Prediction of Inflammatory Breast Cancer Survival Outcomes Using Computed Tomography-Based Texture Analysis

Background: Although inflammatory breast cancer (IBC) has poor overall survival (OS), there is little information about using imaging features for predicting the prognosis. Computed tomography (CT)-based texture analysis, a non-invasive technique to quantify tumor heterogeneity, could be a potentially useful imaging biomarker. The aim of the article was to investigate the usefulness of chest CT-based texture analysis to predict OS in IBC patients. Methods: Of the 3,130 patients with primary breast cancers between 2006 and 2016, 104 patients (3.3%) with IBC were identified. Among them, 98 patients who underwent pre-treatment contrast-enhanced chest CT scans, got treatment in our institution, and had a follow-up period of more than 2 years were finally included for CT-based texture analysis. Texture analysis was performed on CT images of 98 patients, using commercially available software by two breast radiologists. Histogram-based textural features, such as quantification of variation in CT attenuation (mean, standard deviation, mean of positive pixels [MPP], entropy, skewness, and kurtosis), were recorded. To dichotomize textural features for survival analysis, receiver operating characteristic curve analysis was used to determine cutoff points. Clinicopathologic variables, such as age, node stage, metastasis stage at the time of diagnosis, hormonal receptor positivity, human epidermal growth factor receptor 2 positivity, and molecular subtype, were assessed. A Cox proportional hazards model was used to determine the association of textural features and clinicopathologic variables with OS. Results: During a mean follow-up period of 47.9 months, 41 of 98 patients (41.8%) died, with a median OS of 20.0 months. The textural features of lower mean attenuation, standard deviation, MPP, and entropy on CT images were significantly associated with worse OS, as was the M1 stage among clinicopathologic variables (all P-values < 0.05). In multivariate analysis, lower mean attenuation (hazard ratio [HR], 3.26; P = 0.003), lower MPP (HR, 3.03; P = 0.002), and lower entropy (HR, 2.70; P = 0.009) on chest CT images were significant factors independent from the M1 stage for predicting worse OS. Conclusions: Lower mean attenuation, MPP, and entropy on chest CT images predicted worse OS in patients with IBC, suggesting that CT-based texture analysis provides additional predictors for OS

Contribution of the cyclic nucleotide gated channel subunit, CNG-3, to olfactory plasticity in Caenorhabditis elegans.

In Caenorhabditis elegans, the AWC neurons are thought to deploy a cGMP signaling cascade in the detection of and response to AWC sensed odors. Prolonged exposure to an AWC sensed odor in the absence of food leads to reversible decreases in the animal's attraction to that odor. This adaptation exhibits two stages referred to as short-term and long-term adaptation. Previously, the protein kinase G (PKG), EGL-4/PKG-1, was shown necessary for both stages of adaptation and phosphorylation of its target, the beta-type cyclic nucleotide gated (CNG) channel subunit, TAX-2, was implicated in the short term stage. Here we uncover a novel role for the CNG channel subunit, CNG-3, in short term adaptation. We demonstrate that CNG-3 is required in the AWC for adaptation to short (thirty minute) exposures of odor, and contains a candidate PKG phosphorylation site required to tune odor sensitivity. We also provide in vivo data suggesting that CNG-3 forms a complex with both TAX-2 and TAX-4 CNG channel subunits in AWC. Finally, we examine the physiology of different CNG channel subunit combinations

Scapular deformity in obstetric brachial plexus palsy: a new finding

While most obstetric brachial plexus palsy patients recover arm and hand function, the residual nerve weakness leads to muscle imbalances about the shoulder which may cause bony deformities. In this paper we describe abnormalities in the developing scapula and the glenohumeral joint. We introduce a classification for the deformity which we term Scapular Hypoplasia, Elevation and Rotation. Multiple anatomic parameters were measured in bilateral CT images and three-dimensional CT reconstruction of the shoulder girdle of 30 obstetric brachial plexus palsy patients (age range 10 months–10.6 years). The affected scapulae were found to be hypoplastic by an average of 14% while the ratio of the height to the width of the body of scapula (excluding acromion) were not significantly changed, the acromion was significantly elongated by an average of 19%. These parameters as well as subluxation of the humeral head (average 14%) and downward rotation in the scapular plane were found to correlate with the area of scapula visible over the clavicle. This finding provides a classification tool for diagnosis and objective evaluation of the bony deformity and its severity in obstetric brachial plexus palsy patients

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer

Anyonic interferometry and protected memories in atomic spin lattices

Strongly correlated quantum systems can exhibit exotic behavior called topological order which is characterized by non-local correlations that depend on the system topology. Such systems can exhibit remarkable phenomena such as quasi-particles with anyonic statistics and have been proposed as candidates for naturally fault-tolerant quantum computation. Despite these remarkable properties, anyons have never been observed in nature directly. Here we describe how to unambiguously detect and characterize such states in recently proposed spin lattice realizations using ultra-cold atoms or molecules trapped in an optical lattice. We propose an experimentally feasible technique to access non-local degrees of freedom by performing global operations on trapped spins mediated by an optical cavity mode. We show how to reliably read and write topologically protected quantum memory using an atomic or photonic qubit. Furthermore, our technique can be used to probe statistics and dynamics of anyonic excitations.Comment: 14 pages, 6 figure

Apium plants: Beyond simple food and phytopharmacological applications

Apium plants belong to the Apiaceae family and are included among plants that have been in use in traditional medicine for thousands of years worldwide, including in the Mediterranean, as well as the tropical and subtropical regions of Asia and Africa. Some highlighted medical benefits include prevention of coronary and vascular diseases. Their phytochemical constituents consist of bergapten, flavonoids, glycosides, furanocoumarins, furocoumarin, limonene, psoralen, xanthotoxin, and selinene. Some of their pharmacological properties include anticancer, antioxidant, antimicrobial, antifungal, nematocidal, anti-rheumatism, antiasthma, anti-bronchitis, hepatoprotective, appetizer, anticonvulsant, antispasmodic, breast milk inducer, anti-jaundice, antihypertensive, anti-dysmenorrhea, prevention of cardiovascular diseases, and spermatogenesis induction. The present review summarizes data on ecology, botany, cultivation, habitat, medicinal use, phytochemical composition, preclinical and clinical pharmacological efficacy of Apium plants and provides future direction on how to take full advantage of Apium plants for the optimal benefit to mankind.N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the strategic project ref. UID/BIM/04293/2013 and “NORTE2020-Northern Regional Operational Program” (NORTE-01-0145-FEDER-000012)

Joint IARC/NCI International Cancer Seminar Series Report: Expert consensus on future directions for ovarian carcinoma research

Recently, ovarian cancer research has evolved considerably because of the emerging recognition that rather than a single disease, ovarian carcinomas comprise several different histotypes that vary by etiologic origin, risk factors, molecular profiles, therapeutic approaches, and clinical outcome. Despite significant progress in our understanding of the etiologic heterogeneity of ovarian cancer, as well as important clinical advances, it remains the eighth most frequently diagnosed cancer in women worldwide and the most fatal gynecologic cancer. The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) jointly convened an expert panel on ovarian carcinoma to develop consensus research priorities based on evolving scientific discoveries. Expertise ranged from etiology, prevention, early detection, pathology, model systems, molecular characterization, and treatment/clinical management. This report summarizes the current state of knowledge and highlights expert consensus on future directions to continue advancing etiologic, epidemiologic, and prognostic research on ovarian carcinoma

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

Nonlinear and nonreciprocal transport effects in untwinned thin films of ferromagnetic Weyl metal SrRuO3_3

The identification of distinct charge transport features, deriving from nontrivial bulk band and surface states, has been a challenging subject in the field of topological systems. In topological Dirac and Weyl semimetals, nontrivial conical bands with Fermi-arc surfaces states give rise to negative longitudinal magnetoresistance due to chiral anomaly effect and unusual thickness dependent quantum oscillation from Weyl-orbit effect, which were demonstrated recently in experiments. In this work, we report the experimental observations of large nonlinear and nonreciprocal transport effects for both longitudinal and transverse channels in an untwinned Weyl metal of SrRuO$_3$ thin film grown on a SrTiO$_{3}$ substrate. From rigorous measurements with bias current applied along various directions with respect to the crystalline principal axes, the magnitude of nonlinear Hall signals from the transverse channel exhibits a simple sin$\alpha$ dependent at low temperatures, where $\alpha$ is the angle between bias current direction and orthorhombic [001]$_{\rm o}$, reaching a maximum when current is along orthorhombic [1-10]$_{\rm o}$. On the contrary, the magnitude of nonlinear and nonreciprocal signals in the longitudinal channel attains a maximum for bias current along [001]$_{\rm o}$, and it vanishes for bias current along [1-10]$_{\rm o}$. The observed $\alpha$-dependent nonlinear and nonreciprocal signals in longitudinal and transverse channels reveal a magnetic Weyl phase with an effective Berry curvature dipole along [1-10]$_{\rm o}$ from surface states, accompanied by 1D chiral edge modes along [001]$_{\rm o}$.Comment: 24 pages, 6 figure