DeepBrain: Functional Representation of Neural In-Situ Hybridization Images for Gene Ontology Classification Using Deep Convolutional Autoencoders

This paper presents a novel deep learning-based method for learning a functional representation of mammalian neural images. The method uses a deep convolutional denoising autoencoder (CDAE) for generating an invariant, compact representation of in situ hybridization (ISH) images. While most existing methods for bio-imaging analysis were not developed to handle images with highly complex anatomical structures, the results presented in this paper show that functional representation extracted by CDAE can help learn features of functional gene ontology categories for their classification in a highly accurate manner. Using this CDAE representation, our method outperforms the previous state-of-the-art classification rate, by improving the average AUC from 0.92 to 0.98, i.e., achieving 75% reduction in error. The method operates on input images that were downsampled significantly with respect to the original ones to make it computationally feasible

SPIRITS 16tn in NGC 3556: A Heavily Obscured and Low-luminosity Supernova at 8.8 Mpc

We present the discovery by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) of a likely supernova (SN) in NGC 3556 (M108) at only 8.8 Mpc that was not detected by optical searches. A luminous infrared (IR) transient at M [4.5] = −16.7 mag (Vega), SPIRITS 16tn is coincident with a dust lane in the inclined, star-forming disk of the host. Using observations in the IR, optical, and radio, we attempt to determine the nature of this event. We estimate A V ≈ 8–9 mag of extinction, placing it among the three most highly obscured IR-discovered SNe. The [4.5] light curve declined at a rate of 0.013 mag day−1, and the [3.6]–[4.5] color increased from 0.7 to gsim1.0 mag by 184.7 days post discovery. Optical/IR spectroscopy shows a red continuum but no clearly discernible features, preventing a definitive spectroscopic classification. Radio observations constrain the radio luminosity of SPIRITS 16tn to L ν lesssim 1024 erg s−1 Hz−1 between 3 and 15 GHz, excluding many varieties of core-collapse SNe. An SN Ia is ruled out by the observed IR color and lack of spectroscopic features from Fe-peak elements. SPIRITS 16tn was fainter at [4.5] than typical stripped-envelope SNe by ≈1 mag. Comparison of the spectral energy distribution to SNe II suggests that SPIRITS 16tn was both highly obscured and intrinsically dim, possibly akin to the low-luminosity SN 2005cs. We infer the presence of an IR dust echo powered by an initial peak luminosity of the transient of 5 × 1040 erg s−1 lesssim L peak lesssim 4 × 1043 erg s−1, consistent with the observed range for SNe II. This discovery illustrates the power of IR surveys to overcome the compounding effects of visible extinction and optically subluminous events in completing the inventory of nearby SNe

Logical Development of the Cell Ontology

<p>Abstract</p> <p>Background</p> <p>The Cell Ontology (CL) is an ontology for the representation of <it>in vivo </it>cell types. As biological ontologies such as the CL grow in complexity, they become increasingly difficult to use and maintain. By making the information in the ontology computable, we can use automated reasoners to detect errors and assist with classification. Here we report on the generation of computable definitions for the hematopoietic cell types in the CL.</p> <p>Results</p> <p>Computable definitions for over 340 CL classes have been created using a genus-differentia approach. These define cell types according to multiple axes of classification such as the protein complexes found on the surface of a cell type, the biological processes participated in by a cell type, or the phenotypic characteristics associated with a cell type. We employed automated reasoners to verify the ontology and to reveal mistakes in manual curation. The implementation of this process exposed areas in the ontology where new cell type classes were needed to accommodate species-specific expression of cellular markers. Our use of reasoners also inferred new relationships within the CL, and between the CL and the contributing ontologies. This restructured ontology can be used to identify immune cells by flow cytometry, supports sophisticated biological queries involving cells, and helps generate new hypotheses about cell function based on similarities to other cell types.</p> <p>Conclusion</p> <p>Use of computable definitions enhances the development of the CL and supports the interoperability of OBO ontologies.</p

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

Cardiovascular magnetic resonance of myocardial edema using a short inversion time inversion recovery (STIR) black-blood technique: Diagnostic accuracy of visual and semi-quantitative assessment

<p>Abstract</p> <p>Background</p> <p>The short inversion time inversion recovery (STIR) black-blood technique has been used to visualize myocardial edema, and thus to differentiate acute from chronic myocardial lesions. However, some cardiovascular magnetic resonance (CMR) groups have reported variable image quality, and hence the diagnostic value of STIR in routine clinical practice has been put into question. The aim of our study was to analyze image quality and diagnostic performance of STIR using a set of pulse sequence parameters dedicated to edema detection, and to discuss possible factors that influence image quality. We hypothesized that STIR imaging is an accurate and robust way of detecting myocardial edema in non-selected patients with acute myocardial infarction.</p> <p>Methods</p> <p>Forty-six consecutive patients with acute myocardial infarction underwent CMR (day 4.5, +/- 1.6) including STIR for the assessment of myocardial edema and late gadolinium enhancement (LGE) for quantification of myocardial necrosis. Thirty of these patients underwent a follow-up CMR at approximately six months (195 +/- 39 days). Both STIR and LGE images were evaluated separately on a segmental basis for image quality as well as for presence and extent of myocardial hyper-intensity, with both visual and semi-quantitative (threshold-based) analysis. LGE was used as a reference standard for localization and extent of myocardial necrosis (acute) or scar (chronic).</p> <p>Results</p> <p>Image quality of STIR images was rated as diagnostic in 99.5% of cases. At the acute stage, the sensitivity and specificity of STIR to detect infarcted segments on visual assessment was 95% and 78% respectively, and on semi-quantitative assessment was 99% and 83%, respectively. STIR differentiated acutely from chronically infarcted segments with a sensitivity of 95% by both methods and with a specificity of 99% by visual assessment and 97% by semi-quantitative assessment. The extent of hyper-intense areas on acute STIR images was 85% larger than those on LGE images, with a larger myocardial salvage index in reperfused than in non-reperfused infarcts (p = 0.035).</p> <p>Conclusions</p> <p>STIR with appropriate pulse sequence settings is accurate in detecting acute myocardial infarction (MI) and distinguishing acute from chronic MI with both visual and semi-quantitative analysis. Due to its unique technical characteristics, STIR should be regarded as an edema-weighted rather than a purely T2-weighted technique.</p

Dendritic Cells/Natural Killer Cross-Talk: A Novel Target for Human Immunodeficiency Virus Type-1 Protease Inhibitors

BACKGROUND: HIV-1 Protease Inhibitors, namely PIs, originally designed to inhibit HIV-1 aspartic protease, can modulate the immune response by mechanisms largely unknown, and independent from their activity on viral replication. Here, we analyzed the ability of PIs to interfere with differentiation program of monocytes toward dendritic cell (DCs) lineage, a key process in the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: Monocytes from healthy donors were isolated and induced to differentiate in vitro in the presence or absence of saquinavir, ritonavir, nelfinavir, indinavir or amprenavir (sqv, rtv, nlfv, idv, apv, respectively). These drugs demonstrated a differential ability to sustain the generation of immature DCs (iDCs) with an altered phenotype, including low levels of CD1a, CD86, CD36 and CD209. DCs generated in the presence of rtv also failed to acquire the typical phenotype of mature DCs (mDCs), and secreted lower amounts of IL-12 and IL-15. Accordingly, these aberrant mDCs failed to support activation of autologous Natural Killer (NK) cells, and resulted highly susceptible to NK cell-mediated cytotoxicity. CONCLUSIONS/SIGNIFICANCE: Our findings uncover novel functional properties of PIs within the DC-NK cell cross-talk, unveiling the heterogeneous ability of members of this class drugs to drive the generation of atypical monocyte-derived DCs (MDDCs) showing an aberrant phenotype, a failure to respond appropriately to bacterial endotoxin, a weak ability to prime autologous NK cells, and a high susceptibility to NK cell killing. These unexpected properties might contribute to limit inflammation and viral spreading in HIV-1 infected patients under PIs treatment, and open novel therapeutical perspectives for this class drugs as immunomodulators in autoimmunity and cancer

Characterisation of male breast cancer: a descriptive biomarker study from a large patient series

Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically