Leveraging Epigenetic Alterations in Pancreatic Ductal Adenocarcinoma for Clinical Applications.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease.

Everything you ever wanted to know about cancer stem cells in neuroendocrine neoplasms but were afraid to ask.

While the role of cancer stem cells (CSCs) in tumorigenesis, chemoresistance, metastasis, and relapse has been extensively studied in solid tumors, such as adenocarcinomas or sarcomas, the same cannot be said for neuroendocrine neoplasms (NENs). While lagging, CSCs have been described in numerous NENs, including gastrointestinal and pancreatic NENs (PanNENs), and they have been found to play critical roles in tumor initiation, progression, and treatment resistance. However, it seems that there is still skepticism regarding the role of CSCs in NENs, even in light of studies that support the CSC model in these tumors and the therapeutic benefits of targeting them.

Organoids, tissue slices and organotypic cultures: Advancing our understanding of pancreatic ductal adenocarcinoma through in vitro and ex vivo models.

Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of all common solid cancers. For the large majority of PDAC patients, only systemic therapies with very limited efficacy are indicated. In addition, immunotherapies have not brought the advances seen in other cancer types.

Should We Offer Universal Germline Genetic Testing to All Patients with Pancreatic Cancer? A Multicenter Study.

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a significant percentage of germline pathogenic variants (GPVs). Unlike in the United States, routine universal genetic testing is not performed in Europe. The aim of the study is to evaluate the diagnostic yield of germline genetic testing in all patients with PDAC.

Establishing a Relationship between In Vitro Potency in Cell-Based Assays and Clinical Efficacious Concentrations for Approved GLP-1 Receptor Agonists.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) play an important role in the treatment of type 2 diabetes (T2D) and obesity. The relationship between efficacy and dosing regimen has been studied extensively for this class of molecules. However, a comprehensive analysis of the translation of in vitro data to in vivo efficacious exposure is still lacking.

Combined analysis of a serum mRNA/miRNA marker signature and CA 19-9 for timely and accurate diagnosis of recurrence after resection of pancreatic ductal adenocarcinoma: A prospective multicenter cohort study.

Background And Aims: Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples.

Methods: In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection.

Understanding activity and physiology at scale: The Apple Heart & Movement Study.

Physical activity or structured exercise is beneficial in a wide range of circumstances. Nevertheless, individual-level data on differential responses to various types of activity are not yet sufficient in scale, duration or level of annotation to understand the mechanisms of discrete outcomes nor to support personalized recommendations. The Apple Heart & Movement Study was designed to passively collect the dense physiologic data accessible on Apple Watch and iPhone from a large real-world cohort distributed across the US in order to address these knowledge gaps.

Tumor and α-SMA-expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade.

Alpha-smooth muscle actin (α-SMA) expression in the stroma is linked to the presence of cancer-associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a GeoMx digital spatial profiling approach, we characterized the gene expression of the tumor and α-SMA-expressing stromal cell compartments in pancreatic neuroendocrine tumors (PanNETs). The profiling was performed on tissues from eight retrospective cases (three grade 1, four grade 2, and one grade 3).

Pancreatic cancer screening in high-risk individuals.

The incidence of pancreatic cancer is increasing, although globally it represents less than 3% of all cancers. Despite advances in medical and surgical management, survival rates have not significantly improved in recent years. Consequently, pancreatic cancer, though relatively uncommon, is the third leading cause of cancer-related deaths.

The Social Value Misconception in Clinical Research.

Clinical researchers should help respect the autonomy and promote the well-being of prospective study participants by helping them make voluntary, informed decisions about enrollment. However, participants often exhibit poor understanding of important information about clinical research. Bioethicists have given special attention to "misconceptions" about clinical research that can compromise participants' decision-making, most notably the "therapeutic misconception.

SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population.

Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population.

Characterization of the family-level Borreliaceae pan-genome and development of an episomal typing protocol.

Background: The family includes many obligate parasitic bacterial species which are etiologically associated with a myriad of zoonotic borrelioses including Lyme disease and vector-borne relapsing fevers. Infections by the are difficult to detect by both direct and indirect methods, often leading to delayed and missed diagnoses. Efforts to improve diagnoses center around the development of molecular diagnostics (MDx), but due to deep tissue sequestration of the causative spirochaetes and the lack of persistent bacteremias, even MDx assays suffer from a lack of sensitivity.

The best linear unbiased prediction (BLUP) method as a tool to estimate the lifetime risk of pancreatic ductal adenocarcinoma in high-risk individuals with no known pathogenic germline variants.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the Western world. The number of diagnosed cases and the mortality rate are almost equal as the majority of patients present with advanced disease at diagnosis. Between 4 and 10% of pancreatic cancer cases have an apparent hereditary background, known as hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC), when the genetic basis is unknown.

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM): a decade follow-up of individuals at high-risk for pancreatic cancer.

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening.

The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium.

Strong philopatry in an estuarine-dependent fish.

Understanding fish movement is critical in determining the spatial scales in which to appropriately manage wild populations. Genetic markers provide a natural tagging approach to assess the degree of gene flow and population connectivity across a species distribution. We investigated the genetic structure of black bream across its entire distribution range in Australia, as well as regional scale gene flow across south-eastern Australia by undertaking a comprehensive analysis of the populations in estuaries across the region.

factor H-binding proteins are not required for serum resistance and infection in mammals.

The causative agent of Lyme disease (LD), , binds factor H (FH) and other complement regulatory proteins to its surface. B31 (type strain) encodes five FH-binding proteins (FHBPs): CspZ, CspA, and the OspE paralogs OspE, OspE, and OspE. This study assessed potential correlations between the production of individual FHBPs, FH-binding ability, and serum resistance using a panel of infectious clonal populations recovered from dogs.