Schmidtcamp0988
Our exploratory results suggest that self-report neuropsychological measures and structural MRI hold promise as sensitive measures for quantifying the long-term, cumulative effects of blast exposure in breachers. We discuss the limitations of our study and the need for prospective longitudinal data for drawing causal inferences regarding the impact of blast exposure on breachers' health and performance.
Our exploratory results suggest that self-report neuropsychological measures and structural MRI hold promise as sensitive measures for quantifying the long-term, cumulative effects of blast exposure in breachers. We discuss the limitations of our study and the need for prospective longitudinal data for drawing causal inferences regarding the impact of blast exposure on breachers' health and performance.
Copy number variants (CNVs) are known to play an important role in the development and progression of several diseases. However, detection of CNVs with whole-exome sequencing (WES) experiments is challenging. Usually, additional experiments have to be performed.
We developed a novel algorithm for somatic CNV calling in matched WES data called "CopyDetective". Different from other approaches, CNV calling with CopyDetective consists of a 2-step procedure first, quality analysis is performed, determining individual detection thresholds for every sample. Second, actual CNV calling on the basis of the previously determined thresholds is performed. Our algorithm evaluates the change in variant allele frequency of polymorphisms and reports the fraction of affected cells for every CNV. Analyzing 4 WES data sets (n = 100) we observed superior performance of CopyDetective compared with ExomeCNV, VarScan2, ControlFREEC, ExomeDepth, and CNV-seq.
Individual detection thresholds reveal that not every WES data set is equally apt for CNV calling. Initial quality analyses, determining individual detection thresholds-as realized by CopyDetective-can and should be performed prior to actual variant calling.
Individual detection thresholds reveal that not every WES data set is equally apt for CNV calling. Initial quality analyses, determining individual detection thresholds-as realized by CopyDetective-can and should be performed prior to actual variant calling.
Trimethylamine N-oxide (TMAO) has been considered to be an independent risk factor of heart failure (HF).
To further determine the plasma levels of TMAO in patients who have HF with preserved ejection fraction (HFpEF), and to analyze the relationship between TMAO and HFpEF risk.
A total of 57 control participants and 61 patients with HFpEF were recruited. We measured and analyzed plasma levels of TMAO and performed biochemical examination of all patients.
The mean (SD) plasma levels of TMAO in patients with HFpEF (6.84 [1.12] μmol/L) were significantly higher than in controls (1.63 [0.08] μmol/L; P <.01). The area under the curve (AUC) of TMAO and N-terminal pro b-type natriuretic peptide (NT-proBNP) was 0.817 and 0.924, respectively, which were determined by receiver operating characteristic (ROC) analysis. TMAO was an independent risk factor in patients with HFpEF, as revealed by univariate and multivariate logistic regression analysis. The level of TMAO was correlated with blood urea nitrogen (BUN), creatinine, and NT-proBNP.
TMAO level was highly associated with HFpEF risk.
TMAO level was highly associated with HFpEF risk.
The mechanisms underlying Roux-en-Y gastric bypass (RYGB) surgery-induced weight loss and the immediate postoperative beneficial metabolic effects associated with the operation remain uncertain. Enteroendocrine cell (EEC) secretory function has been proposed as a key factor in the marked metabolic benefits from RYGB surgery.
To identify novel gut-derived peptides with therapeutic potential in obesity and/or diabetes by profiling EEC-specific molecular changes in obese patients following RYGB-induced weight loss.
Genome-wide expression analysis was performed in isolated human small intestinal EECs obtained from 20 gut-biopsied obese subjects before and after RYGB. Targets of interest were profiled for preclinical and clinical metabolic effects.
Roux-en-Y gastric bypass consistently increased expression levels of the inverse ghrelin receptor agonist, liver-expressed antimicrobial peptide 2 (LEAP2). A secreted endogenous LEAP2 fragment (LEAP238-47) demonstrated robust insulinotropic properties, stimulating insulin release in human pancreatic islets comparable to the gut hormone glucagon-like peptide-1. LEAP238-47 showed reciprocal effects on growth hormone secretagogue receptor (GHSR) activity, suggesting that the insulinotropic action of the peptide may be directly linked to attenuation of tonic GHSR activity. The fragment was infused in healthy human individuals (n = 10), but no glucoregulatory effect was observed in the chosen dose as compared to placebo.
Small intestinal LEAP2 expression was upregulated after RYGB. The corresponding circulating LEAP238-47 fragment demonstrated strong insulinotropic action in vitro but failed to elicit glucoregulatory effects in healthy human subjects.
Small intestinal LEAP2 expression was upregulated after RYGB. The corresponding circulating LEAP238-47 fragment demonstrated strong insulinotropic action in vitro but failed to elicit glucoregulatory effects in healthy human subjects.
Whole blood (WB) is the optimal resuscitation fluid in hemorrhagic shock. Military research focuses on mortality benefits of WB acquired through walking blood banks (WBBs). Few military-based studies on donation effects exist, almost exclusively performed on small special operation forces. No Department of Defense regulations for postdonation precautions in nonaviation crew members exist. Further study is warranted regarding safety and limitations in postdonation populations.
A feasibility (n = 25) prospective interventional study examined the safety of exertion (defined as a 1.6-km treadmill run at volunteers' minimum passing pace for the Army Physical Fitness Test) following 1 unit of WB donation. Subjects served as their own controls, performing baseline testing 7 days before donation, with repeat testing 1 h following donation conducted by Armed Services Blood Program personnel. Adverse events, pre- and postexertion vital signs (VS) were evaluated.
There were no adverse events throughout testing. Onpand duration and intensity of exertion to match combat conditions.
A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We reanalyzed the series after a median 119 months, adding retrospectively patients' molecular features.
Follow-up of all patients was updated. DNA copy-number analysis and gene-fusion detection could be completed for 94/160 patients, methylation classification for 68.
PFS and OS at five/ten years were 66/58%, and 80/73%. Ten patients had late relapses (range 66-126 months), surviving after relapse no longer than those relapsing earlier (0-5 years). On multivariable analysis a better PFS was associated with grade 2 tumor and complete surgery at diagnosis and/or at RT; female sex and complete resection showed a positive association with OS. Posterior fossa(PF) tumors scoring ≥0.80 on DNA methylation analysis were classified as PFA (41) and PFB (8). PFB patients had better PFS and OS. Eighteen/32 supratentorial(ST) tumors were classified as RELA, and 3 as other molecular entities (atification and long-term follow-up.
In the modeling of biological systems by Boolean networks a key problem is finding the set of fixed points of a given network. Some constructed algorithms consider certain structural properties of the regulatory graph like those proposed by Akutsu et al. (1998b); Zhang et al. (2007) which consider a feedback vertex set of the graph. However, these methods do not take into account the type of action (activation, inhibition) between its components.
In this paper we propose a new algorithm for finding the set of fixed points of a Boolean network, based on a positive feedback vertex set P of its regulatory graph and which works, by applying a sequential update schedule, in time O(2 |P| · n2+k), where n is the number of components and the regulatory functions of the network can be evaluated in time O(nk), k ≥ 0. The theoretical foundation of this algorithm is due a nice characterization, that we give, of the dynamical behavior of the Boolean networks without positive cycles and with a fixed point.
An executable file of FixedPoint algorithm made in Java and some examples of input files are available at www.inf.udec.cl/~lilian/FPCollector/.
Supplementary material is available at Bioinformatics online.
Supplementary material is available at Bioinformatics online.
The study of the evolutionary history of biological networks enables deep functional understanding of various bio-molecular processes. Network growth models, such as the Duplication-Mutation with Complementarity (DMC) model, provide a principled approach to characterizing the evolution of protein-protein interactions (PPI) based on duplication and divergence. Current methods for model-based ancestral network reconstruction primarily use greedy heuristics and yield sub-optimal solutions.
We present a new Integer Linear Programming (ILP) solution for maximum likelihood reconstruction of ancestral PPI networks using the DMC model. Anti-infection chemical We prove the correctness of our solution that is designed to find the optimal solution. It can also use efficient heuristics from general-purpose ILP solvers to obtain multiple optimal and near-optimal solutions that may be useful in many applications. Experiments on synthetic data show that our ILP obtains solutions with higher likelihood than those from previous methods, and is robust to noise and model mismatch. We evaluate our algorithm on two real PPI networks, with proteins from the families of bZIP transcription factors and the Commander complex. On both the networks, solutions from our ILP have higher likelihood and are in better agreement with independent biological evidence from other studies.
A Python implementation is available at https//bitbucket.org/cdal/network-reconstruction.
A Python implementation is available at https//bitbucket.org/cdal/network-reconstruction.
The maintenance of military surgeons' operative skills is challenging. Different and specific training strategies have been implemented in this context; however, little has been evaluated with regard to their effectiveness. Cancer surgery is a part of military surgeons' activities in their home hospitals. This study aimed to assess the role of oncological surgery in the improvement of military surgeons' operative skills.
Between January and June 2019, the surgical activities of the departments of visceral, ear, nose, and throat, urological, and thoracic surgery were retrospectively reviewed and assessed in terms of the operative time (OT). All surgeons working at the Sainte Anne Military Teaching Hospital were sent a survey to rate on a 5-point scale the current surgical practices on their usefulness in improving surgical skills required for treating war injuries during deployment (primary endpoint) and to compare on a 10-point visual analog scale the influence of cancer surgery and specific training on surgical fluency (secondary endpoint).