Publications by authors named "Manuel Nietert"

Article Synopsis
  • * Researchers differentiated induced pluripotent stem cells from both a CF patient and a healthy donor into macrophages to study the effects of CFTR deficiency on macrophage function.
  • * The study found that CF macrophages (iMac) had reduced ability to kill bacteria, altered cellular environment, and exhibited signs of inflammation and dysfunctional responses, indicating an impaired immune response in CF.
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Article Synopsis
  • Microglia play a key role in post-stroke inflammation, impacting neurological recovery.
  • The study examines how lipid droplet (LD) buildup in microglia under stroke conditions leads to pro-inflammatory responses and worsens brain damage.
  • Findings reveal that LD-rich microglia (LDRM) exhibit increased inflammatory markers and distinct lipid profiles, highlighting their contribution to worsened outcomes in neuroinflammatory conditions.
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Objectives: To develop an automatic segmentation model for solid renal tumors on contrast-enhanced CTs and to visualize segmentation with associated confidence to promote clinical applicability.

Materials And Methods: The training dataset included solid renal tumor patients from two tertiary centers undergoing surgical resection and receiving CT in the corticomedullary or nephrogenic contrast media (CM) phase. Manual tumor segmentation was performed on all axial CT slices serving as reference standard for automatic segmentations.

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This investigation explores the potential of plasma lipidomic signatures for aiding in the diagnosis of Multiple Sclerosis (MS) and evaluating the clinical course and disease activity of diseased patients. Plasma samples from 60 patients with MS (PwMS) were clinically stratified to either a relapsing-remitting (RRMS) or a chronic progressive MS course and 60 age-matched controls were analyzed using state-of-the-art direct infusion quantitative shotgun lipidomics. To account for potential confounders, data were filtered for age and BMI correlations.

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Evidence for the efficiency of highly-effective triple-CFTR-modulatory therapy with elexacaftor/tezacaftor/ivacaftor (ETI), either demonstrated in clinical trials or by testing, is lacking for about 10% of people with cystic fibrosis (pwCF) with rare mutations. Comprehensive assessment of CFTR function can provide critical information on the impact of ETI on CFTR function gains for such rare mutations, lending argument of the prescription of ETI. The mutation c.

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Cystic fibrosis is a genetic disease caused by mutation of the CFTR gene, which encodes a chloride and bicarbonate transporter in epithelial cells. Due to the vast range of geno- and phenotypes, it is difficult to find causative treatments; however, small-molecule therapeutics have been clinically approved in the last decade. Still, the search for novel therapeutics is ongoing, and thousands of compounds are being tested in different assays, often leaving their mechanism of action unknown.

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An adequate visualization form is required to gain an overview and ultimately understand the complex and diverse biological mechanisms of diseases. Recently, disease maps have been introduced for this purpose. A disease map is defined as a systems biological map or model that combines metabolic, signaling, and physiological pathways to create a comprehensive overview of known disease mechanisms.

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Cystic fibrosis (CF) is a genetic disease caused by mutations in , which encodes a chloride and bicarbonate transporter expressed in exocrine epithelia throughout the body. Recently, some therapeutics became available that directly target dysfunctional CFTR, yet research for more effective substances is ongoing. The database CandActCFTR aims to provide detailed and comprehensive information on candidate therapeutics for the activation of CFTR-mediated ion conductance aiding systems-biology approaches to identify substances that will synergistically activate CFTR-mediated ion conductance based on published data.

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The MINERVA platform is currently the most widely used platform for visualizing and providing access to disease maps. Disease maps are systems biological maps of molecular interactions relevant in a certain disease context, where they can be used to support drug discovery. For this purpose, we extended MINERVA's own drug and chemical search using the MINERVA plugin starter kit.

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Background: The cystic fibrosis (CF) sweat gland is defective in β-adrenergically-stimulated sweat secretion in the coil and chloride reabsorption in the duct. Whereas chloride reabsorption is regularly assessed by quantitative pilocarpine iontophoresis (QPIT), the measurement of β-adrenergic sweat secretion is not yet established in clinical practice.

Methods: A novel sweat bubble imaging protocol was developed that determines sweat secretion rates by automatic recording, processing and quality control of the kinetics of sweat droplet formation.

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Different causative therapeutics for CF patients have been developed. There are still no mutation-specific therapeutics for some patients, especially those with rare CFTR mutations. For this purpose, high-throughput screens have been performed which result in various candidate compounds, with mostly unclear modes of action.

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Background: Brain metastasis represents a major complication with a significantly shorter overall survival of many oncological diseases, in particular of lung cancer, breast cancer and malignant melanoma patients. However, despite the poor prognosis, sometimes clinical decision-making, between on the one hand not to harm the patient and on the other hand not withholding a potential therapeutic option, is very challenging. Thus the aim of this retrospective study was to compare various scores, including scores for activities of daily living (ADL) before resection of brain metastases and to analyse their impact on survival.

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Introduction: Oncogenic mutation within the KRAS gene represents a negative predictor for treatment response to anti-epidermal growth factor receptor (EGFR) in patients with colorectal cancer. Recently, we have shown no relevant heterogeneity for KRAS mutation status within and between pre- and posttherapeutic samples from the primary tumor in patients with locally advanced rectal cancer. The aim of this study was to evaluate the intertumoral heterogeneity of KRAS mutation status between the primary tumor and the corresponding metastasis or local recurrence in the similar cohort and to evaluate the ideal representative tissue for KRAS mutation testing.

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The aim of this study was to discriminate malignant and benign clinical T1 renal masses on routinely acquired computed tomography (CT) images using radiomics and machine learning techniques.Adult patients undergoing surgical resection and histopathological analysis of clinical T1 renal masses were included. Preoperative CT studies in venous phase from multiple referring centers were included, without restriction to specific CT scanners, slice thickness, or degrees of artifacts.

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Background: The optimal extent of thyroidectomy for papillary thyroid cancer (PTC) ≥ 10 mm und < 10 mm is still controversial. Therefore, the purpose of this study was to investigate factors predictive for bilaterality in patients with papillary thyroid carcinoma (PTC).

Material And Methods: We retrospectively reviewed 123 PTC patients in a single centre study who underwent either completion or total thyroidectomy and analysed the predictive value of tumour size, histological parameters, multifocality, and lymph node metastases with primary tumour size of ≥ 10 mm and < 10 mm as well as for ≥ 7 mm and < 7 mm.

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Purpose: Multidisciplinary tumor boards (MDT) have been advocated as standard of care in modern oncology. German guidelines for metastasized colorectal cancer (mCRC) recommend MDT discussion of colon cancer patients after completion of primary tumor therapy but stage IV colon cancer as well as rectal cancer patients prior to any therapy. In this health care research study, we evaluated application and decisional consequences of this approach in clinical routine.

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The cellular sarcoma gene (SRC) is a proto-oncogene encoding for a tyrosine kinase. SRC expression was determined in locally advanced rectal adenocarcinoma tissue from pretreatment biopsies and resection specimens. The expression level was correlated with clinicopathological parameters to evaluate the predictive and prognostic capacity.

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Translational research relies on high-quality biospecimens. In patients with rectal cancer treated preoperatively with radiochemotherapy tissue based analyses are challenging. To assess quality challenges we analyzed tissue samples taken over the last years in a multicenter setting.

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Objective: In this study, we evaluate the frequency of HER-2 and HER-3 expression in liver metastases from patients with colorectal cancer (CRLM). We analyzed the potential of HER-2 and HER-3 as therapeutic targets and evaluated their prognostic value.

Patients And Methods: Overall 208 patients with CRLM were enrolled.

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Intrinsic and acquired resistance to the monoclonal antibody drug trastuzumab is a major problem in the treatment of HER2-positive breast cancer. A deeper understanding of the underlying mechanisms could help to develop new agents. Our intention was to detect genes and single nucleotide polymorphisms (SNPs) affecting trastuzumab efficiency in cell culture.

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In patients with advanced rectal cancer (cUICC II and III) multimodality therapy resulted in better long-term local tumor control. Ongoing clinical trials are focusing on therapy intensification to improve disease-free (DFS) and cancer-specific survival (CSS), the integration of biomarkers for prediction of individual recurrence risk, and the identification of new targets. In this context, we investigated HER-2, a member of the epidermal growth factor receptor family, whose expression pattern and role was unclear in rectal cancer.

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