Prostate artery embolization (PAE) requires precise visualization of complex pelvic arterial anatomy and can be aided by advanced vessel navigation tools. Photon counting detector (PCD) CT provides simultaneous ultra-high resolution and material-specific imaging, potentially improving automatic vessel tracing workflow for procedural planning and guidance.

To identify, within a PCD-CT workflow, the reconstruction that provides the most robust and consistent automatic vessel tracing for pre-procedural PAE planning.

Ten patients underwent PCD-CT angiography of the prostate arteries in ultra-high-resolution mode. Four reconstruction approaches were evaluated: conventional reconstructions with (1) standard of care kernel and (2) sharper kernel (Bv64), along with (3) monoenergetic 50 keV, and (4) iodine map spectral results. Using commercial embolization guidance software, three vessels were manually traced for each patient to establish ground truth segmentation. Subsequently, automatic vessel traces were generated using identical start/end points as the ground truth. Root mean squared error (RMSE) between automatic traces and ground truth was used to quantify tracing accuracy.

Comparing individual traces, iodine maps demonstrated consistency with median RMSE of 0.7 mm (0.4 mm interquartile range (IQR)) versus 0.7 mm (12.5 mm IQR), 1.5 mm (14.7 mm IQR), and 0.8 mm (6.7 mm IQR) for Bv56, Bv64, and 50 keV reconstructions, respectively. Iodine maps produced fewer outliers, with 13.3% of traces and 40.0% of patients having one or more traces exceeding 5 mm RMSE, compared with 26.7%-36.7% of traces and 60.0%-80.0% of patients for the other reconstructions.

Material-specific iodine reconstructions from PCD-CT yield more robust automatic vessel tracing for PAE planning, offering a workflow-compatible solution requiring minimal protocol modifications.

The diagnostic landscape for the Philadelphia-negative myeloproliferative neoplasms (MPNs), particularly in distinguishing Essential Thrombocythemia (ET) from Polycythemia Vera (PV), is compromised. The gold standard for diagnosing PV-measurement of red cell mass (RCM) by radioisotope dilution-has been largely abandoned, leading to widespread misclassification. Thus, an estimated 30%-50% (varying by diagnostic center and testing practice) of JAK2V617F-positive ET patients may, in fact, have "hidden" PV, depriving them of the cornerstone PV therapy: phlebotomy. This diagnostic inaccuracy exposes a sizable patient population to an unfortunate high risk of life-threatening thrombotic events. Concurrently, the management of established PV is suboptimal, often relying solely on hematocrit, a flawed parameter especially in iron-deficient or hydroxyurea-treated patients. This perspective calls for the revival and clinical implementation of the Carbon Monoxide (CO)-rebreathing technique as a promising, rapid, and nonradioactive alternative for RCM assessment. Herein, we review the history of this methodology and discuss its potential to improve MPN care by ensuring precise diagnosis, guiding rational phlebotomy, and ultimately reducing thrombotic morbidity and mortality, while also candidly addressing the current evidentiary and practical limitations that must be resolved before clinical adoption, while also offering potential health-economic benefits.

Epigenetic regulation and gene transcription are dynamically modulated by extracellular signals, including focal adhesions; however, the role of integrins in these processes remains poorly understood. In this study in HPV-negative head and neck squamous cell carcinoma, (HNSCC), we combined investigations in physiological three-dimensional, matrix-embedded cell models and patient-derived organoids with multi-omics analyses, bioinformatics and artificial intelligence, to unmask the integrin effector signaling network that reshapes chromatin to drive cancer. Among the 12 α/β1 integrin receptors, α7 integrin (ITGA7) emerged as the most potent modulator of histone post-translational modifications, associated with significant changes in gene transcription and chromatin accessibility. Depletion of ITGA7, achieved independently by CRISPR/Cas9 knockout and RNA interference, reduced chromatin accessibility at the AURKA locus and downregulated an AURKA-centered transcriptional program. Mechanistically, phosphoproteomics revealed significant inhibition of MAPK- and PI3K/AKT-dependent signaling with concomitant functional impairment of cell cycling and cell survival upon ITGA7 depletion. Across all analyses, machine-learning-based feature selection consistently nominated AURKA as the dominant downstream node, and tumor ITGA7 expression stratified patient overall survival in a non-linear manner. In summary, these findings establish α7 integrin as a key co-regulator of chromatin accessibility and gene transcription in HPV-negative HNSCC, acting through an AURKA-centered axis that couples adhesion signaling to cell cycle control and patient survival, and nominate AURKA, potentially targetable with clinical Aurora-A inhibitors such as alisertib, as an actionable therapeutic node downstream of the currently non-druggable ITGA7.

We conducted a randomized surgical window-of-opportunity trial ( NCT04606316 ) in recurrent, resectable glioblastoma. Between 2021 and 2024, 71 patients were screened, and 63 were randomized (intention-to-treat [ITT] population), and 58 received study treatment. Patients received pre-surgical immune checkpoint blockade (ICB) with dual anti-PD1 nivolumab + anti-CTLA4 ipilimumab (Arm 1), nivolumab alone (Arm 2), or placebo (Arm 3). Following surgery, Arms 1 and 3 received dual ICB, while Arm 2 continued nivolumab until progression or unacceptable toxicity. The primary endpoint, tumor-infiltrating lymphocyte (TIL) density, was met for Arm 1, as neoadjuvant dual ICB significantly increased TIL density compared with untreated control (Arm 3). As a secondary endpoint, median overall survival in the ITT population was 402 days (95% CI, 265-571) among patients who received dual ICB (Arms 1 and 3) and 273 days (95% CI, 166-506) for those assigned to nivolumab alone (Arm 2). No unanticipated toxicities were observed. Exploratory analyses showed that dual ICB elicited robust intratumoral and systemic immune activation, including increased interferon-related gene expression in blood. Higher TIL density and early systemic interferon-signature induction were associated with improved survival, whereas tumor mutational burden was not. Our results demonstrate pharmacodynamic activity of dual ICB in glioblastoma, with survival outcomes comparing favorably to similar studies.

The nervous and immune systems interact to form a complex network that sustains homeostasis and finely tunes immune responses. These interactions significantly influence the pathogenesis and progression of various diseases, such as tumors, immune-related disorders, and infections. Consequently, these interactions have become promising therapeutic targets. However, insufficient mechanistic research and the lack of candidate drugs have restricted the application of therapeutic strategies targeting neuro-immune interactions. In this review, we summarize three modes of neuro-immune interactions: local mechanisms, reflex-level organization, and central nervous system-wide regulation. Next, we elucidate the mechanisms of neuro-immune interactions across different diseases, discuss their variations, and highlight the spatiotemporal heterogeneity of these interactions. Additionally, understanding the dynamic crosstalk between specific neuronal and immune cell subtypes could reveal novel biomarkers and intervention points, facilitating more precise and personalized therapeutic strategies in diverse disease contexts. Furthermore, we dissect the current status of clinical trials and analyze the major challenges hindering effective clinical translation. Finally, we explore the potential of high-throughput sequencing technologies, such as single-cell omics and spatial omics, as well as neuro-electrophysiological methods, for in-depth investigation of related mechanisms. By integrating preclinical and clinical perspectives, this review aims to provide valuable insights into the therapeutic potential and future directions in the burgeoning field of neuro-immune interactions.

The transcription factor zinc finger protein 143 (ZNF143) plays a crucial role in regulating diverse biological processes, including cell cycle progression, development, and cellular differentiation. Similarly, c-Myc is well-established as a key regulator of cell proliferation, differentiation, and metabolic homeostasis. While studies have demonstrated ZNF143's involvement in the proliferation of both normal hepatocytes and hepatoma cells, the precise mechanisms underlying ZNF143-mediated regulation of hepatocyte proliferation, as well as its potential functional interplay with c-Myc in this process, remain to be fully elucidated. In this study, we investigated the dynamic expression patterns of ZNF143 and c-Myc during distinct phases of liver regeneration using a 2/3 partial hepatectomy (PHx) mouse model. To elucidate the regulatory roles of these factors in hepatocyte proliferation, we employed the mouse normal hepatocyte line AML12 and the human hepatoma cell line Huh7 as experimental models. Through MTT, CCK-8, EdU, quantitative real-time PCR (qRT-PCR), and Western blot, we examined the individual and combined effects of ZNF143 and c-Myc on hepatocyte proliferation. Our findings reveal that ZNF143 inhibits proliferation and cell cycle progression in AML12 cells but promotes these processes in Huh7 cells. Notably, co-overexpression (OE) of ZNF143 and c-Myc in AML12 cells inhibited proliferation and cell cycle progression, suggesting that ZNF143 exerts a dominant regulatory effect over c-Myc in normal hepatocytes. This study establishes a critical foundation for investigating the role of ZNF143 in hepatocyte proliferation in vivo, with potential implications for liver regeneration and transplantation therapies.

Mitochondrial metabolism and oxidative stress (OS) play critical roles in the progression of hepatocellular carcinoma (HCC). However, reliable prognostic biomarkers for these processes remain unidentified. This study integrated bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) to identify OS&mitochondrial metabolism-related genes (OMRGs). A prognostic model was constructed using LASSO regression, followed by external validation. Associations of the model with clinicopathological features, tumor microenvironment (TME), immune functions, therapeutic response, and drug sensitivity were systematically explored. Finally, the relationships between key OMRGs and mitochondrial metabolism as well as OS were validated. A risk score based on five key OMRGs (LPCAT1, IMPDH1, RAMP3, FZD7, and B4GALT5) was established. Low OMRS was significantly associated with improved overall survival and identified as an independent prognostic factor. Two subtypes (C1/C2) were characterized based on the OMRGs: the C1 subtype exhibited poorer survival and epithelial-mesenchymal transition (EMT) enrichment, whereas the C2 subtype showed greater immune infiltration and sensitivity to immunotherapy. High OMRS was associated with higher predicted IC₅₀ values to oxaliplatin and cisplatin, while low OMRS indicated favorable responses to TACE, sorafenib, and immunotherapy. FZD7 knockdown increased reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential in HCC cells. FZD7, a key gene among OMRGs, represent promising prognostic biomarkers and therapeutic targets in HCC.

Normal tissue in a tumor-bearing organ shows morphological and molecular differences from normal tissue in a tumor-free organ. One explanation to this is that tumors actively instruct adjacent normal tissues to support growth and invasion. The aim of this study was to examine if changes in gene-expression patterns in tumor-adjacent histologically benign prostate tissue, termed tumor instructed normal tissue (TINT), were associated with tumor proximity, grade and molecular subtype and, furthermore, whether they could indicate the presence of high-grade cancer elsewhere in the prostate.

Gene-expression analysis using Clariom D microarrays was performed on matched formalin-fixed paraffin-embedded samples including tumor tissue (n = 44), benign prostate tissue taken near (TINT-N, n = 44) or distant (TINT-D, n = 42) to the tumor in 44 men with unifocal cancer treated by prostatectomy. TINT changes related to cell proliferation and immune cell infiltration were examined using immunohistochemical markers. In addition, gene expression was compared between tumor-negative biopsies from men later diagnosed with high-grade cancer (Bx-later-tumor, n = 46), tumor-negative biopsies from men who remained cancer-free (Bx-control, n = 49), and cancer-containing biopsies (Bx-tumor, n = 28). Gene set enrichment analysis (GSEA) was performed to explore hallmark gene sets in tumor and TINT tissue in relation to tumor grade (high vs. low) and molecular subtype (Luminal B vs. Luminal A).

The transcriptome in TINT differed significantly from that in cancer-free biopsy control tissue and was related to tumor grade (high- vs. low), molecular subtype (Luminal B vs. Luminal A), and tumor proximity (TINT-N vs. TINT-D). Hallmarks related to cell proliferation and increased Ki67 staining as well as signs of increased metabolism were generally enriched in both tumor and TINT tissue of high grade and Luminal B tumors. In contrast, some immune responses were unique to TINT areas of high-grade and Luminal A tumors, respectively, and more obvious in TINT-N than in TINT-D. Analysis of Bx-later-tumor indicated enriched metabolism compared to Bx-control, without clear proliferative or immunological differences.

TINT effects involving proliferation, metabolism and immune responses are related to distance, tumor grade and molecular subtype. TINT alterations hold potential as diagnostic and prognostic biomarkers and may provide a basis for further exploration of tumor-host interactions and potential targets for intervention.

Patients in intensive care units (ICU) under mechanical ventilation, particularly those with SARS-CoV-2 infection, are highly susceptible to Herpes simplex virus (HSV) reactivation. Given the lack of data on the SARS-CoV-2 Omicron and Delta variants, this study aimed to assess the prevalence of pulmonary HSV reactivation in mechanically ventilated patients with SARS-CoV-2 pneumonia. The impact of HSV replication on SARS-CoV-2 replication, and conversely, was investigated, along with the susceptibility of HSV strains to antiviral therapies. This retrospective study included 381 mechanically ventilated ICU patients in Lyon. Overall, 103 patients (27.0%) experienced HSV reactivation, with a trend toward a higher prevalence among SARS-CoV-2-positive patients (32.8%) compared to SARS-CoV-2-negative (24.1%; p value = 0.058). HSV reactivation was significantly higher with the Delta variant (46.2%) compared to Omicron (27.1%; p value = 0.045); the Delta variant was associated with a 2.38-fold increased risk of HSV reactivation. HSV-positive patients exhibited a 1-log lower SARS-CoV-2 viral load compared to HSV-negative patients, a finding indicative of the natural course of SARS-CoV-2 infection followed by HSV reactivation, rather than viral interference. Unexpectedly, acyclovir resistance mutations appeared in the UL23 gene in at least 13.6% of HSV-1 strains in patients with an HSV load above 10⁵ copies/mL. Complementary phenotypic and genotypic approaches allowed to identify three novel substitutions in UL30: Q217R, D741A, and E756K, classified as polymorphisms. Further optimization is needed in the management of mechanically ventilated ICU patients with pulmonary HSV reactivation, especially regarding antiviral resistance testing.

Aging is associated with profound alterations in gut microbiota composition and function, including reduced production of short-chain fatty acids (SCFAs), yet it remains unclear whether these age-related microbial changes directly contribute to impaired antiviral defense during influenza A virus (IAV) infection. To address this question, we first characterized age-associated alterations of the gut microbiome and SCFA-related metabolic potential in a murine model of IAV infection. We then used a complementary human senescent lung fibroblast model to determine whether acetate, a major microbiota-derived SCFA, directly modulates antiviral responses in aging-associated lung cells. In old mice, IAV infection was associated with marked microbiota dysbiosis, including reduced abundance of SCFA-producing commensals such as Akkermansia muciniphila and Faecalibaculum rodentium, accompanied by decreased expression of microbial pathways involved in carbohydrate fermentation and acetate production. These findings suggested impaired microbiota-derived metabolic support of antiviral immunity during aging. Based on these observations, mechanistic studies in senescent human lung fibroblasts demonstrated that acetate supplementation significantly reduced viral replication and inflammatory responses. These protective effects were associated with FFAR2/FFAR3 signaling and enhanced histone H3 acetylation, indicating metabolic and epigenetic modulation of the antiviral response. Together, our findings establish a translational link between aging-associated gut microbiota dysfunction and impaired antiviral defense by combining a murine model of aging and influenza infection with mechanistic validation in human senescent lung cells. They identify acetate as a potential mediator of the gut-lung axis and support microbiota-targeted interventions to reduce influenza severity in older individuals.