Decoding pan-cancer treatment outcomes using multimodal real-world data and explainable artificial intelligence.

Despite advances in precision oncology, clinical decision-making still relies on limited variables and expert knowledge. To address this limitation, we combined multimodal real-world data and explainable artificial intelligence (xAI) to introduce AI-derived (AID) markers for clinical decision support. We used xAI to decode the outcome of 15,726 patients across 38 solid cancer entities based on 350 markers, including clinical records, image-derived body compositions, and mutational tumor profiles.

Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth.

Prostate cancer (PCa) growth depends on de novo lipogenesis controlled by the mitochondrial pyruvate dehydrogenase complex (PDC). In this study, we identify lysine methyltransferase (KMT)9 as a regulator of PDC activity. KMT9 is localized in mitochondria of PCa cells, but not in mitochondria of other tumor cell types.

Comparison of laparoscopic performance using low-cost laparoscopy simulators versus state-of-the-art simulators: a multi-center prospective, randomized crossover trial.

Introduction: Simulator training is an efficient method for the development of basic laparoscopic skills. We aimed to investigate if low-cost simulators are comparable to more expensive box trainers regarding surgeons usability, likability, and performance.

Methods: This multi-center, randomized crossover study included 16 medical students, seven abdominal surgeons, and seven urological surgeons.

One-day dual-tracer examination in neuroendocrine neoplasms: a real advantage of low activity LAFOV PET imaging.

Purpose: Somatostatin receptor (SSTR)-PET is crucial for effective treatment stratification of neuroendocrine neoplasms (NENs). In highly proliferating or poorly differentiated NENs, dual-tracer approaches using additional [F]FDG PET can effectively identify SSTR-negative disease, usually requiring separate imaging sessions. We evaluated the feasibility of a one-day dual-tracer imaging protocol with a low activity [F]FDG PET followed by an SSTR-PET using the recently introduced [F]SiFAlin-TATE tracer in a long axial field-of-view (LAFOV) PET/CT scanner and its implications in patient management.

The impact of updated imaging software on the performance of machine learning models for breast cancer diagnosis: a multi-center, retrospective study.

Purpose: Artificial Intelligence models based on medical (imaging) data are increasingly developed. However, the imaging software on which the original data is generated is frequently updated. The impact of updated imaging software on the performance of AI models is unclear.

Longitudinal assessment of diffusion-weighted imaging during magnetic resonance-guided radiotherapy in head and neck cancer.

Background: For radiotherapy of head and neck cancer (HNC) magnetic resonance imaging (MRI) plays a pivotal role due to its high soft tissue contrast. Moreover, it offers the potential to acquire functional information through diffusion weighted imaging (DWI) with the potential to personalize treatment. The aim of this study was to acquire repetitive DWI during the course of online adaptive radiotherapy on an 1.

Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics.

The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility.

Self-reported determinants for subjective financial distress: a qualitative interview study with German cancer patients.

Objectives: Patient-reported financial effects of a tumour disease in a universal healthcare setting are a multidimensional phenomenon. Actual and anticipated objective financial burden caused by direct medical and non-medical costs as well as indirect costs such as loss of income can lead to subjective financial distress. To better understand subjective financial distress, the presented study explores self-reported determinants for subjective financial distress in German patients with cancer, aiming to inform a new German-language patient-reported outcome measure for determining the financial effects of a tumour disease.

Bots in white coats: are large language models the future of patient education? a multi-center cross-sectional analysis.

Objectives: Every year, around 300 million surgeries are conducted worldwide, with an estimated 4.2 million deaths occurring within 30 days after surgery. Adequate patient education is crucial, but often falls short due to the stress patients experience before surgery.

Molecular and functional profiling unravels targetable vulnerabilities in colorectal cancer.

Colorectal cancer (CRC) patients with microsatellite-stable (MSS) tumors are mostly treated with chemotherapy. Clinical benefits of targeted therapies depend on mutational states and tumor location. Many tumors carry mutations in KRAS proto-oncogene, GTPase (KRAS) or B-Raf proto-oncogene, serine/threonine kinase (BRAF), rendering them more resistant to therapies.

Steatohepatitis-induced vascular niche alterations promote melanoma metastasis.

Background: In malignant melanoma, liver metastases significantly reduce survival, even despite highly effective new therapies. Given the increase in metabolic liver diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), this study investigated the impact of liver sinusoidal endothelial cell (LSEC)-specific alterations in MASLD/MASH on hepatic melanoma metastasis.

Methods: Mice were fed a choline-deficient L-amino acid-defined (CDAA) diet for ten weeks to induce MASH-associated liver fibrosis, or a CDAA diet or a high fat diet (HFD) for shorter periods of time to induce early steatosis-associated alterations.

Factors influencing role preferences in decision-making of healthy women with BRCA1/2 pathogenic variants: subanalysis from a randomised controlled decision coaching trial.

Background: Patients who actively engage in their medical decision-making processes can experience better health outcomes. This exploratory study aimed to identify predictors of preferred and actual roles in decision-making in healthy women with BRCA1/2 pathogenic variants (PVs).

Methods: Women with BRCA1/2 PVs without a history of breast and/or ovarian cancer were recruited in six centres across Germany.

Dental and oral health assessments in the German National Cohort (NAKO).

Background: Despite considerable improvements in oral health in recent decades, caries and periodontitis are still widespread, ranking among the most prevalent diseases worldwide and requiring future research. The German National Cohort (NAKO Gesundheitsstudie, NAKO) is a large-scaled, multidisciplinary, nationwide, multi-centre, population-based, prospective cohort study with oral examinations that aims to provide a resource to study risk factors for major diseases. The aim of the present article is to provide the methodological background, to report on the data quality, and to present initial results of the oral examinations.

Cancer risk in carriers of TP53 germline variants grouped into different functional categories.

Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups.

A gut instinct for childhood leukemia prevention: microbiome-targeting recommendations aimed at parents and caregivers.

Childhood leukemia accounts for 30% of all pediatric cancer cases with acute lymphoblastic leukemia (ALL) being the most common subtype. Involvement of the gut microbiome in ALL development has recently garnered interest due to an increasing recognition of the key contribution the microbiome plays in maintaining the immune system's homeostatic balance. Commensal gut microbiota provide a first line of defense against different pathogens and gut microbiome immaturity has been implicated in ALL pathogenesis.

Validity of one-time phantomless patient-specific quality assurance in proton therapy with regard to the reproducibility of beam delivery.

Background: Patient-specific quality assurance (PSQA) is a crucial yet resource-intensive task in proton therapy, requiring special equipment, expertise and additional beam time. Machine delivery log files contain information about energy, position and monitor units (MU) of all delivered spots, allowing a reconstruction of the applied dose. This raises the prospect of phantomless, log file-based QA (LFQA) as an automated replacement of current phantom-based solutions, provided that such an approach guarantees a comparable level of safety.

Effective eradication of acute myeloid leukemia stem cells with FLT3-directed antibody-drug conjugates.

Refractory disease and relapse are major challenges in acute myeloid leukemia (AML) therapy attributed to survival of leukemic stem cells (LSC). To target LSCs, antibody-drug conjugates (ADCs) provide an elegant solution, combining the specificity of antibodies with highly potent payloads. We aimed to investigate if FLT3-20D9h3-ADCs delivering either the DNA-alkylator duocarmycin (DUBA) or the microtubule-toxin monomethyl auristatin F (MMAF) can eradicate quiescent LSCs.

Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

Laboratory-Engineered Glioblastoma Organoid Culture and Drug Screening.

Glioblastoma (GBM) is described as a group of highly malignant primary brain tumors and stands as one of the most lethal malignancies. The genetic and cellular characteristics of GBM have been a focal point of ongoing research, revealing that it is a group of heterogeneous diseases with variations in RNA expression, DNA methylation, or cellular composition. Despite the wealth of molecular data available, the lack of transferable pre-clinic models has limited the application of this information to disease classification rather than treatment stratification.

estiMAge: development of a DNA methylation clock to estimate the methylation age of single cells.

Motivation: Since their introduction about 10 years ago, methylation clocks have provided broad insights into the biological age of different species, tissues, and in the context of several diseases or aging. However, their application to single-cell methylation data remains a major challenge, because of the inherent sparsity of such data, as many CpG sites are not covered. A methylation clock applicable on single-cell level could help to further disentangle the processes that drive the ticking of epigenetic clocks.

Molecular docking and molecular dynamics simulation studies of inhibitor candidates against 3-hydroxykynurenine transaminase and implications on vector control.

Isoxazole and oxadiazole derivatives inhibiting 3-hydroxykynurenine transaminase (3HKT) are potential larvicidal candidates. This study aims to identify more suited potential inhibitors of 3HKT (3HKT) through molecular docking and molecular dynamics simulation. A total of 958 compounds were docked against 3HKT (PDB ID: 2CH2) using Autodock vina and Autodock4.

Maternal weight during pregnancy and risk of childhood acute lymphoblastic leukemia in offspring.

In addition to biological factors, maternal exposures during pregnancy can contribute to leukemogenesis in offspring. We conducted a population-based cohort study in Sweden to investigate the association between risk of acute lymphoblastic leukemia (ALL) in offspring and maternal anthropometrics during pregnancy. A total of 2,961,435 live-born singletons during 1983-2018 were followed from birth to ALL diagnosis, end of age 18, or end of 2018.

Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.

Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits a high frequency of neural invasion (NI). Schwann cells (SCs) have been shown to be reprogrammed to facilitate cancer cell migration and invasion into nerves. Since extracellular vesicles (EVs) affect the tumour microenvironment and promote metastasis, the present study analysed the involvement of EVs from pancreatic cancer cells and their microenvironment in altering SC phenotype as part of the early events in the process of NI.