Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Tailored education for older patients to facilitate engagement in falls prevention strategies after hospital discharge—A pilot randomized controlled trial

Background The aims of the study were to evaluate the effect of providing tailored falls prevention education in hospital on: i) engagement in targeted falls prevention behaviors in the month after discharge: ii) patients’ self-perceived risk and knowledge about falls and falls prevention strategies after receiving the education. Methods A pilot randomized controlled trial (n = 50): baseline and outcome assessments conducted by blinded researchers. Participants: hospital inpatients 60 years or older, discharged to the community. Participants were randomized into two groups. The intervention was a tailored education package consisting of multimedia falls prevention information with trained health professional follow-up, delivered in addition to usual care. Outcome measures were engagement in falls prevention behaviors in the month after discharge measured at one month after discharge with a structured survey, and participants’ knowledge, confidence and motivation levels before and after receiving the education. The feasibility of providing the intervention was examined and falls outcomes (falls, fall-related injuries) were also collected. Results Forty-eight patients (98%) provided follow-up data. The complete package was provided to 21 (84%) intervention group participants. Participants in the intervention group were significantly more likely to plan how to safely restart functional activities [Adjusted odds ratio 3.80, 95% CI (1.07, 13.52), p = 0.04] and more likely to complete other targeted behaviors such as completing their own home exercise program [Adjusted odds ratio 2.76, 95% CI (0.72, 10.50), p = 0.14] than the control group. The intervention group was significantly more knowledgeable, confident and motivated to engage in falls prevention strategies after receiving the education than the control group. There were 23 falls (n = 5 intervention; n = 18 control) and falls rates were 5.4/1000 patient days (intervention); 18.7/1000 patient days (control). Conclusion This tailored education was received positively by older people, resulted in increased engagement in falls prevention strategies after discharge and is feasible to deliver to older hospital patients. Trial registration The study was registered with the Australian New Zealand Clinical Trials Registry; ACTRN12611000963921 on 8th November 2011

Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer

In the last decade, optimized treatment for non-small cell lung cancer had lead to improved prognosis, but the overall survival is still very short. To further understand the molecular basis of the disease we have to identify biomarkers related to survival. Here we present the development of an online tool suitable for the real-time meta-analysis of published lung cancer microarray datasets to identify biomarkers related to survival. We searched the caBIG, GEO and TCGA repositories to identify samples with published gene expression data and survival information. Univariate and multivariate Cox regression analysis, Kaplan-Meier survival plot with hazard ratio and logrank P value are calculated and plotted in R. The complete analysis tool can be accessed online at: www.kmplot.com/lung. All together 1,715 samples of ten independent datasets were integrated into the system. As a demonstration, we used the tool to validate 21 previously published survival associated biomarkers. Of these, survival was best predicted by CDK1 (p<1E-16), CD24 (p<1E-16) and CADM1 (p = 7E-12) in adenocarcinomas and by CCNE1 (p = 2.3E-09) and VEGF (p = 3.3E-10) in all NSCLC patients. Additional genes significantly correlated to survival include RAD51, CDKN2A, OPN, EZH2, ANXA3, ADAM28 and ERCC1. In summary, we established an integrated database and an online tool capable of uni- and multivariate analysis for in silico validation of new biomarker candidates in non-small cell lung cancer

Protective Ag :TiO2 thin films for pressure sensors in orthopedic prosthesis: the importance of composition, structural and morphological features on the biological response of the coatings

DC reactive magnetron sputtered Ag:TiO2 nanocomposite thin films were developed to be used as protective coatings in pressure sensor devices. The coatings, with Ag content varying from 0 to about 30 at.%, were prepared and characterized in order to study their biological response. The as-deposited samples were annealed in vacuum at 500 °C in order to evaluate the influence of their morphological and structural differences over the response elicited upon contact with simulated bodily fluids and cultured human cells, as well as selected microorganisms. The results showed that the annealing treatment produced less porous films with an enhanced structure, with a significant reduction in structural defects and improved crystallinity. Additionally, samples with higher Ag contents (≥12.8 at.%) exhibited Ag agglomerates/clusters at the surface, a result anticipated from the XRD data. The crystallization of the TiO2 matrix was also observed by XRD analysis, albeit delayed by the dispersion of Ag into the matrix. Biological characterization showed that the antimicrobial activity and cytotoxicity of the coatings were directly related with their composition, closely followed by the particular structural and morphological features, namely those resulting from annealing process.This research is partially sponsored by FEDER funds through the program COMPETE—Programa Operacional Factores de Competitividade and by national funds through FCT—Fundação para a Ciência e a Tecnologia, under the projects PEst-C/EME/UI0285/2011, PTDC/SAU-ENB/116850/2010, PTDC/CTM-NAN/112574/2009P. T Matamá acknowledges FCT for Grant SFRH/BPD/47555/2008