BACKGROUND: Maternal serum alpha-fetoprotein (AFP) levels are used in screening for open neural tube defects (ONTD). Historical reports show that AFP levels and maternal weights are higher in self-reported Black than White individuals, but recent reports question the need to account for these variables in screening. Our study compares screening performance with and without accounting for race.
METHODS: Retrospective analysis was performed on deidentified prenatal screening records including maternal weight and self-reported race of White or Black. Gestational age-specific medians and weight-adjusted multiples of the median levels were calculated separately for each group and using a race-agnostic analysis. Outcome measures included the proportion of screen-positive results.
RESULTS: Records for analysis (n = 13 316) had an ultrasound confirmed gestational age between 15 and 21 completed weeks, singleton pregnancy, and self-reported race. Race was Black for 26.3%. AFP levels for pregnancies in Black individuals were higher than in White individuals: 6% to 11% depending on gestational age. Race-specific gestational age and maternal weight analyses resulted in similar screen-positive rates for self-reported White and Black individuals at 0.74% vs 1.00%, respectively (P = 0.14). However, use of race-agnostic analyses resulted in a screen-positive rate that was 2.4 times higher in Black than White individuals (P < 0.001).
CONCLUSIONS: These data show that the historical method of accounting for maternal race and weight in prenatal screening for ONTD provides equitable performance. Using a race-agnostic methodology results in an increased screen-positive rate and a disproportionate rate of required follow-up care for individuals who self-identify as Black.

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher\'s exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann-Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM\'s role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.

OBJECTIVE: The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in Hepatocellular Carcinoma (HCC), and determine their correlation with clinicopathological parameters of this type of cancer to determine their diagnostic value in combination.
METHODS: Seventy-five patients with HCC were assessed for the expression of PIWIL2 in serum and tissue using real-time polymerase chain reaction (RT-PCR) and IHC was performed for PIWIL2 and HepPar1 was performed on all patients.
RESULTS: A statistically significantly higher level of PIWIL2 was found in HCC compared to controls (p≤0.001). Both HepPar1 and PIWIL2 were detected in 84% of HCC cases, the diagnostic and prognostic factors for PIWIL2 were found to be significant in liver tumour tissue samples and non-tumorous sections p<0.001, and the same was observed for serum samples and results of healthy serum controls (p<0.001) when compared to AFP.
CONCLUSIONS: Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development, and that a possible panel maybe used for these markers HCC diagnosis.

The conventional electrochemical detection strategy for alpha-fetoprotein (AFP) is limited by the antigen-antibody (Ag-Ab) reactions and suffers from low sensitivity and poor reproducibility due to the inconsistency of Ab-modified electrodes. Herein, we designed and explored a sandwich-type electrochemical sensor for highly sensitive detection of AFP based on aptamer (Apt)-AFP-Ab interaction mode with silver@gold (Ag@Au) core-shell nanoparticles (NPs) as a signal amplifier. AuNPs were electrodeposited onto MXene (Ti3C2TX)-modified glassy carbon electrode (GCE) to get AuNPs/MXene/GCE and further used as the signal amplification substrate. The tetrahedral DNA-linked AFP aptamers were immobilized onto AuNPs/MXene/GCE surface via Au-S bonds and used as the sensing and recognition platform for AFP capturing. Ag@AuNPs with core-shell structures were synthesized, characterized, and bound with Ab as detection elements by catalyzing H2O2 reduction. In the presence of AFP, a stable Apt-AFP-Ab sandwich structure was formed owing to the high affinities of aptamer and Ab toward the target AFP. The catalytic current produced by H2O2 reduction increased linearly with the logarithm of AFP concentration from 5 × 10-4 ng/mL to 1 × 105 ng/mL, accompanied by a low detection limit (1.6 × 10-4 ng/mL). Moreover, the novel sandwich-type electrochemical sensor shows high sensitivity, outstanding selectivity, and promising performance in the analysis of actual samples, displaying a broad application prospect in bioanalysis.

BACKGROUND: At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs.
OBJECTIVE: To develop a model for predicting prognosis after LT in patients with HCC.
METHODS: Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms.
RESULTS: The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability.
CONCLUSIONS: The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.

BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors.
METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the \"LAD Score.\" An independent cohort of 117 patients with HCC was used for external validation.
RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors <2 cm in diameter (AUROC of the LAD score 0.721 vs. imaging 0.595, p = 0.02). In the validation data set, the LAD score had an AUROC of 0.832 (95% CI: 0.753, 0.911) with a sensitivity of 72.5% and a specificity of 89.4% at the cutoff of 0.927.
CONCLUSIONS: Our findings suggest the utility of LAD score in treatment response assessment after locoregional therapy for HCC, particularly in detecting small tumors. A larger prospective study is in progress to validate its accuracy and evaluate its performance in recurrence monitoring.

BACKGROUND: The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport.
METHODS: To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer.
RESULTS: Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer.
CONCLUSIONS: We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer.
BACKGROUND: Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute.

A novel construction strategy is introduced for an ultrasensitive dynamic light scattering (DLS) immunosensor targeting alpha fetoprotein (AFP). This approach relies on a self-assembled heptamer fusion protein (A1-C4bpα), incorporating the dual functions of multivalent recognition and crosslinking aggregation amplification due to the presence of seven AFP-specific A1 nanobodies on the A1-C4bpα heptamer. Leveraging antibody-functionalized magnetic nanoparticles for target AFP capture and DLS signal output, the proposed heptamer-assisted DLS immunosensor offers high sensitivity, strong specificity, and ease of operation. Under the optimized conditions, the designed DLS immunosensor demonstrates excellent linear detection of AFP in the concentration range 0.06 ng mL-1 to 512 ng mL-1, with a detection limit of 15 pg mL-1. The selectivity, accuracy, precision, practicability, and reliability of this newly developed method were further validated through an assay of AFP levels in spiked and actual human serum samples. This work introduces a novel approach for constructing ultrasensitive DLS immunosensors, easily extendable to the sensitive determination of other targets via simply replacing the nanobody sequence, holding great promise in various applications, particularly in disease diagnosis.

BACKGROUND: Chronic HC leads to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The treatment of chronic HC with DAAs reduces mortality from LC and HCC. The study aimed to investigate the serological markers specific to HCC (PIVKA-II and AFP) in patients with chronic HC before and after DAA treatment.
METHODS: The study involved 35 HCV patients (mean age: 56.23 ± 1.45) divided into two groups. Group 1 included 15 HCV + HCC patients and Group 2 included 20 HCV non-HCC patients.
RESULTS: At the end of treatment all the patients were HCV RNA negative. Three months after the end of antiviral treatment, HCV RNA was undetectable in all patients, while a complete biochemical and virological response was observed in 66.7% of HCV + HCC patients and 85.0% of HCV non-HCC patients. PIVKA-II levels before the initiation of antiviral treatment were high in all patients. At the end of the treatment, in the HCV non-HCC group, normalization of PIVKA-II levels was observed only in 20.0% cases, and in 60.0% of cases 3 months after the treatment. Meanwhile, in patients with HCC and chronic HCV, PIVKA-II levels were within the normal range 3 months after treatment in only 13.3% of patients.
CONCLUSIONS: It is necessary to monitor HCV patients with cirrhosis (F4) and severe fibrosis (F3) without HCC, who have high PIVKA-II and AFP levels and/or ALT activity despite obtaining sustained virologic response 3 months after treatment with DAAs.

Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive application of Ppy as a biorecognition film encapsulated with an antibody (Ab) as an alternative strategy for the on-site multistep functionalization of thiol-based self-assembled monolayers. The fabrication steps of the recognition films were followed by dropping pyrrole and Ab mixed solutions onto the electrode and obtaining a thin film by direct current electropolymerization. The efficiency of Ab immobilization was studied by using fluorescence microscopy and electrochemical (EC) methods. Finally, the Ab density was increased and immobilized in 1 min, and the sensing performance as an EC immunosensor was demonstrated using α-fetoprotein with a limit of detection of 3.13 pg/mL and sensing range from 1 pg/mL to 100 ng/mL. This study demonstrates the potential for electrochemical functionalization of biomolecules with high affinity and rapidity.