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Radiomics is an emerging translational field of medicine based on the extraction of high-dimensional data from radiological images, with the purpose to reach reliable models to be applied into clinical practice for the purposes of diagnosis, prognosis and evaluation of disease response to treatment. We aim to provide the basic information on radiomics to radiologists and clinicians who are focused on breast cancer care, encouraging cooperation with scientists to mine data for a better application in clinical practice. We investigate the workflow and clinical application of radiomics in breast cancer care, as well as the outlook and challenges based on recent studies. Currently, radiomics has the potential ability to distinguish between benign and malignant breast lesions, to predict breast cancer’s molecular subtypes, the response to neoadjuvant chemotherapy and the lymph node metastases. Even though radiomics has been used in tumor diagnosis and prognosis, it is still in the research phase and some challenges need to be faced to obtain a clinical translation. In this review, we discuss the current limitations and promises of radiomics for improvement in further research.

Aims: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Methods: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. Results: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients. Conclusions: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good–excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Germline variants of the melanocortin-1-receptor (MC1R) gene are the most common genetic trait predisposing to cutaneous melanoma (CM). Here, we performed a literature review and meta-analysis of the association between MC1R gene variants and the frequency of somatic mutations of the BRAF, NRAS, and TERT genes in CM patients. We included studies published until January 2020 in MEDLINE, EMBASE, Ovid Medline, and two grey literature databases. Random effect models were used to pool study-specific estimates into summary odds ratio (SOR) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and assess the robustness of pooled estimates. Twelve studies published between 2006 and 2018 (encompassing 3566 CM, mostly on nonacral sites) were included. MC1R gene variants were not significantly associated with the frequency of somatic mutations of the BRAF and NRAS genes. Only three studies focused on somatic mutations of the TERT gene promoter, all of which reported moderate-to-strong positive associations with MC1R germline variants. MC1R gene variants appear to make only moderate changes, if any, to the risk of BRAF- or NRAS-mutant CM. The association with TERT promoter mutations is suggestive, yet it warrants confirmation as it is based on a still limited number of studies.

Radiomic involves testing the associations of a large number of quantitative imaging features with clinical characteristics. Our aim was to extract a radiomic signature from axial T2-weighted (T2-W) magnetic resonance imaging (MRI) of the whole prostate able to predict oncological and radiological scores in prostate cancer (PCa). This study included 65 patients with localized PCa treated with radiotherapy (RT) between 2014 and 2018. For each patient, the T2-W MRI images were normalized with the histogram intensity scale standardization method. Features were extracted with the IBEX software. The association of each radiomic feature with risk class, T-stage, Gleason score (GS), extracapsular extension (ECE) score, and Prostate Imaging Reporting and Data System (PI-RADS v2) score was assessed by univariate and multivariate analysis. Forty-nine out of 65 patients were eligible. Among the 1702 features extracted, 3 to 6 features with the highest predictive power were selected for each outcome. This analysis showed that texture features were the most predictive for GS, PI-RADS v2 score, and risk class; intensity features were highly associated with T-stage, ECE score, and risk class, with areas under the receiver operating characteristic curve (ROC AUC) ranging from 0.74 to 0.94. MRI-based radiomics is a promising tool for prediction of PCa characteristics. Although a significant association was found between the selected features and all the mentioned clinical/radiological scores, further validations on larger cohorts are needed before these findings can be applied in the clinical practice. • A radiomic model was used to classify PCa aggressiveness. • Radiomic analysis was performed on T2-W magnetic resonance images of the whole prostate gland. • The most predictive features belong to the texture (57%) and intensity (43%) domains.

BackgroundThe contribution of children to viral spread in schools is still under debate.We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting.MethodsLiterature searches from April, 2021 and repeated on May, 15th 2021 yielded a total of 1088 publications: screening, contact tracing and seroprevalence studies.MOOSE guidelines were followed and data analyzed using random-effects models.ResultsFrom screening studies involving more than 120,000 subjects, we estimated 0.31% (95% Confidence Interval [CI] 0.05-0.81%) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%; 95%CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (Odds Ratio [OR]=0.26; 95%CI 0.11-0.63) and were less susceptible to infection (OR=0.60; 95% CI 0.25-1.47). Finally, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children are 43% significantly less likely than adults to test positive for antibodies (OR=0.57; 95%CI: 0.49-0.68).In conclusion, testing all subjects in schools, independently of symptoms, students less likely than adults favor viral spread and SARS-CoV-2 circulation in schools was found to be limited.KEY POINTSQuestionWhat is the infectivity and susceptibility of students and staff exposed to SARS-CoV-2 in the school setting?FindingsThis systematic review and meta-analysis of all available data shows that SARS-CoV-2 viral spread is limited and child-to-adult transmission in the school setting scarce.Summary estimates indicate that young index cases were 74% significantly less likely than adults to favor viral spread and children are 43% less susceptible than adults.MeaningOverall, SARS-CoV-2 circulation in schools was limited and could be reasonably controlled with appropriate mitigation measures.

Stillbirths affect more than 2.5 million pregnancies worldwide every year and the progress in reducing stillbirth rates is slower than that required by World Health Organization. The aim of the present study was to investigate which factors were associated with stillbirths in a University Hospital in the North of Italy, over a time span of 30 years. The goal was to identify which factors are potentially modifiable to reduce stillbirth rate.Retrospective case-control study (358 stillbirths, 716 livebirths) subdivided into two study periods (1987-2006 and 2007-2017).The prevalence of conception obtained by assisted reproductive technologies, pregnancy at advanced maternal age, and complications of pregnancy such as preeclampsia, fetal growth restriction (FGR), and other fetal diseases (abnormal fetal conditions including fetal anemia, fetal hydrops, TORCH infections) increased through the years of the study. Despite a rising prevalence, the last 10 years showed a significant reduction in stillbirths associated with preeclampsia and FGR. Similarly, the risk of stillbirth related to abnormal fetal conditions decreased in the second study period and a history of previous stillbirth becomes a nonsignificant risk factor.Altogether these results suggest that in pregnancies perceived as "high risk" (i.e. previous stillbirth, preeclampsia, FGR, abnormal fetal conditions) appropriate care and follow-up can indeed lower stillbirth rates. In conclusion, the road to stillbirth prevention passes inevitably through awareness and recognition of risk factors.

The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at individual patients' level to capture the possible effect of ethnicity, gene-gene interaction or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived. This article is protected by copyright. All rights reserved.

Simple Summary Radiomics aims to extract high-dimensional features from clinical images and associate them to clinical outcomes. These associations may be further investigated with machine learning models; however, guidelines on the most suitable method to support clinical decisions are still missing. To improve the reliability and the accuracy of radiomic features in the prediction of a binary variable in a lung cancer setting, we compared several machine learning classifiers and feature selection methods on simulated data. These account for important characteristics that may vary in real clinical datasets: sample size, outcome balancing and association strength between radiomic features and outcome variables. We were able to suggest the most suitable classifiers for each studied case and to evaluate the impact of method choices. Our work highlights the importance of these choices in radiomic analyses and provides guidelines on how to select the best models for the data at hand. Abstract Radiomics uses high-dimensional sets of imaging features to predict biological characteristics of tumors and clinical outcomes. The choice of the algorithm used to analyze radiomic features and perform predictions has a high impact on the results, thus the identification of adequate machine learning methods for radiomic applications is crucial. In this study we aim to identify suitable approaches of analysis for radiomic-based binary predictions, according to sample size, outcome balancing and the features–outcome association strength. Simulated data were obtained reproducing the correlation structure among 168 radiomic features extracted from Computed Tomography images of 270 Non-Small-Cell Lung Cancer (NSCLC) patients and the associated to lymph node status. Performances of six classifiers combined with six feature selection (FS) methods were assessed on the simulated data using AUC (Area Under the Receiver Operating Characteristics Curves), sensitivity, and specificity. For all the FS methods and regardless of the association strength, the tree-based classifiers Random Forest and Extreme Gradient Boosting obtained good performances (AUC ≥ 0.73), showing the best trade-off between sensitivity and specificity. On small samples, performances were generally lower than in large–medium samples and with larger variations. FS methods generally did not improve performances. Thus, in radiomic studies, we suggest evaluating the choice of FS and classifiers, considering specific sample size, balancing, and association strength.

Objectives: We aimed to determine whether radiomic features extracted from a highly homogeneous database of breast MRI could non-invasively predict pathological complete responses (pCR) to neoadjuvant chemotherapy (NACT) in patients with breast cancer. Methods: One hundred patients with breast cancer receiving NACT in a single center (01/2017–06/2019) and undergoing breast MRI were retrospectively evaluated. For each patient, radiomic features were extracted within the biopsy-proven tumor on T1-weighted (T1-w) contrast-enhanced MRI performed before NACT. The pCR to NACT was determined based on the final surgical specimen. The association of clinical/biological and radiomic features with response to NACT was evaluated by univariate and multivariable analysis by using random forest and logistic regression. The performances of all models were assessed using the areas under the receiver operating characteristic curves (AUC) with 95% confidence intervals (CI). Results: Eighty-three patients (mean (SD) age, 47.26 (8.6) years) were included. Patients with HER2+, basal-like molecular subtypes and Ki67 ≥ 20% presented a pCR to NACT more frequently, the clinical/biological model’s AUC (95% CI) was 0.81 (0.71–0.90). Using 136 representative radiomics features selected through cluster analysis from the 1037 extracted features, a radiomic score was calculated to predict the response to NACT, with AUC (95% CI): 0.64 (0.51–0.75). After combining the clinical/biological and radiomics models, the AUC (95% CI) was 0.83 (0.73–0.92). Conclusions: MRI-based radiomic features slightly improved the pre-treatment prediction of pCR to NACT, in addiction to biological characteristics. If confirmed on larger cohorts, it could be helpful to identify such patients, to avoid unnecessary treatment.

There appears to be a sex-specific association between obesity and colorectal neoplasia in patients with Lynch Syndrome (LS). We meta-analyzed studies reporting on obesity and colorectal cancer (CRC) risk in LS patients to test whether obese subjects were at increased risk of cancer compared to those of normal weight. We explored also a possible sex-specific relationship between adiposity and CRC risk among patients with LS. The summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We investigated the causes of between-study heterogeneity and assessed the presence of publication bias. We were able to retrieve suitable data from four independent studies. We found a twofold risk of CRC in obese men compared to nonobese men (SRR = 2.09, 95%CI: 1.23–3.55, I2 = 33%), and no indication of publication bias (p = 0.13). No significantly increased risk due to obesity was found for women. A 49% increased CRC risk for obesity was found for subjects with an MLH1 mutation (SRR = 1.49, 95%CI: 1.11–1.99, I2 = 0%). These results confirm the different effects of sex on obesity and CRC risk and also support the public measures to reduce overweight in people with LS, particularly for men.

The relationship between physical exercise and improvement in specific cognitive domains in children and adolescents who play sport has been recently reported, although the effects on visuospatial abilities have not yet been well explored. This study is aimed at evaluating in school-age children practicing artistic gymnastics the visuospatial memory by using a table version of the Radial Arm Maze (table-RAM) and comparing their performances with those ones who do not play any sport. The visuospatial performances of 14 preadolescent girls practicing artistic gymnastics aged between 7 and 10 years and those of 14 preadolescent girls not playing any sport were evaluated in the table-RAM forced-choice paradigm that allows disentangling short-term memory from working memory abilities. Data showed that the gymnasts obtained better performances than control group mainly in the parameters evaluating working memory abilities, such as within-phase errors and spatial span. Our findings emphasizing the role of physical activity on cognitive performances impel to promote physical exercise in educational and recreational contexts as well as to analyse the impact of other sports besides gymnastics on cognitive functioning.

Vitamin D receptors polymorphisms are found to be associated with several cancers. Since their prevalence vary across ethnicities and ethnicity itself seems to influence the cancer risk, a comprehensive meta-analysis was performed to investigate the role of VDR Fok1, Bsm1, Taq1, Apa1, Cdx2 and cancer risk at specific organ sites. Odds ratios, calculated with random-effects models, summarized one-hundred-ninety-two independent studies for twenty-two cancer sites. Evidence was provided that Fok1, Bsm1, Cdx2, Apa1 and Taq1 are linked to cancer susceptibility for colorectal, lung, ovarian, skin, multiple myeloma and brain cancer. Stratifying by ethnicity, some differences were found, partially explained by minor allele frequency (MAF), for colorectal cancer, ovarian and prostate cancer in Caucasian and prostate cancer in Asian populations. In summary, ethnicity may be a modifier of cancer risk, in particular for hormone dependent cancers and it should be considered evaluating the effect of VDR on cancer risk.

Background: Although the contribution of children to SARS-CoV-2 spread is still a matter of debate, school closure has been largely implemented as part of the strategies to mitigate the pandemic. In this meta-analysis, we reviewed the current evidence for SARS-CoV-2 transmission in the educational setting. Methods: We conducted a systematic literature search and review following MOOSE guidelines regarding meta-analysis of observational studies using PUBMED, Ovid MEDLINE, ISI Web of Science and Living Evidence on COVID databases. The search was undertaken during the first week of April, 2021 and repeated on May, 15th 2021 with no restriction by language. Screening, contact tracing and seroprevalence studies were included in the meta-analysis. We analysed data using random-effects meta-regressions. Findings: The searches yielded a total of 1088 publications. In educational setting, we identified 21 screening studies reporting infections, (n>120,000), 15 studies on contact tracing (n=112,622), 9 studies on seroprevalence (n=17,879). From screening studies, we estimated 0·31% (95% CI 0·05-0·81%), point prevalence in schools (I2 = 97%). In contact tracing studies, onward viral transmission was limited (SAR = 2·54%; 95% CI 0·76-5·31%), (I2 = 100%). Summary estimates indicate that young index cases were 74% significantly less likely than adults to favor viral spread (OR = 0·26; 95% CI 0·11-0·63) and data from seroprevalence studies shows that children are 43% less likely than adults to test positive for antibodies (OR = 0·57; 95% CI: 0·49-0·68). Interpretation: This systematic review and meta-analysis suggests that schools did not develop into hotspots for SARS-CoV-2 transmission. With mitigation measures, SARS-CoV-2 viral spread is limited and child-to-adult transmission in the school setting scarce. Young index cases are significantly less likely than adults to favor viral spread and children are significantly less susceptible than adults. The greater percentages of positive people found with contact tracing compared to screening suggests that testing all subjects in schools, independently of symptoms, do not help in reducing clusters. Funding Information: The European Institute of Oncology, Milan, Italy is partially supported by the Italian Ministry of Health with Ricerca Corrente and 5×1,000 funds. Declaration of Interests: We declare no competing interests.

Several studies have investigated the beneficial effects of vitamin D on survival of cancer patients. Overall evidence has been accumulating with contrasting results. This paper aims at narratively reviewing the existing articles examining the link between vitamin D supplementation and cancer mortality. We performed two distinct searches to identify observational (ObS) studies and randomized clinical trials (RCTs) of vitamin D supplementation (VDS) in cancer patients and cohorts of general population, which included cancer mortality as an outcome. Published reports were gathered until March 2021. We identified 25 papers published between 2003 and 2020, including n. 8 RCTs on cancer patients, n. 8 population RCTs and n. 9 ObS studies. There was some evidence that the use of VDS in cancer patients could improve cancer survival, but no significant effect was found in population RCTs. Some ObS studies reported evidence that VDS was associated with a longer survival among cancer patients, and only one study found an opposite effect. The findings do not allow conclusive answers. VDS may have the potential as treatment to improve survival in cancer patients, but further investigations are warranted. We strongly support investment in well-designed and sufficiently powered RCTs to fully evaluate this association.

Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged 2 statistics to quantify the degree of heterogeneity of risk estimates across studies. Eleven independent studies encompassing a total of over 30,000 NMSC cases were included in quantitative analyses. No evidence of an increased NMSC risk emerged among ever vs. never users of oral contraceptives (SRR 1.13, 95% CI 0.88–1.45) or hormones for menopause (SRR 1.09, 95% CI 0.87–1.37). Likewise, age at menarche or at menopause and parity were not associated with NMSC risk. Heterogeneity across studies was low, and pooled results were comparable between NMSC subtypes. We found no evidence that hormonal factors play a role in the pathogenesis of NMSC among women.

Background: To evaluate whether a model based on radiomic and clinical features may be associated with lymph node (LN) status and overall survival (OS) in lung cancer (LC) patients; to evaluate whether CT reconstruction algorithms may influence the model performance. Methods: patients operated on for LC with a pathological stage up to T3N1 were retrospectively selected and divided into training and validation sets. For the prediction of positive LNs and OS, the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression model was used; univariable and multivariable logistic regression analysis assessed the association of clinical-radiomic variables and endpoints. All tests were repeated after dividing the groups according to the CT reconstruction algorithm. p-values < 0.05 were considered significant. Results: 270 patients were included and divided into training (n = 180) and validation sets (n = 90). Transfissural extension was significantly associated with positive LNs. For OS prediction, high- and low-risk groups were different according to the radiomics score, also after dividing the two groups according to reconstruction algorithms. Conclusions: a combined clinical–radiomics model was not superior to a single clinical or single radiomics model to predict positive LNs. A radiomics model was able to separate high-risk and low-risk patients for OS; CTs reconstructed with Iterative Reconstructions (IR) algorithm showed the best model performance.

The worldwide incidence of melanoma has increased rapidly over the last 50 years. Melanoma is the most common cancer found in the young adult population, and its incidence is very high among geriatric popula-tions. The incidence of melanoma varies by sex, and this factor is also associated with differences in the anatomical site melanoma. Adolescent and young adult women have a higher incidence than men. This may be, in part, due to the greater use of sunbeds, as well as intentional sun exposure among girls and, in general, risky behaviours in seeking to suntan, due to socially-determined aesthetic needs. Indeed, the World Health Organization declared that there is sufficient evidence to classify exposure to ultraviolet radiation (sunbed use and sun exposure) as carcinogenic to humans. Although pigmentation characteristics, such as skin colour, hair and eye colour, freckles and number of common and atypical naevi, do influence susceptibility to melanoma, recommendations regarding prevention should be directed to the entire population and should include avoiding sunbed, covering sun-exposed skin, wearing a hat and sunglasses. Sunscreen use should not be used to prolong intentional sun exposure. Primary prevention should be focused mainly on young adult women, while secondary prevention should be focused mainly on elderly men. In fact, after the age of 40 years, incidence rates reverse, and the incidence of melanoma among men is greater than among women. This is probably due to the fact that men are less likely than women to examine their own skin or present to a dermatologist for skin examination., SCOPUS: ar.j, info:eu-repo/semantics/published

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hierarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p = 0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p = 0.03) and lower values of GOH/90Percentile (p = 0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p = 0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p = 0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.

BACKGROUND: Little is known on whether melanocortin 1 receptor (MC1R) associated cutaneous melanoma (CM) risk varies depending on histological subtype and body site, and whether tumour thickness at diagnosis (the most important prognostic factor for CM patients) differs between MC1R variant carriers and wild-type individuals. OBJECTIVE: We studied the association between MC1R variants and CM risk by histological subtype, body site, and Breslow thickness, using the database of the M-SKIP project. METHODS: We pooled individual data from fifteen case-control studies conducted during 2005–2015 in Europe and the USA. Study-specific, multi-adjusted odds ratios were pooled into summary odds ratios (SOR) and 95% confidence intervals (CI) using random-effects models. RESULTS: 6891 CM cases and 5555 controls were included. CM risk was increased among MC1R variant carriers vs. wild-type individuals. The increase in risk was comparable across histological subtypes (SOR for any variant vs. wild-type ranged between 1.57 and 1.70, always statistical significant) except acral lentiginous melanoma, for which no association emerged; and slightly greater on chronically (1.74, 95% CI 1.47–2.07) than intermittently (1.55, 95% CI 1.34–1.78) sun-exposed skin. CM risk was greater for those carrying ‘R’ vs. ‘r’ variants; correlated with the number of variants; and was more evident among individuals not showing the red hair colour phenotype. Breslow thickness was not associated with MC1R status. CONCLUSION: MC1R variants were associated with an increased risk of CM of any histological subtype (except ALM) and occurring on both chronically and intermittently sun-exposed skin.

We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.

Background Selenium (Se) and selenoproteins have been shown to be involved in lipid metabolism mainly due to their ability to modulate redox homeostasis in adipose tissue. The underlying mechanisms are yet to be evaluated. In the light of few data related to the association between polymorphic variants of selenoprotein encoding genes and metabolic syndrome or obesity in humans, the role of selenoprotein polymorphisms in lipid metabolism remains unclear. The aim of this study was to investigate the impact of allelic combination within selenoprotein and redox related genes on the markers of lipid metabolism and oxidative stress. Methods The study comprised 441 healthy individuals from Poland, in the 18−74 year age group. Allelic combinations were investigated within the polymorphic variants of four selenoprotein encoding genes (GPX1 rs1050450, GPX4 rs713041, SELENOP rs3877899 and SELENOF rs5859) and the redox related gene (SOD2 rs4880). The impact of the most common allelic GPX1-GPX4-SELENOP-SELENOF-SOD2 combinations was assessed on the following markers: triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glutathione peroxidase activities (GPX1, GPX3), lipid peroxidation (as TBARS), ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1). Results Multivariable analysis revealed significant associations between three allelic combinations and markers of lipid metabolism, including HDL-C and TC/HDL-C ratio (AAAAa), LDL-C (aaAaa), and triglycerides (aaaaA), whereas two allelic combinations (aAaAA, aaaAA) were associated with GPX3 activity. Conclusion This study confirms the possible implication of selenoproteins in lipid metabolism and warrants further research on specific allele combinations within selenoprotein and redox related genes in order to identify functional genetic combinations linked to metabolic phenotype.

To determine if radiomic features, alone or combined with clinical data, are associated with residual tumour (RT) at surgery, and predict the risk of disease progression within 12 months (PD12) in ovarian cancer (OC) patients. This retrospective study enrolled 101 patients according to the following inclusion parameters: cytoreductive surgery performed at our institution (9 May 2007–23 February 2016), assessment of BRCA mutational status, preoperative CT available. Radiomic features of the ovarian masses were extracted from 3D structures drawn on CT images. A phantom experiment was performed to assess the reproducibility of radiomic features. The final radiomic features included in the analysis (n = 516) were grouped into clusters using a hierarchical clustering procedure. The association of each cluster’s representative radiomic feature with RT and PD12 was assessed by chi-square test. Multivariate analysis was performed using logistic regression models. P values < 0.05 were considered significant. Patients with values of F2-Shape/Compactness1 below the median, of F1- GrayLevelCooccurenceMatrix25/0-1InformationMeasureCorr2 below the median and of F1-GrayLevelCooccurenceMatrix25/-333-1InverseVariance above the median showed higher risk of RT (36%, 36% and 35%, respectively, as opposed to 18%, 18% and 18%). Patients with values of F4-GrayLevelRunLengthMatrix25/-333RunPercentage above the median, of F2 shape/Max3DDiameter below the median and F1-GrayLevelCooccurenceMatrix25/45-1InverseVariance above the median showed higher risk of PD12 (22%, 24% and 23%, respectively, as opposed to 6%, 5% and 6%). At multivariate analysis F2-Shape/Max3DDiameter remained significant (odds ratio (95% CI) = 11.86 (1.41–99.88)). To predict PD12, a clinical radiomics model performed better than a base clinical model. This study demonstrated significant associations between radiomic features and prognostic factors such as RT and PD12. • No residual tumour (RT) at surgery is the most important prognostic factor in OC. • Radiomic features related to mass size, randomness and homogeneity were associated with RT. • Progression of disease within 12 months (PD12) indicates worse prognosis in OC. • A model including clinical and radiomic features performed better than only-clinical model to predict PD12.

Melanoma represents an important public health problem, due to its high case-fatality rate. Identification of individuals at high risk would be of major interest to improve early diagnosis and ultimately survival. The aim of this study was to evaluate whether MC1R variants predicted melanoma risk independently of at-risk phenotypic characteristics.Data were collected within an international collaboration - the M-SKIP project. The present pooled analysis included data on 3,830 single, primary, sporadic, cutaneous melanoma cases and 2,619 controls from seven previously published case-control studies. All the studies had information on MC1R gene variants by sequencing analysis and on hair color, skin phototype, and freckles, ie, the phenotypic characteristics used to define the red hair phenotype.The presence of any MC1R variant was associated with melanoma risk independently of phenotypic characteristics (OR 1.60; 95% CI 1.36-1.88). Inclusion of MC1R variants in a risk prediction model increased melanoma predictive accuracy (area under the receiver-operating characteristic curve) by 0.7% over a base clinical model (P=0.002), and 24% of participants were better assessed (net reclassification index 95% CI 20%-30%). Subgroup analysis suggested a possibly stronger role of MC1R in melanoma prediction for participants without the red hair phenotype (net reclassification index: 28%) compared to paler skinned participants (15%).The authors suggest that measuring the MC1R genotype might result in a benefit for melanoma prediction. The results could be a valid starting point to guide the development of scientific protocols assessing melanoma risk prediction tools incorporating the MC1R genotype.

Obesity leads to the clustering of cardiovascular (CV) risk factors and the metabolic syndrome (MetS) also in children and is often accompanied by non-alcoholic fatty liver disease. Quality of dietary fat, beyond the quantity, can influence CV risk profile and, in particular, omega-3 fatty acids (FA) have been proposed as beneficial in this setting. The aim of the study was to evaluate the associations of individual CV risk factors, characterizing the MetS, with erythrocyte membrane FA, markers of average intake, in a group of 70 overweight/obese children. We conducted an observational study. Erythrocyte membrane FA were measured by gas chromatography. Spearman correlation coefficients (rS) were calculated to evaluate associations between FA and features of the MetS. Mean content of Omega-3 FA was low (Omega-3 Index = 4.7 ± 0.8%). Not omega-3 FA but some omega-6 FA, especially arachidonic acid (AA), were inversely associated with several features of the MetS: AA resulted inversely correlated with waist circumference (rS = − 0.352), triglycerides (rS = − 0.379), fasting insulin (rS = − 0.337) and 24-h SBP (rS = − 0.313). Total amount of saturated FA (SFA) and specifically palmitic acid, correlated positively with waist circumference (rS = 0.354), triglycerides (rS = 0.400) and fasting insulin (rS = 0.287). Fatty Liver Index (FLI), a predictive score of steatosis based on GGT, triglycerides and anthropometric indexes, was positively correlated to palmitic acid (rS = 0.515) and inversely to AA (rS = − 0.472). Our data suggest that omega-6 FA, and especially AA, could be protective toward CV risk factors featuring the MetS and also to indexes of hepatic steatosis in obese children, whereas SFA seems to exert opposite effects.

Metabolic rewiring is a hallmark of cancer and a predominant feature of aggressive lymphoproliferative disorders such as diffuse large B-cell lymphomas (DLBCL), which need a reshaped metabolism in order to meet the increased demands related to rapid cell proliferation. Emerging evidence indicates that chemoresistance is closely related to altered metabolism in cancer. However, the relationship between metabolic rewiring and chemoresistance in lymphoma is yet to be elucidated. Radiomic analysis applied to functional imaging with fluoroedoxyglucose positron emission tomography (FDG-PET) provides a unique opportunity to explore DLBCL metabolism. In this study we hypothesized that distinct gene expression (GEP) signatures might be correlated with specific FDG-PET radiomics signatures, which in turn could be associated with resistance to standard chemoimmunotherapy and DLBCL outcome. First, we retrospectively analyzed a discovery cohort of 48 consecutive DLBCL patients (pts) treated at our center with standard first line R-CHOP/R-CHOP-like chemoimmunotherapy from 2010 to 2018, with available formalin-fixed paraffin embedded (FFPE) tissue from the initial diagnostic biopsy and FDG-PET radiomics data extracted from the same target lesion. Median follow-up was 55 months (range 18-110). We profiled this cohort with targeted-GEP (T-GEP) (NanoString platform), using a custom panel to define the cell of origin (COO) and MYC/BCL-2 levels, and a dedicated panel comprising 180 genes encompassing the most relevant cancer metabolism pathways. By applying the maxstat package we found that a 6-gene metabolic signature was strongly associated with outcome and outperformed the COO, the MYC/BCL-2 status and the International Prognostic Index (IPI) score for progression free survival (PFS) and overall survival (OS) in multivariate analysis. The 6-gene metabolic signature included genes regulating oxidative metabolism and fatty acid oxidation (SCL25A1, PDK4, PDPR) which were upregulated, and was inversely associated with genes involved in glycolytic pathways (MAP2K1, HIF1A, GBE1) which were downregulated. Notably 5-year PFS and OS were 100% and 95% in metabolic signature (met-Sig) low pts vs 24% and 45% in met-Sig high pts respectively (p These data indicate that oxidative metabolic rewiring could be a powerful adverse prognostic predictor, suggesting the possibility of targeting oxidative metabolism to overcome chemorefractoriness in DLBCL. This study provides the proof of principle for the use of FDG-PET radiomics as a tool for non-invasive assessment of cancer metabolism, and for predicting metabolic vulnerabilities in DLBCL. Figure 1 Figure 1. Disclosures Tarella: ADC-THERAPEUTICS: Other: ADVISORY BOARD; Abbvie: Other: ADVISORY BOARD. Pileri: CELGENE: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY-BOARD; NANOSTRING: Other: ADVISORY BOARD. Derenzini: TAKEDA: Research Funding; BEIGENE: Other: ADVISORY BOARD; ASTRA-ZENECA: Consultancy, Other: ADVISORY-BOARD; TG-THERAPEUTICS: Research Funding; ADC-THERAPEUTICS: Research Funding.

Simple Summary Vitamin D has been extensively studied in relation to cancer risk at several body sites, but its relationship with non-melanoma skin cancer (NMSC), the most frequent malignancy in humans, is still unclear. Here, we performed a systematic literature search and meta-analysis of published studies and did not find convincing evidence that a causal association exists between vitamin D intake (from foods and supplements), vitamin D blood concentration, or polymorphisms of the genes coding for the vitamin D receptor and binding protein, and NMSC risk. Abstract We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February 2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61–4.56), although with large heterogeneity across studies (I2 = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the VDR and VDBP genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation.

Background and aim: Over the last decades, the incidence of melanoma has been steadily growing, with 4.2% of the population worldwide affected by cutaneous melanoma (CM) in 2020 and with a higher incidence and mortality in men than in women. We investigated both the risk factors for CM development and the prognostic and predictive factors for survival, stratifying for both sex and gender. Methods: We conducted a systematic review of studies indexed in PUB-MED, EMBASE, and Scopus until 4 February 2021. We included reviews, meta-analyses, and pooled analyses investigating differences between women and men in CM risk factors and in prognostic and predictive factors for CM survival. Data synthesis: Twenty-four studies were included, and relevant data extracted. Of these, 13 studies concerned potential risk factors, six concerned predictive factors, and five addressed prognostic factors of melanoma. Discussion: The systematic review revealed no significant differences in genetic predisposition to CM between males and females, while there appear to be several gender disparities regarding CM risk factors, partly attributable to different lifestyles and behavioral habits between men and women. There is currently no clear evidence of whether the mutational landscapes of CM differ by sex/gender. Prognosis is justified by a complex combination of phenotypes and immune functions, while reported differences between genders in predicting the effectiveness of new treatments are inconsistent. Overall, the results emerging from the literature reveal the importance of considering the sex/gender variable in all studies and pave the way for including it towards precision medicine. Conclusions: Men and women differ genetically, biologically, and by social construct. Our systematic review shows that, although fundamental, the variable sex/gender is not among the ones collected and analyzed.

To assess the diagnostic accuracy of MRI performed using surface coils, with and without contrast medium, in predicting thyroid and cricoid cartilage infiltration in laryngeal tumours, and to investigate whether the radiologist’s experience influences diagnostic accuracy. We retrospectively enrolled patients with biopsy-proven laryngeal cancer who had undergone preoperative staging MRI and open surgery. Two radiologists with different experience (senior vs. junior) reviewed the MR images without (session A1) and with contrast medium (session A2) separately. We calculated the accuracy of MRI with and without contrast medium in detecting infiltration of the thyroid and cricoid cartilages. Interobserver agreement was calculated by Cohen’s Kappa (k). Forty-two patients were enrolled, for a total of 62 cartilages. In session A1 the senior and junior radiologists showed an accuracy of 85% and 71%, respectively, with k = 0.53 (0.33–0.72). In session A2 the senior and junior radiologists showed an accuracy of 84% and 77%, respectively, with k = 0.68 (0.49-0.86). Staging of laryngeal tumours with surface coil MRI showed good diagnostic accuracy in assessing cartilaginous infiltration. We observed similar values of diagnostic accuracy for the analysis performed with and without contrast medium for the senior radiologist. • Surface coil MRI demonstrated good accuracy in assessing laryngeal cartilage invasion. • The radiologist’s experience can influence the diagnostic accuracy. • Gadolinium administration may increase interobserver concordance.

Aggregation of islet amyloid polypeptide (IAPP) and amyloid deposition in the islets of Langerhans may significantly contribute to the multifactorial pathogenic mechanisms leading to type 2 diabetes. A direct toxic effect on β-cells of oligomeric IAAP has been demonstrated in in vitro models, but the mechanism operating in vivo is still unclear. Mice models presenting amyloid deposition and glucose intolerance represent a good tool for exploring in vivo a putative mechanism of toxicity directly related to the physical expansion of the extracellular matrix by the amyloid fibrillar aggregates. Based on our hypothesis that deposition of amyloid may influence the oxygen perfusion, we have calculated that the mean distribution of oxygen partial pressure would drop by more than 50 % in the presence of amyloid deposits in the islet. This condition of hypoxia caused by the remodelling of the extracellular space may explain the metabolic abnormalities in the Langerhans islets, otherwise interpreted as pseudo-hypoxic response to IAPP oligomers.

The variance in intensities of MRI scans is a fundamental impediment for quantitative MRI analysis. Intensity values are not only highly dependent on acquisition parameters, but also on the subject and body region being scanned. This warrants the need for image normalization techniques to ensure that intensity values are consistent within tissues across different subjects and visits. Many intensity normalization methods have been developed and proven successful for the analysis of brain pathologies, but evaluation of these methods for images of the prostate region is lagging. In this paper, we compare four different normalization methods on 49 T2-w scans of prostate cancer patients: 1) the well-established histogram normalization, 2) the generalized scale normalization, 3) an extension of generalized scale normalization called generalized ball-scale normalization, and 4) a custom normalization based on healthy prostate tissue intensities. The methods are compared qualitatively and quantitatively in terms of behaviors of intensity distributions as well as impact on radiomic features. Our findings suggest that normalization based on prior knowledge of the healthy prostate tissue intensities may be the most effective way of acquiring the desired properties of normalized images. In addition, the histogram normalization method outperform the generalized scale and generalized ball-scale methods which have proven superior for other body regions.

We conducted a systematic review and meta-analysis of the association between somatic mutations of the TERT gene promoter and melanoma survival. Data from nineteen independent studies (>2,500 melanoma overall) were pooled using random effects meta-analysis models. TERT-mutated melanoma patients had a significantly worse overall survival (OS) (summary hazard ratio 1.43, 95 % confidence intervals (CI) 1.05–1.95) compared to wild-type ones. The association became stronger when combining risk estimates for overall and melanoma-specific survival (MSS) (1.52, 95 % CI 1.14–2.02), and when restricting the analysis to studies mostly based on invasive non-acral cutaneous melanomas (1.77, 95 % CI 1.00–3.15). Limited, yet suggestive evidence of a detrimental effect of TERT promoter mutations on melanoma prognosis emerged also for other survival measures (e.g. disease-free and distant metastasis-free survival). We found suggestive evidence of a detrimental effect of TERT mutations on melanoma patients’ survival.

We reviewed and meta-analysed the available evidence (until December 2019) about circulating tumour DNA (ctDNA) levels and melanoma patients survival. We included twenty-six studies (>2000 patients overall), which included mostly stage III-IV cutaneous melanoma patients and differed widely in terms of systemic therapy received and somatic mutations that were searched. Patients with detectable ctDNA before treatment had worse progression-free survival (PFS) (summary hazard ratio (SHR) 2.47, 95 % confidence intervals (CI) 1.85-3.29) and overall survival (OS) (SHR 2.98, 95 % CI 2.26-3.92), with no difference by tumour stage. ctDNA detectability during follow-up was associated with poorer PFS (SHR 4.27, 95 %CI 2.75-6.63) and OS (SHR 3.91, 95 %CI 1.97-7.78); in the latter case, the association was stronger (p = 0.01) for stage IV vs. III melanomas. Between-estimates heterogeneity was low for all pooled estimates. ctDNA is a strong prognostic biomarker for advanced-stage melanoma patients, robust across tumour (e.g. genomic profile) and patients (e.g. systemic therapy) characteristics.

Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta-blocker (BB) drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta-analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study-specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between-study heterogeneity by meta-regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26-0.73 with I(2) = 78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19-1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC-specific survival. Clinical trials addressing this hypothesis are warranted.

To assess the independent prognostic value of standardized uptake value (SUV) and apparent diffusion coefficient (ADC), separately and combined, in order to evaluate if the combination of these two variables allows further prognostic stratification of patients with head and neck squamous cell carcinomas (HNSCC). Pretreatment SUV and ADC were calculated in 57 patients with HNSCC. Mean follow-up was 21.3 months. Semiquantitative analysis of primary tumours was performed using SUVmaxT/B, ADCmean, ADCmin and ADCmax. The prognostic value of SUVmaxT/B, ADCmean, ADCmin and ADCmax in predicting disease-free survival (DFS) was evaluated with log-rank test and Cox regression models. Patients with SUVmaxT/B ≥5.75 had an overall worse prognosis (p = 0.003). After adjusting for lymph node status and diameter, SUVmaxT/B and ADCmin were both significant predictors of DFS with hazard ratio (HR) = 10.37 (95 % CI 1.22–87.95) and 3.26 (95 % CI 1.20–8.85) for SUVmaxT/B ≥5.75 and ADCmin ≥0.58 × 10−3 mm2/s, respectively. When the analysis was restricted to subjects with SUVmaxT/B ≥5.75, high ADCmin significantly predicted a worse prognosis, with adjusted HR = 3.11 (95 % CI 1.13–8.55). The combination of SUVmaxT/B and ADCmin improves the prognostic role of the two separate parameters; patients with high SUVmaxT/B and high ADCmin are associated with a poor prognosis. • High SUV maxT/B is a poor prognostic factor in HNSCC • High ADC min is a poor prognostic factor in HNSCC • In patients with high SUV maxT/B , high ADC min identified those with worse prognosis

Vitamin D plays a significant role in our health, including cancer incidence and mortality. Vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) may affect its activity, influencing the risk of cancer. Several studies have investigated VDR SNPs, but the association with the risk of cancer is controversial. Here, we present a meta-analysis to assess the association of TaqI, ApaI, and Cdx2 SNPs with the risk of cancer. A systematic literature search was performed following a predefined protocol and using validated search strategies. This meta-analysis shows the summary odd ratio (SOR) overall, by cancer sites and by ethnicity. Up to January 2014, we identified 73 independent studies with 35 525 cases and 38 675 controls. The meta-analysis of Cdx2 gg versus GG showed a significant 12% increased risk for all cancers [SOR=1.12; 95% confidence interval (CI): 1.00-1.25]. The other SNPs analyzed did not show an overall significant association with the risk of cancer: SOR=0.98 (95% CI: 0.90-1.07) and 1.06 (95% CI: 0.95-1.19) for TaqI tt versus TT and ApaI aa versus AA, respectively. TaqI shows a significant 43% increased risk for colorectal cancer (SOR=1.43; 95% CI: 1.30-1.58 for tt vs. TT). Strong frequency variations are present among different ethnic groups. This meta-analysis showed an overall increased risk of cancer associated with Cdx2 SNP and a specific higher risk of colorectal cancer associated with the TaqI polymorphism. The VDR genotype might become more relevant when clustered in a specific haplotype, associated with other SNPs of genes involved in vitamin D metabolism, or for specific tumors and/or patient characteristics.

Radiomics is an emerging translational field of research aiming to extract mineable high-dimensional data from clinical images. The radiomic process can be divided into distinct steps with definable inputs and outputs, such as image acquisition and reconstruction, image segmentation, features extraction and qualification, analysis, and model building. Each step needs careful evaluation for the construction of robust and reliable models to be transferred into clinical practice for the purposes of prognosis, non-invasive disease tracking, and evaluation of disease response to treatment. After the definition of texture parameters (shape features; first-, second-, and higher-order features), we briefly discuss the origin of the term radiomics and the methods for selecting the parameters useful for a radiomic approach, including cluster analysis, principal component analysis, random forest, neural network, linear/logistic regression, and other. Reproducibility and clinical value of parameters should be firstly tested with internal cross-validation and then validated on independent external cohorts. This article summarises the major issues regarding this multi-step process, focussing in particular on challenges of the extraction of radiomic features from data sets provided by computed tomography, positron emission tomography, and magnetic resonance imaging.

Objective: To validate previously identified associations between radiological features and clinical features with Epidermal Growth Factor Receptor (EGER)/Kirsten RAt Sarcoma (KRAS) alterations in an independent group of patients with Non-Small Cell Lung Cancer (NSCLC).Material and methods: A total of 122 patients with NSCLC tested for EGFR/KRAS alterations were included. Clinical and radiological features were recorded.Univariate analysis were performed to look at the associations of the studied features with EGFR/KRAS alterations. Previously calculated composite model parameters for each gene alteration prediction were applied to this validation cohort. ROC (Receiver Operating Characteristic) curves were drawn using the previously validated composite models, and also for each significant individual characteristic of the previous training cohort model. The Area Under the ROC Curve (AUC) with 95% Confidence Intervals (CI) was calculated and compared between the full models.Results: At univariate analysis, EGFR + confirmed an association with an internal air bronchogram, pleural retraction, emphysema and lack of smoking; KRAS + with round shape, emphysema and smoking. The AUC (95%CI) in the new cohort was confirmed to be high for EGFR + prediction, with a value of: 0.82 (0.69-0.95) vs. 0.82 in the previous cohort, whereas it was smaller for KRAS + prediction, with a value of 0.60 (0.48-0.72) vs. 0.67 in the previous cohort. Looking at single features in the new cohort, we found that the AUC for the models including only smoking was similar to that of the full model (including radiological and clinical features) for both gene alterations.Conclusions: Although this study validated the significant association of clinical and radiological features with EGFR/KRAS alterations, models based on these composite features are not superior to smoking history alone to predict the mutations.

Background Many data highlight the benefits of the Mediterranean diet and its main lipid component, extra-virgin olive oil (EVOO). EVOO contains many phenolic compounds that have been found effective against several aging- and lifestyle-related diseases, including neurodegeneration. Oleuropein, a phenolic secoiroid glycoside, is the main polyphenol in the olive oil. It has been reported that the aglycone form of Oleuropein (OleA) interferes in vitro and in vivo with amyloid aggregation of a number of proteins/peptides involved in amyloid, particularly neurodegenerative, diseases avoiding the growth of toxic oligomers and displaying protection against cognitive deterioration. Methods In this study, we carried out a cellular and biophysical study on the relationships between the effects of OleA on the aggregation and cell interactions of the D76N β2-microglobulin (D76N b2m) variant associated with a familial form of systemic amyloidosis with progressive bowel dysfunction and extensive visceral amyloid deposits. Results Our results indicate that OleA protection against D76N b2m cytotoxicity results from i) a modification of the conformational and biophysical properties of its amyloid fibrils; ii) a modification of the cell bilayer surface properties of exposed cells. Conclusions This study reveals that OleA remodels not only D76N b2m aggregates but also the cell membrane interfering with the misfolded proteins-cell membrane association, in most cases an early event triggering amyloid–mediated cytotoxicity. General significance The data provided in the present article focus on OleA protection, featuring this polyphenol as a promising plant molecule useful against amyloid diseases.

Purpose Selenium, both essential and toxic element, is considered to protect against cancer, though human supplementation trials have generated many inconsistent data. Genetic background may partially explain a great variability of the studies related to selenium and human health. The aim of this study was to assess whether functional polymorphisms within two selenoprotein-encoding genes modify the response to selenium at the level of oxidative stress, DNA damage, and mRNA expression, especially in the individuals with a relatively low selenium status. Methods The trial involved 95 non-smoking individuals, stratified according to GPX1 rs1050450 and SEPP1 rs3877899 genotypes, and supplemented with selenium yeast (200 µg) for 6 weeks. Blood was collected at four time points, including 4 weeks of washout. Results After genotype stratification, the effect of GPX1 rs1050450 on lower GPx1 activity responsiveness was confirmed; however, in terms of DNA damage, we failed to indicate that individuals homozygous for variant allele may especially benefit from the increased selenium intake. Surprisingly, considering gene and time interaction, GPX1 polymorphism was observed to modify the level of DNA strand breaks during washout, showing a significant increase in GPX1 wild-type homozygotes. Regardless of the genotype, selenium supplementation was associated with a selectively suppressed selenoprotein mRNA expression and inconsistent changes in oxidative stress response, indicating for overlapped, antioxidant, and prooxidant effects. Intriguingly, DNA damage was not influenced by supplementation, but it was significantly increased during washout. Conclusions These results point to an unclear relationship between selenium, genotype, and DNA damage. Electronic supplementary material The online version of this article (doi:10.1007/s00394-015-1118-4) contains supplementary material, which is available to authorized users.

International audience; The mechanisms underlying transthyretin-related amyloidosis in vivo remain unclear. The abundance of the 49-127 transthyretin fragment in ex vivo deposits suggests that a proteolytic cleavage has a crucial role in destabilizing the tetramer and releasing the highly amyloidogenic 49-127 truncated protomer. Here, we investigate the mechanism of cleavage and release of the 49-127 fragment from the prototypic S52P variant, and we show that the proteolysis/fibrillogenesis pathway is common to several amyloidogenic variants of transthyretin and requires the action of biomechanical forces provided by the shear stress of physiological fluid flow. Crucially, the non-amyloidogenic and protective T119M variant is neither cleaved nor generates fibrils under these conditions. We propose that a mechano-enzymatic mechanism mediates transthyretin amyloid fibrillogenesis in vivo. This may be particularly important in the heart where shear stress is greatest; indeed, the 49-127 transthyretin fragment is particularly abundant in cardiac amyloid. Finally, we show that existing transthyretin stabilizers, including tafamidis, inhibit proteolysis-mediated transthyretin fibrillogenesis with different efficiency in different variants; however, inhibition is complete only when both binding sites are occupied.

Objective The aim of this study is the evaluation of inter-observer variability in the measurement of liver metastases according to RECIST and its influence on response classification. Patients and methods A total of 100 radiologists measured liver target lesions, on pre- and post-chemotherapy CT scans of three patients. Each observer filled out a questionnaire about his personal and work features. The evaluations of a well experienced radiologist, considered as “the gold standard”, were compared to those taken by the observers. The percentage of the observers in agreement with the reviewer, in terms of the response category and in terms of inter-observer variability, was calculated for each patient. Results The percentage of the inter-observer agreement was elevated. Most of the observers in agreement with the reviewer were senior radiologists, while those who disagreed were junior radiologist, but this result did not reach a statistical significance. More than 30% of observers disagreed with the reviewer at least in one of the three cases. Conclusions RECIST measurements are reproducible on a large and heterogeneous population of radiologists. Age and expertise of the radiologist remain the most critical factors: this suggests a revision by well-experienced radiologists in clinical trials.