Evaluation of Thermal Liquid Biopsy Analysis of Saliva and Blood Plasma Specimens as a Novel Diagnostic Modality in Head and Neck Cancer.

Background: Over the past decade, saliva-based liquid biopsies have emerged as promising tools for the early diagnosis, prognosis, and monitoring of cancer, particularly in high-risk populations. However, challenges persist because of low concentrations and variable modifications of biomarkers linked to tumor development when compared to normal salivary components.

Methods: This study explores the application of differential scanning calorimetry (DSC)-based thermal liquid biopsy (TLB) for analyzing saliva and blood plasma samples from head and neck cancer (HNC) patients.

Characterization of myocardial injury phenotype by thermal liquid biopsy.

Background And Aims: With the advent and implementation of high-sensitivity cardiac troponin assays, differentiation of patients with distinct types of myocardial injuries, including acute thrombotic myocardial infarction (TMI), acute non-thrombotic myocardial injury (nTMi), and chronic coronary atherosclerotic disease (cCAD), is of pressing clinical importance. Thermal liquid biopsy (TLB) emerges as a valuable diagnostic tool, relying on identifying thermally induced conformational changes of biomolecules in blood plasma. While TLB has proven useful in detecting and monitoring several cancers and autoimmune diseases, its application in cardiovascular diseases remains unexplored.

Plasma Thermogram Parameters Differentiate Status and Overall Survival of Melanoma Patients.

Melanoma is the fifth most common cancer in the United States and the deadliest of all skin cancers. Even with recent advancements in treatment, there is still a 13% two-year recurrence rate, with approximately 30% of recurrences being distant metastases. Identifying patients at high risk for recurrence or advanced disease is critical for optimal clinical decision-making.

Sample Processing Considerations for Protein Stability Studies of Low Concentration Biofluid Samples using Differential Scanning Calorimetry.

Background: The analysis of biofluid samples with low protein content (e.g., urine or saliva) can be challenging for downstream analysis methods with limited sensitivity.

The Utility of Differential Scanning Calorimetry Curves of Blood Plasma for Diagnosis, Subtype Differentiation and Predicted Survival in Lung Cancer.

Early detection of lung cancer (LC) significantly increases the likelihood of successful treatment and improves LC survival rates. Currently, screening (mainly low-dose CT scans) is recommended for individuals at high risk. However, the recent increase in the number of LC cases unrelated to the well-known risk factors, and the high false-positive rate of low-dose CT, indicate a need to develop new, non-invasive methods for LC detection.

Arsenite Exposure Displaces Zinc from ZRANB2 Leading to Altered Splicing.

Exposure to arsenic, a class I carcinogen, affects 200 million people globally. Skin is the major target organ, but the molecular etiology of arsenic-induced skin carcinogenesis remains unclear. Arsenite (As)-induced disruption of alternative splicing could be involved, but the mechanism is unknown.

Multi-group diagnostic classification of high-dimensional data using differential scanning calorimetry plasma thermograms.

The thermoanalytical technique differential scanning calorimetry (DSC) has been applied to characterize protein denaturation patterns (thermograms) in blood plasma samples and relate these to a subject's health status. The analysis and classification of thermograms is challenging because of the high-dimensionality of the dataset. There are various methods for group classification using high-dimensional data sets; however, the impact of using high-dimensional data sets for cancer classification has been poorly understood.

Thermal liquid biopsy for monitoring melanoma patients under surveillance during treatment: A pilot study.

Background: Differential Scanning Calorimetry (DSC) is a technique traditionally used to study thermally induced macromolecular transitions, and it has recently been proposed as a novel approach for diagnosis and monitoring of several diseases. We report a pilot study applying Thermal Liquid Biopsy (TLB, DSC thermograms of plasma samples) as a new clinical approach for diagnostic assessment of melanoma patients.

Methods: Multiparametric analysis of DSC thermograms of patient plasma samples collected during treatment and surveillance (63 samples from 10 patients) were compared with clinical and diagnostic imaging assessment to determine the utility of thermograms for diagnostic assessment in melanoma.

Characterization and classification of lupus patients based on plasma thermograms.

Objective: Plasma thermograms (thermal stability profiles of blood plasma) are being utilized as a new diagnostic approach for clinical assessment. In this study, we investigated the ability of plasma thermograms to classify systemic lupus erythematosus (SLE) patients versus non SLE controls using a sample of 300 SLE and 300 control subjects from the Lupus Family Registry and Repository. Additionally, we evaluated the heterogeneity of thermograms along age, sex, ethnicity, concurrent health conditions and SLE diagnostic criteria.

Application and interpretation of functional data analysis techniques to differential scanning calorimetry data from lupus patients.

Background: DSC is used to determine thermally-induced conformational changes of biomolecules within a blood plasma sample. Recent research has indicated that DSC curves (or thermograms) may have different characteristics based on disease status and, thus, may be useful as a monitoring and diagnostic tool for some diseases. Since thermograms are curves measured over a range of temperature values, they are considered functional data.

Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N-terminal trimethylation.

A subset of B-cell lymphoma patients have dominant mutations in the histone H3 lysine 27 (H3K27) methyltransferase EZH2, which change it from a monomethylase to a trimethylase. These mutations occur in aromatic resides surrounding the active site and increase growth and alter transcription. We study the N-terminal trimethylase NRMT1 and the N-terminal monomethylase NRMT2.

Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities.

Diluted (1%) plasma induces migration of malignant cell lines much more strongly than potent pro-metastatic factors. To characterize the factor(s) present in diluted plasma responsible for this phenomenon we performed i) heat inactivation, ii) dialysis, iii) proteinase K treatment, and iv) molecular size filtration studies. We found that this remarkable pro-migratory activity of diluted normal plasma is associated with a ~50-100-kD protein that interacts with GαI protein-coupled receptors and activates p42/44 MAPK and AKT signaling in target cells.

Differential scanning calorimetry as a complementary diagnostic tool for the evaluation of biological samples.

Background: Differential scanning calorimetry (DSC) is a tool for measuring the thermal stability profiles of complex molecular interactions in biological fluids. DSC profiles (thermograms) of biofluids provide specific signatures which are being utilized as a new diagnostic approach for characterizing disease but the development of these approaches is still in its infancy.

Methods: This article evaluates several approaches for the analysis of thermograms which could increase the utility of DSC for clinical application.

Clinical application of plasma thermograms. Utility, practical approaches and considerations.

Differential scanning calorimetry (DSC) studies of blood plasma are part of an emerging area of the clinical application of DSC to biofluid analysis. DSC analysis of plasma from healthy individuals and patients with various diseases has revealed changes in the thermal profiles of the major plasma proteins associated with the clinical status of the patient. The sensitivity of DSC to the concentration of proteins, their interactions with other proteins or ligands, or their covalent modification underlies the potential utility of DSC analysis.

Pooled preventable death rates in trauma patients : Meta analysis and systematic review since 1990.

Purpose: To estimate the pooled PDRs (preventable death rates) with articles being published since 1990, and compare the differences of PDRs over time and according to the evaluation approaches to determine preventable deaths.

Methods: Articles concerning preventable deaths of trauma patients published between 1990 and 2013 were systematically reviewed, and the pooled PDRs with 95 % confidence intervals were estimated using meta-analysis. It was also observed whether the PDRs differed over time and according to the evaluation approaches employed for determining preventable deaths.

Detection of cervical cancer biomarker patterns in blood plasma and urine by differential scanning calorimetry and mass spectrometry.

Improved methods for the accurate identification of both the presence and severity of cervical intraepithelial neoplasia (CIN) and extent of spread of invasive carcinomas of the cervix (IC) are needed. Differential scanning calorimetry (DSC) has recently been shown to detect specific changes in the thermal behavior of blood plasma proteins in several diseases. This methodology is being explored to provide a complementary approach for screening of cervical disease.

Calorimetric analysis of the plasma proteome: identification of type 1 diabetes patients with early renal function decline.

Background: Microalbuminuria (MA) has been questioned as a predictor of progressive renal dysfunction in patients with type 1 diabetes (T1D). Consequently, new clinical end points are needed that identify or predict patients that are at risk for early renal function decline (ERFD). The potential clinical utility of differential scanning calorimetry (DSC) analysis of blood plasma and other biofluids has recently been reported.

Thermodynamic studies for drug design and screening.

Introduction: A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions.

Areas Covered: This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process.

Structure and stability of higher-order human telomeric quadruplexes.

G-quadruplex formation in the sequences 5'-(TTAGGG)(n) and 5'(TTAGGG)(n)TT (n = 4, 8, 12) was studied using circular dichroism, sedimentation velocity, differential scanning calorimetry, and molecular dynamics simulations. Sequences containing 8 and 12 repeats formed higher-order structures with two and three contiguous quadruplexes, respectively. Plausible structures for these sequences were determined by molecular dynamics simulations followed by experimental testing of predicted hydrodynamic properties by sedimentation velocity.

Allosteric interaction of nucleotides and tRNA(ala) with E. coli alanyl-tRNA synthetase.

Alanyl-tRNA synthetase, a dimeric class 2 aminoacyl-tRNA synthetase, activates glycine and serine at significant rates. An editing activity hydrolyzes Gly-tRNA(ala) and Ser-tRNA(ala) to ensure fidelity of aminoacylation. Analytical ultracentrifugation demonstrates that the enzyme is predominately a dimer in solution.

Statistical analysis of plasma thermograms measured by differential scanning calorimetry.

Melting curves of human plasma measured by differential scanning calorimetry (DSC), known as thermograms, have the potential to markedly impact diagnosis of human diseases. A general statistical methodology is developed to analyze and classify DSC thermograms to analyze and classify thermograms. Analysis of an acquired thermogram involves comparison with a database of empirical reference thermograms from clinically characterized diseases.

An integrated molecular dynamics (MD) and experimental study of higher order human telomeric quadruplexes.

Structural knowledge of telomeric DNA is critical for understanding telomere biology and for the utilization of telomeric DNA as a therapeutic target. Very little is known about the structure of long human DNA sequences that may form more than one quadruplex unit. Here, we report a combination of molecular dynamics simulations and experimental biophysical studies to explore the structural and dynamic properties of the human telomeric sequence (TTAGGG)(8)TT that folds into two contiguous quadruplexes.

Sedimentation velocity ultracentrifugation analysis for hydrodynamic characterization of G-quadruplex structures.

Analytical ultracentrifugation (AUC) is a powerful technique for the characterization of hydrodynamic and thermodynamic properties. The intent of this article is to demonstrate the utility of sedimentation velocity (SV) studies to obtain hydrodynamic information for G-quadruplex (GQ) systems and to provide insights into one part of this process, namely, data analysis of existing SV data. An array of data analysis software is available, mostly written and continually developed by established researchers in the AUC field, with particularly rapid advances in the analysis of SV data.