Tumor-intrinsic kinome landscape of pancreatic cancer reveals new therapeutic approaches.

Effective therapies for pancreatic ductal adenocarcinoma (PDAC) have been largely elusive. Here, we perform Multiplexed kinase Inhibitor Bead Mass Spectrometry on 102 patient derived xenografts derived from 14 unique primary PDAC to define the tumor-intrinsic kinome landscape. Our findings uncover three kinome subgroups making up two tumor-intrinsic kinome subtypes that we call kinotypes.

Non-contrast-enhanced MR-angiography of Extracranial Arteries in Acute Ischemic Stroke at 1.5 Tesla Using Relaxation-Enhanced Angiography Without Contrast and Triggering (REACT).

Purpose: To evaluate a novel flow-independent sequence (Relaxation-Enhanced Angiography without Contrast and Triggering (REACT)) for imaging of the extracranial arteries in acute ischemic stroke (AIS) at 1.5 T.

Methods: This retrospective single-center study included 47 AIS patients who received REACT (scan time: 3:01 min) and contrast-enhanced MRA (CE-MRA) of the extracranial arteries at 1.

Regulatory network analysis of gene expression reveals a tuft cell-ILC2 axis that inhibits pancreatic tumor progression.

expression defines a rare population of cells in the normal pancreas whose frequency is increased at early stages of pancreatic tumorigenesis. The identity and the precise roles of expressing cells in pancreas have been matter of debate, although evidence suggests their involvement in a number of key functions, including regeneration and neoplasia. We employed a recently developed Dclk1 reporter mouse model and single cell RNAseq analysis to define expressing cells in normal pancreas and pancreatic neoplasia.

Generative Pre-trained Transformer 4 analysis of cardiovascular magnetic resonance reports in suspected myocarditis: A multicenter study.

Background: Diagnosing myocarditis relies on multimodal data, including cardiovascular magnetic resonance (CMR), clinical symptoms, and blood values. The correct interpretation and integration of CMR findings require radiological expertise and knowledge. We aimed to investigate the performance of Generative Pre-trained Transformer 4 (GPT-4), a large language model, for report-based medical decision-making in the context of cardiac MRI for suspected myocarditis.

Radiomics workflow definition & challenges - German priority program 2177 consensus statement on clinically applied radiomics.

Objectives: Achieving a consensus on a definition for different aspects of radiomics workflows to support their translation into clinical usage. Furthermore, to assess the perspective of experts on important challenges for a successful clinical workflow implementation.

Materials And Methods: The consensus was achieved by a multi-stage process.

Potential of GPT-4 for Detecting Errors in Radiology Reports: Implications for Reporting Accuracy.

Background Errors in radiology reports may occur because of resident-to-attending discrepancies, speech recognition inaccuracies, and large workload. Large language models, such as GPT-4 (ChatGPT; OpenAI), may assist in generating reports. Purpose To assess effectiveness of GPT-4 in identifying common errors in radiology reports, focusing on performance, time, and cost-efficiency.

Reconstruction of 3D knee MRI using deep learning and compressed sensing: a validation study on healthy volunteers.

Background: To investigate the potential of combining compressed sensing (CS) and artificial intelligence (AI), in particular deep learning (DL), for accelerating three-dimensional (3D) magnetic resonance imaging (MRI) sequences of the knee.

Methods: Twenty healthy volunteers were examined using a 3-T scanner with a fat-saturated 3D proton density sequence with four different acceleration levels (10, 13, 15, and 17). All sequences were accelerated with CS and reconstructed using the conventional and a new DL-based algorithm (CS-AI).

Five-minute knee MRI: An AI-based super resolution reconstruction approach for compressed sensing. A validation study on healthy volunteers.

Purpose: To investigate the potential of combining Compressed Sensing (CS) and a newly developed AI-based super resolution reconstruction prototype consisting of a series of convolutional neural networks (CNN) for a complete five-minute 2D knee MRI protocol.

Methods: In this prospective study, 20 volunteers were examined using a 3T-MRI-scanner (Ingenia Elition X, Philips). Similar to clinical practice, the protocol consists of a fat-saturated 2D-proton-density-sequence in coronal, sagittal and transversal orientation as well as a sagittal T1-weighted sequence.

The worldwide COVID-19 pandemic caused a decline in sonographic examinations - is this a continuing trend?

Purpose: Due to the increasing number of COVID-19 infections since spring 2020 the patient care workflow underwent changes in Germany. To minimize face-to-face exposure and reduce infection risk, non-time-critical elective medical procedures were postponed. Since ultrasound examinations include non-time-critical elective examinations and often can be substituted by other imaging modalities not requiring direct patient contact, the number of examinations has declined significantly.

Cytotoxic chemotherapy potentiates the immune response and efficacy of combination CXCR4/PD-1 inhibition in models of pancreatic ductal adenocarcinoma.

Purpose: The CXCL12-CXCR4 chemokine axis plays a significant role in modulating T-cell infiltration into the pancreatic tumor microenvironment. Despite promising preclinical findings, clinical trials combining inhibitors of CXCR4 (AMD3100/BL-8040) and anti-programmed death 1/ligand1 (anti-PD1/PD-L1) have failed to improve outcomes.

Experimental Design: We utilized a novel ex vivo autologous patient-derived immune/organoid (PDIO) co-culture system using human peripheral blood mononuclear cells and patient derived tumor organoids, and in vivo the autochthonous LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) pancreatic cancer mouse model to interrogate the effects of either monotherapy or all combinations of gemcitabine, AMD3100, and anit-PD1 on CD8+ T cell activation and survival.

Plasticity of intragraft alloreactive T cell clones in human gut correlates with transplant outcomes.

The site of transition between tissue-resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity, and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single-cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells were mainly distributed to TRM, effector T (Teff)/TRM, and T follicular helper compartments.

Reconstruction of shoulder MRI using deep learning and compressed sensing: a validation study on healthy volunteers.

Background: To investigate the potential of combining compressed sensing (CS) and deep learning (DL) for accelerated two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) of the shoulder.

Methods: Twenty healthy volunteers were examined using at 3-T scanner with a fat-saturated, coronal, 2D proton density-weighted sequence with four acceleration levels (2.3, 4, 6, and 8) and a 3D sequence with three acceleration levels (8, 10, and 13), all accelerated with CS and reconstructed using the conventional algorithm and a new DL-based algorithm (CS-AI).

Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial.

Objective: We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE).

Methods: We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo.

Transfer-Learning Deep Radiomics and Hand-Crafted Radiomics for Classifying Lymph Nodes from Contrast-Enhanced Computed Tomography in Lung Cancer.

Objectives: Positron emission tomography (PET) is currently considered the non-invasive reference standard for lymph node (N-)staging in lung cancer. However, not all patients can undergo this diagnostic procedure due to high costs, limited availability, and additional radiation exposure. The purpose of this study was to predict the PET result from traditional contrast-enhanced computed tomography (CT) and to test different feature extraction strategies.

GPT-4 for Automated Determination of Radiological Study and Protocol based on Radiology Request Forms: A Feasibility Study.

Published under a CC BY 4.0 license.

Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators.

Due to their immunosuppressive role, tumor-infiltrating regulatory T cells (TI-Tregs) represent attractive immuno-oncology targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate master regulators (MRs) as mechanistic determinants of TI-Treg transcriptional state.

A deep learning-based reconstruction approach for accelerated magnetic resonance image of the knee with compressed sense: evaluation in healthy volunteers.

Objectives: To evaluate the feasibility of combining compressed sense (CS) with a newly developed deep learning-based algorithm (CS-AI) using convolutional neural networks to accelerate 2D MRI of the knee.

Methods: In this prospective study, 20 healthy volunteers were scanned with a 3T MRI scanner. All subjects received a fat-saturated sagittal 2D proton density reference sequence without acceleration and four additional acquisitions with different acceleration levels: 2, 3, 4 and 6.

Effect of Proton Pump Inhibitor Treatment in "PPI Non-responsive" Patients with Eosinophilic Esophagitis.

Background And Aims: Some eosinophilic esophagitis (EoE) patients can have a decline in eosinophil count after proton pump inhibitor (PPI) treatment without achieving histologic response, but little is known about this group. We aimed to determine the effect of PPIs on reducing esophageal eosinophilia in patients deemed non-responsive to PPI therapy.

Methods: We analyzed prospectively collected cohort data from newly diagnosed adults with EoE who were histologic non-responders (≥15 eos/hpf) to PPI-only therapy.

Ras-dependent activation of BMAL2 regulates hypoxic metabolism in pancreatic cancer.

To identify drivers of malignancy in human pancreatic ductal adenocarcinoma (PDAC), we performed regulatory network analysis on a large collection of expression profiles from laser capture microdissected samples of PDAC and benign precursors. We discovered that BMAL2 plays a role in the initiation, progression, post resection survival, and KRAS activity in PDAC. Functional analysis of BMAL2 target genes led us to hypothesize that it plays a role in regulating the response to hypoxia, a critical but poorly understood feature of PDAC physiology.