Exploring drivers of overnight stays and same-day visits in the tourism sector.

We employ mobile network data referred to the area of Lombardy in Italy to investigate alternative touristic behaviours, such as same-day visits and overnight stays in Italy. We show that larger availability of tourism accommodations, cultural and natural endowments are relevant factors explaining overnight stays. Conversely, temporary entertainment and transportation facilities increase municipalities attractiveness for same-day visits. The results also highlight a trade-off in the capability of municipalities of being attractive in connection to both the tourism behaviours. For instance, higher tourists arrivals are observed in areas receiving limited visitors, coming from municipalities with low same-day visits outflows. We highlight mobile data offer an adequate level of spatial and temporal granularity and can be thus employed to support policy makers in the design of effective tourist management strategies.

A look at the spatio-temporal mortality patterns in Italy during the COVID-19 pandemic through the lens of mortality densities.

With the tools and perspective of Object Oriented Spatial Statistics, we analyze official daily data on mortality from all causes in the provinces and municipalities of Italy for the year 2020, the first of the COVID-19 pandemic. By comparison with mortality data from 2011 to 2019, we assess the local impact of the pandemic as perturbation factor of the natural spatio-temporal death process. For each Italian province and year, mortality data are represented by the densities of time of death during the calendar year. Densities are regarded as functional data belonging to the Bayes space B 2 . In this space, we use functional-on-functional linear models to predict the expected mortality in 2020, based on mortality in previous years, and we compare predictions with actual observations, to assess the impact of the pandemic. Through spatial downscaling of the provincial data down to the municipality level, we identify spatial clusters characterized by mortality densities anomalous with respect to the surroundings. The proposed analysis pipeline could be extended to indexes different from death counts, measured at a granular spatio-temporal scale, and used as proxies for quantifying the local disruption generated by the pandemic.

Association rule mining to identify transcription factor interactions in genomic regions.

MOTIVATION: Genome regulatory networks have different layers and ways to modulate cellular processes, such as cell differentiation, proliferation, and adaptation to external stimuli. Transcription factors and other chromatin-associated proteins act as combinatorial protein complexes that control gene transcription. Thus, identifying functional interaction networks among these proteins is a fundamental task to understand the genome regulation framework. RESULTS: We developed a novel approach to infer interactions among transcription factors in user-selected genomic regions, by combining the computation of association rules and of a novel Importance Index on ChIP-seq datasets. The hallmark of our method is the definition of the Importance Index, which provides a relevance measure of the interaction among transcription factors found associated in the computed rules. Examples on synthetic data explain the index use and potential. A straightforward pre-processing pipeline enables the easy extraction of input data for our approach from any set of ChIP-seq experiments. Applications on ENCODE ChIP-seq data prove that our approach can reliably detect interactions between transcription factors, including known interactions that validate our approach. AVAILABILITY AND IMPLEMENTATION: A R/Bioconductor package implementing our association rules and Importance Index-based method is available at http://bioconductor.org/packages/release/bioc/html/TFARM.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

FunChIP: an R/Bioconductor package for functional classification of ChIP-seq shapes.

SUMMARY: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) generates local accumulations of sequencing reads on the genome ("peaks"), which correspond to specific protein-DNA interactions or chromatin modifications. Peaks are detected by considering their total area above a background signal, usually neglecting their shapes, which instead may convey additional biological information. We present FunChIP, an R/Bioconductor package for clustering peaks according to a functional representation of their shapes: after approximating their profiles with cubic B-splines, FunChIP minimizes their functional distance and classifies the peaks applying a k-mean alignment and clustering algorithm. The whole pipeline is user-friendly and provides visualization functions for a quick inspection of the results. An application to the transcription factor Myc in 3T9 murine fibroblasts shows that clusters of peaks with different shapes are associated with different genomic locations and different transcriptional regulatory activity. AVAILABILITY AND IMPLEMENTATION: The package is implemented in R and is available under Artistic Licence 2.0 from the Bioconductor website (http://bioconductor.org/packages/FunChIP). CONTACT: marco.morelli@iit.it. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Peak shape clustering reveals biological insights.

BACKGROUND: ChIP-seq experiments are widely used to detect and study DNA-protein interactions, such as transcription factor binding and chromatin modifications. However, downstream analysis of ChIP-seq data is currently restricted to the evaluation of signal intensity and the detection of enriched regions (peaks) in the genome. Other features of peak shape are almost always neglected, despite the remarkable differences shown by ChIP-seq for different proteins, as well as by distinct regions in a single experiment. RESULTS: We hypothesize that statistically significant differences in peak shape might have a functional role and a biological meaning. Thus, we design five indices able to summarize peak shapes and we employ multivariate clustering techniques to divide peaks into groups according to both their complexity and the intensity of their coverage function. In addition, our novel analysis pipeline employs a range of statistical and bioinformatics techniques to relate the obtained peak shapes to several independent genomic datasets, including other genome-wide protein-DNA maps and gene expression experiments. To clarify the meaning of peak shape, we apply our methodology to the study of the erythroid transcription factor GATA-1 in K562 cell line and in megakaryocytes. CONCLUSIONS: Our study demonstrates that ChIP-seq profiles include information regarding the binding of other proteins beside the one used for precipitation. In particular, peak shape provides new insights into cooperative transcriptional regulation and is correlated to gene expression.

Object Oriented Data Analysis: A few methodological challenges.

This is a discussion of the paper "Overview of object oriented data analysis" by J. Steve Marron and Andrés M. Alonso.

Aortic valve replacement in octogenarians: analysis of risk factors for early and late mortality.

BACKGROUND AND AIM OF THE STUDY: Cardiac surgery can be performed on elderly patients in good physical and mental health, thus improving their mortality, morbidity, and quality of life. Nevertheless, for some elderly patients aortic valve replacement (AVR) is still denied because of the presence of preoperative characteristics, such as older age and left ventricular dysfunction. The study aim was to review early and long-term results in patients aged > or = 80 years who underwent AVR for severe aortic stenosis, and to identify risk factors for in-hospital and late mortality. METHODS: A total of 165 patients (mean age 82 +/- 2.1 years) underwent AVR for severe aortic stenosis, with or without concomitant coronary revascularization, at the authors' institution. The mean aortic valve area was 0.61 +/- 0.2 cm2. Preoperatively, 20 patients (12%) had a left ventricular ejection fraction < 35%. The mean EuroSCORE was 9.45 +/- 1.52. RESULTS: Seven patients (4%) experienced low cardiac output syndrome, and acute renal failure occurred in 24. No perioperative myocardial infarction, stroke or sternal wound infection was detected. In total, 23 patients (14%) required prolonged ventilatory support. The in-hospital mortality was 3%. After a mean follow up of 43 +/- 35.6 months there were 18 late deaths: the cardiac-related mortality was 7%. The mean NYHA class was improved from 2.86 +/- 0.67 to 1.44 +/- 0.57 (p < 0.0001). CONCLUSION: Conventional AVR remains the standard of care, and can be performed with satisfactory in-hospital mortality, long-term life expectancy and quality of life in high-risk elderly patients. Although the transcatheter aortic valve technique seems to be a promising option, its long-term value must be established in prospective, randomized trials.

pT1 penile squamous cell carcinoma: a clinicopathologic study of 56 cases treated by CO2 laser therapy.

OBJECTIVE: To evaluate the pathologic characteristics that are associated with outcomes in pT1 penile squamous cell carcinoma (SCC) treated with laser excision. STUDY DESIGN: Peniscopic magnification and 5% acetic acid application were performed prior to CO2 laser excision. Specimens were reviewed to reassess stage, grade, invasion depth, carcinoma in situ, margins, tumor extension, lymphovascular invasion and human papillomavirus infection. Association between local recurrence (LR) and prognostic factors was established with Fisher exact test, chi2 test for categorical variables and Wilcoxon rank sum test for continuous variables. RESULTS: After a median follow-up of 66 months, 53 of 56 patients were alive and disease free; 3 died of unrelated and intercurrent diseases. Thirteen had an LR, with 4 experiencing multiple recurrences and 1 needing a partial amputation. Two patients had inguinal nodal metastasis in 1 node. LR had a positive correlation with positive surgical margins and depth of invasion and a negative correlation with tumor extension. CONCLUSION: Histopathologic parameters such as margin status, depth of invasion and tumor extension are predictors of LR in T1 penile SCC treated by CO2 laser excision. A logistic model could estimate each patient's risk of LR.

IFN-gamma produced by human papilloma virus-18 E6-specific CD4+ T cells predicts the clinical outcome after surgery in patients with high-grade cervical lesions.

Cervical neoplastic lesions are associated with infection by high-risk human papilloma viruses (HPVs). HPV-16 and HPV-18 are the most common genotypes. It has been proposed that development of HPV-16-positive cervical lesions is associated with impaired CD4(+) T cell immunity against early Ags. The aim of the study was to evaluate whether this impairment also applies to HPV-18. We investigated the presence and the quality of anti-HPV-18 E6 CD4(+) T cell responses in the blood of 37 consecutive patients with high-grade cervical lesions, 25 normal donors, and 20 cord bloods. The immune infiltrate in the cervical lesions was also evaluated. The characteristics of the responses were correlated to the clinical outcome. We found that one or more HPV-18 E6 peptides, containing naturally processed epitopes, were able to induce a response in 40-50% of the patients, depending on the effector function tested. Importantly, these percentages rose to 80-100% when HPV-18-positive patients were considered. HPV-18 E6-specific CD4(+) T cells produced mixed Th1/Th2 responses and statistical analysis of the cytokines produced revealed that the amount of IFN-gamma released could predict infection persistence and/or disease relapse after surgery. Finally, we found that a higher number of infiltrating CD4(+) and T-bet(+) T cells in the lesions correlated with a favorable clinical outcome. Our results strongly suggest a relevant role for CD4(+) T cells in the control of the HPV-18 compared with HPV-16 infections in patients with high-grade cervical lesions and identify an immunologic parameter potentially useful for patients' stratification.