Search Results (159)

Background/Objectives: Alterations in polyunsaturated fatty acid (PUFA) metabolites have been linked to the development of hepatocellular carcinoma (HCC). However, the association between PUFA metabolites and HCC development during nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B virus infection remains unclear. Methods: This study enrolled 195 NUC-naïve patients who received NUC therapy. Associations between metabolic factors—especially PUFA metabolites—and HCC development during NUC therapy were evaluated. Baseline serum concentrations of 158 PUFA metabolites were quantified using targeted lipidomic analysis. Results: Nineteen patients developed HCC during the follow-up period. The cumulative incidences of HCC at 5 and 10 years were 7.7% and 12.4%, respectively. Variable importance in projection analysis identified 12-hydroxyheptadecatrienoic acid (12-HHT) as the top-ranked metabolite differentiating patients with and without HCC development. Furthermore, 14 metabolites were significantly associated with HCC development based on the log-rank test with 12-HHT being the most significant predictor. The cumulative incidences of HCC at 5 and 10 years were 13.7% and 24.7%, respectively, in patients with 12-HHT concentration ≤ 3.82 ng/mL compared with 3.3% at both time points in those with 12-HHT concentration > 3.82 ng/mL (p < 0.001). In multivariate analysis, low 12-HHT concentration (≤3.82 ng/mL; p = 0.027; hazard ratio [HR], 4.28; 95% confidence interval [CI], 1.18–15.55) and a fibrosis-4 index ≥ 4.08 (p = 0.005; HR, 5.19; 95% CI, 1.64–16.41) were significantly associated with HCC development during NUC therapy. Conclusions: Pre-treatment 12-HHT represents a novel predictive biomarker for HCC development during NUC therapy. Full article

Background: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma characterized by a poor prognosis due to high relapse rates and a lack of standardized treatment. This study aimed to evaluate the impact of induction/consolidation therapy on long-term survival and to provide extended follow-up data. Methods: In this retrospective analysis, 140 immunocompetent patients with diffuse large B-cell PCNSL (DLBCL-PCNSL) treated at two centers between 2014 and 2024 were enrolled. Treatment efficacy was assessed based on baseline characteristics, therapeutic regimens, and treatment response. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and prognostic factors were identified using multivariate Cox proportional hazards regression models. Results: With a median follow-up of 5.3 years (range: 0.1–11.0 years), the 2- and 5-year PFS rates were 50.4% (95% CI: 42.1–60.2) and 34.1% (95% CI: 25.5–45.0), respectively, while the corresponding OS rates were 85.3% (95% CI: 79.4–91.6) and 60.8% (95% CI: 52.0–71.1). No survival plateau was observed. Among patients, 94% received methotrexate-based induction therapy: 94 received rituximab–methotrexate–temozolomide (R-MT) and 17 received MT alone, with 2-year PFS rates of 57.7% and 39.7%, respectively. Overall, 75% of patients achieved remission (CR/CRu/PR) after induction, and among these, 55% underwent consolidation therapy, predominantly autologous stem cell transplantation (ASCT, 90%) or whole-brain radiotherapy (10%). Patients receiving ASCT exhibited superior survival outcomes compared to those who did not. Conclusions: R-MT induction combined with ASCT consolidation is associated with improved survival in PCNSL, although relapse risk remains substantial. Outcomes remain poor in refractory subgroups, highlighting the need for novel therapeutic strategies. Full article

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) causes half a million deaths each year; therefore, it is essential to understand the factors that affect patient prognosis. Many studies fail to investigate the biological drivers behind survival disparities, especially sex-specific differences within racial groups. This study serves as a foundational project to begin elucidating biological differences in the tumor microenvironment between male and female African American HNSCC patients. Methods: A total of 111 patients who were diagnosed with HNSCC and identify as African American were grouped by sex. Analyses of socioeconomic status, co-morbidities, tumor characteristics, and treatment were conducted. Spatial transcriptomic analysis was performed on four randomly selected primary HNSCC tumor tissues. Results: No sex-based differences were observed in socioeconomic measures, treatments, tumor stage, follow-up, recurrence, or cause of death (all p > 0.15), though females had higher median income than males (p = 0.035). Comorbidity profiles were also largely comparable between males and females. Evaluating tumor microenvironments, we found that male tumors were dominated by malignant cells and fibroblasts, with limited adaptive immune infiltration. By contrast, female tumors displayed markedly higher proportions of immune cells, including T cells and B cells. Male tumors harbored sparse T cells, largely skewed toward exhausted phenotypes while female tumors displayed abundant T cell infiltration consistent with immunologically active tumor microenvironment. Conclusions: Clinical and demographic factors showed minimal sex-based differences among African American HNSCC patients, spatial transcriptomic profiling revealed strikingly distinct immune microenvironments by sex. These findings suggest that biological, rather than simply clinical, differences may drive survival disparities. This project serves as a novel and foundational study promoting the use of spatial transcriptomics to evaluate possible survival disparities within HNSCC populations to alleviate survival disparities. Full article

Background/Objectives: Environmental exposure to heavy metals is an established risk factor for breast cancer development; however, the molecular mechanisms underlying the contribution of lead (Pb) to disease progression remain unclear. This study aimed to investigate the effects of Pb exposure on breast cancer cells and to delineate the associated mechanisms. Methods: We examined Pb-induced migration and invasion of breast cancer cells using wound-healing and Transwell assays; assessed cell proliferation by flow cytometry and MTT assay; identified potential target genes via RNA sequencing; and further elucidated the underlying mechanisms using integrated molecular biology approaches (including immunofluorescence, Western blotting, and ELISA), functional cellular assays, and bioinformatics analysis. Results: Pb exposure significantly enhanced the migratory and invasive capabilities of breast cancer cells by upregulating aldo-keto reductase family 1 member C3 (AKR1C3), without markedly affecting cell proliferation. Mechanistically, AKR1C3 promoted migration and invasion through activation of NF-κB signaling, leading to upregulated expression of MMP-2 and MMP-9. Conclusions: This study reveals a novel molecular axis—Pb exposure promotes breast cancer cell migration and invasion via the AKR1C3–NF-κB–MMP-2/MMP-9 pathway—and identifies AKR1C3 as a potential therapeutic target for breast cancer associated with environmental heavy metal exposure. Full article

Postoperative delirium (POD) is a frequent and serious complication among elderly surgical patients. Despite its clinical relevance, reliable biomarkers for early identification and pathophysiological insight remain limited. Recent evidence implicates systemic immune activation and complements dysregulation as contributors to cognitive decline after surgery. This study investigated the association between perioperative levels of selected complement pathway proteins and both the incidence and severity of POD. Methods: We performed a secondary analysis of 22 patients aged ≥ 60 years from the prospective CONFESS cohort undergoing elective spine surgery. Complement proteins (C1q, C2, C4), mannose-binding lectin (MBL), Factor D [FD], Factor B [FB], Factor I [FI] were quantified from blood samples collected at baseline, preoperatively, and on postoperative days 1 and 2. POD was assessed using the Nursing Delirium Screening Scale (Nu-DESC) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Delirium severity was rated with the Confusion Assessment Method–Severity (CAM-S) scale. Associations were tested using univariate and multivariate regression analyses. Preoperative levels of FD and C2 were significantly elevated in patients who developed POD (FD: p = 0.023; C2: p = 0.044), while C4 levels trended lower. FD remained an independent predictor of POD in multivariate regression (p = 0.049), although cognitive performance was the only significant predictor when adjusted for surgery duration. Delirium severity was associated with perioperative reductions in C1q, FI, and FB and with increased MBL levels, explaining up to 43% of CAM-S score variance. These findings highlight the role of complement activation—particularly FD, C2, MBL—in the development and clinical expression of POD. Complement profiling may offer a novel approach for risk stratification and therapeutic targeting in perioperative neurocognitive disorders. Full article

Background/Objectives: Pacing-induced cardiomyopathy (PiCM) is a recognized complication of chronic right ventricular pacing (RVP), characterized by left ventricular (LV) dysfunction, adverse remodeling, and progression to heart failure. MicroRNAs (miRs) regulate gene expression and play an important role in ventricular remodeling. This study aimed to observe whether dynamic changes in miRs according to a novel peripheral blood mononuclear cell (PBMC)-based approach could serve as early predictive biomarkers of PiCM. Methods: A prospective, single-center cohort study was conducted in adult patients undergoing pacemaker implantation. Clinical characteristics, echocardiographic parameters and expression levels of miR-208b-3p and miR-9 were assessed immediately and 3 months post-pacemaker implantation. PiCM was defined as a ≥10% reduction in LVEF at one year, with no alternative cause. Statistical analyses included correlation testing, ROC curve analysis, and multivariate regression to identify factors associated with PiCM. Results: Among 126 patients, 11.1% developed PiCM. Compared with the non-PiCM group, those who developed PiCM exhibited more pronounced 3-month changes in miR-208b-3p (median Δ₃log miR: +1.3 vs. −0.4, p = 0.013) and miR-9 (median Δ₃log miR: −1.7 vs. +0.21, p = 0.011). In multivariate analyses, Δ₃LV-GLS, Δ₃logmiR-208b-3p, and Δ₃logmiR-9 were associated with a higher likelihood of PiCM. Among PiCM patients, Δ₃logmiR-208b-3p correlated inversely with Δ₃LV-GLS (r = −0.73, p = 0.016), while Δ₃logmiR-9 correlated positively (r = 0.88, p < 0.001). ROC analyses demonstrated good predictive ability for Δ₃LV-GLS (AUC = 0.924), Δ₃log miR-208b-3p (AUC = 0.783), and Δ₃log miR-9 (AUC = 0.835), with no significant differences between curves. Conclusions: Early LV-GLS deterioration and dynamic changes in expression of miR-208b-3p and miR-9 in PBMCs precede overt LV systolic dysfunction. These miRs may serve as early predictive biomarkers for PiCM. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) remains a major global health problem, affecting over 300 million people worldwide. Its high morbidity and mortality rates impose substantial psychosocial and financial burdens on patients and healthcare systems. In the emergency setting, managing acute exacerbations of COPD (AECOPD) poses a major clinical challenge, as these patients often present with multi-organ dysfunction secondary to hypoxia and hypercapnia. Identifying reliable prognostic biomarkers could improve early risk stratification, guide therapeutic decisions, and enhance patient outcomes. Methods: This multicenter, prospective, observational study aims to evaluate the prognostic significance of several novel biomarkers—resistin, club cell secretory protein 16 (CC16), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), S100β protein—alongside conventional markers such as N-terminal-pro–B-type-Natriuretic-Peptide (NT-proBNP), D-dimer, high-sensitivity troponin I (hs-cTnI), C-reactive protein (CRP), and procalcitonin in patients with AECOPD admitted to the Emergency Department (ED). Blood samples will be collected at admission. The novel biomarkers (resistin, CC16, IL-6, TNF-α, S100β) will be measured using standardized ELISA kits, while conventional biomarkers (NT-proBNP, troponin I, CRP, procalcitonin) will be analyzed using routine automated clinical laboratory methods. Correlations between biomarker levels, clinical and imaging data, severity scores (GCS, SOFA, CFS, Ottawa COPD Risk Scale, DECAF, BAP-65), and short-term outcomes (hospital discharge status and 28-day survival) will be assessed. The study has received approval from the Ethics Committee of the “Iuliu-Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, and all participating hospitals. Written informed consent will be obtained from all participants or their legal representatives. Results: This study protocol does not report results, as data collection and analysis are ongoing. Conclusions /Expected Impact: By identifying novel biomarkers with prognostic and pathophysiological relevance, this research aims to inform the development of early risk stratification tools and support future evidence-based approaches to the management of critically ill COPD patients in the ED. Full article

This paper presents a novel multi-loop control strategy for Vienna rectifiers that eliminates coordinate transformations while achieving superior performance under adverse grid conditions. Unlike conventional $dq$-frame controllers that suffer from computational complexity and degraded performance during unbalanced conditions, the proposed $abc$-frame scheme achieves a power factor of $98\%$ with total harmonic distortion (THD) below $5\%$ across all operating conditions. The system exhibits a settling time under 120 μs for $90\%$ load transients and ensures robust operation during Type A voltage sags while maintaining a $94\%$ power factor. Furthermore, it guarantees zero steady-state neutral point deviation. The controller employs a dual-loop architecture with high-gain current tracking and PI-based voltage regulation, validated through extensive PSIM/C++ co-simulations at 120 kw. Comparative analysis demonstrates a $35\%$ reduction in computational burden relative to $dq$-frame alternatives, while fully complying with IEEE-519:2022 standards. These results highlight the proposed method as a practical and robust solution for industrial rectification applications requiring grid-fault tolerance. Full article

Notch and size effects significantly influence the fatigue performance of engineering components, which is crucial for ensuring structural integrity. A novel probabilistic fatigue life prediction Kt-V-L model considering both the size and the notch effect, based on the theory of critical distance L (TCD) and the improved highly stressed volume V (HSV) method, is proposed in this study. The new definition more accurately characterizes fatigue damage and accumulation, overcoming the underestimation issues of traditional HSV methods under high-stress or low cycle fatigue (LCF) conditions. Specifically, the Weibull distribution is also proposed to characterize the material fatigue failure probability. The experimental data of 26Cr2Ni4MoV, En3B, and TC4 materials with varying notched sizes are utilized for the model validation and comparison. In addition, the predictive ability of the point method (Kt-V-L-PM) and line method (Kt-V-L-LM) under the novel proposed model was explored and evaluated. The predicted lives of 26Cr2Ni4MoV specimens fall within the ±2 scatter band of the Kt-V-L-LM, while the Kt-V-L-PM shows increasing deviation with larger notches due to its limited ability to capture stress gradients. For En3B and TC4, the predicted lives are within ± 2 life factors, verifying the model’s reliability and accuracy. Furthermore, fracture morphology analysis reveals the influence of notches on fatigue performance and elucidates the fracture failure mechanisms. Full article

Pancreatic cancer poses a major clinical challenge due to its aggressiveness, frequent recurrence, and limited response to current chemotherapeutic approaches. Cancer stem cells (CSCs), particularly pancreatic CSCs (PCSCs), are key drivers of tumor initiation, therapeutic resistance, and disease relapse. MicroRNAs (miRNAs) have emerged as critical regulators of CSC biology and influence self-renewal, pluripotency, and drug resistance through key signaling pathways. To identify PCSC-specific miRNAs, we enriched these cells using the pancreosphere culture method and isolated PCSC+ and PCSC− populations using FACS based on their expression of CD44, CD24, and CD133 surface markers. MicroRNA microarray analysis revealed 31 differentially expressed miRNAs (DEmiRNAs), of which 10 downregulated miRNAs were involved in pathways regulating pluripotency, including the Wnt/β-catenin, TGF-β, MAPK, and PI3K/AKT pathways. Then, 2 of these 10 DEmiRNAs, let-7b-5p and miR-24-3p, were selected for experimental validation. Their overexpression in PCSC+ cells inhibited these pathways, downregulated pluripotency factors, and induced differentiation into endocrine and exocrine phenotypes, as confirmed by RT-qPCR, Western blot, and RNA-seq. Functionally, each miRNA reduced sphere formation, increased gemcitabine sensitivity, and suppressed tumorigenicity in vivo, highlighting their potential as therapeutic candidates. Restoring tumor-suppressive miRNA expression may offer a novel strategy to overcome chemoresistance and improve outcomes in pancreatic cancer. Full article

Background: Genetic variants in Pre-B cell Leukemia Factor 1 (PBX1) transcription factor (TF) have been associated with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). This study aims to functionally characterize a novel missense variant in a 4-year-old patient presenting with horseshoe kidney with preserved function, in the absence of a positive familial history. Methods: Clinical exome sequencing was performed on a 4-year-old child, followed by Sanger sequencing and family segregation studies to validate the identified variant. Functional assays to study the protein expression, molecular interactions and localization were then performed. Results: Genetic analysis identified a novel de novo variant [c.712C>T, p.(Arg238Trp), NM_002585.3], mapping in the first nuclear localization signal (NLS) of PBX1. When introduced in HEK293T cells, PBX1^c.712C>T did not affect protein expression, which was comparable to the wild-type (WT) counterpart. Similar results were obtained when modeling a missense variant [c.863G>A; p.(Arg288Gln)], located in the second NLS of the protein, previously reported in the literature but never functionally characterized. As a TF, PBX1 may work in association with MEIS and PKNOX1/2 cofactors, but none of the two variants modified the interactions with its cofactor PKNOX1. However, both variants significantly affected the nuclear localization of PBX1, increasing its retention in the cytoplasm while limiting its availability in the nucleus. Conclusions: In conclusion, we identified a novel de novo heterozygous missense variant in PBX1 that impairs nuclear localization of the protein, potentially limiting its role as a TF and possibly explaining the clinical phenotype of the patient. Full article

Background/Objectives: Secondary hyperparathyroidism (SHPT) affects 30–50% of end-stage renal disease patients. Parathyroidectomy (PTX), while effective for medication-refractory SHPT, carries 20–70% risk of hungry bone syndrome (HBS)—severe sustained hypocalcemia requiring intensive care and prolonged hospitalization. Accurate preoperative risk stratification using biochemical markers and validated prediction tools is critical for optimal preventive management. Methods: We conducted a comprehensive narrative review synthesizing evidence on HBS predictors after PTX in SHPT, evaluating traditional and novel bone turnover markers, clinical risk factors, and multivariate prediction models, through a structured literature search and analysis. Results: Preoperative bone turnover status represents the strongest contributor to HBS risk. Traditional biomarkers—particularly parathyroid hormone (PTH > 1000–2400 pg/mL) and alkaline phosphatase (ALP > 150–300 U/L)—demonstrate moderate-to-strong individual predictive power. Novel bone turnover markers (bone-specific ALP, P1NP, TRAP-5b) offer incremental value, especially in CKD populations where renal clearance affects traditional markers. Combined risk prediction models substantially outperform single biomarkers, achieving area under curve values of 0.87–0.95. The simple NYU 2-point score (ALP > 150 U/L + PTH > 1000 pg/mL) showed 96.8% accuracy, with 100% negative predictive value. More complex tools like nomograms (C-index 0.92–0.94) and machine-learning algorithms (AUC 0.88) provide enhanced discrimination by integrating multiple continuous parameters. Additional clinical factors—younger age (<48 years), prolonged dialysis (≥5 years), low preoperative calcium, high gland weight, and absence of autotransplantation—further refine risk assessment. Postoperative calcium typically reaches nadir at 48–72 h, defining the critical monitoring window. Conclusions: High-turnover bone biomarkers and combined risk models effectively identify high-risk SHPT patients. Risk-stratified protocols (i.e., prophylactic supplementation, intensive monitoring, and selective ICU admission) can substantially reduce HBS-related morbidity. Ongoing efforts should focus on validating these predictive tools across diverse populations and integrating them into clinical practice, thereby facilitating real-time HBS risk assessment and protocol-driven care. Full article

Background/Objectives: Breast cancer is a heterogeneous disease, and the role of the transcription factor SPDEF remains controversial. We aimed to clarify the prognostic value of SPDEF, explore demographic and molecular correlates of its expression, and investigate potential regulatory mechanisms underlying its dysregulation. Methods: Genomic and clinical data for 1218 breast cancer tumors were obtained from The Cancer Genome Atlas (TCGA). SPDEF mRNA expression was compared across intrinsic subtypes, age, and race, and prognostic significance was evaluated by Kaplan–Meier analysis. Promoter methylation patterns and DNA methyltransferase (DNMT) expression were examined as potential regulatory drivers. Co-expression analysis was performed using gene panels representing luminal differentiation, basal identity, EMT, proliferation, DNA repair, and immune signaling. Results: Low SPDEF expression was significantly associated with worse overall, relapse-free, and metastasis-free survival across all breast cancers. Expression was lowest in Basal tumors, as well as among younger and Black or African American patients. Promoter methylation at six CpG islands correlated with both reduced SPDEF expression and inferior survival, and DNMT1, DNMT3A, and DNMT3B overexpression also aligned with poor prognosis and Basal enrichment. Co-expression analysis revealed that SPDEF downregulation coincided with loss of luminal markers and increased EMT, proliferation, DNA repair, and immune pathways. Conclusions: SPDEF functions as a tumor suppressor in breast cancer, with reduced expression linked to poor outcomes, aggressive molecular features, and epigenetic regulation. These findings highlight SPDEF and DNMT-driven methylation as potential prognostic biomarkers for enhanced risk stratification and targets for novel therapies, particularly in Basal breast cancers. Full article

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease characterized by immune dysregulation, vasculopathy, and fibrosis. Objectives: To evaluate the genetic architecture and autoantibody profile in a Kazakh cohort of patients with SSc. Methods: A total of 26 Kazakh patients with diffuse SSc were examined for disease activity and organ impairment using EScSG and the modified Rodnan skin score (mRSS). Eighteen healthy volunteers were enrolled in the control group. Antinuclear factor (ANF) was estimated on HEp-2 cells, while antibodies to Scl-70, CENP-B, U1-snRNP, SS-A/Ro52, SS-A/Ro60, Sm/RNP, Sm, SS-B, Rib-P0, and nucleosomes were determined by immunoblotting. The level of IL-6 cytokine was detected using ELISA. To investigate the genetic basis of SSc in Kazakh patients, a custom AmpliSeq panel including targeting immune/fibrosis pathways and 120 genes was used on the Ion Proton sequencer. The statistical analysis of categorical variables was conducted using Fisher’s exact test and Chi-square (χ²) test. Results: The examination of SSc patients (mRSS 16 ± 7.2; EScSG 3.54 ± 2.18) revealed a broad range of antibodies to Scl-70, CENP-B, SS-A/Ro60, SS-A/Ro52, U1-snRNP, and RNP/Sm, which were undetectable in the control group. Genetic analysis identified multiple variants across immune regulatory genes, including likely pathogenic changes in SAMD9L, REL, IL6ST, TNFAIP3, ITGA2, ABCC2, AIRE, IL6R, AFF3, and TREX1. Variants of uncertain clinical significance were detected in LY96, IRAK1, RBPJ, IL6ST, ITGA2, AIRE, IL6R, JAZF1, IKZF3, IL18, IL12B, PRKCQ, PXK, and DNASE1L3. Novel variants at the following genomic coordinates were identified and have not been previously reported in association with SSc: LY96 (chr8:74922341 CT/C), PTPN22 (chr1:114381166 CT/C), IRAK1 (indels at chrX:153278833), and SAMD9L (chr7:92761606 GT/G; chr7:92764981 T/TT). Conclusions: The first immunogenetic investigation of SSc in Kazakhstan revealed a polygenic architecture involving immune signalling pathways that partially overlap with international cohorts while exhibiting region-specific variation. Although the limited sample size and lack of functional validation constrain the interpretability of the findings, the results provide a framework for larger research to confirm the pathogenic mechanisms and establish clinical relevance. Full article

Background: Hepatitis C Virus (HCV) remains a global health challenge as WHO elimination targets are not achievable in most countries, mainly due to the high number of undiagnosed individuals. In Italy, where national elimination efforts are ongoing, regional disparities further hinder progress. This study aimed to characterize the hidden burden of chronic HCV infection across t he territory of the Province of Salerno, Southern Italy, to suggest a novel municipal-level screening approach, with implications for national strategies. Methods: We analyzed records of residents diagnosed with chronic HCV infection and linked to care between 2015 and 2022. Data included age, sex, municipality of residence, HCV genotype, and fibrosis stage. Observed prevalence was compared with expected prevalence derived from national/regional benchmarks. Municipalities were categorized as urban or rural based on the resident population. Results: A total of 3528 cases were identified across 139 municipalities. Patients had a mean age of 63 years, and 54% were male. Half were diagnosed at an advanced stage (F3–F4), with genotype 1b being predominant. The hidden burden increased with age and showed a higher prevalence in rural areas compared to urban ones, with values of about 7 vs. 3 per 1000 inhabitants respectively. Logistic regression analysis identified age, male sex, urban residence, and genotype 1b as factors associated with advanced fibrosis or cirrhosis. Conclusions: This is the first Italian study to apply a standardized municipal-level classification to quantify the hidden burden of HCV. The model identifies underdiagnosed areas, highlights urban–rural disparities (a higher degree of underdiagnosis in rural areas versus a higher frequency of late diagnosis in urban ones), and provides a replicable tool for precision public health. Its adoption could enhance national HCV elimination efforts by supporting targeted screening, optimized resource allocation, and equitable access to care. Full article