Background: The potential of artificial intelligence (AI)–based large language models, such as ChatGPT, has gained significant attention in the medical field. This enthusiasm is driven not only by recent breakthroughs and improved accessibility, but also by the prospect of democratizing medical knowledge and promoting equitable health care. However, the performance of ChatGPT is substantially influenced by the input language, and given the growing public trust in this AI tool compared to that in traditional sources of information, investigating its medical accuracy across different languages is of particular importance. Objective: This study aimed to compare the performance of GPT-3.5 and GPT-4 with that of medical students on the written German medical licensing examination. Methods: To assess GPT-3.5’s and GPT-4's medical proficiency, we used 937 original multiple-choice questions from 3 written German medical licensing examinations in October 2021, April 2022, and October 2022. Results: GPT-4 achieved an average score of 85% and ranked in the 92.8th, 99.5th, and 92.6th percentiles among medical students who took the same examinations in October 2021, April 2022, and October 2022, respectively. This represents a substantial improvement of 27% compared to GPT-3.5, which only passed 1 out of the 3 examinations. While GPT-3.5 performed well in psychiatry questions, GPT-4 exhibited strengths in internal medicine and surgery but showed weakness in academic research. Conclusions: The study results highlight ChatGPT’s remarkable improvement from moderate (GPT-3.5) to high competency (GPT-4) in answering medical licensing examination questions in German. While GPT-4’s predecessor (GPT-3.5) was imprecise and inconsistent, it demonstrates considerable potential to improve medical education and patient care, provided that medically trained users critically evaluate its results. As the replacement of search engines by AI tools seems possible in the future, further studies with nonprofessional questions are needed to assess the safety and accuracy of ChatGPT for the general population.

Macrophages and immuno-modulation play a dominant role in the pathology of pancreatic cancer. Gas plasma is a technology recently suggested to demonstrate anticancer efficacy. To this end, two murine cell lines were employed to analyze the inflammatory consequences of plasma-treated pancreatic cancer cells (PDA) on macrophages using the kINPen plasma jet. Plasma treatment decreased the metabolic activity, viability, and migratory activity in an ROS- and treatment time-dependent manner in PDA cells in vitro. These results were confirmed in pancreatic tumors grown on chicken embryos in the TUM-CAM model (in ovo). PDA cells promote tumor-supporting M2 macrophage polarization and cluster formation. Plasma treatment of PDA cells abrogated this cluster formation with a mixed M1/M2 phenotype observed in such co-cultured macrophages. Multiplex chemokine and cytokine quantification showed a marked decrease of the neutrophil chemoattractant CXCL1, IL6, and the tumor growth supporting TGFβ and VEGF in plasma-treated compared to untreated co-culture settings. At the same time, macrophage-attractant CCL4 and MCP1 release were profoundly enhanced. These cellular and secretome data suggest that the plasma-inactivated PDA6606 cells modulate the inflammatory profile of murine RAW 264.7 macrophages favorably, which may support plasma cancer therapy.

Background: Gram-negative infections of the peritoneal cavity result in profound modifications of peritoneal B cell populations and induce the migration of peritoneal B cells to distant secondary lymphoid organs. However, mechanisms controlling the egress of peritoneal B cells from the peritoneal cavity and their subsequent trafficking remain incompletely understood. Sphingosine-1-phosphate (S1P)-mediated signaling controls migratory processes in numerous immune cells. The present work investigates the role of S1P-mediated signaling in peritoneal B cell trafficking under inflammatory conditions. Methods: Differential S1P receptor expression after peritoneal B cell activation was assessed semi‑quantitatively using RT-PCR in vitro. The functional implications of differential S1P₁ and S1P₄ expression were assessed by transwell migration in vitro, by adoptive peritoneal B cell transfer in a model of sterile lipopolysaccharide (LPS)‑induced peritonitis and in the polymicrobial colon ascendens stent peritonitis (CASP) model. Results: The two sphingosine-1-phosphate receptors (S1PRs) expressed in peritoneal B cell subsets S1P₁ and S1P₄ are differentially regulated upon stimulation with the TLR4 agonist LPS, but not upon PMA/ionomycin or B cell receptor (BCR) crosslinking. S1P₄ deficiency affects both the trafficking of activated peritoneal B cells to secondary lymphoid organs and the positioning of these cells within the functional compartments of the targeted organ. S1P₄ deficiency in LPS-activated peritoneal B cells results in significantly reduced numbers of splenic innate response activator B cells. Conclusions: The S1P-S1PR system is implicated in the trafficking of LPS-activated peritoneal B cells. Given the protective role of peritoneal B1a B cells in peritoneal sepsis, further experiments to investigate the impact of S1P₄-mediated signaling on the severity and mortality of peritoneal sepsis are warranted.

Gemcitabine/Cisplatin (Gem/Cis) chemotherapy is a standard treatment for muscle‐invasive bladder cancer (MIBC) but yields suboptimal response rates. The contribution of tumor‐stromal crosstalk and macrophage recruitment to chemoresistance remains poorly understood. This study investigated these mechanisms using a functional ex vivo bladder cancer tissue slice model combined with n = 64 spatial transcriptomics. Spatial analysis revealed transcriptomic changes involving the immunomodulating gene SPP1 that has been also recently presented as a putative predictive biomarker for neoadjuvant chemotherapy in bladder cancer. Moreover, Non‐Responders exhibited upregulation of chemokines including CXCL1 and CXCL8 and enrichment of immunoregulatory M2 macrophages in tumor regions, suggesting active macrophage recruitment from the stroma. On the contrary, Responders showed upregulation of complement components, proinflammatory macrophage subsets and signals associated with cytotoxic lymphocyte recruitment. Tissue slices corresponding cell cultures confirmed overexpression of immunomodulating markers including checkpoints PD‐L1 and PD‐L2 in Non‐Responder cancer cells upon Gem/Cis treatment. Using TCGA bladder cancer data, the transcriptomic gene set was further validated revealing a prognostic signature associated with patients' outcome. These findings uncover a novel mechanism of chemotherapy resistance in bladder cancer driven by tumor–stromal interactions and macrophage recruitment and suggest that targeting macrophage infiltration may improve chemotherapy response in bladder cancer.

Background: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene ITIH5, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediating tumor suppressive properties. Recently, it was surprisingly found that the ITIH5 protein is specifically upregulated in CCAs and that ITIH5 detection in blood could be an excellent liquid biopsy marker for indicating the presence of a CCA tumor in a patient. We therefore investigated whether patients with CCAs with abundant versus low ITIH5 protein expression also differ in their prognosis. Methods: To clarify this question, a large CCA cohort (n = 175) was examined using immunohistochemistry on a tissue microarray (TMA). Results: Abundant ITIH5 expression in CCA was associated with favorable survival, a low UICC stage and the absence of perineural invasion (PNI). Conclusions: ITIH5 has biomarker potential not only for the early detection of CCA from blood-based liquid biopsies but also as a prognostic tissue biomarker for risk stratification. Our results suggest that the upregulation of ITIH5 is particularly abundant in intrahepatic CCAs (iCCA). The mechanisms mediating the strong initial upregulation of ITIH5 during the oncogenic transformation of bile duct cells are still unclear.