Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

A two-stage deep-learning model for determination of the contact of mandibular third molars with the mandibular canal on panoramic radiographs.

Objectives: This study aimed to assess the accuracy of a two-stage deep learning (DL) model for (1) detecting mandibular third molars (MTMs) and the mandibular canal (MC), and (2) classifying the anatomical relationship between these structures (contact/no contact) on panoramic radiographs.

Method: MTMs and MCs were labeled on panoramic radiographs by a calibrated examiner using bounding boxes. Each bounding box contained MTM and MC on one side.

Development and validation of a clinical risk model for postoperative outcome in newly diagnosed glioblastoma: a report of the RANO resect group.

Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

The Infiltrative Margins in Glioblastoma: Important Is What Has Been Left behind.

Supramaximal resection beyond the contrast-enhancing tumor borders represents an emerging surgical strategy for patients with newly diagnosed glioblastoma. A recent study provides evidence detailing the interactive effects of more aggressive surgery on other clinical predictors of outcome, supporting guidance for surgical decision-making and informing clinical trialists about the need to stratify for extent of resection. See related article by Park et al.

Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study.

Purpose: We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial.

Patients And Methods: Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders.

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group.

Background: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement.

Peripheral cholinesterase activity is not correlated with postoperative delirium in urological surgery.

The value of biomarkers, such as acetylcholinesterase and butyrylcholinesterase, for guiding perioperative patients suffering from postoperative delirium and/or (possibly related) postoperative cognitive dysfunction is unclear. Only recently have different biomarkers are being explored to assess postoperative delirium's occurrence and/or course. The aim of this work is to investigate whether acetylcholinesterase and butyrylcholinesterase can help detect increased risks of the development and course of postoperative delirium in urological patients undergoing surgery.

Chronic inhaled antibiotic therapy in people with cystic fibrosis with Pseudomonas aeruginosa infection in Germany.

Background: Several clinical guidelines recommend chronic inhaled therapy for pwCF (people with cystic fibrosis) and chronic Pseudomonas aeruginosa infection of the lungs.

Methods: To demonstrate what kind of therapy regimens are used in Germany, we retrospectively analysed chronic inhaled antibiotic therapy within the cohort of the German CF Registry in 2020. For comparison we also analysed the use of inhaled antibiotics in pwCF with intermittent Pseudomonas or without Pseudomonas infection.

Viral Etiology and Clinical Characteristics of Acute Respiratory Tract Infections in Hospitalized Children in Southern Germany (2014-2018).

Background: Viral acute respiratory tract infections (ARTIs) are a leading cause of hospitalization in infants and young children.

Methods: During the winter seasons of 2014-2018, hospitalized children (<18 years) with symptoms of ARTI were prospectively included at the University Hospital Heidelberg, Germany. Nasopharyngeal swabs were obtained for multiplex molecular analysis of 10 groups of respiratory viruses, and clinical data were obtained using a standardized questionnaire.

dynamics and anti-tumor effects of EpCAM-directed CAR T-cells against brain metastases from lung cancer.

Lung cancer patients are at risk for brain metastases and often succumb to their intracranial disease. Chimeric Antigen Receptor (CAR) T-cells emerged as a powerful cell-based immunotherapy for hematological malignancies; however, it remains unclear whether CAR T-cells represent a viable therapy for brain metastases. Here, we established a syngeneic orthotopic cerebral metastasis model in mice by combining a chronic cranial window with repetitive intracerebral two-photon laser scanning-microscopy.

Toll-like receptors 2 and 4 stress signaling and sodium-glucose cotransporter-2 in kidney disease.

Kidney disease is the 6th fastest-growing cause of death and a serious global health concern that urges effective therapeutic options. The inflammatory response is an initial reaction from immune and parenchymal cells in kidney diseases. Toll-like receptors (TLR) 2 and 4 are highly expressed by various kidney cells and respond to 'signaling danger' proteins, such as high mobility group box binding protein 1 (HMGB1) and prompt the progression of kidney disease by releasing inflammatory mediators.

Receptor-mediated mitophagy: An emerging therapeutic target in acute kidney injury.

Acute kidney injury (AKI) is a global health concern associated with high morbidity and mortality. AKI etiology is linked to mitochondrial dysfunction along with oxidative stress and inflammation. The defective mitochondria are removed via mitophagy for maintaining cellular integrity.

Epigenetic regulation of Toll-like receptors 2 and 4 in kidney disease.

Kidney disease affects more than 10% of the worldwide population and causes significant morbidity and mortality. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) play a pivotal role in the progression of kidney disease. These epigenetic mechanisms are reversible and majorly involved in regulating gene expression of inflammatory, fibrotic, and apoptotic proteins.

Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience.

Objective: Evaluation of the efficacy and safety of atezolizumab/bevacizumab in a real-world HCC cohort, including patients with impaired liver function and prior systemic therapy.

Methods: Retrospective analysis of 147 HCC patients treated with atezolizumab/bevacizumab at six sites in Germany and Austria.

Results: The overall response rate and disease control rate were 20.

Healthcare Utilization and Costs in Sepsis Survivors in Germany-Secondary Analysis of a Prospective Cohort Study.

: Survivors of sepsis often face long-term sequelae after intensive care treatment. Compared to the period of hospitalization, little is known about the ambulatory healthcare utilization in sepsis patients. The study evaluated healthcare utilization and associated costs of sepsis care including allied health professions after initial hospitalization.

Transparency on Platelet Transfusion in Routine Cancer Care: The Key for Optimal Blood Usage?

Introduction: In Germany, up to 75% of platelet concentrates (PCs) are administered to haematological and oncological patients. Only limited transparency exists on the characteristics of haematological/oncological patients receiving PC transfusions, treatment patterns, and guideline adherence in daily clinical routine care. This information would be key for managing platelet supply and optimal platelet usage strategies.

Seizure in Neurodegeneration with Brain Iron Accumulation: A Systematic Review.

Background: Neurodegeneration with brain iron accumulation (NBIA) is a rare genetic disorder. Its clinical manifestations comprise a wide spectrum mainly movement disorders. Seizure as a clinical manifestation is known to occur in some NBIAs, but the exact prevalence of epilepsy in each individual disorder is not well elucidated.

Long non-coding RNAs as emerging regulators of miRNAs and epigenetics in diabetes-related chronic kidney disease.

Diabetes is one of the major cause of chronic kidney disease (CKD), including "diabetic nephropathy," and is an increasingly prevalent accelerator of the progression of non-diabetic forms of CKD. The long non-coding RNAs (lncRNAs) have come into the limelight in the past few years as one of the emerging weapons against CKD in diabetes. Available data over the past few years demonstrate the interaction of lncRNAs with miRNAs and epigenetic machinery.

Atopic diseases and airway-related symptoms in Bavarian children before starting primary school: Time trend analyses.

Background: After decades of rising prevalence of atopic and airway-related diseases, studies showed stagnating prevalence in western industrialised countries. Objective of this study is to analyse the time trend of prevalence of atopic diseases and airway-related symptoms among Bavarian children before starting primary school.

Materials And Methods: Five cross-sectional studies from 2004/2005, 2006/2007, 2012/2013, 2014/2015 and 2016/2017 took place in urban and rural regions in Bavaria, Germany.

Infrared molecular fingerprinting of blood-based liquid biopsies for the detection of cancer.

Recent omics analyses of human biofluids provide opportunities to probe selected species of biomolecules for disease diagnostics. Fourier-transform infrared (FTIR) spectroscopy investigates the full repertoire of molecular species within a sample at once. Here, we present a multi-institutional study in which we analysed infrared fingerprints of plasma and serum samples from 1639 individuals with different solid tumours and carefully matched symptomatic and non-symptomatic reference individuals.