Can PSMA PET detect intratumour heterogeneity in histological PSMA expression of primary prostate cancer? Analysis of [Ga]Ga-PSMA-11 and [F]PSMA-1007.

Purpose: Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [Ga]Ga-PSMA-11 or [F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression.

Methods: Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled.

Postoperative pancreatic fistula risk assessment using digital pathology based analyses at the parenchymal resection margin of the pancreas - Results from the randomized multicenter RECOPANC trial.

Background: In pancreatic surgery Postoperative pancreatic fistula (POPF) represents the most dreaded complication, for which pancreatic texture is acknowledged as one of the strongest predictors. No consensual objective reference has been defined to evaluate the pancreas composition. The presented study aimed to mine histology data of the pancreatic tissue composition with AI assist and correlate it with clinic-pathological parameters derived from the RECOPANC study.

Impact of ALDH1A1 Expression in Intrahepatic Cholangiocellular Carcinoma.

Intrahepatic cholangiocarcinoma (iCC) is a rare malignant liver tumor with limited therapeutic advancements. Despite its increasing global incidence knowledge of treatment options remains stagnant, leading to poor five-year patient survival rates and high recurrence post-surgery. ALDH1A1, a member of the ALDH superfamily, is associated with cancer stem cells and has conflicting reports regarding its prognostic role in iCC.

AI-Assisted High-Throughput Tissue Microarray Workflow.

Immunohistochemical (IHC) studies of formalin-fixed paraffin-embedded (FFPE) samples are a gold standard in oncology for tumor characterization, and the identification of prognostic and predictive markers. However, despite the abundance of archived FFPE samples, their research use is limited due to the labor-intensive nature of IHC on large cohorts. This study aimed to create a high-throughput workflow using modern technologies to facilitate IHC biomarker studies on large patient groups.

Renal phenotyping in a hypomorphic murine model of propionic aciduria reveals common pathomechanisms in organic acidurias.

Mutations in the mitochondrial enzyme propionyl-CoA carboxylase (PCC) cause propionic aciduria (PA). Chronic kidney disease (CKD) is a known long-term complication. However, good metabolic control and standard therapy fail to prevent CKD.

EOMES establishes mesoderm and endoderm differentiation potential through SWI/SNF-mediated global enhancer remodeling.

Mammalian pluripotent cells first segregate into neuroectoderm (NE), or mesoderm and endoderm (ME), characterized by lineage-specific transcriptional programs and chromatin states. To date, the relationship between transcription factor activities and dynamic chromatin changes that guide cell specification remains ill-defined. In this study, we employ mouse embryonic stem cell differentiation toward ME lineages to reveal crucial roles of the Tbx factor Eomes to globally establish ME enhancer accessibility as the prerequisite for ME lineage competence and ME-specific gene expression.

The role of the co-chaperone DNAJB11 in polycystic kidney disease: Molecular mechanisms and cellular origin of cyst formation.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), which are required for the regulation of the renal tubular diameter. Loss of polycystin function results in cyst formation. Atypical forms of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)-resident proteins through mechanisms that are not well understood.

Advancements in mass spectrometry-based proteomics: a new era in pathology research and diagnostics.

Background: Mass spectrometry (MS)-based proteomics is rapidly transforming pathology research and diagnostics by enabling comprehensive studies of protein expression and post-translational modifications (PTMs).

Objective: This article discusses recent advancements in MS-based proteomics, focusing on emerging technologies in sample preparation, MS instrumentation, and data analysis. These developments are scrutinized for their applications in clinical cohort studies and molecular pathology diagnostics.

Size exclusion chromatography based proteomic and degradomic profiling of inflammasome-activated, murine bone marrow-derived dendritic cells highlights complex retention and release of cleavage products.

Coupling size exclusion chromatography (SEC) with mass spectrometry-based proteomics enables investigating protein complexes, with degradomic profiling providing deeper insights into complex-associated proteolytic processing and retaining of cleavage products. This study aims to map protein complex formation upon inflammasome activation in bone marrow-derived dendritic cells (BMDCs) from gasdermin D-deficient mice, focusing on proteolytic enzymes and truncated proteins in higher molecular weight complexes. Cultured BMDCs were primed with LPS and subsequently treated with nigericin or Val-boroPro (VbP).

Rapid phagosome isolation enables unbiased multiomic analysis of human microglial phagosomes.

Microglia are the resident macrophages of the central nervous system (CNS). Their phagocytic activity is central during brain development and homeostasis-and in a plethora of brain pathologies. However, little is known about the composition, dynamics, and function of human microglial phagosomes under homeostatic and pathological conditions.

TermineR: Extracting information on endogenous proteolytic processing from shotgun proteomics data.

State-of-the-art mass spectrometers combined with modern bioinformatics algorithms for peptide-to-spectrum matching (PSM) with robust statistical scoring allow for more variable features (i.e., post-translational modifications) being reliably identified from (tandem-) mass spectrometry data, often without the need for biochemical enrichment.

Do early midlife work characteristics predict 20-year change in control beliefs?

Previous research showed the importance of control beliefs for many life outcomes. The present study examines associations between subjectively perceived work environment and objectively measured work activities at the beginning of midlife as a central developmental phase in the context of work, with control beliefs across the subsequent 20 years. We analyzed four-wave longitudinal data from = 374 participants (born 1950-1952; baseline = 44 years, = 1; 44% women) from the Interdisciplinary Longitudinal Study of Adult Development and Aging within a structural equation modeling framework.

Data-Independent Acquisition: A Milestone and Prospect in Clinical Mass Spectrometry-Based Proteomics.

Data-independent acquisition (DIA) has revolutionized the field of mass spectrometry (MS)-based proteomics over the past few years. DIA stands out for its ability to systematically sample all peptides in a given m/z range, allowing an unbiased acquisition of proteomics data. This greatly mitigates the issue of missing values and significantly enhances quantitative accuracy, precision, and reproducibility compared to many traditional methods.

Mass Spectrometry-Based Proteomics of Poly(methylmethacrylate)-Embedded Bone.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a widely employed technique in proteomics research for studying the proteome biology of various clinical samples. Hard tissues, such as bone and teeth, are routinely preserved using synthetic poly(methyl methacrylate) (PMMA) embedding resins that enable histological, immunohistochemical, and morphological examination. However, the suitability of PMMA-embedded hard tissues for large-scale proteomic analysis remained unexplored.

Enrichment, Characterization, and Proteomic Profiling of Small Extracellular Vesicles Derived from Human Limbal Mesenchymal Stromal Cells and Melanocytes.

Limbal epithelial progenitor cells (LEPC) rely on their niche environment for proper functionality and self-renewal. While extracellular vesicles (EV), specifically small EVs (sEV), have been proposed to support LEPC homeostasis, data on sEV derived from limbal niche cells like limbal mesenchymal stromal cells (LMSC) remain limited, and there are no studies on sEVs from limbal melanocytes (LM). In this study, we isolated sEV from conditioned media of LMSC and LM using a combination of tangential flow filtration and size exclusion chromatography and characterized them by nanoparticle tracking analysis, transmission electron microscopy, Western blot, multiplex bead arrays, and quantitative mass spectrometry.

Development of combination therapies with BTK inhibitors and dasatinib to treat CNS-infiltrating E2A-PBX1+/preBCR+ ALL.

The t(1;19) translocation, encoding the oncogenic fusion protein E2A (TCF3)-PBX1, is involved in acute lymphoblastic leukemia (ALL) and associated with a pre-B-cell receptor (preBCR+) phenotype. Relapse in patients with E2A-PBX1+ ALL frequently occurs in the central nervous system (CNS). Therefore, there is a medical need for the identification of CNS active regimens for the treatment of E2A-PBX1+/preBCR+ ALL.

Cathepsin D inhibition during neuronal differentiation selectively affects individual proteins instead of overall protein turnover.

Cathepsin D (CTSD) is a lysosomal aspartic protease and its inherited deficiency causes a severe pediatric neurodegenerative disease called neuronal ceroid lipofuscinosis (NCL) type 10. The lysosomal dysfunction in the affected patients leads to accumulation of undigested lysosomal cargo especially in none-dividing cells, such as neurons, resulting in death shortly after birth. To explore which proteins are mainly affected by the lysosomal dysfunction due to CTSD deficiency, Lund human mesencephalic (LUHMES) cells, capable of inducible dopaminergic neuronal differentiation, were treated with Pepstatin A.

Protocol of the HISTOTHERM study: assessing the response to hyperthermia and hypofractionated radiotherapy in recurrent breast cancer.

Introduction: Breast cancer is globally the leading cancer in women, and despite the high 5-year survival rate the most frequent cause of cancer related deaths. Surgery, systemic therapy and radiotherapy are the three pillars of curative breast cancer treatment. However, locoregional recurrences frequently occur after initial treatment and are often challenging to treat, amongst others due to high doses of previous radiotherapy treatments.

Tpr Misregulation in Hippocampal Neural Stem Cells in Mouse Models of Alzheimer's Disease.

Nuclear pore complexes (NPCs) are highly dynamic macromolecular protein structures that facilitate molecular exchange across the nuclear envelope. Aberrant NPC functioning has been implicated in neurodegeneration. The translocated promoter region (Tpr) is a critical scaffolding nucleoporin (Nup) of the nuclear basket, facing the interior of the NPC.