Use Of Biomarkers Research Articles

Abstract IA025: A DNA methylation atlas of normal human cell types

Abstract DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies. Citation Format: Tommy Kaplan. A DNA methylation atlas of normal human cell types [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA025.

Implications of molecular classifications in glioma surgery.

The incorporation of molecular markers into neuro-oncology has transformed our understanding of adult diffuse gliomas. While surgical resection is the mainstay of treatment for many patients with gliomas, surgical management strategies warrant re-exploration in the context of characteristic molecular profiles. We reviewed the neurosurgical and neuro-oncological literature for studies investigating surgery in molecularly defined cohorts of adult diffuse gliomas. We discuss key molecular markers associated with the three subtypes of adult diffuse glioma: glioblastoma IDH-wildtype, astrocytoma IDH-mutant, and oligodendroglioma IDH-mutant and 1p/19q codeleted. We additionally discuss surgical strategies and extent of resection in these tumors, framing them in the context of key molecular alterations. Finally, we briefly discuss the practical utility of molecular markers in guiding surgical decision making. Molecular markers in gliomas are of growing relevance to surgical intervention. Advancements in preoperative and intraoperative molecular diagnostics will increase the utility of molecular biomarkers in informing surgical decision-making for patients with gliomas.

Abstract 4120196: Temporal Trends and Predictors of Cardiac Biomarker Testing in the Emergency Department, 2014-2021

Background: Presenting symptoms risk stratify patients presenting to the Emergency Department (ED) to determine their likelihood of having a myocardial infarction (MI) and need for cardiac biomarker testing. Since the 2014 AHA/ACC non-ST segment elevation MI (NSTEMI) guideline, little is known regarding cardiac biomarker testing trends in the United States. Methods: We analyzed data from the National Hospital Ambulatory Medical Care Survey for consecutive adult ED visits between 2014 and 2021 in the United States. The primary outcome was the proportion of ED visits where cardiac biomarker testing occurred. Subgroup analysis was performed for visits with chest pain, non-chest pain anginal equivalents, and non-anginal symptoms. Survey-weighted multivariable logistic regression was used to generate adjusted odds ratios (aOR) to assess predictors of cardiac biomarker utilization. Results: In total, 87,965 ED visits were sampled, representing a weighted total of 644,531,395 visits. Cardiac biomarker testing occurred in 7.21% of all ED visits (95% CI, 6.27%-8.29%) and increased over time (Figure, P =0.03 for trend). When stratified by symptoms, utilization of testing mainly increased among patients with non-chest pain anginal equivalents (Figure, P =0.02 for trend). Cardiac biomarker testing was most frequently used for patients with chest pain (34.9%) and non-chest pain anginal equivalents (39.3%). Nonetheless, 25.8% of patients who underwent testing had no chest pain or anginal equivalents. Cardiac biomarker testing was more frequent among patients with older age (aOR 1.03 per year, 95% CI 1.03-1.04), tachycardia (aOR 1.26, 95% CI 1.13-1.41), tachypnea (aOR 1.71, 95% CI 1.47-1.98), history of heart failure (aOR 1.33, 95% CI 1.15-1.54), prior venous thromboembolism (aOR 1.43, 95% CI 1.12-1.83), and those treated in a rural setting (aOR 1.63, 95% CI 1.14-2.32). Conclusion: Cardiac biomarker testing in the ED has increased over time, mostly attributed to increased utilization among patients with a low pre-test probability of MI. Notably, 25% of individuals who underwent cardiac biomarker testing had no chest pain or anginal-equivalent symptoms. More judicious utilization of cardiac biomarker testing may be needed.

The Emergence of Saliva as a Diagnostic and Prognostic Tool for Viral Infections

Saliva has emerged as a promising diagnostic fluid for viral infections, enabling the direct analysis of viral genetic material and the detection of infection markers such as proteins, metabolites, microRNAs, and immunoglobulins. This comprehensive review aimed to explore the use of saliva as a diagnostic tool for viral infections, emphasizing its advantages and limitations. Saliva stands out due to its simplicity and safety in collection, along with the convenience of self-collection without the need for healthcare supervision, while potentially being comparable to urine and blood in terms of effectiveness. Herein, we highlighted the significant potential of saliva in assessing viral loads and diagnosing viral infections, such as herpesviruses, HPV, PyV, TTV, SARS-CoV-2, and MPXV. The detection of viral shedding in saliva underscores its utility in early diagnosis, the monitoring of infection progression, and evaluating treatment responses. The non-invasive nature of saliva collection makes it an appealing alternative to more invasive methods, promoting better patient compliance and facilitating large-scale screening and surveillance. As such, we further highlight current evidence on the use of saliva as a prognostic tool. Although a significant amount of data is already available, further investigations are warranted to more comprehensively assess the added benefit from the utilization of salivary biomarkers in the clinics. Salivary biomarkers show great promise for the early detection and prevention of viral infection complications, potentially improving disease management and control at the population level. Integrating these non-invasive tools into routine clinical practice could enhance personalized healthcare strategies and patient outcomes. Future studies should focus on establishing standardization protocols, validating the accuracy of salivary diagnostics, and expanding clinical research to enhance the diagnostic and monitoring capabilities of salivary biomarkers.

Neutrophil-albumin ratio serves as a superior prognostic biomarker for traumatic brain injury.

Traumatic brain injury (TBI) represents a common and severe medical condition necessitating prompt risk stratification to enhance patient outcomes. Although substantial research has been conducted on the prognostic utility of various biomarkers for TBI, no single biomarker has been definitively recognized as the most precise predictor of disease outcomes. In comparison to other markers, the neutrophil-albumin ratio (NAR) has emerged as a cost-effective and reproducible inflammatory biomarker, demonstrating potential in evaluating the severity of inflammation and prognosticating outcomes in infections and cerebrovascular diseases. This study evaluated the prognostic significance of the NAR in comparison to two other readily accessible and cost-effective composite indices: the Neutrophil-Lymphocyte Ratio (NLR) and the Platelet-Lymphocyte Ratio (PLR) in individuals with TBI. We conducted a retrospective cohort analysis involving 297 hospitalized TBI patients, gathering comprehensive demographic, anthropometric, medical, clinical, laboratory, and imaging data to assess the expression changes of these biomarkers. Our findings suggest that both the NAR and the NLR possess predictive value regarding prognosis following TBI. However, receiver operating characteristic (ROC) curve analysis revealed that NAR outperformed NLR as a prognostic predictor. In conclusion, our examination of blood biochemistry composite indicators indicates that, while both NAR and NLR serve as significant prognostic markers, NAR is a more effective predictor of outcomes in patients with TBI.

Epigenomic biomarkers of cardiometabolic disease: How far are we from daily practice?

Determining whether someone has cardiometabolic disease (CMD), especially in the early stages, can be complicated. Risk stratification ordinarily depends on an extended process relying on medical history that typically considers blood pressure, cholesterol, smoking and diabetes status. Physicians have long relied on these key patient characteristics to assess CMD risk. However, these widely used clinical assessments are often identified later in life and by definition, in those individuals with progressed disease. This is partly because the onset of CMD naturally occurs in adulthood, however, the underlying processes can occur much earlier in life, even in the absence of obvious symptoms. For one thing, the pathways towards pathology may exist for years before symptom onset. Thus, among other things, there are opportunities to provide doctors with better insights into future disease prediction especially in younger adults with diabetes. The rapid rise in CMD together with the increased rates of obesity and diabetes in this population only emphasises the importance of predictive molecular biomarkers. One notable aspect is that traditional risk scores, such as those based on cholesterol measurements, are frequently found to be within normal ranges in younger populations. At the same time, given the significant overlap in risk factors for cardiovascular disease (CVD) and diabetes, the unmet clinical need is for early biomarkers of CMD that may help improve risk assessment in younger adults. This editorial highlights advances in the use of polygenic risk scores and emerging utility of genetic biomarkers to define intermediate CMD phenotypes discussing new classification criteria involving DNA methylation of genes to improve risk assessment. CMD is the number one cause of mortality and accounts for 31% of all global deaths. CMD is also multifactorial, comprising cardiovascular disease (CVD) and diabetes that have significant overlap in risk factors and disease biology. Diabetes is arguably the strongest risk factor for CVD development. Accounting for almost 90% of diabetes cases worldwide, type 2 diabetes (T2D) affects about 527 million people. The global economic burden is estimated at 1.3 trillion USD annually and is close to 1.8% of global GDP [1]. Despite the progress in preventive and therapeutic measures of CVD, the increasing CMD rates only underscore the important need of molecular biomarkers for early detection [2]. Determining whether someone has CMD usually involves an extended diagnostic process that has become essential for risk stratification and disease prevention [3]. While the onset of CMD typically occurs in adulthood, disease development commences much earlier, and this has scientists questioning whether molecular biomarkers could improve current prognostic risk scores. Predicting which people with T2D are most likely to develop CVD remains a significant challenge despite the recent advances in genetic mapping.Graphical abstract

Current approaches and future perspectives on hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by significant myocardial hypertrophy and varying degrees of fibrosis, affecting approximately 0.2% of the general population, with a higher prevalence in those with cardiac conditions. Despite its frequency, HCM remains underdiagnosed due to its broad clinical spectrum. The disease is equally prevalent in men and women, presenting in forms ranging from mild to severe, and it is the leading cause of sudden cardiac death in adolescents and young adults, particularly athletes. Recent advances in genetic engineering and biotechnology have significantly improved the understanding, diagnosis, and treatment of HCM, emphasizing the importance of early diagnosis in preventing severe complications. This review synthesizes findings from a narrative literature review, highlighting advances in risk stratification, gene therapy, biomarker utilization, and the need for further research to make these innovations more widely available in clinical practice. The study also examines the disease's pathophysiology, genetics, diagnostic methods, and treatment strategies, underlining the importance of personalized approaches to managing HCM.

Comprehensive serum biomarker analysis reveals IL-8 changes as the only predictor of the effectiveness of immune checkpoint inhibitors for patients with advanced non-small cell lung cancer

ObjectivesProgrammed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting. Materials and MethodsThis was a sub-study of J-TAIL, a prospective observational study of atezolizumab monotherapy in pre-treated patients with advanced NSCLC. From April to October 2019, 262 patients were enrolled from 73 sites in Japan. Serum samples were collected at baseline and at the second dose of atezolizumab. Quantification of the 51 serum cytokines, chemokines, growth factors, and vascular endothelial growth factors was performed using the Luminex platform. Baseline values and fold changes of the time of the second dose to the baseline were examined in association with the effectiveness of atezolizumab. ResultsAmong the 51 proteins assessed, a higher baseline interleukin (IL)-12 level, a higher soluble CD40 ligand fold change, a lower IL-8 fold change were associated with higher objective response rate (ORR). Of these, only the lower IL-8 fold change was associated with better progression-free survival (PFS) (adjusted hazard ratio, 1.98; 95 % confidence interval, 1.45–2.70; P < 0.01). Multivariate analysis demonstrated that the lower IL-8 fold change was an independent factor for both the ORR and PFS. The IL-8 fold change was independent of the neutrophil/lymphocyte ratio, and durable PFS was observed in patients with both low. ConclusionComprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab.

MicroRNA Biomarkers on Day of Injury Among Patients with Post Concussive Symptoms at 28-Days: A Prospective Cohort Study.

After mild traumatic brain injury (mTBI), some patients experience symptoms that persist for weeks to months. Recovery from mTBI is primarily assessed using selfreported symptom questionnaires. Blood biomarkers, including microRNA species, have shown promise to assist diagnosis of mTBI, however, little is known about how blood microRNA measures might predict symptom recovery. The aim of this study was to investigate the variances in plasma microRNAs on the day of injury between individuals with mTBI who report post-concussive symptoms at the 28- day mark and those who do not. Patients who presented to an adult, tertiary referral hospital emergency department on the day of the injury and were diagnosed with isolated mTBI (n=35) were followed up for 28 days. Venous blood samples were collected and symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 28 days. Patients who reported ongoing symptoms of total RPQ score ≥10 or at least one symptom severity ≥2, were compared to those with lesser symptom severity or symptom resolution. There were 9 (25.7%; 95%CI: 12.5-43.3) patients who reported persistent symptoms. Day of injury plasma miR-223-3p levels were significantly higher in individuals with ongoing symptoms compared to those without, however, no such differences were observed for miRs 142- 3p, 423-3p, 32-5p, 144-3p, and let-7f-5p. Acute plasma miR-223-3p levels appear to detect patients who later have persistent symptoms after mTBI. The results demonstrate the potential utility for such biomarkers to assist in decisions towards early referral for therapy after mTBI.

Exploring Salivary Alpha-Amylase as a Biomarker in Periodontitis: A Comparative Analysis of Disease Stages and Clinical Correlations

Periodontal disease, characterized by bacterial plaque accumulation and subsequent immune response, can lead to gingivitis and periodontitis if untreated. Salivary alpha-amylase (sAA) has emerged as a potential biomarker with implications in periodontal disease progression. Objectives: This study aimed to assess and compare salivary alpha-amylase levels in individuals with periodontitis and healthy controls and to investigate its relationship with clinical parameters of periodontal disease. Forty-five participants were categorized into periodontally healthy (n = 13), Stage I and II Periodontitis (n = 17), and Stage III and IV periodontitis (n = 15) groups. Saliva samples were collected and analyzed using ELISA kits. Statistical analyses included tests for normality, group comparisons, post hoc analysis, and correlation analysis. Significant differences in salivary alpha-amylase levels were observed among severity groups (p &lt; 0.05), with higher levels in periodontitis patients than healthy controls. Spearman correlation revealed moderate positive associations between alpha-amylase levels and probing depth (PD) and clinical attachment loss (CAL). Elevated salivary alpha-amylase levels were found to be associated with more severe periodontal disease, suggesting its potential as a biomarker for periodontitis severity. These findings support the utility of salivary biomarkers in periodontal disease diagnosis and monitoring, although further validation and standardization are warranted for clinical application.

The role of inflammation in neurological disorders: a brief overview of multiple sclerosis, Alzheimer's, and Parkinson's disease'.

Neuroinflammation is a central feature in the pathophysiology of several neurodegenerative diseases, including MS, AD, and PD. This review aims to synthesize current research on the role of inflammation in these conditions, emphasizing the potential of inflammatory biomarkers for diagnosis and treatment. We highlight recent findings on the mechanisms of neuroinflammation, the utility of biomarkers in disease differentiation, and the implications for therapeutic strategies. Advances in understanding inflammatory pathways offer promising avenues for developing targeted interventions to improve patient outcomes. Future research should focus on validating these biomarkers in larger cohorts and integrating them into clinical practice to enhance diagnostic accuracy and therapeutic efficacy.

Identifying the best candidate for focal therapy: a comprehensive review.

Despite the evidence supporting the use of focal therapy (FT) in patients with localized prostate cancer (PCa), considerable variability exists in the patient selection criteria across current studies. This study aims to review the most recent evidence concerning the optimal approach to patient selection for FT in PCa. PubMed database was systematically queried for studies reporting patient selection criteria in FT for PCa before December 31, 2023. After excluding non-relevant articles and a quality assessment, data were extracted, and results were described qualitatively. There is no level I evidence regarding the best patient selection approach for FT in patients with PCa. Current international multidisciplinary consensus statements recommend multiparametric magnetic resonance imaging (mpMRI) followed by MRI-targeted and systematic biopsy for all candidates. FT may be considered in clinically localized, intermediate risk (Gleason 3 + 4 and 4 + 3), and preferably unifocal disease. Patients should have an acceptable life expectancy. Those with prostate volume >50 ml and erectile dysfunction should not be excluded from FT. Prostate-specific antigen (PSA) level of < 20 (ideally < 10) ng/mL is recommended. However, the utility of other molecular and genomic biomarkers in patient selection for FT remains unknown. FT may be considered in well-selected patients with localized PCa. This review provides a comprehensive insight regarding the optimal approach for patient selection in FT.

Inclusion body myositis: an update.

To review recent advances in our understanding of the epidemiology, pathophysiology, and management of inclusion body myositis (IBM). Recent epidemiologic studies have highlighted the morbidity and mortality associated with IBM, including the impact of dysphagia. Multiomic analyses of IBM tissues have identified new pathogenic pathways and biomarkers for use in clinical trials. New diagnostic criteria and outcome measures have been proposed to improve clinical trial design. Ongoing clinical trials are targeting T cells and autophagy. Improvements in our understanding of IBM pathogenesis are identifying new pathways and biomarkers that need validation in larger cohorts. Exercise remains the primary therapeutic modality available, and new treatment targets are needed.

The Role of Tumor Biomarkers in Tailoring the Approach to Advanced Ovarian Cancer

Growing evidence has demonstrated the role of mutations of tumor biomarkers in diagnosing and treating epithelial ovarian cancer. This review aims to analyze recent literature on the correlation between tumor biomarkers and chemotherapy in nonmucinous ovarian cancer, providing suggestions for personalized treatment approaches. An extensive literature search was conducted to identify relevant studies and trials. BRCA1/2 mutations are central in homologous recombination repair deficiency (HRD) in ovarian cancer, but several other genetic mutations also contribute to varying cancer risks. While the role of MMR testing in ovarian cancer is debated, it is more commonly linked to non-serous ovarian cancer, often associated with Lynch syndrome. A significant proportion of ovarian cancer patients have HRD, affecting treatment decisions in both first-line (especially in advanced stages) and second-line therapy due to HRD’s connection with platinum-based therapy and PARP inhibitors’ response. However, validated genetic tests to identify HRD have not yet been universally implemented. There is no definitive therapeutic algorithm for advanced ovarian cancer, despite ongoing efforts and multiple proposed tools. Future research should focus on expanding the utility of biomarkers, reducing resistance, and increasing the actionable biomarker pool.

Molecular and cell phenotype programs in oral epithelial cells directed by co-exposure to arsenic and smokeless tobacco.

Chronic arsenic exposure can lead to various health issues, including cancer. Concerns have been mounting about the enhancement of arsenic toxicity through co-exposure to various prevalent lifestyle habits. Smokeless tobacco products are commonly consumed in South Asian countries, where their use frequently co-occurs with exposure to arsenic from contaminated groundwater. To decipher the in vitro molecular and cellular responses to arsenic and/or smokeless tobacco, we performed temporal multi-omics analysis of the transcriptome and DNA methylome remodelling in exposed hTERT-immortalized human normal oral keratinocytes (NOK), as well as arsenic and/or smokeless tobacco genotoxicity and mutagenicity investigations in NOK cells and in human p53 knock-in murine embryonic fibroblasts (Hupki MEF). RNAseq results from acute exposures to arsenic alone and in combination with smokeless tobacco extract revealed upregulation of genes with roles in cell cycle changes, apoptosis and inflammation responses. This was in keeping with global DNA hypomethylation affecting genes involved in the same processes in response to chronic treatment in NOK cells. At the phenotypic level, we observed a dose-dependent decrease in NOK cell viability, induction of DNA damage, cell cycle changes and increased apoptosis, with the most pronounced effects observed under arsenic and SLT co-exposure conditions. Live-cell imaging experiments indicated that the DNA damage likely resulted from induction of apoptosis, an observation validated by a lack of exome-wide mutagenesis in response to chronic exposure to arsenic and/or smokeless tobacco. In sum, our integrative omics study provides novel insights into the acute and chronic responses to arsenic and smokeless tobacco (co-)exposure, with both types of responses converging on several key mechanisms associated with cancer hallmark processes. The generated rich catalogue of molecular programs in oral cells regulated by arsenic and smokeless tobacco (co-)exposure may provide bases for future development of biomarkers for use in molecular epidemiology studies of exposed populations at risk of developing oral cancer.

On the utility of cerebrospinal fluid biomarkers in canine neurological disorders

The cerebral biomarkers, neurofilament light chain (NfL), amyloid-β, tau, and neuron specific enolase (NSE) reflect a wide spectrum of neurological damage in the brain and spinal cord. With this study, we aimed to assess whether these biomarkers hold any potential diagnostic value for the three most common canine neurological diseases. Canines suffering from meningoencephalitis of unknown origin (MUO), brain tumors, and selected non-infectious myelopathies were included. For each diagnosis, we analyzed these biomarkers in the cerebrospinal fluid collected via cranial puncture from the cisterna magna. Elevated levels of CSF tau, NfL, and NSE were observed in MUO, with all three biomarkers being intercorrelated. Tau and NSE were increased while amyloid-β was decreased in dogs suffering from tumors. In contrast, no biomarker changes were observed in dogs with myelopathies. Covariates such as age, sex, or castration had minimal impact. CSF biomarkers may reflect molecular changes related to MUO and tumors, but not to non-infectious myelopathies. The combination of NfL, tau, and NSE may represent useful biomarkers for MUO as they reflect the same pathology and are not influenced by age.

High-Sensitivity Troponin: Finding a Meaningful Delta.

High-sensitivity cardiac troponin (hs-cTn) assays have significantly refined the resolution of biomarker-level detection and have emerged as the gold standard cardiac biomarker in evaluating myocardial injury. Since its introduction, hs-cTn has been integrated into the Fourth Universal Definition of Myocardial Infarction and various European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the evaluation and diagnosis of chest pain syndromes. However, despite its integral role in caring for patients with chest pain, there are still substantive gaps in our knowledge of the clinical interpretation of dynamic changes in hs-cTn values. Whether a relative or absolute hs-cTn delta should be used to detect acute myocardial injury remains debatable. There are also emerging considerations of possible sex and racial/ethnic differences in clinically significant troponin deltas. In the emergency department, there is debate about the optimal time frame to recheck hs-cTn after symptom onset for myocardial infarction rule-out and whether hs-cTn deltas should be integrated into clinical risk scores. In this review, we will provide an overview of the history of clinical utilization of cardiac biomarkers, the development of hs-cTn assays, and the ongoing search for a meaningful delta that can be clinically applicable.

Multidimensional analysis of the impact of Gemmatimonas, Rhodothermus, and Sutterella on drug and treatment response in colorectal cancer.

Colorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer. This study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response. An integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined. A thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer. This study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it.

The utility of MRI radiological biomarkers in determining intracranial pressure

Intracranial pressure (ICP) is a physiological parameter that conventionally requires invasive monitoring for accurate measurement. Utilising multivariate predictive models, we sought to evaluate the utility of non-invasive, widely accessible MRI biomarkers in predicting ICP and their reversibility following cerebrospinal fluid (CSF) diversion. The retrospective study included 325 adult patients with suspected CSF dynamic disorders who underwent brain MRI scans within three months of elective 24-h ICP monitoring. Five MRI biomarkers were assessed: Yuh sella grade, optic nerve vertical tortuosity (VT), optic nerve sheath distension, posterior globe flattening and optic disc protrusion (ODP). The association between individual biomarkers and 24-h ICP was examined and reversibility of each following CSF diversion was assessed. Multivariate models incorporating these radiological biomarkers were utilised to predict 24-h median intracranial pressure. All five biomarkers were significantly associated with median 24-h ICP (p < 0.0001). Using a pair-wise approach, the presence of each abnormal biomarker was significantly associated with higher median 24-h ICP (p < 0.0001). On multivariate analysis, ICP was significantly and positively associated with Yuh sella grade (p < 0.0001), VT (p < 0.0001) and ODP (p = 0.003), after accounting for age and suspected diagnosis. The Bayesian multiple linear regression model predicted 24-h median ICP with a mean absolute error of 2.71 mmHg. Following CSF diversion, we found pituitary sella grade to show significant pairwise reversibility (p < 0.001). ICP was predicted with clinically useful precision utilising a compact Bayesian model, offering an easily interpretable tool using non-invasive MRI data. Brain MRI biomarkers are anticipated to play a more significant role in the screening, triaging, and referral of patients with suspected CSF dynamic disorders.

The application and interpretation of laboratory biomarkers for the evaluation of vitamin B12 status.

Vitamin B12 (cobalamin; B12) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B12 deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B12 status include the measurement of serum B12 (also known as total B12 or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B12 status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B12 test, which is readily available and highly automated. In some cases, the sequential use of different B12 status biomarkers or the calculation of a composite B12 status score, derived from a panel of B12 biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarises the utility of B12-related biomarkers and describes approaches to their application and interpretation.