Components Of Body Fluids Research Articles

The Role of Liquid Biopsy in Gastroenteropancreatic Neuroendocrine Neoplasms.

Neuroendocrine neoplasms incidence has been increasing, arising the need for precise and early diagnostic tools. Liquid biopsy (LB) offers a less invasive alternative to tissue biopsy, providing real-time molecular information from circulating tumour components in body fluids. The aim of this review is to analyse the current evidence concerning LB in NENs and its role in clinical practice. We conducted a systematic review in July 2024 focusing on LB applications in NENs, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), micro RNA (miRNA), messenger RNA (mRNA) and extracellular vesicles. Sixty-five relevant articles were analysed. The LB showed potential in diagnosing and monitoring NENs. While CTCs face limitations due to low shedding, ctDNA provides valuable information on high-grade neoplasms. MiRNA and mRNA (e.g., the NETest) offer high sensitivity and specificity for diagnosis and prognosis, outperforming traditional markers like chromogranin A. The LB has significant potential for NEN diagnosis and monitoring but lacks widespread clinical integration due to limited prospective studies and guidelines, requiring further validation. Advances in sequencing technologies may enhance the clinical utility of LB in NENs. Future research should focus on refining LB methods, standardising protocols and exploring applications in high-grade NENs.

Liquid Biopsy in the Clinical Management of Cancers.

Liquid biopsy, a noninvasive diagnosis that examines circulating tumor components in body fluids, is increasingly used in cancer management. An overview of relevant literature emphasizes the current state of liquid biopsy applications in cancer care. Biomarkers in liquid biopsy, particularly circulating tumor DNA (ctDNA), circulating tumor RNAs (ctRNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), and other components, offer promising opportunities for early cancer diagnosis, treatment selection, monitoring, and disease assessment. The implementation of liquid biopsy in precision medicine has shown significant potential in various cancer types, including lung cancer, colorectal cancer, breast cancer, and prostate cancer. Advances in genomic and molecular technologies such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR) have expanded the utility of liquid biopsy, enabling the detection of somatic variants and actionable genomic alterations in tumors. Liquid biopsy has also demonstrated utility in predicting treatment responses, monitoring minimal residual disease (MRD), and assessing tumor heterogeneity. Nevertheless, standardizing liquid biopsy techniques, interpreting results, and integrating them into the clinical routine remain as challenges. Despite these challenges, liquid biopsy has significant clinical implications in cancer management, offering a dynamic and noninvasive approach to understanding tumor biology and guiding personalized treatment strategies.

Microfluidic platform for the enzymatic pretreatment of human serum for the detection of the tuberculosis biomarker mannose-capped lipoarabinomannan.

Tuberculosis (TB) represents a major public health threat, with millions of new cases reported worldwide each year. A major hurdle to curtailing the spread of this disease is the need for low-cost, point-of-care (PoC) diagnostics. Mannose-capped lipoarabinomannan, a significant component of the Mycobacterium tuberculosis bacillus, has been heavily studied as a biomarker for TB, but with little success due to its complexation with endogenous components of body fluids in a manner that sterically interferes with its detection by ELISA and other immunoassays. Recent work by our group and others has shown that complexation can be disrupted with protein-denaturing protocols. By way of followup, we recently described an enzymatic digestion (Proteinase K) sample pretreatment that enables quantitative recovery of ManLAM spiked into healthy human control serum. Herein, we report on the transfer of our benchtop sample pretreatment methodology to an automated microfluidic platform. We show that this platform can be configured to: (1) carry out the pretreatment process with very little user interaction and, (2) yield recoveries for ManLAm spiked into control serum which are statistically indistinguishable from those achieved by the benchtop process. Plans to integrate this device with a portable sample reader as a possible basis for a PoC TB diagnostic system and analyze patient samples are briefly discussed.

Evaluation of Physiochemical and Biological Properties of Biofunctionalized Mg-Based Implants Obtained via Large-Scale PEO Process for Dentistry Applications.

An increasing number of tooth replacement procedures ending with implant failure generates a great need for the delivery of novel biomedical solutions with appropriate mechanical characteristics that would mimic natural tissue and undergo biodegradation. This phenomenon constitutes a significant difficulty for scientists, since currently applied biomaterials dedicated for this purpose are based on stainless steel, Ti, and Ti and CoCr alloys. One of the most promising raw materials is magnesium, which has been proven to promote bone regeneration and accelerate the tissue healing process. Nevertheless, its high reactivity with body fluid components is associated with fast and difficult-to-control biocorrosion, which strongly limits the application of Mg implants as medical devices. The achievement of appropriate functionality, both physiochemical and biological, to enable the commercial use of Mg biomaterials is possible only after their superficial modification. Therefore, the obtainment of uniform, reproducible coatings increasing resistance to the aqueous environment of the human body combined with a nanostructured surface that enhances implant-cell behaviors is an extremely important issue. Herein, we present a successful strategy for the modification of Mg implants via the PEO process, resulting in the obtainment of biomaterials with lower corrosion rates and superior biological properties, such as the promotion of extracellular matrix formation and a positive impact on the proliferation of MG-63 cells. The implants were investigated regarding their chemical composition using the FT-IR and XRD methods, which revealed that MgO layer formation, as well as the incorporation of electrolyte components such as fluorine and silica, were responsible for the increased microhardness of the samples. An extensive study of the biomaterials' morphology confirmed that successful surface modification led to a microporous structure suitable for the attachment and proliferation of cells. The three-layer nature of the newly-formed coatings, typical for PEO modification, was confirmed via cross-section analysis. A biocorrosion and biodegradation study proved that applied modification increased their resistance to body fluids. The cell culture study performed herein confirmed that the correct adjustment of modification parameters results in a lack of cytotoxicity of the magnesium implants, cell proliferation enhancement, and improvement in extracellular matrix formation.

Amplification of SERS Signal of Methotrexate Using Beta-Cyclodextrin Modified Silver Nanoparticles

The paper describes the use of native β-cyclodextrin (CD) for the modification of silver nanoparticles (AgNPs) in order to improve the determination of the anticancer drug methotrexate (MTX) using surface-enhanced Raman spectroscopy (SERS). A control experiment with unmodified AgNPs showed that the strong SERS signal of MTX can only be achieved in alkaline media. However, competitive interactions and the strong background signal of human body fluid components significantly challenge MTX determination in real samples. While previous reports propose the use of thorough sample pretreatment (e.g., solid phase extraction), the application of CD-modified AgNPs increases the SERS signal of MTX in neutral media by seven times which enables simplifying the analysis and improving its accuracy by reducing the influence of endogenous components of body fluids. A detailed study of the synthesis conditions (CD concentration and reaction time) and SERS registration conditions (pH, NaCl concentration, dilution of urine samples) was performed to maximize the analytical signal and signal-to-noise ratio. The final assay was tested for MTX determination in artificially spiked samples of real human urine. The results demonstrated that MTX can be determined within the concentration range suitable for therapeutic drug monitoring (20–300 μg mL−1) with satisfactory precision (6–15% RSD), accuracy (95–111% apparent recovery), and limit of detection (0.3 μg mL−1).

Cyclodextrin-assisted SERS determination of fluoroquinolone antibiotics in urine and blood plasma

This paper describes the use of cyclodextrins (CDs) to improve the determination of fluoroquinolone antibiotics in human body fluids using surface-enhanced Raman spectroscopy (SERS). CDs were used to (i) prepare the CD-SERS substrate (synthesis and stabilization of silver nanoparticles), (ii) increase the sensitivity of the assay by enhancing the interaction between analyte molecules and the substrate, and (iii) improve the analysis accuracy by reducing the interaction between the substrate and endogenous components of body fluids. Two native CDs (α-CD and β-CD) and two of their derivatives with hydroxypropyl groups were tested, and the best results were obtained with CD-SERS substrate prepared using native β-CD. The CD-SERS assay has been developed and optimized for the determination of commonly used and structurally related fluoroquinolones (ciprofloxacin, norfloxacin, pefloxacin, and levofloxacin) in urine and blood plasma samples. Importantly, the non-significant difference in the interaction of the CD-modified SERS substrate with various fluoroquinolones has been successfully used to develop a versatile assay suitable for the analyte-class-specific analysis. Calibration plots were obtained for concentration ranges suitable for the determination of the antibiotics in urine (50–500 μg mL−1) and blood plasma (1–6 μg mL−1). The following figures of merit were obtained (for urine and blood plasma, respectively): RSD values are ≤15% and ≤23%, LOD values are 2.9–5.8 and 0.05–0.34 μg mL−1, recovery ranges are 96–105% and 91–111%. In addition, the influence of excessive concentrations of some main endogenous components of the body fluids on the analytical signal was studied. This step was used to evaluate possible limitations of the assay associated with the deviation of the composition of the body fluid matrix. Therefore, accounting for the short analysis time (≤15 min) and the use of a portable Raman spectrometer, the proposed assay can be suggested for therapeutic drug monitoring in hospitals.

Accelerating the Development and Validation of Liquid Biopsy for Early Cancer Screening and Treatment Tailoring.

Liquid biopsy (LB) is a minimally invasive method which aims to detect circulating tumor-derived components in body fluids. It provides an alternative to current cancer screening methods that use tissue biopsies for the confirmation of diagnosis. This paper attempts to determine how far the regulatory, policy, and governance framework provide support to LB implementation into healthcare systems and how the situation can be improved. For that reason, the European Alliance for Personalised Medicine (EAPM) organized series of expert panels including different key stakeholders to identify different steps, challenges, and opportunities that need to be taken to effectively implement LB technology at the country level across Europe. To accomplish a change of patient care with an LB approach, it is required to establish collaboration between multiple stakeholders, including payers, policymakers, the medical and scientific community, and patient organizations, both at the national and international level. Regulators, pharma companies, and payers could have a major impact in their own domain. Linking national efforts to EU efforts and vice versa could help in implementation of LB across Europe, while patients, scientists, physicians, and kit manufacturers can generate a pull by undertaking more research into biomarkers.

Water quality and the impact to the health

Water is the major constituent of the human body. Water is essential for life and maintaining optimal levels of hydration is important for humans to function well. Water makes up a large proportion of our body weight, distributed between the intracellular (inside cells) and extracellular (water in the blood and in between cells) compartments. Water is the major component of body fluids, such as blood, synovial fluid (fluid in the joints), saliva and urine, which perform vital functions in the body. Human body cannot produce enough water by metabolism or obtain enough water by food ingestion to fulfil its needs. As a consequence, we need to pay attention to what we drink throughout the day to ensure that we are meeting our daily water needs, as not doing so may have negative health effects.

Predicting Corrosion Delamination Failure in Active Implantable Medical Devices: Analytical Model and Validation Strategy.

The ingress of body fluids or their constituents is one of the main causes of failure of active implantable medical devices (AIMDs). Progressive delamination takes its origin at the junctions where exposed electrodes and conductive pathways enter the implant interior. The description of this interface is considered challenging because electrochemically-diffusively coupled processes are involved. Furthermore, standard tests and specimens, with clearly defined 3-phase boundaries (body fluid-metal-polymer), are lacking. We focus on polymers as substrate and encapsulation and present a simple method to fabricate reliable test specimens with defined boundaries. By using silicone rubber as standard material in active implant encapsulation in combination with a metal surface, a corrosion-triggered delamination process was observed that can be universalised towards typical AIMD electrode materials. Copper was used instead of medical grade platinum since surface energies are comparable but corrosion occurs faster. The finding is that two processes are superimposed there: First, diffusion-limited chemical reactions at interfaces that undermine the layer adhesion. The second process is the influx of ions and body fluid components that leave the aqueous phase and migrate through the rubber to internal interfaces. The latter observation is new for active implants. Our mathematical description with a Stefan-model coupled to volume diffusion reproduces the experimental data in good agreement and lends itself to further generalisation.

Beneficial Effects on Brain Micro-Environment by Caloric Restriction in Alleviating Neurodegenerative Diseases and Brain Aging.

Aging and neurodegenerative diseases are frequently associated with the disruption of the extracellular microenvironment, which includes mesenchyme and body fluid components. Caloric restriction (CR) has been recognized as a lifestyle intervention that can improve long-term health. In addition to preventing metabolic disorders, CR has been shown to improve brain health owing to its enhancing effect on cognitive functions or retarding effect on the progression of neurodegenerative diseases. This article summarizes current findings regarding the neuroprotective effects of CR, which include the modulation of metabolism, autophagy, oxidative stress, and neuroinflammation. This review may offer future perspectives for brain aging interventions.

Hand-Held Raman Spectrometer-Based Dual Detection of Creatinine and Cortisol in Human Sweat Using Silver Nanoflakes.

The conventional tissue biopsy method yields isolated snapshots of a narrow region. Therefore, it cannot facilitate comprehensive disease characterization and monitoring. Recently, the detection of tumor-derived components in body fluids─a practice known as liquid biopsy─has attracted increased attention from the biochemical research and clinical application viewpoints. In this vein, surface-enhanced Raman scattering (SERS) has been identified as one of the most powerful liquid-biopsy analysis techniques, owing to its high sensitivity and specificity. Moreover, it affords high-capacity spectral multiplexing for simultaneous target detection and a unique ability to obtain intrinsic biomolecule-fingerprint spectra. This paper presents the fabrication of silver nanosnowflakes (SNSFs) using the polyol method and their subsequent dropping onto a hydrophobic filter paper. The SERS substrate, which comprises the SNSFs and hydrophobic filter paper, facilitates the simultaneous detection of creatinine and cortisol in human sweat using a hand-held Raman spectrometer. The proposed SERS system affords Raman spectrometry to be performed on small sample volumes (2 μL) to identify the normal and at-risk creatinine and cortisol groups.

Serum levels of macro minerals (trace elements) in some local fresh water fishes during breeding period

The role of macro minerals (trace mineral elements) in biological systems has been described in several animals. However, the knowledge in fish is mainly limited to iron, copper, manganese, zinc and selenium as components of body fluids, cofactors in enzymatic raactions, structural units of non- enzymatic macromolecules, etc. Investigations in fish are comparatively complicated as both dietary intake and water borne mineral uptake have to be considered in deterging the mineral budgets. The importance of trace minerals as essential ingredients in diets, although in small quantities, is also evident in fish. Serum levels of some important macro minerals such as sodium (Na+), potassium (K+), calcium (Ca),phosphorous and magnesium (Mg) have been studied in four freshwater fishes collected from a local market as these fishes are edible fishes and are extensively purchased by the local public in the Kalaburagi city. These minerals play significant role in accumulation of nutrients, osmoregulation, homeostasis and other physiological activities of the fish particularly during breeding period. The blood serum level of these macro minerals determined in four local fresh water fishes are, Labeo rohita, Catla catla, Cirrhana mrigala and Pangusius becocurti. The results of macro mineral concentration level were compared among them and it is indicated that there is difference. The serum sodium level in all the four types of fishes is at higher level in comparison to other minerals. The variation and the order of concentration of minerals in all four types of fishes found to be as: sodium> potassium> phosphorous> calcium> magnesium. The aquatic body in which these fishes are harbored has required mineral concentration needed for various physiological activities in the process of nutritional absorption, osmoregulation and homeostatic mechanisms. Hence, the levels of blood serum macro minerals found in these fishes are though lesser during breeding period in the present study are considered to be in normal levels as reported in other fishes.

Molecular and Circulating Biomarkers of Brain Tumors.

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations. While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.

Combining ion chromatography with mass spectrometry and inductively coupled plasma-mass spectrometry: Annual review 2020.

The demand for analyzing low molecular weight polar and ionic components in body fluids, pharmaceutical formulations, food, environmental samples, and drinking water is increasing. Ion chromatography (IC) offers significant advantages over RPLC and HILIC due to a complementary chromatographic selectivity, a different retention mechanism, and a high tolerance toward complex matrices. A continuously regenerated membrane desalter simplifies the combination of IC-applications with MS- or MS/MS-detection, improving the sensitivity and specificity. Analytical workflows are streamlined, providing higher sample throughput. Combining IC with ICP-MS simplifies the speciation analysis of inorganic and organic polar components. The knowledge about the distribution of an element among chemical species in a sample is essential due to significantly different toxicological or environmental properties. This annual review evaluates the literature published from late 2019 until November 2020.

Molecular Characterizations of Double-Stranded RNA Degrading Nuclease Genes from Ostrinia nubilalis.

Simple SummaryRNA interference is a gene suppression tool that uses double-stranded RNA to prevent specific genes from producing proteins. By targeting essential genes RNA interference can be developed for control of insect pests. Unfortunately, RNA interference is not equally effective for all insects. Previous investigation suggested that RNA is rapidly digested by unidentified components of body fluids in the European corn borer caterpillar. We characterized genes encoding proteins from European corn borer that are associated with RNA digestion in other insects. Our results suggest that two proteins (RNA interference efficiency-related nuclease and double-stranded RNA-degrading endonuclease 2) may be responsible for digesting RNAs in the European corn borer gut, whereas two other proteins (double-stranded RNA-degrading endonuclease 1 and double-stranded RNA-degrading endonuclease 4) may be responsible for digesting RNA in European corn borer body fluid. These findings suggest digestion of RNA in the European corn borer is likely due to the activity of these proteins. These findings provide information about the mechanism(s) influencing RNA stability in insects. The knowledge generated by this study will facilitate the development of strategies for enhancing RNA interference in insects.Variable RNA interference (RNAi) efficiencies limit RNAi-based pest management strategies for many pests. Previous efforts to understand mechanisms contributing to low RNAi efficiency indicate that double-stranded RNA (dsRNA) is degraded in the European corn borer (ECB), Ostrinia nubilalis, due to nuclease activity. To investigate the contribution of dsRNA-degrading endonucleases (dsRNases) and lepidopteran-specific RNAi efficiency-related nucleases (REases) to dsRNA instability and low RNAi efficiency in ECB, five complementary DNAs putatively encoding four dsRNases (OndsRNase1, 2, 3, and 4) and one REase (OnREase) were sequenced. Characterization of these transcripts revealed that substrate specificity might vary among the four dsRNases due to different amino acid combinations in the substrate-binding sites. Gene expression analysis indicated that OndsRNase2 and OnREase were highly expressed in the larval gut, and OndsRNase1 showed the highest expression in hemolymph, especially in older developmental stages. Transcript level analysis after dsRNA exposure revealed that expression of OnREase rapidly increased upon dsRNA ingestion or injection, whereas OndsRNase4 expression only increased after long-term ingestion of dsRNA. While the biological function of these nucleases remains to be verified, our results suggest that OnREase and OndsRNase2, and OndsRNase1 and OndsRNase4 may be responsible for degradation of dsRNAs in the ECB gut and hemolymph, respectively, thereby contributing to low RNAi efficiency.

Analysis of Contents of Calcium, Magnesium and Total Hardness in Water for Pharmaceutical Use

Water is one of the most frequently used raw materials in pharmaceutical industry. Water for pharmaceutical purposes includes the two primary water types: purified water and water for injection. Drinking water used for obtaining purified water is not official in pharmacopoeia. Depending on quality prescribed for a certain product preparation, various water types and procedures have been used to prepare pharmaceutical industry water. Possible ways to obtain water for pharmaceutical purposes are: reverse osmosis, demineralization, electrodeionization, ultrafiltration, distillation. Reasons for the widespread use of water lie in the facts that it is capable of dissolving a great number of therapeutic substances, compatible with a large number of substances, appropriate to be used from a physiological aspect given that it is an integral part of the cell and the major component of body fluids and whenever the drug is administered in the form of an aqueous solution, reabsorption is rapid and complete, it also has suitable physical-chemical properties. In this study, analysis results of 15 samples of water were obtained using pharmacopoeial methods for pharmaceutical purposes. Results showed that 86.6% of water samples were accurate and 13.3% did not have appropriate calcium content, magnesium content and total hardness values.

Functionalization of the Parylene C Surface Enhances the Nucleation of Calcium Phosphate: Combined Experimental and Molecular Dynamics Simulations Approach.

Interactions at the solid–body fluid interfaces play a vital role in bone tissue formation at the implant surface. In this study, fully atomistic molecular dynamics (MD) simulations were performed to investigate interactions between the physiological components of body fluids (Ca2+, HPO42–, H2PO4–, Na+, Cl–, and H2O) and functionalized parylene C surface. In comparison to the native parylene C (−Cl surface groups), the introduction of −OH, −CHO, and −COOH surface groups significantly enhances the interactions between body fluid ions and the polymeric surface. The experimentally observed formation of calcium phosphate nanocrystals is discussed in terms of MD simulations of the calcium phosphate clustering. Surface functional groups promote the clustering of calcium and phosphate ions in the following order: −OH > −CHO > −Cl (parent parylene C) ≈ −COO–. This promoting role of surface functional groups is explained as stimulating the number of Ca2+ and HPO42– surface contacts as well as ion chemisorption. The molecular mechanism of calcium phosphate cluster formation at the functionalized parylene C surface is proposed.

Pulsed Electrical Stimulation Enhances Body Fluid Transport for Collagen Biomineralization.

Mechanical loads from physiologic activities such as walking and running generate bioelectricity in bones. By mimicking bioelectricity, external electrical stimulations have also been used therapeutically to stimulate bone-forming cells and, thus, to promote bone regeneration. However, little is known about the physicochemical mechanism(s) by which electrical stimulations drives calcium phosphate mineralization of collagen. Here, we showed that, during in vitro collagen mineralization in the absence of cells, application of pulsed electrical stimulation significantly enhanced the transport of ionic body fluid components through a micrometer-scale channel (∼100-200 μm gap space between the inner surfaces of tube-like collagen scaffolds and a cathode placed inside the collagen scaffolds). The enhanced transport of ionic precursors increased diffusion of the charged precursors from the channel to the inner collagen surface, where bone mineralization was otherwise restricted. The results indicate that pulsed electrical signals can locally accelerate the nucleation of calcium phosphate nanocrystals in or on collagen, allowing us to better control the spatial distribution of the nanocrystals at the microscale. The findings from this study provide insights into the utilization of electrical stimulation for applications such as facilitating bone-fracture healing and designing better bone-specific biomaterials.

Progress in Microfluidics-Based Exosome Separation and Detection Technologies for Diagnostic Applications.

Exosomes are secreted by most cell types and circulate in body fluids. Recent studies have revealed that exosomes play a significant role in intercellular communication and are closely associated with the pathogenesis of disease. Therefore, exosomes are considered promising biomarkers for disease diagnosis. However, exosomes are always mixed with other components of body fluids. Consequently, separation methods for exosomes that allow high-purity and high-throughput separation with a high recovery rate and detection techniques for exosomes that are rapid, highly sensitive, highly specific, and have a low detection limit are indispensable for diagnostic applications. For decades, many exosome separation and detection techniques have been developed to achieve the aforementioned goals. However, in most cases, these two techniques are performed separately, which increases operation complexity, time consumption, and cost. The emergence of microfluidics offers a promising way to integrate exosome separation and detection functions into a single chip. Herein, an overview of conventional and microfluidics-based techniques for exosome separation and detection is presented. Moreover, the advantages and drawbacks of these techniques are compared.

Liquid biopsy in central nervous system metastases: a RANO review and proposals for clinical applications.

Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a surrogate for tumor tissue in the management of both primary and secondary brain tumors. Herein we critically review available literature on spinal fluid and plasma circulating tumor cells (CTCs) and cell-free tumor (ctDNA) for diagnosis and monitoring of leptomeningeal and parenchymal brain metastases. We discuss technical issues and propose several potential applications of liquid biopsies in different clinical settings (ie, for initial diagnosis, for assessment during treatment, and for guidance of treatment decisions). Last, ongoing clinical studies on CNS metastases that include liquid biopsies are summarized, and recommendations for future clinical studies are provided.