Search Results (11,107)

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease), represent a growing global health burden characterized by progressive neuronal loss and functional decline. Despite decades of intensive research, effective disease-modifying therapies remain limited, underscoring the urgent need for innovative therapeutic strategies. This review highlights recent advances in the understanding of disease etiology and emerging treatment approaches, with a particular focus on modalities with translational potential. We discussed novel disease-modifying interventions, including gene and cell therapies, RNA-targeting strategies, and immunotherapies aimed at clearing misfolded proteins such as amyloid-β, tau, and α-synuclein. In parallel, we examined the evolving recognition of neuroinflammation and mitochondrial dysfunction as actionable therapeutic targets, alongside progress in precision medicine and biomarker-guided approaches that enable early diagnosis and individualized treatment. Additionally, we summarized developments in repurposed pharmacological agents, neuroprotective compounds, and lifestyle interventions, emphasizing the importance of integrative, multimodal strategies. Across AD, PD, and ALS, convergent molecular mechanisms, including protein misfolding, oxidative stress, and disrupted proteostasis, present opportunities for cross-disease therapeutic targeting. Finally, we addressed key challenges and future directions, including translating preclinical efficacy into clinical success, optimizing CNS-targeted delivery systems, and navigating ethical considerations surrounding gene editing and stem cell therapies. Full article

Largemouth bass (Micropterus salmoides) represents an important freshwater aquaculture species. Dietary protein strategies significantly influence growth performance, immune markers, and intestinal microbiota homeostasis. This study evaluated the physiological effects of five phased protein regimens on juvenile largemouth bass (9.77 ± 0.03 g) over 60 days. A constant 46% protein diet (CON) served as the control, compared with four dynamic regimens (LLH, LMH, LHH, HML) comprising low (L, 43%), medium (M, 46%), or high (H, 50%) protein levels across three 20-day phases. Seven hundred fish were randomly allocated into five groups (four replicates each). Daily feed intake was recorded, body weight was measured at the start and end, and survival rates were monitored. Post-trial assessments included body composition, serum biomarkers, intestinal morphology, and intestinal microbiota. Results showed that the LHH regimen significantly increased immunoglobulin M, complement C3 and C4, lysozyme activity, catalase, glutathione peroxidase, and total antioxidant capacity compared to the CON group. The LHH group also exhibited a reduced relative abundance of Stenotrophomonas_A. Functional predictions indicated downregulation of limonene/pinene degradation and the renin–angiotensin system. The LHH feeding regimen synergistically enhances immune-antioxidant function and optimizes intestinal microbiota in juvenile largemouth bass. Full article

Background: Spinal cord ischemia (SCI) is a severe complication of thoracoabdominal aortic aneurysm (TAAA) repair, associated with substantial morbidity and mortality. Despite advances in operative techniques, its pathophysiology remains incompletely understood, with no reliable biomarkers available for early detection or risk stratification. Methods: This narrative review synthesizes current evidence on the pathophysiology of SCI following aortic intervention, integrating insights from ischemic stroke and traumatic spinal cord injury to identify key mechanistic pathways and potential biomarker targets. Results: SCI results from multifactorial impairment of spinal cord perfusion pressure (SCPP) driven by extensive aortic coverage, disruption of segmental arterial inflow, hypotension, and impaired collateral circulation. While acute hypoperfusion initiates injury, secondary processes—including excitotoxicity, oxidative stress, and neuroinflammation—drive progression. Cytokine signaling and immune activation contribute to blood–spinal cord barrier disruption and vasogenic edema, with Aquaporin-4 playing a central role in delayed injury. Candidate biomarkers, including neuron-specific enolase, S100β, and glial fibrillary acidic protein, reflect neuronal damage but lack sufficient sensitivity and temporal resolution for clinical use. Emerging evidence supports a multimodal biomarker approach incorporating inflammatory, structural, and Aquaporin-4-dependent edema-related pathways. Conclusions: Spinal cord ischemia following thoracoabdominal aortic aneurysm repair is a dynamic and multifactorial process in which reduced spinal cord perfusion pressure represents a final common pathway linking diverse perioperative factors to ischemic injury. Secondary mechanisms, particularly neuroinflammation and Aquaporin-4-driven vasogenic edema, play a central role in injury propagation and represent promising targets for biomarker development. Future strategies should focus on longitudinal, multimodal biomarker approaches to improve early detection, risk stratification, and therapeutic intervention. Full article

Pleiotrophin (PTN), a heparin-binding growth factor with potent mitogenic and angiogenic activity, has emerged as a key regulator of mammary gland biology and a potential driver of breast cancer progression. This review integrates current evidence on PTN’s roles from normal mammary development, where it can delay ductal outgrowth, to triple negative breast cancer, where it promotes lung metastasis and correlates with poor survival. Though frequently reported as being overexpressed in breast cancer, the published data indicates that PTN transcription is reduced in cancer relative to normal breast cells. By contrast, serum PTN protein levels have been shown by multiple studies to be elevated in breast cancer patients relative to healthy controls. We examine the expression and function of PTN at a cellular level and explore the interplay between PTN and the tumour microenvironment. We evaluate preclinical models, clinical correlations, and emerging biomarker data that position PTN as a candidate prognostic indicator and therapeutic target. Despite growing interest, significant gaps remain regarding context-specific signalling. By integrating developmental and oncogenic perspectives, this review highlights PTN as a pivotal but underexplored factor in mammary gland physiology and breast cancer and outlines future research directions needed to translate PTN-targeted strategies into clinical benefit. Full article

Exosomes are a kind of nanoscale extracellular vesicle secreted by almost all cell types and considered promising biomarkers for disease diagnosis since they could carry abundant proteins, nucleic acids, and lipids that reflect parental cell states. However, conventional exosome detection methods suffer from several limitations including insufficient specificity, low throughput, high costs, and inadequate sensitivity for clinical applications. By contrast, field-effect transistor (FET) biosensors are a promising alternative by enabling label-free, real-time, and ultrasensitive detection of exosomes through direct transduction of biorecognition events into electrical signals. This review first introduces the fundamental principles and device structure of FET biosensors, as well as exosome isolation strategies. The recent advances in exosome analysis using FET-based biosensors are then presented, which are categorized into two primary strategies: (1) direct detection of intact exosomes based on surface markers, including tetraspanin proteins (CD9, CD63, CD81, etc.) and disease-specific biomarkers, and (2) detection of exosomal contents including microRNA and protein biomarkers following exosome lysis. Finally, we discuss current challenges of FET-based exosome detection and provide perspectives on future developments. Full article

Background/Objectives: Sepsis is clinically dynamic, and isolated admission biomarker values may insufficiently capture early biological evolution after treatment initiation. This study evaluated whether routine biomarker reassessment at approximately 48 h provides incremental prognostic information beyond admission Sequential Organ Failure Assessment (SOFA) score for 28-day mortality in sepsis. The analysis was framed as an exploratory 48 h landmark prognostic assessment among patients who were alive and had complete biomarker reassessment data at 48 ± 6 h. Methods: We conducted a prospective single-center observational cohort study including adult patients with sepsis. Clinical and laboratory data were collected at baseline (M1) and repeated 48 ± 6 h later (M2). The primary outcome was 28-day mortality. Candidate biomarkers included C-reactive protein (CRP), procalcitonin (PCT), lactate (LAC), and neutrophil-to-lymphocyte ratio (NLR). PCT clearance and NLR change were calculated as relative changes between M1 and M2, whereas 48 h CRP and 48 h lactate were evaluated as early reassessment values. Exploratory logistic regression models were constructed using admission SOFA as the clinical reference model. Model discrimination and fit were summarized using receiver operating characteristic analysis, likelihood-ratio testing, and Nagelkerke R²; the models were not intended as validated individual-level risk calculators. Results: The 48 h landmark analytical cohort included 126 patients, of whom 44 (34.9%) died within 28 days. Admission biomarker values showed limited prognostic signal. SOFA alone showed fair discrimination (AUC 0.740). Among the primary SOFA-augmented models, SOFA plus PCT clearance showed the highest discrimination and explanatory performance (AUC 0.810; Nagelkerke R² 0.332) and significantly improved model fit compared with SOFA alone. SOFA plus NLR change and SOFA plus 48 h lactate also provided incremental prognostic information, although their gains were more modest. In exploratory combined modeling, SOFA plus PCT clearance and NLR change provided the most coherent additional signal, with all predictors retaining independent associations with 28-day mortality. Conclusions: In this exploratory single-center 48 h landmark analysis, selected routine biomarker reassessment measures were associated with 28-day mortality beyond admission SOFA. PCT clearance provided the clearest incremental prognostic signal, while NLR change offered complementary information. Persistent 48 h lactate elevation was also informative, whereas lactate clearance was not. These findings should be interpreted as hypothesis-generating and require validation in larger cohorts, ideally including serial organ dysfunction measures such as 48 h SOFA or SOFA change. Full article

Background: Peripheral artery disease (PAD) impacts more than 200 million individuals globally. Despite its prevalence, management remains suboptimal, partly due to the lack of reliable blood-based biomarkers. The ankle–brachial index (ABI), the current gold-standard test for PAD, is limited by inter-operator variability, misinterpretation, and reduced accuracy in patients with diabetes. Fatty acid binding protein 3 (FABP3) has emerged as a potential biomarker for PAD; however, its prognostic performance relative to ABI remains unclear. This study compared FABP3 and ABI for predicting PAD outcomes using statistical and machine learning approaches. Methods: A total of 1001 participants were prospectively recruited, including 644 patients with PAD and 357 without PAD. The primary outcome was 2-year major adverse limb event (MALE), defined as a composite of vascular intervention, major amputation, or acute limb ischemia. At enrollment, plasma FABP3 was quantified using a validated multiplex immunoassay. Kaplan–Meier analysis of MALE-free survival was performed across pre-specified FABP3 tertiles (high [>3.55 ng/mL], moderate [1.55–3.55 ng/mL], and low [<1.55 ng/mL]) and ABI tertiles (severe [<0.40], moderate [0.40–<0.70], and mild [0.70–0.90]), with curve separation assessed using log-rank tests. Multivariable Cox proportional hazards modelling was used to evaluate the independent relationships of FABP3 and ABI with 2-year MALE after adjustment for baseline demographic and clinical covariates. To assess predictive performance for 2-year MALE, an extreme gradient boosting (XGBoost) classification model incorporating 10-fold cross-validation was trained using a combination of clinical covariates, plasma FABP3 levels, and ABI. Discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: The average participant age was 68 years (SD 12), and 34% (n = 340) were women. Mean ABI was 0.75 ± 0.25 and mean FABP3 concentration was 2.97 ± 2.06 ng/mL. Among the 644 participants with PAD, 558 (86.6%) had complete time-to-event data for MALE status, FABP3, and ABI. Over the median follow-up period of 2 years, 140 (25.1%) participants with PAD experienced MALE. Kaplan–Meier analyses demonstrated significant separation in MALE-free survival across FABP3 tertiles (log-rank p < 0.001). At 24 months, MALE-free survival was 100.0% in the FABP3 < 1.55 group, compared with 71.1% in the FABP3 1.55–3.55 group and 67.7% in the FABP3 > 3.55 group. In contrast, ABI severity groups showed less pronounced separation, with 24-month MALE-free survival rates of 80.3% for mild ABI, 73.2% for moderate ABI, and 71.3% for severe ABI, without a statistically significant overall difference (p = 0.170). In adjusted Cox proportional hazards models, FABP3 demonstrated strong prognostic performance for 2-year MALE. A 1 SD increase in log-transformed FABP3 was independently associated with a higher risk of 2-year MALE (HR 1.90, 95% CI 1.60–2.25; p < 0.001), with minimal change after additional adjustment for ABI (HR 1.90, 95% CI 1.60–2.24; p < 0.001). Machine learning analyses similarly favored FABP3 over ABI, with the FABP3-based model achieving an AUC of 0.773 compared to 0.686 for the ABI-based model. Adding ABI to the FABP3 model did not improve discrimination. Conclusions: Circulating plasma levels of FABP3 are strongly associated with PAD outcomes. Specifically, FABP3 demonstrated a stronger and more robust association with 2-year MALE compared to ABI. This study validates the prognostic value of FABP3 for PAD outcomes in comparison to ABI. Full article

Breast cancer is prevalent and deadly, affecting women worldwide. Increasing research suggests that lysine lactylation (KLA) and DNA damage repair (DDR) play critical roles in tumor progression and that KLA and DDR are interconnected, as KLA can modulate DDR protein function, thereby influencing genome stability and drug response, while DDR signaling can reciprocally reshape lactate metabolism and KLA activity. In this study, we developed a novel prognostic gene signature (KLA and DDR index, KLDRI) based on KLA- and DDR-related genes. Model genes (PGK1, MORF4L2, RAD54B, RPA3, CCND2) were generated via LASSO-Cox regression. Patients were stratified into high- and low-risk groups according to KLDRI, the robust prognostic value of which was demonstrated via survival and validation analyses in the TCGA cohort and the METABRIC and GSE96058 cohorts, respectively. Tumor microenvironment analysis indicated an immunologically suppressed phenotype in high-risk patients, whereas low-risk patients exhibited an immune-inflamed microenvironment. Drug sensitivity analysis indicated reduced sensitivity to multiple chemotherapy and targeted therapy drugs in the high-risk group. Single-cell transcriptomic analysis revealed differential gene expression patterns between risk groups. A prognostic nomogram based on KLDRI was developed to predict overall survival. Furthermore, functional experiments demonstrated that RPA3 knockdown suppressed cancer cell proliferation and migration, sensitized cells to cisplatin treatment, and reduced global lactylation, which may serve as a novel biomarker and potential therapeutic target. These findings enhance our understanding of the interplay between KLA, DDR, and breast cancer progression, facilitating the development of personalized therapeutic strategies. Full article

Coronary artery bypass grafting (CABG) using the autologous saphenous vein (SV) remains widely performed for obstructive atherosclerosis; however, vein graft disease drives recurrent ischaemia through early thrombosis and progressive intimal hyperplasia, and accelerated atherosclerosis developing within the grafts. Extracellular vesicles (EVs) are membrane-bound particles that transfer proteins, lipids, and microRNAs between cells. They modulate endothelial dysfunction, vascular smooth muscle cell phenotypic switching, inflammation, and coagulation, which are core processes in vein graft remodelling. Arterialisation exposes the vein to abrupt rises in shear stress, cyclic stretch, and intraluminal pressure. These forces increase EV release and reshape EV cargo in experimental systems, suggesting a potential mechanism for amplifying early graft injury which warrants direct investigation in vein tissue. This review synthesises current evidence for cell-specific EV contributions from ECs, vascular smooth muscle cells, platelets, and macrophages, and appraises EV-associated microRNAs with biomarker potential relevant to graft failure pathways. We also review therapeutic strategies that may modulate EV signalling including antiplatelet therapy, statins, KCa3.1 inhibition, and pro-reparative mesenchymal stromal cell-derived EVs. No published clinical studies evaluate EV-based biomarkers specifically for saphenous vein graft patency, and none prospectively predict saphenous graft failure. CABG provides a well-defined time zero event that enables longitudinal sampling and risk stratification. Prospective studies linking EV phenotypes and miRNA signatures to imaging-defined graft outcomes are needed to support clinical translation. Full article

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by complex and interconnected pathophysiological mechanisms, including mitochondrial dysfunction, oxidative stress, neuroinflammation, lysosomal impairment, and altered neurotransmitter metabolism. Unlike cerebrospinal fluid or blood, urine offers a truly non-invasive source of biomarkers, reflecting systemic metabolic changes and renal protein excretion linked to neurodegeneration. This review aims to critically synthesize current evidence on urinary biomarkers in PD and to organize this heterogeneous literature into pathophysiologically meaningful domains. Methods: A comprehensive literature search of human studies investigating urinary biomarkers in PD was performed. Eligible studies were comprehensively analyzed and classified according to dominant biological pathways. To facilitate interpretation, findings were organized into six thematic domains: genetic and protein-based biomarkers; metabolic pathways and mitochondrial dysfunction; oxidative stress and neuroinflammation; gut–brain-axis-related metabolites; hormonal and systemic biomarkers; and emerging exploratory markers. Results were summarized in domain-specific tables and integrated using a conceptual framework. Results: A total of 32 human studies met the inclusion criteria, revealing diverse urinary molecular signatures associated with PD across multiple biological domains. Genetic and protein-based markers, including LRRK2-related proteins, α-synuclein species, and lysosomal lipids, showed potential for disease stratification. Metabolomic studies consistently identified alterations in acylcarnitines, organic acids, and amino acid metabolism, reflecting mitochondrial dysfunction. Biomarkers related to oxidative stress, immune activation, gut microbiota metabolism, and hormonal regulation further highlighted the systemic nature of PD. However, most individual biomarkers lacked disease specificity and exhibited methodological heterogeneity. Conclusions: Current evidence supports urine as a valuable source of systemic biomarkers reflecting multiple pathophysiological processes in PD. While single urinary markers remain insufficient for clinical application, integrated omics-based approaches—particularly metabolomics and peptidomics/proteomics—hold promise for identifying combinatorial biomarker signatures. Future longitudinal and standardized studies are required to enhance specificity and translational potential for non-invasive diagnosis and disease monitoring in PD. Full article

Protein lactylation, an emerging post-translational modification (PTM) driven by the metabolite lactate, has surfaced as an important regulatory layer contributing to the crosstalk between metabolic reprogramming and cellular functional plasticity in colorectal cancer (CRC). Within the unique “host–microbiota” symbiotic microenvironment of CRC, the Warburg effect—fueled jointly by oncogene activation and microbial metabolism—provides abundant substrates for lactylation. This modification is dynamically regulated by a complex enzymatic system comprising “Writers” (e.g., p300/CREB-binding protein [p300/CBP], alanyl-tRNA synthetase 1/2 [AARS1/2]) and “Erasers” (e.g., histone deacetylases [HDACs] and Sirtuins). Through intricate crosstalk with other PTMs, such as acetylation and ubiquitination, lactylation exerts critical regulatory effects on both the histone epigenetic landscape and non-histone protein functions. Functionally, lactylation not only drives malignant proliferation, invasion, and metastasis but also systematically remodels the immunosuppressive “cold” tumor microenvironment. Furthermore, it confers broad-spectrum resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy by orchestrating a ferroptosis defense network, enhancing DNA damage repair (DDR), and activating protective autophagy. This review systematically synthesizes the regulatory networks and biological functions of lactylation in CRC, deeply elucidating the core mechanisms underlying therapy resistance. Finally, we discuss the clinical translational potential of lactylation as a novel diagnostic/prognostic biomarker and therapeutic target, aiming to provide new theoretical foundations and strategic directions for overcoming current bottlenecks in CRC clinical treatment. Full article

Alpha-enolase (ENO1) is a multifunctional protein best known for its canonical role in glycolysis, but growing evidence indicates that it also plays important roles in cancer development and progression. This review summarizes the current knowledge regarding the biological and clinical significance of ENO1 across multiple cancer types. We first outline the physiological characteristics of ENO1 and its distribution in normal tissues. Then, we discuss its aberrant expression patterns and genomic alterations in human cancers. We further examine the evidence linking ENO1 to major cancer-related processes, including proliferation, apoptosis resistance, cancer stemness, autophagy, metastasis, drug resistance, and angiogenesis. In addition, we review studies that evaluate the association between ENO1 expression and patient prognosis in pan-cancer datasets and individual malignancies. Collectively, the available literature indicates that ENO1 is closely associated with malignant progression through its involvement in metabolic reprogramming and broader tumor-promoting cellular functions. These findings suggest that ENO1 may serve as a context-dependent biomarker and a candidate therapeutic target in selected cancer settings; however, further mechanistic validation and clinically annotated studies are required before its translational value can be firmly established. Full article

Suicide is a major public health concern and cause of death worldwide. While progress has been made in understanding molecular pathways involved in suicide, much more work is needed to identify clinically useful biomarkers of suicidality. Disturbed cellular proteostasis and aggregation of specific misfolded proteins are established pathological factors of neurodegenerative diseases. Increasing evidence also suggests that such aggregates often occur in patients with chronic mental illnesses. Recently, genes related to disturbed proteostasis showed differential methylation in individuals who died by suicide compared to controls. These include five genes encoding proteins that aggregate in neurodegenerative and/or mental illness: CRMP1 (also called DPYSL1), DISC1, MAPT (encoding the Tau protein), PRKN (also called PARK2, encoding Parkin), and SOD1. Given the possibility that altered methylation in these genes could affect expression of the proteins they encode, we aimed to review evidence for whether disturbed proteostasis may be a point of overlap between suicidality, neurodegenerative disease, and/or mental illnesses. Epigenetic changes in most of these genes also occur in other neurological disorders. Autophagy, and, to a lesser extent, the ubiquitin–proteasome system, are emerging as potentially impaired in individuals with suicidal tendencies and individuals who died by suicide. Based on this accumulated data, we hypothesise that disturbed proteostasis is likely to be a pathological component of suicidality. It is also plausible that this may lead to the accumulation of aggregated proteins in a similar manner to, and potentially overlapping with, those seen in major mental illnesses. If true, this would have consequences for potential identification of biomarkers for suicidality and should be a priority for future research in the field. Full article

Background/Objectives: The vitamin B12 (VB12)/C-reactive protein (CRP) index (BCI), a clinically derived index calculated as serum VB12 multiplied by CRP, has shown prognostic value in several cancers. However, its association with survival outcomes in metastatic renal cell carcinoma (mRCC) remains unclear. Therefore, the aim of the present study was to evaluate the prognostic significance of BCI in patients with mRCC treated with targeted therapy. Methods: The BCI was calculated as serum VB12 concentration (pg/mL) × serum CRP concentration (mg/L). The patients were categorized into two BCI prognostic subgroups, high BCI (BCI > 40,000) and low BCI (≤40,000). Survival differences between prognostic subgroups were measured using the Kaplan–Meier method with a log-rank test. Univariate and multivariable analyses were used to determine the association between the selected variables and survival outcomes. Results: We included 213 patients with mRCC, with a median follow-up time of 76 months. The median progression-free survival (PFS) and overall survival (OS) were 10.9 months and 47.7 months, respectively. Patients with high BCI had poorer PFS and OS times than those with low BCI (7.8 months vs. 12.6 months, p = 0.002 for PFS; 22.6 months vs. 68 months, p < 0.001 for OS, respectively). After adjusting for potential confounders, high BCI remained independently associated with poorer PFS and OS (hazard ratio [HR]: 2.40, 95% confidence interval [CI] 1.35–4.26, p = 0.003 for PFS; HR 2.01, 95% CI 1.40–2.88, p < 0.001 for OS). Conclusions: BCI appears to be a promising prognostic biomarker in patients with mRCC treated with first-line targeted therapy. However, its applicability to immune checkpoint inhibitor-based or combination regimens requires prospective validation. Full article

At present, the gold standard for gastric cancer (GC) confirmation relies mostly on histopathology, an invasive procedure. Noninvasive detection methods using serum for large-scale screening may be useful for the early diagnosis of GC. Helicobacter pylori (HP) infection and chronic atrophic gastritis are major GC risk factors. We recently developed a noninvasive test called the DSC test-based on the patient’s age, sex, their serum PGI and PGII, anti-HP immunoglobulin (IgG), and gastrin G17 levels-predicting GC risk as low (score 0, S0) or high (score 2, S2). The comparative investigation at the serum protein level of the two different patient groups detected by our DCS test (S0 and S2) may undoubtedly help to identify gastric disease-dependent proteins, resulting from bacterial infection or gastric mucosa inflammation, as well as get better insight into the molecular scenario associated with pre-cancerous conditions. We used an untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based proteomic profiling approach, followed by univariate statistical analysis to compare the different DSC groups across two patient cohorts (exploratory and validation). Significantly differentially abundant proteins differing more than 1.5-fold between S0 and S2 groups were selected and validated, and their putative role(s) in gastritis and GC were discussed. In both the exploratory and the validation cohorts, four proteins (beta-2-microglobulin, EGF-containing fibulin-like extracellular matrix protein 1, complement factor D, and Cystatin-C) were more abundant, while two (sex hormone-binding globulin and pregnancy zone protein) were less abundant in the sera of S2 individuals (|fold change| ≥ 0.6, p < 0.05, t-test). The higher presence of beta-2-microglobulin (B2M) and the lower content of pregnancy zone protein (PZP) in S2 sera were validated by immunoblotting. Replacing age and sex in our DSC model with two specific candidate biomarkers can lead to a refined, albeit modest, improvement in classification accuracy. This study identified a proteomic signature that was differentially associated with the sera of patients with a different risk to develop advanced atrophy/GC according to the DSC test. Moving from a demographic model to a proteomic-driven model can better reflect the personalized biology of pathological processes associated with DSC. Full article