Disease Biomarkers Research Articles

Assessing the feasibility of breath collection from conscious young children to support volatilome analysis: insights into age limitations and breath sampling requirements.

Breath volatile organic compounds (VOCs) are increasingly under consideration as biomarkers of respiratory disease. Although numerous studies have identified VOCs that distinguish patient groups, a lack of standardisation among published studies has impeded translation into clinical diagnostics. Standardised breath collection protocols have been proposed for adults and children aged >4 years, but optimal methods for collecting breath from younger children remain to be determined. The aim of this study was to assess the feasibility and acceptability of breath sampling among a young paediatric cohort. A total of 61 children (age 6 months-12 years) were recruited prospectively to observational studies of chronic cough at two study sites. Mixed expiratory breath was collected into 1 l Tedlar Bags using either a drinking straw, mouthpiece, or mask. After concentrating onto thermal desorption tubes, the breath was analysed using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry. Breath collection via a mouthpiece was highly feasible for children aged >2 years. Mask-based collection was required for younger children but was poorly tolerated. Drinking straw-based collections were unsuitable for some children aged <4 years due to challenges maintaining a sufficient seal. At least 700 ml of breath was sampled from 72.6% of children. The number of peaks per sample, total peak area per sample, and composition of breath VOCs were all consistent with successful breath sampling. The high feasibility of breath collection via a mouthpiece in our study suggests established protocols designed for children aged over 4 years can be used with confidence for children from as young as 2 years of age.

Gut Microbiota Serves as a Crucial Independent Biomarker in Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD), ulcerative colitis (UC), and IBD unclassified (IBD-U), is a complex intestinal disorder influenced by genetic, environmental, and microbial factors. Recent evidence highlights the gut microbiota as a pivotal biomarker and modulator in IBD pathogenesis. Dysbiosis, characterized by reduced microbial diversity and altered composition, is a hallmark of IBD. A consistent decrease in anti-inflammatory bacteria, such as Faecalibacterium prausnitzii, and an increase in pro-inflammatory species, including Escherichia coli, have been observed. Metabolomic studies reveal decreased short-chain fatty acids (SCFAs) and secondary bile acids, critical for gut homeostasis, alongside elevated pro-inflammatory metabolites. The gut microbiota interacts with host immune pathways, influencing morphogens, glycosylation, and podoplanin (PDPN) expression. The disruption of glycosylation impairs mucosal barriers, while aberrant PDPN activity exacerbates inflammation. Additionally, microbial alterations contribute to oxidative stress, further destabilizing intestinal barriers. These molecular and cellular disruptions underscore the role of the microbiome in IBD pathophysiology. Emerging therapeutic strategies, including probiotics, prebiotics, and dietary interventions, aim to restore microbial balance and mitigate inflammation. Advanced studies on microbiota-targeted therapies reveal their potential to reduce disease severity and improve patient outcomes. Nevertheless, further research is needed to elucidate the bidirectional interactions between the gut microbiome and host immune responses and to translate these insights into clinical applications. This review consolidates current findings on the gut microbiota’s role in IBD, emphasizing its diagnostic and therapeutic implications, and advocates for the continued exploration of microbiome-based interventions to combat this debilitating disease.

Ceramide as a Promising Tool for Diagnosis and Treatment of Clinical Diseases: A Review of Recent Advances

Background/Objectives: Ceramide, a sphingolipid metabolite, has emerged as a key player in various physiological and pathological processes. Changes in ceramide levels are associated with the occurrence and development of various diseases, highlighting its potential as a biomarker of various clinical diseases. Methods: The biosynthesis and metabolism of ceramide are discussed, along with its functions in cell signaling, apoptosis, and inflammation. This study further examines the potential of ceramide as a biomarker for disease diagnosis and treatment. Results: This article highlights the involvement of ceramide in several diseases, including cardiovascular diseases, dermatosis, cancer, neurodegenerative disorders and metabolic syndromes. For each disease, the potential of ceramide as a biomarker for disease diagnosis and prognosis is explored, and the feasibility of therapeutic strategies targeting ceramide metabolism are reviewed. Additionally, the challenges and future directions in the field of ceramide research are addressed. Conclusions: This review article provides an overview of the recent advances in understanding the role of ceramide in clinical diseases and its potential as a diagnostic and therapeutic tool.

Cardiovascular Health and Biomarkers of Neurodegenerative Disease in Older Adults.

Cardiovascular health (CVH), defined by the American Heart Association as Life's Simple 7 to promote a healthy lifestyle and manage vascular risk factors, has been associated with a low risk of Alzheimer disease and less vascular dementia. However, the association between CVH and biomarkers of neurodegeneration remains less understood. To investigate the association of CVH with serum biomarkers of neurodegeneration, including neurofilament light chain (NfL) and total tau (t-tau). This cohort study was conducted within the biracial, population-based Chicago Health and Aging Project (CHAP) of adults aged 65 years or older between 1993 and 2012. Participants who had measured serum NfL and t-tau levels and data on all components of the CVH score were included. The statistical analysis was conducted from April 10 to September 26, 2024. The CVH score includes 7 components: a healthy diet; regular exercise; normal body mass index; nonsmoking status; and the absence of dyslipidemia, diabetes, and hypertension. The scores were divided into 3 groups from lowest to highest CVH (0-6 points, 7-9 points, and 10-14 points). The main outcome was the association of CVH score with serum biomarkers of NfL and t-tau as measured using linear regression and mixed-effects models. A total of 1018 CHAP participants were included in the analysis (mean [SD] age, 73.1 [6.1] years; 625 female [61.4%]; 610 Black or African American [59.9%] and 408 White [40.1%]). Participants with a high CVH score (ie, 10-14 points) were predominantly White (151 [64.3%]) and had a higher education (mean [SD], 13.6 [3.7] years). Compared with participants with low CVH scores (ie, 0-6 points), those with CVH scores of 10 to 14 points had significantly lower serum levels of NfL (relative difference, -18.9%; β = -0.091; SE, 0.025). A higher CVH score was associated with a slower annual increase in NfL levels as participants aged (relative difference in rate, -1.7%; β = -0.008; SE, 0.004). Cardiovascular health was not associated with serum levels of t-tau. These findings suggest that promoting CVH in older adults may help alleviate the burden of neurodegenerative diseases, particularly among Black adults, who are known to experience a higher prevalence of cardiovascular disease.

Circulating Tumor DNA as a Real-Time Biomarker for Minimal Residual Disease and Recurrence Prediction in Stage II Colorectal Cancer: A Systematic Review and Meta-Analysis

The role of adjuvant chemotherapy (adj-CT) in stage II colon cancer remains controversial. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and predicting recurrence. This systematic review and meta-analysis evaluated the prognostic value of ctDNA in stage II colorectal cancer (CRC), focusing on postoperative detection, post adj-CT outcomes, and dynamic surveillance. A literature search identified studies correlating ctDNA positivity in stage II CRC with recurrence risk, recurrence-free survival (RFS), and disease-free survival (DFS). Seven studies met the inclusion criteria. Postoperative ctDNA positivity significantly increased the risk of recurrence (pooled risk ratio [RR:] 3.66; 95% confidence interval [CI]: 1.25–10.72; p = 0.002). CtDNA positivity after adj-CT was strongly associated with poor survival, while dynamic ctDNA monitoring detected recurrence earlier than conventional methods, including carcinoembryonic antigen (CEA) and imaging. CtDNA is a robust prognostic biomarker in stage II CRC, enabling personalized treatment. High-risk ctDNA-positive patients may benefit from intensified therapy, while ctDNA-negative patients could avoid unnecessary treatments. However, the standardization of detection methods and large-scale validation studies are needed before integrating ctDNA into routine clinical practice as a non-invasive, dynamic tool for personalized care.

Unbiased CSF Proteomics in Patients With Idiopathic Normal Pressure Hydrocephalus to Identify Molecular Signatures and Candidate Biomarkers.

Idiopathic normal pressure hydrocephalus (iNPH) is a reversible neurologic disorder that remains poorly understood. Accurate differential diagnosis of iNPH and Alzheimer disease (AD) is complicated by overlapping clinical manifestations. Beyond neuroimaging, there are currently no biomarkers available for iNPH leading to frequent misdiagnosis, and proteomic studies into iNPH have been limited by low sample sizes and inadequate analytical depth. In this study, we report the results of a large-scale proteomic analysis of CSF from patients with iNPH to elucidate pathogenesis and identify potential disease biomarkers. CSF samples were collected through lumbar puncture during diagnostic visits to the Mass General Brigham neurology clinic. Samples were analyzed using mass spectrometry. Differential expression of proteins was studied using linear regression models. Results were integrated with publicly available single-nucleus transcriptomic data to explore potential cellular origins. Biological process enrichment was analyzed using gene-set enrichment analyses. To identify potential diagnostic biomarkers, decision tree-based machine learning algorithms were applied. Participants were classified as cognitively unimpaired (N = 53, mean age: 66.5 years, 58.5% female), AD (N = 124, mean age: 71.2 years, 46.0% female), or iNPH (N = 44, mean age: 74.6 years, 34.1% female) based on clinical diagnosis and AD biomarker status. Gene Ontology analyses indicated upregulation of the immune system and coagulation processes and downregulation of neuronal signaling processes in iNPH. Differential expression analysis showed a general downregulation of proteins in iNPH. Integration of differentially expressed proteins with transcriptomic data indicated that changes likely originated from neuronal, endothelial, and glial origins. Using machine learning algorithms, a panel of 12 markers with high diagnostic potential for iNPH were identified, which were not all detected using univariate linear regression models. These markers spanned the various molecular processes found to be affected in iNPH, such as LTBP2, neuronal pentraxin receptor (NPTXR), and coagulation factor 5. Leveraging the etiologic insights from a typical neurologic clinical cohort, our results indicate that processes of immune response, coagulation, and neuronal signaling are affected in iNPH. We highlight specific markers of potential diagnostic interest. Together, our findings provide novel insights into the pathophysiology of iNPH and may facilitate improved diagnosis of this poorly understood disorder.

Optimization for Simultaneous Determination of a Panel of Advanced Glycation End Products as Biomarkers for Metabolic Diseases

Optimization for Simultaneous Determination of a Panel of Advanced Glycation End Products as Biomarkers for Metabolic Diseases

Chiral Gold Nanostructure Monolayers as SERS Substrates for Ultrasensitive Detection of Enantiomer Biomarkers of Alzheimer's Disease

Sensitive and specific biomarkers are needed for early diagnosis of neurodegenerative diseases, such as Alzheimer's disease (AD). Herein, a new type of chiral gold nanostructure induced by D‐/L‐cysteine‐leucine dipeptides with a g‐factor of 0.1 was successfully synthesized. To enhance the discrimination performance, the chiral gold nanostructures were assembled into D‐/L‐Au monolayers. As surface‐enhanced Raman scattering (SERS) substrates, the D‐/L‐Au monolayers simultaneously deliver molecular structural specificity and enantioselectivity within a single spectrum, which can be a versatile, label‐free chiral discrimination strategy for the detection of D‐/L‐kynurenine (Kyn). The mechanism was unveiled to involve high enantioselective adsorption energies between L‐ and D‐Kyn on the lattice plane (221), resulting in enantioselective sensing. The results showed that L‐Au monolayer reached a limit of detection (LOD) of 3.7 nM for L‐Kyn, while D‐Au monolayer reached a LOD of 3.6 nM for D‐Kyn, respectively. Notably, there was a significant difference in D‐Kyn levels between AD patients and healthy individuals in serum samples, a distinction not observed for L‐Kyn, which positioned D‐Kyn as a potential novel biomarker for clinical prediagnosis of AD patients, marking the first report of its kind worldwide. This study provides a robust tool for biomedical science and clinical diagnostics.

MicroRNA-143-3p and miR-452-5p: A Fingerprint for the Diagnosis of Aortic Stenosis in the Geriatric Population

Background/Objectives: Aortic stenosis (AS) is the most common valvular pathology in the geriatric population and is the primary cause of valve replacement. However, misdiagnoses and delays in treatment are common due to comorbidities, frailty, and sedentary lifestyles among elderly individuals. MicroRNAs (miRNAs) are highly conserved molecular regulators involved in various cellular processes and have gained recognition as reliable biomarkers in cardiovascular diseases. In the present study, we evaluated plasma miRNAs as potential biomarkers for the early diagnosis of AS in the geriatric population to identify early therapeutic strategies. Methods: This prospective, case–control study included 87 individuals over 75 years of age. The participants were divided into AS (n = 58) and control (n = 29) groups. Results: Fifty-four miRNAs were differentially expressed between patients with AS and controls. Among those genes, 29 were upregulated and 25 were downregulated in patients with AS relative to controls. We selected seven candidate genes (miR-185-5p, miR-143-3p, miR-370-3p, let-7d-3p, miR-452-5p, miR-6787-3p, and miR-21-3p) for experimental validation by qRT–PCR. Only miR-143-3p and miR-452-5p were significantly upregulated in the plasma of patients with AS compared with controls. We developed a multiparametric model by combining the two-miRNA signature with echocardiographic parameters (left ventricular ejection fraction, stroke volume, and global longitudinal strain) to increase diagnostic power; this model yielded sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) values of 78.2%, 70.7%, and 0.837, respectively. Conclusions: In clinical practice, the use of a multiparametric model involving this set of miRNAs combined with echocardiographic variables may improve the accuracy of AS diagnosis and risk stratification.

Examination of Intermolecular Forces Influencing Headspace Analysis of Biological Samples

Headspace analysis is an effective method for assessing the concentrations of volatile and semi-volatile metabolites in biological samples. In particular, solid-phase microextraction (SPME) is an efficient tool for headspace analyses. Metabolites present in the sample are the typical targets of headspace analysis (rather than the vapor phase concentration) for making measurements on sample donors (e.g., biomarkers of health or disease). Accordingly, intermolecular forces between metabolites and matrix may prevent a complete profile of the metabolite composition in the biosamples from being revealed. To assess sources of such interactions, several volatile compounds in various sample mediums were examined. Small volatile metabolites typical of human biosamples were the volatile compounds selected for this study. Test media included lipid or serum solution to simulate biological samples commonly encouraged in biomarker discovery. Headspace concentrations of volatile analytes were compared using solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC-MS). Observed levels of metabolites in headspace varied among the different media, despite being fortified at equal concentrations in the samples. Overall, lower headspace responses were observed in samples containing proteins or lipids. It was found that these strong intermolecular interactions arose from irreversible chemical bonds between the volatile molecules and component of the sample matrix. However, headspace responses could be maximized when the analysis was performed at temperatures ranging from 60 to 70 °C. Furthermore, normalization of peak responses to an internal standard did not always account for these interactions.

Copeptin and Mid-Regional Proadrenomedullin Are Not Useful Biomarkers of Cardiometabolic Disease in Patients with Acromegaly—A Preliminary Study

Background/Objectives: Cardiovascular complications are a leading cause of premature mortality in patients with acromegaly. Copeptin (CPP) correlates strongly with plasma osmolality and is regulated by non-osmotic stimuli involved in the pathophysiology of cardiovascular disease. Mid-regional proadrenomedullin (MR-proADM), synthesized mainly in the adrenal medulla, vascular endothelial cells, and the heart, has vasodilatory effects. The study aimed to assess two cardiovascular biomarkers (CPP and MR-proADM) in acromegaly patients in relation to disease activity and compare findings with a control group. Methods: The study examined CPP and MR-proADM levels alongside hormonal and biochemical parameters and cardiovascular and metabolic disease prevalence in 53 acromegaly patients and 26 controls. Results: No significant differences in CPP or MR-proADM concentrations were observed between the two groups. However, a positive correlation occurred between growth hormone (GH) and CPP concentrations, and there was a negative correlation between fasting glucose and CPP concentrations in acromegaly patients. The study also found a positive correlation between low-density lipoprotein (LDL) cholesterol and MR-proADM concentrations and between high-density lipoprotein (HDL) cholesterol and MR-proADM levels in the study group. Moreover, atherogenic dyslipidemia was significantly more common in the active form of acromegaly and pituitary macroadenoma patients than in the control group. Acromegaly patients had significantly higher fasting glucose and fasting insulin levels compared to controls, and the homeostasis model assessment of the insulin resistance (HOMA-IR) index was significantly lower in the study group than in the controls. Conclusions: Neither CPP or MR-proADM are significant diagnostic or monitoring indicators of cardiovascular or metabolic complications in acromegaly.

Neutrophil/Lymphocyte Ratio (NLR) as a Predictive Marker for p16 Positivity and Cervical Cancer Progression: Insights from the SCOPE Study

Background: Cervical cancer, primarily driven by persistent high-risk human papillomavirus (HPV) infections, remains a significant global health challenge. Systemic inflammatory markers, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR), may reflect disease progression. This study examines the association between these markers and p16 positivity in cervical intraepithelial neoplasia (CIN) cases. Methods: This retrospective analysis included 395 patients undergoing LEEP conization. Data on HPV status, p16 immunostaining, and hematological parameters were collected. Statistical analyses, including Mann–Whitney U and chi-square tests, assessed relationships between markers and outcomes, with significance set at p &lt; 0.05. Results: Elevated NLR was significantly associated with p16 positivity (p = 0.011) and HPV DNA positivity (p = 0.04). HPV-positive individuals showed higher mean NLR (2.15) compared to HPV-negative individuals (1.61). Receiver operating characteristic (ROC) analysis demonstrated moderate diagnostic accuracy for NLR (AUC = 0.610), highlighting its potential as a biomarker. No significant associations were observed for PLR or LMR with p16 positivity. These findings suggest systemic inflammation, indicated by NLR, contributes to HPV persistence and CIN progression. Conclusions: NLR is a valuable prognostic biomarker for HPV-related cervical disease, correlating with both p16 and HPV DNA positivity. Incorporating hematological and immunohistochemical markers may enhance personalized cervical cancer management.

Emerging, novel gene-modulating therapies for transthyretin amyloid cardiomyopathy.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease caused by the pathological deposition of misfolded transthyretin (TTR) protein in the myocardium, leading to restrictive cardiomyopathy and heart failure. While TTR stabilizers such as tafamidis and acoramidis are the only FDA-approved treatments, novel gene-modulating therapies are emerging as transformative approaches. Small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapies effectively reduce TTR production and have demonstrated promising clinical outcomes, though their use in cardiac amyloidosis remains investigational. CRISPR-Cas9 therapies represent a paradigm shift, offering a potential one-time treatment by permanently silencing the TTR gene. Recent clinical trials have shown significant TTR reduction and stabilization of disease biomarkers, although long-term safety and efficacy require further evaluation. Despite the lack of direct comparisons among these modalities, their emergence highlights a promising future for ATTR-CM management. This review discusses the pathogenesis of ATTR-CM, mechanisms of novel gene-modulating therapies, clinical evidence, challenges, and the future outlook for advancing treatment options.

Secreted neurofilament light chain after neuronal damage induces myeloid cell activation and neuroinflammation.

Secreted neurofilament light chain after neuronal damage induces myeloid cell activation and neuroinflammation.

Multimodal Metagenomic Analysis Reveals Microbial InDels as Superior Biomarkers for Pediatric Crohn's Disease.

The gut microbiome is closely associated with pediatric Crohn's disease (CD), while the multidimensional microbial signature and their capabilities for distinguishing pediatric CD are underexplored. This study aims to characterize the microbial alterations in pediatric CD and develop a robust classification model. A total of 1,175 fecal metagenomic sequencing samples, predominantly from three cohorts of pediatric CD patients, were re-analyzed from raw sequencing data using uniform process pipelines to obtain multidimensional microbial alterations in pediatric CD, including taxonomic profiles, functional profiles, and multi-type genetic variants. Random forest algorithms were used to construct classification models after comparing multiple machine learning algorithms. We found pediatric CD samples exhibited reduced microbial diversity and unique microbial characteristics. Pronounced abundance differences in 45 species and 1,357 KO genes. Particularly, Enterocloster bolteae emerged as a pivotal pediatric CD-associated species. Additionally, we identified a vast amount of microbial genetic variants linked to pediatric CD, including 192 structural variants, 1,256 insertions/deletions (InDels), and 3,567 single nucleotide variants, with a considerable portion of these variants occurred in non-genic regions. The InDel-based model outperformed other predictive models against multidimensional microbial signatures, achieving an AUC of 0.982. The robustness and disease specificity were further confirmed in an independent CD cohort (AUC=0.996) and five other microbiome-associated pediatric cohorts. Our study provided a comprehensive landscape of microbial alterations in pediatric CD and introduced a highly effective diagnostic model rooted in microbial InDels, which contributes to the development of the non-invasive diagnostic tools and targeted therapies.

The association of serum CHI3L1 levels with the presence of Kawasaki disease

Chitinase 3-like protein 1(CHI3L1) has been found to be a biomarker for inflammatory diseases, but the diagnostic value of Kawasaki disease (KD) is not investigated. A total of 180 subjects, including 80 KD patients, 70 febrile controls and 30 healthy controls were recruited. Serum of CHI3L1 were measured with an enzyme-linked immunosorbent assay. The correlation between CHI3L1 and clinical parameters was assessed by Spearman correlation coefficient. Multiple logistic regression was employed to investigate the association between CHI3L1 and the incidence of KD. The diagnostic power was evaluated with the receiver operating characteristic curve analysis. Serum CHI3L1 levels in the KD group were significantly higher than those in the fever control group and healthy group. Compared with fever patients, both patients with incomplete KD and complete KD had higher serum CHI3L1 levels. Serum CHI3L1 levels were positively associated with white blood cell counts, neutrophils, platelet, erythrocyte sedimentation rate, C-reactive protein, alanine aminotransferase and the incidence of KD, and negatively associated with hemoglobin, aspartate aminotransferase and albumin. High CHI3L1 tertiles was significantly associated with the high incidence of KD in the unadjusted or adjusted models. Analysis of the Receiver operating characteristic curves, it was showed that the area under the curve was 0.908, with sensitivity of 0.838 and specificity of 0.8 for continuous CHI3L1, and was 0.884 for categorical CHI3L1, with sensitivity of 0.938 and specificity of 0.643 to distinguish all types of KD, respectively. CHI3L1 had the AUC of 0.901, with sensitivity of 0.826 and specificity of 0.8, and had the area under curve of 0.952, with sensitivity of 0.818 and specificity of 0.971 to discriminate complete KD and incomplete KD from febrile diseases, respectively. Serum of CHI3L1 may be a novel and reliable biomarker for the diagnosis of KD.

Association between chronic diseases and lifestyle risk factors among community-dwelling older adults: a retrospective cross-sectional Chinese population-based study

BackgroundChronic diseases among older adults are recognised as a serious public health problem in China, causing rising social and economic burden. The aim of the study was to evaluate the association between chronic diseases and lifestyle risk factors among community-dwelling older adults who attended community health service centres (CHSC) in Southern China.MethodsA retrospective cross-sectional study (n = 361) was conducted using a random sample of cases from a primary care database registry of two CHSC in Guangzhou city, Guangdong province, China. The sample consisted of community-dwelling older adults aged 60 years and over who receive free annual medical examinations provided by the Chinese government. Data collected included biomarkers for chronic diseases, medical history, levels of physical activity, and lifestyle risk factors.ResultsThere were 361 cases [mean age 74.65 (SD = 5.61) years] included in the sample (from total registry records n = 6,351). The top five chronic diseases were hypertension (55.68%), being overweight or obese (43.77%), hyperuricemia (40.60%), fatty liver disease (34.35%) and hypercholesterolemia (17.17%). Being overweight or obese was significantly associated with having fatty liver disease (OR = 1.22, 95% CI 1.05–1.41), higher WC was significantly associated with having hypertension (OR = 1.05, 95% CI 1.02–1.07), hyperuricemia (OR = 1.04, 95% CI 1.01–1.07), dyslipidemia (OR = 1.09, 95% CI 1.03–1.16), and fatty liver disease (OR = 1.22, 95% CI 1.05–1.41). Smoking was significantly associated with having hyperuricemia (OR = 2.40, 95% CI 1.13–5.07).ConclusionData collected via medical examination identified the top five chronic diseases among older adults of Guangzhou city, China. Lifestyle risk factors are significantly associated with chronic diseases. Findings from the study will inform future design and evaluation of targeted, new services for these older adults. Further research to evaluate lifestyle interventions that can improve the health of older adults living with chronic disease is required.Trial registrationEthical approval ([2022]02-014-01) was obtained from the Health Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. The study was registered on the Chinese Clinical Trial Registry Centre (registry number: ChiCTR2200066750).

Development of amyloid β (1-42) certified reference material NMIJ CRM 6210-a.

Amyloid β is a well-known peptide biomarker for Alzheimer's disease. Various methods for amyloid β such as immunological assays have been reported. It is important to establish metrological traceability using a certified reference material (CRM) at the highest level in the calibration hierarchy to assess equivalence of measured values obtained from each method. Herein, we developed a CRM for amyloid β, named as NMIJ CRM 6210-a, with a concentration traceable to the International System of Units (SI). This CRM comprises a lyophilized synthetic peptide with a human amyloid β (1-42) sequence (hereafter, amyloid β) and includes oxidated, deamidated, and isomerized forms of amyloid β. Two certified values were assigned for the mass concentration of total amyloid β (a mixture of amyloid β and its oxidized, deamidated, and isomerized forms) and amyloid β, determined via amino acid analyses with two different hydrolysis methods with different liquid chromatography mass spectrometry methods coupled to isotope-dilution mass spectrometry on the reconstituted solution of the candidate material with (1.00 0.01) g of 0.1% ammonia aqueous solution. The quantitative results obtained from amino acid analyses were converted into mass concentration using the density and molar mass, resulting in certified values of (46 11) mg/L for total amyloid β and (42.6 7.0) mg/L for amyloid β, respectively. The amyloid β content in total amyloid β was determined by calculating the relative area percentage using liquid chromatographywithultraviolet detection. Furthermore, the storage stability of this CRM was evaluated along with its stability in use, both of which were shown to be stable.

Precision Medicine in Rheumatology: The Role of Biomarkers in Diagnosis and Treatment Optimization

Rheumatic diseases encompass a wide range of autoimmune and inflammatory disorders, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and systemic sclerosis (SSc). These conditions often result in chronic pain, disability, and reduced quality of life, with unpredictable disease courses that may lead to joint destruction, organ damage, or systemic complications. Biomarkers, defined as measurable indicators of biological processes or conditions, have the potential to transform clinical practice by improving disease diagnosis, monitoring, prognosis, and treatment decisions. While significant strides have been made in identifying and validating biomarkers in rheumatic diseases, challenges remain in their standardization, clinical utility, and integration into routine practice. This review provides an overview of the current state of biomarkers in rheumatic diseases, their roles in clinical settings, and the emerging advancements in the field.

Trends in Choroidal Vascularity Index in Cognitively Normal Individuals

Purpose: To establish a normative database of choroidal vascularity index (CVI) in cognitively normal adults. Methods: Cognitively healthy volunteers who had a Montreal Cognitive Assessment (MoCA) score of 23 or higher were included. Exclusion criteria included diabetes mellitus, uncontrolled hypertension, glaucoma, optic neuropathy, vitreoretinal disorders, intraocular surgery other than cataract or refractive, and visual acuity worse than 20/40. Enhanced depth optical coherence tomography images were taken. CVI was calculated from total choroidal area (TCA) and luminal area (LA). Results: Overall average CVI was 67.0% ± 0.026%, mean TCA was 7.105 ± 4.618, and LA was 4.676 ± 2.843. There was no significant influence of sex on CVI (mean 66.9% females, 67.2% males, p-value 0.444). Age was not strongly associated with CVI with R-squared values all below 0.021. 504 eyes (89.4%) were from White participants, 43 from Black participants (7.50%), 6 from Asian participants, and 12 from other/unreported race. Race did not have a significant influence on mean CVI (67.1% White, 67.3% Black, 66.5% Asian, 64.0% other/not reported, p = 0.073). No statistically significant associations were identified between CVI and the presence of hypertension or cardiac disease. Conclusions: CVI is a durable metric across several demographic factors and presence of hypertension and/or cardiac disease. Following additional studies, CVI may be a useful biomarker for neurologic, retinal, and choroidal diseases.