Circulating microRNA-155-3p levels predicts response to first line immunotherapy in patients with metastatic renal cell carcinoma.

Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment (TME) and the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties. We evaluated the presence of immune-specific extracellular vesicle (EV) microRNAs in the plasma of patients with metastatic RCC (mRCC) prior to initiation of ICI. We found significantly lower levels of microRNA155-3p (miR155) in responders to ICI, when compared to non-responders. This microRNA has unique immunomodulatory properties, thus providing potential biological rationale for our findings. Our results support further work in exploring microRNAs as potential biomarkers of response to immunotherapy.

Belzutifan: a novel therapeutic for the management of von Hippel-Lindau disease and beyond.

The identification of the VHL gene and its role in regulating the hypoxia-inducible factor signaling pathway has helped to revolutionize the treatment of renal cell carcinoma (RCC). Belzutifan is a novel small-molecule inhibitor of hypoxia-inducible factor 2α which has demonstrated efficacy in treating von Hippel-Lindau (VHL) disease, earning regulatory approvals for this indication. There is also early evidence for efficacy in sporadic RCC. Belzutifan has a favorable safety profile. Several clinical trials are currently ongoing, which should help in identifying this promising drug's role in RCC and beyond. This review summarizes the history, pharmacology and clinical evidence for belzutifan use to date, and also explores unanswered questions as they relate to this novel therapeutic agent.

The novel drug belzutifan was developed after years of research in identifying the VHL gene and how genetic abnormalities in VHL may result in tumor growth. Belzutifan has been approved for use in patients with VHL disease ­ a rare familial disorder first described in the 19th century that presents with a variety of cancerous and noncancerous tumors, including kidney cancer. Growing evidence supports belzutifan's use in non-familial kidney cancer as well. This is important because most patients eventually develop resistance to the currently available cancer treatments, highlighting the need for drugs with a different mechanism of action. Belzutifan works by blocking a protein called HIF-2a, which causes tumor growth in patients with VHL disease. Belzutifan is well tolerated, with the most common side effects being low energy, hemoglobin and blood oxygen. This review summarizes the history, mechanism of action and research evidence to date supporting the use of belzutifan in VHL disease and cancer treatment. We also discuss future directions, including remaining clinical questions and areas of ongoing research.

Graphsene as a novel porous two-dimensional carbon material for enhanced oxygen reduction electrocatalysis.

Graphene allotropes with varied carbon configurations have attracted significant attention for their unique properties and chemical activities. This study introduces a novel two-dimensional carbon-based material, termed Graphsene (GrS), through theoretical study. Comprising tetra-, penta-, and dodeca-carbon rings, GrS's cohesive energy calculations demonstrate its superior structural stability over existing graphene allotropes, including graphyne and graphdiyne families. Phonon dispersion analysis confirms GrS's dynamic stability and its relatively low thermal conductivity. All calculated GrS elastic constants meet the Born criteria, ensuring mechanical stability. Ab-initio molecular dynamic simulations show GrS maintains its structure at 300 K. HSE06 calculations reveal a narrow electronic bandgap of 20 meV, with the electronic band structure featuring a highly anisotropic Dirac-like cone due to its intrinsic structural anisotropy along armchair and zigzag directions. Notably, GrS is predicted to offer exceptional catalytic performance for the oxygen reduction reaction, favoring the four-electron reduction pathway with high selectivity under both acidic and alkaline conditions. This discovery opens promising avenues for developing metal-free catalyst materials in clean energy production.

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer.

No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org ). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

Corpus Callosum Functional Activities in Children with Cerebral Palsy.

Background: Since cerebral palsy (CP) is a corollary to brain damage, persistent treatment should accompany an alteration in brain functional activity in line with clinical improvements. In this regard, the corpus callosum (CC), as a connecting bridge between the two hemispheres, plays an essential role. Objective: This study aimed to investigate the therapeutic effects of occupational therapy (OT) on CC functional activity and walking capacity in children with cerebral palsy. Material and Methods: In this clinical trial study, 4 children with CP (8.25±1.71 years) received 45 min OT sessions 3 times weekly for 8 weeks. Functional magnetic resonance imaging (fMRI) was acquired while conducting passive motor tasks to quantify CC activation. The pre-post activation changes in CC following therapy were quantified in terms of activated voxels. Walking capacity was evaluated using the timed-up-and-go (TUG), 6-minute walk test (6 MWT), and 10-meter walk test (10 MWT) in pre-and post-treatment. Results: The number of activated voxels in CC indicated significant improvement in participants. Post-treatment activated voxels substantially exceeded pre-treatment active voxels. Clinical measures, including TUG, 6 MWT, and 10 MWT are improved by 11.9%, 12.6%, and 25.4%, respectively. Conclusion: Passive task-based fMRI can detect the effects of OT on CC functional activity in children with CP. According to the results, OT improves CC functional activity in addition to gait and balance performance.

Confirmatory factor analysis and gender invariance of Persian version of the modified Yale food addiction scale (mPYFAS) 2.0: insight from a large scale Iranian sample.

BACKGROUND: The Modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) was developed with the primary objective of evaluating food addiction (FA). The present study aimed to undertake the translation, pilot testing, and evaluation of the psychometric properties of the mYFAS 2.0 within the Persian-speaking population. METHODS: The transcultural adaptation of the mYFAS 2.0 to the Persian language was conducted. Data collection was carried out through an anonymous online questionnaire. Participants completed the Persian versions of the mYFAS 2.0, Binge Eating Scale (BES), Barratt Impulsivity Scale (BIS-11), and Connor-Davidson Resilience Scale (CD-RISC). The assessment encompassed the evaluation of internal consistency reliability, factor structure, as well as convergent and discriminant validity of the aforementioned questionnaires. RESULTS: Confirmatory factor analysis revealed that the single-factor model of the Persian translation of mYFAS 2.0 performed satisfactorily, with comparative fit index (CFI) and Tucker-Lewis index (TLI) values exceeding 0.95, standardized root mean square residual (SRMR) less than or equal to 0.09, and root mean square error of approximation (RMSEA) below 0.03. The internal consistency and composite reliability of the mYFAS 2.0 were favorable in the entire sample, as well as in both male and female groups, with alpha (α) values of 0.83, ordinal alpha (αord) of 0.93, and composite reliability (CR) of 0.86. Additionally, significant relationships were observed between the total score of BES (r = 0.59, p < 0.001), BIS-11 (r = - 0.16, p < 0.001), and CD-RISC (r = 0.22, p < 0.001) with mYFAS 2.0-diagnosed FA presence, severity, and symptom count. CONCLUSIONS: The Persian version of the mYFAS 2.0 exhibited satisfactory psychometric properties.

In this study, researchers developed a Persian version of the Modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) to assess food addiction in Persian-speaking individuals. They translated and tested the scale's reliability and validity through an online survey with 9606 Persian speaking participants. The results showed that the Persian mYFAS 2.0 performed well, with a reliable single-factor model. The internal consistency and reliability were good across the entire sample and in both male and female groups. The relationships between mYFAS 2.0 and other scales measuring binge eating, impulsivity, and resilience were significant. The findings suggest that the Persian version of mYFAS 2.0 is a reliable tool for assessing food addiction in the Persian-speaking population. The study used statistical analyses like confirmatory factor analysis, indicating the scale's robustness. Overall, the psychometric properties of the Persian mYFAS 2.0 were satisfactory, providing a valuable instrument for researchers and healthcare professionals studying and addressing food addiction in this population. The study contributes to cross-cultural research and enhances our understanding of food addiction in diverse linguistic communities.

Cell death classification: A new insight based on molecular mechanisms.

Cells tend to disintegrate themselves or are forced to undergo such destructive processes in critical circumstances. This complex cellular function necessitates various mechanisms and molecular pathways in order to be executed. The very nature of cell death is essentially important and vital for maintaining homeostasis, thus any type of disturbing occurrence might lead to different sorts of diseases and dysfunctions. Cell death has various modalities and yet, every now and then, a new type of this elegant procedure gets to be discovered. The diversity of cell death compels the need for a universal organizing system in order to facilitate further studies, therapeutic strategies and the invention of new methods of research. Considering all that, we attempted to review most of the known cell death mechanisms and sort them all into one arranging system that operates under a simple but subtle decision-making (If \ Else) order as a sorting algorithm, in which it decides to place and sort an input data (a type of cell death) into its proper set, then a subset and finally a group of cell death. By proposing this algorithm, the authors hope it may solve the problems regarding newer and/or undiscovered types of cell death and facilitate research and therapeutic applications of cell death.

Evaluation of the c-Fos expression in the hippocampus after fatigue caused by one session of endurance exercise in pre-pubertal and adult rats.

PURPOSE: Central fatigue plays an important role in reducing endurance exercise activity during brain development. c-Fos gene expression in the hippocampus was examined as an indicator of neuronal activation after exhaustion. METHODS: Eighteen pre-pubertal male rats at four weeks old and 18 adult rats at eight weeks were randomly divided into three groups: Control (C), Constant time exercise (CTEx), Endurance Exercise until Exhaustion (ExhEx), which started at two minutes and ended in 20 min, the main swimming test was performed with a weight equal to 5% of the bodyweight attached to the rats' tail as a single session in experimental groups and was recorded at the end of their time, while to evaluate the force loss, the Grip strength was measured before and after the activity. The brain activation rate was examined by c-Fos gene expression and Nissl staining in CA3 and dentate gyrus (DG) in the hippocampus of all groups. RESULTS: Power grip and Nissl positive neurons in CA3 and DG have been significantly higher in pre-pubertal rats than in adults, both in the CTEx group (p = 0.04) and in the ExhEx group (p < 0.001). Also, real-time exhaustion in the pre-pubertal group was significantly longer than in adults. c-Fos gene expression was significantly reduced in adults' hippocampus in comparison to preadolescence (p < 0.01) and control (p < 0.001). CONCLUSION: These findings clarified that increased strength and longer fatigue in pre-puberal rats may lead to c-Fos gene expression and decreased neurons in the hippocampus. Perhaps this is a protective effect to suppress stress hormones.

Less force loss and longer real-time exhaustion in pre-pubertal subjects.There was no significant reduction in c-Fos gene expression in the hippocampus of pre-pubertal rats after exhaustion.The Nissl positive neurons in CA3 and DG of the Hippocampus are significantly lower in the exhausted adult rat in comparison with the pre-pubertal group.

Correlation Between Serum Homocysteine Levels and Carotid Intima-media Thickening in Hemodialysis Patients.

NTRODUCTION: Hyperhomocysteinemia is an important risk factor for cardiovascular disease in ESKD patients. Homocysteine, as an inflammatory factor, and carotid intima-media thickness (CIMT) could predict atherosclerosis in hemodialysis-treated ESKD patients. In this regard, the present study was conducted to investigate serum homocysteine level and its relationship with internal carotid intima thickness in ESKD patients undergoing routine hemodialysis. METHODS: This study comprised 56 ESKD patients, older than 40 years, undergoing hemodialysis for at least 1 year. All participants were taking Nephrovit for at least 6 months. The study participants were patients who underwent ultrasonography for CIMT determination and laboratory test Results. There was no statistically significant relationship between the mean homocysteine level and hypertension, diabetes mellitus, duration of dialysis, and body mass index (BMI). Among the study participants, the results also showed that the mean value of CMIT homocysteine and C-reactive protein (CRP) were 0.89 millimeters, 30.44 (mcmol/L), and 35.60 mg/L; respectively. Despite hypertension, there was a significant difference between the mean values of CMIT in patients with diabetes mellitus and those who had been on dialysis for a longer period (more than 3 years). Also, the mean value of CMIT was significantly higher in obese patients than those with normal BMI. None of the other variables including homocysteine serum level, C-reactive protein (CRP), and CMIT showed a significant correlation. CONCLUSION: The results of the study suggest that there is no relationship between serum homocysteine level and carotid intima-media thickness in hemodialysis patients.  DOI: 10.52547/ijkd.7424.

Biomarkers for Immune Checkpoint Inhibitors in Renal Cell Carcinoma.

Immune checkpoint inhibitor (ICI) therapy has revolutionized renal cell carcinoma treatment. Patients previously thought to be palliative now occasionally achieve complete cures from ICI. However, since immunotherapies stimulate the immune system to induce anti-tumor immunity, they often lead to adverse autoimmunity. Furthermore, some patients receive no benefit from ICI, thereby unnecessarily risking adverse events. In many tumor types, PD-L1 expression levels, immune infiltration, and tumor mutation burden predict the response to ICI and help inform clinical decision making to better target ICI to patients most likely to experience benefits. Unfortunately, renal cell carcinoma is an outlier, as these biomarkers fail to discriminate between positive and negative responses to ICI therapy. Emerging biomarkers such as gene expression profiles and the loss of pro-angiogenic proteins VHL and PBRM-1 show promise for identifying renal cell carcinoma cases likely to respond to ICI. This review provides an overview of the mechanistic underpinnings of different biomarkers and describes the theoretical rationale for their use. We discuss the effectiveness of each biomarker in renal cell carcinoma and other cancer types, and we introduce novel biomarkers that have demonstrated some promise in clinical trials.

Novel Hybrid Inulin-Soy Protein Nanoparticles Simultaneously Loaded with (-)-Epicatechin and Quercetin and Their In Vitro Evaluation.

(-)-Epicatechin and quercetin have attracted considerable attention for their potential therapeutic application in non-communicable chronic diseases. A novel hybrid inulin-soy protein nanoparticle formulation was simultaneously loaded with (-)-epicatechin and quercetin (NEQs) to improve the bioavailability of these flavonoids in the human body, and NEQs were synthesized by spray drying. After process optimization, the physicochemical and functional properties of NEQs were characterized including in vitro release, in vitro gastrointestinal digestion, and cell viability assays. Results showed that NEQs are an average size of 280.17 ± 13.42 nm and have a zeta potential of -18.267 ± 0.83 mV in the organic phase. Encapsulation efficiency of (-)-epicatechin and quercetin reached 97.04 ± 0.01 and 92.05 ± 1.95%, respectively. A 3.5% soy protein content conferred controlled release characteristics to the delivery system. Furthermore, NEQs presented inhibitory effects in Caco-2, but not in HepG-2 and HDFa cell lines. These results contribute to the design and fabrication of inulin-soy protein nanoparticles for improving the bioavailability of multiple bioactive compounds with beneficial properties.

A comprehensive investigation of the plasmonic-photocatalytic properties of gold nanoparticles for CO2 conversion to chemicals.

Understanding the interactions between plasmonic gold (Au) nanoparticles and the adsorbate is essential for photocatalytic and plasmonic applications. However, it is often challenging to identify a specific reaction mechanism in the ground state and to explore the optical properties in the excited states because of the complicated pathways of carriers. In this study, photocatalytic reduction of carbon dioxide (CO2) to C1 products (for example, CO and CH4) on the Au(111) nanoparticle (NP) surface was studied based on reaction pathway analysis, adsorbate reactivity, and its ability to stabilize or deactivate the surface. The calculated reaction Gibbs free energies and activation barriers revealed that the first step in CO reduction via a direct hydrogen transfer mechanism on Au(111) is the formation of formyl (*CHO) instead of hydroxymethylidyne (*COH). Furthermore, the size enhanced and symmetry sensitive optical responses of cuboctahedral Au(111) NPs on localized surface plasmon resonance (LSPR) were investigated by using time-dependent DFT (TDDFT) calculations. Although near field enhancement around cuboctahedral Au(111) NPs is only weakly dependent on the morphology of NPs, it was observed that corner sites stabilize *C-species to drive the CO2 reduction to CO. The density of active surface states interacting with the adsorbate states near the Fermi level gradually decreases from the (111) on-top site toward the corner site of the Au(111) NP-CO system, which strongly affects the molecule's binding on catalytic sites and, in particular, electronic excitation. Finally, the spatial distribution of the charge oscillations was determined as a guide for the fabrication of Au NPs with an optimal LSPR response.

Autophagic Molecular Alterations in the Mouse Cerebellum Experimental Autoimmune Encephalomyelitis Model Following Treatment with Cannabidiol and Fluoxetine.

The crosstalk between autophagy and apoptosis is one of the most important processes involved in the cell program death, and several mechanisms including oligodendrocyte apoptosis and autophagy play significant roles in activating macrophages, microglial cells, and finally demyelination in neurodegenerative disease. The antidepressants and anti-apoptotic mechanisms of fluoxetine (FLX) and cannabidiol (CBD) commence an autophagic event that can effectively repair myelin. This study aimed to investigate the effect of those reagents on the rate of demyelination in the cerebellum, an important site for white matter in a mouse model of experimental autoimmune encephalomyelitis (EAE). EAE was induced in twenty four adult female C57Bl/6 mice were inducted the EAE model; FLX treatment which was performed (10 mg/kg/IP) and CBD; were treated (5 mg/kg/IP); and their cerebellum was used for Western blotting, real-time PCR to autophagic markers of LC3II, Beclin-1, and apoptotic markers Bax and Bcl2 evaluation and Luxol Fast Blue staining to the assessment of demyelination. The level of autophagic markers was expressively elevated (P < 0.01) but the pro-apoptotic markers and Bax/Bcl2 ratio were reduced (P < 0.05). Luxol Fast Blue staining confirmed the noteworthy diminution of demyelination in treatment groups (P < 0.001). This finding clarified that FLX and CBD ameliorate the severity of the EAE model. Combinatory treatments of these two agents are suggested for future investigations.

Morin improves Bisphenol-A-induced toxicity in the rat testicular mitochondria and sperms.

OBJECTIVE: The present study aimed to examine the ameliorative effects of Morin (MRN) on Bisphenol-A (BPA)-induced oxidative stress in testicular mitochondria and sperm quality of rats. METHODS: BPA and MRN (25, 50, and 100 µM) were given to the spermatozoa and testicular tissue mitochondria. The sperm quality, mitochondrial viability, and MMP (mitochondrial membrane potential) were examined. Superoxide dismutase, CAT (catalase), malondialdehyde, and reactive oxygen species (ROS) levels of rat testicular mitochondria were measured. RESULTS: BPA raised mitochondrial oxidative stress biomarkers, whereas antioxidant acclivity and MMP were significantly lowered. BPA significantly lowered the normality, viability, and motility of the sperms. MRN dose-dependently lowered oxidative stress of the mitochondria, raised MMP, as well as improved the percentage of abnormality, motility, and viability of the sperms. CONCLUSIONS: These data demonstrated that MRN dose-dependently attenuated BPA-induced mitochondrial damage and improved sperm quality by preventing oxidative stress.

Validation and Psychological Properties of the Persian Version of DSM 5 Yale Food Addiction Scale 2.0 (PYFAS 2.0) in Non-clinical Population.

Background: The Yale Food Addiction Scale version 2.0 (YFAS 2.0) is used for the assessment of food addiction (FA). This research intended to evaluate the validity of the Persian translation of the questionnaire and to investigate the psychological properties and the association between FA and anthropometric indices. Methods: In a sample of 473 nonclinical participants, FA, binge eating, and objectively measured anthropometric indices were assessed. Internal consistency, convergent, and validity of the PYFAS 2.0 were examined. Also, the factor structure (confirmatory factor analysis following the 11 diagnostic indicators in addition to the significant distress) and the construct of the scale were evaluated. Findings: The frequencies of mild, moderate, and severe FA based on PYFAS 2.0 were 0.2%, 10%, and 5.5%, respectively. The findings supported a one-factor structure. The confirmatory factor analysis revealed a good construct validity (RMSEA=0.043, χ2=76.38, df=41, χ2 (CMIN)/df=1.862, GFI=0.975, AGFI=0.957, IFI=0.986, RFI=0.958, ECVI=0.319, TLI=0.978). For both the diagnostic and symptom count versions, the PYFAS 2.0 presented acceptable internal consistency (IC) (Kuder-Richardson 20=0.99 and McDonald omega=0.91). Conclusion: The PYFAS 2.0 was a psychometrically sound instrument in an Iranian non-clinical population. This questionnaire can be used to study FA in Persian non-clinical populations. Future research should study the psychometric characteristics of this scale in high-risk groups.

TP53 Alterations Are Associated With Poor Survival in Patients With Primary Mediastinal Nonseminoma Germ Cell Tumors.

BACKGROUND: Primary mediastinal nonseminoma germ cell tumors (PMNSGCT) are a subgroup of nonseminoma germ cell tumors (GCT) with poor prognosis. In this study, PMNSGCT-specific genomic landscape was analyzed and correlated with clinical outcomes. METHODS: DNA was extracted and sequenced from 28 archival tumor tissue of patients with mediastinal GCT (3 seminoma and 25 nonseminoma). Overall survival (OS) and association with gene alterations were estimated using the Kaplan-Meier and univariate Cox regression methods. RESULTS: Three patients (11%) had a karyotype XXY, 17/28 (61%) tumor samples presented chromosome 12p amplification. Somatic mutations were detected in 19/28 (68%) samples. The most frequently mutated genes were: TP53 (13/28; 46%), KIT (5/28; 18%), and KRAS (5/28; 18%). Deleterious TP53 alterations were associated with significantly reduced overall survival (HR: 7.16; P = .012). CONCLUSIONS: TP53 alterations are common in PMNSGCT and are associated with reduced overall survival, potentially underlying the poor sensitivity to chemotherapy observed in these patients.

Protective effects of Herbal Compound (IM253) on the inflammatory responses and oxidative stress in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a multifactorial chronic inflammatory demyelinating disease of the central nervous system with both immune and neurodegenerative components as the underlying causes. Cytokines are key components of the inflammatory processes and their crucial roles in the inflammatory aspect of MS are undeniable. Several studies have pointed to the apparent change in Cytokines in MS. The aim of this study was to investigate the effects of IM253 treatment on inflammation and antioxidant defense in the cerebral corpus callosum of the C57BL/6 mouse, an Experimental autoimmune encephalomyelitis (EAE) model and as a most commonly used experimental model of MS. During the course of study, clinical evaluation was performed and eventually histological and molecular analysis on brain samples was carried out. Gene expression analyses demonstrated that treatment with IM253 causes a significant reduction in the expression of pro-inflammatory cytokine coding genes including IL-6, TNF-α, IFN-γ, and IL-17 as well as a significant increase in the expression of anti-inflammatory and anti-oxidant enzyme coding genes including TGF-ß, GPX-1, and Cat. Histological studies also show that treatment with IM253 can reduce demyelination and inflammation (p<0.001). In addition, the GPX-1 enzyme activity evaluation also demonstrated that total antioxidant capacity was significantly higher in IM253 treated mice (p<0.001). Overall, our results suggest that IM253 could ameliorate the severity of EAE, probably because of its anti-inflammatory and anti-oxidant properties, and support the preclinical effects of IM253 as a potential therapeutic intervention.

Emerging Role of Biomarkers in Testicular Germ Cell Tumors.

PURPOSE OF REVIEW: This review will focus on biomarkers in testicular germ cell tumors (TGCT), focusing on microRNAs with high potential clinical application to drive management of TGCT. We explore the mechanism of action of microRNAs, literature to date, and how microRNAs may be incorporated into clinical practice in the near future. RECENT FINDINGS: MicroRNAs are small non-coding RNAs found in blood which play an important role in post-transcriptional gene regulation and have been explored in TGCT for the past 15 years. More recently, results show they are promising biomarkers for diagnosis with impressive sensitivity and specificity, while also being cost-effective. MicroRNAs will likely play a critical role in areas of unmet need in GCT in the next decade, as they have many of the characteristics of an ideal biomarker. Ongoing prospective clinical trials evaluating microRNA-371 will be eagerly awaited and will help inform decision-making in real-world application.