A probabilistic network for the diagnosis of acute cardiopulmonary diseases.

In this paper, the development of a probabilistic network for the diagnosis of acute cardiopulmonary diseases is presented in detail. A panel of expert physicians collaborated to specify the qualitative part, which is a directed acyclic graph defining a factorization of the joint probability distribution of domain variables into univariate conditional distributions. The quantitative part, which is a set of parametric models defining these univariate conditional distributions, was estimated following the Bayesian paradigm. In particular, we exploited an original reparameterization of Beta and categorical logistic regression models to elicit the joint prior distribution of parameters from medical experts, and updated it by conditioning on a dataset of hospital records via Markov chain Monte Carlo simulation. Refinement was iteratively performed until the probabilistic network provided satisfactory concordance index values for several acute diseases and reasonable diagnosis for six fictitious patient cases. The probabilistic network can be employed to perform medical diagnosis on a total of 63 diseases (38 acute and 25 chronic) on the basis of up to 167 patient findings.

Relationship between increasing concentrations of two carcinogens and statistical image descriptors of foci morphology in the cell transformation assay.

Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i.e. the step in which transformed colonies or foci are evaluated through morphological features. An objective evaluation of morphological features has been previously obtained through automated digital processing of foci images to extract the value of three statistical image descriptors. In this study a further potential of the CTA using BALB/c 3T3 cells is addressed by analysing the effect of increasing concentrations of two known carcinogens, benzo[a]pyrene and NiCl2 , with different modes of action on foci morphology. The main result of our quantitative evaluation shows that the concentration of the considered carcinogens has an effect on foci morphology that is statistically significant for the mean of two among the three selected descriptors. Statistical significance also corresponds to visual relevance. The statistical analysis of variations in foci morphology due to concentration allowed to quantify morphological changes that can be visually appreciated but not precisely determined. Therefore, it has the potential of providing new quantitative parameters in CTAs, and of exploiting all the information encoded in foci. Copyright © 2016 John Wiley & Sons, Ltd.

Chain graph models to elicit the structure of a Bayesian network.

Bayesian networks are possibly the most successful graphical models to build decision support systems. Building the structure of large networks is still a challenging task, but Bayesian methods are particularly suited to exploit experts' degree of belief in a quantitative way while learning the network structure from data. In this paper details are provided about how to build a prior distribution on the space of network structures by eliciting a chain graph model on structural reference features. Several structural features expected to be often useful during the elicitation are described. The statistical background needed to effectively use this approach is summarized, and some potential pitfalls are illustrated. Finally, a few seminal contributions from the literature are reformulated in terms of structural features.

Welfare of invertebrates: a pilot study on a new land snail stunning technique.

The almost complete absence of regulations to protect invertebrates is a common condition in legal systems, including the European one, especially when it comes to invertebrates intended for human consumption. Thus, in the vast majority of cases, edible invertebrates do not receive even the most basic protection at slaughter. Despite recent research indicating that invertebrates are capable of feeling pain and stress, the humane step of stunning is not used on them. This is also the case for land snails, which are gastropod invertebrates whose consumption has now reached significant levels, already involving tonnes and that is expected to increase significantly as edible snail farming becomes more popular as a relatively low-cost, easy-to-perform, and sustainable alternative animal husbandry, thereby making land snails an increasingly economically important species. This paper presents and investigates a proposed stunning method based on the immersion of mollusks in CO2-supplemented and refrigerated water that could be used in the snail meat production chain to reduce the slaughter suffering of millions of these invertebrates. To this end, body condition descriptors (hemolymph parameters) in snails were determined before and after CO2 treatment in cold water, while generating useful data for defining a preliminary set of reference intervals for basal values.

Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis.

Glioblastoma multiforme (GBM) is usually treated with surgery followed by adjuvant partial radiotherapy combined with temozolomide (TMZ) chemotherapy. Recent studies demonstrated a better survival and good response to TMZ in methylguanine-DNA methyltransferase (MGMT)-methylated GBM cases. However, approximately 20% of patients with MGMT-unmethylated GBM display an unexpectedly favorable outcome. Therefore, additional mechanisms related to the TMZ response need to be investigated. As such, we decided to investigate the clinical relevance of six miRNAs involved in brain tumorigenesis (miR-181c, miR-181d, miR-21, miR-195, miR-196b, miR-648) as additional markers of response and survival in patients receiving TMZ for GBM. We evaluated miRNA expression and the interplay between miRNAs in 112 IDH wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients' clinical outcomes. Upon bivariate analyses, we found a significant association between the expression levels of the miRNAs analyzed, but, more interestingly, the OS curves show that the combination of low miR-648 and miR-181c or miR-181d expressions is associated with a worse prognosis than cases with other low-expression miRNA pairs. To conclude, we found how specific miRNA pairs can influence survival in GBM cases treated with TMZ.

A Bayesian model for control strategy selection against Plasmopara viticola infections.

Plant pathogens pose a persistent threat to grape production, causing significant economic losses if disease management strategies are not carefully planned and implemented. Simulation models are one approach to address this challenge because they provide short-term and field-scale disease prediction by incorporating the biological mechanisms of the disease process and the different phenological stages of the vines. In this study, we developed a Bayesian model to predict the probability of Plasmopara viticola infection in grapevines, considering various disease management approaches. To aid decision-making, we introduced a multi-attribute utility function that incorporated a sustainability index for each strategy. The data used in this study were derived from trials conducted during the production years 2018-2020, involving the application of five disease management strategies: conventional Integrated Pest Management (IPM), conventional organic, IPM with substantial fungicide reduction combined with host-defense inducing biostimulants, organic management with biostimulants, and the use of biostimulants only. Two scenarios were considered, one with medium pathogen pressure (Average) and another with high pathogen pressure (Severe). The results indicated that when sustainability indexes were not considered, the conventional IPM strategy provided the most effective disease management in the Average scenario. However, when sustainability indexes were included, the utility values of conventional strategies approached those of reduced fungicide strategies due to their lower environmental impact. In the Severe scenario, the application of biostimulants alone emerged as the most effective strategy. These results suggest that in situations of high disease pressure, the use of conventional strategies effectively combats the disease but at the expense of a greater environmental impact. In contrast to mechanistic-deterministic approaches recently published in the literature, the proposed Bayesian model takes into account the main sources of heterogeneity through the two group-level effects, providing accurate predictions, although precise estimates of random effects may require larger samples than usual. Moreover, the proposed Bayesian model assists the agronomist in selecting the most effective crop protection strategy while accounting for induced environmental side effects through customizable utility functions.

Identification of MGMT Downregulation Induced by miRNA in Glioblastoma and Possible Effect on Temozolomide Sensitivity.

Glioblastoma multiforme (GBM) remains one of the tumors with the worst prognosis. In recent years, a better overall survival (OS) has been described in cases subjected to Gross Total Resection (GTR) that were presenting hypermethylation of Methylguanine-DNA methyltransferase (MGMT) promoter. Recently, also the expression of specific miRNAs involved in MGMT silencing has been related to survival. In this study, we evaluate MGMT expression by immunohistochemistry (IHC), MGMT promoter methylation and miRNA expression in 112 GBMs and correlate the data to patients' clinical outcomes. Statistical analyses demonstrate a significant association between positive MGMT IHC and the expression of miR-181c, miR-195, miR-648 and miR-767.3p between unmethylated cases and the low expression of miR-181d and miR-648 and between methylated cases and the low expression of miR-196b. Addressing the concerns of clinical associations, a better OS has been described in presence of negative MGMT IHC, in methylated patients and in the cases with miR-21, miR-196b overexpression or miR-767.3 downregulation. In addition, a better progression-free survival (PFS) is associated with MGMT methylation and GTR but not with MGMT IHC and miRNA expression. In conclusion, our data reinforce the clinical relevance of miRNA expression as an additional marker to predict efficacy of chemoradiation in GBM.

A human-neutral large carnivore? No patterns in the body mass of gray wolves across a gradient of anthropization.

The gray wolf (Canis lupus) expanded its distribution in Europe over the last few decades. To better understand the extent to which wolves could re-occupy their historical range, it is important to test if anthropization can affect their fitness-related traits. After having accounted for ecologically relevant confounders, we assessed how anthropization influenced i) the growth of wolves during their first year of age (n = 53), ii) sexual dimorphism between male and female adult wolves (n = 121), in a sample of individuals that had been found dead in Italy between 1999 and 2021. Wolves in anthropized areas have a smaller overall variation in their body mass, during their first year of age. Because they already have slightly higher body weight at 3-5 months, possibly due to the availability of human-derived food sources. The difference in the body weight of adult females and males slightly increases with anthropization. However, this happens because of an increase in the body mass of males only, possibly due to sex-specific differences in dispersal and/or to "dispersal phenotypes". Anthropization in Italy does not seem to have any clear, nor large, effect on the body mass of wolves. As body mass is in turn linked to important processes, like survival and reproduction, our findings indicates that wolves could potentially re-occupy most of their historical range in Europe, as anthropized landscapes do not seem to constrain such of an important life-history trait. Wolf management could therefore be needed across vast spatial scales and in anthropized areas prone to social conflicts.

A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-Radiotherapy in Patients With Locally Advanced Rectal Cancer: The LiBReCa Study.

Introduction: Circulating tumor DNA (ctDNA) correlates with the response to therapy in different types of cancer. However, in patients with locally advanced rectal cancer (LARC), little is known about how ctDNA levels change with neoadjuvant chemoradiation (Na-ChRT) and how they correlate with treatment response. This work aimed to explore the value of serial liquid biopsies in monitoring response after Na-ChRT with the hypothesis that this could become a reliable biomarker to identify patients with a complete response, candidates for non-operative management. Materials and Methods: Twenty-five consecutive LARC patients undergoing long-term Na-ChRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded diagnostic biopsy and resection tissue and plasma ctDNA collected at the following time points: the first and last days of radiotherapy (T0, Tend), at 4 (T4), 7 (T7) weeks after radiotherapy, on the day of surgery (Top), and 3-7 days after surgery (Tpost-op). On the day of surgery, a mesenteric vein sample was also collected (TIMV). The relationship between the ctDNA at those time-points and the tumor regression grade (TRG) of the surgical specimen was statistically explored. Results: We found no association between the disappearance of ctDNA mutations in plasma samples and pathological complete response (TRG1) as ctDNA was undetectable in the majority of patients from Tend on. However, we observed that the poor (TRG 4) response to Na-ChRT was significantly associated with a positive liquid biopsy at the Top. Conclusions: ctDNA evaluation by NGS technology may identify LARC patients with poor response to Na-ChRT. In contrast, this technique does not seem useful for identifying patients prone to developing a complete response.

The cell transformation assay: toward a statistical classification of mixed and intermediate foci images.

The human carcinogenicity evaluation of chemicals has a great impact on public health. In vitro methods, such as the cell transformation assay (CTA), allow for a fast and reliable assessment of the carcinogenic potential of a chemical compound in comparison with the standard two-year bioassay. The scoring and classification of foci in selected cell lines is performed, after staining, by light microscopy. Foci can be separated into three classes: type I, which are scored as non-transformed, and types II and III that are considered to include fully transformed foci. However, in a number of cases, even an expert is uncertain about the attribution of a focus to a given class, due to its mixed or intermediate nature. Here, we suggest a simple approach to classifying mixed or intermediate foci by exploiting the quantitative information available from images, which is captured by statistical descriptors. A quantitative index is proposed, to describe the degree of dissimilarity of mixed and intermediate images to the three well-distinguished classes.

Lung Ultrasound Is Often, but Not Always, Normal in Healthy Subjects: Considerations for COVID-19 Pandemic.

BACKGROUND: Lung ultrasound (LU) is becoming an increasingly important diagnostic tool in detecting lung involvement in Corona Virus Disease 2019 (COVID-19). The aim of this study was to ascertain the likelihood of finding LU abnormalities; mimicking lung involvement; in COVID-19 negative healthy individuals. METHODS: We performed LU on 265 healthcare workers; not presenting COVID-19 major symptoms and in good health; during the course of a serological screening program for COVID-19 in our General Hospital. LU results were reported as total Lung Ultrasound Score (LUS) using a 12-zone method of reporting. RESULTS: 250/265 subjects were included in the COVID-19 negative group. LU was not completely normal (LUS ≠ 0) in 65/250 COVID-19 negative subjects (26%) and in 12/15 (80%) poorly symptomatic COVID-19 positive subjects; with a multifocal pattern in 12.7% vs. 66.7% of cases respectively. Age and COVID-19 positivity were independent predictors of total LUS. A total LUS ≥ 2 had a sensitivity of 66.67% and a specificity of 85.60% in detecting COVID-19 positivity. CONCLUSIONS: A slightly altered LU can be quite frequent in healthy COVID-19 negative subjects. LU can have a role in confirming but not screening COVID-19 poorly symptomatic cases.

Retrospective analysis of safety of ultrasound-guided percutaneous liver biopsy in the 21st century.

BACKGROUND: Ultrasound-guided percutaneous liver biopsy is a standard procedure, but it might be burdened with serious adverse events, mainly hemorrhagic. Literature lacks recent studies taking into account new ultrasound machines, more sensitive to tiny vessels and the evolution of the bioptic technique, including ultrasound guidance in all instances. Hence, the primary aim of this study was to evaluate complication rates of ultrasound-guided percutaneous liver biopsy in a recent population. Secondary aims were to evaluate if the experience of operator is a determinant of risk of complication and to identify other potential risk factors. METHODS: We evaluated 800 procedures carried out in one hospital in the period 2010-2018. RESULTS: Complication rate resulted in 4%, with the occurrence of moderate hemorrhagic complications in 0.75%. No cases of severe events or death were registered. A higher risk of bleeding was found to be associated with less experienced operators, while the need to perform multiple needle insertions increased the probability of adverse events. CONCLUSION: The present findings confirmed ultrasound-guided percutaneous liver biopsy to be a substantially safe procedure with a low risk of overall adverse events and bleeding in particular, especially when performed by expert operators.

P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2.

Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. Results: HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.

Accounting for soil respiration variability - Case study in a Mediterranean pine-dominated forest.

The number of spots to monitor to evaluate soil respiration (Rs) is often chosen on an empirical or conventional basis. To obtain an insight into the necessary number of spots to account for Rs variability in a Mediterranean pine-dominated mixed forest, we measured Rs all year long on sixteen dates with a portable gas-analyser in 50 spots per date within an area 1/3 ha wide. Linear mixed-effects models with soil temperature and litter moisture as descriptors, were fitted to the collected data and then evaluated in a Monte Carlo simulation on a progressively decreasing number of spots to identify the minimum number required to estimate Rs with a given confidence interval. We found that monitoring less than 14 spots would have resulted in a 10% probability of not fitting the model, while monitoring 20 spots would have reduced the same probability to about 5% and was the best compromise between field efforts and quality of the results. A simple rainfall index functional to select sampling dates during the summer drought is proposed.

Surveillance for Hepatocellular Carcinoma Also Improves Survival of Incidentally Detected Intrahepatic Cholangiocarcinoma Arisen in Liver Cirrhosis.

BACKGROUND: Due to its poor survival, intrahepatic cholangiocarcinoma (ICC) is held to be a much more aggressive cancer than hepatocellular carcinoma (HCC). In most published series, patients were diagnosed when symptomatic. However, ICC is now increasingly being discovered during the surveillance for HCC in cirrhosis. Whether this earlier detection of ICC is associated with an equally dismal prognosis or not is unknown. METHODS: This is amulticenter retrospective study of consecutive ICC patients. Patients were stratified into subgroups according to the absence/presence of cirrhosis. A propensity score matching was performed to reduce the potential biases. Cirrhotic patients were further stratified according to their surveillance status. The lead-time bias and its potential effects were also estimated. RESULTS: We gathered 184 patients. Eighty-five patients (46.2%) were cirrhotic. Liver cirrhosis was not related to a worse overall survival (33.0 vs. 32.0 months, p = 0.800) even after the propensity score analysis (43.0 in vs. 44.0 months in 54 pairs of patients, p = 0.878). Among the cirrhotic population, 47 (55.3%) patients had received a diagnosis of ICC during a surveillance programme. The 2 subgroups differed in maximum tumour dimensions (30 vs. 48 mm in surveyed and non-surveyed patients, respectively). Surveyed patients were more likely to receive surgical treatments (59.8 vs. 28.9%, p = 0.003). Overall survival was higher in surveyed patients (51.0 vs. 21.0 months, p < 0.001). These benefits were confirmed after correcting for the lead-time bias. CONCLUSIONS: Cirrhotic patients have different clinical presentation and outcomes of ICC according to their surveillance status. In our series, ICC in cirrhosis was not associated with worse OS. Cirrhosis itself should not discourage either surgical or non-surgical treatments.

Conditional independence relations among biological markers may improve clinical decision as in the case of triple negative breast cancers.

The associations existing among different biomarkers are important in clinical settings because they contribute to the characterisation of specific pathways related to the natural history of the disease, genetic and environmental determinants. Despite the availability of binary/linear (or at least monotonic) correlation indices, the full exploitation of molecular information depends on the knowledge of direct/indirect conditional independence (and eventually causal) relationships among biomarkers, and with target variables in the population of interest. In other words, that depends on inferences which are performed on the joint multivariate distribution of markers and target variables. Graphical models, such as Bayesian Networks, are well suited to this purpose. Therefore, we reconsidered a previously published case study on classical biomarkers in breast cancer, namely estrogen receptor (ER), progesterone receptor (PR), a proliferative index (Ki67/MIB-1) and to protein HER2/neu (NEU) and p53, to infer conditional independence relations existing in the joint distribution by inferring (learning) the structure of graphs entailing those relations of independence. We also examined the conditional distribution of a special molecular phenotype, called triple-negative, in which ER, PR and NEU were absent. We confirmed that ER is a key marker and we found that it was able to define subpopulations of patients characterized by different conditional independence relations among biomarkers. We also found a preliminary evidence that, given a triple-negative profile, the distribution of p53 protein is mostly supported in 'zero' and 'high' states providing useful information in selecting patients that could benefit from an adjuvant anthracyclines/alkylating agent-based chemotherapy.

Imaging of combined hepatocellular-cholangiocarcinoma in cirrhosis and risk of false diagnosis of hepatocellular carcinoma.

Background: Diagnosis of hepatocellular carcinoma can be achieved by imaging in cirrhotic patients. Combined hepatocellular-cholangiocarcinoma is a primary liver tumor and its imaging patterns have been poorly investigated. Misdiagnosis for either hepatocellular carcinoma or benign lesions can occur. We aimed to evaluate the enhancement pattern of combined hepatocellular-cholangiocarcinoma in cirrhosis with imaging techniques and to estimate the risk of misdiagnosis for hepatocellular carcinoma. Methods: All histology-confirmed combined hepatocellular-cholangiocarcinoma in cirrhosis seen in two Italian centers between 2003 and 2016, in which at least one imaging technique had been performed, was retrospectively collected. The enhancement pattern was analyzed for all available imaging modalities. Results: A total of 37 combined hepatocellular-cholangiocarcinoma nodules were identified. Contrast-enhanced ultrasound, computed tomography, and magnetic resonance imaging had been performed in 27, 34, and 17 nodules, respectively. Contrast-enhanced ultrasound was at higher risk of misdiagnosis for pure hepatocellular carcinoma than computed tomography (p = 0.005) or magnetic resonance imaging (p = 0.040). Only six of 24 combined hepatocellular-cholangiocarcinoma lesions submitted to both contrast-enhanced ultrasound and computed tomography showed coincident patterns; contrast-enhanced ultrasound correctly suggested a condition of malignancy in a higher number of cases than computed tomography (p < 0.001) and magnetic resonance imaging (p = 0.002). Conclusions: Contrast-enhanced ultrasound misdiagnosed a higher number of combined hepatocellular-cholangiocarcinoma as hepatocellular carcinoma than computed tomography and magnetic resonance imaging. However, the latter techniques were able to identify features of malignancy less often.

The Impact of Surgery in IDH 1 Wild Type Glioblastoma in Relation With the MGMT Deregulation.

Object: The treatment of choice in glioblastoma (GBM) is the maximal surgical extent of resection (EOR) followed by adjuvant chemo-radiotherapy. Furthermore, methylguanine-DNA methyltransferase (MGMT) promoter methylation is associated with prolonged overall survival (OS) and progression free survival (PFS). The objective of the present study is correlate the biomolecular aspects in relation with EOR. Materials and methods: We analyzed a series of 116 patients with IDH-1 wild type GBM and different EOR (Gross Total Resection-GTR-, Partial Resection-PR- and Biopsy), treated with adjuvant chemo-radiotherapy. The MGMT status was analyzed in terms of promoter methylation and protein expression. Results: When GTR was possible, OS and PFS were significantly better compared to the other two groups (p = 0.001 and p = 0.035, respectively). MGMT methylation was significantly associated with better OS in the biopsy group (p = 0.022) and better OS and PFS in PR (p = 0.02 and p = 0.012, respectively), but not in the GTR group (p = 0.252 for OS, p = 0.256 for PFS) nor the PFS in the biopsy group (p = 0.259). MGMT protein expression levels do not show any association with OS and PFS, regardless of the type of surgery. Conclusions: Our study confirms the positive association of a safe maximal EOR with better OS and PFS, and indicates a positive prognostic value of MGMT methylation status only in case of the presence of residual tumor tissue. MGMT protein expression seems not to play a clinical role in relation with the type of surgery.

Deregulation of sialidases in human normal and tumor tissues.

BACKGROUND: Aberrant sialylation is a characteristic feature associated with cancer. The four types of mammalian sialidases identified to date have been shown to behave in different manners during carcinogenesis. While NEU1, NEU2 and NEU4 have been observed to oppose malignant phenotypes, the membrane-bound sialidase NEU3 was revealed to promote cancer progression. OBJECTIVES: With the aim of improving the knowledge about sialidases deregulation in various cancer types, we investigated the amount of NEU1, NEU3 and NEU4 transcripts in paired normal and tumor tissues from 170 patients with 11 cancer types. METHODS: mRNA was extracted from patients' tissue specimens and retrotranscribed into cDNA, which was quantified by Real-Time PCR. RESULTS: We found NEU1 and NEU3 to be up regulated, while NEU4 was down regulated in most cancer types. In particular, colorectal cancer tissues showed the highest increase in NEU3 expression. Both NEU1 and NEU3 showed a strong up-regulation in ovarian cancer. CONCLUSIONS: Our data show that human sialidases are expressed at different levels in healthy tissues and are strongly deregulated in tumors. Moreover, sialidases expression in our European cohort showed significant differences from Asian populations. Some of these peculiar features open potential applications of sialidases in cancer diagnosis and therapy.