Tool For Disease Monitoring Research Articles

Importance of circulating tumor DNA analysis at diagnosis in early triple-negative breast cancer patients.

Circulating tumor DNA (ctDNA) enables non-invasive evaluation and is considered a promising tool for diagnosis, treatment selection, risk stratification, and disease monitoring. However, while the utility of ctDNA has been demonstrated in advanced-stage cancers, its detection in early breast cancer (EBC) remains limited. This study investigated the characteristics of EBC patients associated with higher ctDNA detectability. A total of 101 patients with EBC were enrolled. Formalin-fixed paraffin-embedded samples (FFPEs) were obtained from biopsy tissue, and plasma samples were collected before and after neoadjuvant chemotherapy (NAC). Forty-seven breast cancer-related genes were analyzed using next-generation sequencing. The diagnostic performance of ctDNA was evaluated, and logistic regression analyses were conducted to assess the impact of clinical and molecular factors on ctDNA status. The most frequently identified gene was TP53 (FFPE, 66.7%; ctDNA, 46.4%), followed by PIK3CA (FFPE, 36.2%; ctDNA, 17.4%). The diagnostic performance of the three most common genes showed a sensitivity range of 11.1-58.7%, specificity of 78.3-100%, and diagnostic accuracy of 65.2-78.3%. The triple-negative breast cancer (TNBC) subtype exhibited the strongest association with ctDNA detection (odds ratio [OR] 209.50, p = 0.005) in multivariate analysis. Also, those who exhibited ctDNA clearance after NAC had a higher pathological complete response rate compared to those without clearance (38.5% vs. 11.1%, p = 0.238). Our study highlights that ctDNA analysis can complement genetic testing from a single tissue biopsy in breast cancer patients. Furthermore, ctDNA analysis may be particularly important in patients with TNBC.

P0398 Point of Care Intestinal ultrasound – is it the key to reducing the carbon footprint of IBD Care?

Abstract Background Sustainability of IBD care has been identified as a key priority for the coming years by ECCO as part of the REACH strategy. Additionally, the Irish Health Service Climate Action Strategy aims to achieve net-zero emissions by 2050 and provide healthcare that is environmentally and socially sustainable. The STRIDE II consensus discusses new treatment goals in the care of IBD such as endoscopic healing which would require more frequent monitoring. However this poses an environmental burden as one MRI generates approximately 20kg CO2e, 3 times more than a CT scan (7kg CO2e), and 20 times more than an ultrasound (1kg CO2e) and 1 colonoscopy is estimated to generate between 28-55kg CO2e. Decontamination of the endoscope generate a further 11.19 kg CO2e. Point of Care Intestinal ultrasound (POC-IUS) offers a low carbon alternative compared to CT, MRI and endoscopy for disease assessment and monitoring. Aim To calculate the potential reduction in Greenhouse Gas (GHG) emissions from the use of POC-IUS for disease monitoring. Methods A retrospective analysis of all POC-IUS performed over a 12mth period was conducted. We focused on the impact of utilising IUS in the IBD clinic instead of interval MRE or colonoscopy to assess disease activity. The immediate carbon emissions saved as a result of utilising IUS alone was calculated. The long term reduction of carbon emissions over a three year period from using IUS as an alternative tool for disease monitoring was also calculated. Data on patient travel, investigations and associated emissions were collected from the patient health record and calculated on ecotree.green. Results 259 patients were identified who underwent IUS, 92% had Crohns disease. 20% (n=52) of patients had active disease which was followed up by POC-IUS alone. Mean F.Calpro was 495. Consequently, 14 fewer colonoscopies and 43 fewer MRE were performed over the 12mth period due to the immediate assessment offered by IUS corresponding to at least 5460km reduction in travel to and from appointments with an overall reduction in GHG emission of 1,485kg CO2e. Overall, the use of POC-IUS instead of MRE and/or colonoscopy led to an estimated reduction in GHG of 3269kg CO2e. Projecting these results over an interval period where IUS is used as the only primary monitoring tool to assess disease activity showed potential carbon emission savings of 36,531kg C02e.This is equivalent to 15 Round-Trip Flights from New York to London. Conclusion The findings emphasise the role IUS delivered within the IBD clinic might play in reducing the carbon footprint of IBD care. POC-IUS is a low carbon alternative and is a tool in providing a lean care system which are two key principles of delivering a sustainable clinical practice.

Exosomes in Autoimmune Diseases: A Review of Mechanisms and Diagnostic Applications.

Exosomes, small extracellular vesicles secreted by various cell types, have emerged as key players in the pathophysiology of autoimmune diseases. These vesicles serve as mediators of intercellular communication, facilitating the transfer of bioactive molecules such as proteins, lipids, and nucleotide. In autoimmune diseases, exosomes have been implicated in modulating immune responses, oxidative stress, autophagy, gut microbes, and the cell cycle, contributing to disease initiation, progression, and immune dysregulation. Recent advancements in exosome isolation techniques and their molecular characterization have paved the way for exploring their clinical potential as biomarkers and therapeutic targets. This review focuses on the mechanisms by which exosomes influence autoimmune disease development and their potential clinical applications, particularly in diagnosis. The role of exosomes in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), inflammatory bowel disease (IBD), and Sjögren's syndrome (SS), is discussed in relation to their involvements in antigen presentation, T-cell activation, and the induction of inflammatory pathways. Additionally, exosome-based biomarkers offer promising non-invasive diagnostic tools for early diagnostic, disease monitoring, and therapeutic response assessment. However, challenges such as standardization of exosome isolation protocols and validation of their clinical significance remain. This review highlights the potential of exosomes as both diagnostic biomarkers and therapeutic targets in autoimmune diseases, emphasizing the need for further research to overcome current limitations and fully harness their clinical value.

Epidemiology of Mucopolysaccharidosis Type II According to the Register of the Russian Federation.

Objective: The study aimed to evaluate the epidemiological, clinical, and molecular data of mucopolysaccharidosis type II (MPS II) patients and their outcomes using the national registry of patients in the Russian Federation (RF). Materials and Methods: In the retrospective cohort study, the authors included data from the Russian national registry of MPS II. Results: The prevalence of MPS II in RF is 0.62 per 100 000 live births or 0.09 per 100 000 population with the majority of patients in the Central (n = 36) and the Volga Federal District (n = 35). Males were 157 (99.4%), positive MPS II family history had 47 (29.7%) patients. The median age of the first symptoms was 1.8 (0.8-2.6) years, ranging from 0.1 to 19 years, and the age of diagnosis was 4.0 (2.5; 5.9) years, ranging from 0.1 to 38.9 years. A genetic study was available for the analysis in 116 (73.4%) patients. Single nucleotide variants in the IDS gene were found in 98/116 (84.5%) patients, and 18 further patients (15.5%) had gross rearrangements. About 59/98 (60.2%) patients had missense, 15/98 (15.3%) had frame-shift variants, 12/98 (12.2%) had splice site, and 11/98 (11.2%) had nonsense variants. One (1.0%) patient out of 98 patients had a small deletion. Pathogenic, likely pathogenic variants, and variants with uncertain significance were found in 54 (55.1%), 36 (36.7%), and 8 (8.2%) patients, respectively. About 138 (87.3%) patients received enzyme replacement therapy. Conclusion: The prevalence of MPS II in the RF is higher than that in some European countries and closer to the Asian population. The registry is a convenient tool for disease epidemiology and monitoring.

Ingestible Electrochemical Sensors: Emerging Tools for Gastrointestinal Disease Detection and Monitoring

Ingestible Electrochemical Sensors: Emerging Tools for Gastrointestinal Disease Detection and Monitoring

Extracellular Vesicles: Advanced Tools for Disease Diagnosis, Monitoring, and Therapies.

Extracellular vesicles (EVs) are a heterogeneous group of membrane-encapsulated vesicles released by cells into the extracellular space. They play a crucial role in intercellular communication by transporting bioactive molecules such as proteins, lipids, and nucleic acids. EVs can be detected in body fluids, including blood plasma, urine, saliva, amniotic fluid, breast milk, and pleural ascites. The complexity and diversity of EVs require a robust and standardized approach. By adhering to standardized protocols and guidelines, researchers can ensure the consistency, purity, and reproducibility of isolated EVs, facilitating their use in diagnostics, therapies, and research. Exosomes and microvesicles represent an exciting frontier in modern medicine, with significant potential to transform the diagnosis and treatment of various diseases with an important role in personalized medicine and precision therapy. The primary objective of this review is to provide an updated analysis of the significance of EVs by highlighting their mechanisms of action and exploring their applications in the diagnosis and treatment of various diseases. Additionally, the review addresses the existing limitations and future potential of EVs, offering practical recommendations to resolve current challenges and enhance their viability for clinical use. This comprehensive approach aims to bridge the gap between EV research and its practical application in healthcare.

An international disease monitoring tool to estimate the likelihood of entry of animal health hazards from legal trade of live animals and products of animal origin imported from different countries (IDM+)

An international disease monitoring tool to estimate the likelihood of entry of animal health hazards from legal trade of live animals and products of animal origin imported from different countries (IDM+)

BIOM-36. DETECTION OF CIRCULATING TUMOR DNA (CTDNA) IN CEREBROSPINAL FLUID (CSF) IN PATIENTS WITH GLIOBLASTOMA TREATED IN PHASE I CLINICAL TRIAL

Abstract BACKGROUND As circulating tumor DNA (ctDNA) has been shown to be a source of tumor-specific biomarkers, liquid biopsy has emerged as a novel noninvasive tool in diagnosis, disease monitoring and treatment selection in several solid tumors. However, its use in brain tumors remains challenging because ctDNA is commonly not detected in blood. Thus, CSF (cerebrospinal fluid) has emerged as a potential source of ctDNA in the context of brain tumors. PATIENTS AND METHODS We prospectively evaluated the detection of ctDNA in CSF (CSF-ctDNA) +/- blood of patients with pre-treated MTAP-deleted glioblastoma, currently treated in a phase I clinical trial evaluating PRMT5 inhibitors. We did CSF samples at C2D15 and at progression, after patient’s oral and written consent. CSF was collected by lumbar puncture and analyzed with a panel of 35 genes including IDH1-2, TERT promoter and EGFR. Blood was collected, synchronously with CSF, by peripheral veinous punction and analyzed with the Foundation One Liquid CDx panel. RESULTS Between January and April 2024, five patients were included. All of them undergone initial surgical resection and received at least one previous systemic treatment associated with radiotherapy. At least one somatic mutation was identified in each patient, including EGFR amplification in 2/5 patients (40%). CSF was not available at baseline. One patient provided CSF only at progression. Four patients provided CSF at C2D15 on treatment, and among them, one patient was also collected at progression. At data cut-off, one patient was still on treatment. We identified a detectable level of CSF-ctDNA in only one patient with occipital tumor localization, with detection of EGFR amplification known at diagnosis. Synchronous blood analysis showed only clonal hematopoiesis variants. CONCLUSION We showed in this small cohort of patients that detection of CSF-ctDNA is technically feasible. The type of panel used might be optimized for this population especially to monitor patients as a potential surrogate biomarker for treatment response.

Novelty Seeking in Parkinson’s Disease: A Candidate Biomarker for Cognitive Changes

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by motor impairments, cognitive decline, and affective changes. Beyond the well-described motor symptoms, neuropsychiatric symptoms play a crucial role in PD disability burden. Novelty seeking, a trait extensively studied within various models of personality, may influence the manifestation of these non-motor symptoms. Methods: A narrative review of articles determined relevant by the author(s) was undertaken. Results: The literature indicates that PD patients typically exhibit low novelty seeking initially. However, dopaminergic therapies can increase novelty-seeking behaviors, sometimes leading to impulse control disorders (ICD). Studies using the Temperament and Character Inventory (TCI) suggest a complex interplay between disease state, medication, and baseline personality, which is not fully elucidated. High novelty seeking scores predict a higher risk of ICDs, yet they also correlate with a more benign clinical phenotype and improved quality of life post-DBS surgery. Conclusions: Novelty seeking is a significant trait in PD, influencing non-motor symptoms and treatment responses. Understanding its neurobiological basis and clinical implications could lead to better diagnostic and therapeutic strategies through the use of objective, practical tools for disease monitoring, individualized therapy, and pharmacological development.

Liquid Biopsy in Neuropsychiatric Disorders: A Step Closer to Precision Medicine.

Psychiatric disorders are among the leading causes of disease burden worldwide. Despite their significant impact, their diagnosis remains challenging due to symptom heterogeneity, psychiatric comorbidity, and the lack of objective diagnostic tests and well-defined biomarkers. Leveraging genomic, epigenomic, and fragmentomic technologies, circulating cell-free DNA (ccfDNA)-based liquid biopsies have emerged as a potential non-invasive diagnosis and disease-monitoring tool. ccfDNA is a DNA species released into circulation from all types of cells through passive and active mechanisms and can serve as a biomarker for various diseases, namely, cancer. Despite their potential, the application of ccfDNA in neuropsychiatry remains underdeveloped. In this review, we provide an overview of liquid biopsies and their components, with a particular focus on ccfDNA. With a summary of pre-analytical practices and current ccfDNA technologies, we highlight the current state of research regarding the use of ccfDNA as a biomarker for neuropsychiatric disorders. Finally, we discuss future steps to unlock ccfDNA's potential in clinical practice.

The Role of Deep Learning and Gait Analysis in Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is the second most common movement disorder in the world. It is characterized by motor and non-motor symptoms that have a profound impact on the independence and quality of life of people affected by the disease, which increases caregivers' burdens. The use of the quantitative gait data of people with PD and deep learning (DL) approaches based on gait are emerging as increasingly promising methods to support and aid clinical decision making, with the aim of providing a quantitative and objective diagnosis, as well as an additional tool for disease monitoring. This will allow for the early detection of the disease, assessment of progression, and implementation of therapeutic interventions. In this paper, the authors provide a systematic review of emerging DL techniques recently proposed for the analysis of PD by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Scopus, PubMed, and Web of Science databases were searched across an interval of six years (between 2018, when the first article was published, and 2023). A total of 25 articles were included in this review, which reports studies on the movement analysis of PD patients using both wearable and non-wearable sensors. Additionally, these studies employed DL networks for classification, diagnosis, and monitoring purposes. The authors demonstrate that there is a wide employment in the field of PD of convolutional neural networks for analyzing signals from wearable sensors and pose estimation networks for motion analysis from videos. In addition, the authors discuss current difficulties and highlight future solutions for PD monitoring and disease progression.

Unveiling therapeutic biomarkers and druggable targets in ALS: An integrative microarray analysis, molecular docking, and structural dynamic studies

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a debilitating neurodegenerative disorder characterized by the progressive degeneration of nerve cells in the brain and spinal cord. Despite extensive research, its precise etiology remains elusive, and early diagnosis is challenging due to the absence of specific tests. This study aimed to identify potential blood-based biomarkers for early ALS detection and monitoring using datasets from whole blood samples (GSE112680) and oligodendrocytes, astrocytes, and fibroblasts (GSE87385) obtained from the NCBI-GEO repository. Through bioinformatics analysis, including protein-protein interactions and molecular pathway analyses, we identified differentially expressed genes (DEGs) associated with ALS. Notably, ALS2, ADH7, ALDH8A1, ALDH3B1, ABHD2, ABHD17B, ABHD12, ABHD13, PGAM2, AURKB, ANAPC11, VAPA, UNC45B, and TNNT2 emerged as top-ranked DEGs, implicated in drug metabolism, protein depalmytilation, and the AKT/mTOR signaling pathways. Among these, AurKB established as a potential therapeutic biomarker with relevance to various neurological conditions. Consequently, AurKB was selected for identifying potential therapeutic molecules and utilized for in silico structural characterization studies. Exploration of the IMPATT database led to the discovery of a lead compound similar to Fostamatinib, currently used for AurKB. Initial molecular docking and MMGBSA-based binding energy analysis were followed by molecular dynamics simulation (MDS) and free energy landscape (FEL) analysis to validate the ligand's binding efficacy and understand dynamic processes within the biological system. The identified potential biomarkers and lead molecule provide novel insights into the correlation between blood cell transcripts and ALS pathology, paving the way for blood-based diagnostic tools for early ALS detection and ongoing disease monitoring.

New Approaches to Plant Pathogen Detection and Disease Diagnosis.

Detecting plant pathogens and diagnosing diseases are critical components of successful pest management. These key areas have undergone significant advancements driven by breakthroughs in molecular biology and remote sensing technologies within the realm of precision agriculture. Notably, nucleic acid amplification techniques, with recent emphasis on sequencing procedures, particularly next-generation sequencing, have enabled improved DNA or RNA amplification detection protocols that now enable previously unthinkable strategies aimed at dissecting plant microbiota, including the disease-causing components. Simultaneously, the domain of remote sensing has seen the emergence of cutting-edge imaging sensor technologies and the integration of powerful computational tools, such as machine learning. These innovations enable spectral analysis of foliar symptoms and specific pathogen-induced alterations, making imaging spectroscopy and thermal imaging fundamental tools for large-scale disease surveillance and monitoring. These technologies contribute significantly to understanding the temporal and spatial dynamics of plant diseases.

Artificial Intelligence- and Physician-Interpreted Stool Image Characteristics Correlate With C-Reactive Protein Among Inpatients With Acute Severe Ulcerative Colitis: A Pilot Study.

Stool characteristics are used as a measure of ulcerative colitis (UC) disease activity, but they have not been validated against objective inflammation. We aimed to determine whether stool characteristics measured by trained artificial intelligence (AI) and physicians correlate with inflammation in UC. Patients hospitalized with acute severe UC (ASUC) were asked to capture images of all bowel movements using a smartphone application (Dieta®). Validated AI was used to measure five stool characteristics including the Bristol stool scale. Additionally, four physicians scored each image for blood amount, mucus amount, and whether stool was in a toilet or commode. AI measurements and mean physician scores were rank-normalized and correlated with rank-normalized CRP values using mixed linear regression models. Mann-Whitney tests were used to compare median CRP values of images with and without mucus and with and without blood. We analyzed 151 stool images collected from 5 patients admitted with ASUC (mean age 42 years, 40% male). Overall, Bristol stool scale and fragmentation positively correlated with CRP, while stool consistency negatively correlated with CRP. The median CRP of images with mucus was higher than that of images without mucus. Smartphone application AI measurements of Bristol stool scale, stool consistency, and stool fragmentation significantly correlate with CRP values in hospitalized patients with ASUC. Additionally, median CRPs are higher when mucus is seen. Further training of smartphone-based AI algorithms to validate the association of stool characteristics with objective inflammation may yield a novel, noninvasive tool for UC disease monitoring.

Utilization and impact of esophageal string testing in children with eosinophilic esophagitis: A 1 year experience.

The 1-h esophageal string test (EST) is a minimally invasive test that can be used to monitor eosinophilic esophagitis (EoE) disease activity and guide treatment without endoscopy. We aimed to describe the real-world utilization and impact of EST on the care of children with EoE over the first year this was used at our center. Between 12/1/2022 and 11/30/2023, 39 ESTs were successful in 45 attempts (87% completion rate) in 31 patients. Five patients underwent multiple ESTs. Adverse events during the EST included vomiting. Reasons for failure to complete the EST (13%, n = 6) were patients could not swallow the capsule (n = 5) and vomiting (n = 1). EST was used to assess EoE without the need for endoscopy in 95% (n = 37) of cases. Treatment approach varied based on whether the EST indicated active (38.5%) or inactive (61.5%) EoE. The EST is a well-tolerated minimally invasive disease monitoring tool for patients with EoE.

Exploring Canine Mammary Cancer through Liquid Biopsy: Proteomic Profiling of Small Extracellular Vesicles.

(Background). Canine mammary tumors (CMTs) have emerged as an important model for understanding pathophysiological aspects of human disease. Liquid biopsy (LB), which relies on blood-borne biomarkers and offers minimal invasiveness, holds promise for reflecting the disease status of patients. Small extracellular vesicles (SEVs) and their protein cargo have recently gained attention as potential tools for disease screening and monitoring. (Objectives). This study aimed to isolate SEVs from canine patients and analyze their proteomic profile to assess their diagnostic and prognostic potential. (Methods). Plasma samples were collected from female dogs grouped into CMT (malignant and benign), healthy controls, relapse, and remission groups. SEVs were isolated and characterized using ultracentrifugation (UC), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Proteomic analysis of circulating SEVs was conducted using liquid chromatography-mass spectrometry (LC-MS). (Results). While no significant differences were observed in the concentration and size of exosomes among the studied groups, proteomic profiling revealed important variations. Mass spectrometry identified exclusive proteins that could serve as potential biomarkers for mammary cancer. These included Inter-alpha-trypsin inhibitor heavy chain (ITIH2 and ITI4), phosphopyruvate hydratase or alpha enolase (ENO1), eukaryotic translation elongation factor 2 (eEF2), actin (ACTB), transthyretin (TTR), beta-2-glycoprotein 1 (APOH) and gelsolin (GSN) found in female dogs with malignant tumors. Additionally, vitamin D-binding protein (VDBP), also known as group-specific component (GC), was identified as a protein present during remission. (Conclusions). The results underscore the potential of proteins found in SEVs as valuable biomarkers in CMTs. Despite the lack of differences in vesicle concentration and size between the groups, the analysis of protein content revealed promising markers with potential applications in CMT diagnosis and monitoring. These findings suggest a novel approach in the development of more precise and effective diagnostic tools for this challenging clinical condition.

Exploring the biology of ctDNA release in colorectal cancer

BackgroundCirculating tumor DNA (ctDNA) has emerged as a promising tool for early cancer detection and minimal residual disease monitoring. However, the biology underlying ctDNA release and its variation across cancer types and histologies remains poorly understood. This study investigated the biology behind ctDNA shedding in colorectal cancer. MethodsThe study included a local cohort of 747 stage I-III colorectal cancer patients. All patients had ctDNA measurement prior to treatment and extensive clinical data. Primary tumor RNA sequencing and whole exome sequencing was performed in 95 and 652 patients respectively. Additionally, the study evaluated 89 non-small cell lung cancer patients from the TRACERx cohort, comprising primary tumor RNA sequencing and ctDNA measurement. ResultsWe found tumor size and proliferative capacity to be key factors associated with ctDNA shedding in colorectal cancer. Furthermore, we found that the secretory and CMS3 colorectal cancer subtypes exhibited lower ctDNA shedding, while microsatellite instability (MSI) tumors had higher levels of ctDNA. Mutational analysis did not reveal any genes or pathways associated with ctDNA shedding in colorectal cancer. A comparison of transcriptomic profiles across multiple cancer types demonstrated that colorectal cancer and lung squamous cell carcinoma tumors shared a high-proliferative ctDNA shedding phenotype, while lung adenocarcinoma tumors displayed a distinct low-proliferative subgroup. Additionally, proliferation levels correlated with ctDNA detection sensitivity across multiple cancer types. ConclusionThese findings suggest that tumor size and proliferative capacity are drivers of ctDNA release in colorectal cancer and provide insights into the biology of ctDNA shedding on a pan-cancer level.

Molecular characterization and biomarker identification in pediatric B-cell acute lymphoblastic leukemia.

6524 Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent hematologic malignancy in children and a leading cause of mortality. Despite high cure rates, the management of B-ALL remains challenging due to its high heterogeneity and propensity for relapse. This study aimed to delineate molecular features of pediatric B-ALL and explore the clinical utility of circulating tumor DNA (ctDNA) as a biomarker in B-ALL. Methods: The study analyzed 146 primary pediatric B-ALL patients who were diagnosed from August 2020 to April 2023 and received systemic chemotherapy in Wuhan Children's Hospital. Baseline bone marrow (BM) and plasma samples were collected for next-generation sequencing (NGS) to profile the mutational landscape. BM samples collected on day 19 of the treatment were utilized for minimal residual disease (MRD) testing to assess treatment efficacy. Transcriptomic profiling of baseline BM samples was performed via bulk RNA sequencing. Fisher's exact test and the Wilcoxon rank sum test were utilized to compare categorical and continuous variables between groups, respectively. A two‐tailed P-value<0.05 was considered statistically significant unless indicated otherwise. Results: Transcriptomic analysis revealed that 86.3% of patients (126 out of 146) could be categorized into 13 distinct molecular subtypes, with hyperdiploidy emerging as the predominant subtype. Baseline BM NGS identified gene fusions in 61% of patients, including 37 novel fusions previously unreported in B-ALL. Specifically, the KMT2A-TRIM29 novel fusion was detected and validated in a male child diagnosed with the KMT2A-rearranged subtype. Despite initially responding well to therapy, the patient experienced disease progression after a year, indicating a poor prognosis. We also found that elevated mutant counts and maximum-variant-allele-frequency (maxVAF) in baseline BM were associated with significantly poorer response to chemotherapy ( P=0.0012 and 0.028, respectively). Additionally, MRD-negative patients exhibited upregulated expression of immune-related pathways ( P<0.01) and increased CD8+ T cell infiltration ( P=0.047), indicating a more active immune microenvironment in better responding tumors. Baseline plasma ctDNA, which exhibited high mutational concordance with paired baseline BM samples, also demonstrated significant associations with chemotherapy efficacy, highlighting its potential as a non-invasive tool for disease monitoring and treatment outcome prediction. Conclusions: This study elucidated novel gene fusions and potential biomarkers for treatment response in pediatric B-ALL. Importantly, both baseline plasma ctDNA and BM samples offer promising prognostic insights into chemotherapy responses, paving the way for non-invasive monitoring strategies in the management of pediatric B-ALL.

Evaluation of the clinical use of MGMT methylation in extracellular vesicle-based liquid biopsy as a tool for glioblastoma patient management

Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings.

Optimisation of analytical methods for tuberculosis drug detection in wastewater: A multinational study

Wastewater-based epidemiology (WBE) is a robust tool for disease surveillance and monitoring of pharmaceutical consumption. However, monitoring tuberculosis (TB) drug consumption faces challenges due to limited data availability. This study aimed to optimise methods for detecting TB drugs in treated and untreated wastewater from four African countries: South Africa, Nigeria, Kenya, and Cameroon. The limit of detection (LOD) for these drugs ranged from a minimum of 2.20 (±1.02) for rifampicin to a maximum of 2.95 (±0.79) for pyrazinamide. A parallel trend was observed concerning the limit of quantification (LOQ), with rifampicin reporting the lowest average LOQ of 7.33 (±3.44) and pyrazinamide showing the highest average LOQ of 9.81 (±2.64). The variance in LOD and LOQ values could be attributed to factors such as drug polarity. Erythromycin and rifampicin exhibited moderately polar LogP values (2.6 and 2.95), indicating higher lipid affinity and lower water affinity.Conversely, ethambutol, pyrazinamide, and isoniazid displayed polar LogP values (−0.059, −0.6, and −0.7), suggesting lower lipid affinity and greater water affinity. The study revealed that storing wastewater samples for up to 5 days did not result in significant drug concentration loss, with concentration reduction remaining below 1 log throughout the storage period. Application of the optimised method for drug detection and quantification in both treated and untreated wastewater unveiled varied results. Detection frequencies varied among drugs, with ethambutol consistently most detected, while pyrazinamide and isoniazid were least detected in wastewater from only two countries. Most untreated wastewater samples had undetectable drug concentrations, ranging from 1.21 ng/mL for erythromycin to 54.61 ng/mL for isoniazid. This variability may suggest differences in drug consumption within connected communities. In treated wastewater samples, detectable drug concentrations ranged from 1.27 ng/mL for isoniazid to 10.20 ng/mL for ethambutol. Wastewater treatment plants exhibited variable removal efficiencies for different drugs, emphasising the need for further optimisation. Detecting these drugs in treated wastewater suggests potential surface water contamination and subsequent risks of human exposure, underscoring continued research's importance.