Entropy-based approach to missing-links prediction

Link-prediction is an active research field within network theory, aiming at uncovering missing connections or predicting the emergence of future relationships from the observed network structure. This paper represents our contribution to the stream of research concerning missing links prediction. Here, we propose an entropy-based method to predict a given percentage of missing links, by identifying them with the most probable non-observed ones. The probability coefficients are computed by solving opportunely defined null-models over the accessible network structure. Upon comparing our likelihood-based, local method with the most popular algorithms over a set of economic, financial and food networks, we find ours to perform best, as pointed out by a number of statistical indicators (e.g. the precision, the area under the ROC curve, etc.). Moreover, the entropy-based formalism adopted in the present paper allows us to straightforwardly extend the link-prediction exercise to directed networks as well, thus overcoming one of the main limitations of current algorithms. The higher accuracy achievable by employing these methods - together with their larger flexibility - makes them strong competitors of available link-prediction algorithms

Transformed epithelia trigger non-tissue-autonomous tumor suppressor response by adipocytes via activation of toll and Eiger/TNF signaling

High tumor burden is associated with increased levels of circulating inflammatory cytokines that influence the pathophysiology of the tumor and its environment. The cellular and molecular events mediating the organismal response to a growing tumor are poorly understood. Here, we report a bidirectional crosstalk between epithelial tumors and the fat body—a peripheral immune tissue—in Drosophila. Tumors trigger a systemic immune response through activation of Eiger/TNF signaling, which leads to Toll pathway upregulation in adipocytes. Reciprocally, Toll elicits a non-tissue-autonomous program in adipocytes, which drives tumor cell death. Hemocytes play a critical role in this system by producing the ligands Spätzle and Eiger, which are required for Toll activation in the fat body and tumor cell death. Altogether, our results provide a paradigm for a long-range tumor suppression function of adipocytes in Drosophila, which may represent an evolutionarily conserved mechanism in the organismal response to solid tumors

A faster horse on a safer trail: generalized inference for the efficient reconstruction of weighted networks

Due to the interconnectedness of financial entities, estimating certain key properties of a complex financial system (e.g. the implied level of systemic risk) requires detailed information about the structure of the underlying network. However, since data about financial linkages are typically subject to confidentiality, network reconstruction techniques become necessary to infer both the presence of connections and their intensity. Recently, several "horse races" have been conducted to compare the performance of the available financial network reconstruction methods. These comparisons, however, were based on arbitrarily-chosen similarity metrics between the real and the reconstructed network. Here we establish a generalised maximum-likelihood approach to rigorously define and compare weighted reconstruction methods. Our generalization maximizes the conditional entropy to solve the problem represented by the fact that the density-dependent constraints required to reliably reconstruct the network are typically unobserved. The resulting approach admits as input any reconstruction method for the purely binary topology and, conditionally on the latter, exploits the available partial information to infer link weights. We find that the most reliable method is obtained by "dressing" the best-performing binary method with an exponential distribution of link weights having a properly density-corrected and link-specific mean value and propose two unbiased (in the sense of maximum conditional entropy) variants of it. While the one named CReMA is perfectly general (as a particular case, it can place optimal weights on a network whose topology is known), the one named CReMB is recommended both in case of full uncertainty about the network topology and if the existence of some links is certain. In these cases, the CReMB is faster and reproduces empirical networks with highest generalised likelihood.Comment: 19 pages, 4 figures, 1 tabl

Pyridostigmine in pediatric Intestinal pseudo-obstruction. case report of a 2-year old girl and literature review

Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, longacting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility

A cohort study on acute ocular motility disorders in pediatric emergency department

Background: Acute ocular motility disorders (OMDs) in children admitted to Emergency Department (ED) represents a not so rare condition with a wide spectrum of different etiologies. The emergency physician must be skilled in rapidly identifying patients with potentially life threatening (LT) forms, requiring further diagnostic procedures. The aim of the study was to assess characteristics of children with acute Ocular Motility Disorders (OMDs), and to identify "red flags" for recognition of underlying life-threatening (LT) conditions. Methods: A retrospective cohort study evaluated children (2 months-17 years) admitted to a tertiary Emergency Department in 2009-2014. A subgroup analysis was performed comparing children with and without LT conditions. Results: Of 192 visits for OMDs, the isolated strabismus occurred most frequently (55.6%), followed by pupil disorders (31.8%), ptosis (5.2%) and combined OMDs (11.5%). The majority of acute OMDs involved no underlying LT conditions (n = 136) and most of them were infants or toddlers (50%). In a multivariable analysis, LT conditions included especially children over 6 years of age, increasing the odds ratio by 2% for each months of age (p = 0.009). LT etiologies were 16 times more likely in combined OMDs (p = 0.018), were over 13 times more likely to report associated extra-ocular signs/symptoms (p = 0.017) and over 50 times more likely to report co-morbidity (p = 0.017). Conclusion: OMDs are not an uncommon presentation at ED. Although most of them involve non-LT conditions, the ED physician should consider potential "red flags" for appropriate management of children such as age > 6 years, combined OMDs, extra-ocular symptoms and co-morbidity

Long-term motor deficit in brain tumour surgery with preserved intra-operative motor-evoked potentials

Muscle motor-evoked potentials are commonly monitored during brain tumour surgery in motor areas, as these are assumed to reflect the integrity of descending motor pathways, including the corticospinal tract. However, while the loss of muscle motor-evoked potentials at the end of surgery is associated with long-term motor deficits (muscle motor-evoked potential-related deficits), there is increasing evidence that motor deficit can occur despite no change in muscle motor-evoked potentials (muscle motor-evoked potential-unrelated deficits), particularly after surgery of non-primary regions involved in motor control. In this study, we aimed to investigate the incidence of muscle motor-evoked potential-unrelated deficits and to identify the associated brain regions. We retrospectively reviewed 125 consecutive patients who underwent surgery for peri-Rolandic lesions using intra-operative neurophysiological monitoring. Intraoperative changes in muscle motor-evoked potentials were correlated with motor outcome, assessed by the Medical Research Council scale. We performed voxel-lesion-symptom mapping to identify which resected regions were associated with short- and long-term muscle motor-evoked potential-associated motor deficits. Muscle motor-evoked potentials reductions significantly predicted long-term motor deficits. However, in more than half of the patients who experienced long-term deficits (12/22 patients), no muscle motor-evoked potential reduction was reported during surgery. Lesion analysis showed that muscle motor-evoked potential-related long-term motor deficits were associated with direct or ischaemic damage to the corticospinal tract, whereas muscle motor-evoked potential-unrelated deficits occurred when supplementary motor areas were resected in conjunction with dorsal premotor regions and the anterior cingulate. Our results indicate that long-term motor deficits unrelated to the corticospinal tract can occur more often than currently reported. As these deficits cannot be predicted by muscle motor-evoked potentials, a combination of awake and/or novel asleep techniques other than muscle motor-evoked potentials monitoring should be implemented

Recurrent extreme bilateral gigantomastia caused by pseudoangiomatous stromal hyperplasia (PASH) syndrome: a case report

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare and benign medical condition in which the breast tissue is affected by an abnormal myofibroblastic proliferation, which mimics a low-grade sarcoma angiomatous proliferation. PASH usually presents itself either as a palpable mass or as an incidental diagnosis during breast specimens' histological examination. A few cases have been reported in the literature of a diffuse form of breast PASH syndrome in which the clinical presentation is a bilateral form of gigantomastia without palpable masses. In such cases, the optimal surgical management is still debated due to a significant risk of relapse after breast reduction. Mastectomy seems to be the endpoint of this condition in relapsing cases. Recent studies report a good outcome with a Tamoxifen regimen when surgery cannot be performed, supporting a hormonal component for the etiology of the condition. This study reports on an extremely rare case of bilateral, rapid, and severe PASH in a young patient, presenting as a truly disabling gigantomastia that forced the patient to use a wheelchair due to the excessive breast weights (25 kg the right breast and 21 kg the left). We describe her complicated medical history, her diagnosis, and our course of treatment

Intramural Ganglion Structures in Esophageal Atresia: A Morphologic and Immunohistochemical Study

Introduction and Aim. Disorders of esophageal motility causing dysphagia and gastroesophageal reflux are frequent in survivors to esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The aim of the present study was to investigate the histologic and immunohistochemical features in both esophageal atretic segments to further understand the nature of the motor disorders observed in these patients. Material and Methods. Esophageal specimens from 12 newborns with EA/TEF and 5 newborns dead of unrelated causes were examined. The specimens were fixed in 5% buffered formalin, included in paraffin and cut in 5 micron sections that were stained with hematoxilin and eosin (H and E), and immunohistochemical stainings for Actin, S-100 protein, Neurofilament, Neuron-Specific-Enolase, Chromogranin A and Peripherin were evaluated under the microscope. Results. In controls, the distribution of the neural elements was rather homogenous at both levels of the esophagus. In contrast, the atretic segments showed quantitative and qualitative differences between them with sparser nervous tissue in the distal one in comparison with the proximal one and with controls. Conclusions. These results further support the assumption that histomorphological alterations of the muscular and nervous elements within the esophageal wall might contribute to esophageal dysmotility in patients surviving neonatal operations for EA/TEF

Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo

<p>Abstract</p> <p>Background</p> <p>Genetic studies in <it>Drosophila melanogaster </it>reveal an important role for Myc in controlling growth. Similar studies have also shown how components of the insulin and target of rapamycin (TOR) pathways are key regulators of growth. Despite a few suggestions that Myc transcriptional activity lies downstream of these pathways, a molecular mechanism linking these signaling pathways to Myc has not been clearly described. Using biochemical and genetic approaches we tried to identify novel mechanisms that control Myc activity upon activation of insulin and TOR signaling pathways.</p> <p>Results</p> <p>Our biochemical studies show that insulin induces Myc protein accumulation in <it>Drosophila </it>S2 cells, which correlates with a decrease in the activity of glycogen synthase kinase 3-beta (GSK3<it>β </it>) a kinase that is responsible for Myc protein degradation. Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1. Treatment with amino acids that directly activate the TOR pathway results in Myc protein accumulation, which also depends on the ability of S6K kinase to inhibit GSK3<it>β </it>activity. Myc upregulation by insulin and TOR pathways is a mechanism conserved in cells from the wing imaginal disc, where expression of Dp110 and Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR pathways result in the opposite effect. Our functional analysis, aimed at quantifying the relative contribution of Myc to ommatidial growth downstream of insulin and TOR pathways, revealed that Myc activity is necessary to sustain the proliferation of cells from the ommatidia upon Dp110 expression, while its contribution downstream of TOR is significant to control the size of the ommatidia.</p> <p>Conclusions</p> <p>Our study presents novel evidence that Myc activity acts downstream of insulin and TOR pathways to control growth in <it>Drosophila</it>. At the biochemical level we found that both these pathways converge at GSK3<it>β </it>to control Myc protein stability, while our genetic analysis shows that insulin and TOR pathways have different requirements for Myc activity during development of the eye, suggesting that Myc might be differentially induced by these pathways during growth or proliferation of cells that make up the ommatidia.</p

The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study

Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n=20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n=10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p<0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications