Staging systems and nomograms in soft tissue sarcoma: outcome prediction by categorization or personalization?

Soft tissue sarcomas (STS) are rare cancers that most commonly develop in the extremities and trunk, but can develop in any location throughout the body. Similar to other cancers, staging systems have been available, but for STS these have historically been criticized as inadequate and poorly applicable to daily clinical practice. In 2018, the American Joint Cancer Committee's (AJCC) TNM staging system was updated (8 th edition) with changes such as separation by tumor location and categorization of all node-positive disease as Stage 4

Influence of nanostructured ceria support on platinum nanoparticles for methanol electrooxidation in alkaline media

The catalytic activity of platinum (Pt) nanoparticles (NPs) towards methanol electrooxidation in alkaline media was demonstrated to be dependent on their interactions with their nanostructured ceria support. Ceria nanorods (NRs) with diameters of 5 to 10 nm and lengths of 15 to 50 nm as well as ceria NPs with diameters of 2 to 6 nm were applied as supports for similarly sized Pt NPs with diameters of 2 to 5 nm. Cyclic voltammetry data showed that Pt NPs supported on ceria NPs exhibited a 2-to-5-fold higher catalytic current density versus ceria NRs. X-ray photoelectron spectroscopic data indicated that Pt NPs deposited onto ceria NRs were disproportionally composed of oxidized species (Pt2+, Pt4+ and Pt–O–M) rather than Pt0 while Pt NPs on ceria NPs mainly consisted of Pt0. Stronger metal-support interactions between Pt NPs and ceria NRs are postulated to induce preferential oxidation of Pt NPs and consequently decrease the catalytic sites and overall activity

Determinants of Use of Insecticide Treated Nets for the Prevention of Malaria in Pregnancy: Jinja, Uganda

One established means of preventing the adverse consequences of malaria during pregnancy is sleeping under an insecticide treated net (ITN) throughout pregnancy. Despite increased access to this intervention over time, consistent ITN use during pregnancy remains relatively uncommon in sub-Saharan Africa.We sought to identify determinants of ITN use during pregnancy. Utilizing a population-based random sample, we interviewed 500 women living in Jinja, Uganda, who had been pregnant in the past year. ITN ownership at the start of pregnancy was reported by 359 women (72%) and 28 women (20%) acquired an ITN after the first trimester of pregnancy. Among 387 ITN owners, 73% reported either always sleeping under the ITN during all trimesters of pregnancy, or after acquiring their net. Owning more than 1 net was slightly associated with always sleeping under an ITN during pregnancy (RR: 1.13; 95% CI: 1.00, 1.28). Women who always slept under an ITN during pregnancy were more likely to be influenced by an advertisement on the radio/poster than being given an ITN free of charge (RR: 1.48; 95% CI: 1.24, 1.76). No differences were found between other socio-demographic factors, pregnancy history, ANC use or socio-cultural factors.While self-reported ITN ownership and use was common throughout pregnancy, we were unable to pinpoint why a sizable fraction of Ugandan women did not always adhere to recommendations for use of an ITN during pregnancy. More data are needed on the capacity of individual households to support the installation of ITNs which may provide insight into interventions targeted at improving the convenience and adherence of daily ITN use

A Genome-Wide Screen for Genetic Variants That Modify the Recruitment of REST to Its Target Genes

Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from DNA sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that SNPs within the binding sites of the transcriptional repressor REST alter the degree of repression of target genes. Given that changes in the effective concentration of REST contribute to several pathologies—various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation—these SNPs should alter disease-susceptibility in carriers. We devised a strategy to identify SNPs that affect the recruitment of REST to target genes through the alteration of its DNA recognition element, the RE1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic RE1 sequences with robust and statistically significant differences of affinity between alleles. These SNPs have a considerable effect on the the functional recruitment of REST to DNA in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in RE1 affinity. Amongst the targets of polymorphic RE1 elements are important disease genes including NPPA, PTPRT, and CDH4. Thus, considerable genetic variation exists in the DNA motifs that connect gene regulatory networks. Recently available ChIP–seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism

Mediterranean Diet and Breast Density in the Minnesota Breast Cancer Family Study

Mediterranean populations’ lower breast cancer incidence has been attributed to a traditional Mediterranean diet, but few studies have quantified Mediterranean dietary pattern intake in relation to breast cancer. We examined the association of a Mediterranean diet scale (MDS) with mammographic breast density as a surrogate marker for breast cancer risk. Participants completed a dietary questionnaire and provided screening mammograms for breast density assessment using a computer-assisted method. Among 1,286 women, MDS was not clearly associated with percent density in multivariate linear regression analyses. Because of previous work suggesting dietary effects limited to smokers, we conducted stratified analyses and found MDS and percent density to be significantly, inversely associated among current smokers (β = –1.68, P = 0.002) but not among nonsmokers (β = –0.08, P = 0.72; P for interaction = 0.008). Our results confirm a previous suggestion that selected dietary patterns may be protective primarily in the presence of procarcinogenic compounds such as those found in tobacco smoke

Predictions for the future of kallikrein-related peptidases in molecular diagnostics

Kallikrein-related peptidases (KLKs) form a cancer-related ensemble of serine proteases. This multigene family hosts the most widely used cancer biomarker that is PSA-KLK3, with millions of tests performed annually worldwide. The present report provides an overview of the biomarker potential of the extended KLK family (KLK1-KLK15) in various disease settings and envisages approaches that could lead to additional KLK-driven applications in future molecular diagnostics. Particular focus is given on the inclusion of KLKs into multifaceted cancer biomarker panels that provide enhanced diagnostic, prognostic and/or predictive accuracy in several human malignancies. Such panels have been described so far for prostate, ovarian, lung and colorectal cancers. The role of KLKs as biomarkers in non-malignant disease settings, such as Alzheimer’s disease and multiple sclerosis, is also commented upon. Predictions are given on the challenges and future directions regarding clinically oriented KLK research

First results on ProtoDUNE-SP liquid argon time projection chamber performance from a beam test at the CERN Neutrino Platform

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber with an active volume of 7.2× 6.1× 7.0 m3. It is installed at the CERN Neutrino Platform in a specially-constructed beam that delivers charged pions, kaons, protons, muons and electrons with momenta in the range 0.3 GeV/c to 7 GeV/c. Beam line instrumentation provides accurate momentum measurements and particle identification. The ProtoDUNE-SP detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment, and it incorporates full-size components as designed for that module. This paper describes the beam line, the time projection chamber, the photon detectors, the cosmic-ray tagger, the signal processing and particle reconstruction. It presents the first results on ProtoDUNE-SP\u27s performance, including noise and gain measurements, dE/dx calibration for muons, protons, pions and electrons, drift electron lifetime measurements, and photon detector noise, signal sensitivity and time resolution measurements. The measured values meet or exceed the specifications for the DUNE far detector, in several cases by large margins. ProtoDUNE-SP\u27s successful operation starting in 2018 and its production of large samples of high-quality data demonstrate the effectiveness of the single-phase far detector design

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all ΑCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all ΑCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22θ13 to current reactor experiments

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all δ_(CP) values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all δ_(CP) values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin²θ₁₃ to current reactor experiments