Post-COVID-19 complement-mediated TMA: A case report.

Systemic COVID-19 disease is associated with a variety of organ involvement in infected patients. A rarely reported complication is the induction of complement-mediated thrombotic microangiopathy (TMA). TMA is an extremely rare pathological condition that results in thrombosis in capillaries and small arterioles, due to an endothelial injury.

Prognostic significance of EGFR, AREG and EREG amplification and gene expression in muscle invasive bladder cancer.

Introduction: Muscle invasive bladder cancer (MIBC) remains a prevalent cancer with limited therapeutic options, obviating the need for innovative therapies. The epidermal growth factor receptor () is a linchpin in tumor progression and presents a potential therapeutic target in MIBC. Additionally, the ligands and have shown associations with response to anti-EGFR therapy and improved progression-free survival in colorectal carcinoma.

Cyclin A2 Expression as Predictive Biomarker in Muscle-Invasive Upper Tract Urothelial Carcinoma.

Introduction: The aim was to evaluate the prognostic value of altered Cyclin A2 (CCNA2) gene expression in upper tract urothelial carcinoma (UTUC) and to assess its predictive potential as a prognostic factor for overall survival (OS) and disease-free survival.

Methods: 62 patients who underwent surgical treatment for UTUC were included. Gene expression of CCNA2, MKI67, and p53 was analyzed by quantitative reverse transcriptase polymerase chain reaction.

A self-supervised vision transformer to predict survival from histopathology in renal cell carcinoma.

Purpose: To develop and validate an interpretable deep learning model to predict overall and disease-specific survival (OS/DSS) in clear cell renal cell carcinoma (ccRCC).

Methods: Digitised haematoxylin and eosin-stained slides from The Cancer Genome Atlas were used as a training set for a vision transformer (ViT) to extract image features with a self-supervised model called DINO (self-distillation with no labels). Extracted features were used in Cox regression models to prognosticate OS and DSS.

Medium-term Oncological Efficacy and Patient-reported Outcomes After Focal High-intensity Focused Ultrasound: The FOXPRO Trial.

Background: Multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound (TRUS) fusion-guided high-intensity focused ultrasound (HIFU) is a focal treatment option for MRI-visible localized prostate cancer (PCa). High-quality evidence regarding the clinical efficacy remains limited.

Objective: To assess medium-term oncological efficacy along with patient-reported outcome measures (PROMs).

Deep learning can predict survival directly from histology in clear cell renal cell carcinoma.

For clear cell renal cell carcinoma (ccRCC) risk-dependent diagnostic and therapeutic algorithms are routinely implemented in clinical practice. Artificial intelligence-based image analysis has the potential to improve outcome prediction and thereby risk stratification. Thus, we investigated whether a convolutional neural network (CNN) can extract relevant image features from a representative hematoxylin and eosin-stained slide to predict 5-year overall survival (5y-OS) in ccRCC.

Upper Tract Urinary Cancer Recurrence after Radical Cystectomy: Risk Assessment of Intraoperative Frozen Section.

Introduction: Upper tract urinary cancer recurrence (UTUCR) after radical cystectomy (RC) is outcome-limiting. Surgical recommendations on intraoperative performance of frozen section analysis (FSA) and management of positive ureteral margin (PUM) are lacking.

Methods: 634 RC cases were identified (2010-2018).

Assessment of glomerular morphological patterns by deep learning algorithms.

Background: Compilation of different morphological lesion signatures is characteristic of renal pathology. Previous studies have documented the potential value of artificial intelligence (AI) in recognizing relatively clear-cut glomerular structures and patterns, such as segmental or global sclerosis or mesangial hypercellularity. This study aimed to test the capacity of deep learning algorithms to recognize complex glomerular structural changes that reflect common diagnostic dilemmas in nephropathology.

GTF2I Mutation in Thymomas: Independence From Racial-Ethnic Backgrounds. An Indian/German Comparative Study.

Thymomas are the most frequent adult mediastinal cancers. Their etiology is unknown and their pathogenesis poorly understood. Racial, ethnic and environmental factors influence tumorigenesis in many cancers, but their role in thymomas remains unclear to date.

CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease.

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies.

The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma.

Renal cell carcinoma (RCC) is the deadliest primary genitourinary malignancy typically associated with asymptomatic initial presentation and poorly predictable survival. Next to established risk factors, tumor microenvironment may alter metastatic capacity and immune landscape. Due to their high concentrations, sulfoglycolipids (sulfatides) were among the first well-described antigens in RCC that are associated with worse prognosis.

A comprehensive molecular characterization of the 8q22.2 region reveals the prognostic relevance of OSR2 mRNA in muscle invasive bladder cancer.

Technological advances in molecular profiling have enabled the comprehensive identification of common regions of gene amplification on chromosomes (amplicons) in muscle invasive bladder cancer (MIBC). One such region is 8q22.2, which is largely unexplored in MIBC and could harbor genes with potential for outcome prediction or targeted therapy.

Molecular pathology of thymomas: implications for diagnosis and therapy.

Thymomas exhibit a unique genomic landscape, comprising the lowest on average total mutational burden among adult human cancers; a unique point mutation in the GTF2I gene in WHO type A and AB thymomas (and rarely others); almost unique KMT2A-MAML2 translocations in rare WHO type B2 and B3 thymomas; a unique YAP1-MAML2 translocation in almost all metaplastic thymomas; and unique miRNA profiles in relation to GTF2I mutational status and WHO histotypes. While most thymomas can be diagnosed solely on the basis of morphological features, mutational analyses can solve challenging differential diagnostic problems. No molecular biomarkers have been identified that predict the response of unresectable thymomas to chemotherapy or agents with known molecular targets.

Thymic Hyperplasia with Lymphoepithelial Sialadenitis (LESA)-Like Features: Strong Association with Lymphomas and Non-Myasthenic Autoimmune Diseases.

Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32-80; lesion diameter 7.

Short-Range Order in VI.

We present a detailed investigation of the crystal structure of VI, a two-dimensional van der Waals material of interest for studies of low-dimensional magnetism. As opposed to the average crystal structure that features 3̅ symmetry of the unit cell, our Raman scattering and X-ray atomic pair distribution function analysis supported by density functional theory calculations point to the coexistence of short-range ordered 3̅1 and long-range ordered 3̅ phases. The highest-intensity peak, , exhibits a moderate asymmetry that might be traced back to the spin-phonon interactions, as in the case of CrI.

Cancer Acidity and Hypertonicity Contribute to Dysfunction of Tumor-Associated Dendritic Cells: Potential Impact on Antigen Cross-Presentation Machinery.

Macrophages (MΦ) and dendritic cells (DC), major players of the mononuclear phagocyte system (MoPh), are potent antigen presenting cells that steadily sense and respond to signals from the surrounding microenvironment, leading to either immunogenic or tolerogenic outcomes. Next to classical MHC-I/MHC-II antigen-presentation pathways described in the vast majority of cell types, a subset of MoPh (CD8, XCR1, CLEC9A, BDCA3 conventional DCs in human) is endowed with a high competence to cross-present external (engulfed) antigens on MHC-I molecules to CD8 T-cells. This exceptional DC function is thought to be a crucial crossroad in cytotoxic antitumor immunity and has been extensively studied in the past decades.

Inhibition of hepatocellular carcinoma growth by blockade of glycosphingolipid synthesis.

Hepatocellular carcinoma (HCC) is one of the most frequent cancers. studies suggest that growth and response to therapy of human carcinomas may depend on glycosphingolipid (GSL) expression. Glucosylceramide synthase (GCS), encoded by the gene , is the basic enzyme required for the synthesis of GSLs.

Glucosylceramide Synthase Is Involved in Development of Invariant Natural Killer T Cells.

Invariant natural killer T (iNKT) cells represent a unique population of CD1d-restricted T lymphocytes expressing an invariant T cell receptor encoded by Vα14-Jα18 and Vα24-Jα18 gene segments in mice and humans, respectively. Recognition of CD1d-loaded endogenous lipid antigen(s) on CD4/CD8-double positive (DP) thymocytes is essential for the development of iNKT cells. The lipid repertoire of DP thymocytes and the identity of the decisive endogenous lipid ligands have not yet been fully elucidated.

Hyperosmolarity impedes the cross-priming competence of dendritic cells in a TRIF-dependent manner.

Tissue osmolarity varies among different organs and can be considerably increased under pathologic conditions. Hyperosmolarity has been associated with altered stimulatory properties of immune cells, especially macrophages and dendritic cells. We have recently reported that dendritic cells upon exposure to hypertonic stimuli shift their profile towards a macrophage-M2-like phenotype, resulting in attenuated local alloreactivity during acute kidney graft rejection.

Deficiency of N-myristoylation reveals calcineurin activity as regulator of IFN-γ-producing γδ T cells.

γδ T cell subsets can be characterized, in part, by their secretion of select proinflammatory cytokines. The molecular mechanisms driving the diverse fates of γδ T cells have not been elucidated. We have previously shown that the attachment of myristic acid to the N-terminal glycine of proteins, termed N-myristoylation, is essential for αβ T cell development and activation.

Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis.

Renal tubular atrophy and interstitial fibrosis are common hallmarks of etiologically different progressive chronic kidney diseases (CKD) that eventually result in organ failure. Even though these pathological manifestations constitute a major public health problem, diagnostic tests, as well as therapeutic options, are currently limited. Members of the dickkopf (DKK) family, DKK1 and -2, have been associated with inhibition of Wnt signaling and organ fibrosis.

Transcriptional profiling of dendritic cells matured in different osmolarities.

Tissue-specific microenvironments shape the fate of mononuclear phagocytes [1-3]. Interstitial osmolarity is a tissue biophysical parameter which considerably modulates the phenotype and function of dendritic cells [4]. In the present report we provide a detailed description of our experimental workflow and bioinformatic analysis applied to our gene expression dataset (GSE72174), aiming to investigate the influence of different osmolarity conditions on the gene expression signature of bone marrow-derived dendritic cells.

The renal microenvironment modifies dendritic cell phenotype.

Renal dendritic cells are a major component of the renal mononuclear phagocytic system. In the renal interstitium, these cells are exposed to an osmotic gradient, mainly sodium, whose concentration progressively increases towards inner medulla. Renal allograft rejection affects predominantly the cortex, suggesting a protective role of the renal medullary micromilieu.

Immunosuppression and Aberrant T Cell Development in the Absence of N-Myristoylation.

N-myristoylation refers to the attachment of myristic acid to the N-terminal glycine of proteins and substantially affects their intracellular targeting and functions. The thymus represents an organ with a prominent N-myristoylation activity. To elucidate the role of protein N-myristoylation for thymocyte development, we generated mice with a T cell lineage-specific deficiency in N-myristoyl transferase (Nmt)1 and 2.

Dickkopf-3, a tissue-derived modulator of local T-cell responses.

The adaptive immune system protects organisms from harmful environmental insults. In parallel, regulatory mechanisms control immune responses in order to assure preservation of organ integrity. Yet, molecules involved in the control of T-cell responses in peripheral tissues are poorly characterized.