Mrs-based Metabolomics in Cancer Research

Metabolomics is a relatively new technique that is gaining importance very rapidly. MRS-based metabolomics, in particular, is becoming a useful tool in the study of body fluids, tissue biopsies and whole organisms. Advances in analytical techniques and data analysis methods have opened a new opportunity for such technology to contribute in the field of diagnostics. In the MRS approach to the diagnosis of disease, it is important that the analysis utilizes all the essential information in the spectra, is robust, and is non-subjective. Although some of the data analytic methods widely used in chemical and biological sciences are sketched, a more extensive discussion is given of a 5-stage Statistical Classification Strategy. This proposes powerful feature selection methods, based on, for example, genetic algorithms and novel projection techniques. The applications of MRS-based metabolomics in breast cancer, prostate cancer, colorectal cancer, pancreatic cancer, hepatobiliary cancers, gastric cancer, and brain cancer have been reviewed. While the majority of these applications relate to body fluids and tissue biopsies, some in vivo applications have also been included. It should be emphasized that the number of subjects studied must be sufficiently large to ensure a robust diagnostic classification. Before MRS-based metabolomics can become a widely used clinical tool, however, certain challenges need to be overcome. These include manufacturing user-friendly commercial instruments with all the essential features, and educating physicians and medical technologists in the acquisition, analysis, and interpretation of metabolomics data.

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Justifying the data analytical choice in single case research in relation to the expected data pattern

10.31234/osf.io/2b9mu ◽

2019 ◽

Author(s):

Rumen Manolov

Keyword(s):

Data Analysis ◽

Visual Analysis ◽

Multilevel Models ◽

Single Case ◽

Analytical Techniques ◽

Real Data ◽

Small Scale ◽

Data User ◽

Single Case Research ◽

User Friendly

The lack of consensus regarding the most appropriate analytical techniques for single-case experimental designs data requires justifying the choice of any specific analytical option. The current text mentions some of the arguments, provided by methodologists and statisticians, in favor of several analytical techniques. Additionally, a small-scale literature review is performed in order to explore if and how applied researchers justify the analytical choices that they make. The review suggests that certain practices are not sufficiently explained. In order to improve the reporting regarding the data analytical decisions, it is proposed to choose and justify the data analytical approach prior to gathering the data. As a possible justification for data analysis plan, we propose using as a basis the expected the data pattern (specifically, the expectation about an improving baseline trend and about the immediate or progressive nature of the intervention effect). Although there are multiple alternatives for single-case data analysis, the current text focuses on visual analysis and multilevel models and illustrates an application of these analytical options with real data. User-friendly software is also developed.

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Simple Equations Pertaining to the Particle Number and Surface Area of Metallic, Polymeric, Lipidic and Vesicular Nanocarriers

Scientia Pharmaceutica ◽

10.3390/scipharm89020015 ◽

2021 ◽

Vol 89 (2) ◽

pp. 15

Author(s):

M. R. Mozafari ◽

E. Mazaheri ◽

K. Dormiani

Keyword(s):

Drug Delivery ◽

Surface Area ◽

Particle Number ◽

Analytical Techniques ◽

Metallic Particles ◽

Nutraceutical Compounds ◽

Mathematical Formulas ◽

Simple Equations

Introduction: Bioactive encapsulation and drug delivery systems have already found their way to the market as efficient therapeutics to combat infections, viral diseases and different types of cancer. The fields of food fortification, nutraceutical supplementation and cosmeceuticals have also been getting the benefit of encapsulation technologies. Aim: Successful formulation of such therapeutic and nutraceutical compounds requires thorough analysis and assessment of certain characteristics including particle number and surface area without the need to employ sophisticated analytical techniques. Solution: Here we present simple mathematical formulas and equations used in the research and development of drug delivery and controlled release systems employed for bioactive encapsulation and targeting the sites of infection and cancer in vitro and in vivo. Systems covered in this entry include lipidic vesicles, polymeric capsules, metallic particles as well as surfactant- and tocopherol-based micro- and nanocarriers.

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cROStalk for Life: Uncovering ROS Signaling in Plants and Animal Systems, from Gametogenesis to Early Embryonic Development

Genes ◽

10.3390/genes12040525 ◽

2021 ◽

Vol 12 (4) ◽

pp. 525

Author(s):

Valentina Lodde ◽

Piero Morandini ◽

Alex Costa ◽

Irene Murgia ◽

Ignacio Ezquer

Keyword(s):

Signal Transduction ◽

Signaling Pathways ◽

Analytical Techniques ◽

Antioxidant Systems ◽

Developmental Studies ◽

Science Field ◽

Ros Signaling ◽

Reproductive Processes

This review explores the role of reactive oxygen species (ROS)/Ca2+ in communication within reproductive structures in plants and animals. Many concepts have been described during the last years regarding how biosynthesis, generation products, antioxidant systems, and signal transduction involve ROS signaling, as well as its possible link with developmental processes and response to biotic and abiotic stresses. In this review, we first addressed classic key concepts in ROS and Ca2+ signaling in plants, both at the subcellular, cellular, and organ level. In the plant science field, during the last decades, new techniques have facilitated the in vivo monitoring of ROS signaling cascades. We will describe these powerful techniques in plants and compare them to those existing in animals. Development of new analytical techniques will facilitate the understanding of ROS signaling and their signal transduction pathways in plants and mammals. Many among those signaling pathways already have been studied in animals; therefore, a specific effort should be made to integrate this knowledge into plant biology. We here discuss examples of how changes in the ROS and Ca2+ signaling pathways can affect differentiation processes in plants, focusing specifically on reproductive processes where the ROS and Ca2+ signaling pathways influence the gametophyte functioning, sexual reproduction, and embryo formation in plants and animals. The study field regarding the role of ROS and Ca2+ in signal transduction is evolving continuously, which is why we reviewed the recent literature and propose here the potential targets affecting ROS in reproductive processes. We discuss the opportunities to integrate comparative developmental studies and experimental approaches into studies on the role of ROS/ Ca2+ in both plant and animal developmental biology studies, to further elucidate these crucial signaling pathways.

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Stereoelectroencephalography

Neurosurgery ◽

10.1227/neu.0b013e31827d1161 ◽

2012 ◽

Vol 72 (3) ◽

pp. 353-366 ◽

Cited By ~ 267

Author(s):

Francesco Cardinale ◽

Massimo Cossu ◽

Laura Castana ◽

Giuseppe Casaceli ◽

Marco Paolo Schiariti ◽

...

Keyword(s):

Interquartile Range ◽

Entry Point ◽

Target Point ◽

Epileptogenic Zone ◽

Localization Error ◽

Drug Resistant ◽

Robot Assisted ◽

Data Set ◽

Essential Information

Abstract BACKGROUND: Stereoelectroencephalography (SEEG) methodology, originally developed by Talairach and Bancaud, is progressively gaining popularity for the presurgical invasive evaluation of drug-resistant epilepsies. OBJECTIVE: To describe recent SEEG methodological implementations carried out in our center, to evaluate safety, and to analyze in vivo application accuracy in a consecutive series of 500 procedures with a total of 6496 implanted electrodes. METHODS: Four hundred nineteen procedures were performed with the traditional 2-step surgical workflow, which was modified for the subsequent 81 procedures. The new workflow entailed acquisition of brain 3-dimensional angiography and magnetic resonance imaging in frameless and markerless conditions, advanced multimodal planning, and robot-assisted implantation. Quantitative analysis for in vivo entry point and target point localization error was performed on a sub-data set of 118 procedures (1567 electrodes). RESULTS: The methodology allowed successful implantation in all cases. Major complication rate was 12 of 500 (2.4%), including 1 death for indirect morbidity. Median entry point localization error was 1.43 mm (interquartile range, 0.91-2.21 mm) with the traditional workflow and 0.78 mm (interquartile range, 0.49-1.08 mm) with the new one (P < 2.2 × 10−16). Median target point localization errors were 2.69 mm (interquartile range, 1.89-3.67 mm) and 1.77 mm (interquartile range, 1.25-2.51 mm; P < 2.2 × 10−16), respectively. CONCLUSION: SEEG is a safe and accurate procedure for the invasive assessment of the epileptogenic zone. Traditional Talairach methodology, implemented by multimodal planning and robot-assisted surgery, allows direct electrical recording from superficial and deep-seated brain structures, providing essential information in the most complex cases of drug-resistant epilepsy.

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Size-based characterization of adalimumab and TNF-α interactions using flow induced dispersion analysis: assessment of avidity-stabilized multiple bound species

Scientific Reports ◽

10.1038/s41598-021-84113-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Morten E. Pedersen ◽

Ragna M. S. Haegebaert ◽

Jesper Østergaard ◽

Henrik Jensen

Keyword(s):

Protein Interactions ◽

Free Ligand ◽

Local Environment ◽

Dispersion Analysis ◽

Surface Immobilization ◽

Covalent Bonds ◽

Essential Information ◽

Tnf Α

AbstractThe understanding and characterization of protein interactions is crucial for elucidation of complicated biomolecular processes as well as for the development of new biopharmaceutical therapies. Often, protein interactions involve multiple binding, avidity, oligomerization, and are dependent on the local environment. Current analytical methodologies are unable to provide a detailed mechanistic characterization considering all these parameters, since they often rely on surface immobilization, cannot measure under biorelevant conditions, or do not feature a structurally-related readout for indicating formation of multiple bound species. In this work, we report the use of flow induced dispersion analysis (FIDA) for in-solution characterization of complex protein interactions under in vivo like conditions. FIDA is an immobilization-free ligand binding methodology employing Taylor dispersion analysis for measuring the hydrodynamic radius (size) of biomolecular complexes. Here, the FIDA technology is utilized for a size-based characterization of the interaction between TNF-α and adalimumab. We report concentration-dependent complex sizes, binding affinities (Kd), kinetics, and higher order stoichiometries, thus providing essential information on the TNF-α–adalimumab binding mechanism. Furthermore, it is shown that the avidity stabilized complexes involving formation of multiple non-covalent bonds are formed on a longer timescale than the primary complexes formed in a simple 1 to 1 binding event.

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CPVA: a web-based metabolomic tool for chromatographic peak visualization and annotation

Bioinformatics ◽

10.1093/bioinformatics/btaa200 ◽

2020 ◽

Vol 36 (12) ◽

pp. 3913-3915

Author(s):

Hemi Luan ◽

Xingen Jiang ◽

Fenfen Ji ◽

Zhangzhang Lan ◽

Zongwei Cai ◽

...

Keyword(s):

False Positive ◽

Supplementary Information ◽

Liquid Chromatography Mass Spectrometry ◽

Targeted Metabolomics ◽

Metabolomics Data ◽

Web Based ◽

Tremendous Amount ◽

Chromatographic Peaks ◽

User Friendly

Abstract Motivation Liquid chromatography–mass spectrometry-based non-targeted metabolomics is routinely performed to qualitatively and quantitatively analyze a tremendous amount of metabolite signals in complex biological samples. However, false-positive peaks in the datasets are commonly detected as metabolite signals by using many popular software, resulting in non-reliable measurement. Results To reduce false-positive calling, we developed an interactive web tool, termed CPVA, for visualization and accurate annotation of the detected peaks in non-targeted metabolomics data. We used a chromatogram-centric strategy to unfold the characteristics of chromatographic peaks through visualization of peak morphology metrics, with additional functions to annotate adducts, isotopes and contaminants. CPVA is a free, user-friendly tool to help users to identify peak background noises and contaminants, resulting in decrease of false-positive or redundant peak calling, thereby improving the data quality of non-targeted metabolomics studies. Availability and implementation The CPVA is freely available at http://cpva.eastus.cloudapp.azure.com. Source code and installation instructions are available on GitHub: https://github.com/13479776/cpva. Supplementary information Supplementary data are available at Bioinformatics online.

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Mapping and Functional Characterization of the TAF11 Interaction with TFIIA

Molecular and Cellular Biology ◽

10.1128/mcb.25.3.945-957.2005 ◽

2005 ◽

Vol 25 (3) ◽

pp. 945-957 ◽

Cited By ~ 19

Author(s):

M. M. Robinson ◽

G. Yatherajam ◽

R. T. Ranallo ◽

A. Bric ◽

M. R. Paule ◽

...

Keyword(s):

Functional Characterization ◽

Regulation Of Gene Expression ◽

Small Subunit ◽

Molecular Organization ◽

Functional Link ◽

Essential Information ◽

Histone Fold ◽

Histone Fold Domain ◽

Promoter Dna

ABSTRACT TFIIA interacts with TFIID via association with TATA binding protein (TBP) and TBP-associated factor 11 (TAF11). We previously identified a mutation in the small subunit of TFIIA (toa2-I27K) that is defective for interaction with TAF11. To further explore the functional link between TFIIA and TAF11, the toa2-I27K allele was utilized in a genetic screen to isolate compensatory mutants in TAF11. Analysis of these compensatory mutants revealed that the interaction between TAF11 and TFIIA involves two distinct regions of TAF11: the highly conserved histone fold domain and the N-terminal region. Cells expressing a TAF11 allele defective for interaction with TFIIA exhibit conditional growth phenotypes and defects in transcription. Moreover, TAF11 imparts changes to both TFIIA-DNA and TBP-DNA contacts in the context of promoter DNA. These alterations appear to enhance the formation and stabilization of the TFIIA-TBP-DNA complex. Taken together, these studies provide essential information regarding the molecular organization of the TAF11-TFIIA interaction and define a mechanistic role for this association in the regulation of gene expression in vivo.

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Catheter microelectrode assembly for in-vivo and in-vitro voltammetric analysis of body fluids

Talanta ◽

10.1016/0039-9140(83)80030-7 ◽

1983 ◽

Vol 30 (2) ◽

pp. 121-123 ◽

Cited By ~ 4

Author(s):

J. Wang ◽

L.D. Hutchins ◽

S. Selim ◽

L.B. Cumming

Keyword(s):

Body Fluids ◽

Voltammetric Analysis

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Ex Vivo Mitochondrial Respiration Parallels Biochemical Response to Ibrutinib in CLL Cells

Cancers ◽

10.3390/cancers13020354 ◽

2021 ◽

Vol 13 (2) ◽

pp. 354

Author(s):

Subir Roy Chowdhury ◽

Cheryl Peltier ◽

Sen Hou ◽

Amandeep Singh ◽

James B. Johnston ◽

...

Keyword(s):

Mitochondrial Respiration ◽

Ex Vivo ◽

Standard Dose ◽

Cell Receptor ◽

Lymphocytic Leukemia ◽

Clinical Tool ◽

Potential Biomarker ◽

Apoptotic Pathways ◽

The Impact

Mitochondrial respiration is becoming more commonly used as a preclinical tool and potential biomarker for chronic lymphocytic leukemia (CLL) and activated B-cell receptor (BCR) signaling. However, respiration parameters have not been evaluated with respect to dose of ibrutinib given in clinical practice or the effect of progression on ibrutinib treatment on respiration of CLL cells. We evaluated the impact of low and standard dose ibrutinib on CLL cells from patients treated in vivo on mitochondrial respiration using Oroboros oxygraph. Cytokines CCL3 and CCL4 were evaluated using the Mesoscale. Western blot analysis was used to evaluate the BCR and apoptotic pathways. We observed no difference in the mitochondrial respiration rates or levels of plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4), β-2 microglobulin (β-2 M) and lactate dehydrogenase (LDH) between low and standard doses of ibrutinib. This may confirm why clinical observations of the safety and efficacy of low dose ibrutinib are observed in practice. Of interest, we also observed that the mitochondrial respiration of CLL cells paralleled the increase in β-2 M and LDH at progression. Our study further supports mitochondrial respiration as a biomarker for response and progression on ibrutinib in CLL cells and a valuable pre-clinical tool.

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