive research and monitoring of non-breast implants. [ABSTRACT FROM AUTHOR]

The dietary supplementation of olive oil by-products, including olive mill waste-water (OMWW) in animal diets, is a novel application that allows for their re-utilization and recycling and could potentially decrease the use of antibiotics, antimicrobial resistance risk in livestock species, and the occurrence of intestinal diseases. Salmonella serovar typhimurium is one of the most widespread intestinal pathogens in the world, causing enterocolitis in pigs. The aim of this study was to investigate the effect of an OMWW extract enriched in polyphenols (hydroxytyrosol and tyrosol) in the immune response of an intestinal porcine epithelial cell line (IPEC-J2) following S. typhimurium infection. Cells were pre-treated with OMWW-extract polyphenols (OMWW-EP, 0.35 and 1.4 µg) for 24 h and then infected with S. typhimurium for 1 h. We evaluated bacterial invasiveness and assayed IPEC-J2 gene expression with RT-qPCR and cytokine release with an ELISA test. The obtained results showed that OMWW-EP (1.4 µg) significantly reduced S. typhimurium invasiveness; 0.35 µg decreased the IPEC-J2 gene expression of IL1B, MYD88, DEFB1 and DEFB4A, while 1.4 µg down-regulated IL1B and DEFB4A and increased TGFB1. The cytokine content was unchanged in infected cells. This is the first study demonstrating the in vitro immunomodulatory and antimicrobial activity of OMWW extracts enriched in polyphenols, suggesting a protective role of OMWW polyphenols on the pig intestine and their potential application as feed supplements in farm animals such as pigs.

We present an overview of Sherpa, an open-source Python project, and discuss its development history, broad design concepts, and capabilities. Sherpa contains powerful tools for combining parametric models into complex expressions that can be fit to data using a variety of statistics and optimization methods. It is easily extensible to include user-defined models, statistics, and optimization methods. It provides a high-level user interface for interactive data analysis, such as within a Jupyter notebook, and it can also be used as a library component, providing fitting and modeling capabilities to an application. We include a few examples of Sherpa applications to multiwavelength astronomical data.

Papillomas are benign epithelial lesions protruding on the epithelial surfaces as finger-like or warty projections. These lesions are often caused by papillomavirus (PV) infection. Congenital papillomas have been reported in foals. However, to date, no evidence of PV infection has been provided. In the present paper, we describe the main clinical–pathological features of a congenital papilloma observed in a foal. In addition, biomolecular tests demonstrated BPV1 infection in the case under study. Such data stimulate further investigations, even on archived samples, aiming to clarifying the etiology of equine congenital papilloma and the clinical relevance, if any, of BPV1 vertical transmission in horses.

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Dietary changes expose consumers to risks from Anisakis larvae in seafood, leading to parasitic diseases and allergies. Anisakis is recognized by EFSA as a significant hazard, with potential oncogenic implications. Diagnostic advancements, like the Basophil Activation Test (BAT), enhance sensitivity and accuracy in identifying Anisakis sensitization, complementing traditional IgE tests. We conducted a cross-sectional study on patients with allergic symptoms from April 2021 to April 2023 at two outpatient clinics in western Sicily. Our goal was to assess the prevalence of Anisakis-related allergies and to identify risk profiles using specific Anisakis IgE and the BAT, especially in regions with high raw fish consumption. The study evaluated specific Anisakis IgE as a screening tool for Anisakis sensitization, using questionnaires, blood samples, and immuno-allergology analyses. Anisakis-specific IgE values were compared with the BAT results, with statistical analyses including Fisher's exact test and logistic regression. The results showed an 18.5% seroprevalence of Anisakis IgE, while the BAT as a second-level test showed 4.63%, indicating the BAT's superior specificity and accuracy. The study highlighted the importance of the BAT in diagnosing Anisakis sensitization, especially in cases of cross-reactivity with Ascaris and tropomyosin. The findings confirm the BAT's exceptional specificity in identifying Anisakis sensitization and support using Anisakis-specific IgE for population-based risk profiling. The BAT can effectively serve as a confirmatory test. [ABSTRACT FROM AUTHOR]

The rising popularity of undercooked or raw seafood containing larvae of the Anisakis parasite has led to issues of public health concern due to allergic manifestations. We conducted an observational study on the use of an innovative Anisakis allergy diagnostic algorithm in a convenience sample of 53 allergic outpatients recruited in Western Sicily, between April 2021 and March 2022. We included individuals with an anamnesis suggestive of IgE sensitization to Anisakis reporting clinical manifestation in the last month due to allergic reactions after eating fresh fish, or in subjects at high exposure risk with sea products while abstaining from fish ingestion, excluding those with documented fish sensitization. Outpatients were tested via Skin Prick Test, IgE-specific dosage and Basophil Activation Test (BAT). Twenty-six outpatients were diagnosed with Anisakis, while 27 with Chronic Urticaria (CU). We found a seven-fold excess risk for Anisakis (p4) positivity in the Anisakis allergic outpatients, as compared to the CU ones. BAT showed the best diagnostic accuracy (92.45%) and specificity (100%), while specific IgE to Ascaris (p1) documented the best sensitivity (92.31%) but a very low specificity (37.04%). In conclusion, our findings may represent a potentially useful contribution to the future development of updated clinical guidelines.

Papillomaviruses (PVs) are small, non-enveloped viruses, ubiquitous across the animal kingdom. PVs induce diverse forms of infection, such as cutaneous papillomas, genital papillomatosis, and carcinomas. During a survey on the fertility status of a mare, a novel Equus caballus PV (EcPV) has been identified using Next Generation Sequencing, and it was further confirmed with genome-walking PCR and Sanger sequencing. The complete circular genome 7607 bp long shares 67% average percentage of identity with EcPV9, EcPV2, EcPV1, and EcPV6, justifying a new classification as Equus caballus PV 10 (EcPV10). All EcPV genes are conserved in EcPV10, and phylogenetic analysis indicates that EcPV10 is closely related to EcPV9 and EcPV2, genus Dyoiota 1. A preliminary EcPV10 genoprevalence study, carried out on 216 horses using Real Time PCRs, suggested a low incidence of this isolate (3.7%) compared to EcPVs of the same genus such as EcPV2 and EcPV9 in the same horse population. We hypothesize a transmission mechanism different from the one observed in the closely related EcPV9 and EcPV2 that particularly infect Thoroughbreds. This horse breed is usually submitted to natural mating, thus indicating a possible sexual diffusion. No differences were detected for breeds in terms of susceptibility to EcPV10. Further studies are needed to investigate the molecular mechanisms behind the host and EcPV10 infection to explain the reduced viral spread.

The Cygnus OB2 association is the largest concentration of young and massive stars within 2 kpc of the Sun, including an estimated ∼65 O-type stars and hundreds of OB stars. The Chandra Cygnus OB2 Legacy Survey is a large imaging program undertaken with the Advanced CCD Imaging Spectrometer on board the Chandra X-ray Observatory. The survey has imaged the central 0.5 deg ^2 of the Cyg OB2 association with an effective exposure of ∼120 ks and an outer 0.35 deg ^2 area with an exposure of ∼60 ks. Here we describe the survey design and observations, discuss the data reduction and source detection, and present a catalog of ∼8000 X-ray point sources. The survey design employs a grid of 36 heavily (∼50%) overlapping pointings, a method that overcomes Chandra's low off-axis sensitivity and produces a highly uniform exposure over the inner 0.5 deg ^2 . The full X-ray catalog is described here and is made available online.

Extracellular Vesicles (EVs) are nano-sized double-lipid-membrane-bound structures, acting mainly as signalling mediators between distant cells and, in particular, modulating the immune response and inflammation of targeted cells. Milk and colostrum contain high amounts of EVs that could be exploited as alternative natural systems in antimicrobial fighting. The aim of this study is to evaluate cow colostrum-derived EVs (colosEVs) for their antimicrobial, anti-inflammatory and immunomodulating effects in vitro to assess their suitability as natural antimicrobial agents as a strategy to cope with the drug resistance problem. ColosEVs were evaluated on a model of neonatal calf diarrhoea caused by Escherichia coli infection, a livestock disease where antibiotic therapy often has poor results. Colostrum from Piedmontese cows was collected within 24 h of calving and colosEVs were immediately isolated. IPEC-J2 cell line was pre-treated with colosEVs for 48 h and then infected with EPEC/NTEC field strains for 2 h. Bacterial adherence and IPEC-J2 gene expression analysis (RT-qPCR) of CXCL8, DEFB1, DEFB4A, TLR4, TLR5, NFKB1, MYD88, CGAS, RIGI and STING were evaluated. The colosEVs pre-treatment significantly reduced the ability of EPEC/NTEC strains to adhere to cell surfaces (p = 0.006), suggesting a role of ColosEVs in modulating host–pathogen interactions. Moreover, our results showed a significant decrease in TLR5 (p < 0.05), CGAS (p < 0.05) and STING (p < 0.01) gene expression in cells that were pre-treated with ColosEVs and then infected, thus highlighting a potential antimicrobial activity of ColosEVs. This is the first preliminarily study investigating ColosEV immunomodulatory and anti-inflammatory effects on an in vitro model of neonatal calf diarrhoea, showing its potential as a therapeutic and prophylactic tool.