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The information are related to the quantified morphological parameters of the arterial network of a human kidney, which was scanned using Hierarchical phase-contrast tomography (HiP-CT) at the European Synchrotron Radiation Facility (ESRF) with a voxel resolution of 25 micrometers (https://mecheng.ucl.ac.uk/hip-ct/). To obtain access to the raw image data, please refer to the Human Organ Atlas website at following link: https://human-organ-atlas.esrf.eu/ Code folder: This folder contains Python and MATLAB files for calculating morphological parameters of the renal arterial network, including topological and Strahler generations, branching angle, colored Strahler generation representation, Murray's law, and radius correction for collapsed vessels. Data_and_Calculated_parameters folder: The folder contains Excel files, network labels, and the network spatial graph. The Excel files contain skeletonized data on the renal arterial network in the human kidney, including information such as segments, nodes, node coordinates, and points. An additional Excel file contains various calculated parameters such as branching angle, radius vs. Strahler generation, radius over length vs. Strahler generation, tortuosity, Strahler and topological generations, and branching ratio., The authors would like to express their gratitude for the financial support provided by the Chan Zuckerberg Initiative DAF (2020-225394), an advised fund of SVCF, the MRC (MR/R025673/1), and ESRF beamtimes (md1252 & md1290). P.D.L. is supported by a Royal Academy of Engineering Chair in Emerging Technologies (CiET1819/10). D.J.J. is supported by a Foulkes Foundation Postdoctoral Fellowship. D.A.L. is supported by a Wellcome Trust Investigator Award (220895/Z/20/Z) and by the National Institute for Health Research (NIHR) Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. This research was funded in part by the Wellcome Trust [209553/Z/17/Z]. M.A. is supported by the National Institutes of Health (NIH) (HL94567 and HL134229). For the purpose of open access, the author has applied a CC-BY public copyright licence to any author accepted manuscript version arising from this submission. JJ, was also supported by the NIHR UCLH Biomedical Research Centre, UK.

The family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.

Hintergrund: Die COVID-19-Pandemie stellt den dritten weltweiten Coronavirus-assoziierten Erkrankungsausbruch der letzten 20 Jahre dar. Klinisch dominiert die pulmonale Beteiligung mit einem akuten Lungenversagen (ARDS) bei schweren Verläufen, jedoch können auch andere Organsysteme wie das Herz-Kreislauf-System, Zentralnervensystem und der Gastrointestinaltrakt betroffen sein. Der Pathomechanismus der Organschädigung sowohl für die Lunge wie auch für die nichtpulmonalen Organsysteme war zu Beginn der Pandemie weitestgehend unklar. Methode: Selektive Literaturübersicht bezüglich der morphologischen Veränderungen und zugrunde liegenden Pathomechanismen bei COVID-19 mit Fokussierung auf bildgebende Verfahren. Ergebnisse: Immunhistochemische, elektronenmikroskopische und molekularpathologische Analysen an Autopsiegewebe führten zu einem besseren Verständnis der Pathophysiologie von COVID-19 einschließlich der molekularen Regulationsmechanismen. Hierbei konnte gezeigt werden, dass die sogenannte intussuszeptive Angiogenese (IA) in den betroffenen Organen von COVID-19-Patienten ein zentrales Schadensmuster darstellt. Bei der IA verändert sich ein bestehendes Gefäß durch Einstülpung des Endothels und Ausbildung eines intraluminalen Septums, wodurch schließlich zwei neue Lumina entstehen. Hierdurch verändert sich die Hämodynamik, unter anderem durch Verlust der laminaren Strömung mit Ausbildung turbulenter inhomogener Flussgeschwindigkeiten. Die Induktion der IA ist einerseits auf eine thrombotisch bedingte Ischämie zurückzuführen, doch geht sie andererseits selbst mit einem erhöhten Risiko für weitere Mikrothromben einher, die bei COVID-19-Patientinnen und Patienten in Lunge, Herz, Leber, Nieren, Gehirn und Plazenta nachgewiesen wurden. Schlussfolgerung: In Autopsiematerial von Patientinnen und Patienten mit COVID-19 konnten ultrastrukturell in verschiedenen Geweben eine veränderte Mikrovaskularität, eine IA sowie multifokale Thromben nachgewiesen werden. Diese Veränderungen sind als mögliche Faktoren für postakute interstitiell-fibrotische Organveränderungen wie auch das klinische Bild des Long COVID zu betrachten.

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since publication of the international IPF guideline in the year 2011 and Update 2018 several studies and technical advances occurred, which made a new assessment of the diagnostic process mandatory. In view of the antifibrotic drugs which have been approved for the treatment of IPF patients, the goal of this guideline is to foster early, confident and effective diagnosis of IPF. The guideline focusses on the typical clinical setting of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardised questionnaires, serologic testing and cellular analysis of bronchoalveolar lavage. High resolution computed tomography remains crucial in the diagnostic work-up. If it is necessary to obtain specimen for histology transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom bronchoscopic diagnosis did not provide the information needed. Despite considerable progress, IPF remains a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis., Die idiopathische Lungenfibrose (IPF) ist eine schwerwiegende, chronische Lungenerkrankung, deren Diagnosestellung eine profunde fachliche Expertise verlangt. Seit Veröffentlichung der internationalen IPF-Leitlinie im Jahr 2011 mit Update 2018 haben zahlreiche Studien und technische Fortschritte eine Neubewertung des diagnostischen Vorgehens notwendig gemacht. Angesichts der Indikation, symptomatischen Patienten eine antifibrotische Therapie sofort nach Diagnosestellung zu empfehlen, hat die aktuelle IPF-Diagnostik-Leitlinie zum Ziel, die Diagnose der IPF möglichst ohne Verzögerung, wenig invasiv und zuverlässig zu ermöglichen. Sie beschreibt den typischen klinischen Kontext der IPF sowie die Untersuchungen, die zum Ausschluss bekannter Ursachen einer Lungenfibrose erforderlich sind, einschließlich standardisierter Anamneseerhebung, serologischer Testungen und zellulärer Analyse der bronchoalveolären Lavage. Zentrale Bedeutung kommt dem hochauflösenden Computertomogramm in Dünnschichttechnik zu. Sofern eine Histologie zur Diagnoseeingrenzung erforderlich ist, soll diese in erster Linie mittels der transbronchialen Lungen-Kryobiopsie gewonnen werden. Die chirurgische Lungenbiopsie soll Patienten vorbehalten bleiben, die in ausreichender Verfassung für diesen Eingriff sind und bei denen die endoskopische Diagnostik keine Klärung der Diagnose ergab. Goldstandard ist auch weiterhin die interdisziplinäre Diskussion der erhobenen Befunde, um nach Ausschluss anderer Formen chronisch progredienter Lungenfibrosen die Diagnose der IPF zu stellen.

Asymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiological significance of anthracosis is debatable. Using in situ 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 (PAHs), tobacco-specific nitrosamines, or aromatic amines, in a series of 330 lung cancer patients in highly variable and unique patterns. The characteristic nature of carbon-bound exogenous compound had a strong association with patient outcome, tumor progression, the tumor immune microenvironment, PD-L1 expression, and DNA damage. Spatial correlation network analyses revealed substantial differences in the metabolome of tumor cells compared to tumor stroma depending on carbon-bound exogenous compounds. Overall, the bioactive pool of exogenous compounds is associated with several changes in lung cancer pathophysiology and correlates with patient outcome. Given the high prevalence of anthracosis in the lungs of adult humans, future work should investigate the role of carbon-bound exogenous compounds in lung carcinogenesis and lung cancer therapy.

Background. Idiopathic pulmonary fibrosis (IPF) is a progressive disease for which two antifibrotic drugs recently were approved. However, an unmet need exists to predict responses to antifibrotic treatment, such as pirfenidone. Recent data suggest that upregulated expression of CXCR4 is indicative of outcomes in IPF. Research Question. Can quantitative, molecular imaging of pulmonary CXCR4 expression as a biomarker for disease activity predict response to the targeted treatment pirfenidone and prognosis in patients with IPF? Study Design and Methods. CXCR4 expression was analyzed by immunohistochemistry examination of lung tissues and reverse-transcriptase polymerase chain reaction analysis of BAL. PET-CT scanning with the specific CXCR4 ligand 68Ga-pentixafor was performed in 28 IPF patients and compared with baseline clinical characteristics. In 16 patients, a follow-up scan was obtained 6 to 12 weeks after initiation of treatment with pirfenidone. Patients were followed up in our outpatient clinic for > 12 month. Results. Immunohistochemistry analysis showed high CXCR4 staining of epithelial cells and macrophages in areas with vast fibrotic remodeling. Targeted PET scanning revealed CXCR4 upregulation in fibrotic areas of the lungs, particularly in zones with subpleural honeycombing. Baseline CXCR4 signal demonstrated a significant correlation with Gender Age Physiology stage (r = 0.44; P = .02) and with high-resolution CT scan score (r = 0.38; P = .04). Early changes in CXCR4 signal after initiation of pirfenidone treatment correlated with the long-term course of FVC after 12 months (r = −0.75; P = .0008). Moreover, patients with a high pulmonary CXCR4 signal on follow-up PET scan after 6 weeks into treatment demonstrated a statistically significant worse outcome at 12 months (P = .002). In multiple regression analysis, pulmonary CXCR4 signal on follow-up PET scan emerged as the only independent predictor of long-term outcome (P = .0226). Interpretation. CXCR4-targeted PET imaging identified disease activity and predicted outcome of IPF patients treated with pirfenidone. It may serve as a future biomarker for personalized guidance of antifibrotic treatment.