To evaluate the impact of stopping-power ratio (SPR) predictions derived from dual-layer detector-based spectral CT (DLCT) on conventional single-energy CT (SECT)-based carbon-ion treatment planning for thoracic cancer.

Twenty patients with thoracic cancer who underwent non-contrast DLCT were retrospectively included. DLCT-based SPR images were generated from effective atomic number and relative electron density maps using the Bethe equation. SECT-based SPR was derived using a Hounsfield unit look-up table generated via stoichiometric calibration of a commercial electron density phantom. Using the same phantom, a phantom-based prediction assessment was performed by comparing SECT- and DLCT-based SPR predictions with theoretical SPR values for the inserts. For patient analysis, normal-tissue SPR values derived from SECT and DLCT were compared. Carbon-ion treatment plans were first generated based on SECT images and then recalculated using DLCT-derived SPR images. Range differences in the beam's-eye view and dose-volume histogram parameters for the planning target volume and organs at risk were evaluated.

In the phantom-based assessment, the root-mean-square error relative to the theoretical SPR was 5.57% for SECT and 2.83% for DLCT. In patient images, mean SPR differences between SECT and DLCT were 3.62% for the lungs, 1.93% for the esophagus, 0.04% for the heart, 0.93% for the spinal cord, and 1.53% for the ribs. Across the patient cohort, the mean recalculated range difference was 0.71 ± 0.89 mm, corresponding to a relative difference of 0.60 ± 0.67%. No statistically significant differences were observed in target dose metrics, whereas selected organ-at-risk metrics showed statistically significant differences between SECT-based plans and DLCT-based recalculations.

DLCT-derived SPR prediction showed better agreement with theoretical phantom SPR values in the phantom-based prediction assessment and produced tissue-dependent SPR differences in thoracic patient images compared with conventional SECT-based prediction. Recalculation on DLCT-derived SPR maps resulted in modest but systematic range differences and limited changes in selected dose metrics. These results may inform the implementation and future independent validation of patient-specific DLCT-based SPR workflows in carbon-ion treatment planning for thoracic cancer.

Lung adenocarcinoma (LUAD), the most prevalent lung cancer subtype, has witnessed a dramatic upsurge in frequency over the past 20 years. This study intended to construct a predictive risk model and analyze melatonin (ME)-associated genes in LUAD.

Differentially expressed genes (DEGs) were found by using DESeq2 to analyze the TCGA-LUAD dataset. ME-DEGs were discovered near the junction, and ME critical module genes were identified by WGCNA. To build a risk model, model genes from ME-DEGs were chosen using univariate and multivariate Cox analysis. The samples were categorized as either low-risk or high-risk. The model was verified using the GSE31210 dataset. Gene expression was confirmed by RT-qPCR, immunological studies were performed, and a nomogram was developed.

The 98 ME-DEGs were obtained by combining 1,052 ME key module genes with 5,449 LUAD-DEGs. Eight model genes were selected using univariate and multivariate cox regression analyses. The risk model, which was constructed using model genes, showed good predictive performance in both the TCGA-LUAD and GSE31210 datasets. Additionally, the nomogram's superior predictive accuracy for LUAD was confirmed by calibration and receiver operating characteristic (ROC) curves. Additionally, the results of immune analysis showed that ALG3 and FRY had significant relationships with immune cells and immune checkpoints, and that E2F1 had a significant negative association with FRY.

We developed and validated a novel ME-related prognostic model for LUAD. This algorithm may be able to predict patient outcomes and provide recommendations for tailored immunotherapy.

To evaluate the diagnostic performance metrics, referral patterns, and real-world implementation characteristics associated with a Breast AI™-supported ultrasound assessment pathway across multiple heterogeneous healthcare settings.

This prospective multi-site observational study included 1,129 women undergoing routine or symptom-driven breast assessment across five healthcare facilities in South Africa between April 2023 and April 2025. Breast AI™ was used as an adjunctive ultrasound-based clinical decision-support tool alongside standard clinical assessment and breast ultrasound imaging. Referral outcomes and histopathological diagnoses were recorded where clinically indicated. Diagnostic performance metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated using predefined dichotomised Breast AI™ risk categories. Site-level comparisons were assessed using chi-square analysis.

Among 1,129 clinical assessments, 417 patients underwent referral for further diagnostic evaluation, with 405 histopathologically confirmed malignancies identified. Referral-associated malignancy rates remained relatively consistent across participating healthcare sites, with no statistically significant site-level differences observed (χ² = 1.67, p = 0.795). Diagnostic performance analysis demonstrated a sensitivity of 99.3% (95% CI: 97.8-99.8), specificity of 69.8% (95% CI: 66.3-73.1), PPV of 64.7% (95% CI: 61.2-68.0), and NPV of 99.4% (95% CI: 98.3-99.8). Higher Breast AI™ risk classifications were more frequently associated with invasive ductal carcinoma and invasive lobular carcinoma, whereas approximately 30% of ductal carcinoma in situ cases were classified within the low-risk category. The median interval between Breast AI™ assessment and histopathological confirmation was 18 days (IQR: 10-32 days).

In this prospective observational multi-site cohort, Breast AI™-supported ultrasound assessment demonstrated high observed negative predictive value and reproducible risk stratification across heterogeneous healthcare environments. However, interpretation of diagnostic accuracy metrics is limited by differential histopathological verification and the absence of long-term interval cancer follow-up among low-risk patients. The findings support the feasibility of integrating AI-supported ultrasound assessment into resource-variable clinical settings, while highlighting the need for future comparative, longitudinal, and health-economic evaluation studies.

N-glycans modulate glycoprotein structure and function and are altered during chronic inflammation. We sought to define the extent of serum and IgG N-glycan disruption in patients with decompensated liver cirrhosis from alcohol-related liver disease (ALD), primary sclerosing cholangitis (PSC), and ALD-related hepatocellular carcinoma (HCC). Finally, we aimed to examine whether serum and IgG glycosylation is associated with changes in Model for End-stage Liver Disease-Sodium (MELD-Na) scores, a clinical marker used to prioritise liver transplantation.

Serum samples were obtained from patients with ALD (n = 17), PSC (n = 7), ALD-related HCC (n = 4), and healthy controls (n = 10). N-glycans were released, fluorescently labelled, and profiled by hydrophilic interaction ultra performance liquid chromatography (HILIC-UPLC). Chromatograms were integrated into 46 and 23 glycan peaks for serum and IgG respectively. These peaks and their associated glycosylation traits were statistically compared with healthy controls using age- and sex-adjusted linear regression models.

In serum, decompensated cirrhosis shows statistically significant shifts toward less complex, agalactosylated and asialylated biantennary glycans, accompanied by significant losses of highly branched, galactosylated and sialylated structures. IgG mirrored this pattern, which is characteristic of a pro-inflammatory signature, with increased agalactosylation and bisected glycan levels, along with reduced levels of digalactosylated and sialylated species. N-glycan profiles showed significant associations with MELD-Na scores, indicating that inflammatory processes in decompensated liver cirrhosis continue to reshape serum glycoproteins.

Decompensated liver cirrhosis shows profound remodelling of serum and IgG N-glycans. These data establish a reference framework for terminal glycomic disruption in liver disease and highlight the potential value of incorporating glycosylation analysis into broader assessments of liver disease progression.

To the best of our knowledge, no previous systematic review has comprehensively quantified cancer prevalence across the broad spectrum of cardiovascular and cardiometabolic conditions included in the present study. We aimed to estimate pooled prevalence of active cancer (primary outcome) and other cancer categories among patients with coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), hypertension, Type 2 diabetes mellitus (DM), stroke, peripheral artery disease (PAD), and valvular heart disease (VHD).

PubMed, Web of Science, and Scopus were searched from 2010 to July 2024. Secondary outcomes included prevalence of any, previous, haematological, solid, and metastatic cancer. Prevalence estimates were calculated using one-step generalized linear mixed models.

A total of 676 studies comprising approximately 180 million participants were included. The primary analysis of active cancer included 59 studies (4,759,695 patients). Active cancer prevalence ranged from 4.22% (95% confidence interval [CI] 2.18-5.32) in Type 2 DM to 5.55% (95% CI 3.97-7.01) in AF. The prevalence of any cancer, a secondary outcome with more heterogeneous ascertainment, ranged from 7.04% (95% CI 6.05-8.03) in CAD to 14.10% (95% CI 12.20-15.99) in AF.

Cancer represents a substantial comorbidity across cardiovascular and cardiometabolic conditions. Although cancer ascertainment methods varied across studies, particularly for any cancer, the findings provide contemporary estimates of cancer burden that may inform future cardio-oncology research, healthcare planning, risk stratification, and the design of cardiovascular and cardiometabolic clinical trials.

PROSPERO CRD42023494764.

To examine how biological sex and gender influence the tumorigenesis of neuroendocrine neoplasms (NEN), integrating epidemiological evidence with hormonal, molecular, lifestyle and environmental factors.

Recent population-based studies demonstrate sex differences in NEN incidence, pathological characteristics and survival across multiple anatomical sites. Emerging evidence suggests that sex-hormone signalling, epigenetic regulation and the tumour microenvironment may contribute to these differences. Lifestyle and metabolic factors, including smoking and obesity, may further modify NEN susceptibility and interact with sex- and gender-related factors. Biological sex appears to be an important modifier of NEN development rather than simply a demographic characteristic. However, mechanistic evidence remains limited and the contribution of gender is poorly characterised. Prospective, sex-stratified studies integrating hormonal, molecular and environmental data are required to clarify these interactions and their potential clinical relevance.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection in immunocompromised patients. The aim of this study was to identify risk factors associated with in-hospital 30-day all-cause mortality among PJP in patients with HIV and hematologic malignancies where PJP is the most prevalent.

We conducted a multicenter, international, retrospective cohort study of consecutive hospitalized patients aged > 17 years with PJP between January 1, 2010, and March 1, 2024. Only patients with laboratory-confirmed PJP were included.

Overall, 156 patients were included to study. Of the 156 patients, 115 (73.7%) were male, and the median age was 43 years (IQR 35-52). Of the patients, 130 (83.3%) were people living with HIV, including 126 newly diagnosed cases, while 26 (16.7%) had hematologic malignancies. Overall, PJP prophylaxis was used in only 4.5% of patients. According to the immunofluorescence assay or conventional staining methods used as the reference standard, the positivity rate of P. jirovecii PCR in BAL samples was 96.4%. Intensive care unit admission was required for 60 patients (38.5%), of whom 51 (85.0%) required mechanical ventilation. The overall in-hospital 30-day all-cause mortality rate was 14.1%. In the multivariable logistic regression analysis, higher respiratory rate (OR 1.092; 95% CI 1.002-1.190), higher SOFA score (OR 1.757; 95% CI 1.311-2.356), increased neutrophil count (OR 1.332; 95% CI 1.141-1.555), pleural effusion on chest X-ray (OR 7.268; 95% CI 1.382-38.212), and a prior history of PJP (OR 19.537; 95% CI 1.462-261.2) were independently associated with increased in-hospital 30-day all-cause mortality.

Our findings indicate that greater clinical severity and respiratory compromise are associated with increased mortality risk, underscoring the value of early recognition of high-risk patients to guide timely management.

IL-6 level in serum has been shown to have predictive value for postoperative infectious complications and prognostic value in acute pancreatitis. Evidence on its role after pancreatic resection is limited. The aim of the study was to analyse the predictive role of early postoperative serum IL-6 regarding complications after pancreatic resection.

A retrospective analysis of patients with pancreatic resection at a tertiary German centre was performed. All IL-6 values per patient within 48 h after resection were delineated. Values at fixed postoperative time points were interpolated between each patient's measurements and, beyond them, predicted from a linear mixed-effects model. Receiver operating characteristic curve analysis was performed, and optimal time and cut-off points for prediction of postoperative pancreatic fistula (POPF), postpancreatectomy acute pancreatitis (PPAP) and overall complications were set out.

Out of 316 patients, 157 patients with more than one IL-6 value were included. IL-6 at 36 h after resection showed the best diagnostic performance for all three endpoints. For PPAP B/C, the AUC was 0.800 (95% CI 0.685-0.916) at a cut-off of 296 pg/ml (sensitivity 62%, specificity 80%, PPV 26%, NPV 95%), and for POPF B/C 0.715 (0.632-0.798) at 192 pg/ml (sensitivity 70%, specificity 59%, PPV 52%, NPV 76%). Discrimination for major complications (Clavien-Dindo ≥ 3b) was weaker, with an AUC of 0.636 (0.539-0.733) at 208 pg/ml (sensitivity 55%, specificity 62%, PPV 44%, NPV 73%).

Serum IL-6 within 48 h after pancreatic resection could be useful in risk assessment for pancreas-specific complications.

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading cause of treatment failure in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), yet effective maintenance strategies are currently lacking. The combination of chidamide (CHI) and venetoclax (VEN) represents a novel approach. However, real-world data on its use are limited. In this study, eighteen high-risk transplant recipients received maintenance therapy with CHI (5 mg/day on days 1-7 or 1-14) plus VEN (100 mg on day 1, then 200 mg on days 2-7 or 2-14) every 2 months. Endpoints included overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and safety. After a median follow-up of 708 days, the 2-year OS and DFS were 73.9% and 56.6%, respectively. The 2-year CIR was 28.9%, and the 2-year NRM rate was 22.5%. The most common adverse events were hematologic, including neutropenia (13 episodes), thrombocytopenia (7), and anemia (7), all of which were manageable. No treatment-related mortality, tumor lysis syndrome, or severe acute graft-versus-host disease (GVHD) occurred. In conclusion, CHI plus VEN as post-transplant maintenance therapy shows encouraging efficacy and a manageable safety profile in high-risk AML/MDS patients, representing a promising strategy for relapse prevention.

Safe and effective gastric cancer surgery requires detailed knowledge of vascular anatomy, but vascular complexity and heterogeneity relevant to gastrectomy have not been comprehensively quantified. This study aimed to determine whether this anatomy can be categorized into a limited set of patterns or whether its heterogeneity requires patient-level characterization. This retrospective multicenter study included patients at five tertiary institutions who underwent standardized preoperative abdominopelvic computed tomography angiography between April 2021 and October 2023. Patient-specific three-dimensional reconstructions were reviewed using a surgical navigation system to characterize 23 gastrectomy-related vessels by number, origin, drainage, or position. Combined arterial and venous structures were encoded as a 92-digit sequence to identify unique configurations. Interindividual heterogeneity was quantified using diversity indices. Among 310 patients, only 4 of 23 gastrectomy-related vessels exhibited a single anatomical pattern: celiac artery, anterior superior pancreaticoduodenal artery, left gastroepiploic artery, and left gastroepiploic vein. The remaining vessels showed variable patterns in number, origin, drainage, or position. Combined arterial and venous assessment identified 292 unique vascular configurations; 277 were each observed in a single patient (277 patients, 89.4%), 12 were shared by 2 patients (24 patients, 7.7%), and 3 were shared by 3 patients (9 patients, 2.9%). Diversity indices indicated marked interindividual heterogeneity (Shannon, 5.651; Simpson, 0.996), with the Simpson index corresponding to a 99.6% probability that two randomly selected patients had different vascular configurations. Gastrectomy-related vascular anatomy showed substantial complexity and heterogeneity, suggesting that reliance on a limited set of patterns may be insufficient. These findings provide an anatomical framework for patient-specific vascular mapping and a basis for future validation in image-guided surgery.