Metavert synergises with standard cytotoxics in human PDAC organoids and is associated with transcriptomic signatures of therapeutic response.

Background: Despite some recent advances, pancreatic ductal adenocarcinoma (PDAC) remains a growing oncological challenge. New drugs capable of targeting more than one oncogenic pathway may be one way to improve patient outcomes. This study characterizes the effectiveness of Metavert a first-in-class dual inhibitor of GSK3-β and histone deacetylase in treating PDAC as a single agent or in combination with standard cytotoxics.

The radiomorphological appearance of the invasive margin in pancreatic cancer is associated with tumor budding.

Purpose: Pancreatic cancer (PDAC) is characterized by infiltrative, spiculated tumor growth into the surrounding non-neoplastic tissue. Clinically, its diagnosis is often established by magnetic resonance imaging (MRI). At the invasive margin, tumor buds can be detected by histology, an established marker associated with poor prognosis in different types of tumors.

The simulation experiment description markup language (SED-ML): language specification for level 1 version 5.

Modern biological research is increasingly informed by computational simulation experiments, which necessitate the development of methods for annotating, archiving, sharing, and reproducing the conducted experiments. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Information About a Simulation Experiment (MIASE) guidelines outline the information needed to share simulation experiments.

N-cadherin: A diagnostic marker to help discriminate primary liver carcinomas from extrahepatic carcinomas.

Distinguishing primary liver cancer (PLC), namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), from liver metastases is of crucial clinical importance. Histopathology remains the gold standard, but differential diagnosis may be challenging. While absent in most epithelial, the expression of the adherens junction glycoprotein N-cadherin is commonly restricted to neural and mesenchymal cells, or carcinoma cells that undergo the phenomenon of epithelial-to-mesenchymal transition (EMT).

Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC.

Neoadjuvant chemotherapy can improve the survival of individuals with borderline and unresectable pancreatic ductal adenocarcinoma; however, heterogeneous responses to chemotherapy remain a significant clinical challenge. Here, we performed RNA sequencing (n = 97) and multiplexed immunofluorescence (n = 122) on chemo-naive and postchemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) to define the impact of neoadjuvant chemotherapy. Transcriptome analysis combined with high-resolution mapping of whole-tissue sections identified GATA6 (classical), KRT17 (basal-like) and cytochrome P450 3A (CYP3A) coexpressing cells that were preferentially enriched in post-CTX resected samples.

The pH-dependent lactose metabolism of Lactobacillus delbrueckii subsp. bulgaricus: An integrative view through a mechanistic computational model.

The fermentation process of milk to yoghurt using Lactobacillus delbrueckii subsp. bulgaricus in co-culture with Streptococcus thermophilus is hallmarked by the breakdown of lactose to organic acids such as lactate. This leads to a substantial decrease in pH - both in the medium, as well as cytosolic.

Farnesoid X receptor activation inhibits pancreatic carcinogenesis.

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily that controls bile acid (BA) homeostasis, has also been proposed as a tumor suppressor for breast and liver cancer. However, its role in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis remains controversial. We recently found that FXR attenuates acinar cell autophagy in chronic pancreatitis resulting in reduced autophagy and promotion of pancreatic carcinogenesis.

A fast and sensitive high-throughput assay to assess polysorbate-degrading hydrolytic activity in biopharmaceuticals.

Hydrolysis of polysorbate in biopharmaceutical products has been ascribed to the enzymatic activity from trace levels of residual host cell proteins. In recent years, significant efforts to identify the causative enzymes typically used elaborate, material-intensive and time-consuming approaches. Therefore, the lack of fast and sensitive assays to monitor their activity remains a major bottleneck for supporting process optimization and troubleshooting activities where time and sample throughput are crucial constraints.

A Stepped Health Services Intervention to Improve Care for Mental and Neurological Diseases: Protocol for a Prospective Cohort Trial.

Background: Mental and neurological disorders cause a large proportion of morbidity burden and require adequate health care structures. However, deficits in the German health care system like long waiting times for access to specialized care and a lack of coordination between health care providers lead to suboptimal quality of care and elevated health care costs.

Objective: To overcome these deficits, we implement and evaluate a unique stepped and coordinated model of care (the Neurologisch-psychiatrische und psychotherapeutische Versorgung [NPPV] program) for patients with mental and neurological diseases.

A histopathological study of artery wall involvement in pancreatic cancer surgery.

Purpose: This study aims to study the depth of artery wall tumour invasion in patients undergoing surgery for pancreatic ductal adenocarcinoma.

Methods: Specimens from 47 pancreatic cancer patients with major arterial (splenic, SA; celiac, CA; common hepatic, CHA) invasion were examined: 45 left (distal) pancreatectomies, including 11 celiac artery resections, and two total pancreatectomies. Dissection of tumour-invaded arteries in 25 fresh specimens was attempted ex vivo using the sub-adventitial dissection technique (SDT).

Presence of low-grade IPMN at the pancreatic transection margin does not have prognostic significance after resection of IPMN-associated pancreatic adenocarcinoma.

Introduction: Resection margin status is a well-established prognosticator in pancreatic cancer. The prognostic impact of IPMN dysplasia at the pancreatic transection margin in IPMN-associated carcinoma (IPMN-Ca) remains unclear, hence institutional practices on additional resections vary.

Methods: Patients undergoing partial pancreatectomy or attempted partial pancreatectomy converted to total pancreatectomy for IPMN-Ca between 04/2002 and 12/2018 were identified.

BioSimulators: a central registry of simulation engines and services for recommending specific tools.

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface.

The simulation experiment description markup language (SED-ML): language specification for level 1 version 4.

Computational simulation experiments increasingly inform modern biological research, and bring with them the need to provide ways to annotate, archive, share and reproduce the experiments performed. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Information About a Simulation Experiment (MIASE) guidelines outline the information needed to share simulation experiments.

The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms.

MEN1, which encodes menin protein, is the most frequently mutated gene in pancreatic neuroendocrine neoplasms (pNEN). Pleiotrophin (PTN) has been reported as a downstream factor of menin that promotes metastasis in different tumor entities. In this study, the effect of menin and its link to PTN were assessed using features of pNEN cells and the outcome of patients with pNEN.

Inspecting the Solution Space of Genome-Scale Metabolic Models.

Genome-scale metabolic models are frequently used in computational biology. They offer an integrative view on the metabolic network of an organism without the need to know kinetic information in detail. However, the huge solution space which comes with the analysis of genome-scale models by using, e.

Epithelial-to-Mesenchymal Transition in Pancreatic Cancer is associated with Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging.

This study aimed to evaluate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) as imaging biomarker for epithelial-to-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC). In forty-two patients, preoperative apparent diffusion coefficient (ADC) values of therapy-naive PDAC were compared with immunohistochemical expression profiles of the epithelial marker E-cadherin as well as mesenchymal transcription factors Runt-related transcription factor 2 (Runx2) and Zinc finger E-box-binding homeobox 1 (Zeb1), as determined by Allred immunoreactivity score. We observed a significant positive rank correlation between the ADC and the E-cadherin Allred score (ρ = 0.

IPMN-associated pancreatic cancer: Survival, prognostic staging and impact of adjuvant chemotherapy.

Background: Intraductal papillary mucinous neoplasm (IPMN)-associated carcinoma is a subtype of pancreatic cancer for which prognostic factors, the validity of the AJCC/UICC staging system and the role of adjuvant chemotherapy remain unknown.

Materials And Methods: Clinicopathological, treatment and follow-up data of patients with IPMN-associated carcinoma undergoing resection between 2002 and 2018 were analyzed. Uni- and multivariable survival analyses were performed to identify prognostic factors.

EnzymeML-a data exchange format for biocatalysis and enzymology.

EnzymeML is an XML-based data exchange format that supports the comprehensive documentation of enzymatic data by describing reaction conditions, time courses of substrate and product concentrations, the kinetic model, and the estimated kinetic constants. EnzymeML is based on the Systems Biology Markup Language, which was extended by implementing the STRENDA Guidelines. An EnzymeML document serves as a container to transfer data between experimental platforms, modeling tools, and databases.

Collagen Organization Does Not Influence T-Cell Distribution in Stroma of Human Pancreatic Cancer.

The dominant intrastromal T-cell infiltration in pancreatic cancer is mainly caused by the contact guidance through the excessive desmoplastic reaction and could represent one of the obstacles to an effective immune response in this tumor type. This study analyzed the collagen organization in normal and malignant pancreatic tissues as well as its influence on T-cell distribution in pancreatic cancer. Human pancreatic tissue was analyzed using immunofluorescence staining and multiphoton and SHG microscopy supported by multistep image processing.

Refined prognostic staging for resected pancreatic cancer by modified stage grouping and addition of tumour grade.

Background: With changes in T and N categories the 8th edition of the AJCC/UICC TNM staging system for pancreatic cancer resulted in improved prognostic staging, but inconsistencies were observed with specific stage groups. Tumour grading remains disregarded in prognostic staging. We aimed to validate the current staging system and to investigate the possibility of further optimization by integration of grading.

Impact of EGFR and EGFR ligand expression on treatment response in patients with metastatic colorectal cancer.

Up to 50% of patients with colorectal cancer (CRC) have either synchronous or metachronous hepatic metastases in the course of their disease. Patients with metastatic CRC (mCRC) whose tumors express wild-type KRAS benefit from treatment with monoclonal antibodies (such as cetuximab or panitumumab) that target the epidermal growth factor receptor (EGFR). However, the therapeutic response to these antibodies is variable, and further predictive models are required.

KRAS/GNAS-testing by highly sensitive deep targeted next generation sequencing improves the endoscopic ultrasound-guided workup of suspected mucinous neoplasms of the pancreas.

Pancreatic cysts or dilated pancreatic ducts are often found by cross-sectional imaging, but only mucinous lesions can become malignant. Therefore, distinction between mucinous and non-mucinous lesions is crucial for adequate patient management. We performed a prospective study including targeted next generation sequencing (NGS) of cell-free DNA in the diagnostic endoscopic ultrasound (EUS)-guided workup.