New techniques for wound management: A systematic review of their role in the management of chronic wounds

International audienceDebridement is a crucial component of wound management. Recent technologies such as hydrosurgery (Versajet), ultrasound therapy (the MIST therapy device), or plasma-mediated bipolar radio-frequency ablation therapy (Coblation) seem to represent interesting alternatives for wound debridement. The purpose of this systematic review was to describe, evaluate, and compare these three recently developed methods for the management of chronic wounds. In January 2016, an electronic database search was conducted of MEDLINE, PubMed Central, and Embase for articles concerning these three innovative methods for the management of chronic wounds. A total of 389 references were identified by our search strategy, and 15 articles were included. We extracted data regarding the number and age of patients, indications, operating time, number of procedures, costs, wound healing time, decrease in exudation, perioperative blood loss, bacterial load, and the occurrence of complications. The 15 articles included studies that involved 563 patients who underwent hydrosurgery (7 studies), ultrasound therapy (6 studies), or Coblation (2 studies). Six randomized controlled trials were included that compared the use of a scalpel or curette to hydrosurgery (2 studies) or ultrasound therapy (6 studies). Hydrosurgery, in addition to being a very precise and selective tool, allows significantly faster debridement. Ultrasound therapy provides a significant reduction of exudation, and improves the wound healing time. No comparative study dedicated to Coblation was identified. Despite the obvious clinical interest of the topic, our review of the current literature revealed a lack of prospective randomized studies comparing these devices with each other or with standard techniques, particularly for Coblation and hydrosurgery

Assessing the robustness of Antarctic temperature reconstructions over the past 2 millennia using pseudoproxy and data assimilation experiments

The Antarctic temperature changes over the past millennia remain more uncertain than in many other continental regions. This has several origins: (1) the number of high-resolution ice cores is small, in particular on the East Antarctic plateau and in some coastal areas in East Antarctica; (2) the short and spatially sparse instrumental records limit the calibration period for reconstructions and the assessment of the methodologies; (3) the link between isotope records from ice cores and local climate is usually complex and dependent on the spatial scales and timescales investigated. Here, we use climate model results, pseudoproxy experiments and data assimilation experiments to assess the potential for reconstructing the Antarctic temperature over the last 2 millennia based on a new database of stable oxygen isotopes in ice cores compiled in the framework of Antarctica2k (Stenni et al.,). The well-known covariance between δ 18 O and temperature is reproduced in the two isotope-enabled models used (ECHAM5/MPI-OM and ECHAM5-wiso), but is generally weak over the different Antarctic regions, limiting the skill of the reconstructions. Furthermore, the strength of the link displays large variations over the past millennium, further affecting the potential skill of temperature reconstructions based on statistical methods which rely on the assumption that the last decades are a good estimate for longer temperature reconstructions. Using a data assimilation technique allows, in theory, for changes in the δ 18 O-temperature link through time and space to be taken into account. Pseudoproxy experiments confirm the benefits of using data assimilation methods instead of statistical methods that provide reconstructions with unrealistic variances in some Antarctic subregions. They also confirm that the relatively weak link between both variables leads to a limited potential for reconstructing temperature based on δ 18 O. However, the reconstruction skill is higher and more uniform among reconstruction methods when the reconstruction target is the Antarctic as a whole rather than smaller Antarctic subregions. This consistency between the methods at the large scale is also observed when reconstructing temperature based on the real δ 18 O regional composites of Stenni et al. (2017). In this case, temperature reconstructions based on data assimilation confirm the long-term cooling over Antarctica during the last millennium, and the later onset of anthropogenic warming compared with the simulations without data assimilation, which is especially visible in West Antarctica. Data assimilation also allows for models and direct observations to be reconciled by reproducing the east-west contrast in the recent temperature trends. This recent warming pattern is likely mostly driven by internal variability given the large spread of individual Paleoclimate Modelling Intercomparison Project (PMIP)/Coupled Model Intercomparison Project (CMIP) model realizations in simulating it. As in the pseudoproxy framework, the reconstruction methods perform differently at the subregional scale, especially in terms of the variance of the time series produced. While the potential benefits of using a data assimilation method instead of a statistical method have been highlighted in a pseudoproxy framework, the instrumental series are too short to confirm this in a realistic setup

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

The social dimension of globalization: A review of the literature

With globalization affecting so many inter-connected areas, it is difficult to grasp its full impact. This literature review of over 120 sources considers the impact of globalization on wages and taxes, poverty, inequality, insecurity, child labour, gender, and migration. Opening with some stylized facts concerning globalization in 1985-2002, the authors then highlight recent findings on these areas, reporting on controversies and on emerging consensus where it exists. There follows a review of national and international policy responses designed to make globalization more sustainable and equitable and to deliver decent jobs, security and a voice in decision-making

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies