Noninvasive Biomarkers For Diagnosis Research Articles

Integration of Single-Cell and Spatial Transcriptomic Data Reveals Spatial Architecture and Potential Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the gradual loss of neurons and the accumulation of amyloid plaques and neurofibrillary tangles. Despite advancements in the understanding of AD's pathophysiology, the cellular organization and interactions in the prefrontal cortex (PFC) remain elusive. Eight single-cell RNA sequencing (scRNA-seq) datasets from both normal controls and individuals with AD were harmonized. Stringent preprocessing protocols were implemented to uphold dataset integrity. Unsupervised clustering and annotation revealed 22 distinct cell clusters corresponding to 19 unique cell types. The spatial architecture of the PFC region was constructed using the CARD tool. Further analyses encompassed trajectory examination of Oligodendrocyte subtypes, evaluation of regulon activity scores, and spot clustering within white matter regions (WM). Differential expression analysis and functional enrichment assays unveiled molecular signatures linked to AD progression and were validated using microarray data sourced from neurodegenerative disorder patients. Our investigation employs scRNA-seq and spatial transcriptomics to uncover the cellular atlas and spatial architecture of the human PFC in AD. Moreover, our results indicate that Oligodendrocytes are more prevalent in AD patients, showcasing diverse subtypes and spatial organization within WM regions. Each subtype appears to be associated with distinct biological processes and transcriptional regulators, shedding light on their involvement in AD pathology. Notably, the Oligodendrocyte_C6 subtype is linked to neurological damage in AD patients, characterized by heightened expression of genes involved in cell-cell connections, cell membrane stability, and myelination. Additionally, 12 target genes regulated by NFIA were identified, which are upregulated in AD patients and associated with disease progression. Elevated PLXDC2 expression in peripheral blood was also identified, suggesting its potential as a non-invasive biomarker for early AD detection. Our study provides novel insights into the role of Oligodendrocytes in AD and highlights the potential of PLXDC2 as a blood biomarker for non-invasive diagnosis and monitoring of AD patients.

Breath Analysis: Identification of Potential Volatile Biomarkers for Non-Invasive Diagnosis of Chronic Kidney Disease (CKD).

Recently, volatile organic compound (VOC) determination in exhaled breath has seen growing interest due to its promising potential in early diagnosis of several pathological conditions, including chronic kidney disease (CKD). Therefore, this study aimed to identify the breath VOC pattern providing an accurate, reproducible and fast CKD diagnosis at early stages of disease. A cross-sectional observational study was carried out, enrolling a total of 30 subjects matched for age and gender. More specifically, the breath samples were collected from (a) 10 patients with end-stage kidney disease (ESKD) before undergoing hemodialysis treatment (DIAL); (b) 10 patients with mild-moderate CKD (G) including 3 patients in stage G2 with mild albuminuria, and 7 patients in stage G3 and (c) 10 healthy controls (CTRL). For each volunteer, an end-tidal exhaled breath sample and an ambient air sample (AA) were collected at the same time on two sorbent tubes by an automated sampling system and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry. A total of 110 VOCs were detected in breath samples but only 42 showed significatively different levels with respect to AA. Nonparametric tests, such as Wilcoxon/Kruskal-Wallis tests, allowed us to identify the most weighting variables able to discriminate between AA, DIAL, G and CTRL breath samples. A promising multivariate data mining approach incorporating only selected variables (showing p-values lower than 0.05), such as nonanal, pentane, acetophenone, pentanone, undecane, butanedione, ethyl hexanol and benzene, was developed and cross-validated, providing a prediction accuracy equal to 87% and 100% in identifying patients with both mild-moderate CKD (G) and ESKD (DIAL), respectively.

Fetuin-A: a relevant novel serum biomarker for non-invasive diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD): a retrospective case-control study

ObjectivesTo determine how fetuin-A contributes to diagnosing and assessing MASLD severity.MethodsFifty MASLD patients and fifty healthy control participants were involved in this retrospective case-control research. Abdominal ultrasonography, fibroscan with controlled attenuated parameter scan (CAP scan), laboratory investigation (including fetuin-A assessment), clinical examination, and history-taking were performed on every case.ResultsFetuin-A level was considerably higher in the Cases group (1154.85 ± 629.89) than in the Control group (505.29 ± 150.4) (p < 0.001). Fetuin-A had significant validity in the prediction of MASLD at a cut-off > 702.5 with 82% sensitivity, 90% specificity, and 86% overall accuracy.ConclusionOne possible marker for MASLD diagnosis could be fetuin-A. Furthermore, a substantial association between such marker and the severity of the disease as it revealed a significant correlation with ultrasound grading and fibroscan with controlled attenuated parameters.Trial registration1- Pan African Clinical Trial Registry.Unique Identifying number/registration ID: PACTR202309644280965.URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=26860.Registration Approval date: 21/09/2023.2- ClinicalTrials.gov.Unique Identifying number /registration ID: NCT06097039.URL: https://clinicaltrials.gov/study/NCT06097039?cond=NCT06097039&rank=1.Registration Approval date: 25/10/2023.

Coding and Non-Coding Transcriptomic Landscape of Aortic Complications in Marfan Syndrome.

Marfan syndrome (MFS) is a rare congenital disorder of the connective tissue, leading to thoracic aortic aneurysms (TAA) and dissection, among other complications. Currently, the most efficient strategy to prevent life-threatening dissection is preventive surgery. Periodic imaging applying complex techniques is required to monitor TAA progression and to guide the timing of surgical intervention. Thus, there is an acute demand for non-invasive biomarkers for diagnosis and prognosis, as well as for innovative therapeutic targets of MFS. Unraveling the intricate pathomolecular mechanisms underlying the syndrome is vital to address these needs. High-throughput platforms are particularly well-suited for this purpose, as they enable the integration of different datasets, such as transcriptomic and epigenetic profiles. In this narrative review, we summarize relevant studies investigating changes in both the coding and non-coding transcriptome and epigenome in MFS-induced TAA. The collective findings highlight the implicated pathways, such as TGF-β signaling, extracellular matrix structure, inflammation, and mitochondrial dysfunction. Potential candidates as biomarkers, such as miR-200c, as well as therapeutic targets emerged, like Tfam, associated with mitochondrial respiration, or miR-632, stimulating endothelial-to-mesenchymal transition. While these discoveries are promising, rigorous and extensive validation in large patient cohorts is indispensable to confirm their clinical relevance and therapeutic potential.

Construction of mesoporous silica-implanted tungsten oxides for selective acetone gas sensing

As a key biomarker for noninvasive diagnosis of diabetes, the selective detection of trace acetone in exhaled gas using a portable and low-cost device remains a great challenge. Semiconductor metal oxide (SMO) based gas sensors have drawn signification attention due to their potential in miniaturization, user-friendliness, high cost-effectiveness and selective real-time detection for noninvasive clinical diagnosis. Herein, we propose a one-pot solvent evaporation induced tricomponent co-assembly strategy to design a novel ordered mesoporous SMO of silica-implanted WO3 (SiO2/WO3) as sensing materials for trace acetone detection. The controlled co-assembly of silicon and tungsten precursors and amphiphilic diblock copolymer poly(ethylene oxide)-block-polystyrene (PEO-b-PS), and the subsequent thermal treatment enable the local lattice disorder of WO3 induced by the amorphous silica and the formation of ordered mesoporous SiO2/WO3 hybrid walls with a unique metastable ε-phase WO3 framework. The obtained mesoporous SiO2/WO3 composites possess highly crystalline framework with large uniform pore size (12.0–13.3 nm), high surface area (99–113 m2/g) and pore volume (0.17–0.23 cm3/g). Typically, the as-fabricated gas sensor based on mesoporous 2.5%SiO2/WO3 exhibits rapid response/recovery rate (5/17 s), superior sensitivity (Rair/Rgas = 105 for 50 ppm acetone), as well as high selectivity towards acetone. The limit of detection is as low as 0.25 ppm, which is considerably lower than the thresh value of acetone concentration (>1.1 ppm) in the exhaled breath of diabetic patients, demonstrating its great prospect in real-time monitoring in diabetes diagnosis. Moreover, the mesoporous 2.5%SiO2/WO3 sensor is integrated into a wireless sensing module connected to a smart phone, providing a convenient real-time detection of acetone.

Circ_0006949 as a potential non-invasive diagnosis biomarker promotes the proliferation of NSCLC cells via miR-4673/GLUL axis

The 5-year survival for non-small cell lung cancer (NSCLC) remains <20 %, primarily due to the early symptoms of lung cancer are inconspicuous. Prompt identification and medical intervention could serve as effective strategies for mitigating the death rate. We therefore set out to identify biomarkers to help diagnose NSCLC. CircRNA microarray and qRT-PCR reveal that sputum circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC, which can enhance the proliferation and clone formation, regulate the cell cycle, and accelerate the migration and invasion of NSCLC cells. Circ_0006949 and miR-4673 are predominantly co-localized in the cytoplasm of NSCLC cell lines and tissues; it upregulates GLUL by adsorption of miR-4673 through competing endogenous RNAs mechanism. The circ_0006949/miR-4673/GLUL axis exerts pro-cancer effects in vitro and in vivo. Circ_0006949 can boost GLUL catalytic activity, and they are highly expressed in NSCLC tissues and correlate with poor prognosis. In summary, circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC. This novel sputum circRNA is statistically more predictive than conventional serum markers for NSCLC diagnosis. Non-invasive detection of patients with early-stage NSCLC using sputum has shown good potential for routine diagnosis and possible screening.

Urinary Biomarkers for Non-Invasive Diagnosis of Acute Interstitial Nephritis.

Urinary Biomarkers for Non-Invasive Diagnosis of Acute Interstitial Nephritis.

Systematic genome-wide Mendelian randomization reveals the causal links between miRNAs and Parkinson's disease.

MicroRNAs (miRNAs) have pivotal roles in gene regulation. Circulating miRNAs have been developed as novel candidate non-invasive biomarkers for diagnosis, prognosis, and treatment response for diseases. However, miRNAs that have causal effects on Parkinson's Disease (PD) remain largely unknown. To investigate the causal relationships between miRNAs and PD, here we conduct a Mendelian randomization (MR) study. This study utilized the summary-level data of respective genome-wide association studies (GWAS) for 2083 miRNAs and seven PD-related outcomes to comprehensively reveal the causal associations between the circulating miRNAs and PD. Two-sample MR design was deployed and the causal effects were estimated with inverse variance weighted, MR-Egger, and weighted median. Comprehensively sensitive analyses were followed, including Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis, to validate the robustness of our results. Finally, we investigated the potential role of the MR significant miRNAs by predicting their target genes and functional enrichment analysis. Inverse variance weighted estimates suggested that two miRNAs, miR-205-5p (β = -0.46, 95%CI: -0.690 to -0.229, p = 9.3 × 10-5) and miR-6800-5p (β = -0.389, 95%CI: -0.575 to -0.202, p = 4.32 × 10-5), significantly decreased the rate of cognitive decline among PD patients. In addition, eight miRNAs were nominally associated with more than three PD-related outcomes each. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. Gene Ontology (GO) analysis showed that the targets of these causal miRNAs were significantly enriched in cell cycle, apoptotic, and aging pathways. This MR study identified two miRNAs whose genetically regulated expression might have a causal role in the development of PD dementia. Our findings provided potential miRNA biomarkers to make better and early diagnoses and risk assessments of PD.

Automated Multi-Injection Gas Chromatography-Photoionization Detection (AMI-GC-PID) for Qualitative and Quantitative Determination of Urinary Acetone

Acetone is produced from fat metabolism which is increased in diabetic patients due to the disruption of glucose metabolism. Therefore, urinary acetone is expected to be a biomarker for noninvasive diagnosis of diabetes. Although several techniques have been developed for urinary acetone, none meet the clinical needs of automated multi-injection for numerous samples. In this study, we developed automated multi-injection gas chromatography-photoionization detection (AMI-GC-PID) to determine urinary acetone. First, we optimized the sample preprocessing during urine collection and storage before detection and established a standard protocol. The urine was immediately sealed in headspace bottles, stored at 20 °C for 1 h, and equilibrated for 20 min at 80 °C before analysis. Next we evaluated the repeatability of the method and the influence of the urine matrix. The relative standard deviations (RSDs) of the intra-day (nine measurements) and inter-day (three days) measurements were less than 5%. The recovery rate was 97.4% ± 4.6%. AMI-GC-PID was applied to determine urinary acetone in 44 diabetic patients and 29 healthy subjects. The median concentration of urinary acetone was much higher in diabetic patients than in healthy controls (2019 μg/L compared 699 μg/L). The results show that AMI-GC-PID possesses suitable analytical figures of merit for urinary acetone with broad applications in the noninvasive diagnosis of diabetes.

Extracellular vesicles as potential diagnostic markers for kidney allograft rejection.

Kidney transplantation is a highly effective treatment for end-stage kidney disease. However, allograft rejection remains a significant clinical challenge in kidney transplant patients. Although kidney allograft biopsy is the gold-standard diagnostic method, it is an invasive procedure. Since the current monitoring methods, including screening of serum creatinine and urinary protein, are not of sufficient sensitivity, there is a need for effective post-transplant monitoring to detect allograft rejection at an early stage. Extracellular vesicles are vesicles with a lipid bilayer that originate from different cell types in pathological and physiological conditions. The content of extracellular vesicles reflects the status of cells at the time of their production. This review comprehensively summarizes clinical, in vivo, and in vitro reports that highlight the potential of extracellular vesicles as diagnostic biomarkers for kidney allograft rejection. Clarification would facilitate differentiation between rejection and non-rejection and identification of the mechanisms involved in the allograft rejection. Despite increasing evidence, further research is necessary to establish the clinical utility of extracellular vesicles in the diagnosis and monitoring of allograft rejection in kidney transplant recipients. Using extracellular vesicles as non-invasive biomarkers for diagnosis of kidney allograft rejection could have tremendous benefits in improving patient outcomes and reduce the need for invasive procedures.

Non-Invasive Biomarkers for Diagnosis, Risk Prediction, and Therapy Guidance of Glomerular Kidney Diseases: A Comprehensive Review.

Effective management of glomerular kidney disease, one of the main categories of chronic kidney disease (CKD), requires accurate diagnosis, prognosis of progression, assessment of therapeutic efficacy, and, ideally, prediction of drug response. Multiple biomarkers and algorithms for the assessment of specific aspects of glomerular diseases have been reported in the literature. Though, the vast majority of these have not been implemented in clinical practice or are not available on a global scale due to limited access, missing medical infrastructure, or economical as well as political reasons. The aim of this review is to compile all currently available information on the diagnostic, prognostic, and predictive biomarkers currently available for the management of glomerular diseases, and provide guidance on the application of these biomarkers. As a result of the compiled evidence for the different biomarkers available, we present a decision tree for a non-invasive, biomarker-guided diagnostic path. The data currently available demonstrate that for the large majority of patients with glomerular diseases, valid biomarkers are available. However, despite the obvious disadvantages of kidney biopsy, being invasive and not applicable for monitoring, especially in the context of rare CKD etiologies, kidney biopsy still cannot be replaced by non-invasive strategies.

Diagnostic, prognostic, and therapeutic potential of exosomal microRNAs in renal cancer.

Renal cell carcinoma (RCC) arises from the tubular epithelial cells of the nephron. It has the highest mortality rate among urological cancers. There are no effective therapeutic approaches and no non-invasive biomarkers for diagnosis and follow-up. Thus, suitable novel biomarkers and therapeutic targets are essential for improving RCC diagnosis/prognosis and treatment. Circulating exosomes such as exosomal microRNAs (Exo-miRs) provide non-invasive prognostic/diagnostic biomarkers and valuable therapeutic targets, as they can be easily isolated and quantified and show high sensitivity and specificity. Exosomes secreted by an RCC can exhibit alterations in the miRs' profile that may reflect the cellular origin and (patho)physiological state, as a ''signature'' or ''fingerprint'' of the donor cell. It has been shown that the transportation of renal-specific miRs in exosomes can be rapidly detected and measured, holding great potential as biomarkers in RCC. The present review highlights the studies reporting tumor microenvironment-derived Exo-miRs with therapeutic potential as well as circulating Exo-miRs as potential diagnostic/prognostic biomarkers in patients with RCC.

Urinary exosomal miRNA-451a can be used as a potential noninvasive biomarker for diagnosis, reflecting tubulointerstitial damage and therapeutic response in IgA nephropathy

To investigate the potential clinical value of urinary exosomal (uE) miR-451a as a biomarker for IgAN, urinary exosomes were isolated from 40 patients with IgAN, 30 patients with primary renal diseases without IgA as disease controls (non-IgAN group) and 21 healthy controls (HCs). The expression of miR-451a within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). uE miR-451a was significantly upregulated in patients with IgAN compared to non-IgAN and HCs. The uE miR-451a level was positively correlated with the change in eGFR and negatively correlated with serum creatinine, urinary macrophage migration inhibitory factor (MIF), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). A dual-luciferase reporter assay confirmed that MIF was a direct target of miR-451a. Receiver operating characteristic (ROC) curve analysis revealed that the expression of uE miR-451a showed potential diagnostic value for IgAN. Additionally, the uE miR-451a level could distinguish patients with IgAN with mild tubular atrophy/interstitial fibrosis from those with severe tubular atrophy/interstitial fibrosis. After a mean follow-up of 14.2 months, the levels of eGFR loss (ml/min/1.73 m2/year) were negatively correlated with baseline miR-451a. The levels of baseline miR-451a in the complete remission group were significantly higher than those in the non-complete remission group. uE miR-451a expression was significantly elevated in patients with IgA nephropathy and may serve as a potential biomarker for the diagnosis of IgAN and evaluation of tubulointerstitial damage, while the baseline levels of uE miR-451a may be predictors of therapeutic efficacy and disease progression.

Identification of four snoRNAs (SNORD16, SNORA73B, SCARNA4, and SNORD49B) as novel non-invasive biomarkers for diagnosis of breast cancer

BackgroundEmerging data point to the critical role of snoRNA in the emergence of different types of cancer, but scarcely in breast cancer (BC). This study aimed to clarify the differential expressions and potential diagnostic value of SNORD16, SNORA73B, SCARNA4, and SNORD49B in BC.MethodsWe screened differential snoRNAs in BC tissues and adjacent tissues through SNORic datasets, and then we further verified them in the plasma of BC patients and healthy volunteers by quantitative polymerase chain reaction (qPCR).ResultsThese four snoRNAs: SNORD16, SNORA73B, SCARNA4, and SNORD49B were considerably more abundant in cancerous tissues than in neighboring tissues in the TCGA database. Their plasma levels were also higher in BC and early-stage BC patients when compared to healthy controls. Furthermore, the ROC curve demonstrated that BC (AUC = 0.7521) and early-stage BC (AUC = 0.7305) might be successfully distinguished from healthy people by SNORD16, SNORA73B, SCARNA4, and SNORD49B.ConclusionPlasma snoRNAs: SNORD16, SNORA73B, SCARNA4, and SNORD49B were upregulated in BC and early-stage BC and can be used as potential diagnostic markers for BC and early-stage BC.

Emerging biomarkers for non-invasive diagnosis and treatment of cancer: a systematic review.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023474749 PROSPERO, identifier CRD42023474749.

Plasma long non-coding RNAs as biomarkers for bone marrow infiltration and stage in diffuse large B-cell lymphoma.

We aimed to evaluate the expression profiles of five circulating lncRNAs (HOTAIR, MALAT-1, XIST, SNHG15, and H19) in DLBCL patients and explore potential associations between their expression and different clinicopathological features. Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma (NHL), exhibits marked genetic and clinical heterogeneity, emphasizing the need for improved tools for risk stratification. Long non-coding RNAs (lncRNAs) emerged as regulators in different cellular processes and have been linked to cancer pathogenesis. Real-time quantitative PCR (qRT-PCR) was used to evaluate lncRNA expression in the plasma of 65 newly diagnosed adult DLBCL patients and 30 age-matched controls. HOTAIR expression was significantly elevated in DLBCL patients, while SNHG15 was significantly downregulated. Interestingly, both HOTAIR and SNHG15 demonstrated robust discriminatory power between DLBCL and healthy individuals, achieving area under the curve (AUC) values of 69% and 71%, respectively. H19 expression displayed a significant association with early-stage (stage I) DLBCL. While upregulated HOTAIR was a significant independent predictor of poor prognosis, high SNHG15 expression appeared to have a protective effect on mortality rates. Our findings suggest that circulating lncRNA expression patterns are promising tools as non-invasive biomarkers for diagnosis of DLBCL. Specific lncRNAs, such as HOTAIR, SNHG15, and H19, could offer potential for disease staging and patient prognosis. Long-term follow-up studies are recommended to further elucidate the interplay between these lncRNAs and survival rates, as well as their interactions with other genetic and pathological features of DLBCL.

Evaluation of Plasma Glycosaminoglycan in monitoring the patients of Renal cell carcinoma after Nephrectomy

Renal cell carcinoma is the thirteenth most widespread malignancy worldwide and is the leading cause of urogenital tract cancers. Worldwide, renal cell carcinoma is sixth most prevalent cancer in males and tenth most in females. Its diagnosis is based on histological findings and CT scans that were performed for isolated symptoms. Treatment options include chemotherapy, radiofrequency ablation, nephron-sparing surgery, and radical nephrectomy. Therefore, there is a need for an early non-invasive bio marker for diagnosis, disease surveillance, as well as for monitoring of RCC after therapy. Objective: To determine the role of plasma glycosaminoglycans levels for monitoring and prognosis of renal cell carcinoma patients after nephrectomy. Methods: A Cross sectional study was taken place at Armed forces institute of Pathology in collaboration with Armed forces institute of urology from July 2021 to Dec 2022. A total of 124 samples were included in study, out of which 62 samples were collected from pre-operated patients and another 62 from same RCC patients after operation. Plasma Glycosaminoglycans levels were analyzed through manual enzyme linked immunosorbent assay by non-competitive sandwich technique. Quantitative variables were calculated by means and standard deviation while qualitative variables were assessed as frequency and percentage. Paired t test was applied to check statistical significance of the difference between the means of pre-operative and post-operative cases. Results: Mean age of total population was 39.24±15.90 years. Taking in account age, gender and staging of pre- and post-operative patients, the results revealed significant post-Surgical decrease in plasma glycosaminoglycans levels (p value &lt;0.05). In renal cell carcinoma patients 74(61.7%) were in T2NM0 stage while 31(25.8%) in T3NM0 stage and 15(12.5%) in T4NM0 stage. Majority of patients lied in T2NM0 stage while T3NM0 stage was common in males and T4NM0 stage in females. Conclusion: Plasma glycosaminoglycans levels is a potential biomarker in post-surgical phase of RCC patients. It can be utilised as a promising marker to monitor RCC patients after nephrectomy. The non-invasive nature of the test will help monitoring of such patients which will prove convenient for both patient and treating surgeon.&#x0D;

Immune Profiling of Patients with Systemic Sclerosis through Targeted Proteomic Analysis.

High-throughput proteomic analysis could offer new insights into the pathogenesis of systemic sclerosis (SSc) and reveal non-invasive biomarkers for diagnosis and severity. This study aimed to assess the protein signature of patients with SSc compared to that of healthy volunteers, decipher various disease endotypes using circulating proteins, and determine the diagnostic performance of significantly expressed plasma analytes. We performed targeted proteomic profiling in a cohort of fifteen patients with SSc and eighteen controls using the Olink® (Olink Bioscience, Uppsala, Sweden)Target 96 Inflammation Panels. Seventeen upregulated proteins involved in angiogenesis, innate immunity, and co-stimulatory pathways discriminated between patients with SSc and healthy controls (HCs) and further classified them into two clusters, a low-inflammatory and a high-inflammatory endotype. Younger age, shorter disease duration, and lack of reflux esophagitis characterized patients in the low-inflammatory endotype. TNF, CXCL9, TNFRSF9, and CXCL10 positively correlated with disease progression, while the four-protein panel comprising TNF, CXCL9, CXCL10, and CX3CL1 showed high diagnostic performance. Collectively, this study identified a distinct inflammatory signature in patients with SSc that reflects a persistent T helper type 1 (Th 1) immune response irrespective of disease duration, while the multi-protein panel might improve early diagnosis in SSc.

Association of Blood-Based DNA Methylation Markers With Late-Onset Alzheimer Disease: A Potential Diagnostic Approach.

There is an urgent need to identify novel noninvasive biomarkers for Alzheimer disease (AD) diagnosis. Recent advances in blood-based measurements of phosphorylated tau (pTau) species are promising but still insufficient to address clinical needs. Epigenetics has been shown to be helpful to better understand AD pathogenesis. Epigenetic biomarkers have been successfully implemented in other medical disciplines, such as oncology. The objective of this study was to explore the diagnostic accuracy of a blood-based DNA methylation marker panel as a noninvasive tool to identify patients with late-onset Alzheimer compared with age-matched controls. A case-control study was performed. Blood DNA methylation levels at 46 cytosine-guanine sites (21 genes selected after a comprehensive literature search) were measured by bisulfite pyrosequencing in patients with "probable AD dementia" following National Institute on Aging and the Alzheimer's Association guidelines (2011) and age-matched and sex-matched controls recruited at Neurology Department-University Hospital of Navarre, Spain, selected by convenience sampling. Plasma pTau181 levels were determined by Simoa technology. Multivariable logistic regression analysis was performed to explore the optimal model to discriminate patients with AD from controls. Furthermore, we performed a stratified analysis by sex. The final study cohort consisted of 80 patients with AD (age: median [interquartile range] 79 [11] years; 58.8% female) and 100 cognitively healthy controls (age 77 [10] years; 58% female). A panel including DNA methylation levels at NXN, ABCA7, and HOXA3 genes and plasma pTau181 significantly improved (area under the receiver operating characteristic curve 0.93, 95% CI 0.89-0.97) the diagnostic performance of a single pTau181-based model, adjusted for age, sex, and APOE ɛ4 genotype. The sensitivity and specificity of this panel were 83.30% and 90.00%, respectively. After sex-stratified analysis, HOXA3 DNA methylation levels showed consistent association with AD. These results highlight the potential translational value of blood-based DNA methylation biomarkers for noninvasive diagnosis of AD. Research Ethics Committee of the University Hospital of Navarre (PI17/02218).

Role of Fetuin-A as a Noninvasive Biomarker in Diagnosis and Assessment of Severity of Non-Alcoholic Fatty Liver Disease.

Role of Fetuin-A as a Noninvasive Biomarker in Diagnosis and Assessment of Severity of Non-Alcoholic Fatty Liver Disease.