Sense-antisense pairs in mammals: functional and evolutionary considerations

Analysis of a catalog of S-AS pairs in the human and mouse genomes revealed several putative roles for natural antisense transcripts and showed that some are artifacts of cDNA library construction

Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14.

Published versio

Anti-malarial prescriptions in three health care facilities after the emergence of chloroquine resistance in Niakhar, Senegal (1992–2004)

<p>Abstract</p> <p>Background</p> <p>In the rural zone of Niakhar in Senegal, the first therapeutic failures for chloroquine (CQ) were observed in 1992. In 2003, the national policy regarding first-line treatment of uncomplicated malaria was modified, replacing CQ by a transitory bi-therapy amodiaquine/sulphadoxine-pyrimethamine (AQ/SP), before the implementation of artemisinin-based combination therapy (ACT) in 2006.</p> <p>The aims of the study were to assess the evolution of anti-malarial prescriptions in three health care facilities between 1992 and 2004, in parallel with increasing CQ resistance in the region.</p> <p>Methods</p> <p>The study was conducted in the area of Niakhar, a demographic surveillance site located in a sahelo-sudanese region of Senegal, with mesoendemic and seasonal malaria transmission. Health records of two public health centres and a private catholic dispensary were collected retrospectively to cover the period 1992–2004.</p> <p>Results</p> <p>Records included 110,093 consultations and 292,965 prescribed treatments. Twenty-five percent of treatments were anti-malarials, prescribed to 49% of patients. They were delivered all year long, but especially during the rainy season, and 20% of patients with no clinical malaria diagnosis received anti-malarials. Chloroquine and quinine represented respectively 55.7% and 34.6% of prescribed anti-malarials. Overall, chloroquine prescriptions rose from 1992 to 2000, in parallel with clinical malaria; then the CQ prescription rate decreased from 2000 and was concomitant with the rise of SP and the persistence of quinine use. AQ and SP were mainly used as bi-therapy after 2003, at the time of national treatment policy change.</p> <p>Conclusion</p> <p>The results show the overall level of anti-malarial prescription in the study area for a considerable number of patients over a large period of time. Even though resistance to CQ rapidly increased from 1992 to 2001, no change in CQ prescription was observed until the early 2000s, possibly due to the absence of an obvious decrease in CQ effectiveness, a lack of therapeutic options or a blind follow-up of national guidelines.</p

Diagnostic accuracy of telestroke consultation: a Louisiana based tele-network experience

Background and purposeTelestroke has grown significantly since its implementation. Despite growing utilization, there is a paucity of data regarding the diagnostic accuracy of telestroke to distinguish between stroke and its mimics. We aimed to evaluate diagnostic accuracy of telestroke consultations and explore the characteristics of misdiagnosed patients with a focus on stroke mimics.MethodsWe conducted a retrospective study of all the consultations in our Ochsner Health’s TeleStroke program seen between April 2015 and April 2016. Consultations were classified into one of three diagnostic categories: stroke/transient ischemic attack, mimic, and uncertain. Initial telestroke diagnosis was compared with the final diagnosis post review of all emergency department and hospital data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR−) for diagnosis of stroke/TIA versus mimic were calculated. Area under receiver-operating characteristic curve (AUC) analysis to predict true stroke was performed. Bivariate analysis based on the diagnostic categories examined association with sex, age, NIHSS, stroke risk factors, tPA given, bleeding after tPA, symptom onset to last known normal, symptom onset to consult, timing in the day, and consult duration. Logistic regression was performed as indicated by bivariate analysis.ResultsEight hundred and seventy-four telestroke evaluations were included in our analysis. Accurate diagnosis through teleneurological consultation was seen in 85% of which 532 were strokes (true positives) and 170 were mimics (true negatives). Sensitivity, specificity, PPV, NPV were 97.8, 82.5, 93.7 and 93.4%, respectively. LR+ and LR− were 5.6 and 0.03. AUC (95% CI) was 0.9016 (0.8749–0.9283). Stroke mimics were more common with younger age and female gender and in those with less vascular risk factors. LR revealed OR (95% CI) of misdiagnosis for female gender of 1.9 (1.3–2.9). Lower age and lower NIHSS score were other predictors of misdiagnosis.ConclusionWe report high diagnostic accuracy of the Ochsner Telestroke Program in discriminating stroke/TIA and stroke mimics, with slight tendency towards over diagnosis of stroke. Female gender, younger age and lower NIHSS score were associated with misdiagnosis

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

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

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

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s}=1.96 TeV using Lepton + Jets Events with Secondary Vertex b-tagging

We present a measurement of the ttbar production cross section using events with one charged lepton and jets from ppbar collisions at a center-of-mass energy of 1.96 TeV. In these events, heavy flavor quarks from top quark decay are identified with a secondary vertex tagging algorithm. From 162 pb-1 of data collected by the Collider Detector at Fermilab, a total of 48 candidate events are selected, where 13.5 +- 1.8 events are expected from background contributions. We measure a ttbar production cross section of 5.6^{+1.2}_{-1.1} (stat.) ^{+0.9}_{0.6} (syst.) pb.Comment: 28 pages, 20 figures. Published in Physical Review

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns