306 results match your criteria: "Institute of Pathology and Molecular Pathology[Affiliation]"

Technological advancements in X-ray imaging using bright and coherent synchrotron sources now allows the decoupling of sample size and resolution while maintaining high sensitivity to the microstructures of soft, partially dehydrated tissues. The continuous developments in multiscale X-ray imaging resulted in hierarchical phase-contrast tomography, a comprehensive approach to address the challenge of organ-scale (up to tens of centimeters) soft tissue imaging with resolution and sensitivity down to the cellular level. Using this technique, we imaged ex vivo an entire human left lung at an isotropic voxel size of 25.

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Smoking Impairs Hematoma Formation and Dysregulates Angiogenesis as the First Steps of Fracture Healing.

Bioengineering (Basel)

April 2022

Siegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, Germany.

Bone fracture healing is an overly complex process in which inflammation, osteogenesis, and angiogenesis are tightly coupled, and delayed fracture repair is a very common health risk. One of the major causes of delayed healing is the formation of insufficient vasculature. Precise regulation of blood vessels in bone and their interplay with especially osteogenic processes has become an emerging topic within the last years; nevertheless, regulation of angiogenesis in (early) diseased fracture repair is still widely unknown.

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Benchmarking weakly-supervised deep learning pipelines for whole slide classification in computational pathology.

Med Image Anal

July 2022

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany; Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany. Electronic address:

Artificial intelligence (AI) can extract visual information from histopathological slides and yield biological insight and clinical biomarkers. Whole slide images are cut into thousands of tiles and classification problems are often weakly-supervised: the ground truth is only known for the slide, not for every single tile. In classical weakly-supervised analysis pipelines, all tiles inherit the slide label while in multiple-instance learning (MIL), only bags of tiles inherit the label.

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SS18-SSX drives CREB activation in synovial sarcoma.

Cell Oncol (Dordr)

June 2022

Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, Münster University Hospital, Münster, Germany.

Purpose: Synovial sarcoma (SySa) is a rare soft tissue tumor characterized by a reciprocal t(X;18) translocation. The chimeric SS18-SSX fusion protein represents the major driver of the disease, acting as aberrant transcriptional dysregulator. Oncogenic mechanisms whereby SS18-SSX mediates sarcomagenesis are incompletely understood, and strategies to selectively target SySa cells remain elusive.

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Article Synopsis
  • - The study reveals that type I interferons (IFNs) are crucial for controlling viral infections and preventing excessive tissue damage, known as immunopathology, which can worsen disease outcomes.
  • - Researchers found that when the type I IFN receptor is absent, severe immunopathology occurs after viral infections due to macrophages and IL-6, and inhibiting these can reduce tissue damage.
  • - The research highlights that macrophage-derived matrix metalloproteinases (MMPs) are involved in tissue destruction during viral infections, suggesting that targeting MMPs could be a potential treatment strategy.
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Purpose: Most surgeons perform right-sided semicircular clearance of the superior mesenteric artery (SMA) nerve plexus for pancreatic head carcinoma, presuming a linear course of the SMA nerve fibers. The hypothesis was that the SMA nerve plexus fibers follow a non-linear course, and the goal of the present study was to assess the neural fibers distribution along the SMA.

Methods: The course of neural fibers along the retropancreatic and suprapancreatic SMA was assessed in 7 cadavers.

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Sudden cardiac death (SCD) is an important public health issue. In young persons aged between 1 and 40 years, most SCDs are caused by potentially inherited cardiac diseases, often not detectable during conventional medico-legal investigations and therefore termed as sudden unexplained deaths (SUD). In this study, we describe the implementation, feasibility and importance of a standardized procedure to investigate SUD cases within the forensic framework at the Zurich Institute of Forensic Medicine in Switzerland.

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Objectives: The aim of this study was to investigate the feasibility, the image quality, and the correlation with histology of dedicated spiral breast computed tomography (B-CT) equipped with a photon-counting detector in patients with suspicious breast lesions after application of iodinated contrast media.

Materials And Methods: The local ethics committee approved this prospective study. Twelve women with suspicious breast lesions found in mammography or B-CT underwent contrast-enhanced spiral B-CT and supplementary ultrasound.

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Human CtIP is best known for its role in DNA end resection to initiate DNA double-strand break repair by homologous recombination. Recently, CtIP has also been shown to protect reversed replication forks from nucleolytic degradation upon DNA replication stress. However, still little is known about the DNA damage response (DDR) networks that preserve genome integrity and sustain cell survival in the context of CtIP insufficiency.

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Time-Dependent Molecular Motifs of Pulmonary Fibrogenesis in COVID-19.

Int J Mol Sci

January 2022

Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany.

Article Synopsis
  • COVID-19 survivors exhibit a higher risk of pulmonary fibrosis, but the specific molecular processes behind this condition remain unclear.* -
  • In a study involving 12 COVID-19 patients who died from respiratory failure, researchers analyzed gene expression profiles compared to 11 healthy individuals to understand how pulmonary fibrosis develops over time.* -
  • Findings indicate that after the first week of hospitalization, patients shift from inflammation-related gene activity to fibrosis-related gene activity, suggesting potential targets for future treatment.*
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Salivary gland carcinomas (SGC) are rare (3-6 % of all head and neck cancers) and show biological heterogeneity depending on the respective histological subtype. While complete surgical resection is the standard treatment for localized disease, chemotherapy or radiation therapy are frequently insufficient for the treatment of unresectable or metastasized SGC. Therefore, new therapeutic approaches such as molecularly targeted therapy or the application of immune checkpoint inhibition enhance the treatment repertoire.

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Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas.

Biomedicines

December 2021

Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany.

T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood.

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Background: The BRAF V600E mutation is present in approximately 50% of patients with melanoma brain metastases and an important prerequisite for response to targeted therapies, particularly BRAF inhibitors. As heterogeneity in terms of BRAF mutation status may occur in melanoma patients, a wild-type extracranial primary tumor does not necessarily rule out a targetable mutation in brain metastases using BRAF inhibitors. We evaluated the potential of MRI radiomics for a noninvasive prediction of the intracranial BRAF mutation status.

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Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models.

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Purpose: Ascorbic acid is a strong antioxidant and has potent radioprotective effects on radiation injuries. Ascorbic acid 2-glucoside (AA2G) is a stabilized derivative of ascorbic acid and rapidly hydrolyzed into ascorbic acid and glucose. Since there is the possibility that AA2G treatment interferes with the antitumor activity of radiotherapy, we investigated the effect of AA2G treatment during radiotherapy on acute radiation enteritis and antitumor activity of radiotherapy in rats.

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Lung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis.

Am J Respir Crit Care Med

January 2022

Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA).

Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. To identify the molecular determinants associated with progression of fibrosis. Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 samples/lung).

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Asymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiologic significance of anthracosis is debatable. Using high mass resolution matrix-assisted laser desorption/ionization (MALDI) fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging analysis, we discovered noxious carbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAH), tobacco-specific nitrosamines, or aromatic amines, in a series of 330 patients with lung cancer in highly variable and unique patterns.

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Risk stratification of COVID-19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe-Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting outcomes (e.

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When SUV Matters: FDG PET/CT at Baseline Correlates with Survival in Soft Tissue and Ewing Sarcoma.

Life (Basel)

August 2021

Department of Medical Oncology and Hematology, University Hospital Zürich, University of Zürich, 8091 Zürich, Switzerland.

Introduction: The role of positron-emission tomography/computed-tomography (PET/CT) in the management of sarcomas and as a prognostic tool has been studied. However, it remains unclear which metric is the most useful. We aimed to investigate if volume-based PET metrics (Tumor volume (TV) and total lesions glycolysis (TLG)) are superior to maximal standardized uptake value (SUVmax) and other metrics in predicting survival of patients with soft tissue and bone sarcomas.

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Objectives: Respiratory failure is the major cause of death in coronavirus disease 2019 (COVID-19). Autopsy-based reports describe diffuse alveolar damage (DAD), organizing pneumonia, and fibrotic change, but data on early pathologic changes and during progression of the disease are rare.

Methods: We prospectively enrolled three patients with COVID-19 and performed full clinical evaluation, including high-resolution computed tomography.

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Article Synopsis
  • Researchers are studying a type of kidney cancer called ccRCC and how a specific treatment involving anti-PD-1 can work better when combined with certain therapies.
  • They found that changes in DNA, called promoter hypomethylation, can help predict how well patients will respond to the treatment.
  • Analysis of patient samples showed that those with hypomethylation had better treatment outcomes but also faced poorer overall survival when first diagnosed with ccRCC.
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Development and validation of deep learning classifiers to detect Epstein-Barr virus and microsatellite instability status in gastric cancer: a retrospective multicentre cohort study.

Lancet Digit Health

October 2021

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany; Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany. Electronic address:

Background: Response to immunotherapy in gastric cancer is associated with microsatellite instability (or mismatch repair deficiency) and Epstein-Barr virus (EBV) positivity. We therefore aimed to develop and validate deep learning-based classifiers to detect microsatellite instability and EBV status from routine histology slides.

Methods: In this retrospective, multicentre study, we collected tissue samples from ten cohorts of patients with gastric cancer from seven countries (South Korea, Switzerland, Japan, Italy, Germany, the UK and the USA).

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