Characteristics Associated with COVID-19 Breakthrough Infections after Booster Vaccinations in Healthcare Workers: Insights from the TüSeRe:exact Study.

The prevalence of COVID-19 breakthrough infections in healthcare workers (HCWs) remains an issue of concern. This study examines the different characteristics associated with breakthrough infections in HCWs. From the total participants in the TüSeRe:exact study (n = 1046), we specifically included study participants who had received three vaccinations and were not infected prior to the third vaccination.

Microglia-neuron interactions in schizophrenia.

Multiple lines of evidence implicate increased neuroinflammation mediated by glial cells to play a key role in neurodevelopmental disorders such as schizophrenia. Microglia, which are the primary innate immune cells of the brain, are crucial for the refinement of the synaptic circuitry during early brain development by synaptic pruning and the regulation of synaptic plasticity during adulthood. Schizophrenia risk factors as genetics or environmental influences may further be linked to increased activation of microglia, an increase of pro-inflammatory cytokine levels and activation of the inflammasome resulting in an overall elevated neuroinflammatory state in patients.

Symmetrical Bispyridinium Compounds Act as Open Channel Blockers of Cation-Selective Ion Channels.

Current treatments against organophosphate poisoning (OPP) do not directly address effects mediated by the overstimulation of nicotinic acetylcholine receptors (nAChR). Non-oxime bispyridinium compounds (BPC) promote acetylcholine esterase-independent recovery of organophosphate-induced paralysis. Here, we test the hypothesis that they act by positive modulatory action on nAChRs.

Immunoaffinity proteomics for kidney injury biomarkers in male beagle dogs.

Drug-induced kidney injury (DIKI) is a cause of drug development failure. Dogs represent a common non-rodent animal model in pre-clinical safety studies; however, biomarker assays for detecting nephrotoxicity in dogs are limited. To identify novel proteins and gain insight into the molecular mechanisms involved in DIKI, we developed an assay to evaluate proteomic changes associated with DIKI in male beagle dogs that received nephrotoxic doses of tobramycin for 10 consecutive days.

Functionally-instructed modifiers of response to ATR inhibition in experimental glioma.

Background: The DNA damage response (DDR) is a physiological network preventing malignant transformation, e.g. by halting cell cycle progression upon DNA damage detection and promoting DNA repair.

Evaluation of dispensaries' cannabis flowers for accuracy of labeling of cannabinoids content.

Background: Cannabis policies have changed drastically over the last few years with many states enacting medical cannabis laws, and some authorizing recreational use; all against federal laws. As a result, cannabis products are marketed in dispensaries in different forms, most abundantly as flowers intended for smoking and sometimes vaping. All samples used in this study were obtained directly from law enforcement.

Microphysiological pancreas-on-chip platform with integrated sensors to model endocrine function and metabolism.

Pancreatic research is of major importance to advance mechanistic understanding and development of treatment options for diseases such as diabetes mellitus. We present a thermoplastic-based microphysiological system aiming to model the complex microphysiological structure and function of the endocrine pancreas with concurrent real-time read-out capabilities. The specifically tailored platform enables self-guided trapping of single islets at defined locations: β-cells are assembled to pseudo-islets and injected into the tissue chamber using hydrostatic pressure-driven flow.

Defined co-cultures of glutamatergic and GABAergic neurons with a mutation in DISC1 reveal aberrant phenotypes in GABAergic neurons.

Background: Mutations in the gene DISC1 are associated with increased risk for schizophrenia, bipolar disorder and major depression. The study of mutated DISC1 represents a well-known and comprehensively characterized approach to understand neuropsychiatric disease mechanisms. However, previous studies have mainly used animal models or rather heterogeneous populations of iPSC-derived neurons, generated by undirected differentiation, to study the effects of DISC1 disruption.

Integrated Analysis of the Transcriptome and Microbial Diversity in the Intestine of Miniature Pig Obesity Model.

Obesity, a key contributor to metabolic disorders, necessitates an in-depth understanding of its pathogenesis and prerequisites for prevention. Guangxi Bama miniature pig (GBM) offers an apt model for obesity-related studies. In this research, we used transcriptomics and 16S rRNA gene sequencing to discern the differentially expressed genes (DEGs) within intestinal (jejunum, ileum, and colon) tissues and variations in microbial communities in intestinal contents of GBM subjected to normal diets (ND) and high-fat, high-carbohydrate diets (HFHCD).

Exploring the current state of clinical and practical teaching in obstetrics and gynecology in the era of competency-based education: a nationwide survey among German teaching coordinators.

Background: Obstetrics and gynecology (OB/GYN) is an essential medical field that focuses on women's health. Universities aim to provide high-quality healthcare services to women through comprehensive education of medical students. In Germany, medical education is undergoing a phase of restructuring towards the implementation of competency-based learning.

and models define a molecular signature reference for human embryonic notochordal cells.

Understanding the emergence of human notochordal cells (NC) is essential for the development of regenerative approaches. We present a comprehensive investigation into the specification and generation of NC using a straightforward pluripotent stem cell (PSC)-based system benchmarked with human fetal notochord. By integrating and transcriptomic data at single-cell resolution, we establish an extended molecular signature and overcome the limitations associated with studying human notochordal lineage at early developmental stages.

A microphysiological system for parallelized morphological and electrophysiological read-out of 3D neuronal cell culture.

Three-dimensional models in microfluidic systems are promising tools for studying cell biology, with complex models using multiple cell types combined with high resolution imaging. Neuronal models demand electrical readout of the activity of networks of single neurons, yet classical planar microelectrode arrays struggle to capture extracellular action potentials when neural soma are suspended distant from the microelectrodes. This study introduces sophisticated microfluidic microelectrode arrays, specifically tailored for electrophysiology of 3D neuronal cultures.

The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma.

Fibroblast growth factor receptor (FGFR)-2 can be inhibited by FGFR-selective or non-selective tyrosine kinase inhibitors (TKIs). Selective TKIs are approved for cholangiocarcinoma (CCA) with FGFR2 fusions; however, their application is limited by a characteristic pattern of adverse events or evocation of kinase domain mutations. A comprehensive characterization of a patient cohort treated with the non-selective TKI lenvatinib reveals promising efficacy in FGFR2-driven CCA.

Prediction of chlorophyll a and risk assessment of water blooms in Poyang Lake based on a machine learning method.

Four different methods were used to identify the important factors influencing chlorophyll-a (Chl-a) content: correlation analysis (CC-NMI), principal component analysis (PCA), decision tree (DT), and random forest recursive feature elimination (RF-RFE). Considering the relationship between Chl-a and its active and passive factors, we established machine learning combination models based on multiple linear regression (MLR), multi-layer perceptron (MLP), and support vector regression (SVR) to predict Chl-a content for Poyang Lake, China. Then, the predictive effects of different combination models were compared and evaluated from multiple perspectives.

Systemic inflammation relates to neuroaxonal damage associated with long-term cognitive dysfunction in COVID-19 patients.

Background And Objectives: Cognitive deficits are increasingly recognized as a long-term sequela of severe COVID-19. The underlying processes and molecular signatures associated with these long-term neurological sequalae of COVID-19 remain largely unclear, but may be related to systemic inflammation-induced effects on the brain. We studied the systemic inflammation-brain interplay and its relation to development of long-term cognitive impairment in patients who survived severe COVID-19.

Cancer-mediated axonal guidance of sensory neurons in a microelectrode-based innervation MPS.

Despite recent advances in the field of microphysiological systems (MPSs), availability of models capable of mimicking the interactions between the nervous system and innervated tissues is still limited. This represents a significant challenge in identifying the underlying processes of various pathological conditions, including neuropathic, cardiovascular and metabolic disorders. In this novel study, we introduce a compartmentalized three-dimensional (3D) coculture system that enables physiologically relevant tissue innervation while recording neuronal excitability.

Phase Angle of Bioelectrical Impedance Analysis as an Indicator for Diabetic Polyneuropathy in Type 2 Diabetes Mellitus.

Context: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routines, leading to increased morbidity and mortality.

Objective: We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory, and physical markers of DPN to evaluate PhA as a possible diagnostic method for DPN.

Materials And Methods: In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications, we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), among which 63 had DPN.

Elements and development processes for test methods in toxicology and human health-relevant life science research.

Many laboratory procedures generate data on properties of chemicals, but they cannot be equated with toxicological "test methods". This apparent discrepancy is not limited to in vitro testing, using animal-free new approach methods (NAM), but also applies to animal-based testing approaches. Here, we give a brief overview of the differences between data generation and the setup or use of a complete test method.

The extracellular matrix as hallmark of cancer and metastasis: From biomechanics to therapeutic targets.

The extracellular matrix (ECM) is essential for cell support during homeostasis and plays a critical role in cancer. Although research often concentrates on the tumor's cellular aspect, attention is growing for the importance of the cancer-associated ECM. Biochemical and physical ECM signals affect tumor formation, invasion, metastasis, and therapy resistance.

Two birds with one stone: human SIRPα nanobodies for functional modulation and imaging of myeloid cells.

Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the "don't eat me" ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both approaches, we developed a set of novel human SIRPα (hSIRPα)-specific nanobodies (Nbs). We identified high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis.

Sensitization of cholangiocarcinoma cells to chemotherapy through BCRP inhibition with β-caryophyllene oxide.

Cholangiocarcinomas (CCAs) are cancers originated in the biliary tree, which are characterized by their high mortality and marked chemoresistance, partly due to the activity of ATP-binding cassette (ABC) export pumps, whose inhibition has been proposed as a strategy for enhancing the response to chemotherapy. We have previously shown that β-caryophyllene oxide (CRYO) acts as a chemosensitizer in hepatocellular carcinoma by inhibiting ABCB1, MRP1, and MRP2. Here, we have evaluated the usefulness of CRYO in inhibiting BCRP and improving the response of CCA to antitumor drugs.

Efficacy of HDAC Inhibitors in Driving Peroxisomal β-Oxidation and Immune Responses in Human Macrophages: Implications for Neuroinflammatory Disorders.

Elevated levels of saturated very long-chain fatty acids (VLCFAs) in cell membranes and secreted lipoparticles have been associated with neurotoxicity and, therefore, require tight regulation. Excessive VLCFAs are imported into peroxisomes for degradation by β-oxidation. Impaired VLCFA catabolism due to primary or secondary peroxisomal alterations is featured in neurodegenerative and neuroinflammatory disorders such as X-linked adrenoleukodystrophy and multiple sclerosis (MS).