TERT-TP53 mutations: a novel biomarker pair for hepatocellular carcinoma recurrence and prognosis.

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, and ranks among the most lethal malignancies globally, primarily due to its high rates of recurrence and metastasis. Despite the urgency, no reliable biomarkers currently exist for predicting tumor recurrence in HCC. Telomerase reverse transcriptase (TERT) promoter mutations (TERTpm) and cellular tumor antigen p53 mutations (TP53m) have been frequently documented in HCC, but their combined clinical significance remains undefined.

Risk factors associated with higher WHO grade in meningiomas: a multicentric study of 552 skull base meningiomas.

The histological grade is crucial for therapeutic management, and its reliable preoperative detection can significantly influence treatment approach. Lacking established risk factors, this study identifies preoperative predictors of high-grade skull base meningiomas and discusses the implications of non-invasive detection. A multicentric study was conducted on 552 patients with skull base meningiomas who underwent primary surgical resection between 2014 and 2019.

[Treatment of ankle osteoarthritis : Analysis of a German nationwide survey].

Background: In most cases osteoarthritis of the ankle is of posttraumatic origin. Younger people are more frequently affected, which makes treatment a particular challenge. In addition to conservative treatment numerous surgical procedures are available for the treatment of advanced arthrosis.

Mitochondrial dysfunction-driven AMPK-p53 axis activation underpins the anti-hepatocellular carcinoma effects of sulfane sulfur.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, notoriously refractory to conventional chemotherapy. Historically, sulfane sulfur-based compounds have been explored for the treatment of HCC, but their efficacy has been underwhelming. We recently reported a novel sulfane sulfur donor, PSCP, which exhibited improved chemical stability and structural malleability.

Artificial intelligence for image recognition in diagnosing oral and oropharyngeal cancer and leukoplakia.

Visual diagnosis is one of the key features of squamous cell carcinoma of the oral cavity (OSCC) and oropharynx (OPSCC), both subsets of head and neck squamous cell carcinoma (HNSCC) with a heterogeneous clinical appearance. Advancements in artificial intelligence led to Image recognition being introduced recently into large language models (LLMs) such as ChatGPT 4.0.

Gemistocytic tumor cells programmed for glial scarring characterize T cell confinement in IDH-mutant astrocytoma.

Isocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytoma is considered a T cell-deprived tumor, yet little is known regarding the phenotypes underlying T cell exclusion. Using bulk, single nucleus and spatial RNA and protein profiling, we demonstrate that a distinct spatial organization underlies T cell confinement to the perivascular space (T cell cuff) in IDHmt astrocytoma. T cell cuffs are uniquely characterized by a high abundance of gemistocytic tumor cells (GTC) in the surrounding stroma.

Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting.

Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments.

Lobectomy Increases Postoperative Pulmonary Artery Enlargement to a Greater Extent than Segmentectomy.

Purpose: The underlying mechanism why segmentectomy has demonstrated the non-inferiority to lobectomy in several randomized trials remains unclear. Computed tomography (CT)-measured pulmonary artery (PA) enlargement reflects PA pressure and predicts the prognosis of certain respiratory diseases. We compared the preoperative and postoperative PA diameter to the ascending aorta diameter (PA/A) ratio, investigating its impact on right ventricular function in lung resection.

Management of Pancreatic Duct Strictures, Leaks, and Disconnected Pancreatic Duct Syndrome.

Pancreatic duct (PD) strictures, leaks, and disconnected ducts are important morphologic consequences of inflammatory disease of the pancreas, resulting in abdominal pain, pancreatic ascites, pancreatic pleural effusion, and external pancreatic fistula. Traditionally, these PD complications were treated surgically, but a better understanding of their pathophysiology, along with advancement in endoscopic interventions, has transformed the therapy from morbid surgical interventions to minimally invasive, safe, and effective endoscopic treatment. This review discusses the current diagnostic and management strategies for PD strictures, leaks, and disconnected pancreatic ducts.

Updates in the Surgical Management of Pancreatic Ductal Adenocarcinoma.

Surgical management of pancreas cancer is complex, including the timing of surgery, surgical approach, intraoperative techniques, and postoperative management, which are reviewed in detail in this manuscript. Ultimately, referral to a high-volume pancreatic surgeon or pancreatic surgery center is critical to ensuring appropriate short-term and long-term outcomes.

Clinicopathological and prognostic significance of the microcystic elongated and fragmented pattern in endometrial cancer: a systematic review and meta-analysis.

Objective: The presence of the microcystic elongated and fragmented (MELF) pattern, distinguished by its microcystic, elongated and fragmented attributes, constitutes a common manifestation of myometrial invasion (MI) within endometrial carcinoma. However, the prognostic significance of this pattern has not been definitively established. Consequently, this research aimed to clarify the prognostic implications of the MELF pattern for individuals diagnosed with endometrial carcinoma.

Autophagy activation within inflammatory microenvironment improved the therapeutic effect of MSC-Derived extracellular Vesicle in SLE.

Introduction: Developing strategies to improve the therapeutic efficacy of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in autoimmune diseases have garnered increased attention.

Objectives: To evaluate whether rapamycin-induced autophagy within the systemic lupus erythematosus (SLE) inflammatory microenvironment (Rapa-SLE) augments the therapeutic effects of MSC-derived EVs in SLE.

Methods: The therapeutic potential of the resulting EVs (Rapa-SLE-EV) was assessed in MRL/lpr mice.

Cognitive Deficits in Anti-LGI1 Encephalitis Are Linked to Immunotherapy-Resistant White Matter Network Changes.

Background And Objectives: Cognitive deficits represent a major long-term complication of anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E). Although severely affecting patient outcomes, the structural brain changes underlying these deficits remain poorly understood. In this study, we hypothesized a link between white matter (WM) networks and cognitive outcomes in LGI1-E.

MELANOMAS, SARCOMAS, AND RENAL METASTASES IN THE LIVER: HOW TO TREAT?

Liver metastases from melanomas, sarcomas, and renal tumors are less frequent. Treatment and prognosis will depend on whether they are isolated or multiple, size and location, the presence or absence of extrahepatic neoplastic disease, age, stage of the initial disease, initial treatments instituted, time of evolution, and clinical condition of the patient. Recently, a high number of oncological therapies including monotherapy or in combination, neoadjuvants or adjuvants, and immuno-oncological treatments have been developed and tested, increasing disease-free time and survival.

Study of the role of transmembrane emp24 domain-containing protein 2 in oral squamous cell carcinoma.

Objective: This study aimed to investigate the role of transmembrane emp24 domain-containing protein 2 (TMED2) in oral squamous cell carcinoma (OSCC).

Methodology: A bioinformatics analysis was first conducted to explore TMED2 expression in OSCC and its relation with overall survival. The analysis results were further verified by assessing TMED2 expression levels in human normal oral keratinocyte cells and human OSCC cell lines using quantitative real-time polymerase chain reaction and the Western blot.

Lycopene supplementation reduces inflammatory, histopathological and DNA damage in an acute lung injury rabbit model.

Objective: To investigate the effects of lycopene supplementation on inflammation, lung histopathology and systemic DNA damage in an experimentally induced lung injury model, ventilated by conventional mechanical ventilation and high-frequency oscillatory ventilation, compared with a control group.

Methods: Fifty-five rabbits sampled by convenience were supplemented with 10mg/kg lycopene for 21 days prior to the experiment. Lung injury was induced by tracheal infusion of warm saline.

Inferring the genetic relationships between unsupervised deep learning-derived imaging phenotypes and glioblastoma through multi-omics approaches.

This study aimed to investigate the genetic association between glioblastoma (GBM) and unsupervised deep learning-derived imaging phenotypes (UDIPs). We employed a combination of genome-wide association study (GWAS) data, single-nucleus RNA sequencing (snRNA-seq), and scPagwas (pathway-based polygenic regression framework) methods to explore the genetic links between UDIPs and GBM. Two-sample Mendelian randomization analyses were conducted to identify causal relationships between UDIPs and GBM.

Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.

Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.

Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models.

Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic and mutation carriers exhibited increased wakefulness and reduced non-rapid eye movement sleep.

Correcting a pathogenic mitochondrial DNA mutation by base editing in mice.

Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.

AGER-dependent macropinocytosis drives resistance to KRAS-G12D-targeted therapy in advanced pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.

PD-L1-CD80 interactions are required for intracellular signaling necessary for dendritic cell migration.

Programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) interactions are targets for immunotherapies aimed to reinvigorate T cell function. Recently, it was documented that PD-L1 regulates dendritic cell (DC) migration through intracellular signaling events. In this study, we find that both preclinical murine and clinically available human PD-L1 antibodies limit DC migration.

One-dimensional nanosonosensitizer boosted multiple branches of immune responses against MHC-deficient immune-evasive urologic tumor.

Cancer immunotherapies rely on CD8 cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese-bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I-deficient tumors.

Inotodiol induces hepatocellular carcinoma apoptosis by activation of MAPK/ERK pathway.

Hepatocellular carcinoma(HCC) has a high mortality and morbidity rate and seriously jeopardizes human life. Chemicals and chemotherapeutic agents have been experiencing problems such as side effects and drug resistance in the treatment of HCC, which cannot meet the needs of clinical treatment. Therefore, finding novel low-toxicity and high-efficiency anti-hepatocellular carcinoma drugs and exploring their mechanisms of action have become the current problems to be solved in the treatment of HCC.