BEBOP: Bidirectional dEep Brain cOnnectivity maPping

Functional connectivity mapping provides information about correlated brain areas, useful for many applications such as on mental disorders. This work aims to improve this mapping by using deep metric learning considering the directionality of information flow and time-domain features. To deal with the computational cost of a complete pairwise combination network, we trained a network able to recognize similar signals and, after training, feed it with all combinations of signals from each brain area. The labels of similarity or dissimilarity are determined by agglomerative clustering using the Jensen-Shannon Distance as a metric. To validate our approach we employed a resting-state eye-open functional MRI dataset from ADHD and healthy subjects. Once registered, the signals are filtered and averaged by area with a functional trimmed mean. After obtaining the connectivity maps from each subject, we perform a feature importance selection using logistic regression. The ten most promising areas were extracted, such as the frontal cortex and the limbic system. These results are in complete agreement with previous literature. It is well known those areas are mainly involved in attention and impulsivity

Math Skills: a New Look from Functional Data Analysis

: Mental calculations involve various areas of the brain. The frontal, parietal and temporal lobes of the left hemisphere have a principal role in the completion of this typology of tasks. Their level of activation varies based on the mathematical competence and attentiveness of the subject under examination and the perceived difficulty of the task. Recent literature often investigates patterns of cerebral activity through fMRI, which is an expensive technique. In this scenario, EEGs represent a more straightforward and cheaper way to collect information regarding brain activity. In this work, we propose an EEG based method to detect differences in the cerebral activation level of people characterized by different abilities in carrying out the same arithmetical task. Our approach consists in the extraction of the activation level of a given region starting from the EEG acquired during resting state and during the completion of a subtraction task. We then analyze these data through Functional Data Analysis, a statistical technique that allows operating on biomedical signals as if they were functions. The application of this technique allowed for the detection of distinct cerebral patterns among the two groups and, more specifically, highlighted the presence of higher levels of activation in the parietal lobe in the population characterized by a lower performance

Autonomic cardiac profile in male and female healthcare professionals with and without preschoolers: differences evidenced by heart rate variability analysis

A reduced nocturnal cardiac vagal modulation has been observed in working women with preschoolers. Whether this adaptation also occurs in men remains an open question. The aim of this study was to analyze the cardiac autonomic profile of two groups of healthcare male professionals, one with and one without preschoolers, to be compared to females. Twenty-five working men with preschoolers (M_KID, age 35.41 ± 4.01 years) and 25 without (M_NOKID, 34.48 ± 6.00 years) were compared with 25 working women with preschoolers (W_KID, 37.7 ± 5.6 years) and 25 without (W_NOKID, 35.4 ± 7.2 years). A 24-h Holter electrocardiogram was performed for time and frequency domain analysis of the beat-to-beat variations of RR interval (RR) variability, during daytime (DAY) and nighttime (NIGHT). The power of RR variability in the high frequency band (HFRR) was considered as an index of cardiac vagal modulation. RR variability indices were similar in M_KID and M_NOKID during both DAY and NIGHT. In contrast, W_KID showed a reduced nocturnal HFRR compared to W_NOKID. The comparison of working men with and without preschoolers revealed no differences in the cardiac autonomic profile, in contrast with women. This suggests that sex and/or gender may represent a crucial factor in the cardiac neural control in the parental condition

Chemically stable inhibitors of 14-3-3 protein–protein interactions derived from BV02

14-3-3 are regulatory proteins that through protein–protein interactions (PPI) with numerous binding partners could be involved in several human diseases, including cancer, neurodegenerative disorders, and pathogens infections. Following our research interest in the development of 14-3-3 PPI inhibitors, here we exploited the privileged 4-aminoantipyrine scaffold in the design and synthesis of some derivatives endowed with antiproliferative activity against K-562 cells, and capable of binding to recombinant 14-3-3σ as evidenced by NMR spectroscopy. The binding mode was further explored by molecular modelling, while coupling confocal microscopy with intensitometric analysis showed that compound 1 was able to promote the nuclear translocation of c-Abl at low micromolar concentrations. Overall, 1 is chemically stable compared to parent 14-3-3 PPI inhibitors, and thus emerged as a confirmed hit for further development

From microscopic taxation and redistribution models to macroscopic income distributions

We present here a general framework, expressed by a system of nonlinear differential equations, suitable for the modelling of taxation and redistribution in a closed (trading market) society. This framework allows to describe the evolution of the income distribution over the population and to explain the emergence of collective features based on the knowledge of the individual interactions. By making different choices of the framework parameters, we construct different models, whose long-time behavior is then investigated. Asymptotic stationary distributions are found, which enjoy similar properties as those observed in empirical distributions. In particular, they exhibit power law tails of Pareto type and their Lorenz curves and Gini indices are consistent with some real world ones.Comment: 12 pages, 4 figures. Version submitted to Physica A on Feb 15, 201

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

A Functional Data Analysis Approach to Left Ventricular Remodeling Assessment

Left ventricular remodeling is a mechanism common to various cardiovascular diseases affecting myocardial morphology. It can be often overlooked in clinical practice since the parameters routinely employed in the diagnostic process (e.g., the ejection fraction) mainly focus on evaluating volumetric aspects. Nevertheless, the integration of a quantitative assessment of structural modifications can be pivotal in the early individuation of this pathology. In this work, we propose an approach based on functional data analysis to evaluate myocardial contractility. A functional representation of ventricular shape is introduced, and functional principal component analysis and depth measures are used to discriminate healthy subjects from those affected by left ventricular hypertrophy. Our approach enables the integration of higher informative content compared to the traditional clinical parameters, allowing for a synthetic representation of morphological changes in the myocardium, which could be further explored and considered for future clinical practice implementation

Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned So Far

Src is the prototypal member of Src Family tyrosine Kinases (SFKs), a large non-receptor kinase class that controls multiple signaling pathways in animal cells. SFKs activation is necessary for the mitogenic signal from many growth factors, but also for the acquisition of migratory and invasive phenotype. Indeed, oncogenic activation of SFKs has been demonstrated to play an important role in solid cancers; promoting tumor growth and formation of distant metastases. Several drugs targeting SFKs have been developed and tested in preclinical models and many of them have successfully reached clinical use in hematologic cancers. Although in solid tumors SFKs inhibitors have consistently confirmed their ability in blocking cancer cell progression in several experimental models; their utilization in clinical trials has unveiled unexpected complications against an effective utilization in patients. In this review, we summarize basic molecular mechanisms involving SFKs in cancer spreading and metastasization; and discuss preclinical and clinical data highlighting the main challenges for their future application as therapeutic targets in solid cancer progressio

Inhibition of autophagy in prostate cancer cells stimulates Tau accumulation and aberrant mitotic spindle

INTRODUCTION Autophagy is a self‐degrading adaptation mechanism in which cytoplasmic macromolecules and organelles are delivered to the lysosome for degradation and recycling. In a physiologic context autophagy could be both a cytoprotective driver and a programmed death facilitator. Sustained autophagy has been frequently detected in neoplastic transformation, even though its promoting role in cancer growth is not fully elucidated. In recent years, a significant correlation has emerged between molecular dysfunction leading to Tau protein accumulation and interference with mitosis progression. In our study we investigated the potential association between autophagy and Tau accumulation and its role during cell mitosis. METHODS We evaluated in vitro the role of autophagy in modulating the expression of Tau protein in prostate cancer cell lines, analyzing morphological and molecular consequences during mitosis. RESULTS Tau protein was expressed at low level in prostate cancer lines and western blot analysis showed in these cells the presence of several phosphorylated and oligomeric forms. The pharmacologic inhibition of autophagy by treatment with chloroquine, induced in cancer cells a reduction in proliferation with an increment of number of cells in G2/M phase of cell cycle. In addition, in these cells we observed an accumulation of Tau protein, with an increased expression of both phosphorylated and oligomeric forms. Immunofluorescence analysis of untreated cells revealed that Tau was expressed mainly in dividing cells where it was localized on mitotic spindle. Inhibition of autophagy determined an evident upregulation of Tau signal in dividing cells with a diffuse protein localization in cytoplasm. The accumulation of Tau protein was associated with the presence of aberrant mitotic spindles, with monoastral spindle as major unusual figure. CONCLUSIONS Our data indicate that autophagy could exert a promoting role in cancer growth facilitating degradation of Tau protein and thus blocking the inhibitory effect of accumulated Tau forms on mitosis. Thus, the understanding of molecular mechanisms underlying the homeostatic control of Tau protein degradation during cell mitosis could represent an important goal also in oncology research