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Ovarian cancer (OC) is the most lethal of all gynecological cancers. Due to vague symptoms, OC is mostly detected at advanced stages, with a 5-year survival rate (SR) of only 30%; diagnosis at stage I increases the 5-year SR to 90%, suggesting that early diagnosis is essential to cure OC. Currently, the clinical need for an early, reliable diagnostic test for OC screening remains unmet; indeed, screening is not even recommended for healthy women with no familial history of OC for fear of post-screening adverse events. Salivary diagnostics is considered a major resource for diagnostics of the future. In this work, we searched for OC biomarkers (BMs) by comparing saliva samples of patients with various stages of OC, breast cancer (BC) patients, and healthy subjects using an unbiased, high-throughput proteomics approach. We analyzed the results using both logistic regression (LR) and machine learning (ML) for pattern analysis and variable selection to highlight molecular signatures for OC and BC diagnosis and possibly re-classification. Here, we show that saliva is an informative test fluid for an unbiased proteomic search of candidate BMs for identifying OC patients. Although we were not able to fully exploit the potential of ML methods due to the small sample size of our study, LR and ML provided patterns of candidate BMs that are now available for further validation analysis in the relevant population and for biochemical identification.

The structural collapse of a street lighting pole represents an aspect that is often underestimated and unpredictable, but of relevant importance for the safety of people and things. These events are complex to evaluate since several sources of damage are involved. In addition, traditional inspection methods are ineffective, do not correctly quantify the residual life of poles, and are inefficient, requiring enormous costs associated with the vastness of elements to be investigated. An advantageous alternative is to adopt a distributed type of Structural Health Monitoring (SHM) technique based on the Internet of Things (IoT). This paper proposes the design of a low-cost system, which is also easy to integrate in current infrastructures, for monitoring the structural behavior of street lighting poles in Smart Cities. At the same time, this device collects previous structural information and offers some secondary functionalities related to its application, such as meteorological information. Furthermore, this paper intends to lay the foundations for the development of a method that is able to avoid the collapse of the poles. Specifically, the implementation phase is described in the aspects concerning low-cost devices and sensors for data acquisition and transmission and the strategies of information technologies (ITs), such as Cloud/Edge approaches, for storing, processing and presenting the achieved measurements. Finally, an experimental evaluation of the metrological performance of the sensing features of this system is reported. The main results highlight that the employment of low-cost equipment and open-source software has a double implication. On one hand, they entail advantages such as limited costs and flexibility to accommodate the specific necessities of the interested user. On the other hand, the used sensors require an indispensable metrological evaluation of their performance due to encountered issues relating to calibration, reliability and uncertainty.

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity., Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ≥70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy-seven consecutive patients aged ≥70 diagnosed with non-metastatic hormone-responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES-13 score ≥3 or G-8 score ≤14) and fit (VES-13 score <3 or G-8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients., Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value., Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ≥70.

The frequency of thrombosis in AML has been evaluated only in a few studies and no validated predictive model is currently available. Recently, DIC score was shown to identify patients at higher thrombotic risk. We aimed to evaluate the frequency of thromboembolism in AML patients treated with intensive chemotherapy and to assess the ability of genetic and clinical factors to predict the thrombotic risk. We performed a retrospective observational study including 222 newly diagnosed adult AML (210) and high-risk MDS (12), treated with intensive chemotherapy between January 2013 and February 2020. With a median follow-up of 44 months, we observed 50 thrombotic events (90% were venous, VTE). The prevalence of thrombosis was 22.1% and the 6-months cumulative incidence of thrombosis was 10%. The median time to thrombosis was 84 days and 52% of the events occurred within 100 days from AML diagnosis. Khorana and DIC score failed to stratify patients according to their thrombotic risk. Only history of a thrombotic event (p = 0.043), particularly VTE (p = 0.0053), platelet count above 100 × 10 9 /L at diagnosis (p = 0.036) and active smoking (p = 0.025) significantly and independently increased the risk of thrombosis, the latter particularly of arterial events. AML genetic profile did not affect thrombosis occurrence. Results were confirmed considering only thromboses occurring within day 100 from diagnosis. DIC score at diagnosis, but not thrombosis, was independently associated with reduced survival (p = 0.004). Previous VTE, platelet count above 100 × 10 9 /L and active smoking were the only factors associate with increased thrombotic risk in AML patients treated intensively, but further studies are needed to validate these results., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the field of Smart Cities, especially for Smart Street Lighting and Smart Mobility, the use of low-cost devices is considered an advantageous solution due to their easy availability, cost reduction and, consequently, technological and methodological development. However, this type of transducers shows many critical issues, e.g., in metrological and reliability terms, which can significantly compromise their functionality and safety. Such issue has a large relevance when temperature and humidity are cause of a rapid aging of sensors. The aim of this work is to evaluate the effects of accelerated aging in extreme climatic conditions on the performance of a control system, based on a low-cost ultrasonic distance sensor, for public-lighting management in Smart Cities. The presented architecture allows for the detection of vehicles, pedestrians and small animals and contains a dedicated algorithm, developed in an Edge/Cloud environment, that is able to display the acquired measurements to users connected on the web. The obtained results highlight that the effect of accelerated aging is to significantly reduce the linearity of the calibration curve of the sensor and, moreover, to exponentially increase the number of outliers and invalid measurements. These limitations can be overcome by developing an appropriate self-calibration strategy.

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity., Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ≥70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy-seven consecutive patients aged ≥70 diagnosed with non-metastatic hormone-responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES-13 score ≥3 or G-8 score ≤14) and fit (VES-13 score <3 or G-8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients., Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value., Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ≥70., Competing Interests: None

Viscosupplementation by hyaluronic acid (HA) is recommended for non-surgical management of knee osteoarthritis (OA). This study investigated the efficacy and safety of a single i.a. (32 mg/4 ml) Hymovis MO.RE. injection, a new HA derivative hydrogel, for the treatment of adult regular sports players affected by knee OA arising from overuse injuries. Patients were prospectively enrolled if regularly practicing sports and diagnosed with Kellgren-Lawrence grade I-III OA. They received a single Hymovis MO.RE. intra-articular (i.a.) injection and were evaluated 30, 90, 180, and 360 days thereafter. The assessment involved measuring changes in knee function, pain, the activity of daily living (ADL), and quality of life (QOL) by using the Knee injury and Osteoarthritis Outcome Score (KOOS), GAIT analysis, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for knee pain (WOMAC A) and function (WOMAC C), and a visual analogue scale (VAS) pain score. The study involved thirty-one patients, 23 women and eight men, whose median age was 49. KOOS function subscore, as well as GAIT cadence and velocity, showed a statistically significant increase at each time-point after injection ( p < 0.0001). WOMAC, KOOS pain, symptoms, ADL, and QOL scores also significantly improved at all control visits. No severe adverse events or treatment-related events were detected. A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection provides a rapid, lasting, and safe response in regular sports players affected by knee OA, possibly representing a viable therapeutic option for this demanding patient subgroup. Further investigations are necessary to confirm these findings., Competing Interests: NG is an employee of Fidia Farmaceutici SpA. (Abano Terme, PD, Italy). However, Fidia Farmaceutici SpA did not participate in the decision to submit this manuscript for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bernetti, Agostini, Alviti, Giordan, Martella, Santilli, Paoloni and Mangone.)

Background : We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design : This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results : 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48-0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39-0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients ( p = .0012). Conclusions : FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: It is not clear if progression-free survival (PFS) is a good surrogate end-point for overall survival (OS) for metastatic colorectal cancer if antiangiogenic therapies are used., Materials and Methods: We investigated randomized controlled trials testing antiangiogenic agents against chemotherapy. Log hazard ratios (HR) for PFS and OS were used to construct linear regression models. The surrogate threshold effect (STE) was calculated., Results: Thirteen studies and 24 comparison arms were available, including 7,179 patients. This model returned a significant correlation between PFS and OS (R(2)=0.68, p<0.001) with an STE of 0.83. Analysis restricted to first-line gave similar results (R(2)=0.68, p<0.001, STE=0.75)., Conclusion: There is a significant correlation between the effect of treatment on PFS and OS. PFS remains a good surrogate end-point for OS even if anti-angiogenic agents are used., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: This study addresses a recurrent biological problem, that is to define a formal clustering structure for a set of tissues on the basis of the relative abundance of multiple alternatively spliced isoforms mRNAs generated by the same gene. To this aim, we have used a model-based clustering approach, based on a finite mixture of multivariate Gaussian densities. However, given we had more technical replicates from the same tissue for each quantitative measurement, we also employed a finite mixture of linear mixed models, with tissue-specific random effects., Results: A panel of human tissues was analysed through quantitative real-time PCR methods, to quantify the relative amount of mRNA encoding different IGF-1 alternative splicing variants. After an appropriate, preliminary, equalization of the quantitative data, we provided an estimate of the distribution of the observed concentrations for the different IGF-1 mRNA splice variants in the cohort of tissues by employing suitable kernel density estimators. We observed that the analysed IGF-1 mRNA splice variants were characterized by multimodal distributions, which could be interpreted as describing the presence of several sub-population, i.e. potential tissue clusters. In this context, a formal clustering approach based on a finite mixture model (FMM) with Gaussian components is proposed. Due to the presence of potential dependence between the technical replicates (originated by repeated quantitative measurements of the same mRNA splice isoform in the same tissue) we have also employed the finite mixture of linear mixed models (FMLMM), which allowed to take into account this kind of within-tissue dependence., Conclusions: The FMM and the FMLMM provided a convenient yet formal setting for a model-based clustering of the human tissues in sub-populations, characterized by homogeneous values of concentrations of the mRNAs for one or multiple IGF-1 alternative splicing isoforms. The proposed approaches can be applied to any cohort of tissues expressing several alternatively spliced mRNAs generated by the same gene, and can overcome the limitations of clustering methods based on simple comparisons between splice isoform expression levels.

Aim: EMA licensed eribulin mesylate in 2011 for women with advanced breast cancer already treated with at least two lines of chemotherapy, including anthracyclines and taxanes. Azienda Sanitaria Firenze experience is reported to assess the efficacy and safety of eribulin in the real-life setting., Patients & Methods: Eribulin was infused as per indication. All women treated in the last 2 years were reviewed., Results: A total of 27 women received eribulin. All but one was pretreated with anthracyclines, 97% with taxanes and 87% with capecitabine. Median age was 63 years (range: 27-80). A median of four cycles of eribulin were infused (range: 2-10). Overall response rate was 30% with a 45% of clinical benefit (response plus stable disease for at least 24 weeks). Toxicities have been as expected. Severe toxicities were rare, with one patient experiencing sepsis and 18% developing grade 3 asthenia., Conclusion: Eribulin maintains its activity out of clinical trials, without unexpected toxicities.

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10(-8) ). By combined modeling of linkage and association, we showed that association of longevity with APOEε4 and APOEε2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10(-5) , respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity., (© 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)

Bone is the preferential site of distant metastasis in breast carcinoma (BrCa). Patients with metastasis restricted to bone (BO) usually show a longer overall survival compared to patients who rapidly develop multiple metastases also involving liver and lung. Hence, molecular predisposition to generate bone and visceral metastases (BV) represents a clear indication of poor clinical outcome. We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from BO and BV patients. The unsupervised hierarchical clustering of the resulting transcriptomes correlated with the clinical progression, segregating the BO from the BV profiles. Matching the twofold significantly regulated genes from Affymetrix and Agilent chips resulted in a 15-gene signature with 13 upregulated and two downregulated genes in BV versus BO bone metastasis samples. In order to validate the resulting signature, we isolated different MDA-MB-231 clonal subpopulations that metastasize only in the bone (MDA-BO) or in bone and visceral tissues (MDA-BV). Six of the signature genes were also significantly upregulated in MDA-BV compared to MDA-BO clones. A group of upregulated genes, including Hemoglobin B (HBB), were involved in oxygen metabolism, and in vitro functional analysis of HBB revealed that its expression in the MDA subpopulations was associated with a reduced production of hydrogen peroxide. Expression of HBB was detected in primary BrCa tissue but not in normal breast epithelial cells. Metastatic lymph nodes were frequently more positive for HBB compared to the corresponding primary tumors, whereas BO metastases had a lower expression than BV metastases, suggesting a positive correlation between HBB and ability of bone metastasis to rapidly spread to other organs. We propose that HBB, along with other genes involved in oxygen metabolism, confers a more aggressive metastatic phenotype in BrCa cells disseminated to bone., (Copyright © 2012 American Society for Bone and Mineral Research.)

Motivation: The classification of few tissue samples on a very large number of genes represents a non-standard problem in statistics but a usual one in microarray expression data analysis. In fact, the dimension of the feature space (the number of genes) is typically much greater than the number of tissues. We consider high-density oligonucleotide microarray data, where the expression level is associated to an 'absolute call', which represents a qualitative indication of whether or not a transcript is detected within a sample. The 'absolute call' is generally not taken in consideration in analyses., Results: In contrast to frequently used cluster analysis methods to analyze gene expression data, we consider a problem of classification of tissues and of the variables selection. We adopted methodologies formulated by Ghahramani and Hinton and Rocci and Vichi for simultaneous dimensional reduction of genes and classification of tissues; trying to identify genes (denominated 'markers') that are able to distinguish between two known different classes of tissue samples. In this respect, we propose a generalization of the approach proposed by McLachlan et al. by advising to estimate the distribution of log LR statistic for testing one versus two component hypothesis in the mixture model for each gene considered individually, using a parametric bootstrap approach. We compare conditional (on 'absolute call') and unconditional analyses performed on dataset described in Golub et al. We show that the proposed techniques improve the results of classification of tissue samples with respect to known results on the same benchmark dataset., Availability: The software of Ghahramani and Hinton is written in Matlab and available in 'Mixture of Factor Analyzers' on http://www.gatsby.ucl.ac.uk/~zoubin/software.html while the software of Rocci and Vichi is available upon request from the authors.