Maximum entropy principle in recurrence plot analysis on stochastic and chaotic systems.

The recurrence analysis of dynamic systems has been studied since Poincaré's seminal work. Since then, several approaches have been developed to study recurrence properties in nonlinear dynamical systems. In this work, we study the recently developed entropy of recurrence microstates. We propose a new quantifier, the maximum entropy (Smax). The new concept uses the diversity of microstates of the recurrence plot and is able to set automatically the optimum recurrence neighborhood (ϵ-vicinity), turning the analysis free of the vicinity parameter. In addition, ϵ turns out to be a novel quantifier of dynamical properties itself. We apply Smax and the optimum ϵ to deterministic and stochastic systems. The Smax quantifier has a higher correlation with the Lyapunov exponent and, since it is a parameter-free measure, a more useful recurrence quantifier of time series.

Contralateral Axillary Lymph Node Metastases from Breast Carcinoma: Is it Time to Review TNM Cancer Staging?

BACKGROUND: Contralateral axillary lymph node metastasis (CAM) is an infrequent clinical condition currently considered an M1, stage IV, disease. Due to the absence of shared data on CAM significance and on its therapeutic approach, be it curative or simply palliative, its management is still uncertain and undoubtedly represents a clinical challenge. PATIENTS AND METHODS: Patients with pathologically confirmed metachronous CAM were retrospectively evaluated. All patients had been managed at the European Institute of Oncology, Milan, Italy, from 1997. Patients with distant metastases at the time of CAM were excluded. Possible treatments included surgery, systemic therapy and RT (radiotherapy). Outcomes were evaluated as rates of disease-free survival (DFS) and of overall survival (OS). RESULTS: Forty-seven patients with CAM were included in the study. Metachronous CAM occurred 73 months (range 5-500 months) after diagnosis of the primary tumor. The median follow-up time was 5.4 years (interquartile range 2.9-7.0 years). The estimated OS was 72% at 5 years (95% CI 54-83), and 61% at 8 years (95% CI 43-75). The estimated DFS was 61% at 5 years (95% CI 44-74), and 42% at 8 years (95% CI 25-59). CONCLUSION: These findings, together with those from previous studies, show that CAM outcome, particularly if measured as OS, appear better than at other sites of distant dissemination, when CAM is subjected to surgical and systemic treatments with a curative intent. Therefore, a new clinical scenario is suggested where, in the TNM system, CAM is no longer classified as a stage IV, but as an N3 disease.

Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer.

BACKGROUND: Ipsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed. METHODS: We retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction. All included patients with IBTR previously underwent conserving surgery for BC, and received a postoperative irradiation. Primary endpoints were disease free survival and overall survival. Secondary endpoints were surgical complications and re-interventions. RESULTS: Invasive ductal cancer was the most frequent histotype (60.4%) of breast cancer reappearance. rpT1, rpT2 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Post-operative complication other than seroma occurred in 17,1% of patients, while seroma at the donor site was observed in 61.3% of cases. At 5-year after surgery overall survival was 92% (95% CI: 85%-96%) and disease free survival was 78% (95% CI: 69%-85%). CONCLUSIONS: Immediate latissimus dorsi flap reconstruction in selected patients with isolated breast tumor recurrence, which occurred after breast irradiation, provides an effective treatment with a satisfactory outcome.

Standard and controversies in sentinel node in breast cancer patients.

Axillary management in breast cancer is still controversial. Recent clinical trials have clearly demonstrated that in breast-conserving surgery, axillary dissection could be an overtreatment when metastases are present in only 1-2 sentinel lymph nodes. Nonetheless, axillary dissection remains the principal treatment in patients undergoing mastectomy with at least one metastatic sentinel lymph node and in patients eligible for breast conserving surgery with three or more positive sentinel lymph nodes. In this analytical review, we discuss the clinical evidence, taking into account recent guidelines, for axillary management.

Nipple-sparing mastectomy with different approaches: surgical incisions, complications, and cosmetic results. Preliminary results of 100 consecutive patients at a single center.

Nipple- and areola-sparing mastectomy is a novel surgical approach that preserves the nipple-areolar complex. Patients with moderate and/or severe breast ptosis are usually not eligible for this surgical approach. In this study, we aimed to demonstrate the feasibility of nonconventional surgical approaches for nipple-sparing mastectomy. One hundred consecutive patients diagnosed with primary breast cancer (BC) were enrolled in this study. Clinical and pathological data such as body mass index, smoking status, breast ptosis, complications, and aesthetic satisfaction (Breast-Q test) were collected. According to different types of breast ptosis, surgical procedures were classified as (a) hemi-periareolar, (b) round block, (c) vertical pattern, and (d) wise pattern skin incisions. We performed statistical analysis to assess the correlation with complications, degree of ptosis, and breast-Q scores. Among the 117 surgical procedures performed in 100 patients with BC, no significant associations are verified considering clinical and pathological data, complications, pre- and postsurgery satisfactions, and other parameters. Different surgical approaches represent the evolution of "classic" nipple-sparing mastectomy, thus meeting the cosmetic and oncological results. These procedures are safe and also indicated in cases conventionally considered as not eligible for nipple-areola preservation.

Universal temporal characteristics and vanishing of multifractality in Barkhausen avalanches.

Barkhausen effect in ferromagnetic materials provides an excellent area for investigating scaling phenomena found in disordered systems exhibiting crackling noise. The critical dynamics is characterized by random pulses or avalanches with scale-invariant properties, power-law distributions, and universal features. However, the traditional Barkhausen avalanches statistics may not be sufficient to fully characterize the complex temporal correlation of the magnetic domain walls dynamics. Here we focus on the multifractal scenario to quantify the temporal scaling characteristics of Barkhausen avalanches in polycrystalline and amorphous ferromagnetic films with thicknesses from 50 to 1000 nm. We show that the multifractal properties are dependent on film thickness, although they seem to be insensitive to the structural character of the materials. Moreover, we observe for the first time the vanishing of the multifractality in the domain walls dynamics. As the thickness is reduced, the multifractal behavior gives place to a monofractal one over the entire range of time scales. This reorganization in the temporal scaling characteristics of Barkhausen avalanches is understood as a universal restructuring associated to the dimensional crossover, from three- to two-dimensional magnetization dynamics.

A Novel Multi-step Virtual Screening for the Identification of Human and Mouse mPGES-1 Inhibitors.

We present here the development of a novel virtual screening protocol combining Structure-based and Ligand-based drug design approaches for the identification of mouse mPGES-1 inhibitors. We used the existing 3D structural data of the murine enzyme to hypothesize the inhibitors binding mode, which was the starting point for docking simulations, shape screening, and pharmacophore hypothesis screening. The protocol allowed the identification of 16 mouse mPGES-1 inhibitors with low micromolar activity, which, notably, also inhibit the human enzyme in the same concentration range. The inhibitors predicted binding mode is expected to be the base for the rational drug design of new potent dual species inhibitors of human and murine mPGES-1.

R2R-printed inverted OPV modules--towards arbitrary patterned designs.

We describe the fabrication of roll-to-roll (R2R) printed organic photovoltaic (OPV) modules using gravure printing and rotary screen-printing processes. These two-dimensional printing techniques are differentiating factors from coated OPVs enabling the direct patterning of arbitrarily shaped and sized features into visual shapes and, increasing the freedom to connect the cells in modules. The inverted OPV structures comprise five layers that are either printed or patterned in an R2R printing process. We examined the rheological properties of the inks used and their relationship with the printability, the compatibility between the processed inks, and the morphology of the R2R-printed layers. We also evaluate the dimensional accuracy of the printed pattern, which is an important consideration in designing arbitrarily-shaped OPV structures. The photoactive layer and top electrode exhibited excellent cross-dimensional accuracy corresponding to the designed width. The transparent electron transport layer extended 300 µm beyond the designed values, whereas the hole transport layer shrank 100 µm. We also examined the repeatability of the R2R fabrication process when the active area of the module varied from 32.2 cm(2) to 96.5 cm(2). A thorough layer-by-layer optimization of the R2R printing processes resulted in realization of R2R-printed 96.5 cm(2) sized modules with a maximum power conversion efficiency of 2.1% (mean 1.8%) processed with high functionality.

Erratum - Analysis of extracellular superoxide dismutase and Akt in ascending aortic aneurysm with tricuspid or bicuspid aortic valve.

This correct the article published on European Journal of Histochemistry 2014;58:200-206 doi: 10.4081/ejh.2014.2383.

Assessment of a tumor bank: a thirty years experience of the University of Siena (Italy).

Tumor biobank plays a pivotal role in cancer biomedical research. The collection of a high variety of biological samples, including DNA, RNA, tissues, cells, blood, plasma and other body fluids, represents a necessary step to plan new strategies in the improvement of oncological patient care. Since 1985, a consolidated experience in biobanking management has been developed at the University of Siena (Italy). During these years, some information about clinico-pathology, surgery and a high number of human bispecimens have been collected. Herein, we described our experience in sampling management to improve the cancer research and the patient care.

Ki-67 and p53 expression in ghost cell odontogenic carcinoma: a case report and literature review.

Ghost cell odontogenic carcinomas are rare neoplasms that arise in the maxillary bones either from a calcifying odontogenic cyst or de novo. They are aggressive locally and can metastasize. We report herein a case of a ghost cell odontogenic carcinoma arising in the mandible of a Caucasian male 86 years of age. We have described the clinical and radiographic features, histological characteristics, immunohistochemistry findings, and surgical treatment. We especially focused on how Ki-67 expression guides the treatment choice. Finally, we reviewed 32 cases described in the literature and compared them with the cases described up until 2014 to help clinicians identify the diagnostic characteristics of and select appropriate treatment modalities for ghost cell odontogenic carcinomas.

Mouse activity across time scales: fractal scenarios.

In this work we devise a classification of mouse activity patterns based on accelerometer data using Detrended Fluctuation Analysis. We use two characteristic mouse behavioural states as benchmarks in this study: waking in free activity and slowwave sleep (SWS). In both situations we find roughly the same pattern: for short time intervals we observe high correlation in activity--a typical 1/f complex pattern--while for large time intervals there is anti-correlation. High correlation of short intervals (0.01 s to 2 s: waking state and 0.01 s to 0.1 s: SWS) is related to highly coordinated muscle activity. In the waking state we associate high correlation both to muscle activity and to mouse stereotyped movements (grooming, waking, etc.). On the other side, the observed anti-correlation over large time scales (30 s to 300 s: waking state and 0.3 s to 5 s: SWS) during SWS appears related to a feedback autonomic response. The transition from correlated regime at short scales to an anti-correlated regime at large scales during SWS is given by the respiratory cycle interval, while during the waking state this transition occurs at the time scale corresponding to the duration of the stereotyped mouse movements. Furthermore, we find that the waking state is characterized by longer time scales than SWS and by a softer transition from correlation to anticorrelation. Moreover, this soft transition in the waking state encompass a behavioural time scale window that gives rise to a multifractal pattern. We believe that the observed multifractality in mouse activity is formed by the integration of several stereotyped movements each one with a characteristic time correlation. Finally, we compare scaling properties of body acceleration fluctuation time series during sleep and wake periods for healthy mice. Interestingly, differences between sleep and wake in the scaling exponents are comparable to previous works regarding human heartbeat. Complementarily, the nature of these sleep-wake dynamics could lead to a better understanding of neuroautonomic regulation mechanisms.

Analysis of extracellular superoxide dismutase and Akt in ascending aortic aneurysm with tricuspid or bicuspid aortic valve.

Ascending aortic aneurysm (AsAA) is a consequence of medial degeneration (MD), deriving from apoptotic loss of smooth muscle cells (SMC) and fragmentation of elastin and collagen fibers. Alterations of extracellular matrix structure and protein composition, typical of medial degeneration, can modulate intracellular pathways. In this study we examined the relevance of superoxide dismutase (SOD3) and Akt in AsAA pathogenesis, evaluating their tissue distribution and protein levels in ascending aortic tissues from controls (n=6), patients affected by AsAA associated to tricuspid aortic valve (TAV, n=9) or bicuspid aortic valve (BAV, n=9). The results showed a significant reduction of SOD3, phospho-Akt and Akt protein levels in AsAA tissues from patients with BAV, compared to controls, whereas the differences observed between controls and patients with TAV  were not significant. The decreased levels of SOD3 and Akt in BAV aortic tissues are associated with decreased Erk1/Erk2 phosphorylation and MMP-9 levels increase. The authors suggest a role of decreased SOD3 protein levels in the progression of AsAA with BAV and a link between ECM modifications of aortic media layer and impaired Erk1/Erk2 and Akt signaling in the late stages of the aortopathy associated with BAV.

Long-term follow-up of 5262 breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease.

AIM: It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance. METHODS: We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event. RESULTS: After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95% CI 90.3-92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥ 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy. CONCLUSION: Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival.

Phylogeny and micro-habitats utilized by lizards determine the composition of their endoparasites in the semiarid Caatinga of Northeast Brazil.

Trophic networks can have architectonic configurations influenced by historical and ecological factors. The objective of this study was to analyze the architecture of networks between lizards, their endoparasites, diet, and micro-habitat, aiming to understand which factors exert an influence on the composition of the species of parasites. All networks showed a compartmentalized pattern. There was a positive relation between diet and the diversity of endoparasites. Our analyses also demonstrated that phylogeny and the use of micro-habitat influenced the composition of species of endoparasites and diet pattern of lizards. The principal factor that explained the modularity of the network was the foraging strategy, with segregation between the "active foragers" and "sit-and-wait" lizards. Our analyses also demonstrated that historical (phylogeny) and ecological factors (use of micro-habitat by the lizards) influenced the composition of parasite communities. These results corroborate other studies with ectoparasites, which indicate phylogeny and micro-habitat as determinants in the composition of parasitic fauna. The influence of phylogeny can be the result of coevolution between parasites and lizards in the Caatinga, and the influence of micro-habitat should be a result of adaptations of species of parasites to occupy the same categories of micro-habitats as hosts, thus favoring contagion.

Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis.

We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.

Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer.

BACKGROUND: MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker. METHODS: The 5-aza-2'-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a. RESULTS: The miR-34b/c hypermethylation was found in 97.5% (79 out of 82) of primary colorectal tumours, P=0.0110. In 75% (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16% (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65% (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P=0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65%, P=0.561. CONCLUSIONS: These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker.