Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal ...cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy.
A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue.
ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80; 95% CI 0.71 − 0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83; 95% CI 0.74 − 0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases,RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%.
Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.
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► Hydrolytic enzymes are the first step in the removal of wastewater organic matter. ► Changes in enzyme activities in a SFBBR exposed to saline wastewater were examined. ► High ...salinity of wastewater significantly reduced hydrolytic rates of the biofilms.
The effect of salinity on the hydrolytic enzymatic activities (acid phosphatase, alkaline phosphatase, glucosidase, protease and esterase) released by the microorganisms in a submerged fixed bed bioreactor for real urban wastewater treatment was investigated. The influence of salt (NaCl) on the enzymatic activities was evaluated in four different experiments with concentrations of NaCl of 0, 3.7, 24.1 and 44.1g/L, remaining constant all other operating parameters of the bioreactor. The results show that enzymatic activities were reduced when the salinity was increased in the influent and consequently the biotransformation of organic matter in the submerged fixed bed bioreactor significantly decreased. A redundancy analysis was performed to evaluate the relationships between enzymatic activities and physic-chemical parameters analyzed in the influent. According to the results obtained with the Monte Carlo permutation test, salinity and sampling day significantly contributed to explain the variation of enzymatic activities, showing a negative correlation.
Purpose
In plant-soil systems, phosphorus partitioning during the annual cycle related to nitrogen partitioning remains largely unknown. The present study aims at assessing the soil-plant P ...allocation patterns of four tree species along four phenological stages and its relationship with tissues and soil N concentrations.
Methods
Cryptomeria japonica, Larix kaempferi, Fagus crenata
and
Robinia pseudoacacia
trees were selected to sample coarse roots, sapwood, foliage, litter and soil during four phenological stages where total and Olsen extractable P and nitrogen content were measured respectively.
Results
Intra- and inter plant tissue nitrogen correlated well with phosphorus during the four phenological stages, especially root nitrogen.
Fagus
and
Robinia
were phosphorus limited,
Larix
was nitrogen limited and
Cryptomeria
co-limited. All species reabsorbed phosphorus and nitrogen from foliage prior to leaf abscission and stored nitrogen in roots and sapwood. Phosphorus storage was solely found in sapwood of
Robinia
. Soil dissolved ammonium correlated positively with nitrogen reabsorption efficiency during the green leaf stage, while single soil nutrient variables did not correlate with phosphorus reabsorption efficiency.
Conclusions
Plant tissues nitrogen partitioning correlated well with their respective phosphorus partitioning and the increase of soil NH
4
+
correlated positively with nitrogen reabsorption efficiency, regardless of tree species during the green leaf stage. The results of this study show the intricate relationship that exists between nitrogen and phosphorus in the soil-plant continuum as well as the tree species specific internal cycling of these nutrients.
Highlights ► Caloric and galvanic stimulations and sounds activate the vestibular cortex. ► A meta-analysis was performed to localize the human vestibular cortex. ► The Sylvian fissure, superior ...temporal gyrus and cingulate cortex were activated. ► Canal and otolith afferents converge in the insula, retroinsular cortex and OP2.
Le syndrome confusionnel en oncopédiatrie comme en oncologie adulte est une complication neuropsychiatrique possible au décours d’un traitement oncologique. L’expression clinique en est souvent ...complexe, et le diagnostic étiologique est parfois difficile à poser. Il existe donc un risque de retard et d’errance diagnostiques susceptibles de perturber la prise en charge thérapeutique de ces jeunes patients. Compte tenu de la fréquence et de la complexité diagnostique et thérapeutique de la confusion mentale en oncologie pédiatrique, il est capital de disposer dans ces services de ressources en psychiatrie de liaison. In pediatric oncology, as in adult oncology, delirium is a neuropsychiatric complication that can occur during oncological treatments. Clinical expression of delirium’s symptoms is complex, making it difficult to pinpoint a specific etiological diagnosis. Therefore there is a risk of delay and diagnostic error, which is liable to disrupt the care of these young patients. Given the frequency and the diagnostic and therapeutic complexity of delirium in pediatric oncology, the availability of liaison psychiatric resources in these services is essential.
Multidirectional interactions between metabolic organs in the periphery and the central nervous system have evolved concomitantly with multicellular organisms to maintain whole‐body energy ...homeostasis and ensure the organism's adaptation to external cues. These interactions are altered in pathological conditions such as obesity and type 2 diabetes. Bioactive peptides and proteins, such as hormones and cytokines, produced by both peripheral organs and the central nervous system, are key messengers in this inter‐organ communication. Despite the early discovery of the first hormones more than 100 years ago, recent studies taking advantage of novel technologies have shed light on the multiple ways used by cells in the body to communicate and maintain energy balance. This review briefly summarizes well‐established concepts and focuses on recent advances describing how specific proteins and peptides mediate the crosstalk between gut, brain, and other peripheral metabolic organs in order to maintain energy homeostasis. Additionally, this review outlines how the improved knowledge about these inter‐organ networks is helping us to redefine therapeutic strategies in an effort to promote healthy living and fight metabolic disorders and other diseases.
This review discusses communication and key messengers between peripheral metabolic organs and the central nervous system that crosstalk for the maintenance of whole body energy homeostasis in health and disease.
Abstract
Aims
This study aims to examine the temporal trends and outcomes in patients who undergo percutaneous coronary intervention (PCI) with a previous or current diagnosis of cancer, according to ...cancer type and the presence of metastases.
Methods and results
Individuals undergoing PCI between 2004 and 2014 in the Nationwide Inpatient Sample were included in the study. Multivariable analyses were used to determine the association between cancer diagnosis and in-hospital mortality and complications. 6 571 034 PCI procedures were included and current and previous cancer rates were 1.8% and 5.8%, respectively. Both rates increased over time and the four most common cancers were prostate, breast, colon, and lung cancer. Patients with a current lung cancer had greater in-hospital mortality (odds ratio (OR) 2.81, 95% confidence interval (95% CI) 2.37–3.34) and any in-hospital complication (OR 1.21, 95% CI 1.10–1.36), while current colon cancer was associated with any complication (OR 2.17, 95% CI 1.90–2.48) and bleeding (OR 3.65, 95% CI 3.07–4.35) but not mortality (OR 1.39, 95% CI 0.99–1.95). A current diagnosis of breast was not significantly associated with either in-hospital mortality or any of the complications studied and prostate cancer was only associated with increased risk of bleeding (OR 1.41, 95% CI 1.20–1.65). A historical diagnosis of lung cancer was independently associated with an increased OR of in-hospital mortality (OR 1.65, 95% CI 1.32–2.05).
Conclusions
Cancer among patients receiving PCI is common and the prognostic impact of cancer is specific both for the type of cancer, presence of metastases and whether the diagnosis is historical or current. Treatment of patients with a cancer diagnosis should be individualized and involve a close collaboration between cardiologists and oncologists.
•We discuss nonlinear ill-posed problems in parameter estimation and experiment design.•Identifiability is analyzed by the singular value spectrum of the sensitivity matrix.•Three different ...regularization techniques are applied to exemplary problems.•We show how regularization and experiment design optimization improve the spectrum.•We link common alphabetic experiment design criteria to the singular values.
Discrete ill-posed problems are often encountered in engineering applications. Still, their sound analysis is not yet common practice and difficulties arising in the determination of uncertain parameters are typically not assigned properly. This contribution provides a tutorial review on methods for identifiability analysis, regularization techniques and optimal experimental design. A guideline for the analysis and classification of nonlinear ill-posed problems to detect practical identifiability problems is given. Techniques for the regularization of experimental design problems resulting from ill-posed parameter estimations are discussed. Applications are presented for three different case studies of increasing complexity.
The primary cardiotoxic action of doxorubicin when used as antitumor drug is attributed to the generation of reactive oxygen species (ROS) therefore effective cardioprotection therapies are needed. ...In this sense, the antianginal drug nicorandil has been shown to be effective in cardioprotection from ischemic conditions but the underlying molecular mechanism to cope with doxorubicin-induced ROS is unclear. Our in vitro study using the HL-1 cardiomyocyte cell line derived from mouse atria reveals that the endogenous nitric oxide (NO) production was stimulated by nicorandil and arrested by NO synthase inhibition. Moreover, while the NO synthase activity was inhibited by doxorubicin-induced ROS, the NO synthase inhibition did not affect doxorubicin-induced ROS. The inhibition of NO synthase activity by doxorubicin was totally prevented by preincubation with nicorandil. Nicorandil also concentration-dependently (10 to 100 μM) decreased doxorubicin-induced ROS and the effect was antagonized by 5-hydroxydecanoate. The inhibition profile of doxorubicin-induced ROS by nicorandil was unaltered when an L-arginine derivative or a protein kinase G inhibitor was present. Preincubation with pinacidil mimicked the effect of nicorandil and the protection was eliminated by glibenclamide. Quantitative colocalization of fluorescence indicated that the mitochondrion was the target organelle of nicorandil and the observed response was a decrease in the mitochondrial inner membrane potential. Interference with H+ movement across the mitochondrial inner membrane, leading to depolarization, also protected from doxorubicin-induced ROS. The data indicate that activation of the mitochondrial ATP-sensitive K+ channel by nicorandil causing mitochondrial depolarization, without participation of the NO donor activity, was responsible for inhibition of the mitochondrial NADPH oxidase that is the main contributor to ROS production in cardiomyocytes. Impairment of the cytosolic Ca2+ signal induced by caffeine and the increase in lipid peroxidation, both of which are indicators of doxorubicin-induced oxidative stress, were also prevented by nicorandil.
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