Determining the role of basophil activation testing in reported type 1 allergy to beta-lactam antibiotics.

Background: Allergy to beta-lactam antibiotics (BLA), especially to penicillin, is the most commonly reported drug allergy by patients. Alternative antibiotics can yield negative consequences, such as extended hospitalization days due to less efficacy and overall higher costs. The basophil activation test (BAT) is an assay, in which activation of an individual's own basophils is quantified by flow cytometry.

PSMA-Guided Imaging and Therapy of Advanced Adenoid Cystic Carcinomas and Other Salivary Gland Carcinomas.

SGCs are rare malignancies, accounting for less than 1% of all head and neck cancers [...

Phenol (bio)isosteres in drug design and development.

Due to their versatile properties, phenolic compounds are integral to various biologically active molecules, including many pharmaceuticals. However, their application in drug design is often hindered by issues such as poor oral bioavailability, rapid metabolism, and potential toxicity. This review explores the use of phenol bioisosteres-structurally similar compounds that can mimic the biological activity of phenols while potentially offering improved drug-like properties.

2-[18F]F-p-aminobenzoic acid specifically detects infective endocarditis in positron emission tomography.

Background: To the present day infective endocarditis (IE) represents a life-threatening disease with high mortality rate especially when caused by Staphylococcus aureus (S. aureus), the most common causative pathogen in this disease. Diagnosis of IE is based on clinical manifestations, pathogen detection by blood cultures and echocardiographic or other imaging findings.

Making the effect visible - OX40 targeting nanobodies for imaging of activated T cells.

Purpose: Human OX40 (hOX40/CD134), a member of the TNF receptor superfamily, is mainly expressed on activated T lymphocytes. Triggered by its ligand OX40L (CD252), it provides costimulatory signals that support the differentiation, proliferation and long-term survival of T cells. Besides being a relevant therapeutic target, hOX40 is also an important biomarker for monitoring the presence or infiltration of activated T cells within the tumor microenvironment (TME), the inflammatory microenvironment (IME) in immune-mediated diseases (IMIDs) and the lymphatic organs.

Functional PET/MRI reveals active inhibition of neuronal activity during optogenetic activation of the nigrostriatal pathway.

The dopaminergic system is a central component of the brain's neurobiological framework, governing motor control and reward responses and playing an essential role in various brain disorders. Within this complex network, the nigrostriatal pathway represents a critical circuit for dopamine neurotransmission from the substantia nigra to the striatum. However, stand-alone functional magnetic resonance imaging is unable to study the intricate interplay between brain activation and its molecular underpinnings.

Focal Unspecific Bone Uptake on [F]PSMA-1007 PET: Evaluation Analog PROMISE Criteria and Validation via PET/CT Follow-Up.

Focal unspecific bone uptake (UBU) is common in [F]PSMA-1007 PET/CT, yet its clinical significance remains unclear, causing uncertainty in treatment decisions. We retrospectively analyzed 99 prostate cancer patients (age 69 ± 7) who underwent [F]PSMA-1007 PET/CT scans (3 MBq/kg; uptake time 70 ± 14 min) for staging and follow-up (after 13.0 ± 7.

Ga-Labeled TRAP-Based Glycoside Trimers for Imaging of the Functional Liver Reserve.

The exclusive asialoglycoprotein receptor (ASGR) expression on hepatocytes makes it an attractive target for imaging of the functional liver reserve. Here, we present a set of TRAP-based glycoside trimers and evaluate their imaging properties compared to the gold standard [Tc]Tc-GSA. The click-chemistry-based synthesis approach provided easy access to trimeric low-molecular-weight compounds.

Study on the mechanism of 17-Hydroxy-jolkinolide B on anaplastic thyroid cancer cell.

Background: Anaplastic thyroid cancer (ATC) has a dismal prognosis, and the optimal treatment has not yet been confirmed. Euphorbia fischeriana Steud has been proven to exhibit pharmacological properties, including various antitumor effects, that can be used to treat numerous diseases and has been used to treat cancer. 17-Hydroxy-jolkinolide B (17-HJB) is one of the major diterpenoids produced from plants, but little research has investigated how it affects cancer.

Exploring P2X receptor activity: A journey from cellular impact to electrophysiological profiling.

The development of in vitro pharmacological assays relies on creating genetically modified cell lines that overexpress the target protein of interest. However, the choice of the host cell line can significantly impact the experimental outcomes. This study explores the functional characterization of P2X7 and P2X4 receptor modulators through cellular assays and advanced electrophysiological techniques.

In-depth cross-validation of human and mouse CD4-specific minibodies for noninvasive PET imaging of CD4 cells and response prediction to cancer immunotherapy.

Increasing evidence emphasizes the pivotal role of CD4 T cells in orchestrating cancer immunity. Noninvasive imaging of the temporal dynamics of CD4 T cells and their distribution patterns might provide novel insights into their effector and regulator cell functions during cancer immunotherapy (CIT). We conducted a comparative analysis of Zr-labeled anti-mouse (m) and anti-human (h) CD4-targeting minibodies (Mbs) for positron emission tomography (PET)/magnetic resonance imaging (MRI) of CD4 T cells in human xenografts, syngeneic tumor-bearing wild-type (WT), and human CD4 knock-in (hCD4-KI) mouse models.

MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

Background: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner.

Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme.

The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment.

K channel targeting impairs DNA repair and invasiveness of patient-derived glioblastoma stem cells in culture and orthotopic mouse xenografts which only in part is predictable by K expression levels.

Prognosis of glioblastoma patients is still poor despite multimodal therapy. The highly brain-infiltrating growth in concert with a pronounced therapy resistance particularly of mesenchymal glioblastoma stem-like cells (GSCs) has been proposed to contribute to therapy failure. Recently, we have shown that a mesenchymal-to-proneural mRNA signature of patient derived GSC-enriched (pGSC) cultures associates with in vitro radioresistance and gel invasion.

Optimizing SUV Analysis: A Multicenter Study on Preclinical FDG-PET/CT Highlights the Impact of Standardization.

Purpose: Preclinical imaging, with translational potential, lacks a standardized method for defining volumes of interest (VOIs), impacting data reproducibility. The aim of this study was to determine the interobserver variability of VOI sizes and standard uptake values (SUV and SUV) of different organs using the same [F]FDG-PET and PET/CT datasets analyzed by multiple observers. In addition, the effect of a standardized analysis approach was evaluated.

Advancing Parkinson's Disease Diagnostics: The Potential of Arylpyrazolethiazole Derivatives for Imaging α-Synuclein Aggregates.

The development of positron emission tomography (PET) tracers capable of detecting α-synuclein (α-syn) aggregates in vivo would represent a breakthrough for advancing the understanding and enabling the early diagnosis of Parkinson's disease and related disorders. It also holds the potential to assess the efficacy of therapeutic interventions. However, this remains challenging due to different structures of α-syn aggregates, the need for selectivity over other structurally similar amyloid proteins, like amyloid-β (Aβ), which frequently coexist with α-syn pathology, and the low abundance of the target in the brain that requires the development of a high-affinity ligand.

Optimization and impact of sensitivity mode on abbreviated scan protocols with population-based input function for parametric imaging of [F]-FDG for a long axial FOV PET scanner.

Background: The long axial field of view, combined with the high sensitivity of the Biograph Vision Quadra PET/CT scanner enables the precise deviation of an image derived input function (IDIF) required for parametric imaging. Traditionally, this requires an hour-long dynamic PET scan for [F]-FDG, which can be significantly reduced by using a population-based input function (PBIF). In this study, we expand these examinations and include the scanner's ultra-high sensitivity (UHS) mode in comparison to the high sensitivity (HS) mode and evaluate the potential for further shortening of the scan time.

Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis.

Diet-induced increase in body weight is a growing health concern worldwide. Often accompanied by a low-grade metabolic inflammation that changes systemic functions, diet-induced alterations may contribute to neurodegenerative disorder progression as well. This study aims to non-invasively investigate diet-induced metabolic and inflammatory effects in the brain of an APPPS1 mouse model of Alzheimer's disease.

Retinal metabolism displays evidence for uncoupling of glycolysis and oxidative phosphorylation via Cori-, Cahill-, and mini-Krebs-cycle.

The retina consumes massive amounts of energy, yet its metabolism and substrate exploitation remain poorly understood. Here, we used a murine explant model to manipulate retinal energy metabolism under entirely controlled conditions and utilised H-NMR spectroscopy-based metabolomics, in situ enzyme detection, and cell viability readouts to uncover the pathways of retinal energy production. Our experimental manipulations resulted in varying degrees of photoreceptor degeneration, while the inner retina and retinal pigment epithelium were essentially unaffected.