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Human norovirus (HuNoV) is a leading cause of acute viral gastroenteritis, but despite high impact on public health and healthcare, the mechanisms of viral attachment to and entry into target cells are not yet fully understood. Recent reports indicate that saliva and bile contribute to the transmission of HuNoV. For example, human bile acids increase cell surface ceramide levels in human enteroids, which improves norovirus entry into cells, resulting in enhanced replication. Bile acids can also interact directly with the norovirus capsid, but it is not known whether bile or other gastrointestinal body fluids directly affect HuNoV attachment to host cells. In this study, we investigated the effects of patient-derived gastric juice, pancreatic juice, and bile on HuNoV GII.4 virus-like particle (VLP) attachment to and entry into a human duodenal cell line, HuTu-80. We show that while gastric juice and pancreatic juice do not affect viral attachment or entry, bile—in particular, hydrophobic bile acids—significantly enhance cellular attachment and subsequent entry of GII.4 VLPs into cells. In addition, we show that hydrophobic bile acids induce the accumulation of viral particles in the vicinity of cells. These results suggest the presence of a new en masse infection mechanism, where bile acids aggregate virions and allow direct and more efficient attachment to and entry into target cells.

This international, multidisciplinary consensus report represents the first effort to systematically define and characterize fatty pancreas. A key outcome of this endeavor was the recommendation to adopt "fatty pancreas" as the standardized and inclusive term to describe all forms of fat accumulation in the pancreas. This terminological consensus provides a critical foundation for unified reporting and clinical communication. Another major contribution of the report is the consensus on diagnostic imaging findings, which was based on radiological and endoscopic modalities. The proposed criteria aim to enhance consistency in clinical assessment and support the development of standardized research protocols. In addition to establishing terminology and diagnostic frameworks, the report also synthesizes current knowledge across a wide range of relevant domains. These include the etiology and epidemiology of fatty pancreas, as well as its associations with alcohol consumption, smoking, acute and chronic pancreatitis, pancreatic exocrine insufficiency, type 2 diabetes mellitus, and surgical outcomes. The potential links between fatty pancreas and neoplastic conditions such as intraductal papillary mucinous neoplasms and pancreatic cancer are also addressed, alongside the current understanding of its metabolic implications (beta-cell function and glucose homeostasis) and treatment strategies. Throughout the consensus process, a consistent theme emerged: the limited availability of high-quality, prospective clinical data. Therefore, many of the recommendations in this report are based on expert consensus rather than strong empirical evidence. As such, the statements require rigorous prospective validation before they can be adopted into routine clinical practice. This underscores a critical need for further research, particularly studies aimed at clarifying causal relationships, validating diagnostic tools, and determining the clinical relevance of fatty pancreas across diverse patient populations. This report serves as both a summary of our current understanding and a roadmap for future investigations, aiming to close existing knowledge gaps and guide evidence-based clinical practice in this emerging field.

The p53 tumor suppressor and the c-Myc oncogene are among the most frequently deregulated genes in human cancers, yet the molecular cross talk between these pathways remains poorly understood. MDM2 is a key negative regulator of p53 and a target for emerging cancer therapies designed to activate p53. Likewise, targeting c-Myc is a long-standing but challenging goal in cancer therapy. Here, we report that the small MDM2-binding drug Milademetan promotes an interaction between MDM2 and the 5’ untranslated region of the c-Myc mRNA, causing a suppression of c-Myc mRNA translation without affecting c-Myc RNA levels. The interaction also occurs under nonproliferative conditions in the absence of drug. Milademetan-mediated c-Myc depletion is accompanied by the induction of apoptosis and suppression of cell proliferation and prevents tumor growth, independently of p53 status. These findings reveal an unexpected mechanism by which MDM2 coordinates two of the most frequently altered pathways in cancer and provide a rationale for targeting c-Myc-driven tumors, including those lacking functional p53, through MDM2 modulators.

The biggest impact on increasing survival for pancreatic cancer has come about by combining surgical resection with systemic chemotherapy. This groundbreaking paradigm has come under increasing scrutiny relating to the choice of adding chemoradiotherapy to chemotherapy versus chemotherapy alone, neoadjuvant versus adjuvant therapy and the optimal regimens. The paradigm has also been challenged in that a distinction needs to be made between ‘resected’ with ‘resectable’ pancreatic cancer, since if only the former is considered, this leads to a biased prognostically favourable patient group being analysed. Moreover, the distinction between resectable, borderline resectable and unresectable cancers is claimed to be so unreliable that this classification should be discouraged in favour of upfront chemotherapy for all patients and not necessarily using either FOLFIRINOX or gemcitabine-capecitabine. The results of a series of recent trials including the RTOG0848 trial of adjuvant chemotherapy with or without chemoradiation and the NORPACT-1 trial of neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic cancer have significantly contributed to the clarification of some these questions. The results of long-term follow-up studies of the adjuvant PRODIGE24 trial comparing FOLFIRINOX with gemcitabine and the ESPAC4 trial of gemcitabine-capecitabine versus gemcitabine have also consolidated and expanded the applicability of adjuvant chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer‑related death worldwide in both men and women. While sex‑specific differences are increasingly recognized as critical determinants of health and disease, particularly in oncology, they remain markedly underexplored in PDAC. Emerging evidence suggests that sex differences influence numerous aspects of PDAC, including treatment response and prognosis. This knowledge gap represents a notable barrier to the development of effective, personalized therapeutic strategies for both sexes. The present review provides a comprehensive overview of the current knowledge on sex‑based differences in PDAC, encompassing epidemiology, risk factors, chemotherapy pharmacokinetics and toxicity, prognosis, therapeutic response, immune inter‑ actions, tumor microenvironment, tumor microbiota and molecular biomarkers.