Related Biomarkers Research Articles

Neurophysiological markers of early cognitive decline in older adults: a mini-review of electroencephalography studies for precursors of dementia

The early detection of cognitive decline in older adults is crucial for preventing dementia. This mini-review focuses on electroencephalography (EEG) markers of early dementia-related precursors, including subjective cognitive decline, subjective memory complaints, and cognitive frailty. We present recent findings from EEG analyses identifying high dementia risk in older adults, with an emphasis on conditions that precede mild cognitive impairment. We also cover event-related potentials, quantitative EEG markers, microstate analysis, and functional connectivity approaches. Moreover, we discuss the potential of these neurophysiological markers for the early detection of cognitive decline as well as their correlations with related biomarkers. The integration of EEG data with advanced artificial intelligence technologies also shows promise for predicting the trajectory of cognitive decline in neurodegenerative disorders. Although challenges remain in its standardization and clinical application, EEG-based approaches offer non-invasive, cost-effective methods for identifying individuals at risk of dementia, which may enable earlier interventions and personalized treatment strategies.

Relevance of the basophil activation test in a cohort of 240 patients with chronic spontaneous urticaria.

Basophil activation test (BAT) is considered to be the best biomarker to predict autoimmune chronic spontaneous urticaria (aiCSU). To date, few studies have investigated the utility of BAT in real-life clinical practice, the role of aiCSU biomarkers in relation to omalizumab therapy and the association between aiCSU tests. This study aimed to analyze the clinical and laboratory features of a prospective cohort with CSU according to their BAT status, as well as to study omalizumab efficacy according to aiCSU biomarkers. A prospective study was conducted from 2010 to 2024 in patients with CSU. BAT alongside other laboratory tests were performed, and clinical and therapeutic features were prospectively collected. Data obtained was compared according to BAT status. Furthermore, omalizumab drug survival was typified according to aiCSU biomarkers. A total of 240 patients were included in the study. BAT positive patients presented more frequently low IgE levels, higher occurrence of IgG anti-thyroid peroxidase (anti-TPO) positivity, autologous serum skin test (ASST) positivity, basopenia, and eosinopenia. The multivariate logistic regression revealed that ASST (OR:7.69, 95%CI: 2.81-21.0) and anti-TPO (OR:2.63, 95%CI: 1.05-6.61) were associated to BAT positivity. All aiCSU biomarkers (BAT, ASST, combined ASST/BAT positivity and low IgE/anti-TPO+) associated significantly shorter omalizumab survival due to failure. In the cohort, both low IgE/anti-TPO+ and ASST were concordant and associated to BAT. The use of BAT in clinical practice delineates a subgroup of patients with specific clinical, laboratory and therapeutic features, including increased omalizumab failure.

Mitophagy related diagnostic biomarkers for coronary in-stent restenosis identified using machine learning and bioinformatics

Percutaneous coronary intervention (PCI) combined with stent implantation is currently one of the most effective treatments for coronary artery disease (CAD). However, in-stent restenosis (ISR) significantly compromises its long-term efficacy. Mitophagy plays a crucial role in vascular homeostasis, yet its role in ISR remains unclear. This study aims to identify mitophagy-related biomarkers for ISR and explore their underlying molecular mechanisms. Through differential gene expression analysis between ISR and Control samples in the combined dataset, 169 differentially expressed genes (DEGs) were identified. Twenty-three differentially expressed mitophagy-related genes (DEMRGs) were identified by intersecting with mitophagy-related genes (MRGs) from the GeneCards, and functional enrichment analysis indicated their significant involvement in mitophagy-related biological processes. Using Weighted Gene Co-expression Network Analysis (WGCNA) and three machine learning algorithms (Logistic-LASSO, RF, and SVM-RFE), LRRK2, and ANKRD13A were identified as mitophagy-related biomarkers for ISR. The nomogram based on these two genes also exhibited promising diagnostic performance for ISR. Gene Set Enrichment Analysis (GSEA) as well as immune infiltration analyses showed that these two genes were closely associated with immune and inflammatory responses in ISR. Furthermore, potential small molecule compounds with therapeutic implications for ISR were predicted using the connectivity Map (cMAP) database. This study systematically investigated mitophagy-related biomarkers for ISR and their potential biological functions, providing new insights into early diagnosis and precision treatment strategies for ISR.

Single and combined effects of phenanthrene and cadmium on oxidative stress and detoxification related biomarkers in clams (Meretrix meretrix)

Biomarkers concerning antioxidant reactions and detoxification metabolics were evaluated in Meretrix meretrix exposed to cadmium (Cd, 10 μg/L) and phenanthrene (PHE, 100 μg/L) individually and in combination (10 μg/L Cd + 100 μg/L PHE) for 7 days. The accumulation of Cd and PHE measured in the digestive gland, gill, mantle, and axe foot of the clam showed significant increase in combination treatment and it was higher than the single Cd or single PHE treatment. The activities of oxidative stress-related enzymes, the expression of Cu/Zn SOD, and the content of MDA increased after Cd and PHE exposure in the digestive gland and gill at most cases. In the digestive gland, CAT gene expression was significantly induced in Cd-single group and significantly inhibited in PHE-single group and Cd-PHE mixed group at both day 3 and day 7; in the gill, CAT gene expression was significantly inhibited in all groups at day 3 and except for Cd-single group at day 7. MT expression was significantly induced in Cd-single and Cd-PHE mixed groups at day 7, while hsp70 expression was significantly inhibited in PHE-single and Cd-PHE mixed groups at day 7. The results indicated that SOD, CAT, GST, MDA, Cu/Zn SOD, CAT, MT and hsp70 were sensitive to cadmium and PHE in a water environment, and can be used as indicators of marine heavy metal pollution.

B-147 Enhancing the Detection of Vitamin D Metabolites by LC-MS/MS Using a Novel Derivatization Kit

Abstract Background Vitamin D is crucial for various biological functions and exists in various tissues, including bones, intestines, and kidneys. 25-hydroxyvitamin D serves as a key marker for assessing vitamin D status in the body. Currently, LC-MS/MS is the gold standard for measuring vitamin D levels. The JeoQuant Kit for LC/MS Analysis of Vitamin D Metabolites (JEOL, Tokyo, Japan), which is used for the determination of vitamin D metabolites in serum based on the DAP-PA (Seki et al, 2019), enhances the ionization efficiency in the LC-MS/MS system for four vitamin D metabolites (25(OH)D3, 25(OH)D2, 24,25(OH)2D3 and 3-epi-25(OH)D3), enabling accurate fractionation and quantification. DAP-PA was developed as a caged Cookson-type reagent, demonstrating significantly enhanced stability compared to previous non-caged Cookson-type reagents. Our research aimed to assess whether the kit works practically. Methods The JeoQuant Kit contains internal standards of stable isotope-labelled compounds at appropriate concentrations, derivatization reagents, quality control materials derived from human serum and calibration materials. An Acquity H-Class UPLC coupled with an Acquity TQD mass spectrometer (Waters, MA, US) was used for analysis. CAPCELL CORE C18 2.1mm*100mm (Osaka-soda, Tokyo, Japan) was used as the analytical column. For the pretreatment, an Isolute SLE+ column (Biotage, Tokyo, Japan) was used. Eluent of LC-MS/MS was used 0.1% formic acid aqueous solution and 0.1% formic acid acetonitrile, with binary gradient. Results Using attached control L/H, reproducibility was shown by intra- and inter-assay CVs which were below 10% and 15%, respectively. Storage tests of derivatization agents at -20°C, 4°C, and room temperature for one week showed no significant difference on peak areas (one-way ANOVA). Through this derivatization, it was possible to achieve more than a 20-fold increase in sensitivity compared to measurements without derivatization. Notably, low concentrations of 3-epi-25(OH)D3 were distinctly separated and detected. Conclusions This study showed that the JeoQuant Kit effectively increases the sensitivity of vitamin D metabolites through derivatization. It also emphasized the reagent's notable stability. Furthermore, it enabled the detection of 3-epi-25(OH)D3 with less sensitive LC-MS/MS models, offering clear separation from 25(OH)D3. The kit, which is complete with calibrants, internal standards, and quality control samples, simplifies analytical procedures for vitamin D metabolite quantification, potentially aiding in developing Vitamin D- related biomarkers. Efforts to compare analytical performance of this kit with that of other methods are underway to establish its benefits.

The temporal dynamics of the gut mycobiome and its association with cardiometabolic health in a nationwide cohort of 12,641 Chinese adults

The dynamics of the gut mycobiome and its association with cardiometabolic health remain largely unexplored. Here, we employ internal transcribed spacer (ITS) sequencing to capture the gut mycobiome composition and dynamics within a nationwide human cohort of 12,641 Chinese participants, including 1,946 participants with repeated measurements across three years. We find that the gut mycobiome is associated with cardiometabolic diseases and related biomarkers in both cross-sectional and dynamic analyses. Fungal alpha diversity indices and 19 mycobiome genera are the major contributors to the mycobiome-cardiometabolic disease link. Particularly, Saccharomyces emerges as an effect modifier of traditional risk factors in promoting type 2 diabetes risk. Further integration of multi-omics data reveals key metabolites such as γ-linolenic acid and L-valine linking the gut mycobiome to type 2 diabetes. This study advances our understanding of the potential roles of the gut mycobiome in cardiometabolic health.

Grifola frondosa extract as a fetal bovine serum supplement for the culture of bovine muscle satellite cells under low serum conditions

Expensive fetal bovine serum (FBS) is a major obstacle to the production of cultivated meat. However, because FBS substitutes do not sufficiently induce cell proliferation, a good alternative is to reduce the amount of FBS and use ingestible additives to promote cell proliferation. In this study, Grifola frondosa extract (GFE) was used to investigate its potential as an additive to promote myogenesis of bovine muscle satellite cells from Hanwoo cattle under low serum conditions (10 % FBS). GFE treated with 10 % FBS only during the proliferation period not only increased cell proliferation and related biomarkers in a concentration-dependent manner (0.78–12.5 μg/mL), but also increased cell differentiation. Additionally, differentiation was promoted when cells were with GFE treated only during the differentiation period. Especially GFE at 12.5 µg/mL induced significantly higher proliferation and differentiation rates than 20 % FBS medium. In particular, compared to treatment alone in the proliferation or differentiation periods, GFE treatment in both periods contributed to an increase in the differentiation rate and significantly enhanced total protein production. The integration of GFE into cultivated meat production presents a promising approach to reducing FBS dependence, lowering costs, and enhancing scalability, aligning with sustainability and consumer acceptance goals.

Comparison between standard hematological parameters and blood doping biomarkers in dried blood spots within the athlete population of Swiss Sport Integrity.

The study demonstrated the feasibility of incorporating RNA biomarkers, specifically 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), to improve the hematological module of the Athlete Biological Passport (ABP) in routine antidoping context. The aim was to investigate the implementation of reticulocyte (RET) related biomarkers, specifically ALAS2 and CA1, using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on dried blood spots (DBS) from elite athletes. Hemoglobin changes over time in DBS samples was measured as well. Combining hemoglobin and messenger RNA (mRNA) analyses allowed to monitor alterations of the established marker, "DBS OFF-score". Ten athletes were selected for sampling by the Swiss national antidoping organization, Swiss Sports Integrity (SSI). Samples were collected, transported and analyzed for ABP following the World Anti-Doping Agency (WADA) procedures and spotted onto Protein Saver DBS cards. Most athletes exhibited stable biomarker levels, except for one individual involved in ski mountaineering, who demonstrated a sustained increase in ALAS2 compared to the individual baseline. This elevation could be due to blood withdrawal or other factors, such as doping with substances outside the targeted test menu. In this study, RNA-biomarkers were successfully analyzed in routine blood samples, and the project demonstrated promising results for the implementation of ALAS2 and CA1 in routine analysis to complement the ABP.

New Insight in Using of Mesenchyme Stem Cell Conditioning Medium for the Impaired Muscle related Biomarkers: In vivo Study with Rat Model.

This study aimed to investigate the effects of Umbilical Cord Mesencymal Stem Cell Conditioning Medium (UC MSC-CM) administration on body weight recovery and the level of four molecular biomarkers, namely Superoxide Dismutase (SOD), vascular Endothelial Growth Factor (VEGF), C-Reactive Protein (CRP), and myostatin. Secretome was injected intramuscularly twice at 1.5 mL (day 7 and 14) into the right thigh of high-dose, short-term galactose-induced aging rats. The data of day 7 (before) and day 21 (after the administration) were evaluated. The body weights and the four biomarkers were measured before (day 7) and after intervention (day 21). This study showed that the UC MSC-CM intramuscular administrations did not influence body weight regeneration. However, it could increase SOD and VEGF levels and decrease CRP and myostatin levels. Treatment with UC MSC-CM is a promising and potential agent in treating sarcopenia.

Sarcopenia is a predictor for Alzheimer’s continuum and related clinical outcomes

Low body mass index is closely related to a high risk of Alzheimer’s disease (AD) and related biomarkers including amyloid-β (Aβ) deposition. However, the association between sarcopenia and Aβ-confirmed AD remains controversial. Therefore, we investigated the relationship between sarcopenia and the AD continuum. We explored sarcopenia’s association with clinical implications of participants on the AD continuum. We prospectively enrolled 142 participants on the AD continuum (19 with preclinical AD, 96 with mild cognitive impairment due to AD, and 28 with AD dementia) and 58 Aβ-negative cognitively unimpaired participants. Sarcopenia, assessed using dual-energy X-ray absorptiometry and hand grip measurements, was considered a predictor. AD continuum, defined by Aβ deposition on positron emission tomography served as an outcome. Clinical severity in participants on the AD continuum assessed using hippocampal volume, Mini-Mental State Examination (MMSE), Seoul Verbal Learning Test (SVLT), and Clinical Dementia Rating Scale Sum of Boxes Scores (CDR-SOB) were also considered an outcome. Sarcopenia (odds ratio = 4.99, p = 0.004) was associated independently with the AD continuum after controlling for potential confounders. Moreover, sarcopenia was associated with poor downstream imaging markers (decreased hippocampal volume, β = − 0.206, p = 0.020) and clinical outcomes (low MMSE, β = − 1.364, p = 0.025; low SVLT, β = − 1.077, p = 0.025; and high CDR-SOB scores, β = 0.783, p = 0.022) in participants on the AD continuum. Sarcopenia was associated with the AD continuum and poor clinical outcome in individuals with AD continuum. Therefore, our results provide evidence for future studies to confirm whether proper management of sarcopenia can effective strategies are required for sarcopenia management to prevent the AD continuum and its clinical implications.

Correlation analysis of cofilin-1 with renal prognosis in primary IgA nephropathy

PurposeThe purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN).MethodsPatients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis.Results133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803).ConclusionCofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN.

Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus-Associated Tuberculosis.

Mortality from human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly among hospitalized patients. In 433 people with HIV hospitalized with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10, and PIIINP were associated with Mtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB.

Can integration of Alzheimer's plasma biomarkers with MRI, cardiovascular, genetics, and lifestyle measures improve cognition prediction?

There is increasing interest in Alzheimer's disease related plasma biomarkers due to their accessibility and scalability. We hypothesized that integrating plasma biomarkers with other commonly used and available participant data (MRI, cardiovascular factors, lifestyle, genetics) using machine learning (ML) models can improve individual prediction of cognitive outcomes. Further, our goal was to evaluate the heterogeneity of these predictors across different age strata. This longitudinal study included 1185 participants from the Mayo Clinic Study of Aging who had complete plasma analyte work-up at baseline. We used the Quanterix Simoa immunoassay to measure neurofilament light, Aβ1-42 and Aβ1-40 (used as Aβ42/Aβ40 ratio), glial fibrillary acidic protein, and phosphorylated tau 181 (p-tau181). Participants' brain health was evaluated through gray and white matter structural MRIs. The study also considered cardiovascular factors (hyperlipidemia, hypertension, stroke, diabetes, chronic kidney disease), lifestyle factors (area deprivation index, body mass index, cognitive and physical activities), and genetic factors (APOE, single nucleotide polymorphisms, and polygenic risk scores). An ML model was developed to predict cognitive outcomes at baseline and decline (slope). Three models were created: a base model with groups of risk factors as predictors, an enhanced model included socio-demographics, and a final enhanced model by incorporating plasma and socio-demographics into the base models. Models were explained for three age strata: younger than 65 years, 65-80 years, and older than 80 years, and further divided based on amyloid positivity status. Regardless of amyloid status the plasma biomarkers showed comparable performance (R² = 0.15) to MRI (R² = 0.18) and cardiovascular measures (R² = 0.10) when predicting cognitive decline. Inclusion of cardiovascular or MRI measures with plasma in the presence of socio-demographic improved cognitive decline prediction (R² = 0.26 and 0.27). For amyloid positive individuals Aβ42/Aβ40, glial fibrillary acidic protein and p-tau181 were the top predictors of cognitive decline while Aβ42/Aβ40 was prominent for amyloid negative participants across all age groups. Socio-demographics explained a large portion of the variance in the amyloid negative individuals while the plasma biomarkers predominantly explained the variance in amyloid positive individuals (21% to 37% from the younger to the older age group). Plasma biomarkers performed similarly to MRI and cardiovascular measures when predicting cognitive outcomes and combining them with either measure resulted in better performance. Top predictors were heterogeneous between cross-sectional and longitudinal cognition models, across age groups, and amyloid status. Multimodal approaches will enhance the usefulness of plasma biomarkers through careful considerations of a study population's socio-demographics, brain and cardiovascular health.

Abstract P440: Discovery of clinical candidate GSC002219, a highly selective oral CYP11B2 inhibitor for hypertension

Background: Aldosterone is an important mediator of hypertension and its aberration could contribute to heart and kidney diseases. Aldosterone synthase inhibitors (ASI) attenuate the production of aldosterone directly and have been proposed as an alternative to mineralocorticoid receptor antagonists (MRA) for treatment of resistant hypertension and chronic renal disease. GSC002219 is a potent inhibitor of aldosterone synthase (CYP11B2) with high selectivity over the closely related enzyme CYP11B1. The aim of the study was to evaluate the effect of GSC002219 on aldosterone and blood pressure. Methods: The inhibitory effect of GSC002219 against CYP11B2 and CYP11B1 proteins was assessed in human renal leiomyoblastoma cells expressing recombinant human / cynomolgus CYP11B1or CYP11B2 enzymes, respectively. GSC002219 was further evaluated in Synacthen (ACTH) challenged cynomolgus monkey model for its effects against various related key biomarkers including cortisol, aldosterone and precursors. The effects of GSC002219 on systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated in stroke-prone spontaneously hypertensive rat (SHRSP) model. Results: GSC002219 potently inhibits CYP11B2 with an IC 50 of 27nM, while maintains a &gt;150-fold selectivity over CYP11B1. In ACTH challenged cynomolgus monkey model, single oral doses of GSC002219 at 0.03 mg/kg and 0.1 mg/kg could suppress aldosterone production to 80% and 93%, respectively, comparing to vehicle-treated animals without any effect towards cortisol levels. In the rat SHRSP hypertension model, GSC002219 could effectively lower both SBP and DBP. GSC002219 has an excellent in vitro ADME and toxicology profile as well as a balanced physicochemical property. In 14-day rat and monkey toxicology studies, GSC002219 displayed good tolerance, excellent PK profile and a great safety window (&gt;100 fold). Conclusions: Taken together, GSC002219 is a safe and potent inhibitor of CYP11B2 and efficacious in various disease models of hypertension. GSC002219 is under IND-enabling study and may enter the clinical development early 2025.

Prognostic value of KLFs family genes in renal clear cell carcinoma

Numerous studies have shown that the Krüppel-like factors (KLFs) family of transcription factors regulate various eukaryotic physiological processes including the proliferation, differentiation, senescence, death, and carcinogenesis of animal cells. In addition, they are involved in the regulation of key biological processes such as cell cycle, DNA repair, and immune response. Current studies focus on investigating the role of KLFs in normal physiological conditions and the incidence and development of diseases. However002C the significance of KLFs family genes in clear cell renal cell carcinoma (ccRCC) remains partly understood; therefore, an in-depth investigation of their role and clinical value in this cancer is desired. The study aimed to investigate the role of KLF family genes in the incidence, development, and prognosis of ccRCC, and to identify the related potential biomarkers and therapeutic targets. The expression of KLFs in the RNA sequencing data of 613 ccRCCs from the TCGA database was analyzed using R software, and UALCAN and GEPIA assessed the expression of KLF genes in ccRCC. Real-time fluorescence quantitative PCR analysis was performed using 10 pairs of paired ccRCC sample tissues and renal cancer cell lines from the First Affiliated Hospital of Nanchang University. Overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of Kidney Clear Cell Carcinoma (KIRC) samples at differential expressions of KLFs in the TCGA database were analyzed using the R software, followed by generating a nomogram prediction model. GSCALite assessed the interactions of KLF genes with miRNAs and generated network maps. Protein interaction network maps of 50 neighboring genes associated with KLF mutations were analyzed using STRING with GO and KEGG functional enrichment analyses. The cBioPortal determined the probability of KLF gene mutations and their impact on OS and disease-free survival (DFS) in patients with ccRCC. Immune cell infiltration of KLFs was analyzed using TIMER. Finally, GSCALite was used to analyze the drug sensitivity and associated pathways of action of KLFs. Correlation validation using cellular experiments. KLF3/5/9/15 were significantly downregulated in ccRCC tissues, whereas KLF16/17 were upregulated compared with the adjacent tissues. Patients with high mRNA levels of KLF16/17 showed significantly lower OS, PFI, and DSS, whereas KLF3/5/9 showed a reverse trend. In patients with ccRCC, a significant correlation was observed between KLF mutations and OS and DSS. Furthermore, the correlation of KLF3/5/9 with immune cell infiltration was stronger than that of KLF15/16, while KLF17 was significantly associated with the Epithelial-Mesenchymal Transition (EMT) pathway. Overexpression of KLF5 inhibits the proliferative and migratory capacity of renal cancer cells (786-O and OS-RC-2), as well as their sensitivity to relevant small molecule drugs. Our research revealed the expression levels and biological significance of KLF genes in ccRCC, particularly highlighting the potential of KLF5 as a promising biomarker and therapeutic target for effective prognosis and diagnosis of ccRCC.

Risk factors and cognitive domain markers of progression in subjective cognitive decline.

We evaluated risk factor differences and cognitive domain markers associated with progression in subjects with subjective cognitive decline (SCD) at baseline from the NYU Alzheimer Disease Research Center. We included SCD non-decliners (n = 27), who remained stable, and decliners (n = 24), who progressed to mild cognitive impairment or worse, between the second to sixth yearly follow-up visits. Adjusted mixed-effects models examined group differences and associations between demographic, APOE status, psychometric test performance and comorbidities with longitudinal-decline. Overall, mean (SD) age was 67.4 (9.2) and total follow-up time was 5.1 (1.8) years. Lower education (14.9 (3.2) vs. 17.3 (2.1)), Hispanic ethnicity (50.0% vs. 11.0%), and hypercholesterolemia (aOR: 6.67), p ≤ 0.05 for all, were risk factors for progression in SCD, whereas APOE status was not. Notably, SCD decliners were at increased risk for both amnestic and non-amnestic cognitive-decline with psychometric changes in memory, executive, and language domains (p < 0.001 for all). These findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.

Fully integrated microneedle biosensor array for wearable multiplexed fitness biomarkers monitoring

Fitness monitoring has become increasingly important in modern lifestyles; the current fitness monitoring always relies on physical sensors, making it challenging to detect pertinent issues at a deeper level when exercising. Here, we report a fully integrated wearable microneedle sensor that simultaneously measures fitness related biomarkers (e.g., glucose, lactate, and alcohol) during physical exercise. Such a sensor integrates a biocompatible 3D-printed microneedle array that can comfortably access skin interstitial fluid and a small circuit for signal processing and calibration, and wireless communication. The microneedle array features good biocompatibility and highly sensitive biochemical sensors that can detect even the slightest variations within the biomarkers of this fluid. On-body experimental results indicate that such a sensor can monitor fitness-related biomarkers across multiple subjects and support multi-day monitoring, with results showing a good correlation with commercial devices. The data was transmitted to a smartphone via Bluetooth and uploaded to cloud platforms for further health assessment. This study has the potential to boost intelligent wearable devices in sports health.

Characterization of Ptau181 Among a Diverse Community-Based Cohort: A HABS-HD Study.

Examination of Alzheimer's disease (AD) related biomarkers among diverse communities has remained limited. The aim of this study was to expand on prior work to provide a characterization of ptau181 among a diverse community sample. Consideration was taken regarding the impact of comorbidities on ptau181 levels including medical. 3,228 (n = 770 African American [AA], n = 1,231 Hispanic, and n = 1,227 non-Hispanic white [NHW]) Health and Aging Brain Study- Health Disparities (HABS-HD) participants were included in this study. ANCOVAs were conducted to examine differences in ptau181 levels across race and ethnic groups. Violin plots were also generated stratified by APOEɛ4 carrier status, Amyloid PET positivity status, medical comorbidity (hypertension, dyslipidemia, chronic kidney disease [CKD], and diabetes) and by cognitive diagnosis. Ptau181 levels were found to differ between Hispanics and NHW after covarying for age, sex, and APOEɛ4 status. Amyloid PET positivity was associated with higher ptau181 levels across all groups. APOEɛ4 positivity status was only significantly associated with ptau181 levels among AAs. Across all race and ethnic groups, those with a diagnosis of CKD had higher levels of ptau181. When stratified by cognitive diagnosis, cognitively unimpaired Hispanics had higher ptau181 if they also had a diagnosis of CKD or diabetes. p-values ≤0.01. Differences in ptau181 levels were shown in a diverse community sample. Medical comorbidities had a differing effect on ptau181 levels particularly among Hispanics even without cognitive impairment. Findings support the need for future work to consider comorbid conditions when examining the utility of ptau181.

Virtual multiplexed immunofluorescence staining from non-antibody-stained fluorescence imaging for gastric cancer prognosis

Multiplexed immunofluorescence (mIF) staining, such as CODEX and MIBI, holds significant clinical value for various fields, such as disease diagnosis, biological research, and drug development. However, these techniques are often hindered by high time and cost requirements. Here we present a Multimodal-Attention-based virtual mIF Staining (MAS) system that utilises a deep learning model to extract potential antibody-related features from dual-modal non-antibody-stained fluorescence imaging, specifically autofluorescence (AF) and DAPI imaging. The MAS system simultaneously generates predictions of mIF with multiple survival-associated biomarkers in gastric cancer using self- and multi-attention learning mechanisms. Experimental results with 180 pathological slides from 94 patients with gastric cancer demonstrate the efficiency and consistent performance of the MAS system in both cancer and noncancer gastric tissues. Furthermore, we showcase the prognostic accuracy of the virtual mIF images of seven gastric cancer related biomarkers, including CD3, CD20, FOXP3, PD1, CD8, CD163, and PD-L1, which is comparable to those obtained from the standard mIF staining. The MAS system rapidly generates reliable multiplexed staining, greatly reducing the cost of mIF and improving clinical workflow. Stanford 2022 HAI Seed Grant; National Institutes of Health 1R01CA256890.

Transcriptome combined with single cell to explore hypoxia-related biomarkers in osteoarthritis

Osteoarthritis (OA) is a prevalent degenerative condition among the elderly on a global scale. Research has demonstrated that hypoxia can promote chondrocyte apoptosis and autophagy leading to OA. Hence, it was vital to screen the hypoxia related biomarkers in OA. We introduced transcriptome data to screen out differentially expressed genes (DEGs) in GSE114007 and GSE57218 (OA samples vs control samples). We performed differential expression analysis in key annotated cell to obtain differentially expressed marker genes at the single-cell level (GSE169454). Venn diagram was executed to identify hypoxia related differentially expressed genes (HR-DEGs) associated with OA. Further, feature genes were obtained through the application of least absolute shrinkage and selection operator (LASSO) regression and the Random Forest (RF) algorithm. Receiver operating characteristic (ROC) and expression level analysis were used to identify hypoxia related biomarkers in OA. We further performed immune infiltration and gene set enrichment analysis (GSEA) based on hypoxia related biomarkers. Finally, we analyzed the expression of biomarkers in single-cell level. We identified 2351 DEGs associated with OA. At the single-cell level, 242 differentially expressed marker genes were obtained. 12 HR-DEGs were retained venn diagram. Subsequently, three hypoxia related biomarkers (ADM, DDIT3 and MAFF) were identified. Moreover, we got 15 significantly different immune cells. Finally, we found a lower expression of ADM, DDIT3 and MAFF in OA group compared to the control group in ECs. Overall, we obtained three hypoxia related biomarkers (ADM, DDIT3 and MAFF) associated with OA, which established a theoretical basis for addressing OA.